THE SELECTIVE CATALYTIC OXIDATION

OF D-GLUCONIC ACID TO 2-KETO - D-GLUCONIC ACID

OR D-GLUCARIC ACID

PROEFSCHRIFT

TER VERKRIJGING VAN DE GRAAD VAN DOCTOR IN DE TECHNISCHE WETENSCHAPPEN AAN DE TECHNISCHE HOGESCHOOL EINDHOVEN, OP GEZAG VAN DE RECTOR MAGNIFICUS, PROF. DR. S.T.M. ACKERMANS, VOOR EEN COMMISSIE AANGEWEZEN DOOR HET COLLEGE VAN DEKANEN IN HET OPENBAAR TE VERDEDIGEN OP

DINSDAG 24 APRIL 1984 TE 16.00 UUR

DOOR

PETER CAROLUS CORNELIS SMITS

GEBOREN TE URMOND

Dit proefschrift is goedgekeurd door de

promotoren: prof. drs. H.S. van der Baan

prof. dr. ir. K. van der Wiele

co-promotor: dr. ir. B.F.M. Kuster

Aan mijnouders

i

Page

1. Introduction 1.1. Carbohydrates as a chemical feedstock 1

1.2. Oxidation of monosaccharides 4

1.3. Properties and applications of the oxidation-

products of glucose 6

1.4. Aspects of phosphate reduction 10

1.5. Choice of oxidation system 11 1.6. Aim and outline of this thesis 12

References 15

2. Literature survey

2.1. Introduction 17

2.2. Oxidation of D-glucose to D-gluconic acid 21 2.2.1. Homogeneous oxidation 21

2.2.2. Biochemical oxidation 22

2.2.3. Heterogeneous catalytic oxidation 24

2.3. Oxidation of D-glucose or D-gluconic acid to D-glucaric acid 27 2.3.1. Homogeneous oxidation 27 2.3.2. Heterogeneous catalytic oxidation 27

2.4. Manufacture of 2-keto-D-gluconic acid 28 2.4.1. Oxidation of D-glucose or o-gluconic acid 28 2.4.2. Alternative oxidation methods 32

2.5. Oxidation of L-gulonic acid to 2-keto-L-gulonic acid 33

2.6. Discussion 33 References 34

3. Analysis

3.1. Introduction

3.2. Ion exchange chromatography

3.2.1. Introduction

3.2.2. Experimental

3.2.3. Typical results

3.3. Preparative ion exchange chromatography

3.3.1. Experimental

3.3.2. Typical results

3.4. l3c-nuclear magnetic resonance spectroscopy

3.4.1. Introduction

3.4.2. Experimental

3.4.3. Typical results

3.5. Isotachophoresis 3.5.1. Introduction

3.5.2. Experimental

3.5.3. Typical results 3.6. A specific detection method for a-keto

carboxylic acids 3.6.1. Introduction 3.6.2. Experimental

3.6.3. Typical results

References

4. Equipment and experimental methods

4.1. Introduction

4.2. The catalysts 4.2.1. The platinum on carbon catalyst 4.2.2. The lead platinum on carbon catalyst

4.3. Equipment 4.4. Experimental methods

4.5. Mass transfer in the stirred tank reactor

References

ii

43

44

44

45 46

52

52

53

55

55

55

56

60

60

61 61

65 65

65 66

67

69

69

69

71

74 75 76

76

iii

S. Selective catalytic production of D-glucaric acid

S.1. Introduction 77

S.2. Exploratory experiments of the oxidation of D-gluconic acid with Cu1II) and Co(!I) catalysts 81

S.3. Product distribution during the oxidation of D-gluconic acid with a Pt/C catalyst 82

S.4. Oxidation of D-gluconic acid in the presence

of borate 86 S.S. Oxidation of D-gluconic acid, partly in the

form of o-lacton 93 S.6. Addition of Pb(II) to the oxidation formulation 98

References 99

6. Characteristics and scope of the Pb/Pt/C catalyst in ·the oxidation of carbohydrates and their monocarboxylic ac~ds

6.1. Introduction 101

6.2. Experimental 102

6.3. The effect of lead on the Pt-catalyzed oxidation of D-gluconic acid 102

6.3.1. Addition of a heterogeneous lead compound to the Pt/C catalyst 102

6.3.2. Addition of a homogeneous lead compound to a Pt/C catalyst 106

6.3.3. Addition of Pb3 CP04 ) 2/c to a Pt/C catalyst 108

6.3.4. Addition of EDTA to a Pt/Pb/C catalyst 110

6.4. Influence of the Pb/Pt ratio 111

6.S. Metal ions other than Pb2+ llS 6.6. Other substrates than D-gluconic acid 6.7. Deactivation of the catalyst References

117 123

128

7. Selective catalytic production of 2-keto-D-gluconic

7 .1. Introduction

7.2. Influence of the catalyst concentration 7.3. Influence of the oxygen concentration 7.4. Influence of the pH 7.5. Influence of the temperature

7.6. Product distribution

8. Final discussion 8.1. Introduction 8.2. Coordination of Pb2+ with D-gluconic acid

acid

iv

129 129

134 140 143 146

153

153 8.3. Reaction mechanism 157 8.4. Kinetics of the D-gluconic acid oxidation with

a Pb/Pt/C catalyst 160 8.5. Applications of the Pb/Pt/C catalyst References

Appendix I: Structure formulas

Summary

Samenvatting

Dankwoord

Levensbericht

161 163

165

167

170

173

175

1

Chapter 1

Introduction

1.1. Carbohydrates as a chemicai feedstock

Carbohydrates are produced every year in large quantities

by photosynthesis, mainly in the form of the polysaccharides

cellulose and starch, and the disaccharide sucrose. All can

be hydrolyzed to monosaccharides, yielding glucose, while from

sucrose also fructose is obtained. Starch and sucrose are almost

exclusively used as food, while cellulose is mainly used for

the manufacture of paper and rayon and in the form of wood as

fuel and construction material. Only a very small part of

the available carbohydrates is used as a feedstock for the

chemical industry.

Since the publication of the first report of the Club of

Rome (1) the awareness has grown that the reserves of oil,

natural gas and coal are not unlimited, Therefore, it is

mandatory to look for alternative raw materials for the chemical

industry. In certain instances carbohydrates can offer such an

alternative, the more so because one can try to arrange that

the rate of production by agriculture remains in equilibrium

with the rate of conversion and consumption. Due to the

enormously increased price of oil also the economic attractiveness

of processes based on carbohydrates is improving.

The high oxygen content of the sugars makes it possible

to produce, for some chemicals used at present, substitutes,

that cause fewer environmental problems.

2

From the monosaccharides obtained by hydrolysis, glucose

is the most important raw-material for the chemical indus~ry.

The main products which are of industrial interest are

summarised in table 1.1. More detailed information is given

in the literature (2-7) •

Biocatalytic processes Catalytic processes

ethanol glucitol

acetic acid mannitol (via fructose)

lactic acid gluconic acid

vitamin C (via glucitol) glucaric acid

gluconic acid

fructose

Table 1.1. Produate and proaeesee of industrial

interest, starting from gluaose

The processes can broadly be divided into catalytic and

biochemical (biocatalytic) processes. In this thesis we will

call processes using man made, mainly, although not exclusi­

vely, inorganic catalysts catalytic processes, and processes that use microorganisms or enzymes biocatalytic or enzymatic

processes. Their main features are compared in table 1.2.

Although catalytic processes offer more advantages than

disadvantages than biochemical processes, the former have

yet found little application in the carbohydrate-industry.

This is mainly caused by the fact that the selectivity of the

catalytic processes is not high enough. In general, inorganic

catalysts are less specific than biocatalysts, moreover a

characteristic property of carbohydrate molecules is their

rather high number of almost identical functional groups.

Combination of these two factors will generally lead to a

3

lower selectivity when an inorganic catalyst is substituted

for a biocatalyst in a carbohydrate process. This is especially

true for processes involving conversion of only one hydroxyl

group. Of these processes oxidation processes are commercially

by far the most important.

process type catalytic biocatalytic

reaction time + -concentration level of reactants + -reactor volume + -product separation from catalyst + -continuous operation + -reliability (resistance against poisoning) + -selectivity - +

product purification - +

+ : favourable less favourable

Table 1.2. Comparison between aataZytia and bioaataZytia

aarbohydrate proaesses.

Improvement of the selectivity would take away this

obstacle for the application of catalytic oxidation processes

in carbohydrate industry. Therefore the main aim of the

research work described in this thesis is the improvement

of the selectivity of the catalytic oxidation of D-glucose

to D-glucaric acid or 2-keto-D-gluconic acid.

0 II C-H I

H-C-OH I

HO-C,-H I

H-C-OH I

H-C-OH I CH

20H

D-glucose

TOOH

H-T-OH

HO-T-H

H-C-OH I

H-C-OH I CH 20H

D-gluconic acid

COOH I

H-C-OH I

HO-C-H I

H-C-OH I

H-T-OH

COOH

D-glucaric acid

COOH I c = 0 I

HO-C-H I

H-C-OH I

H-C-OH

tH2

0H

2-keto-D-gluconic acid

4

1.2. O~idation of monosaaaharides

Oxidation of monosaccharides is one of the main reactions

that can be applied to carbohydrates. A well~known industrial

example is the oxidation of L-sorbose to 2-keto-L-gulonic acid

from which vitamin C (L-ascorbic acid) can be readily obtained:

0

.9] HO-C II

HO-C I

H-C I

HO-C-H I CH 20H

L-sorbose 2-keto-L-gulonic acid

L-ascobic acid

Without precautions the oxidation step is accompanied by many

side reactions, so that a protection of the other, also

reactive OH-functions by means of e.g. acetone is necessary.

This oxidation requires therefore three reaction steps:

attachment of the protective groups, oxidation of the remaining

target group, and removal of the protective groups, as shown

below.

fH 20H

f 0 HO-f-H

H-f-OH

HO-f-H CH 20H

L-sorbose

2,3:4,6 d1-D­isopropylidene 2-keto-L-gulonic acid

2,3:4,6 - d1-0-1sopropylidene -n-L-sorbofuranose

f OOH

r = o HO-C-H

I H-C-OH

I HO-C-H

I CH 20H

2-keto-L-gulonic acid

These three steps are part of the present industrial route

for the production of vitamin C and are based on the work

of Reichstein et al. (8) published in 1933 (!).It would be

economically attractive if one could manage to oxidize

L-sorbose without the need of the introduction and subsequent

removal of protective groups. In chapter 6 we will, on basis

of our findings, propose an alternative route for the manu­

facture of vitamin c. Another industrial example is the, at present mainly

biochemical, oxidation of D-glucose to D-gluconic acid. In

5

The Netherlands D-gluconic acid is produced by Glucona, a

joint-venture of Akzo and AVEBE. At the moment they use two

processes, one based on the fungus Aspergillus niger, and the

other predicated the bacterium Gluconobacter oxydans. A logical

development in this field is the use of the immobilized enzyme­

system glucose oxydase-catalase from e.g. Aspergillus niger

in a continuous process as described by Hartmeier and Tegge (9),

Richter and Heinecker (10) and Tramper (30).

An important competitor of this process consists of the

catalytic oxidation with palladium on carbon. An industrial

process (with a high selectivity) is currently in operation

in Japan. Dirkx (29) has found that this oxidation can be

carried out with a high selectivity ( > 95%) too, using a

trickle-bed reactor and (deactivated) platinum on carbon

(Pt/C) as catalyst.

The next step, the oxidation of D-gluconic acid to

D-glucaric acid, is much more difficult. There is no bio­

catalyst known for this reaction, while for the aqueous

alkaline oxidation with oxygen and Pt/C as catalyst, the

highest productivity reported is 50-55 %. For commercial

application this is far from attractive. In this thesis we

will describe some preliminary experiments to improve this

productivity.

6

1. 3. Properties and appZiaations of the o:xidation-produats

of g"luaose

The main product property of the oxidation-products of

monosaccharides derives from their sequestering capacity,

i.e. their ability to form soluble complexes with certain

metal ions.

At a pH above 13 gluconic- , glucaric- , galactonic- ,

galactaric-, and xylaric acid are good sequestrants (12,13).

Gluconic acid is the only sugar acid which is at present

applied on a large commercial scale as a sequestrant. The sequestering capacity of glucaric acid is about a factor 5

higher than that of gluconic acid (3% NaOH, 25°C) (12).

However, the relative high cost of production of glucaric

acid by nitric acid oxidation of glucose has discouraged the

widespread use of glucaric acid as a metal ion sequestrant (14). In weak alkaline medium ( pH 8-13) the sequestering capa­

city of the sugar acids is low, but on complexing the sugar

acids with boric acid the sequestering capacity in a weak

alkaline medium is much improved (15,16). For example, the

sequestering capacity of disodium glucarate increases by a

factor 9 by complexing it with 1 mol boric acid/mol glucarate

(pH= 9.5, 25°C) (15).

One of the main applications of sequestrants nowadays is

in the formulation of detergents. The most important sequestrants

used for this purpose are citric acid, ethylene diamine tetra­acetic acid (EOTA), nitrilo tri-acetic acid (NTA), and scdium

tripolyphosphate.

The choice of the sequestrant for a specific application

depends, among other factors, upon the type of ion to be com­

plexed, pH and temperature. Table 1.3. gives the sequestering

capacity (defined here as g Ca 2 + complexed per 100 g seques­

trant) for a number of sugar acids and the four other se­

questrants. The data are adopted from work described by Heesen

(16) and van der Steen (17).

sequestrant mol boric acid/ sequesterin9 capacity mol sequestran t 9 Ca 2

•;100 9 sequestrant (pH = 9.5, 25•c1

sodium gluconate 0 0.5

1 6.5 disodium glucarate 0 La

1 16.5 disodium galactarate 0 1.3

1 14.0 L(+) sodium tartrate 0 2.0

1 a.a trisodium citrate 0 5.5

1 5.2 Na-NTA 0 16.2 K4-EDTA 0 4.9 sodium tripolyphosphate 0 12.3

table 1.3. Sequestering aapaaity towards ca2 + for some sequestrants

7

From table 1.3. is concluded that the sequestering capa­

city of the sugar acid/boric acid complexes can easily compete

with that of the more conventional sequestrants.

Sodium tripolyphosphate is used on a large scale in syn­

thetic detergents, but it causes serious environmental pollu.­

tion. Therefore, considerable research is carried out by various

industrial laboratories to find alternatives for sodium tri­

polyphosphate (18-26). A computersurvey over the years 1971 -

1981 by International Research Service S.D.C. (20) showed

that no less than 400 patent applications were filed world-

wide by about 40 companies: detergent manufactures, oil-com­

panies, chemical industries, and others.

8

To judge the potential alternatives, the following pro­

perties have to be compared: sequestering capacity, bio­

degradibility, toxicological- and cancerous properties and

of course the price.

From all the possibilities suggested in The Netherlands

only two serious candidates (20) remained: zeolite and NTA.

The zeolite used is a special sodium-aluminium-silicate.

It is a crystalline water-insoluble ion- exchanger that

exchanges its sodium ions with the metal-ions from the solution.

A more recent study at our laboratory (27), however,

showed that the oxidation mixture of D-glucose, prepared by

the use of Pt/C as catalyst and oxygen as oxydant, offers a

clear alternative. The main constituent of this mixture is

D-glucaric acid, which, in combination with boric acid, is a very good sequestrant (table 1.3.). The detergents in use

nowadays already contain borates, consequently they need not

to be added separately. According to this study the price of

the so-called "Glucombinaat" is as low as, or even lower than

the other alternatives.

Akzo successfully (21,26) introduced another alternative,

the so-called "washing-bag", in which a mixture of dicarboxylic

acids (succinic- , glutaric- and adipic acid) is used as

phosphate-substitute.

The sugar acids and their complexes with boric acid not

only are an alternative for sodium tripolyphosphate, but also

are potential alternatives for other sequestrants for other

applications, e.g. bottle washing, cleaning of metal-surfaces,

tanning in the leather industry, and as carrier of certain

metal ions in pharmaceutical applications.

The other oxidation reaction described in this work is

that leading to 2-keto-D-gluconic acid. This product is an

important intermediate. It can be converted into its ascorbic

acid analog D-a~aboascorbic acid (!so-vitamin C) (28) :

TOOH c = 0

HO-~-H I

H-C-OH I

H-C-OH I CH20H

2-keto-D-gluconic acid D-araboascorbic acid (!so-vitamin C)

9

This iso-vitamin C has only a very low anti-scorbutic activity,

but it is potentially a very good anti-oxydant in e.g. food.

The a-keto carboxylic acid can also be transformed into

a dicarboxylic acid. Thus 2-keto-D-gluconic acid reacts with

cyanide and hydrolysis of the product gives a 2-carboxy-D­

gluconic acid.

2-keto-D-gluconic acid

f OOH HO-C-COOH

I HO-C-H

I H-C-OH

H-t-OH I CH20H

+

f OOH HOOC-C-OH

I HO-C-H

H-h-oH I

H-C-OH I CH20H

2-carboxy-D-gluconic acid

These two 2-carboxy-D-gluconic acids are poly-hydroxy-di-car­

boxylic acids. Based on table 1.3. it can be expected that,

eventually in combination with boric acid, the product is a

10

good sequestrant too. The addition product is subject of

extensive industrial research.

1.4. Aspects of phosphate reduction

Phosphates can cause serious environmental pollution by

cutrofication of the surface-water. In The Netherlands the

situation around the phosphate-load of the surface-water is

rather complex (20). Only 52% of it results from activities

in The Netherlands. The rest comes into our country via the

big main rivers, especially the Rhine. From the internal

phosphate load 70% is from domestic origin. Half of it comes from feaces and urine and the other half from synthetic de­

tergents. The latter quantity amounts to about 10 000 ton of

phosphate per year.

To reduce the phosphate content of the surface-water there

are three possibilities:

- replacement of the phosphates in the synthetic detergents

by other sequestrants

- obviation of the need for sequestrants by central water­

softening

- or dephosphatation of the waste water

In the Netherlands at the moment the best solution for this

problem is still under discussion. From the above mentioned

percentages it is clear that the reduction of the phosphate

load, due to the complete replacement of phosphate in the

detergents in The Netherlands will only be about 18% of the total load. However, if the surrounding countries would take

the same measure, the reduction would be about 35%. From these

figures it is clear that replacement of the phosphates in the

detergents will alleviate the phosphate problem considerably.

It will be just a matter of price and policy which solution or

combination of solutions will be chosen. The phosphate substi-

tutes have in their favour the intention of the Dutch

government to completely eliminate the phosphates in the

detergents by 1987.

11

Any possible substitute of the polyphosphates must not

only have good sequestering properties, but must also be able

to compete pricewise. Therefore a process to manufacture such

a substitute must be as simple as possible.

1.5. Choice of oxidation system

We have investigated only catalytic oxidations of mono­

saccharides, because the non-catalytic oxidations by chemical

oxidants are in general much slower, more costly, and less

selective than the catalytic oxidations. In section 1.1. we

already discussed the choice between an inorganic catalytic

and a biocatalytic process. We will now examine the economic

aspects of the inorganic catalytic processes in some detail,

First we have to consider the choice of the oxidizing

agent. In chapter 2 we will discuss some of the possibilities,

and show that there is no oxidizing agent that posseses a

higher selectivity than low pressure oxygen in combination

with a noble metal catalyst. Consequently the process can use

air, the cheapest oxidizing agent available.

The price of the catalyst is in general not so important,

at least when the catalyst losses are low and the catalyst does

not deactivate or can easily be recovered and regenerated. As already mentioned in section 1.3. it is for certain

applications not necessary to purify the oxidation mixture (27).

When a complexing agent has to be produced, the reaction mix­

ture needs only little purification, because almost all of the

by-products act as a sequestrant too, although their sequestering

capacity i~ lower than that of the desired product. This is

one of the main reasons for us to investigate methods to im­

prove the selectivity for the component with the highest

12

sequestering-capacity. A higher selectivity of course also

facilitates, in general, an eventual purification, thus making

the process cheaper.

The only by-product from our oxidation-mixtures that has

to be removed, if the mixture is to serve as a sequestrant, is

oxalate. This is easily removed by precipitation as calcium

oxalate convertable with sulphuric acid to oxalic acid. For

this oxalic acid, currently mostly imported from abroad, there

exists a good market in our country. The only product that may

have a negative value is calcium sulphate.

The utilization of 2-keto-D-gluconic acid as a source of

iso-vitamin C, applicable as a food anti-oxidant will necessi­

tate extensive purification either of the keto acid or the

iso-vitamin c.

1.6. Aim and outiine of this thesis

Biocatalytic oxidation of monosaccharides have found

extensive applications in the carbohydrate industry, while the

(anorganic) catalytic oxidations have found as yet hardly any

application, although recently there is improvement in this

respect (11). The main reason why the catalytic processes, with their potential advantages, lag behind the enzymatic processes,

is the lower selectivity of the former processes. For this

reason we have investigated potential possibilities to improve

the selectivity of some of the catalytic oxidation processes.

Hardly any data are available in this respect. We have chosen

the oxidation of D-glucose, because it is very readily available

and because of its potential applicability of its oxidation

products. From the literature it is known that the first step

in the oxidation-process (D-glucose + D-gluconic acid) can be

carried out with a high selectivity ( > 95%) both catalytically

(29) and with the aid of enzymes (9,10).

This study will largely be devoted to the second step:

the oxidation of D-gluconic acid to D-glucaric acid or

2-keto-D-gluconic acid in aqueous solution with Pt/C and

modified Pt/C catalysts. Dirkx (29) also studied the

13

kinetics of the oxidation of D-gluconic acid to D-glucaric acid,

and the present thesis is in certain respect a continuation

of that work.

In chapter 2 a survey of the literature data on the pre­

paration of D-glucaric acid and 2-keto-D-gluconic acid is given.

The analysis of the various reaction mixtures is described

in chapter 3. For this purpose mainly ion-exchange chromato­graphy is used. At times isotachophoresis, 13c-nuclear magnetic

resonance and a specific detection method for a-keto-carboxylic

acids are used to help the identification and quantification of

the various components of the reaction mixtures. For identifica­

tion purposes we have also made use of preparative liquid chro­

matography for the isolation of certain components out of the

product mixtures.

In chapter 4 a description of the stirred tank reactor,

the preparation of a number of catalysts, and the basic experi­

mental procedure is given.

Some explorative experiments to improve the selectivity

for D-glucaric acid are discussed in chapter 5. During one of

these experiments we discovered the selective catalytic produc­

tion of 2-keto-D-gluconic acid with a lead modified Pt/C

catalyst. As this compound is of potential industrial interest,

we decided to study its manufacture more closely.

In chapter 6 we describe investigations into the potentials

of this oxidation reaction, e.g. with respect of the catalyst

preparation and also in respect to various monosaccharides as

substrate.

In chapter 7 we dis.cuss the experiments to improve the

selectivity of the reaction described in chapter 6 and experi­

ments that are the basis of a reaction model.

Finally in chapter 8 an attempt will be made to give a

consistent description of the factors that determine the charac-

14

teristics of the Pb/Pt/C catalyst. The description will be based

on the results presented in chapter 6 and 7 and a literature

studie on the complexation of D-gluconic acid with Pb2+.

References

1. Rapport van de Club van Rome, Het Spectrum, Utrecht,

Au1a Pocket 500 (1972) 2. van Ling, G., Polytechnisch Tijdschrift, 386 (1970)

3. Dewar, E.T., Manuf. Chemist., 29, 458 (1958)

4. Machell, G., Manuf. Chemist., l!r 520 (1960)

5. Korf, D., Ph.D. thesis, University of Technology, Delft,

The Netherlands (1963)

6. Van Velthuijzen, J.A., Seminar on Sucrochem. (1973)

15

7. Van der Baan, H.S., Kuster, B.F.M~, Innovation study,

University of Technology, Eindhoven, The Netherlands (1982)

8. Reichstein, T.H., Griissner, A., Oppenauer, R., Helv. Chim.

Acta,~, 561/1019 (1933)

9. Hartmeier, w., Tegge, G., Starch, l!• 348 (1979)

10. Richter, G., Heinecker, H., Starch,;!_!, 418 (1979)

11. Kuster, B.F.M., private communication

12. Mehltretter, C.L., Alexander, B.H., Rist, C.E., Ind. Eng.

Chem., !2_, 2782 ( 1953)

13. Yufera, E.P., Easas, C.A., Carrasco, A.A., Rev. Agroquim.

Technol. Alimentos, !• 40 (1961) i C.A. 57, 16384g (1963)

14. Mustakas, G.C., Slatter, R.L., Zipf, R.L., Ind. Eng. Chem.,

46, 427 (1954)

15. Peters, H., Dutch Patent, 99,202 (1961)

16. Heesen, J., Dutch Patent, 7,215,180 (1972)

17. Van der Steen, H.C., Internal report, University of Techno-

logy, Eindhoven, The Netherlands (1974) 18. Chemisch Weekblad, 72 (24) , 1 ( 1976)

19.

20.

21.

22.

23.

24.

25.

Chemisch Weekblad, 73 (30/31), 1

Van Reede, D.' Chemisch Weekblad,

ibid., 77, 353 ( 1 981)

ibid.' 78, 139 ( 1 982)

ibid., 78, 214 (1982)

ibid. I 78, 330 ( 1982)

ibid., 79, 225 ( 1983)

( 1977)

77, 336 ( 1 981 )

16

26. ibid, 22..1 379 (1982)

27. "Glucombinaat", Internal report, University of Technology,

Eindhoven, The Netherlands (1982)

28. Maurer, K., Schiedt, B., Ber., 66, 1054 (1933)

29. Dirkx, J.M.H., Ph. D. thesis, University of Technology,

Eindhoven, The Netherlands (1977)

30. Tramper, J., Luyben, K.C.A.M., Van den Tweel, W.J.J.,

Eur. J. Appl. Microbiol. Biotechnol., ..12 1 13 (1983).

17

Chapter 2

Literature Survey

2.1. Introduation

In this chapter we present a survey of the literature

concerning the oxidation of D-glucose to D-gluconic acid and

of D-gluconic acid to D-glucaric acid or 2-keto-D-gluconic acid.

Furthermore we will pay attention to some other routes for the

production of 2-keto-D-gluconic acid. Because of the commercial

importance of L-ascorbic acid (vitamin C) we also present

literature data on the production of 2-keto-L-gulonic acid, a

precursor of vitamin c. In this literature survey we mainly review those methods

of preparation that are of potential industrial interest. As we

have already pointed out in chapter 1, processes will be only

of interest if they are not too costly. In our survey, therefore,

we pay special attention to the use of air and gaseous oxygen as

oxidizing agents and to the selectivity of the various processes.

The oxidation reactions can in general be grouped in three

main processes: homogeneous oxidation, heterogeneous catalytic

oxidation, and biochemical oxidation. Each of which we discuss

shortly below.

18

Homogeneous oxidation

In the group of homogeneous oxidation we have· gathered

the non-catalytic oxidation with oxidizing agents other than

oxygen and the electrochemical oxidations.

For the oxidation of a hemiacetal or an aldehyde to an acid or a lactone we have, besides oxygen, in general the

following oxidizing agents to our disposal:

- halogens

- nitric acid - Ag! - CuII

- Fe!II

For the homogeneous oxidation of a primary hydroxyl to a

carboxyl, nitric acid or NOx is often used (119,120). In this

reaction the corresponding aldehyde is formed as an intermediate.

In general this type of oxidation is not so very selective be­

cause of concurring side- and consecutive reactions. E.g., with

D-gluconic acid the oxidation of the hydroxyls on c2 and c5 to

keto groups, followed by cleavage of the carbon chain causes

serious reduction of the selectivity towards L-guluronic acid.

The selective oxidation of one of the.secondary hydroxyl­

groups of a hexose to a carboxyl group is rather difficult. The

aldehyde (or hemiacetal) function is almost always oxydized

first, the primary hydroxyl groups thereafter. To avoid this,

these groups have to be protected first e.g. by the formation

of glycosides or acetals. This also goes for those secundary

hydroxyls which we don't want to be oxidized.

Oxidizing agents other than oxygen have the disadvantage

that they are relatively expensive and their products have to

be removed from the reaction mixture.

19

Heterogeneous catalytic oxidation

This group of reactions mainly consists of the noble-metal

catalized oxidations with oxygen. This procedure offers, to­

gether with the biochemical oxidation, the best possibilities

for application on a commercial scale. The selective oxidation of D-glucose to D-gluconic acid can be carried out with

palladium on a carrier in an aqueous solution. For the manu­

facture of D-glucaric acid platinum on a carrier is to be

prefered. The oxidation of the a-hydroxyl of D-gluconic acid

can only be carried out selectively, with platinum on a carrier,

if the other hydroxyls are protected.

Biochemical oxidation

Aerobic microorganisms usually oxidize their organic

substrates completely to carbon dioxide and water. During this degradative process, energy and intermediary metabolites re­

quired for biosynthesis are generated. Under special circum­

stances, however, such as (i) an excess of carbon substrate in the growth medium, (ii) inhibition of certain metabolic path­

ways by the presence of inhibitory compounds and (iii} abnormal

physiological conditions (e.g. extremes of pH or temperature), oxidation of the substrate may be incomplete, leading to the

accumulation of intermediate metabolite in the medium. This type

of incomplete oxidation is not genotypically determined, but

simply reflects a changed phenotypic expression of the organism, induced by environmental conditions.

Microorganisms have been described, which possess only a very limited capacity to oxidize certain substrates, more or

less independent of culture conditions. In many cases, these organisms are not even able to assimilate carbon from the sub­

strates that they convert, and are able to grow only at the

expense of other organic nutrients present in the medium. Many of these so-called "microbial transformations" are

20

carried out by enzymes, that may be present constitutively

or induced by the substrate. On the other hand they may be

effected by other "essential" enzymes of intermediary meta­

bolism acting non-specifically. A survey of the enormous

diversity in oxidative microbial transformations has been

published by Kieslich (1) in 1976.

An important group of aerobic bacteria, which are parti­

cularly characterized by their ability to oxidize organic

substrates incompletely, are the acetic acid bacteria. These

organisms have been used since ancient times f.or the manu­

facture of vinegar. In this connection especially members of

the genus Gluconobacter are known for their relatively rapid

and imcomplete oxidation of a wide range of organic compounds

and the near quantitative excretion of the oxidation products

into the reaction medium. Today, commercial biochemical

processes, such as the production of L-sorbose from D-glucitol

and D-gluconic acid from D-glucose, are carried out with mem­

bers of this genus.

Besides bacteria, fungi are used for the selective oxidation

of monosaccharides. For the manufacture of D-gluconic acid from

D-glucose fungi of the genera Aspergillus and Penicillium are

used.

In general, biochemical oxidations take place in a narrow

pH-range at about 30°C in aerated substrate solutions containing mycelia together with a number of nutrient salts. The process

requires relatively long reaction times and is sensitive to

contamination. The isolation of the products is generally

rather complicated and expensive. This is the main reason why

at present much research is devoted to the immobilization of

the active enzyme species of the fungi and bacteria.

2.2. Oxidation of D-gZucose to D-gZuconic acid

The oxidation of aldoses to the corresponding aldonic

acids has been the subject of numerous publications (2-5),

some of which are related to preparative methods on a labo­

ratory scale only.

2.2.1. Homogeneous oxidation

Considerable attention has been given to studying the

mechanism and kinetics of the oxidation by means of halogen

compounds. In acid solution the free halogen or hypohalous

acid is the active oxidant, whereas in alkaline media the

hypohalous anion plays the major role (6). The most widely

21

used homogeneous method is oxidation with bromine in aqueous

solution having been first used by Hlasiwetz in 1861 (7). The

hydrobromic acid formed as a by-product lowers the rate of

oxidation. To minimize this effect buffered solutions (pH 5-6),

are used, or barium carbonate or barium benzoate is added to

the system (8). According to Isbell and Pigman (9), the

primary oxidation product from the reaction of D-glucose with

bromine in the presence of barium carbonate is D-glucono-o­

lactone. Grover and Mehrotra (10,11) found that the oxidation

of D-glucose to D-gluconic acid by means of bromine in a

strongly alkaline solution can be described as a bimolecular

second order reaction between the monosaccharide and the

hypobromite ion. From the influence of the pH on the reaction

rate, it is concluded that the hypobromite ion is the actual

oxidizing agent. Analogous conclusi9ns have been reported by

Ingles and Israel (12,13) for hypoiodite oxidations. More

recently, Perlmutter-Hayman and Persky (14) concluded from the

dependence of the reaction rate on the molecular bromine

concentration that this species is the oxidizing agent.

22

The dependence of the reaction rate on pH can be explained by

the assumption that the anionic form of glucose is more

reactive than the glucose molecule.

Extensive kinetic studies on the oxidation of D-glucose

in acidic chlorine solutions has been reported by Lichtin and

Saxe (15), Grillo (16), and Urquiza (17).

Processes have been patented in which glucose is oxidized

by bromine-bromate (181 and by bromic acid together with sodium

chlorate (19). Biniecki and Moll (20) reported the oxidation

by potassium chlorate.

The main drawback of the above processes is the difficulty

of separating the gluconate from the large amounts of salts

and the regeneration of the letter. This disadvantage is partly

overcome by indirect electrolytic oxidation in which bromine

or iodine is formed electrolytically from a small quantity of

the hydrohalic acid (20-28). Recently yields of 77% (29) and 70% (30) have been reported. 'l'he direct electrooxidation of

D-glucose to D-gluconic acid on Pt electrodes has been studied

by Rao and Drake (31) in neutral solution.

Besides the oxidation with halogens, other homogeneou~

methods have been described (2). As they are of no great

industrial importance, they will not be discussed here.

2.2.2. Biochemicai oxidation

This is nowadays one of the most widely applied industrial

procedures for manufacturing D-gluconic acid. This acid, the

simplest oxidation product of glucose, is produced by many

microorganisms, particularly by bacteria of the Acetobacter

and Pseudomonas genera and by molds of the Penicillium and

Aspergillus genera. Previous publications (32,33) have re­

viewed some of these oxidations, which will not be discussed

in detail here.

As early as 1880, Boutroux (34) described a biochemical

process for the selective oxidation of D-glucose to D-gluconic

23

acid. The first technical processes were based on surface

techniques with fungi (35). A number of methods based on this

principle were patented about 1930 (36-40), and subsequently

other batch-wise liquid-phase processes have been developed,

that use rotary fermentors (41-45). Aspergillus niger is often

used as the biologically active material. Other processes make

use of a vertical fermentor for which the active mycelium is

cultivated separately in a prefermentor (46). Concentrated

D-glucose solutions can be converted if borax is added to the

reactor to prevent early precipitation of calcium gluconate

(47). A semicontinuous process has been developed in which the

mycelium is separately used (48): after the conversion of one

batch, the mycelium can be separated from the solution by

flotation, so that about 80% of the liquid can be removed

without appreciable loss of active material.

Another method is separation of the mycelium by filtration

or centrifugation, after which it can be added to a fresh

glucose solution (49). In 1959 a continuous process was pa~

tented to produce D-gluconic acid monohydrate (50). In this

field much attention has been devoted to the study of various

types of enzyme-producing bacteria, the isolation of the

enzymes and the mechanism and kinetics of the reaction (51-67).

The following reaction-scheme is a combination of the work of

Gibson et al.(68) and Tsukamoto et al. (69).

1. E0

x + D-glucose + Ered glucono-6-lactone + Ered + glucono-

6-lactone

3. glucono-6-lactone + u2o + gluconic acid

The enzyme in step 1 and 2 is glucose oxidase. This enzyme

catalyzes a dehydrogenation of the glucose through the

24

formation of an enzyme-substrate complex which splits into

glucono-o-lactone and a reduced form of the enzyme. The latter

is oxidized again by dissolved oxygen and hydrogen peroxide is

formed. This peroxide is decomposed by the second vital enzyme

catalase. Glucono-o-lactone can hydrolyze to gluconic acid

either spontaneously or catalyzed by the enzyme gluconolactonase.

The rate-determining step in the overall reaction is dependent

on several factors and can be e.g. the formation of the complex

or the hydrolysis of the lactone.

In enzyme catalysis where the reaction is run in a homo­

geneous batch reactor, it is necessary to separate enzymes from

the reaction mixture at the end of the reaction, for example,

by ultrafiltration, affinity chromatography, etc. In order to

avoid these tedious recovery processes, increasing attention

has been given in recent years to the preparation, utilization,

and stability of immobilized enzymes (70-87). There are still

problems with the stability of the immobilized enzymes. n2o2 causes severe deactivation, and the intraparticle mass transfer

of oxygen can easily be rate-limiting, making the immobilized

enzymes less effective than the homogeneous enzymes. In general

the selectivity is very high (90-100%), but the reaction-rate

is rather low. Reactions still require at least several hours.

Another recent development in the field of biochemical

oxidation is the combined hydrolysis and oxidation of e.g.

sucrose (88), maltose (89), starch hydrolysate (90), molases

(90,91), and starch (92) for the manufacture of D-gluconic acid.

2.2.J. Heterogeneous catalytic oxidation

As early as 1861, von Gorup-Besanez (93) oxidized

mannitol in an aqueous alkaline solution in the presence of

platinum black to yield mannonic acid. In 1953 Heyns and co­

workers initiated an very extensive research program on the

selective oxidation of carbohydrates with oxygen by means of

noble-metal catalysis in alkaline solution. This work is

Ref .no. Author Reaction Catalyst [Cat] [Glucose l Glucose Reaction Yield Notes temp pH type conversion time

•c g/l mmol/l· % hr

( 100) Acres et al. 45 1%Pd/o.-Al 2o 3 1000 92 a)

( 101) Asahi Chem. Ind. 70 Pt/C 57 2 49 b)

{ H.'2) Buckley et al. 25-55 e-11 2%Pd/C 45 1000-2500 7-10 80-90

(103) Dirkx 45-65 9-10.3 5%Pt/C 500-1000 60-90 es a) ( 104) Hattori et al. 45-55 9.3-9.7 5%Pt/C 1.5 650 99.2 1. 7 94 (105) Heyns et al. 22 B-9 5%Pt/C 20 100 5-10 70

(99) Johnson Matthey 40-60 7-14 1%Pd/Al 2o 3 50-2000 90-100 90 al (106) Kao Soap lo. 5%Pd/C 94 (107) !<awaken F.C. Pd:Pt=J,5:1,5 6 800 14 93 ( 108) 'Kimura et al 40 9-10 2%Pd/C 1600 2 96 ( 109) Kiyoura et al. 70 7,0-7,5 Pd/C 1. 5 94 { 110) Nakagawa et al. 35 10 2%Pd/C 2500 10,5 88 c) ( 111) Nakayama et al. 50 l?d/C 1. 7 95 d) (112 I Nishikido et al. 50 5%Pd/C 15 95 61 2 56 b)

( 113) Nishikido et al. 70 21%Pb0/5%Pd/C 40 200 98 83 bl ( 114) Okada et al. 40 7-14 0,5%Pd/BaS04 3-7 50-300 30 0,1-0,3 el (97) Poethke 20 e Pd/MgO:Pd/BaS04 2500

( 115) Saito et al. 75-85 ~7 ~,5%Pd+1,5%Pt)/C 94 15 85 (116) De Wilt et al. 25-65 8-12 10%Pt/C 0-1,6 50-250 100 1-2 90 (117) De Wit et al. 25 13-14 5%Pt/C 10 70 97 0,67 96 fl

al Continuous tricklebed reactor bl Non-aqueous solvent c)1,3% o 3 in air as oxidizing-agent d) Reactor with circulating pipe el Stirred tank reactor + continuous multistage contactor

fl oxygen free + hydrogen. production

Table 2. 1.: Literature aonaerning the heterogeneous aata'tytia oxidation of D-gluaose to D-g'tuconic a aid

26

sununarized in three comprehensive reviews (94-96). They have

given selectivity-rules, which we will discuss in detail in

chapter 5. A catalyst prepared by reduction of chloroplatinic

acid with formaldehyde is reconunended as the most effective

for oxidizing glucose. The produced acids impede the reaction,

because the oxidation proceeds fastest at a pH of about 9.

To avoid this, pH-control by buffers, or (stepwise) addition

of hydroxide are applied.

In general, the selectivity of the platinum catalyzed

oxidation is lower than of the enzymatic processes. According

to Poethke (97), the selectivity can be affected by a conse­

cutive oxidative degradation of the produced D-gluconic acid -

probably by a Ruff mechanism. Furthermore, above pH 12 the

oxidative degradation of D-glucose becomes more important as

a non-platinum catalyzed side reaction. D-glucaric acid has been reported as an important consecutive reaction product depending

on the catalyst quality (98,99). For the selective production

of D-gluconic acid, this consecutive reaction has to be supres­

sed, e.g. by using palladium instead of platinum. A schematic

survey of the literature concerning the heterogeneous catalytic

oxidation of D-glucose to D-gluconic acid is given in Tabel 2.1.

The selective manufacture of D-glucono-o-lactone requires

oxidation in non-aqueous media (101,112,113). In aqueous media

the lactone would hydrolize spontaneously.

Table 2.1. shows that the oxidation of D-glucose to

D-gluconic acid with oxygen can be carried out selectively and

fast by means of a Pd/C catalyst. The highest selectivities

reported approach the biochemical ones. This is substantiated

by the recent start in Japan of the industrial production of

D-gluconic acid by means of a palladium catalyst (118).

27

2.3. Oxidation of D-gluaose or D-gluaonia aaid to D-gluaaria aaid

For the manufacture of D-glucaric acid, only two methods

are known, viz. the homogeneous oxidation with nitric acid, and

the heterogeneous catalytic oxidation with noble-metal catalysts.

As far as we are aware, no selective biochemical method for the

preparation of D-glucaric acid exists yet.

2.3.1. Homogeneous oxidation

D-glucose can be oxidized to D-glucaric acid with nitric

acid (119,120). Mustakas et al. (121) studied this process on

a pilot plant scale and obtained a yield of 44% (as K-H-gluca­

rate). According to Truchan (122), pretreatment of the glucose

with ammonia, followed by the oxidation with nitric acid, would

give a yield of 65%.

Another possible route for the manufacture of D-glucaric

acid is the oxidation of starch to polyglucuronic acid by N02 (123-125). Although glucuronic acid can be oxidized very selec­

tive to D-glucaric acid, yields are low, due to the extensive

degradation during the hydrolysis of the polymer.

2.3.2. Heterogeneous aatalytia oxidation

Platinum and palladium are used as catalyst for the

oxidation of aqueous solutions of carbohydrates with oxygen.

The use of a palladium catalyst for the further oxidation of

D-gluconic acid in alkaline solution leads to many degradation

products, including D-arabinonic acid, D-erythronic acid, and

no D-glucaric acid is obtained at all (97).

Among others, de Wilt (116) has studied the oxidation of

D-glucose to D-gluconic acid with Pt/C as catalyst. The maximum

selectivity for D-gluconic acid was about 95%, which was

obtained at a low pH (8) and low temperature (30°C) (116).

28

At a somewhat higher pH (pH 9-10) and/or temperature (55°C),

attack on the primary hydroxyl group at C-6 of D-gluconic acid

results; thus, a 55% yield of D-glucaric acid is obtained from

D-glucose (98,103,126).

2.4. Manufaature of 2-keto-D-gluaonia aaid

From the literature various methods for the manufacture

of 2-keto-D-gluconic acid are known (127). Those with D-glucose

or D-gluconic acid as substrate will be discussed in section

2.4.1. Some alternative methods, starting from other mono­

saccaride-derivatives, will briefly be discussed in section

2.4.2.

2.4.1. Oxidation of D-gluaoae or D-gluaonia aaid

Oxidizing-agents other than oxygen

Since the molecule of D-gluconic acid contains many

reactive groups, it is obvious that chemical oxydizing agents

must be highly selective in their action if they are to de­

hydrogenate only the second carbon atom. D-gluconic acid or its

lactones can be oxidized with chlorates in the presence of

vanadium pentoxide and phosphoric acid (128-132) to produce

2-keto-D-gluconic acid. When the oxidation is carried out in a

mildly acidic aqueous medium (pH between 3 and 4) after 40

hours a yield of 50% is obtained (130). Improvement of the yield and a simpler recovery of the product is possible by

the addition of a water miscible organic solvent which is sub-•

stantially inert to the oxidizing action of the chlorates in

the presence of the vanadium catalyst. Thus, ammonium-D-gluconate

is converted in an aqueous methanol (50%) medium in 24 hours

to the methyl ester of 2-keto-D-gluconic acid with a yield of

72% (131).

29

The same authors also patented the specific oxidation with

chromic acid (133). The oxidation is catalyzed by the addition

of small amounts of substances such as nickel, cerium, iron,

platinum and their salts. According to this patent, the oxida­

tion of D-gluconic acid with chromic acid in the presence of

feric sulphate at 0°C, yields 40% of 2-keto-D-gluconic acid

after 12 hours.

The electrochemical oxidation of D-glucose to D-gluconic

acid with bromide solution as the electrolyte, have been dis­

cussed in section 2.2. There was no evidence that the 2-keto

acid was formed as a byproduct. However, Pasternack and Regna

(134) have found that an electrolytic process involving the

combined action of a halide, other than an iodide, and soluble

chromium compounds will convert the aldonic acid to the corres­

ponding 2-keto-acid. The relatively small amount of chromium

required in this process compared to the above mentioned chromic

acid oxidation is of great advantage, because of the easier

purification of the product and the lower costs of the oxydizing

agent. Thus, the electrochemical oxidation of calcium-D-gluco­

nate with calcium bromide and chromium trioxide at 20°C gave a

yield of 80% of calcium-2-keto-D-gluconate after about 6 hours.

Oxygen as oxidizing-agent

In their comprehensive review of the heterogeneous cata­

lytic oxidation of carbohydrates with oxygen at a platinum

catalyst, Heyns et al. (96) conclude that for the oxidation of

the secondary hydroxyl groups of open-chain polyhydroxy mono­

saccharide-deri vates, almost no selectivity is to be expected.

This is in agreement with our observations. D-gluconic acid must

suitably be protected to direct the platinum catalyzed oxidation

to 2-keto-D-gluconic acid. Some examples of the oxidation of

protected monosaccaride-derivatives will be given in section

2.4.2. In thi~ thesis, however, we will describe a catalytical

method with which it is possible to oxidize D-gluconic acid

w 0

Ref.no. author reaction pH type of biocatalyst Conv. time yield notes temp % hrs % •c

(135) Agapova et al. Pseudomonas ( 136) Banik et al. Bacillus firmus

B. circulans B. subtilis

(137) Bernhauer et al. Bacterium gluconicum 80 (138) Bernhauer et al. A. suboxydans ( 139) Blais ten Ps. fluorescens a)

Ps. fragi a) Ps. reptilivora a)

( 14 0) Bull et al. Serratia marcescens NRRL B-486 a) ( 141) F!!rber 27 Cyanococcus chromospirans 20 .. 100 ( 14 2) F!!rber et al. Ps. chromospirans

Ps. aeruginosa ( 143) F'ewster A. suboxydans ( 14 4) Ikeda Ps. fluorescens a)

Serratia marcescens (145) Knobloch et al. A. orleanense 720 56

A. ascendens 720 39 (146) Kozhobekova et al. 5 100 12 (147) Kulhanek Ps. aeruginosa 74 b) (148) Lockwood et al. 30 Ps. aeruginosa 192 70 a) ,c)

Ps. fluorescens 82 948 88 949 84 142 75

frag11 4973 86 graveolens 4683 77

4684 82

Ref.no. author reaction pH type of b1ocatalyst time yield notes

t<o~P hrs %

30 Ps. mil de nberg i1 795 192 100 al ,cl oval1s 950 55

pavonacea 951 77

putida 4359 85 schuylk1111ensis 82 vendrelli 7700 81

( 149) Misenheimer 30 Serratia marcescens NRRL B-486 16-32 100 al (1501 Neijssel et al. Klebsiella aerogenes NCTC-418 al (151) Norris et al. Ps. aerug1nosa

(152) Pfeifer et al. Ps. fluorescens al Ps. fragi a) Ps, reptilivora a)

(153) Stoutharner A. suboxydans

(154) Stubbs et al. 25 Bacterium gluconicurn 25 82 al (155) Vondrova-Hovezova et al. Ps. chrornospirans

(1561 Yamazaki 5 Ps. fluorescens 168 40 d) (1571 l:'okosawa Ps. fluorescens a)

a) glucose oxidation instead of gluconic acid oxidation c) the numbers in the column yield are selectivities b) 10 strains of Ps aeruginosa are examined d) simultaneous oxidation of D-gluconate and L-idonate

A,~ Acetobacter B.= Bacillus Ps. Pseudomonas

table 2.2. Literature concerning the biochemical oxidation of D-gZucose or D-gZuconic acid acid to 2-keto-D-gluconic

w ....

32

to 2-keto-D-gluconic acid selectively, obviating the use of

protective groups.

Biochemical oxidation

Special bacteria are cultivated for the fermentative

oxidation of D-glucose or D-gluconic acid to 2-keto-D-gluconic

acid. A schematic survey of the literature concerning this

oxidation is given in table 2.2. In this table we again

encounter the characteristics of a biochemical process: the

yields are generally high, but the processes are slow. In

section 1.1. we already discussed this matter.

2.4.2. Aiternative oxidation methoda

Besides the oxidation of D-glucose or D-gluconic acid,

there are some alternative methods for the manufacture of

2-keto-D-gluconic acid:

- Oxidation of D-glucosone (D-arabino-hexos-2-ulose) with

bromine in water under the influence of light (158,159).

After 3-4 days at room temperature the yield is 68%.

- Direct oxidation of D-fructose, with oxygen in an aqueous

alkaline medium. Heyns (160) describes this reaction u~ing platinum as catalyst.(The analogous oxidation of L-sorbose

to 2-keto-L-gulonic acid has been the subject of more

investigations, as this product is a precursor of vitamin C).

- Oxidation of a D-fructose derivative substituted in such a

way that only the neighbouring ce2oe group remains free.

Thus, 2,3-4,5-di-0-isopropylidene-D-fructopyranose

(S - diacetone-D-fructose) is oxidized with potassium

permanganate to the diacetone derivate of 2-keto-D-gluconic

acid (161-163). The same oxidation can also be carried out

with air in aqueous alcohol with Pt/C as catalyst with a

yield of more than 90% in 2-5 hours (164).

None of these routes is commercially attractive.

33

2.5. Oxidation of L-gulonia acid to 2-keto-L-gulonic acid

The lead/platinum/carbon catalyst is also active in the

oxidation of L-gulonic acid to 2-keto-L-gulonic acid. The latter

product is a direct precursor of vitamin C, and for this

reason this oxidation step can be of great industrial impor­

tance. We want to find out whether our oxidation method can

compete with others. For comparison we will review the litera­

ture concerning the oxidation of L-gulonic acid to 2-keto-L­gulonic acid shortly:

- Oxidation with chl?rate in the presence of vanadium pentoxide and phosphoric acid. After 20 hours the yield

is 68% if the reaction is carried out in an aqueous

solution (130).

- Oxidation with chromic acid. The yield for 2-keto-L­

gulonic acid is 41% and the selectivity is about 70% after

24 hours of reaction (133).

- Electrochemical oxidation with a combination of mainly

bromide and a little chromium trioxide. No yield is

stated (134).

- Biochemical oxidation. Aerobic fermentation with Pseudo­

monas aeruginosa leads to a conversion of 44% after 8

days (165) and with Xantomonas translucens a yield of

minimal 85% is achieved after more than 72 hours at

28-30°C (166).

2.6. Disaussion

In section 1.6 we have given our motivation for investiga­

ting possibilities to improve the selectivity of the catalytic

oxidation of D-glucose to the commercially attractive products

34

D-glu~onic acid, D-glucaric acid and 2-keto-D-gluconic acid.

From the literature survey in this chapter it is clear that the

oxidation of D-glucose to D-gluconic acid can be carried out

with a high selectivity (~95%) either with the aid of enzymes

or with noble metal catalysts. Such a selectivity is not ob­

tained for the oxidation of D-gluconic acid to D-glucaric acid

or to 2-keto-D-gluconic acid, with two exceptions: The micro­

bial manufacture of 2-keto-D-gluconic acid and the electrochemi­

cal oxidation of calcium-D-gluconate to calcium-2-keto-D-gluco­

nate. We have already discussed the disadvantages of the bio­

chemical process in section 1.1. The latter process is slow

and makes use of relatively expensive oxidants. Therefore we

have directed our efforts towards improving the selectivity

of the catalytic oxidation of D-gluconic acid to either

D-glucaric acid or to 2-keto-D-gluconic acid with air as

oxidizing agent.

References

1. Kieslich, K., "Microbial transformation of non-steroid

cyclic compounds", Thieme Stuttgart, (1976)

2. Stanek, J., Cerny, M. , Kocourek, J. , Pacak, J., "The Monosaccharides", p 657, Academic Press, New York (1963)

3. Mehltretter, c., Starch,_!.~_, 313 (1963) 4. de Wilt, H., Ind. Eng. Chem. Prod. Res. Develop., .l..!.1 370

( 1972) 5. Theander, o. , "Carbohydr.: Chem. Biochem. (2nd Ed.) , 1 B,

1013 Ed. Pigman, w., Horton, D., Academic Press, New

York (1980) 6. Green, J.W., "The Carbohydrates", p. 336, W. Pigman, Ed.,

Academic Press, New York (1957)

35

7. Hlasiwetz, H., Ann., 119, 281 (1861)

8. Hudson, c.s., Isbell, H.S., J. Am. Chem. Soc., i:!_, 2225

(1929); Isbell, H.S., Methods in Carbohyd. Chem.,~' 13

(1963)

9. Isbell, H.S., Pigman, W., Bur. Standards J. Res., 1Q, 337

(1933)

10. Grover, K.C., Mehrotra, R.C., z. Physik. Chem. (Frankfurt),

.li1 345 (1958)

11. Mehrotra, R.C., Grover, K.C., Vijana Parishad Anusandhan

Patrika, i• 255 (1961); C.A. 59, 6493e

12. Ingles, O.G., Israel, G.C., J. Chem. Soc., 810 (1948)

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37

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67. Ghose, T.K., Ghosh, P., J. Appl. Chem. Biotechnol., ~'

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75. Takahara, H., Japan. Kokai 78 44,687 (Apr. 21, 1978)

76. Akulova, V.F., Vaitkevicius, R., Kurtinaitiene, B.,

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CA 89, 86 443u

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78. Stankovich, M.T., Schopfer, L.M., Massey, v., J. Biol.

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81. Marumatsu, K., Miura, K., Eguchi, C., Misono, K., Japan. Kokai 78 56,385 (May 22, 1978)

82. Liu, w., Wang, s., Su, Y., Proc. Natl. Sci. Counc.,

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85. Fedoseev, V.N., Treifeldt, E., Tr. Tallin. Politekhn.

39

In-t, 1981, 125 (1981) 1 CA 97, 106 236z

86. Liu, W.H., Chitin Chitosan, Proceedings Int. Conf., 2nd,

1982, 144 (1982)

87. Tramper, J., Luyben, K.C.A.M., Van der Tweel, W.J.J.,

Eur. J. Appl. Microbiol.Biotechnol., .!2, 13 (1983)

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CA J..2, 21 923h 89. Cho, Y.K., Bailey, J.E., Biotechnol. Bioeng., .!2_, 185 (1977)

90. Kundu, P.N., Das, A., Biotechnol. Lett., ii 365 (1982)

91. Sheikh, N.M., Joarder, G.K., Majeed, A., Haroon, S.N.,

Kathoon, M., Sci. Res. (Dacca, Pak.),.§_, 321 (1969)

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(Taiwan), !Q., 143 (1977)

93. Gorup - Besanez, E. von, Ann., 118, 257 (1861)

94. Heyns, K., Paulsen, H., Angew. Chem., §.2_, 600 (1957)

95. Heyns, K., Paulsen, H., Adv. Carbohyd. Chem., ..!2 1 169 (1962)

96. Heyns, K., Paulsen, H., Ruediger, G., Weyer, J., Fortschr.

Chem. Forsch, 1.! 1 285 (1969)

97. Poethke, W.,Pharmazie, ii 214 (1949)

98. Mehltretter, C.L., Rist, C.E., Alexander, B.H., U.S. Patent 2,472,168 (June 7, 1949)

99. Johnson, Matthey and Co. Ltd., Dutch Patent 6,713,891

(Oct. 12, 1967)

100. Acres, G.J.K., Budd, A.E.R., Brit. Patent 1,208,101 (Oct 7, 1970)

101. Asahi Chemical Industry Co., Ltd., Jpn Kokai Tokhyo Koho 80 47,672 (Apr 4, 1980)

102. Buckley, J.S., Embree, H.D., Brit. Patent 786,288 (Nov 13, 1957)

103. Dirkx, J.M.H., Ph.D. thesis, University of Technology,

Eindhoven, The Netherlands (1977)

104. Hattori, K., Miya, B., Matsuda, M., Ishii, M., Saito, H.,

Watanabe, H., Takizawa, H., Japan. Kokai 78 40,713 (Apr 13, 1978)

105. Heyns, K., Heinemann, R., Ann., 558, 187 (1947)

40

106. Kao Soap Co., Ltd., Belg. Patent 851,804 (Jun 16, 1977)

107. Kawaken Fine Chemicals Co., Ltd., Jpn. Kokai Tokhyo Koho

JP 58 72,538 (83 72,538) (Apr 30,1983)

108. Kimura, T., sugiura, T., Kiyoura, T., Japan. Kokai 76

63,12.1 (Jun 1, 1976)

109. Kiyoura, T., Kimura, T., Sugiura, T., Japan. Kokai 76

52,121 (May 8, 1976)

110. Nakagawa, T., Murai, Y., Kazai, N., Japan. 73 30,618 (Sept

21, 1973)

111. Nakayama, M., Kimura, A., Eguchi, H., Matsui, T., Eur. Pat.

Appl. EP 48,974 (Apr 7, 1982)

112. Nishikido, J., Tamura, W., Fukuoka, Y., Jpn. Kokai Tokhyo

Koho 80 40,606 (Mar 22, 1980)

113. Nishikido, J., Tamura, N., Fukuoka, Y., Ger. Offen. 2,

936,652 (Apr 3, 1980)

114. Okada, J., Morita, s., Matsuda, Y., Takenawa, T., Yakugaku

Zasshi, 87, 1326 (1967); CA 68, 96063a

115. Saito, H., Nozue, M., Jpn Kokai Tokhyo Koho 80 07,230

Jan 19, 1980)

116. De Wilt, H.G.J., Ph.D. thesis, University of Technology,

Eindhoven, The Netherlands (1969); De Wilt, n.G.J., van der

Baan, h.S., Ind. Eng. Chem., Proc. Res. Develop., 1.1.• 374 (1972)

117. De Wit, G., de Vlieger, J.J., Rock-van Dalen, A.C.,

Kieboom, A.P.G., van Bekkum, H., Tetrahedron Lett., 1978,

1327 (1978)

118. Kuster, B.F.M., private communication

119. Mehltretter, C.L., Rist, C.E., U.S. Patent 2,436,659

(1948)

120. Bose, R.J., Hullar, T.L., Lewis, B.A., Smith, F., J. Org.

Chem., 3.§. 1 1300 (1961); U.S. Patent 2,809,989 (1958)

121. Mustakas, G.C., Slotter, R.L., Zipf, R.L., Ind. Eng. Chem.,

.!§_, 427 (1954)

122. Truchan, A., U.S. Patent 2,809,989 (1957)

123. Graefe, G., Starch, ~, 205 (1953)

41

124. Heyns, K., Graefe, G., Chem. Ber., 86, 646 (1953)

125. Kozai, Y., Horiguchi, N., Mizuno, T., Nuzu, R., Kobunski

Kagaku, .!2• 461 (1960); CA 55, 21631d (1961)

126. Dirkx, J.M.H., van der Baan, H.S., van den Broek, J.M.A.J.J.,

Carbohydr. Res., 59, 63 (1977)

127. Stanek, J., Cerny, M., Kocourek, J., Pacak, J., "The

Monosaccharides", p722, Academic Press, New York (1963)

128. Regna, P.P., Caldwell, B.P., J. Am. Chem. Soc., 66, 243

(1944)

129. Isbell, H.S., J. Res. Natl. Bur. Std., 33, 45 (1944)

130. Pasternack, R., Regna, P.P., U.S. Patent 2,188,777

131.

132.

133.

134.

(Jan 30, 1940)

Ibid., U.S. Patent

Ibid., U.S. Patent

Ibid., U.S. Patent

Ibid., U.S. Patent

2,203,923

2,207,991

2,153,311

2,222,155

(Jun 11 I 1940)

(Jul 16 I 1940)

(Apr 4, 1939)

(Nov. 19, 1940)

135. Agapova, E.V., Goucharova, L.A., Kapterova, Yu. v., Kozhobekova, K.K., Rubtsov, I.A., Pomortseva, N.V.,

Tarnopol'skaya, I.P., Gofman, L.Kh., U.S.S.R. Patent

603,659 (Apr 25, 1978)

136. Banik, s., Dey, B.K., Indian Agric., 22, 93 (1978)

137. Bernhauer, K., Gorlich, B., Biochem., z., 280, 767 (1937)

138. Bernhauer, K., Knobloch, H., Biochem. Z., 303, 308 (1940)

139. Blaisten, Rev. Asoc. Bioquim. Arg., ..!_!, 181 (1947)

140. Bull, D.N., Young, M.D., Biotechnol. Bioeng, ~. 373 (1981)

141. Farber, G., Sbornik Ceskoslov. Akad. Zemedelske, ~, 355

(1951); CA .i2_, 9 605a

142. Farber, G., Vondrava, o., Luksik, B., Liebster, cs. Mikro­

biol., l• 133 (1958); CA .?_1, 7320

143. Pewster, J.A., Biochem. J., 68, 19P (1958); Ibid., 69,

582 (1958)

144. Ikeda, J. Agric. Chem. Soc. Japan, 24, 56 (1950} 1 CA 195_li

7189

145. Knobloch, H., Tietze, H., Biochem. z., 309, 399 (1941}

146. Kozhobekova, K.K., Kaptereva, Yu. v., Agapova, E.V.,

~oncharova, L.A., Tarnopol'skaya, I.P., V'yunova, G.M.,

42

Deposited Doc. 1976, VINITI 3540-76; CA 89, 127 687x

147. Kulhanek, M., Chem. Listy, fl, 1071 (19531 ibid., 1081 (1953)

148. Lockwood, L.B., Tabenkin, B., Ward, G.E., J. Bacteriol.,

42, 51 (1941)

149. Misenheimer, T.J., U.S. Patent 3,282,795 (Nov 1, 1966)

150. Neijssel, O.M., Tempest, D.W., Arch. Microbiol., 105, 183

( 1975)

151. Norris, F.C., Campbell, J.R., Can. J. Res., 27C, 157 (1949)

Ibid. I 1 6 5 ( 1 9 4 9)

Ibid., 253 (1949)

Ibid., 28C, 203 (1950)

152. Pfeifer et al., Ind. Eng. Chem., 50, 1009 (1958)

153. $touthamer, A.H., Ph. D. thesis, University of Utrecht,

The Netherlands (1960)

154. Stubbs, J.J., Lockwood, L.B., Roe, E.T., Tabenkin, B.,

Ward, G.E., Ind. Eng. Chem., 32, 1626 (1940)

155. Vondrova-Hovezova et al., Csl. Biol., li 99 (1954); CA

1954, 9469

156. Yamazaki, M., J. Fermentation Technol.,1J_, 86 (1953);

Ibid., 126 ( 1953)

Ibid., 230 (1953)

157. Yokosawa, J. Agric. Chem. Soc. Japan, 26, 415 (1952)

158. Neuberg, c., Kitasato, T., Biochem. z., 183, 485 (1927)

159. Kitasato, T., Biochem. z., 207, 217 (1929)

160. Heyns, K., Liebigs Ann. Chem., 558, 177 (1947)

161. Ohle, H., Berend, G., Ber., 60, 1159 (1927)

162. Ohle, H., Wolter, A., Ber., 63, 843 (1930)

163. Ohle, H., Kohler, I.; Berend, G., Ber., 68, 2577 (1935)

164. Csuros, Z., Petro, J., Fogassy, E., Lengyel, A., Period.

Polytech., Chem. Eng., l§_, 167 (1974)

165. Perlman, D., U.S. Patent 2,917,435 (Dec 15, 1959)

166. 1ata, D.A., U.S. Patent 4, 155,812 {ll·:ay 22, 1979)

43

Chapter 3

Analysis

3.1. IntPoduction

For the study of the kinetics of a reaction, its reaction

network, and its selectivity, a fast and accurate analysis of

all the reaction products is a prerequisite. Because the oxi­

dation of D-gluconic acid shows many ramifications, much

attention had to be paid to the analytical aspects of our

investigation. For the noble metal catalyzed oxidation of

D-glucose or D-gluconic acid in aqueous medium the following

products can be expected (1-4). (In Appendix I the structure

formulas are givenl:

(a) c1 , c6 oxidation products: D-gluconic acid, D-glucose

dialdehyde, L-guluronic acid, D-glucaric acid and

D-glucuronic acid

(b) keto carboxylic acids: especially 2- and 5-keto-D-gluconic

acid

(c) products of oxidative c-c bond rupture: c1-c5 monocarboxylic

acids, c2-c5 dicarboxylic acids and carbon dioxide

(d) isomerisation products ( pH ~ 12): D-fructose and D-mannose.

The analysis of the various products has received only

little attention in the literature. No suitable methods for

qualitative determination or separation are given, let alone

their quantification. Verhaar and De Wilt (1,5) developed a

useful gas liquid chromatographic procedure. However, this

procedure requires a very time consuming derivatization

44

(silylation) of the products and therefore can not be auto­

mated. Moreove4D-glucaric acid could not be determined

properly. For these reasons this method was discarded.

Dirkx and Verhaar (2,6) developed a liquid chromatographic

procedure based on ion-exchange chromatography, allowing the

main oxidation products to be determined. We have used an

automated and modified procedure based on this procedure, as

described in section 3.2.

Occasionally we have used preparative liquid chromatography

(section 3 .. 3.) for the separation of certain components out of

the reaction mixture and 13c~nuclear magnetic resonance spec­

troscopy (section 3.4.) for their identification.

Dirkx (2) also described an isotachophoretic procedure for

the separation of the oxidation products. Occasionally we used

a modification of this method to obtain additional information

(section 3.5.).

A specific detection method for u-keto acids (section 3.6.)

was applied to prove the presence and estimate the concentration

of various u-keto acids.

3.2. Ion-e~change chromatography

3.2.1. Introduction

A review of ion-exchange chromatography of carboxylic acids

is given by Jandera and Churacek (7).

In order to improve the separation we replaced Dirkx and

Verhaar's (6) single eluant, a sodium sulphate solution, by a

series of two eluants. The first was a sodium chloride solution,

which gives a good separation of the monocarboxylic acids, but

takes too much time for the dicarboxylic acid elution. For this

we switched, after the elution of the monocarboxylic acids, to

magnesium chloride, which gave a satisfactory separation and

elution time for the dicarboxylic acids, as suggested by Lee and Samuelson (8).

3.2.2. Experimental

45

Table 3.1. summarizes the apparatus and experimental

conditions used for the analysis of our reaction samples, and

fig. 3.1. shows a block-diagram of the liquid chromatograph.

eluant A eluant B eluant C

4-way valve

pump

static + dynamic mixer

r--I injection-valve

I I pre-column

I analytical

.., I

I I I I I column ___ J L ___

UV-detector

automatic sampler

column oven

integrator/ recorder

,_x_r_-_de_t_e~c_t_or __ _J --1 recorder

waste

Figure 3.1. Block diagram of the analytical chromato­graphic system

The columns were slurry-packed at room temperature with a sus­

pension of the ion-exchange resin in a 0.125 M NaCl solution.

A strong basic anion exchange resin serves as column material

(type Aminex A-27 or Alltech Anion Exchange Resin BA-X8).

For pretreatment the samples only needed filtration over

a Millipore type HA filter (0.45 µ).Continuous UV-detection

at 212 nm and, occasionally, differential refractive index

(RI)-detection were used.

46

liquid chromatograph detectors

data-system pre-column dimensions separation-column dimensions:

column-material

column-temperature injection-volume eluant A eluant B eluant-degassing flow program

Spectra Physics type SP 8100

variable wavelength UV/VIS detector, Spectra Physics type SP 8400, detection at

212 nm. (Occasionally) differential refrac­tive index detector, Waters type R 401 Spectra Physics type SP 4100 75 mm x ll 4.6 mm 250 mm x ll 4.6 mm

strong basic anion exchange resin, Biorad

type Arninex A-27 (particle diameter 12-15µ) or Alltech type Anion Exchange Resin BA-XS (particle diameter 7-10µ) as•c 10 µ1

0.125 M NaCl solution

0.0875 M Mgc1 2 solution helium method

time eluant

(min)

0-19 A 19-38 B 38-45 A

flow (ml/ min)

1.0 1.1

1.0

table 3.1. Apparatus and experimental conditions of the ahromatographia system

The. molecular UV response depends on the interaction of

various functional groups within tbe molecule, whereas the

molecular RI response is roughly proportional to the molecular

mass. Therefore, especially the ratio of the UV- and RI-signal

gives valuable information for the identification of the peaks

in the chromatograms.

The (off-line) analytical system operated automatically

and was programmed in such a way that after 5 reaction samples

2 calibration samples were introduced.

3.2.3. Typiaal results

Figure 3.2. shows a chromatogram of a calibration sample.

The upper curve shows the UV-signal and the lower one the RI­

signal. A good separation of the components of the calibration

samples is obtained. Especially the dicarboxylic acids are very

well separated when compared to the results of Dirkx and

Verhaar (2,6).

5 4

6

1ii 7 c:: O> ·;;; 3 8 > ::::>

a:

0 10 20 30 40

time (min) --

figure 3.2. Chromatogram (UV- and RI-eignat) of a aatibration sampte

47

1: D-gtuaonia aaid, 2: D-gataaturonia aaid, 3: D-gtuauronia aaid, 4: 2-keto-L-gutonia aaid, 5: o~aiia aaid, 6: tartro­nia aaid, 7: D-giuaaria aaid, 8: tartaria aaid

The UV-signal shows some discontinuities denoted by arrows.

These are due to programmed baseline corrections. The baseline

drift is caused by the eluant- and flow programming.

The dicarboxylic acids could not be detected by the RI­

detector, due to the difference in refractive index of the NaCl-

48

and the MgC1 2 solution, causing too much shift of the baseline.

In the calibration samples D-galacturonic acid is used

for the calibration of L-guluronic acid, because the latter was

not available in a pure form. We have identified L-guluronic

acid with the aid of a sample containing L-guluronic acid and

D-mannuronic acid, kindly supplied by Mr. Schols of the

Wageningen University of Agriculture.

For the calibration of 2-keto-D-gluconic acid (2KGOZ) and

5-keto-D-gluconic acid (SKGOZ) we used 2-keto-L-gulonic acid

(2KGUZ) to save costs. We have determined the ratios of the

molar responses of 2KGOZ to 2KGUZ and of SKGOZ to 2KGUZ. The

results are summarized in table 3.2.

2KGOZ SKGOZ 2KGUZ 2KGUZ

peak area 1.22 0.88

peak height 1. 20 0.86

table 3.1. Ratios of the peak heights and peak areas of 2-keto-D-gluconic acid to 2-keto-L-gulonic acid, and of 5-keto­D-gluconic acid to 2-keto-L-guZonic acid

Figure 3.3. shows the calibration curves (peak area versus

concentration) of 4 key components. As is seen in this figure,

a non-linear relationship between peak area and concentration

is obtained. The following relation is used to calculate the

concentration of the various components in a reaction sample:

where:

C = concent,ration, A peak area, and a and b are constants

The constants a and b (0.9 - 1.1) in the above formula are

calculated with the least-squares-method.

200

.::::: 0 1150 c: .2 100 i ... t: ~ c: 50

8

49

o D-Gluconic acid

~ 2-keto-D-Gluconic acid <> Oxalic acid a D-Glucaric acid

o.pc:::.:.......,...~-..~.._,,...-~..-~ ....... ~-..-_j. 0 80 160 240

peak area (arbitrary units)

figure 3.3. Calibration aurves of D-gluaonic acid, 2-keto-D-gluconic acid, oxalia acid, and D-glucaric acid

Figure 3.4. illustrates a chromatogram of a sample of the

oxidation of D-gluconic acid with Pt/C as catalyst. The identi­

fication of the components in this - and following chromato­

grams is based on three methods, i.e. liquid chromatography

(this section), preparative l~quid chromatografphy in combi­nation with 13c-nuclear magn~tic resonance spectroscopy (section

3.3. and 3.4.), and isotachophoresis (section 3.5.)

Besides D-gluconic-, 4-guluronic- and D-glucaric acid, viz. the.reactant, the intermediate and the main oxidation product, the following by-products are identified: the monocarboxylic

acids with c 4 up to c 1 , viz. D-erythronic-, D-glyceric -gycolic- and formic acid, the dicarboxylic acids with c 4 up to c 2 , viz. tartaric-, tartronic- and oxalic acid, and the keto­acids 2- and 5-keto-D-gluconic acid. We have not determined the

stereochemistry of the mono- and dicarboxylic acids.

However, as we think that these products mainly arise from

oxidative cleavage of the carbon chain by which at both sides

of the cleavage a carboxylic acid group is formed, the mono­carboxylic acids must have a stereo chemistry corresponding

50

-;;; c: Ol

"iii

> :::>

-;;; c: .Ql fl)

a:

2

0 10

8

10

9 11

! t

20 30 40

time (min)

figuPe J.4. ChPomatogPam (UV- and RI-signal) of a sample of the oxidation of D-gluoonio aoid ~ith a Pt/C aatalyst

1: D-gluoonio aoid, 2: L-guluPonio acid, J: 5-keto­D-gluconic acid + D-epythPonic acid + D-glycePio acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5,8: not identified, ?: foPmic acid, 8: oxalic acid, 9: taPtPonic acid, 10: D-glucaPic acid, 11: taPtaPic acid

to D-gluconic acid.

Figure 3.5. illustrates a chromatogram of a reaction sample

of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst.

Comparison of this chromatogram with the previous one shows a

Cii c: .2' <I)

> :::>

Cii c: .2' <I)

a:

51

4

10

0 10 20 30 40

time (min) -

figure J.5. Chromatogram (UV- and RI-signal) of a sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst

1: D-gluoonio aoi~ 2: L-guluronio aoid, 3: 5-keto-D­gluoonio aoid, 4: 2-keto-D-gluoonio aoid, 5: not iden­tified, 6: formio aoid, ?: oxaZio aoid, 8: tartronio aoid, 9: D-glucario acid, 10: a-keto-D-glucaric acid

marked difference in product composition. Here the main product

is 2-keto-D-gluconic acid and the by-products are L-guluronic-,

D-glucaric-, 5-keto-D-gluconic-, formic-, oxalic-, tartronic­

and a-keto-D-glucaric acid.

52

3.3. Preparative ion exchange chromatography

3.3.1. Experimental

For preparative ion exchange chromatography a large injec­

tion volume is used on a separation column with a high capacity.

The instrument and experimental conditions are described in

table 3.3.

pump

injection-valve

injection volume column-dimensions column-material

column-temperature

detection

eluant A eluant B flow-program

Orlita membrane pump type DMP/AE-10-4. 4

Rheodyne type 7010 2 ml

250 x ill 12 mm

stron9 basic anion exchange resin

Biorad type AG1-X8 {paricle diameter < 63 ~)

es•c UV-detection at 216 nm with a variable wavelength UV-detector Pye Unicam type LC3 0.25 M NaCl-solution 0.15 M MgC1 2-solution

time eluant flow {min) (ml/min)

0-50

50-80 80-100

A

B

A

3,3 3,3

3,3

table 3.3. Apparatus and experimental conditions of the self-assembled preparative liquid chromatographic system

The fractions containing the desired product are collected

from 5-10 injections. The product is then separated from the

excess of salt from the eluant by the following procedure:

Acidification with hydrochloric acid to pH 2, evaporation to

dryness in a film evaporator at 50°C and reduced pressure, ex­

traction of the residue with methanol, filtration of the salt

residue, evaporation of the methanol to dryness in a film eva­

porator, addition of water and adjusting the pH to 7. The

products in these solutions are identified by 13c-NMR.

53

S.S.2. Typical t>esuite

A reaction mixture of the oxidation of D-gluconic acid with

a Pb/Pt/C catalyst was first concentrated three 'fold in a film evaporator. From each of 5· injections of this concentrate

the last 70% of the peak containing the 2- and 5-keto-D-gluconic

acid was collected and worked up. Normal analysis (as described in section 3.2.) now produces the chromatogram of figure 3.6.

I I

a:

4

0 10 20 30 40

time (min) -

figure S.6. Chomatogram (UV- and RI-signal) of a fraction collected from a reaction mixture of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst

1: D-gluconic acid, 2: L-guluronic acid, S: 5-keto-D­gluconic acid + D-glyceric acid + D-erythronic acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5: not identified, 6: oxalic acid

54

Comparison with the chromatogram of the starting product

mixture (figure 3.7) clearly shows the effect of the chroma­

tographic purification and improved peak resolution. The

refined sample was also analyzed with 13c-NMR (section 3.4.)

and isotachophoresis (section 3.5.).

iii c: Cl ·o;

a:: 4

0 10

7

20 30 40

time (min) -

figure 3.7. Chromatogram (UV- and RI-signal) of a sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst

1: D-gluconic acid, 2: L-guluronic acid, 3: 5-keto­D-gluconic acid + D-glyceric acid + D-erythronic acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5: not identified, 6: formic acid, 7: oxalic acid, 8: tartronic acid, 9: D-glucaric acid, 10: tartaric acid, 11: a-keto-D-glucaric acid

55

3.4. 13c- nuaiear magnetia resonanae epeatroeaopy

3.4.l, Introduation

Natural abundance carbon-13 nuclear magnetic resonance

c13c-NMR) spectroscopy is increasingly being utilized for the investigation of carpohydrates. Recent improvements in instru­

mentation have successfully overcome the inherently low sensi­

tivity of 13c-NMR experiments on non-enriched samples which contain, of all the carbon present, only about 1.1% carbon-13.

The present day experimental technique takes advantage of stable

spectrometers, wide-band proton decoupling and pulsed Fourier

transform techniques. A considerable advantage of 13c-NMR

spectroscopy is the large range of chemical shifts. Resonance

frequencies for most organic molecules, including carbohydrates,

are spread over 200 ppm. Additionally, with complete proton decoupling each magnetically non-equivalent carbon appears

as a sharp single line and individual lines are resolvable if

separated by only 0.1 ppm. such considerable resolving power

renders 13c-NMR an effective tool for investigating subtle structural differences and provides a convienient method for

the analysis of complex mixtures. These considerations made us apply this technique for the identification of certain reaction products in the complex reaction mixture.

3.4.2. Experimentai

Proton-decoupled, natural abundance-carbon-13, pulse Fourier­

transform NMR spectra were recorded with a Bruker WM-250 ( 63 MHz) or a Bruker CXP-300 (75.6 MHz) spectrometer. Spectra were

recorded at ambient temperature by using the deuterium resonance

56

of acetone-D6 (external standard) as the lock signal and the

Me4Si (external standard) as reference signal. Sample tubes

of 10 nun diameter were used. Typical measurement conditions

were: number of scans 5000-6000, data points 16K zero-filled

to 32K before Fourier transformation, sweep width 20 KHz and

repetition time 10 s.

3.4.3. Typical re8ults

In figure 3.8. the 13c-NMR spectrum is given for the sample

used for the chromatogram of figure 3.6. (section 3.3.2.). This

spectrum is rather complex, mainly due to the various tautomeric

forms of two of the components of the mixture. Using data

published by Crawford et al. (9) the chemical shifts arising

from the four tautomeric forms of 2-keto-D-gluconate and the

three tautomeric forms of 5-keto-D-gluconate could be identi­

fied and with the aid of a spectrum of D-gluconate (10) also

the chemical shifts of this component could be assigned. Of the

remaining 13 smaller signals, 3 further signals could be assig­ned, as their integrals were of the same order of magnitude,

and at least a factor 2 higher than those of the remainder.

These 3 signals can be ascribed to a -COOH group, a ~ CHOH

group and a -cu2oH group. Combination of this information with our postulate of the oxidative cleavage of the reaction products (section 3.2.3.) leads us to the conclusion that these three

signals belong to D-glyceric acid.

The remaining signals all are rather small and of the

same order of magnitude, so that no further assignments could

be made. These signals are supposed to represent by-products

with a relatively low concentration. This is in agreement with

our isotachophoretic analysis of this sample. Below the various tautomeric forms of 2- and 5-keto-D­

gluconic are shown and in table 3.4. a survey of the chemical

shifts of the components of the above described sample is given.

84 60

8 (ppm)

180 160 140 120 100 BO 60

8 (ppm)

figure 3.8. 13

C-NMR spectrum of a fraction of a sample of the oxidation of D-gZuconic acid with a Pb/Pt/C-cataZyst

58

Tautomeric forms of 2-keto-D-gluconic acid:

! ~ a-pyranose B-pyranose

HOH2V0~ooli

~µOH OH H

HOH2v .. O-~ OH

H~COOH OH H

! a-furanose e-furanose

Tautomeric forms of 5-keto-D-gluconic acid:

Hv.O~ooH HOH2~µH

Oil H

§. a-furanose

COOH I

H-C-OH I

HO-C-H I

H-C-OH

' C=O I

CH 20H

l open chain form

HOH2v.O~H HOµCOOH

OH H

i B-furanose

The D-gluconate ion only exists in the open chain form.

59

Compound chemical shift (ppm)

c, c2 c3 c4 cs c6

D-gluconic acid open chain form 178;3 73.9 72.6 71.1 71.6 62.9

2-keto-D-gluconic acid

a-pyranose 174 .6 97.3 69.5 70 .1 69.4 64.44 6-f uranose 175.3 99.9 78.5 74.8 81.2 62.3 a-f uranose 174.3 104.2 83.0 76.0 62.5 61.5 a-pyranose a a 11.2b 72.4b 67.0b 64.36

5-keto-D-gluconic acid 6-furanose 175.7 79.3 76,6C 76 .sc 103.1 64.0 a-furanose 176.1 62.9 60.1d 76.9d 106.9 62.7 open chain form 178.1 a 72.4e 73.2e a 66.2

I

D-glyceric acid i

open chain form 176.6 75.5 63.1 I

table 3.4. Chemical shifts of D-gluconic-, 2- and 5-keto-D-gluconic- and D-glyceric acid. a: Peaks not assigned. b,c,d and e: Assignments may be interchanged.

To understand the stereochemistry and the stability of the two

keto acids it is nescessary to know the tautomeric equilibria.

From our spectrum we have calculated the following equilibrium

composition:

2-keto-D-gluconate in water

ratio of the average integrals of c3-c6 ~:i:~:l

ratio of the heights of c2 (method of Crawford)

Crawfords data (D20 as solvent)

5-keto-D-gluconate in water

ratio of the average integral of C and 6. 2., 3, 4 ratio of the heigths of c

5

Crawfords data (D2o as solvent)

69:23:4}:3}

76:20:4:traces

80:17:3:traces

6:5:7 70:12:18

79:14:?

79:10:11

60

Our data agree rather well with those of Crawford. We were not able to fully calculate the ratio of the tautomeric forms of

5-keto-D-gluconic acid according to the method of Crawford, because the chemical shift of c5 of the open chain form is

213.4 ppm (9), but unfortunately the spectrum is recorded only up to 206 ppm.

3.5. Iaotaohophoreaia

3.5.1. Introduotion

Isotachophoresis is a useful technique for the separation

of ionic compounds. The principles and theoretical backgrounds

of isotachophoresis have been described by Everaerts et al.

(11-13). The use of isotachophoresis for the analysis of the oxidation products of D-gluconic acid has been described by Dirkx (2). However at the conditions they have used, D-gluconic-,

L-guluronic and 2- and 5-keto-D-gluconic acid can not be sepa­rated. To achieve a good separation of these important compo­nents of our reaction samples, we have modified their method by lowering the pH of the electrolyte. Dirkx used an electrolyte system of pH = 6. At this pH all the above mentioned reaction

products are fully dissociated, so their average electric charge is identical. Also the shapes of the products are almost identi­cal. Therefore the separation can only be caused by the minor variations in structure. These variations were obviously not big enough to cause sufficient differences in effective mobilities for a good separation under Dirkx's conditions. By lowering the

pH of the electrolyte system to 2.95, a value representing

about the average pKa of these acids, greater differences in the degree of dissociation are obtained. This led to a good separa­

tion of the above mentioned sugar acids, and also to an improved separation of the other reaction products.

61

3.5.2. Ezperimental

The analyses were carried out with an apparatus manufac­

tured by THE's department of Instrumental Analysis of professor Everaerts. A conductivity detector, as described by

Everaerts and Verheggen (14) was used. In table 3.5. the

apparatus characteristics and experimental conditions are

sununerized.

leading electrolyte

counter-ion

pH additive

terminator

counter-ion

pH

capillary current strength

injection volume

time for analysis

0.01 M Cl­

B-alanine

2.95

0.2% hydroxy ethyl cellulose

0.05 M propionate sodium

7-8

teflon, 200x ~ 0.45 mm 80 µA

2 µl (after diluting 1:11)

16-17 minutes

table 3.5. Apparatus characteristics and ezperimental conditions of the isotachophoretic analysis

3.5.3. Typical results

Below some typical isotachopherograms of reaction samples of the catalytic oxidation of D-gluconic acid are given. TWo

signals are recorded: the electric resistance (R) of the

electrolyte passing the electrodes of the conductivity detector and the differentiated signal of the former (dR/dt). The

qualitative information of a zone is given by the level of its integr~l signal, while the quantitative information is given by

62

the distance between the two peaks in the differentiated

signal which correspond to the begin and end of the zone. In the

isotachopherograms the zone of .the leading electrolyte is

denoted by L and the zone of the terminating electrolyte by T.

dR dt

I 10 9 8 7 . I ~R

-- time

figure J.9. Isotachophero~ram of a sample of the oxidation of D-gluconic acid with a Pt/C catalyst

1: oxalic acid, 2: tartronic acid, J,4,5,8: not identified, 6: tartaric acid, ?: 2-keto-D-gZuconic acid, 9: formic acid, 10: D-gZucaric acid, 11: D­gZyceric acid, 12: 5-keto-D-gluconic acid + D­erythronic acid, lJ: glycolic acid, 14: L-guZuronic acid, 15: D-gZuconic acid

In figure 3.9. the isotachopherogram of a reaction sample

of the oxidation of D-gluconic acid with a Pt/C catalyst is

presented. The corresponding chromatogram is shown in figure

3.4. The product distribution was already discussed in section

3.2.3., but the identification of the peaks in this chromato­

gram is, as in others, mainly based on isotachophoresis in

combination with 13c-NMR. The molar responses of all of the

63

identified oxidation products are, as opposed to the molar responses from the UV-signals of the liquid chromatograph,

equal within a variation of + 20%. Consequently an isotacho­pherogram gives a good fingerprint of the sample under inves­tigation. Thus, the concentration of the not yet identified component corresponding to zone 8, is of the same order of magnitude of e.g. L-guluronic acid and must therefore be classified as a major byproduct. The less important byproducts corresponding to zones 3,4 and 5 are probably dicarboxylic

acids.

4

time

dR dt

R

figure 3.10. IBotachopherogram of a 8ampie of the oxidation of D-giuconic acid with a Pb/Pt/C cataiyBt

1: oxalic acid, 2: tartronic acid, 3: a-keto-D-gtucaric acid, 4: 2-keto-D-gluconic acid, 5: not identified, 6: formic acid, 7: D-gtucaric acid, 8: 5-keto-D-giu­conic acid, 9: L-guturonic acid, 10: D-giuconic acid

In figure 3.10. the isotachopherogram of a reaction sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst is presented. The corresponding chromatogram is given in figure

64

3.5. This isotachopherogram confirms that 2-keto-D-gluconic acid is the main oxidation product and that the byproducts are, compared to the oxidation with a Pt/C catalyst, present in low

concentrations. It confirms also that in this sample no glycolic

acid is present, as was already concluded from the ratiQ of the

UV- and the RI-signal of the peak of 2-keto-D-gluconic acid in

figure 3.5. In figure 3.11. the isotachopherogram is shown of the sample

used for the chromatogram of figure 3.6. and the 13c-NMR spectrum of figure 3.8. This confirms both the qualitative and quantita­

tive results of 13c-NMR and illustrates that the interpretation of the chromatograms has to be carried out with care, as several components can not be separated.

1 11 1o9 e

4

dR dt

j

2 R 1

L

-- time

figure 3.11. Ieotachopherogram of a fraction collected from a reaction mixture of the oxidation of D-gtuconic acid with a Pb/Pt/C catalyst

1: oxalic acid, 2: tartronic acid, 3: tartaric acid 4: 2-keto-D-gZuconic acid, 5,6: not identified, 7: D­gZyceric acid, 8: 5-keto-D-gZuconic acid, 9: D­erythronic acid, 10: gZycoZia acid, 11: L-guZuronic acid, 12: D-gZuconia acid

J.6. A specific detection method for a.-keto carbozyZic acids

J.6.1. Introduction

0-phenylene diamine reacts with a.-keto carboxylic acids

to form 2-hydroxy quinoxalines.

o~c,,,oH

65

©("": I ------;> @(N'( + H20

NH2 ~c~

0 R ~

N R

o-phenylene a.-keto 2-hydroxy di amine carboxylic acid quinoxaline

This reaction is specific for a.-keto acids and has been used

to determine these acids in the presence of other keto carbo­

xylic acids. Lanning and Cohen (15) have developed a specific

and quantitative spectrophotometric analysis of 2-keto-hexonic

acids based on this reaction. Moghimi et al. (16) have modified

this assay slightly and we have used this method after again

a small modification.

J.6.2. Ezperimentai

The reaction samples are diluted with water until the

(expected) concentration of 2-keto acid comes in the range of

25-250 µmol/l. To 2 ml of the diluted samples, contained in

thick-walled 5 ml test tubes, 1.5 ml of a freshly prepared

reagent solution (0.375 M hydrochloric acid containing 15 mg

of o-phenylene diamine per ml) is added. The closed tubes are

heated for 45 minutes at 100°C and allowed to cool (The reaction

'66

tak.es place during the heating period). With a double beam

spectrophotometer (Perkin Elmer type 124) the extinction of the

samples is recorded. A 2 ml volume of water to which 1.5 ml

of reagent is added and to which the same heat treatment is

applied serves as the blank reference.

3.6.3. TypicaZ resuZts.

Figure 3.12. shows the UV-spectrum of a reaction sample

of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst,

to which the above detection method h~s been applied.

1.0 -------~

~ 2 ::I c: 0

.8

•t; .6

5 x ~

c: .g .4 (,)

.5 x "'

.2

300 400

wavelength (nm)

figure 3.12. UV-spectrum of a sampZe of the oxidation of D-gZuconic acid ~ith a Pb/Pt/C cata­Zyst, to ~hich the specific detection method has been appZied

In accordance with Lanning and Cohen (5) an absorption maximum

at 334 nm was found. In contrast with their results, however,

we did not find a constant ratio between the absorption at

334 nm and at 364 nm, neither in our product mixtures, nor in

67

our calibration samples.

The specificity of this reaction was found to be in agree­

ment with the data of Lanning and Cohen. The contribution of

the byproducts to the total absorption is small. One should

keep in mind, however, that the method gives too high values

in the presence of other 2-keto-acids like a-keto-D-glucaric

acid and 2-keto-D-erythronic acid, which give comparable

absorption. Fortunately, the concentration of these products

is relatively low, and the method is therefore quite useful

to get a quick estimate of the 2-keto-D-gluconic acid concen­

tration. We have used this method also to detect and estimate

the production of 2-keto-D-galactonic acid and 2-keto-D-arabi­

nonic acid in the oxidation of D-galactose and D-arabinose,

respectively.

References

1. De Wilt, H.G.J., Ph.D. thesis, University of Technology,

Eindhoven, The Netherlands (1969)

2. Dirkx, J.M.H., Ph. D. thesis, University of Technology,

Eindhoven, The Netherlands (1977)

3. De Wilt, H.G.J., Kuster, B.F.M., Carbohydr. Res.~. 343

(1972) 4. Dirkx, J.M.H., Van der Baan, H.S., Van den Broek, J.M.A.J.J.,

Carbohyd. Res., 59, 6:3 (1977) 5. verhaar, L.A.Th., De Wilt, H.G.J., J. Chromatogr., !.!.1 168

(1969) 6. Dirkx, J.M.H., Verhaar, L.A.Th., Carbohydr. Res., 73, 287

( 1979) 1. Jandera, P., Churacek, J., J. Chromatogr., 86, 351 (1973)

8. Lee, K.S., Samuelson, Anal. Chim. Acta., 37, 359 (1967)

9. Crawford, T.C., Andrews, G.C., Faubl, tl., Chmurny, G.N.,

J. Am. Chem. Soc., 102, 2220 (1980)

10. sadtler Standard Carbon -13 NMR Spectra, Sadtler Research

Laboratories, Inc. (1976)

68

11. Everaerts, F.M., Ph.D. thesis, University of Technology,

Eindhoven, The Netherlands (1968)

12. Everaerts, F.M., Routs, R.J., J. Chromatogr., 58, 181 (1971)

13. Everaerts, F.M., Beckers, J.L., Verhe99en, Th. P.E.M.,

Isotachophoresis, J. of Chrom. Library, ~, Elsevier Sc.

Publ. Co. (1976)

14. Everaerts, F.M., Verhe9gen, Th. P.E.M., J. Chromato9r.,

11.1 193 (1972)

15. Lanning, M.C., Cohen, S.S., J. Biol. Chem., 189, 109 (1951)

16. Mo9himi, A., Tate, M.E., Oades, J.M., Soil Biol. Biochem.,

.!.Q., 283 ( 1978)

69

Chapter 4

Equipment and Experimental Methods

4.1. Introduction

The present investigations called for a reactor system in

which the temperature, pH and oxygen partial pressure can be

accurately controlled and easily changed from experiment to

experiment. It is also necessary that the catalyst can be

easily replaced. We have developed a stirred tank reactor, in

which the three phases - liquid substrate solution, gaseous oxygen or oxygen containing gas and solid catalyst - are well

mixed, meeting the above requirements.

In sections 4.3. and 4.4. the stirred tank reactor plus

its auxiliary equipment and its mode of operation are described.

The preparation and regeneration of the catalysts used shall

be discussed first.

4.2. The cataiysts

4.2.1. The piatinum on carbon cataiyst

The Pt/C catalysts are prepared according to Dirkx (1),

which is derived from the procedure of Zelinski! (2,3): The

active carbon (Norit PK 10 x 30 or Norit SX-2) is ground in a

mortar or a ball mill to a fine powder, from which the sieve-

70

fraction 50-105 µ is used. A solution of 10 g hexachloroplatinic

acid (H2PtC16 .6u2o) in 100 ml water is added to 72 g of the

sieved active carbon, and about 100 ml water is added to obtain

complete wetting of the carbon. During the adsorption of the

chloroplatinum complex on the active carbon, which takes place

at room temperature, nitrogen is bubbled through the suspension.

After 5 hours the adsorption equilibrium is reached, and the

suspension is cooled to 0°c. After adding 170 ml of 35% form­

aldehyde solution, the platinum (IV) is reduced to Qlatinum

metal by addition of 90 ml 30% KOH solution over a period of

15 hours. The suspension is fi.ltered and the catalyst is washed

with distilled water until the filtrate is neutral. After

drying at 50°C at reduced pressure (about 10 2Pa) the catalyst

is ready for use.

The platinum content, which for this catalyst is about

5% by weight, is determined according to the method of Charlot

(4) and Ayres et al. (5,6): The platinum is dissolved in aqua

regia and converted to a complex with SnC12 followed by measu­

ring the extinction of the solution of 403 nm.

Some platinum loss (10-20%) takes place during the pre­

paration of the catalyst, probably caused by desorption of some

u 2PtC16 from the active carbon, at the start of the treatment.

This u 2PtC16 is then reduced in solution and not readsorbed.

The above procedure gives a catalyst with a reproducible acti­

vity.

According to de Wilt (7) these catalysts have a platinum

dispersion of about 1.0. We did not determine the Pt-surface

by o2 or u 2 titration, as this technique, according to Dirkx

(2), does not give information on the metal surface used for

the oxidation reaction. De Wilt measured the Pt surface of a

number of Pt catalysts, and found large deviations (factor 2-3)

in activity for catalysts with almost the same Pt-surface. The

variation in activity/m2 Pt of catalysts with different Pt

contents was even much higher (factor 15-20)

Besides the home made Pt/C catalyst we have also

71

used a commercial 5% Pt/C catalyst from Degussa (type F 196

RA/W). This catalyst is supplied wet and used as such, because

drying causes a loss of activity. The quantity of catalyst is

always calculated on a dry basis.

After use the catalyst has to be regenerated for economic

reasons. This succeeded fairly well by washing it with about

2 1 hot water (90°C) per 10 gram of catalyst. If the catalyst

was used repeatedly, this procedure did not result in a complete

regeneration. The source of this irreversible deactivation is

not completely clear. In any way, it was not caused by Pt-loss

during prolonged use. A better, although still incomplete,

regeneration was obtained by washing the catalyst with 0.1 M HCl.

4.2.2. The Zead pZatinum on carbon catalyst

As a basis for a lead platinum on carbon (Pb/Pt/Cl catalyst

either a home made or a commercial Pt/C catalyst was used.

A solution containing the required amount of lead (II)

acetate in just enough water to obtain complete wetting is added to the Pt/C catalyst. To completely fill the pores of the catalyst with liquid, the suspension is heated until a small

part of the water is evaporated. The suspension is allowed to

cool and after 18 hours a solution containing 1.8 times the

amount of sodium hydroxide or trisodium phosphate, necessary to precipitate all the lead, is added under vigorous agitation.

After 18 hours the suspension is filtered and the catalyst is

washed with water until the filtrate is neutral. Initially the

catalyst was dried at 50°C at reduced pressure, but later the wet catalyst was used.

The lead content of the Pb(OH) 2/Pt/C or Pb3 (Po) 4) 2/Pt/C ca­

talyst is according to Martens ( 8) determined gravimetrically as

, lead (II) chromate after dissolving the lead in 2 M .. nitric acid.

A used Pb/Pt/C catalyst is also regenerated by washing it

with hot water. This method is not succesful for a heavily deactivated catalyst, as discussed in more detail in chapter 6.

72

:

----€)

---@

figure 4.1. The stirred tank reactor

3, 21 f'langes

S gasket rings (teflon)

7 stirrer shaft

9 turbine stirrer, 12 blades Rushton type

10 baffle

11 0-ring

12 stud

15 : bottom plate

19 inner reactor wall (pyrex glass) diameter 110 mm/height 200 mm

20 outer reactor wall (pyre~ glass) diameter 130 mm/height 200 mm

73

11

13

figure 4.8. Flow sheet of the reactor and auxiliary equipment

List of symbols:

1: reactor

8: turbine-stirrer

J: polarographic oxygen analyser

4: thermostatbath

5: drain

e: sampling tubing

7: KOH burette

8: substrate supply vessel

9: condensor

10: gas circulation pump

11: bubble indicator

18: oxygen supply vessel

lJ: gas burette

14: contact manometer

74

4.3. Equipment

A schematic presentation of the stirred tank reactor is

given in figure 4.1. Unless otherwise mentioned, all parts are

made of stairless steel type AISI 321. A general flow sheet of

the reactor and auxiliary equipment is shown in figure 4.2.

The reaction temperature is regulated by circulating water

from a waterbath through the double-wall of the reactor. The

variation of the temperature in the reactor was + 0.5°C.

The pH of the reaction mixture is measured by a combined

glass-reference electrode (Radiometer GK 2402 B or C) attached

to a pH-meter/controller (Radiometer TTTld). Before each ex­

periment the electrode is equilibrated at the operating tempe­rature in a buffer solution (Merck Titrisol) of the experimental

pH for at least 3 hours. The pH is controlled by automatic

titration with .SN KOH. The alkali consumption is recorded by

measuring the level in the KOH burette.

The total system pressure is controlled at 0,1 MPa by

means of a contact manometer. The oxygen consumption is de­

termined as a function of time by means of a gas burette system. In order to minimize the effect of accumulation of inert gases

from impurities in the oxygen or from the reaction (co2), the

oxygen supply vessel is included in the closed gas circulation

system. The oxygen concentration in the liquid phase is measured

by an oxygen-electrode (Beckman 39553 Oxygen Sensor) attached

to a polarographic oxygen analyzer (Beckman Fieldlab Oxygen

Analyzer) . The electrode is radially mounted in the reactor

wall at the level of the stirrer blades.

75

4.4. ExpePimentat methods

An experiment is prepared and started as follows: The

desired amount of catalyst, suspended in 400 ml of pure water,

is introduced into the stirred batch reactor. The concentrated

substrate solution, having the operating pH, is filled into its

supply vessel. Both reactor and supply vessel are then heated

to the reaction temperature. The reaction is started according

to one of the following two procedures:

StaPting pPoaeduPe A:

The catalyst suspension and the concentrated substrate

solution have been heated in the oxidation gas atmosphere, and

the experiment is started by introducing the concentrated sub­

strate solution into the reactor.

StaPting pPoaeduPe A:

The catalyst suspension and .the concentrated substrate

solution have been heated in a nitrogen atmosphere. After intro­

ducing the concentrated substrate solution into the reactor, the

suspension is kept in a nitrogen atmosphere for 10 minutes.

Thereafter the stirrer and the nitrogen flow are stopped. After

the gas circulation system has been quickly evacuated and refil­

led with oxygen, the experiment is started by switching on

the stirrer.

During the run samples (5 ml) are taken with a syringe.

After sampling the catalyst is filtered off, and the clear

samples are stored in a refrigerator until analysis. The measu­

red concentrations are corrected for the dilution with KOH

(and sampling).

76

4.5. Maas tPanafer in the atiPred tank reactor

In the three phase system gas-liquid-solid the following

mass transfer steps can influence the reaction rate:

1. Oxygen transfer from the gas- to the liquid phase

2. Diffusion of reactants from the bulk of the liquid phase

to the surface of the catalyst

3. Pore diffusion of the reactants

In case of the Pt/C catalyst the stirrer speed could easily be

chosen high enough to prevent mass transfer limitation at the

interface or in the liquid phase, while the particle size was

small enough to prevent pore diffusion effects. On the other

hand, most of the oxidations with a Pb/Pt/C catalyst (chapter

6 and 7) were carried out under conditions where the oxygen

transfer from the gas- to the liquid phase was limiting. This

was checked by measuring the oxygen concentration in the liquid

phase. A low oxygen concentration in the liquid phase was

necessary to prevent a fast deactivation of the lead containing

catalyst (section 7.6).

References

1. Dirkx, J.M.H., Ph.D. thesis, University of Technology,

Eindhoven, The Netherlands (1977) 2. Zelinskii, N.D., Turowa-Pollak, M.B., Ber., 58, 1298 (1925)

3. Liberman, A.L., Schnabel, K.H., Vasina, T.V., Kazanskki,

B.A., Kinet. Katal., ~. 446 (1961) 4. Charlot, C., Les methods de la chimique analitique, Masson,

Paris (1961) 5. Ayres, C.H., Meyer, A.S., Anal. Chem., .!1_, 299 (1951) 6. Ayres, C.H., Meyer, A.S., J. Am. Chem. Soc.,'!.]_, 2671 (1955)

7. De Wilt, H.G.J., Ph. D. thesis, University of Technology,

Eindhoven, The Netherlands (1969) 8. Martens, W.R.M., M.Sc. thesis, University of Technology,

Eindhoven, The Netherlands (1983)

77

Chapter 5

Selective Catalytic Production of D-Glucaric

Acid

5.1. Introduction

On basis of the present day state of the art of the

platinum catalyzed oxidation of D-gluconic acid to D-glucaric

acid, we will discuss some potential possibilities to improve

the selectivity of this reaction. some explorative experiments

are presented in sections 5.2.-5.6.

In 1953 Heyns and co-workers initiated a very extensive

research program on the selective oxidation of carbohydrates

with oxygen by means of noble metal catalysis in alkaline

solution, summarized in three comprehensive reviews (1-3).

The mechanism of the catalytic oxidation falls into two

extreme cases (4):

(1) A pure auto-oxidation can be postulated wherein the adsorbed

oxygen is activated by the platinum and a peroxide inter­

mediate is formed, which decomposes to an aldehyde and

hydrogen peroxide.

RCH20H + Pt-02 + R-THOH + Pt

OOH

78

R-CHOH + R-CHO + H2o2 I OOH

Another possibility is the activation of the adsorbed

substrate

o2 + Pt-RCH20H + Pt-RCHOH I OOH

Pt-~CHOH + Pt-RCHO + H202 OOH

The hydrogen peroxide produced is rapidly decomposed by

the catalyst. Between these extremes intermediate path­

ways, e.g. activation of both substrate and oxygen are

possible.

(2) A pure dehydrogenation can be depicted in which the platinum

abstracts hydrogen from the chemisorbed substrate alcohol.

In a second step the chemisorbed hydrogen is removed from

the metal by reaction with oxygen.

Pt + Pt-RCH20H + RCHO + 2 Pt-H

2 Pt-H + !02 + 2PT + H20

After extensive discussion of all possibilities Heyns

et al (3) concluded that most results of the various oxidation

reactions studied are in favour of a pure dehydrogenation

mechanism, especially for the reactions that take place in the

absence of oxygen. This is in agreement with the observations

of De Wit et al. (5). They have found that in alkaline medium

under ambient conditions in the presence of noble metals, aldoses

can be converted to their aldonic acids with concomitant pro-

79

duction of hydrogen gas. They also showed that this dehydrogena­

tion is accomplished by ionization of the hexose followed by

hydride abstraction by the catalyst.

However, in the presence of oxygen, an alternative mechanism,

in which oxygen plays a role in the first reaction step, can-

not be excluded completely. Perhaps, dependent on the reaction

conditions and the kind of substrate, different mechanisms are

operative.

Heyns et al. (3) have postulated selectivity rules for the

catalytic oxidation of carbohydrates with oxygen by means of

platinum catalysis in alkaline solution. All these can be de­

rived from a dehydrogenation mechanism. Both electronic and

steric effect determine which group or groups in a carbohydrate

molecule will be oxidized preferentially.

Due to electronic effects the oxidation rate decreases

in the series:

hemiacetal > primary hydroxyl > secondary hydroxyl

The steric effects can be understood by the assumption

that the platinum has to attack the hydrogen bonded to the

c-atom of th.e -CHOH- group to accomplish the dehydrogenation. This is evidenced by the observation that in all ring systems

investigated the preferentially oxidized ;:-cHOH group has the

hydrogen (on the c-atom) most exposed.

Application of these electronic- and steric effects to

the platinum catalyzed oxidation of D-gluconic acid with oxygen

in neutral or alkaline medium leads to the following considera­

tions:

In neutral or alkaline medium D-gluconic acid is completely

dissociated (pKa = 3.6 at 25°C). The gluconate anion occurs

only in the open chain form (section 3.4.):

80

0 ~ c-o-

l H-C-OH

I HO-C-H

I H-C-OH

I H-C-OH

I CH 20H

D-gluconate anion

Due to electronic effects the primary hydroxyl group on

c6

will be oxidized with a higher reaction rate than the

secondary hydroxyl groups. To determine the steric hindrance

one has to examine the time averaged positions of the R1- and

R2 group of the R1 R2CHOH group to be oxidized. In the D-gluconate

anion the hydrogen bonded to the C-atom of the R1R2CHOH group

is shielded more in its approach to and contact with platinum.

According to this steric effect the primary hydroxyl group will

be oxidized with a higher reaction rate than the secondary

hydroxyl groups.

From the latter set of CHOH groups the secondary hydroxyl group

on c2 and c5 are expected to be more exposed than those on

c3 and c4 . Besides this steric effect, also the difference in

adjacent groups, e.g. COO- for c2

compared to CH20H for c5

,

will influence the reaction rate (electronic effect) . Also the

way of adsorption of the non-reacting part of the molecule on

the catalyst surface can accelerate or retard the oxidation of

a giveD CHOH group. Therefore it is rather difficult to pre­

dict the resulting reaction rates. Consequently the following

series of (decreasing) oxidation selectivities must be viewed

as being a rough approximation only:

c6 primary hydroxyl > c5 and c 2 secondary hydroxyls >

c3 and c4 secondary hydroxyls

To improve the selectivity for D-glucaric acid, the oxi­

dation must be accelerated at c6

or retarded at especially

81

c5

and c2

. We have tried to achieve the former by the use of

catalysts other than noble metals and by complexing part of the

molecule with cations (section 5.2.) and the latter by complex­

ing the gluconate anion with borate (section 5.3.) and by con­

verting the gluconate anion (partly) into D-glucono-o-lactone

(section 5.4.) .

5.2. Explo~ato~y expe~iments o f the oxidation of D-glueonio

acid with Cu(II) and Co (II) oatalysts

Unless otherwise stated, a standard set of reaction con­

ditions as given in table 5.1., is used for the catalytic

oxidation of D-gluconic acid.

pH T

oc

8 55

[GOZ]O % 02 in the [cat] starting

mmol/1 oxidation gas g/1 procedure

200 100 40 B

tab le 5 .1. Standa~d ~eae ti on condi tio n s fo~ the oataly tio ox idation of D-g luco nie acid

A study of the literature with respect to an alternative

catalyst for the oxidation of D-gluconic acid to D-glucaric

acid in 1980 (6) did not yield much useful information. The most

promising leads were those articles (7-10) that reported on the

oxidation with oxyge n of both prima r y - a nd secondary alcohol

groups to aldehyde-, keto- and carboxylic acid groups with the

aid of copper and cobalt complexes. Therefore we have carried

out some explorative experiments with Cu(II)- and Co(II)- com­

plexes as catalyst for the oxidation of both D-glucose and

82

and D-gluconic acid. The experiments were conducted at

70°C at pH 7-10 with a substrate concentrat1on of

200 mmol/l and a catalyst concentration of about 5% by weight

relative to the substrate. The following compounds and complexes

were tested:

Cu(II) and Co(II) sulphate, -glycinate, -glutaminate, -p-amino

benzoate, -acetyl acetonate, -hystidinate and -1,2-dimethyl-

4-nitro-imidazolate.

The complexes of both metal ions with glycinate and acetyl

acetonate were the most active catalysts. They catalyzed,

however, the degradation of D-glucose at a pH higher than 7.5,

and the degradation of D-gluconic acid at a pH higher than 9.5.

Within the pH range of 7-9 Cu(II)-glycinate accelerates the

degradation of D-glucose by a factor 3 compared to the non­catalytic oxidative degradation.

No L-guluronic acid or D-glucaric acid was found in the

reaction mixture. Only chain cleavage products like formic

acid., glycolic acid, glycerinic acid and oxalic acid, and not

yet identified products were formed. None of these products

were produced selectively enough to make these catalyst

industrially attractive.

5. 3. Pr>oduet distr>ibution during the oxidatio_n of D-glueonie

aeid with a Pt/C eatalyst

The product distribution of the platinum catalyzed oxi­

dation of D-gluconic acid under standard conditions, applying

a standard 5% Pt/C catalyst from Degussa (type F 1961 RA/W) is

shown in figure 5.1. as a function of time for the main compo­

nents, and in figure 5.2. for the identified side- and conse­

cutive products. These figures illustrate that D-glucaric acid

is the main product and that L-guluronic acid is its precursor.

Besides oxidation on c6 also some oxidation on c2 and c5 takes

place, re·sul ting in the formation of 2- and 5-keto-D-gluconic

s ~ 150 E

0 , 1,5 time (ks)

o gluconic acid

A guluronic acid

CJ glucaric acid

83

figure 5.1. Main product distribution in the oxidation of D-gZuconic acid with a standard Pt/C cataZyst under standard conditions

.2 10

i ~ . 0 ...

0 ·• 1 Ui time (ks)

<> 5-lteto-O-gluconic acid

4 2-keto-O-gluconic acid

D oxalic acid

o tartronic acid

v tartaric acid

figure 5.2. By-product distribution in the oxidation of D-gZuconic aci¢ with a standard Pt/C cataZyst under standard conditions

84

acid, respectively (figure 5.2.).

In these figures the curves for 2- and 5-keto-D-gluconic

acid are partly dotted to indicate that their concentrations

are, at those times, not considered reliable anymore. This is

due to the formation of the chain cleavage products glycolic

acid and 0-erythronic acid which elute in our analytical system

at the same time as 2- and 5-keto-D-gluconic acid,· respectively

(see figure 3.4.). The concentration of the two keto-acids are

calculated, however, as if the two corresponding peaks in the

chromatograms represented only keto acid. However, from our

isotachophoretic analyses (see section 3.5.3.) can be conclu­

ded that only after the two keto acids have reached their

maximum concentration the above two chain cleavage products

are formed in significant amounts. This agrees with the assump­

tion that glycolic acid and D-erythronic acid are the chain cleavage products from 5- and 2-keto-D-gluconic acid, respec­

tively (see section 7.6.). This makes the concentration of the

two keto acids reasonably reliable up to their maximum.

From the shape of the curves of the chain cleavage products

oxalic acid, tartronic acid and tartaric acid it can be con­

cluded that D-gluconic acid is not their precursor, but possibly

L-guluronic acid, 5-keto-D-gluconic acid or 2-keto-D-gluconic

acid.

The difference in selectivity for oxidation at c6 , c5 and c2 is best illustrated by figure 5.3. The conversion and

selectivities used are defined as follows:

conversion

[C ] - [GOZ] 6total O [c J 6total 0

(5.1.)

selectivity c6 [GLZ] + [GAZ] (5.2.) [c6

) - [GOZ] total 0

85

selectivity c5 [5 KGOZ]

(5.3.) [C ] - [GOZ] 6total 0

selectivity c2 [2KGOZ]

(5.4.) [C ] - [GOZ] 6total 0

In these definitions we use the total concentration of material

present at time t = 0, expressed in c6 units ([c6totalJ 0), instead of the D-gluconic acid concentration at time t = O.

This is done, because at the time that we indicate with t = O,

under the conditions of starting procedure B, already some

D-gluconic acid is converted.

·• --------·- .. ~ . . 2 "-----...____----------' -

0 ·2 .4 .6 .. conversion i- i

o selectivity c6

'1 selectivity c5

o selectivity c2

figuPe 5.J. Seleativities c6 , C5 and C2 fop the

oxidation of D-gZuaonia aaid ~ith a stan­

daPd Pt/C aatalyst undeP standaPd aonditions

In figure 5.3. only the reliable data on the selectivities

c5

and -c2 are taken into account. This figure demonstrates that

the order of decreasing selectivity is: selectivity c6 > selec­

tivity c5 > selectivity c2 . This is in agreement with our

86

considerations in respect to electronic- and steric effects

discussed in section S.1. That the. (integral) selectivity

CS and -c2 decreases as a function of the conversion is due

to the oxidative cleavage of S- and 2-keto-D-gluconic acid,

respectively. Extrapolation of the selectivity curves to

conversion = 0 gives the following results:

selectivity c6 ~ O.S6

selectivity CS ~ 0.31

selectivity c2 ~ 0.12

This demonstrates that with a Pt/C catalyst D-gluconic acid

is mainly oxidized at c6 , CS and c2 .

5.4. Oxidation of D-gluconic acid in the presence of borate

A possible method to improve the selectivity of the oxi­

dation of D-gluconic acid to D-glucaric acid involves the use

of protective groups. In the introduction (chapter 1) we have

already discussed the use protective groups is economically

not very attractive. This is true in so far as the introduction

and subsequent removal of the protective groups is not very

selective, difficult or slow. If, however, as for borate, the

above two steps are very fast, and would result in a high selec­

tivity, some of these drawbacks are obviated. For the produc­

tion of sequestering agents for laundering, it would not be

necessary to remove the borate from the product mixture.

If required for other purpose, however, the use of borate

immobilized on the catalyst will possibly offer a potential

alternative. However, before trying to find an answer to all

these questions, we first have carried out some explorative

experiments, to find out wether the addition of boLate to the

reaction medium has really a positive influence on the

selectivity for D-glucaric acid.

87

The oxidation of the secondary hydroxyl groups in the

D-gluconate anion probably follows a dehydrogenation mechanism

which includes 2 steps:

(a) The dissociation of the hydroxyl group.

(b) The hydride transfer to the catalyst.

A protective groups thus can have two functions:

(a) To prevent the dissociation of the hydroxyl group, and

thus to retard the transfer of the hydride ion.

(b) To hinder sterically the transfer of the hydride ion.

The formation of borate gluconate complexes has received

hardly any attention in the literature. Therefore we have

carried out some experiments in which gluconate solutions were

mixed with borate solutions of the same pH, whereafter the pH

was measured. In table 5.2. the results are summarized.

pH Borate/gluconate L\pH ratio

8 0.5 -1. 77

1 -1.55

2 -1.26

9 0.5 -1. 72

1 -1. 24

2 -0.85

10 0.5 -.1 .67

1 -0.96

2 -o. 72

11 0.5 -0.62

1 -0.53

2 -0.23

table 5.2. Change of the pH when a gluconate and a borate solution of the same pH are mixed

88

From this table one sees that the pH changes are rather

great. This suggest, according to Boeseken (11), that besides

a mono complex, spirane type of complexes could be formed:

mono complex spirane type complex

Recent results of van Duin et al. (12) indicate that indeed,

besides mono esters, a spirane type of complex is formed in

the analogous system glucarate-borate at molar ratio's of

borate/glucarate about 0.5 and pH above 9.

It is surprising that at pH 11 there is a pH effect when

gluconate solutions are mixed with borate solutions. At this

pH boric acid (pKa ~ 9) and D-gluconic acid (pKa = 3.6) are

completely dissociated and according to the reaction

B- + n GOZ- -----"'- B (GOZ) (n+ 1 ) - + n

the pH change cannot result from borate ester formation.

According to Weigel (13) the geometry and the rig~dity

of the molecule determine which combination of oxygen atoms of

the hydroxyl groups can approach the borate ion close enough, i.e. within a distance of 0.24 nm, to play a role in the complex

formation. For an acyclic compound like the gluconate anion, especially the oxygen atoms of a trans (Fischer projection)

vicinal diol can, in an eclipsed conformation of the molecule,

approach close enough for complex formation. This agrees with

van Duin's work (see above) which indicates that mainly 2,3

and/or 3,4 borate esters are formed with glucarate. Possibly

corresponding gluconate borate esters can be expected.

89

A home-prepared 5% Pt/C catalyst was used at pH's 8,9

and 10 with borate/gluconate ratio's of O, 1 and 2. The other

reaction conditions were standard. Figures S.4.-5.6. show that

the addition of borate to the substrate solution results in

a large decrease of the reaction rate with the decrease being

greater the more borate is added. This suggest the oxidation

rates of the borate-gluconate complexes to be lower than that

of the free gluconate. This is substantiated by the observations

that, although the oxidation rate of the free gluconate increases

with increasing pH, this rate decreases with increasing pH for

experiments with borate added and that the extent of complex­

ation increases in this range with increasing pH (van Duin

et al. (12)). There is, however, one exception to this genera­

lized statement, viz. the experiment at pH 9 and a borate/glu­

conate ratio of 1 (figure S.S.). For this experiment the reac­

tion rate is greater than for the corresponding experiment

at pH 8.

For the conversion and selectivity for these and subsequent

experiments in this chapter we have used other definitions than

before. These experiments are intended to improve the selec­

tivity for D-glucaric acid and thus we use as selectivity the

one for D-glucaric acid. As L-guluronic acid is an intermediate

product, that still can be converted to the desired product,

it can for selectivity purposes be considered as being uncon­

verted starting material. Consequently we have adjusted our

definitions for conversion and selectivity for D-glucaric acid

as follows:

conversion GAZ [C6tota1lo - [GOZ] -[GLZ]

[C6tota1lo

(S.S.)

90

pH 8 o (borate]/[glucooate] = 0

'ii 6 [borate)/(gluconate]

~ 10

• <> [borate]/[glucooate] = 2

N 0 Cl

40 80 time I k$)

120

figure 5.4. D-gZuaonia aaid aonaentration (logarith­mia saale) as a function of 'time for

.§ 'a;

I N 0 C1

pH = 8 with the borate/gluaonate ratio as parameter

101 0 40 80 12()

time 1ks1

pf! 9 o[borato)/[gluconate] o

"[borate]/[gluconate]

<>[borate] I [gluconate]

= 1

figure 5.5. D-gluaonia acid concentration (logarith­mic saale) as a funation of time for pH = 9 with the borate/gluconate ratio as parameter

time I ks)

pH 10 o (boratel/[gluconate] = O

t>[borate]/[gluconate] = l

o [borate) /[gluconate}

figure 5.6. D-gluconic aaid concentration (logarith­mic saale) as a function of time for pH = 10 with the borate/gZuconate ratio as parameter

91

[GAZ] selectivity GAZ = [CGtotalJO - [GOZJ - [GLZ] (5.6.)

The chromatograms of the reaction samples of ~hese

experiments were influenced by the addition of borate. The glu­

conic acid concentrations are at least initially, overestimated

by about 10% at the borate/gluconate ratio 1 and ~Y about 15%

at the borate/gluconate ratio 2. Therefore the calculated initial

selectivities and conversions are not very rialiable. This must

be considered in the interpretation of the figures 5.7.-5.9.

These figures show that at pH 8 the selectivity for D-glucaric

acid indeed has improved by the addition of borate to the

D-gluconic acid solution, but that it remained constant or

got worse at pH 9 and 10.

It will be clear that first more detailed insight is necessary

in the borate gluconate species present under the conditions

of the above experiments in order to be able to give a plausible

explanation for the observed differences in rates and selec­

tivities. The highest selectivity obtained with borate at

pH 8 and a conversion of 0.7 is hardly higher than that found

at pH 9 and 10 without borate.

As the reaction rates for the latter are higher by a factor

10 or more, it can be concluded from these experiments that,

within the ranges examined, the addition of borate to the

D-gluconic acid solution does not result in an industrial

attractive process.

92

pH 8 O [borate]/[9luconate] 0

I .e A [borate]/[gluconate)

<> [borate]/[gluconate] • 2 N < C).6

.2

0 .2

figure 5.?.

,, ·& .9 conversion GAZ 1 - 1

SeZectivity for D-gZucaric acid oxidation of D-gZuconic acid at with the borate/gZuaonate ratio meter

f qr the pH = 8 as para-

pH 9 o [borate]/[gluconate)

"[borate]/[gluconate)

0

I .e <> [borate]/[gluconate) • 2

N < <!).6

. 2

~ ·~~· __..... ...

o+--..,.~-.---..~-.-~~-.--~~~~,----+

0 .2 .. ·8 .&

conversion GAZ 1 - 1

figure 5.8. Selectivity for D-glucaric acid for the oxidation of D-gluconic acid at pH = 9 with the borate/gluaonate ratio as para-

I .e

N .< C).6

meter

~ y ,,,_'·~

-~ . . . ...... I a

0 ,.2 .4 ·O .9 conversion GAZ ; - 1

pH 10 o [boratel/[gluconate] = 0

A {boratel/[gluconatel = 1

<> [borate]/[gluconate] = 2

figure 5.9. SeZectivity for D-glucaric acid for the oxidation of D-gluconic acid at pH = 10 with the borate/gZuconate ratio as para­meter

5.5. Oxidation of D-gluconic acid, paPtly in the foPm of the

6-lactone

93

Another alternative to improve the selectivity for o­glucaric acid could possibly be the transformation of the

D-gluconate anion into the D-glucono-6-lactone. On the analogy of methyl-a-D-glucoside (14) also D-glucono-o-l~cton~

could possibly be oxidized at c6 with a high selectivity.

HO

HO

H

Pt/C -->' 90%

methyl-a-D-glucoside

H

H

Pt/C

0 ~

D-glucono-6-lactone

H

ref ( 14)

methyl-a-D-glucuronide

H

HO

H

D-glucaro-6-lactone

! other lactones of D-glucaric

acid

Methyl-a-D-glucoside is oxidized at the c6 position

with a selectivity of 90% (14), because the possible side

reactions are less favourable, because all the other hydro­gens that could be abstracted are either protected by acetal

formation, or in the for abstraction less favourable

94

axial position. The same is more or less true for the o-lactone

of D-gluconic acid. Due to the double bond between the c and o atoms of the carboxyl group this compound does not possess a

perfect chair form, but is in the vicinity of this group some­

what more flattened. Nevertheless, also in this conformation

the hydrogens on c2-c5 are in a, for abstraction, less

favourable position.

In aqueous medium the following equilibrium exists:

0 II

H-~--:j TOOH coo -I

+ 820 H-C-OH

820 H-C..,.OH

I I HO-C-H 0 HO-C-H; HO-C-H + 820

H-f~ - 820 I -820 I e-cr-oe H-C-OH

I H-C H-C-OH e-1-oe I I

CH20H CH20H CH20H

D-glucono-o- D-gluconic D-gluconate lac tone acid anion

The relatively minor quantity of the y-lactone has been

kept out of the consideration for. simplicity reasons.

The c-lactone can hydrolyze to the free acid, which in its

turn can dissociate to the anion. The pKa of D-gluconic acid

+

at 25°C is about 3.6, so that at pH> 5 gluconic acid is largely

present in the form of the D-gluconate anion. At lower pH,

however, also the other species are present in more or less

significant amounts. After some time an equilibrium will be

established. According to Ansems (15) at pH 4 about 6% of the

total amount of the D-gluconic acid species will be present

in the form of the o-lactone. For pH 3 this figure is about

17%. This illustrates that even at a low pH where most of the

gluconic acid is not dissociated the amount of lactone is

still relatively low. This demonstrates that no big improve-

ments of the selectivity due to the presence of the lactone

are to be expected. Nevertheless we have carried out some

experiments to find out if at these pH's there is any

improvement in selectivity at all. If so, it would be worth­

while to change the reaction medium to a less aqueous, or

non-aqueous composition in order to shift the equilibrium

further in the direction of the lactone. The experiments have been carried out with a home made

95

5% Pt/C catalyst. The only difference with the standard operating

procedure is the use of D-glucono-o-lactone instead of sodium­

D-gluconate. This was done to approach the equilibrium compo­

sition of the gluconic acid species from the lactone side in

order to maximize the presence of the o-lactone. Initially

four experiments were carried out at pH= 8, 7, 6 and 5, while the other conditions were standard. Figure 5.10. shows

::::: 0 E ' E '°

N 0 Cl

10 20 time (ks)

30 40

T • ss•c o pH S

t. pH 7

0 pH 6

o pH 5

figure 5.10. D-gluconic acid concentration (logarith­mic scale) as a function of time with the pH as parameter

that the decrease of the oxidation rate at decreasing pH, which

was observed by Dirkx (16) for the pH range 11-8, is continued

in the pH range 8-5. As the rate determining step in the oxi­

dation is not known with certainty the decrease in reaction

rate with decreasing pH cannot be explained as yet. Figure 5.11.

98

5.6. Addition of Pb(II) to the o~idation formulation

According to the patent literature (17), the use of a

Pt/C catalyst modified with Pb(OHl 2 for the oxidation of

D-glucose in non-aqueous media results in a high yield for

D-glucono-o-lactone. We have tested this modified catalyst

for the oxidation of D-gluconic acid in aqueous medium at a

pH of 8 and a temperature of 55°C. This, however, resulted

rather surprisingly in the formation of 2-keto-D-gluconic acid.

As this compound is of potential industrial interest, we de­

cided to study its manufacture in more detail. The following

chapter of this thesis will be devoted to this study.

99

References

1. Heyns, K., Paulsen, H~, Angew. Chem., 69, 600 (1957)

2. Heyns, K., Paulsen, H., Adv. Carbohyd. Chem., 12 1 169 (1962)

3. Heyns, K., Paulsen, H., Ruediger, G., Weyer, J., Fortschr.

Chem. Forsch., .!...!. 1 285 (1969)

4. Rottenberg, M., Turkauf, M., Helv. Chim. Acta, 42, 226 (1959)

5. De Wit, G., De Vlieger, J.J., Kock-van Dalen, A.C., Kieboom,

A.P.G., van Bekkum, H., Tetrah. Lett.,~, 1327 (1978)

6. Schiffelers, F.X.M.G., M. Sc. thesis, University of

Technology, Eindhoven, The Netherlands (1981)

7. Tsuji, J., Tahayamagi, H., J. Arn. Chem. Soc., 96, 7349 (1974)

8. Tsuji, J., Tahayamagi, H., Sakai, I., Tetrah. Lett., 11. 1

1245 (1975)

9. Munakata, M., Nishibayashi, s., Sakamoto, H., J. Chem. Soc.

Chem. Comm., .11_, 829 (1980)

10. Nigh, W.G., Oxidation in Organic Chemistry, Part B, p.35,

(ed.) Trahanovski, w.s., Academic Press, New York (1973)

11. Boeseken, J., Adv. Carbohydr. Chem., ! 1 189 (1949)

12. van Duin, M., Kieboom, A.P.G., Van Bekkum, H., unpublished

results 13. Weigel, H., Adv. Carbohydr. Chem., ..l§_, 61 (1963) 14. Kremers, J.C.M., M. Sci. thesis, University of Technology,

Eindhoven, The Netherlands (i984) 15. Ansems, A.M.M., Internal Report, University of Technology,

Eindhoven, The Netherlands (1980) 16. Dirkx, J.M.H., Ph. D. thesis, University of Technology,

Eindhoven, The Netherlands (1977)

17. Nishikido, J., Tamura, N., Fukuoka, Y., Fuji, s., Ger.

Offen!. 2,936,652 (1980)

101

Chapter 6

Characteristics and Scope of the Pb/Pt/C Catalyst

in the Oxidation of Carbohydrates and their

monocarboxylic acids.

6~1. IntPoduation

The only literature data available on the oxidation of

carbohydrates with Pb/Pt/C catalyst is the patent (1) claiming

the selective oxidation of D-glucose to D-glucono-o-lactone in

non-aqueous media. Another patent (2), deals with the catalytic

oxidation of a-hydroxy-arylacetatic acids to arylglyoxylic acids

with molecular oxygen in aqueous alkaline medium. At this

process, however, yielding 2-keto-carboxylic acids, there is

no selectivity problem, because the substrate contains only

one oxidizable hydroxyl group.

In these patents no mention is made about the function of

lead in the catalysts. In section 6.3. we describe our investi­

gations in this respect. The influence of the Pb/Pt ratio is

discussed in section 6.4. To determine the scope of our cata­

lytic system we have investigated metal ions other than Pb2+

(section 6.5.) and oxidized substrates other than D-gluconic

acid (section 6.6.). The deactivation of the Pb/Pt/C catalyst

is discussed in section 6.7.

102

6.2. Experimental

Unless otherwise stated, a standard set of reaction condi­

tions as given in table 6.1. is used for the catalytic oxidation

of D-gluconic acid and the other substrates.

pH T

•c

8 55

[substrateJ 0 mmol/l

200

~ o2 in

oxidation 9as

100

catalyst [cat)

9/l

40

Pb/Pt ratio I raol-basis

0.5

table 6.1. Standard reaction conditions for the catalytic oxidation of D-gluconic acid and other substrates

The rate of the non-catalytic oxidation of D-gluconic acid

is negligible under the above mentioned conditions (7). Unless

stated otherwise, starting procedure B (see section 4.4.) is

applied, and as basis for the standard Pb/Pt/C catalyst the 5%

Pt/C type F 196 RA/W from Degussa is used. The experiments are

carried out in reactors of different sizes, applying different

stirrer speeds (320-1500 rpm) to assure that oxygen transfer

limitation from the gas to the liquid phase will occur, keeping

the oxygen concentration in the solution low. This prevents rapid

deactivation of the catalyst, as is discussed in section 6.7.

6.3. The effect of lead on the Pt-catalyzed oxidation of

D-gluconic acid

6.3.1. Addition of a heterogeneous lead compound to the Pt/C

catalyst

Figure 6.1. and 6.2. give the concentrations of the main

components in the reaction mixture of the oxidation of D-glu-

200

~l!IO E E

c .g 100

I 8 !IO

0

0 ·5 1 1.6 time (ks)

o gluconic acid

A guluronic acid

a glucaric aciC

103

figure 6.1. Main product distribution in the oxidation of D-gZuconic acid with a standard Pt/C cataZyst under standard conditions

200

"ii 150 E E

c i 100

~ § 8 50

0

' ' I

0

\

f 1.5 time (kst

o gluconic acid

c 2-keto-D-gluconic acid

" oxalic acid

figure 6.2. Main product distribution in the o~idation of D-gZuconic acid with a standard Pb3(P04J2/ Pt/C catalyst under standard conditions

conic acid with a Pt/C and with a Pb/Pt/C catalyst respectively,

as a function of the reaction time. Comparison of these two

figures demonstrates, that after an initial period, in which

the oxygen transfer limits the reaction rate, the oxidation on

the Pb/Pt/C catalyst is faster. In section 8.3. we will return

to this observation. In the Pb/Pt/C catalyst the lead is added in the form of Pb 3 (P0412 •

The differences in selectivity of the above two catalysts is

best illustrated by figure 6.3. in which the (integral) selecti­

vity for the oxidation at c6 (selectivity c6) and at c2 (selecti­

vity c2) as a function of the conversion is given. The conversion

and the two selectivities are defined as:

104

conversion

[C ] - [GOZ] 6total 0 [C ] 6total 0

(6.1.)

selectivity c6 = [ GL Z ] + [GAZ ]

[C ] - [GOZ] 6total 0

(6.2.)

selectivity c2 [2 KGOZ] (6.3.) [C ] - [GOZ] 6total 0

We use as the initial concentration, [CGtotal]O' the total quantity of material present in the reactor calculated as an

average of the results from the analyses of the second, third

and fourth sample.

.a -­.... -

.4 > 8 .$ conversion ( - I

selectivity c6

o Pt/C

<> Pb/Pt/C

selectivity c 2 a Pt/C

a Pb/Pt/C

figure 6.J. Comparison of the selectivities for the oxidation of D-gluconia acid at C2 and c6 with a standard Pt/C catalyst and a standard PbJ(P04J:;i!Pt/C catalyst under standard conditions

From table 6.2., in which the above defined selectivities

are summarized for a conversion of 0.5, it is clear that the

addition of the lead salt to the Pt/C catalyst changes the

ratio of its c2- and c6-oxidation selectivities with a factor of about 150.

Pt/C Pb 3 (P04) 2/Pt/C

selectivity c2 0.054 0.82

selectivity c6 0.63 0.066

selectivity c 2/selectivity c6 0.086 12.4

tabie 6.2. seiectivities in the D-giuconic acid oxida­tion with a Pt/C versus Pb 3 (P0 4J2/PT/C cata­Zyst at 50% conversion

105

I

The carbon balances of the experiments are initially too

low. This is probably caused by adsorption of D-gluconic acid

on the catalyst in a nitrogen atmosphere. The amount of material

missing is equal to or even higher than would correspond to the

adsorption of 1 mol of D-gluconic acid per mol platinum. This

acid is assumed to desorb slowly when the atmosphere is changed from nitrogen to oxygen. The adsorption results initially also

in an apparent very low selectivity for 2-keto-D-gluconic acid.

This selectivity is so low that even if the reaction would be

100% selective after the first sample is taken, one still could

not obtain the selectivities found for the subsequent samples.

This is another indication that initially a certain quantity of

acids is not noticeable in our analysis. Of course other compo­

nents in the reaction mixture can also adsorb on the catalyst,

We have corrected for adsorption by multiplying the concen­

~rations found for D-gluconic acid and its products in the first

sample by the ratio between the average of the total amount of

material found in the three following samples and the amount

found in the first sample.

The initial part of the curves of the D-gluconic acid concen­tration as a function of time are dotted to indicate the ob­

served mass deficiency. In the first sample the concentration

of the products formed from D-gluconic acid are generally so

low that the correction hardly influences their concentration

curves and these are therefore generally not dotted.

It is evident that the above described correction also will

introduce uncertainties in derived figures, such as conversion

and selectivity. Therefore the initial part of their curves are

106

dotted also.

The oxidation with a Pb 3 (P04) 2/Pt/C catalyst system shows

that the addition of a heterogeneous lead compound to a Pt/C

catalyst changes its selectivity completely. To study the func­

tion of lead in these catalysts we have carried out oxidation

,reactions in which the lead was added to the reacting system

in other forms.

6.3.2. Addition of a homogeneous lead compound to a Pt/C

catalyst

When an oxidation is carried out with a normal Pt/C cata­

lyst and the same Pb/Pt and Pb/gluconic acid ratio as in the

previous experiments, but with a lead (II) acetate solution

added to D-gluconic acid in the substrate supplyvessel at

pH 7 applying starting procedure B, selective production of 2-keto-D-gluconic acid is also obtained (figure 6.4.). This

suggests that a lead (II) gluconate complex could possibly be

the active species in the selective oxidation.

.e

.4 .6 .9 conversion l - ~

selectivity c6

A 1st run

a 2nd run

selectivity c2

o 1st run

O 2nd run

figure 6.4. Selectivities for the o:cidation of D­gluconic acid at C2 and Ce with a Pt/C cataZyst after the addition of lead (II) acetate to the substrate soiution (lat run). In the second run 1/5 of the catalyst of the first run is used, without the addition of lead (II) acetate.

107

In the reaction liquid we found by atomic absorption at

the end of the run only 1.3% of the lead originally added. This

implies that almost all of the lead must be bound to the Pt/C

catalyst and that at the utmost a low concentration of lead (II)

(13 mg/l) in solution is required for the selective oxidation.

The "Pt/C" catalyst*> used in this experiment is washed

with hot water and 1/5 of it is used for a second experiment

under the same conditions as the first, except that no extra

lead is added. In this second experiment initially even a

higher selectivity for oxidation at c2 than in the first run

is observed (figure 6.4.), so that at least a part of the lead

that remained on the "Pt/C" catalyst after washing stayed there

and kept its ability to increase the selectivity for the oxi­

dation at c2 • In fact we observed that it is possible to use

a Pb/Pt/C catalyst over and over again without serious loss

of activity or selectivity.

In the course of the first experiment with the lead (II)

acetate solution, the selectivity c2 is increasing at the ex­

pense of the selectivity c6 . This is a strong indication that

during the experiment catalytic sites are formed that are active

for oxidation at c2 and that the number of these sites increases

during the experiment, possibly at the expense of platinum sites that are more active for oxidation at c6 . Washing of the catalyst

obviously does not result in the removal of the newly formed

sites .. The fact that hardly any lead was found in the reaction

liquid suggests that it probably is involved in the formation

of the new type of sites. The fact that also a Pb

3(P04) 2/Pt/C catalyst gives a high

selectivity c2 can be accomodated either by the assumption that

during the preparation of this catalyst the lead is preferen­

tially adsorbed in the vicinity of the platinum or by a mechanism

*) We write "Pt/C" with quotation marks,. because this catalyst

is not a pure Pt/C catalyst anymore, but most probably con­

taines a quantity of lead.

108

in which a part of the lead salt deposited on the catalyst is

dissolved by complex formation with D-gluconic acid and there­

after the complex is transported to the platinum site. There

the following three processes are possible:

(a) The lead gluconate complex is oxidized on the platinum site

and the lead remains complexed with the product and can

subsequently be transferred to another gluconate ion.

(b) The lead gluconate complex is oxidized on the platinum site, whereafter a Pb-Pt ensemble is formed that is catalytically

active for the oxidation at c2 •

(c) The lead from the lead gluconate complex forms an ensemble

with platinum on which the oxidation of the gluconate ion

at c2 takes place. We will discuss these possibilities in the subsequent sections.

In order to check the hypothesis that some of the lead

is dissolved by complex formation and transported as a complex

to the platinum site, we have carried out an oxidation with a

normal Pt/C catalyst to which lead (II) phosphate precipitated

on a carbon carrier was added, after we had verified that

Pb3 (P04 ) 2/c alone is neither selective nor active. The Pb 3 (P04) 2 /c is priE>r to use washed with a sodium-D­

gluconate solution (200 mmol/l, pH 8) and water to make sure

that no unadsorbed or easily disolvable lead was present in the Pb/C anymore. The Pb/Pt ratio in the reactor is 0.5. From the

high selectivity for oxidation at c2 as compared to c6 (figure

6.5.) it is clear that lead must take part in the oxidation

reaction, and that it must therefore be moved from its own carrier

to the platinum site on the other carrier. This is supported by

the observation that at the end of the reaction the concentration

of lead in the solution amounted 7 mg/l corresponding to 0.7% of the amount of lead originally present as Pb 3 (P04) 2;c. (This demon-

.2

.4 .a .a conversion l- I

selectivity c6

A 1st run

o 2nd run

selectivity c.2

o 1st run

O 2nd run

figure 6.5. Selectivities for the oxidation of D-gluconic acid at C2 and Ce with a combined Pb3(P04J2/C plus Pt/C catalyst system (1st and 2nd run)

109

strates the sequestering power of gluconate, because the solu­

bility of Pb3 (Po4>2 in water is only 0.14 ppm).

The combined Pb/C plus Pt/C catalyst was washed with hot

water and used again in a second experiment. This gave once more

an improvement of the selectivity for oxidation at c2 as com-

O 1st run

A 2nd run

10•+0---,,.r----• ..-.---,,.-, --,..-.• --,-t.o

time I ks;

figure 6.6. First order presentation of D-gZuconic acid as a function of the time for the first and the second run of the oxidation of D­gZuconic acid with a combined Pb3(P04J2/C and Pt/C catalyst system

110

pared to the first run of this section (figure 6.5.), and also

some enhancement of the rate of oxidation (figure 6.6.). This

confirms that lead transported from its own carrier to the

Pt/C is deposited on the latter.

6.3.4. Addition of EDTA to a Pb/Pt/C catalyst

As will be discussed in chapter 8 the selectivity for

oxidation at c2 is supposed to be caused by complex formation

between lead (probably from the lead platinum ensembles on the

catalyst) and the D-gluconate anion. In order to check this pos­

tulate we have added to a suspension of a Pb 3 (P04 ) 2/Pt/C cata­

lyst ethylenediamine tetraacetic acid (EDTA), which is a very

strong ligand for lead (II) (3), before the substate was

added and the reaction started.

There will be a competition between EDTA and D-gluconate to

form a complex with Pb 2+, that may result in one of the following

situations:

(a) EDTA extracts all lead from the catalyst system and from

the gluconate, leaving a clean Pt/C catalyst

(b) EDTA binds to lead on the Pb/Pt/C catalyst and thus hinders

adsorption of the gluconate

The quantification of the results of the HPLC analyses were

hindered by the addition of EDTA (EDTA/Pb = 2), making the ab­

solute values not so accurate. The relative values, however,

are usable. Figure 6.7. illustrates that the selectivity for

c2 oxidation is relatively low whereas the selectivity for c6 oxidation is relatively high, and that the selectivity for c2 decreases and for c6 increases as a function of the conversion.

As both EDTA adsorption on the lead of the Pb/Pt/C catalyst and

attainment of the equilibrium distribution of Pb2+ in solution

between EDTA and gluconate will be fast, it seems that lead

extraction from the Pb/Pt/C catalyst is the process that is

actually happening.

.. I

!''6

·~ " .! .4

" "' .2

0 0

~

~·

~· .2 ..

conversion .6 .a I->

selectivity c6

6 Pt/C + EDTJ\

'1 Pb/Pt/C + EDTJ\

selectivity c2

o Pt/C + EDTA

0 Pb/ Pt/C + EDTA

111

figure 6.?. Comparison of the aeteativitiea for the oxidation of D-gtuconia aaid at C2 and C6 ~ith a Pt/C and Pb/Pt/C aatatyat after addition of EDTA to the aatatyat auapenaion

6.4. Inftuenae of the Pb/Pt ratio

In section 6.3. we have demonstrated the effect of lead in

the Pb/Pt/C catalyst with experiments in which the Pb/Pt ratio

was 0.5. In this section the results of experiment with different

Pb/Pt ratio's are discussed. For these experiments Pb 3 (Po4) 2/Pt/C

catalysts were prepared in the usual manner, except that the

lead content was varied. As the lead gluconate complex may be

the active species in the selective oxidation at c2 , we also

give the Pb/GOZ0 ratio's. In figure 6.8. and 6.9. the results of these experiments

are summarized. The curves for Pb/Pt = 0.5 are dotted because

the corresponding experiment was carried out in another reactor

at another stirrer speed. Therefore we cannot fully compare

the result of this experiment with the others, but from figure

6.8. the conclusion can be drawn that a Pb/Pt ratio of 0.2,

corresponding to a Pb/Goz0 ratio of 10-2 is sufficient for a

selective catalyst. We have also investigated Pb/Pt ratio's of

112

.s

·--~. 0 . 4 . 6 '8

conversion ( - I

. ....

6 Ph/Pt 0

• Pb/Pt 0.01

<> Pb/Pt 0.2

U Pb/Pt = 0. 5

figure 8.8. Seleativity for 2-keto-D-gtuaonia aaid as a funation of the aonversion of D-gtuaonia aaid with the Pb/Pt ratio of the Pb 3 (P0 4J2/Pt/C aatalysts as parameter

200

§ 16 :;, 100

ii g 0

" 50 N

8 0

' \ I I \ \ \

' \ .s !

time (kSJ

o Pb/Pt = 0

A Pb/Pt = 0.01

0 Pb/Pt 0.2

U Pb/Pt = 0.5

figure 6.9. D-gluaonia aaid aonaentration as a funation of time with the Pb/Pt ratio of the Pb3(P04)2/Pt/C aataZysts as parameter

0.5, 1 and 2. The results are not shown here, but they indicate

that the use of Pb/Pt ratio's higher than 0.5 result all in the

same high selectivity.

The fact that with a Pb/Pt/C catalyst with a Pb/Goz0 ratio

of 10-2 selectivities of 90% can be obtained shows clearly that

113

only catalytic amounts of lead are necessary. A Pb/Pt ratio of

0.01 (Pb/GOZ0

= 5.10-4 ) is not sufficient to achieve a

significant increase in selectivity. This can be understood as

follows: The reaction may be (pseudo) first order in the amount of

Pb2+ present for one of the two following reasons:

(a) The number of really active sites, 1.e. Pb/Pt sites is

proportional to the lead content.

(b) The concentration of Pb gluconate complex is proportional to the [Pb 2+J.

We find that with a ratio of lead/gluconate of 10-2 or a Pb/Pt

ratio of 0.2 already the maximal catalytic effect. It is diffi­

cult to understand why the selectivity and activity would not

be further increased by raising the lead/gluconate ratio to

values higher than 10-2 • This makes it rather improbable that

the lead gluconate complex is the active intermediate. On the

other hand it may well be possible that with a Pb/Pt ratio of

0.2 the optimal lead platinum surface modification is already

attained. With a lead/gluconate ratio of 10-2 the ratio of Pb2+­

complexed gluconate/non-complexed gluconate must be smaller than 10-2 , and possibly below 7.10-4 , because that is the ratio

between complexed and non-complexed gluconate that we found

at the end of the Pt/C + Pb/C experiment. This again makes it hard to understand how the dissolved Pb 2+-gluconate compl~x would be the catalytically active species. So also this argu­

ment is in favour of the formation of lead-platinum surface ensembles as the catalytically active species.

Another indication for the assumption that these ensembles are

the catalytically active species is the following:

In the experiment with Pb/Pt = 0.2 the ratio of the selec-' tivity for oxidation at c2 to the selectivity for oxidation at

c6

is 0.9/0.05 = 18 (figure 6.10.). This means that the rate

for oxidation at c2 is a factor 18 higher than the rate for oxidation at c

6• A reduction of the lead content of the

catalyst by a factor 20 (Pb/Pt = 0.2 ~ Pb/Pt = 0.01) would

114

.s

l ?''e :~ .! ... .. .,

• 2

0

0

.,-~

/ .

.2 . 4 . e .a conversion I - !

selectJ.v1ty c6

~ Pb/Pt = 0.01

D Pb/Pt = 0.2

selectivity c2

o Pb/Pt = 0.01

o Pb/Pt = 0.2

figure 6.10. Comparison of the selectivities for the o~idation of D-giuconic acid at C2 and C6 with standard Pb3(P04)2/Pt/C catalysts with a Pb/Pt ratio of 0.01 and 0.2

reduce the amount of Pb-Pt ensembles by a factor 20, which, as

a rough approximation, would result in a ratio of the above

selectivities of about 1. This is initially indeed what we

have observed (figure 6.10.). That this ratio decreases during

the experiment could have two reasons:.

(a) Part of the lead-platinum ensembles deactivates, due to the

adsorption of some product

(b) Part of the lead is extracted from the catalyst by the

gluconate

The latter explanation does not seem very probable, because we

observed no strong loss of selectivity already at the beginning

of the experiment, although the catalyst has already been in

contact with the gluconate for about 1 ks (starting procedure B).

A deactivation of the Pb-Pt ensemble, due to the adsorption

of some product, however, is very well possible. The Pb/Goz 0

-4 ratio amounts 5.10 so only a very small amount of product

is necessary to cover all the lead present.

That Pb3 (P04) 2 really interacts with the platinum of the

catalyst follows from the subsequent experiments:

On 20 g of carbon carrier 1 gr of platinum was deposited

according to the standard procedure (section 4.2.1.). An equal

amount of carbon carrier was treated identically, except that

no H2Ptc16 was added. On both carriers 0.69 g Pb3 (P04 ) 2 (Pb/Pt= 0.5) was deposited in the usual way (section 4.2.2.).

When both lead containing products were exposed for 6 ks at

55oc to half a liter of a 200 mmol/l D-gluconic acid solution

115

at pH 8 in a nitrogen atmosphere, we found the lead concen­tration in the solution contacted with the Pt free Pb3 (Po4>2/c

product to be 1.5 mg/l, whereas for the Pb3 (P04) 2/Pt/C catalyst

the lead content was at or below the detection limit of 0.2 mg/l.

6.5. Metal ions other than Pb 2+

In chapter 8 it will be shown that the selective oxidation

of D-gluconic acid at c 2 is accomplished by complex formation of the Pb(II) on the Pb/Pt/C catalyst, with the D-gluconate

anion. The specificity is probably caused by the fact that

Pb(II) forms a bidentate complex with the carboxylate group

and the oxygen of the a-hydroxyl group. In this section we will describe the use of two other metal ions, which are reported

(4,5) to be able to form this kind of complexes also.

In figure 6.11. the results are summarized of the oxidation of D-gluconic acid with a Bi(OH) 3/Pt/C catalyst and with a

Pt/C catalyst (5% Pt/C, Degussa F 196 RA/W) to the suspension of which copper(II) acetate has been added. The Bi/Pt/C was

prepared from a home made 4% Pt/C catalyst according to an analogous method as for the Pb(OH) 2/Pt/C catalyst (section 4.2.2.).

116

.a

0

-­.-

·• .e conversion (-1

.a

selectivity c6

"' Cu

C Bi

.. Pb

selectivity c2

0 Cu

•Bi

<> Pb

figure 6.11. Comparison of the seZectivities for the o~idation of D-gZuconic acid at C2 and C6 with a Pb3(P04)2/Pt/C aataZyst, a Bi(OH)3/ Pt/C cataZyst, and a Pt/C cataZyst to the suspension of which copper( II) acetate has been added

The catalyst concentrations were both 40 g/l, the Bi/Pt ratio

was 0.5, and the Cu/Pt ratio was 2.

A comparison of the reaction rates is not very informative,

because the experimental conditions and the Pt/C basis for both

experiments were different, but the rates were found to be in

the same order of magnitude as obtained with the Pb/Pt/C

catalysts. Also the same produbts were observed. Figure 6.11.

illustrates that the Bi(OH) 3/Pt/C catalyst was more selective

for c 2 oxidation than the cu2+ - Pt/C system, but that even the

Bi/Pt/C catalyst was not as selective as the Pb/Pt/C catalyst.

These exploratory experiments neither imply that it is impossible

to prepare better catalysts with copper or bismuth,nor that

by using different reaction conditions the selectivity can not

be increased. Certainly bismuth seems to be promissing as an

additive in the Pt-catalyzed oxidation.

11 7

6.6. Other substrates than D-gZuconic acid

The results obtained with a Pb/Pt/C catalyst, for the

selective oxidation of D-gluconic acid, led us to a study of

the oxidation of other substrates. We will first discuss the

oxidation of the following, commercially interesting carbohy­

drates: D-glucose, D-galactose, D-arabinose and L-gulonic acid.

The reactions were all carried out in the same reactor. For

all experiments the same, for that reactor rather low~stirrer

speed (1000 rpm) was used, so that the Pb/Pt/C catalyst

(Pb/Pt 0.5) remained reasonably active, i.e. that the oxygen

concentration in the liquid was kept at a low value. This means

that the reaction rates that can be derived from the figures

6.12.-6.15. (showing the concentrations of the main products

as a function of time) are each influenced by an unknown oxygen

concentration that not necessarily has to be the same in the

four experiments.

The curves for 2-keto-D-galactonic acid and 2-keto-D-ara­

binonic acid are dotted, because their concentration could

only be estimated, as no pure compounds were available for

calibration. Neither did we have mixtures containing the 2-keto

derivative of o~galactonic acid or D-arabinonic acid for

identification. Nevertheless, the peaks of these 2-keto acids

could be assigned, because the peak pattern in the chromato­

grams from the reaction mixtures of all four substrates were

nearly identical. Moreove~with the specific detection method

described in section 3.6., the presence of 2-keto carboxylic

acids in the reaction mixtures was proved. The concentration

of both 2-keto-D-galactonic acid and 2-keto-D-arabinonic acid

in the final reaction mixtures estimated with this method were

about 25% higher than those estimated from the HPLC results. As we know from the oxidation of D-gluconic acid that these

deviations can be caused by smaller 2-keto-carboxylic acids,

that influence the outcome of the method specific for 2-keto

200

:::: ~ 150

E

c: 0 100

~ E "' " c: 0

" 50

0 0

200

~ 150

E

c: 0 100 -~

" "' " c: 0 50

"

0

I) glucose

c qluconic acid

A 2-keto-O-gluconic acid ~ n oxalic acid E

6. 12 c: 2 ~ E e c: 0 <.>

.5 1.5 time i ksl

<0iarabinose

A arabinonic acid

~ o 2-keto-o-arabinonic acid

o oxalic acid E

c: .g 6.14 ~

c .. <.> c: 0 <.>

.5 1.5 time ( ksl

200

150

100

50

0 0

200

' 150 ' ' '

100

50

0

.5 1.s time ( ksJ

.5 1.5 time (ks!

1:;9alactose

A qalactonic acid

ti 2-keto-D-qalacton ic acid

o oxalic acid

6. 13

o gulonic acid

"" 2-keto-1-gulonic acid

o oxalic acid

6. 15

figure 6.12.-6.15. Main product distribution in the oxidation of D-glucose, D-galactose, D-arabinose and L-gulonic acid with a standard Pb 3(P0 4J2 /Pt/C catalyst under standard conditions

acids, we preferred to use only concentrations estimated from

the HPLC results.

The 2-keto-D-galactonic acid concentration was estimated

11 9

by assuming that 2-keto-D-galacton·ic acid and D-galactonic acid

would have the same ratio between their molecular responses

as found between the molecular responses of 2-keto-D-gluconic

acid and D-gluconic acid. When applying this same method to

2-keto-D-arabinonic acid, a substantial surplus in the carbon

balance was found. Therefore we took a sample from the oxidation

of D-arabinose in which only small amounts of (detectable) by­

products were .present. The deficit between the amount of star­

ting material and the mass balance of this sample was ascribed

to 2-keto-D-arabinonic acid. This value. was used to determine

the molecular response for this compound. Consequently the

absolute values of the concentrations of the two 2-keto-carboxylic

acids may each contain a constant systematic deviation.

Figures 6.12.-6.14. show that when an aldose is oxidized

with a Pb3 (P04 l 2/Pt/C catalyst, first the hemiacetal group is

oxidized followed by reaction at c2 . This is caused by two

effects. In the first place the oxidation of an aldehyde group

is fast and secondly the complex formation with lead requires

the presence of a carboxylate group.

The selectivities c2 for these substrates are compared

with the results of the oxidation of D-gluconic acid in figure

6.16. As in the oxidation of D-glucose, D-galactose and

D-arabinose an intermediate is produced (D-gluconic acid, D-·

galactonjc acid, and D-arabinonic acid, respectively), that can

still be converted to the desired product, this intermediate

can for selectivity purposes be considered as being not conver­

ted starting material. Consequently we have adjusted our

definitions. For e.g. the oxidation of D-glucose this leads to

the following expressions:

conversion

[ C ] - [ G] - [ GOZ] 6total 0 c 6total 0

(6. 4.)

120

selectivity c2 = [2 KGOZ] (C ] - [G] - (GOZJ 6total 0

.a

0

·- .... - ~ -----­..... --·-- - --.... -D-...

-2 .• ·6 conversion (-)

..

• 0-qluconic acid

A O-qlucose

v O-galactose

c o-ara.bi.nose

~ L-qulon1c acid

(6. 5.)

figuPe 6.16. Selectivity foP a-keto-eaPboxylie aeid for the oxidation of D-glueoae, D-galaetose, D-arabinose, L-gulonie aeid and D-glueonie aeid with a atandard Pb~(P04 J2/Pt/C eata­lyat at standard eondit~ons.

instead of the original relations (6-1) and (6-3).

For the oxidation of L-gulonic acid the original definitions for

conversion and selectivity c 2 are used. The curves corresponding

to D-galactose and D-arabinose are dotted to indicate the ad­

herent uncertainties.

L-gulonic acid is oxidized with a very high selectivity

(0.97 at a conversion of about o.85), which is even higher than

that for D-gluconic acid. The selectivity for 2-keto-D-gluconic

acid starting from D-glucose, is almost the same as that for

the D-gluconic acid oxidation. Only at high conversions the

selectivity of the D-glucose oxidation is slightly higher than

the D-gluconic acid oxidation. This indicates that the oxidative

cleavage of 2-keto-D-gluconic acid to oxalic acid in the pre­

sence of a little D-glucose is slower than in the absence of

121

D-glucose. This is to be expected if the oxidation of both

D-glucose and 2-keto-D-gluconic acid are competitive catalytic

reactions, but also if the oxygen concentration in th~ solution

is lower as long as D-glucose is present, as will be discussed

in section 6.7.

As discussed earlier, it is difficult to determine the

initial selectivity, but figure 6.16. illustrates that possibly

the initial selectivities c2 for the oxidation of the various

substrates are all relatively high. For a more accurate deter­

mination the complex formation of the aldonic acids with Pb2+

has to be investigated.

The reaction rates of the oxidative splitting of the

a-keto-carboxylic acids can be derived from figure 6.16.

The differences in the slopes of the selectivity curves are

caused by the differences in the rates of cleavage of the

carbon chain. It is clear that these rates are not directly

proportional to the 2-keto acid concentration. Two effects play

a role, viz. the increased oxygen concentration in the liquid

phase as a result of the decreased oxygen consumption rate,

and the change in catalyst activity.

These reaction rates can be ranked as follows:

2-keto-L-gulonic acid < 2-keto-D-gluconic acid ~

2-keto-D-arabinonic acid ~ 2-keto-D-galactonic acid

In order to explain this sequence we will examine the main forms

in which the 2-keto-carboxylic acids are present under

reaction conditions:

H OH

H

OH H

B-pyranose form of 2-keto-D­gl uconate

a-pyranose form of 2-keto-D-galactonate

coo-

122

Vo~00-ii"t--{0H

OH OH

a-furanose form of 2-keto­D-arabinonate

HO

H H

a-pyranose form of 2-keto-L-gulonate

Tne 2-keto-carboxylic acids will exist preferentially in

conformation in which the COO- and OH groups are equatorially

positioned, as this represents energetically the most favourable

geometry. According to the above structure formules it is to be

expected that 2-keto-L-gulonic acid is most stable and there­

fore perhaps most resistant towards oxidative cleavage. This

sequence is also in agreement with the observation that 2-keto­

D-gluconic acid exists for about 75% in the 8-pyranose form

(section 3.4.2.) and 2-keto-L-gulonic acid for more than 97%

in the a-pyranose form (6).

These experiments show that with a Pb/Pt/C catalyst a

hemiacetal function is first oxidized to a carboxyl function,

whereafter the oxidation at c2 takes place. To obtain further

insight in the background of the observed selectivities we

also investigated the oxidation of D-glucuronic acid, D-fructose

and methyl-a-D-glucoside.

D-glucuronic acid has both a hemiacetal and a carboxyl group,

so it was used to see whether the hemiacetal group or the

a-carbon would react first. We found that the hemiacetal function

had to be oxidized first to a carboxyl function before oxi­

dation at the a-position could occur. This seems to indicate that

only a free hydroxyl in the a-position of a polyhydroxy carbo­

xylic acid is able to form the reactive complex with lead.

D-fructose gave cleavage of the carbon chain by which gly­

colic acid and oxalic acid were produced, in accordance to what

has been reported by Dirkx (7) on the Pt/C catalyzed oxidation of L-sorbose.

For methyl-a-D-glucoside we expected oxidation towards

methyl-a-D-glucuronide, as happens on a Pt/C catalyst. We ob­

served indeed this reaction, but it was very much slower (by

123

a factor 8} and about half as selective as on Pt/C. This indi­

cates that the lead-platinum ensembles not only have a very

possitive influence on the c2 oxidation, but possibly also

have a negative influence on the rate of oxidation at c2 •

The results presented thus far are summarized in the

following selectivity rules for Pb/Pt/C catalysts:

An aldose is first oxidized to an aldonic acid, which is sub­

sequently oxidized to a 2-keto-aldonic acid.

- The a-hydroxyl of an aldonic acid will be oxidized preferen­

tially.

6. 7. Deactivation of the catalyst

Our experiments have mainly been carried out under such

conditions that the oxygen transfer from the gas to the liquid

phase limited the oxygen concentration in the liquid phase to

very low levels. If this is not done, a fast deactivation of the

catalyst occurs. This deactivation is a rather complex phenomenon,

as will be shown below. First the two starting procedures are

compared. The reactions were carried out under standard condi­

tions using a standard Pb/Pt/C catalyst, but with such a high

stirrer speed that mass transfer limitation from the gas phase

to the liquid phase was avoided. In figure. 6.17. the influence

of the two starting procedures is given. It can be seen that after an initial period (about 25 s) the starting procedure B

(treatment of the catalyst with nitrogen before the start)

results in a much higher reaction rate than the starting pro­

cedure A (catalyst saturated with oxygen before the start of

the experiment). Dirkx (7) has observed the same effect for a

Pt/C catalyst, but in his case the difference between the two

124

N 0 (.!)

10' .i----~-~--~--~---+ 0 1 1,5

time (ks>

o sta.rtinq procedure A

A starting procedure B

figure 6.1?. Influenae of the starting proaedure on the oxidation rate of D-gluaonia aaid with a standard Pb3(P04J2 /Pt/C aatalyst

10

time t kS I 20

o startinq pro~edure A

1> starting procedure B

figure 6.18. Influenae of the starting proaedure on the oxidation rate of D-gluaonia aaid with a 5% Pt/C aatalyst (Dirkx, (?))

starting procedures (figure 6.18.) was not so pronounced as in

our experiments. Moreover, Dirkx's catalyst could easily be re­

activated by temporarily replacement of the oxygen in the reactor

by nitrogen. In our case, however, this method was not. succes­

ful. We presume that this difference is caused by the one factor

that makes the catalysts different, viz. the lead present in our

125

catalyst. However, even with the starting procedure A we find

an initial activity (first 25 s) that is rather high and of the

same order of magnitude as starting procedure B.

This means that for the deactivation oxygen alone is not enough,

but that both oxygen and substrate are necessary. It is possible

that with this combination certain reaction products are formed

that transform the active sites in less active ones, either by

irreversible adsorption or by chemical reaction. As will be

shown below, indeed certain reaction products have a negative

influence on the catalyst activity. The difference in the deacti­

vation process for the two starting procedures must then be

ascribed to the preferential formation of deactivating compounds

when starting procedure A is used. There is, however, also

another possibility, namely that during the reaction oxygen on

the catalyst is activated to form an inactive platinum oxygen

compound.

Figure 6.19. illustrates that the oxidation on the less

_a I

-2

·---

o-t--.---.~.....--,-~~-.-~~~~-+

• ·' . e .a conversion ( - l

<> starting procedure A

A startinq procedure 6

figure 6.19. Influence of the starting procedure on the selectivity for 2-keto-D-gluconic acid at the oxidation of D-gluconic acid with a standard Pb3(P04)2/Pt/C catalyst

active sites is not only slower, but also less selective. This

again shows that this deactivation has a specific influence on

the lead part of 'the catalyst, as this is the element that

126

causes the high selectivity for c2 oxidation.

To answer the question whether adsorption of certain reac­

tion products or some other change of the catalyst is the main

cause of the deactivation,we have re-used the catalyst and the

reaction liquid resulting from an oxidation reaction in sub­

sequent experiments according to the following scheme:

fresh catalyst """

fresh 0-gluconic acid fresh catalyst solution ""' /

,,__e_x_pe_n_· m_e_n_t_1~[

filtrate / ~ {GOZ] ~ 200 mmol/1 used catalyst

l .--------. e>eperiment 2

washed with hot water

l fresh D-gluconic /acid solution

,------''---,I e>eperiment 3 .

We used the standard conditions and starting procedure A which was modified as follows: Instead of heating the

catalyst suspension in the oxidation gas atmosphere, it was

heated in a nitrogen atmosphere, and after the suspension had

reached the operating temperature, it was treated with oxygen

for 0.9 ks. In experiment 1 fresh catalyst and a fresh D-glu­

conic acid solution were used. After 0.65 ks the catalyst was

filtered off and washed with 3 1 hot water to remove adsorbed

reaction products as completely as possible. The filtrate was

concentrated in a film evaporator at 50°C and D-gluconic acid

was added to obtain again 0.5 1 with a concentration of 200 mmol/l. Thereafter two experiments were carried out: the

filtrate was contacted with fresh catalyst (experiment 2) and the

used catalyst was contacted with a fresh D-gluconic acid solution

(experiment 3).

For these three experiments the D-gluconic acid concentra­

tion as a function of time is given in figure 6.20. Both ex­

periments 2 and 3 show a lower reaction rate than experiment 1,

but the reduction in activity is much greater in experiment 2

5 2 oro E §.

N 0 l!l

10• -i----~-~-....... --...--..---t 0 d 4 d ~ • ~ ~

time (ksl

6. fresh catalyst +

fresh qluconate solution

o fresh catalyst +

filtrate of experiment l

~ used catalyst +

fresh gluconate solu~ion.

127

figure 6.20. InfZuenae of re-use of aataZyst and re­aation mixture on the oxidation rate of D-gZuaonia aaid with a standard Pb 3(P04J2/Pt/C aataZyst

than in experiment 3. We therefore conclude that the deactivation

is mainly caused by adsorption of certain reaction products

specifically on the lead part of the catalyst. This is in agree­

ment with the observed decrease in selectivity for oxidation at

c2 with decreasing activity (figure 6.21.)

_.a I

<3 .e ... j ti ~-· .. ..

.. ·• ·B ·8 conversion I- l

o fresh catalyst +

fresh gluconate solution

A fresh catalyst +

filtrate of experiment l

.0 used catalyst +

fresh qluconate solution

figure 6.21. InfZuenae of re-use of aatatyst and re­aation mixture on the seZeativity for the oxidation at C2 of D-gZuaonia aaid with a standard Pb3(P04)2/Pt/C catalyst

128

References

1. Nishikido, J., Tamura, N., Fukuoka, Y., Fuji, s., Ger.

Offenl. 2,936,652 (1980)

2. Fiege, H., Wedemeyer, K., Bauer, K., Malleken, R., European

Patent 5,779 (1979)

3. Pecsok, R.L., Juvet, R.S., J. Am. Chem. Soc., 78, 3967 (1956)

4. Sawyer, D.T., Chem. Rev., 64, 633 (1964)

5. Sawyer, D.T., Brannan, J.R., Inorg. Chem.,~' 65 (1966)

6. Crawford, T.C., Andrews, G.C., Faubl, H., Chmurny, G.N.,

J. Am. Chem. Soc., 102, 2220 (1980)

7. Dirkx, J.M.H., Ph. D. thesis, University of Technology,

Einhoven, The Netherlands (1977)

129

Chapter 7

Selective Catalytic Production of 2-keto­

D-Gluconic Acid

7.1. Introduction

In the preceding chapter we have discussed the characteris­

tics and scope of the Pb/Pt/C catalyst. In this chapter we

present subsequent investigations that were aimed at improving

the selectivity of the production of 2-keto-D-gluconic acid from

D-gluconic acid with a Pb/Pt/C catalyst. For that reason we have

investigated the influence of the catalyst concentration (section

7.2.), the oxygen partial pressure (section 7.3.), the pH (sec­

tion 7.4.) and the temperature (section 7.5.).

7.2. Influence of the catalyst concentration

The concentration of oxygen in the liquid phase is deter­

mined on the one hand by the net rate of oxygen transfer from

the gas phase to the liquid phase, which is mainly governed by

the stirrer speed, and on the other hand by the rate of oxygen

consumption by the chemical reactions taking place in the

reaction suspension. As long as a reasonable active catalyst is

maintained, the conditions can be chosen so that the oxygen con­

centration in the liquid is kept very low and the transfer of

oxygen from the liquid back to the gas phase can be neglected.

By changing the concentration of the catalyst at a constant

130

stirrer speed, one can change the rate of conversion per

unit of reaction volume, almost without influencing the mass

transfer from the gas phase to the bulk of the liquid and from

the bulk of the liquid to the outer surface of the catalyst

particles. With the stirrer speed selected (750 rpm) for the present series

of experiments we observed in the first 200 seconds of the

experiment with 40 g/l of catalyst a decrease in the oxygen gas

pressure in the reactor. In this period the oxygen pressure

regulating system could not cope with the oxygen demand of the reaction. This problem was not present during the two other ex­

periments with 20 g/l and 10 g/l of catalyst, respectively.

As basis for the Pb/Pt/C catalyst used in this study a home

made Pt/C catalyst, containing 4,85% by weight platinum, is used. The usual standard reaction conditions were applied, except that the pH was adjusted to 9.

-s 0 E ~ 10'

.~ 1 ~ I i \

: •. \ time t ks;

[catalyst)

A 40 g/l

a 20 g/l

.. 10 g/l

figure 7.1. D-gZuconic acid concentration (Zogarith­mic scaZe) as a function of time with the cataZyst concentration as parameter

In figure 7.1. a graph of the D-gluconic acid concentration

as a function of time is given for the three experiments. This illustrates that after an initial period of fast reaction the

131

reaction rate decreases markedly in each experiment (by a factor

4 or more) • If we define the initial activity as being proportional

to the quantity D-gluconic acid converted in the first 300

seconds, the initial activity is proportional to the catalyst

quantity as shown in figure 7.2. This indicates that in the presence of a fresh

-~ 150 E E

S,oo "' :;; ii N 60 g

figuPe 7.2. D-gluconic acid concentPation aftep 300 seconds convePsion as a function of the catalyst concentPation

catalyst the reaction behaves as being first order in

catalyst. This is a rather unexpected result. If we assume that

the oxygen mass transfer from the gas to the liquid is in the

three experiments governed by always the same mass transfer

coefficient and the same transfer area, then the difference

between the equilibrium oxygen saturation concentration and

the actual oxygen concentration in the liquid should be

proportional to the reaction rate:

(7-1)

132

In which:

r = reaction rate

11:,= mass transfer coefficient

a = exchange area

C*= equilibrium oxygen concentration

C = actual oxygen concentration

mol/m3 .s

m/s m2;m3

mol/m3

mol/m3

With C* estimated at 0.9 mol/m3 , and assuming that C is very

low for the experiment with 40 g/l catalyst, say below 0.01

mol/m3 , we would calculate the oxygen concentration for the

experiment with 20 g/l catalyst during the initial period to

be about 0.46 mol/m3 and for the experiment with 10 g/l

catalyst about 0.68 mol/m3 • The corresponding value for

kL·a= 0.25 s-1 , which is normal for the stirrer speed and

reactor geometry used. As we, nevertheless, find the proportio­

nality depicted in figure 7.2., we must conclude that the

initial reaction rate is zero order in oxygen.

In the second part of the curves of figure 7.1. straight

lines are obtained that suggest that the reactions behave in

that part of the experiments as being first order in D-gluconic acid. However, if we accept this first order relation

and express the first order rate constants, that can be derived

from the data of the second part of the curves, per gram of

catalyst, the rate constant obtained for the experiment with

40 g/l of catalyst is 3.3 times higher than the rate constant

for the 20 g/l experiment and 4.8 times higher than the rate

constant for the 10 g/l experiment. This indicates that the

degree of deactivation of the catalyst is more or less inversely

proportional to the quantity of catalyst present. In section 6.7.

we have shown that certain products present in the reaction

mixture have a poisoning effect on the catalyst. Figure 7.2

illustrates that the initial conversion is proportional to the

133

amount of catalyst. This would, as a first approximation, mean

that the degree of deactivation for the three experiments should

be the same. As, however, the concentration of the products is

highest in the experiment with 40 g/l catalyst one would expect

the deactivation in this case also to be the highest. As the

opposite is found we must conclude that another factor is also

operative in the catalyst deactivation. The only variable left

over is the oxygen concentration in the liquid phase. This oxygen

concentration is highest in the experiment with the lowest quan­

tity of catalyst. In accordance with the results of Dirkx (1) on

the oxidation of D-glucose and D-gluconic acid over Pt/C and of

Ostermaier et al. (2) on the low temperature oxidation of ammonia

over a Pt/Al2o3 catalyst, we assume that a surplus of oxygen can

also in our case be responsible for part of the deactivation of

our catalyst.

.&

l ?'.e :~ t; ~-4 .. .,

.2

0 0

. .......... ~--------' .... ---',,,~~ '\

~ -- _____ .,.. __ ............ .2 .4 ·• .&

conversion ( - I

selectivity c2

(catalyst]

0 40 9/l

<> 20 9/l

• I 0 9/ l

selectivity c6

[catalyst]

.. 40 9/ l

• 20 g/ 1

.. 10 9/l

figuPe 7.3. Influenae of the aatalyst aonaentPation on the selectivity c2

Figure 7.3. illustrates that the deactivation of the cata­lyst is accompanied by a decrease in the (integral) selectivity

c2 • This was already demonstrated in section 6.7. The selectivity

C6 , however, increases slightly. This again indicates that

134

at least a part of the deactivation is caused by the

adsorption of certain reaction products on that part of the

catalyst where lead and platinum interact. The graph of the

2-keto-D-gluconic acid concentration as a function of the

D-gluconate conversion (figure 7.4.) shows that the decrease

in the (integral) selectivity c2 is caused by oxidative cleavage of the target product. So it seems.that this reaction

does not need the presence of lead as a co-catalyst. Figure 7.4.

also shows that the oxalic acid is one of the products of the

oxidative cleavage. In section 7.6. the product distribution

will be discussed in more detail.

150

2-keto-D-gluconic acid //,..,.--.\ [catalyst]

s; / 0 40 g/l

~ 100 / .. 20 9/l /

E / " 10 g/l

c

/~/) oxalic acid 0

'i [catalyst] ~ 50

g • 40 9/ l

0 ~ 20 9/l u

a I 0 g/ l 0 /_ ..,,- -- --

0 .a .. .e .a conversion (-)

figure ?.4. 2-keto-D-gluaonia aaid - and o~alia aaid aonaentration with the aatalyst aonaen­tration as parameter

?.5. Influenae of the oxygen aonaentration

In the previous section and in section 6.7. we have demon­

strated that the catalyst starts to deactivate when the oxygen

concentration in the liquid. phase becomes substantially above

zero and that the deactivation is accompanied by a decrease

in selectivity.

135

In order to postpone the onset of the deactivation we carried

out a standard experiment in which instead of pure oxygen air

was used as the oxidizing agent. In this way the oxygen concentration in the liquid phase must be reduced, compared

to the concentration when pure oxygen is used, and the deacti­

vation delayed.

~ §_ ISO

" .!2 e i: 100 .. ll 0

" N 50 0 Cl

.. 1 1.&

time 1 ks I

o air

A pure oxygen

figure 7.5. D-gluconic acid concentration as a function of time with the o~ygen partial pressure as parameter

Figure 7.5. shows the D-gluconic acid concentration as a

function of time, when the oxidation is carried out with pure oxygen and with air. We see that for a large part of the experi­

ment the conversions both are zero order in D-gluconic acid, but

that the reaction rate in the case of air as oxidant is about one fifth of the rate obtained with ~xygen. This demonstrates that

the reaction rates observed are governed by the oxygen transfer rate, and that the oxygen concentration in the liquid must be small compared to the equilibrium oxygen concentration. At these low oxygen concentrations the chemical reaction rate will be

controlled by the oxygen concentration in the liquid.

136

3

time lksl

o air

4 pure oxygen

figure ?.6. D-gluaonia aaid aonaentration (logarith­mic saale) as a funation of time ~ith the o=ygen partial pressure as parameter

From the figure 7.6. where the D-gluconic acid concentration

is plotted on a logarithmic scale we can conclude that the re­

lative deactivation proceeds slower for the oxidation with air

than with pure oxygen.

.e

.2

.2 ·• ·6 ·8 conversion l- I

selectivity c2

o air

o pure oxygen

selectivity c6

A air

g pure oxygen

figure?.?. Influence of the o=ygen partial pressure on the selectivity c2 for the o=idatiori of D-gluconie acid

137

As can be deduced from figure 7.7., where the selectivities are plotted as a function of the conversion, the selectivities c2 are (after an initial period where the data are not too reliable) essentially equal for both oxygen partial pressures. This indicates that under the conditions of these two experi­ments, which are for a large part of the experiment mass transfer limited,the selectivity c2 is more a function of the conversion than of the very low oxygen concentration. This, however, cannot be considered as a proof that the deactivation is purely caused by the products formed, because in both cases the oxygen concen­tration in the liquid is bound to increase when the conversion of D-gluconic acid approaches completeness. We further note that also the selectivities c6 are ~ore or less equal for both experiments. If we compare the rate of disappearance of 2-keto-D-gluconic acid from figures 6.2. and 7.8. we can see that with air as the oxidant t~e rate of conversion of the keto acid is about 60%

~ 'f50 E

0 3

time 1 ks) 4

air

o qluconic acid

A 2-keto~D-qluconic acid

ct oxalic acid

figure ?.8. Main products for the oxidation of D­gluconic acid with air as oxidizing agent

of the rate with pure oxygen. Thus here the proportionality between oxidation rates and oxygen gas phase pressure as was found for the D-gluconic acid conversion (figure 7.5.), is not present anymore. This either means that the rate of oxidative cleavage of 2-keto-D-gluconic acid has a low order in oxygen

138

or that the catalyst has changed differently for the two experi­

ments. On the basis of the identical selectivities c2 we would

prefer the first explanation.

We further studied the influence of the oxygen concentra­

tion on the catalyst deactivation by executing some experiments

with a high stirrer speed (550 rpm), a small quantity of cata­

lyst (5 g/l), pure oxygen and with D-gluconic acid concentrations

of 100, 200 and 400 mmol/l, respectively. Under these conditions

the reaction rates are so low, that the oxygen concentration in

the liquid must be substantial and perhaps approaches the satura­

tion concentration. We now observe, as is illustrated in figure

~ E E

N 0 Cl

,<J.

o'

"' ....

............_.

5 1 u; 2 2.s 3 time lksf

3.5

[9luconic acid) at t=O

<> 400 mmol/l

o 200 mmol/ l

~ I 00 mmol/l

figure ?.9. D~giuconic acid concentration (Zogarith­mic scate) as a function of time with the starting gluconate concentration as para­meter

7.9, that the catalyst is deactivated in a period of one or two

minutes. In that period always some 20% of the D-gluconic acid

has been converted, indicating that on a fresh catalyst the

reaction behaves as being first order in D-gluconic acid. At this

stage of our study we got at our disposal a polarographic oxygen

analyzer, to monitor the oxygen concentration in the liquid.

100

80 .. c " C> 60 > x 0

.t::

" ~ 40 c 0 ~~

" 20 10 "'

0

'?"

·' 'fime (ks i3 .4 .5

[gluconic acid] at t=O

• 400 mmol/l

A 200 mmol/ l

9 l 00 mmol/l

139

figuPe 7.10. Concentpation of oxygen in the Ziquid phase foP the oxidation of D-gZuconic acid at vaPious substPate concentPations

Figure 7.10. shows for the present three experiments the course

of the oxygen concentration. In the active period the oxygen concentration is indeed very low, well below the accuracy of

the instrument: 0.05 ppm. The 100% value in this scale corres­ponds to 29 ppm, viz. the saturation concentration when the solu­tion is in contact with pure oxygen at 0.1 MPa and the reaction

temperature of 55°C. In figure 7.11 we have redrawn those curves from figures 7.9. and 7.10. that correspond to an initial D-gluconic acid concentration of 100 mmol/l. Taking into account that the 95% response time for the polarographic oxygen analyzer

is in the order of 10 seconds, then we must conclude that only at the very beginning of the reaction very low oxygen concen­

trations exist and that quite a part of the deactivation takes place under oxygen concentrations that are near 5aturation.

140

100 100

-l .o

.--.. 80

c: .g15 •+:

j 60 H

0 El!

'! ~8 u so 40 .. c: -0 u .... N :zo "": 0 0 I!)

10 0 .o. .OB .12 time t ks 1

figuPe 7.11. D-gZuaonia acid aonaentPation and the o~ygen aonaentPation in the Ziquid phase fop the e~pePiment with the staPting aonaentPation of 100 mmoZ/Z

7.4. InfZuenae of the pH

The reactivity of carbohydrates is rather strongly influenced

by the pH of the reacting solution. As the pH influence on the

oxidation of D-gluconic acid to 2-keto-D-gluconic acid might be

different from the pH influence on all other unwanted reactions,

it is obvious that a study o~ the influence of the pH on the

course of the oxidation of D-gluconic acid is worthwile. As

carbohydrates generally become more unstable at pH > 9, we have

studied the pH range from 9 to 4. The other reaction conditions

were standard, except that catalysts, regenerated by prolonged

washing with hot water, were used. were used.

The pH of the reacting system was adjusted to the required

pH during the period that the system was still filled with

nitrogen. At the moment the nitrogen was replaced by oxygen a

rise in pH was noticed, that decreased slowly as a result of

the formation of the extra acids until the required pH was

reached and controlled thereafter by the alkali supply

141

system. We assume that in the presence of nitrogen some alkali

is adsorbed on the catalyst, which is desorbed again in an oxygen

atmosphere. As is to be expected, the initial increase of the pH

was most pronounced at the pH's around 7 and about 0.7 pH units at pH 7.

N 0 (!)

0 1 1.5 time (ks)

o pH 9

A pH 8

• pH 7

o pH 6

0 pH 5

V pH 4

figure 7.12. D-giuconic acid concentration riogarith­mic ecaieJ ae a function of time with th• pH aa parameter

Figure 7.12. illustrates that for pH's below 7 the oxi­

dation rate decreases with decreasing pH. The same is true for

the oxidation of D-gluconic acid without lead(1). As all the

experiments were carried out at the same stirrer speed, a slower reaction will, according to the foregoing discussion,

result in a deactivation of the catalyst at a lower conversion. This is illustrated for pH 4, 5 and 6 by figure 7.12. For the

higher pH's the intrinsic reaction rate is high enough to let

the oxygen transfer from the gas phase to the liquid phase limit

the overall reaction rate, and therefore the curves for pH 7, 8

and 9 more or less coincide. The selectivities at pH 4 and 5

(figure 7.13.) are low, possibly because of the deactivation of the catalyst. That the selectivity at pH 6 is still rather high

142

is caused by the fact that the deactivation started when a rather

high conversion was already attained.

_a I

o+-~~.----~--..~~-.-~~....-~--+

0 .2 .4 ·6 conversion I- )

o pH 9

A pH 8

• pH 7

D pH 6

<> pH 5

• pH 4

figure 7.13. InfZuenae of the pH on the seZeativity C2 for the oxidation of D-gZuaonia aaid with a Pb/Pt/C aatalyst

We find that at pH 7 the productivity for 2-keto-D-glu­conic acid is highest. This is caused by the fact that the

high initial selectivity is maintained almost until all D-glu­

conic acid is converted. The high initial selectivity presumably

results from the favourable conditions for complexation with leao{IIJ at that pH. The fact that the high selectivity is main­

tained up to relatively high conversion derives from the obser­

vation that the rate of the oxidative cleavage decreases with

decreasing pH. This is best illustrated by figure 7.14., in

which the oxygen consumption is given as a function of time. The

first part of the curves corresponds {mainly) to the oxi~ation

of D-gluconic acid to 2-keto-D-gluconic acid, and the second part

corresponds (mainly) to the oxidative splitting of 2-keto-D­

gluconic acid. The difference in slope in the second part for the

various pH's demonstrates clearly that the rate of oxidative

cleavage decreases with decreasing pH.

eo

O'

" 60 E c 2 Q. E 40 :I II> c 0 u c ..

20 "' >-" 0

1 1.s time (kst

.. pll

o pa

a pa

143

9

B

7

figure 7.14. Inftuence of the pH on the oxygen con­sumption for the oxidation of D-gtuconic acid with a Pb/Pt/C catatyst

7.5. Inftuence of the temperature

As a number of competing reactions are involved that most

likely have different energies of activation, a study of the

influence of the temperature on the course of the oxidation of

D-gluconic acid may yield valuable information. Experiments were

carried out at pH 7 and in the temperature range from 36-65°c.

The other reaction conditions were standard. The same regenerated

Pb/Pt/C catalyst is used as in the previous experiments (section

7.4.). That the overall reaction rate increases with increasing

temperature can be derived from figure 7.15. In these experiments

again an active period is followed by a less active period. The

latter is, according to earlier findings, caused by a too high

oxygen concentration in the liquid phase. As the maximal oxygen

transfer rate was hardly temperature dependent within the range

examined, as follows from the data for the first 300 seconds of

figure 7.16., and as the oxidation of D-gluconic acid probably is

144

0 .2 ·• . e time ( ltst

.e

oT = 56.2_0 c

AT = 45.6°C

a T = 36. 2<>c

figure 7.15. D-gluaonic acid concentration (logarith­mic saale) as a function of time with the temperature as parameter

g 30

E c ·8 a. 20 E " .. c: 0 u c: .. 10

"' ,.. .. 0

0 ·2 ... ·6

time ; ks 1 ·8

OT = 56.2°C

AT = 45,,6°C

gT = 36.2°C

figure 7.18. Influence of the temperature on the o~ygen consumption

first order in D-gluconic acid, a higher reaction rate constant per unit of reaction volwne will result in a lower concentration of D-gluconic acid at the moment that the oxygen concentration in the liquid phase deflects substantially from zero.

145

Or put in another way, as the reaction rates are initially

limited by oxygen mass transfer from the gas phase, and therefore

rather independent of the temperature, the higher values of

the reaction rate constants at the higher temperature are

compensated by corresponding lower oxygen concentrations in the

solutions. This lower oxygen concentration results in less de­

activation as can be seen in figure 7.15., where the high acti­

vity is maintained longest for the highest temperature.

.2 ·• .e .e conversion 1- l

OT = 56~2°C

AT = 45.6°C

a T = 36.2°C

figure ?.1?. Inftuenae of the temperature on the setea­tivity C2 for the oxidation of D-gtuaonia aaid with a Pb/Pt/C aatatyst

From the fact that the selectivity for oxidation at c2 is hardly temperature dependent (figure 7.17.) can be concluded

that the activation energies for the various oxidation reactions

of D-gluconic acid do not differ to an appreciable extent.

At high conversion the selectivity decrease is noticeable at

a slightly .lower conversion when the reaction temperature is

lower. This is in accordance with our observation that the

deactivation of the catalyst is accompanied with a decrease in

selectivity.

146

7.6. PPoduat distPibution

In chapter 6 and in the previous sections of this chapter

we have mainly discussed the two main components of the reaction

mixture, viz. D-gluconic acid, the reactant, and 2-keto~D-glu­

conic acid, the main product, and to a lesser extent oxalic acid, a product of the oxidative cleavage. In figure 7.18. the

~ 15 E

1 1.5 time (ks>

4 9uluronic acid

°' S-keto-D-9luconic acid

o tartronic acid

D 9lucari~ acid

v ta Ttar ic acid

figuPe 7.18. By-pPoduat distPibution foP the o~idation of D-gluaonia acid with a standaPd Pb/Pt/C catalyst at standaPd Peaation conditions

concentrations of the identified products formed by side and

consecutive reactions are given as a function of time for an experiment under standard conditions applying a standard catalyst.

The corresponding information of the main components is given in

figure 6.2. These results illustrate that D-gluconic acid is

oxidized, not only at c2 , but also to a lesser extent at c6 ,

producing L-guluronic acid (GLZ) and D-glucaric acid (GAZ), and

at c5 , producing 5-keto-D-gluconic acid (SKGOZ). Besides these

products, also chain cleavage products other than oxalic acid,

like tartaric acid (TAA) and tartronic acid (TA) are formed.

147

In the concentration of L-guluronic acid, D-glucaric

acid and 5-keto-D-gluconic acid a maximum occurs. This means

that these components are oxidized further. L-guluronic acid

is transformed into D-glucaric acid. This is in agreement with

our results on the oxidation of D-glucuronic acid (section 6.6.).

D-glucaric acid most probably produces a-keto-D-glucaric acid.

In the chromatograms one finds indeed a peak that probably corresponds to this product. In order to check this, we have

oxidized D-glucaric acid with a standard Pb/Pt/C catalyst

under standard conditions. Liquid chromatography shows that D-glucaric acid is indeed the precursor of the product under

investigation. As this acid has two free a-hydroxyl groups and

the catalyst is selective for the oxidation of free a-hydroxyl

groups, it is most probable that indeed a-keto-D-glucaric acid is

this product. Further identification (by 13c-NMR) is in progress.

The 5-keto-D-gluconic acid can, in analogy to 2-keto-D­

gluconic acid, be oxidized further by carbon chain cleavage,

producing glycolic acid and a c 4 uronic acid or dicarboxylic acid. Another possibility is the reaction to 5-keto-D-glucaric

acid or 2,5-diketo-D-gluconic acid. Indeed the presence of small amount of 2,5-diketo-D-gluconic acid, kindly supplied by

dr. T.C. Crawford of Pfizer Inc., Groton, Connecticut, were

demonstrated in the reaction samples, but these can also result

from 2-keto-D-gluconic acid. carbon dioxide is also a by-product formed. At the standard

operating pH, it is mainly present in the form of bicarbonate.

This is, however, not detected at our liquid chromatographic

analysis. Therefore we (occasionally) determined its concentra­tion as follows: The reaction mixture is acidified, the carbon

dioxide formed is stripped from the solution. with nitrogen and

absorbed in a standard solution of sodium hydroxide. The concen­

tration is determined by titration with hydrochloric acid. The oxidative cleavage of 2-keto-D-gluconic acid is always

accompanied by a systematic deficit in the mass balance. In the

previous sections we have seen that oxalic acid is one of the

148

products of the cleavage of the carbon chain. Besides this c2 fragment another fragment must be formed. In first instance this

most probably is a c4 fragment. The expected c4 fragment either

is D-erythrose or D-erythronic acid. As the latter can be detec­

ted with our analytical system, but is hardly found in the

reaction samples, two possibilities arise:

(a) The c4 fragment is indeed D-erythrose, a product that is not

detected at our analytical system

(b) An intermediate product is (very) strongiy adsorbed on the

catalyst If possibility (a) is true, then the c6-balance must be constant

if oxalic acid is calculated as if it possesses 6 carbon atoms

instead of 2. In figure 7.19. this modified c6-balance is

250 +------'"---~.,...---"----'-----t

230

.... 0 ~ 210

~ ; 190

ii ~ 8 170

(c6

total] + a•(oxalic acid]

--=~~~~ ~ ----~- \

150 +---~,...--......----.---..---0 ·•

[ catalystl 40 g/l

o a = o A a = 2/3

(catalystl 10 9/l

<O a = O

o a • 2/3

figure 7.19. [Cs totail and [Cs totail + 2/3 [ox] as a funation of the aonversion with the aatalyst aonaentration as parameter

compared to the usual c6-balance for the experiments with 40 g/l

catalyst and 10 g/l catalyst (section 7.2.). These results in~

dicate that indeed, in certain cases, at the oxidative splitting

of 2-keto-D-gluconic acid., besides oxalic acid a C 4 fragment is

formed that is not detected. We tentatively assume this c4 frag­

ment to be D-erythrose.

To study the above oxidative cleavage in more detail, we

149

have oxidized a purified reaction mixture, that almost exclusively

contained 2-keto-D-gluconic acid,with 40 g/l of fresh Pb/Pt/C

catalyst. In this experiment the ratio of the increase of the

oxalic acid concentration and the decrease of the 2-keto-D­

gluconic acid concentration rose slightly from 1.7 initially

to 2.2 after a conversion of 76%. At the latter conversion the

mass deficit amounted about 19%. This is roughly in agreement

with the mass deficit from the reaction 1 c6 + 2.2 c2 • The fact

that the above described ratio is higher than 1 and increases

with the conversion, indicates that at the cleavage of the

carbon chain of 2-keto-D-gluconic acid between c2 and c3 most

probably an aldehydic c4 fragment is formed, that on its turn

is rather slowly oxidized and thereafter also split between

c2 and c3 at which oxalic acid and an aldehydic c2 fragment

is formed. That the above ratio reaches values higher than 2

means that the remaining aldehydic c2 fragment must also partly be oxidized to oxalic acid. This observation thus supports our

assumption that the mass deficit is caused by the formation of

non-acidic products that are not detected at our ana,lytical system. That the above ratio is initially higher than 1 means

that the oxidation of D-erythrose on a fresh catalyst is much

faster than on a deactivated catalyst. On the basis of the above considerations, and the assumption

that not yet identified products in our reaction samples are

D-erythronic acid and 2-keto-D-erythronic acid, the following

scheme for the cracking of 2-keto-D-gluconic acid is proposed:

1.?ott T""°

aor-H Hr-OH

H""';-Otl CH 20H

2-keto-o­qluconic ac14

oxalic acid

1-~ H--C-OH

1i-~-OH

CH 20H

D-erythrose

,o 7-oH C-Ol! •o

f'~H H-('.-OH

H-f-oH CH 200

o-erythronic acid

. \

,o ~-()II c-u 'o

qlycoxilie acid

"° ~-OR

HJ:~ Cu2oa

2-keto .. l)oo erythronlc

acid

9lycolic acid

oxalic acid

.J· \ o,

150

This scheme shows that at the very end, l mol of 2-keto-D­

gluconic acid is oxidatively degraded to 3 mol oxalic acid.

For 5-keto-D-gluconic acid an analogous chain cleavage

pattern can be formulated:

,,.0 C-OH

I H-C-OH

I HO-C-H

I H-C-OH

I C=O

' CH 20H

~-keto-o­gluconic

acid

"'° C-OH I

H-C-OH I

HO-C-H I

C-H "o

'L-threuronic acid

+

glycolic acid

' H-C-OH I

OH-C-H I

<;;OH 'o

tartaric acid

It is evident that the resulting tartaric acid and gly­

colic acid can be oxidized too, but as 5-keto-D-gluconic acid

is only formed in small amounts, these consecutive products

are of minor importance.

In chapter 3 we have discussed the analytical results

(figures 3.6., 3.8. and 3.11.) of a fraction collected from

a reaction mixture of the oxidation of D-gluconic acid with a

Pb/Pt/C catalyst applying starting procedure A (section 6.7.).

These results demonstrate that besides the usual products also

smaller monocarboxylic acids are formed: D-glyceric acid,

glycolic acid and possibly a small amount of D-erythronic acid.

This indicates that deactivation of the Pb/Pt/C catalyst makes

it less selective for oxidation at c2 in favour of chain

cleavage.

The above results are summarized in the following general reaction scheme:

,0 ~-OH

H-~-OH

HO-~-H

H-1-oH H-~-OH

CH20H

D-9 l ucon ic actd

<!.o '--oH

'i'"" HO-~-H

H-C-OH

H~-OH CH20H

2-keto-o-9luconic acid

,o <;-OH

H-~-OH

HO-~-H

H-~-OH

1""0 CH20H

:.-keto-D-9luconic

acid

J) ~-OH

H-~-OH

H0-1-H

H-<;-OH

H~-OH

C-H

' 0

L-guluronJ.c acid

<je,H

~"'° cha.in HO-c-H cleavage H~-oH ........,.. products

~=o CH20H

2, 5-di-keto-o­gluconic acid

~~OH H•C-OH

00-~-H

u1-0H H-C-OH

C-oH 'o

D-qlucarJ.c acid

chain cleavage products

oxalic acid

1f0oH h-~-OH

tt-<;-OH

CH2ou

o-erythronic acid

,o ~-OH

u-q-oH HO-C-H

C~u

tartaric acid

glycolic add

.o ~-OH

~"'0 H-<;-OH

CH20H

2-keto-o­crythronic acid

chain cJ.eavaqe products

--[ ... : .. ,o 1-0H CH 20H

glycolic acid

,..... U1 ,.....

152

References

1. Dirkx, J.M.H., Ph. D. thesis, University of Technology,

Eindhoven, The Netherlands (1977) 2. Ostennaier, J.J., Katzer, J.R., Manogue, W.H., J. Catal.,

!!1 277 (1976) 3. Perry, R.H., Chilton, C.H., "Chemical Engineers's Handbook",

(5th ed.), Ch. 3, p. 98, Mc Graw-Hill Kogakusha, Ltd.,

Tokyo ( 1 9 7 3 )

153

Chapter 8

Final Discussion

8.1. Introduction

In chapter 6 and 7 we have presented our study on the

potential of a Pb3 (P04) 2/Pt/C system as a selective catalyst in

the oxidation of aldonic acids in aqueous media. This first study

had as main objective the delineation of the catalyst properties. In this chapter the characteristics of this system will be in­

corporated in a tentative proposal for the reaction mechanism

(section 8.3). A literatury study concerning the complexation of

D-gluconic acid with lead(II), as presented in section 8.2,,

resulted in useful information for the deduction of the adsorp­

tion of the substrate on the catalyst. In section 8.4. a discus­sion on the kinetics of the reaction is given. Potential appli­

cations of the Pb/Pt/C catalyst are presented in section 8.5.

8.2. Coordination of Pb 2+ with D-gluaonia acid

In the preceeding two chapters we have discussed that in the

reaction mixtures the lead(II) of the Pb3 (P04) 2/Pt/C catalyst

system can occur as the following species:

a. adsorbed as lead(II)phosphate in the direct vicinity of the

platinum crystallites, and probably bound to the platinum part

154

of the catalyst (Pb-Pt ensembles) •

b. adsorbed as Pb3 (P04J 2 not in the direct vicinity of the

platinum. 2+

c. dissolved, either as coordinated or as free Pb •

The lead(II) species not in the direct vicinity of platinum

are catalytically not active (section 6.3.3.), and the concen­

trations of the dissolved species are so low (sections 6.3.2.

and 6.3.3.) that it is unlikely that they play an important role

in the conversion. From the fact that Pt/C without lead (chapter

5) has a much different effect on the oxidation of D-gluconic

acid than the Pb3 (Po4 J2/Pt/C catalyst formulation, we concluded

that the lead-platinum ensembles are responsible for the charac­

teristic properties of the modified Pt/C catalyst.

The substrate must be activated and positioned in such a way

in relation to the hydrogen abstracting platinum site of the

catalyst that this abstraction occurs preferentially at the

second carbon atom. We assume that this is caused by the specific

interaction between the substrate and the lead of the catalyst

system. The literature on the complexation of D-gluconic acid

with bivalent lead yields the followin9 information:

Pecsok and Juvet (1) have studied the gluconate complexes

with lead(II). With a combination of optical rotation and polaro­

graphic measurements they proved the existence of a number of

lead-gluconate complexes. Both Pecsok and Juvet (1) and Coccioli

and Vicedomini (2,3) have determined the stability constants for

the various species present. According to them the following

species can occur: + *l A 1:1 species (PbGH4 ) and a 1:2 species (Pb(GH4> 2> are

present in the pH range 1-6. In the pH range 5-10 one solid lead

*) In this chapter we depict D-gluconic acid, in accordance with

the coordination chemistry literature, as HGH4 • The first H

refers to the hydrogen of the carboxyl function and the other

four H's refer to the hydrogens of the four secondary hydroxyl

groups.

gluconate complex or a mixture of. different solid complexes is

formed at a lead gluconate ratio of about 1. At a pH above 10

a 2:2 (Pb 2 (GH2 l 2- 2) and a 3:2 species. exist.

155

According to Carel! and Olin (4,5) lead(II) hydroxyl com­

plex species can also be present. In acid solution the hydroxyl

ion concentration is too low for the formation of such species.

At higher pH's, however, the latter authors have demonstrated,

in the absence of gluconate, the existence of Pb(OH)x (2-x)

species in which x is the average number of hydroxyl ions

coordinated per Pb 2+ ion. This number rises from 0 (only

coordination with H2o) at about pH 6, to 3 at pH 13. Based on these results it is to be expected that, especially at higher

pH's, a competition will occur between the above two ligands,

viz. the gluconate ion and the hydroxyl ion. Indeed Coccioli 2- 2-and Vicedomini (3) have found Pb(GH 2) (OH) and PB 2 (GH) (OH) 2

species in strongly alkaline medium. Melsqn and Pickering (6)

have demonstrated that also at a lower pH hydroxyl functions can be incorporated into a lead gluconate species, by precipitating

the lead hydroxyl gluconate salt Pb 2 (GH4 ) 2 (0H) 2 by adding sodium

hydroxide slowly to a 1:1 lead gluconate solution until the pH reached 7.3.

The above data refer mainly to dissolved lead species. In

our experiments, however, the lead(II) is mainly deposited on

the catalyst surface. Therefore there might be geometric limi­tations to the interaction with the substrate. Nevertheless, one

might expect that the interactions that occur on the catalysts

will show types of bounding that are comparable to those found in

the complexes in homogeneous solution. As we have carried out our oxidations mainly in the pH range

of 5-9 we will examine the types of species present at these con­ditions in more detail. The authors mentioned (1-6),reported for

relatively high Pb 2+/gluconate ratio's the formation of a preci­

pitate in neutral solution. However, we have found that if we 2+ add to the substrate solution, as Pb , the small amount of lead

present in our catalyst system, no precipitation occured. Based

on this observation, one would expect that the gluconate species

156

formed on the active sites of our catalyst are not irreversibly

adsorbed. This is in agreement with the results of our oxida­tions.

From the stability constants reported for the various lead

complexes it can be calculated that under the conditions of our

experiments, pH 5-9, lead(II) complexation with gluconate is

more likely than with hydroxyl.

Brannan and Sawyer (7,8) claim, on basis of unpublished NMR data, that in neutral solution the lead is bonded to the carboxy­

late group and the a-oxygen. They have demonstrated that in alka­line medium (pH 11-13) also they-oxygen is involved. Isbell's

optical rotation measurements and Melson and Pickering's (6) infrared data in combination w:iith Littleton's (11) X-ray data of the lead alkali salt of D-gluconic acid support the conclusion that the a-oxygen is bonded to the lead ion. With respect to the Bi/Pt/C catalyst one might note that the above NMR study (7)

indicates that also in the 1:1 bismuth gluconate complex the bonding involves the carboxylate and the a-oxygen of the ligand and possibly, to a small extent, the carboxylate and $-oxygen.

Coccioli and Vicedomini (3) have determined the following dissociation equilibria for the D-gluconate anion at 25 °c in 1 M Nac104 solution:

+H2o GH 2- + - ____,,.

GH4 3 + H30 13.66 + 0.08

-H20

GH 2-+H20

GH 3- + H O+ 3 2 3 14.06 + 0.10

-H20

The fact that, at a pH as low as 10.5 (1,9), the hydroxyl functions involved in complex formation already start to dis­sociate, indicates that complex formation facilitates this dis­

sociation. The information presented above can be accomodated by the

following structure of a dissolved lead gluconate species, that

157

could occur at our reaction conditions:

fl gO c-o ~

H-d-o ~Pb ----bo I 'H I 'H

HO-C-H HO-C-H I I

H-C-OH H-C-OH I I

H-C-OH H-C-OH I I

CH20H CH20H

As mentioned earlier, such a 1:2 lead gluconate complex is,

because of geometric limitations, rather unlikely at the cata­

lyst surface, but one might perhaps expect an adsorbed species of

the following kind:

HOHH H 0'\\ I I I I

,c-~-9-9-9-cH2oH 0 0 H OHCE \ I \·

\ I H \I

0 Pb 0

I /\ I O-P-0 O-P-0

JI

0 II

0

8.S. Reaation meahanism

The experimental evidence presented in this thesis is

insufficient to decide unequivocally for one special reaction mechanism. To that end further studies are required. It is clear

that these investigations will not be easy, because we have as

yet not been able to maintain an. active catalyst under conditions where oxygen transfer from the gas phase is not limiting. The

following discussion regarding the reaction mechanism must there­

fore be considered as a first approximation only.

158

In section 5.1. we came to the conclusion that the oxidation

of D:-gluconic acid on a Pt/C catalyst probably follows a dehydro­genation mechanism. We would suggest that the oxidation of the

same substrate on a Pb/Pt/C catalyst is also a dehydrogenation

reaction. De Wit et al. (11,12) have shown that the reaction of

reducing sugars, e.g. D-glucose, on a Pt/C catalyst in an alkaline

medium (pH 12-13) and in the absence of oxygen is a dehydrogena­

tion reaction that can be depicted as:

The reaction proceeds via the glucose anion, and the rupture of

the carbon-hydrogen bond on c1 is the rate-determining step. In section 8.2. we have already discussed the existance of

lead-platinum ensembles. In the molecular model shown below it

is suggested that, on the analogy of the model of the Delft group

(12), in our case gluconate can complex with the lead in such a way that the hydrogen on c2 is located favourably for abstraction. Moreover.the coordination with Pb(II) is considered to enhance

the ability of the H at c2 to be transferred as a hydride ion.

As has been pointed out in the previous section the hydroxyl

group on c2 is probably not yet dissociated, but due to complex formation the hydrogen oxygen bond is weakened. Therefore we prefer a mechanism in which the dissociation and the hydride

transfer are concerted processes, as is depicted below.

We further suggest that, on the analogy of the D-glucose

oxidation, here these two concerted reactions determine together

the rate of the oxidation of D-gluconic acid. This is in agreement

with our observations that in the active period of the catalyst

159

e --~r 9--;;? x H :Z:-.0 ,,,- ' (' r

.. KJ ~.

.. I

Pb Pt

the reaction rate is probably first order in catalyst (section

7.2.) and in gluconate (section 7.2.), and zero order in oxygen ~xcept at very low oxygen concentrations (section 7.2.) • In the

latter case the catalyst may become covered with hydrogen, which

will stop further dehydrogenation. The reaction rate then will

be determined by the oxygen supply and presumably be first order

in the oxygen gas pressure. This is in agreement with the results of the experiments with air and pure oxygen (section 7.3.).

The driving force for the dehydrogenation is probably the enhancement of the hydroxyl dissociation which activates the c2-H bond, in combination with the favoured position of the c2 hydrogen towards the platinum site. This explaines the high selectivity for oxidation at c 2 and also ~he observation that the reaction rate on a Pb/Pt/C catalyst is higher than on a Pt/C

catalyst with the same platinum content.

After reaction the product (2-keto-D-gluconic acid) will

desorb and the hemiacetal ring will be formed. Unfortunately we

have no data on the coordination of 2-keto-D-gluconic acid with

160

Pb(II) to predict the competition between the main product and

the substrate in the coordination with the lead(I1) on the cata­lyst and in the solution.

The influence of the pH on the reaction rate (section 7.4.) can possibly be explained by the increase in degree of dis­

sociation of the hydroxyl group at c2 with increasing pH, thus

facilitating the hydride abstraction. However, it must be kept in mind that at relatively high pH's hydroxyl complexation of the lead on the catalyst can compete with the D-gluconic acid coordination.

The cause of the deactivation of the Pb/Pt/C catalyst is uncertain. There are strong indications that the deactivation starts when the oxygen concentration in the liquid phase rises significantly above zero (section 7.3.). This could result in a change of the lead site and/or the platinum site. A change of the platinum site could possibly be the chemisorption of oxygen on this site as suggested by Dirkx for the oxygen deactivation of

Pt/C catalysts in carbohydrate oxidation (13), or a real chemical reaction to a less active site. As was discussed in section 6.6.,

the adsorption of certain reaction products 6n especially the

lead-platinum ensembles is probably another cause of deactivation.

8.4. Kinetics of the D-~iuconic acid oxidation with a

Pb/Pt/C catatyet

As demonstrated in section 7.3. with three experiments at different substrate concentrations, it is not possible to deter­mine the reaction rate constants in the normal way. This is due to the fast deactivation of the catalyst as soon as the oxygen concentration in the liquid phase rises substantially above zero. At the reaction conditions applied up to now, we have provided for

such low oxygen concentrations by limiting the oxygen transfer

from the gas- to the liquid phase. This, however, did also limit

161

the reaction rate, so the data obtained in this way cannot be

used to calculate reaction rate constants. It follows from these

considerations that it will only be possible to determine the

kinetics if either of the following two constraints are satis­

fied:

1. The oxygen transfer from the gas- to the liquid phase must

not limit the overall reaction rate.

2a. The oxygen concentration in the liquid phase must be very

low, or

2b. Ways and means are to be found to maintain the activity of

the catalyst at near equilibrium oxygen concentration in the

solution.

As far as the first mentioned two constraints are concerned,

these seem at first sight to be contradictory, but a combination

with the second possibility may be feasible. If we would use a

low oxygen partial pressure of the oxidation gas mixture in

combination with a very high kL.a (see formula 7.1), i.e. a very

high stirrer speed, and with a low catalyst concentration, it

could be possible to fulfil the above constraints. A further

possibility lies in the search for more stable Pb/Pt/C catalysts.

To this end the deactivation mechanism must be studied in-detail.

8.5. Applications of the Pb/Pt/C catalyst

In the introduction (section 1.3.) we have already discussed

the use of the Pb/Pt/C cai:alyst in the manufacture of iso­

vitamine C, a very good anti-oxidant in e.g. food, and 2-carboxy­

D-gluconic acid, a potential phosphate substitute in detergent

formulations.

Besides these two appl:ications, there seems to be another

important industrial application, viz. an alternative route for

the manufacture of vitamin C, as proposed by Kuster and Godefroi

(14) :

162

starch

methyl-«-O-glucoside

<f H20H H-C-OH

I HO-C-H

I H-C-OH

I H-C-OH

I COCH

L-gulonic acid

L-ascorbic acid

(vitamin Cl

Pt/C

H I

CH 3o-c -----i H-~-OH I

HO-C-H 0

H-~-OH I H-C__j

I COOH

methyl-u-0-glucoronide

Pb/Pt/C

?H20H H-C-OH

I HO-C-H

I H-C-OH

I C=O I COCH

2-keto-L-gulonic acid

To underline the industrial interest for the method, described

in this thesis, for the manufacture of a-keto-carboxylic acids

with the aid of Pb/Pt/C catalysts, it may be mentioned that a

Dutch patent has been applied for this procedure by Akzo N.V.

References

1. Pecsok, R.L., Juvet, R.S., J.Am.Chem.Soc., 78, 3967 (1956)

2. Coccioli, F., Vicedomini, M., J.Inorg.Nucl.Chem., 40, 2103 (1978)

3. ibid., 40, 2106 (1978)

4. Olin, A., Acta Chem. Scand., 14, 126 (1960)

5. Carell, B., Olin, A., Acta Chem. Scand., .!!• 1999 (1960)

6. Melson, G.A.,Pickering, W.F., Aust.J.Chem., 3,! 1 2889 (1968)

7. Brannan, J.R., Sawyer, D.T., unpublished results

8. Sawyer, D.T., Chem.Rev., 64, 633 (1964)

Sawyer, D.T. I Brannan, J .R. I Inorg .Chem., ~I 65 (1966)

Isbell, H. s. I J.Res.Natl.Bur.Std., 14, 305 . (1935)

163

9.

10.

11. De Wit, G. I De Vlieger, J .J., Kock-van Dalen, A.C. I Kieboom,

12.

A.P.G., Van Bekkum, H. I Tetrahedron Lett., 15, 1327 (1978) De Wit, G., De Vlieger, J.J., Kock-van Dalen, A.C., l~eus, R. I

Laroy, R., Van Hengstum, A.J., Kieboom, A.P.G., van Bekkum,

H., Carbohydr.Res., 91, 125 (1981)

13. Dirkx, J.M.H., Ph.D.Thesis, Eindhoven University of Technology,

Eindhoven, The Netherlands {1977)

14. Kuster, B.F.M., Godefroi, E.F., Internal report, Eindhoven

University of Technology, Eindhoven, The Netherlands, {1982).

Appendix I: Structure formulas

-?o C-H I

HO-C-H I

H-C-OH I

H-C-OH I

H-C-OH . I

H

D-arabi-

nose

p C-OH I

H-C-OH I

HO-C-H I

HO-C-H I

H-C-OH I

H-C-OH I H

D-galacto­

nic acid

,p C~H I

HO-C-H I

HO-C-H I

H-C-OH I

HO-C-H I C-OH

" L-guluro­

nic acid

p C-OH I

HO-C-H I

H-C-OH I

H-C-OH I

H-C-OH I

H

D-arabi­

nonic acid

0 c!oe I

H-C-OH I

HO-C-H I

H-C-OH I

H-C-OH I C-OH ~

D-glucaric

acid

0 c!oH I

H-C-OH I H

glycolic

acid

H I

H-C-OH I C=O I

HO-C-H I

H-C-OH I

H-C-OH

' H-C-OH I H

D-fructose

0 c!u I

H-C-OH I

HO-C-H I

H-C-OH I

H-C-OH I C-OH ~o

D-glucuro­

nic acid

p C-OH I

H-C-OH I

HO-C-H I

H-C-OH I

H-C-OH I

H-C-OH I H

D-gluconic

acid

.P c!:.e I

H-C-OH I

HO-C-H I

HO-C-H I

H-C-OH I

H-C-OH I H

D-galactose.

p C-H I

H-C-OH I

HO-C-H I

H-C-OH I

H-C-OH I

H-C-OH I H

D-glucose

p Cloe I C=O I

H-C-OH I

H-C-OH I

H-C-OH I H

2-keto-D-

arabinonic

acid

165

166

~o C~OH

~o C~OH

~o C-oe

?o C-OH

I I I I C=O C=O H-C-OH C=O I I I I

HO-C-H HO-C-H HO-C-H HO-C-H I I I I

HO-C-H H-C-OH H-C-OH H-C-OH I I I I

H-C-OH H-C-OH C=O HO-C-H I I I I

H-C-OH H-C-OH H-C-OH H-C-OH I I I I

H H H H

2-keto-D- 2-keto-D- 5-keto-D- 2-keto-L-

galactonic gluconic gluconic gulonic acid

acid acid acid

c!0oe p I

HO-C-H ~o

C-OH I I

HO-C-H H-C-OH C~OH H-C-OH I ~ I I

H-C-OH C-OH C-OH I ~ ~ HO-C-H I

H-C-OH I H

L-gulonic formic oxalic tartronic

acid acid acid acid

COOH I

CHOH I

CHOH I

COOH

tartaric

acid

167

Summary

This thesis deals with the selective oxidation of D-glucose

and D-gluconic acid to 2-keto-D-gluconic acid with oxygen in

neutral or weak alkaline aqueous medium with the aid of a plati­

num on carbon catalyst that has been modified by addition of an

ins.oluble lead (II) salt. We also report on our endeavours to

improve the manufacture of D-glucaric acid from D-gluconic acid.

D-Glucaric acid and 2-keto-D-gluconic acid are industrially

interesting products. The former and 2-carboxy-D-gluconic acid,

that can be made out of 2-keto-D-gluconic acid, are potential

alternatives for the polyphosphates in detergent formulations.

!so-vitamin C, another product that can be manufactured from

2-keto-D-gluconic acid, can serve as anti-oxidant in e.g. food.

Further a survey of the literature concerning the preparation of

D-gluconic acid, D-glucaric acid and 2-keto-D-gluconic acid is

presented.

Much attention has been directed to the analysis of the

substrates and their products. Ion-exchange chromatography was used successfully for this purpose. At times isothachophoresis, preparative liquid chromatography in combination with 13c-nuclear

magnetic resonance spectroscopy, and a specific detection method

for a-keto acids were applied to obtain additional information.

For the present investigations a batch-wise operated stirred

tank reactor is used. The copper(II) and cobalt(II) compounds and

complexes testes as catalyst for the oxidation of D-gluconic acid,

did not result in the production of D-glucaric acid, but some of

them did catalyze the degradation of D-gluconic acid. The oxida-

168

tion of borate. gluconate esters with a Pt/C catalyst at pH 8-10

and borate/gluconate ratios of land 2 did not result in an

industrially interesting approach for manufacturing D-glucaric

acid. In the Pt/C catalyzed oxidation of D-gluconic acid the selectivity for D-glucaric acid and the reaction rate decreases

with decreasing pH. However, below pH 3.5 the selectivity and reaction rate increases again. Both improvements are, however, not great.

More positive results are obtained by the deposition of a lead(II) compound (e.g. Pb 3 (P04) 2) on Pt/C. This results in a catalyst with which aldoses or aldonic acid can be oxidized with oxygen to the corresponding a-keto-aldonic acids with a high

selectivity (about 90%) • The ratio for oxidation of D-gluconic acid at c2 compared to c6 is about a factor 150 higher for the modified Pt/C catalyst than for the normal Pt/C catalyst. Lead­platinum ensembles are probably the catalytically active species

of the Pb/Pt/C catalyst. This modified catalyst is also more active than the normal Pt/C catalyst. A Pb/Pt ratio of about 0.2 is enough to obtain the maximal selectivity for 2-keto-D-gluconic acid, indicating that with this ratio the optimal lead platinum

surface modification is already obtained. The Pb/Pt/C catalyst deactivates very fast (within a few

minutes) when the oxygen concentration in the liquid phase rises substantially above zero. Adsorption of certain products, probably on the lead-platinum ensembles, also causes deactivation of the catalyst.

With the addition of copper(II) acetate and especially bismuth(III) hydroxyde to a Pt/C catalyst also an improved selec­tivity for oxidation at the a-carbon is found. As lead(II), copper(II) and bismuth(III) all form complexes with D-gluconic acid in which both the carboxylate function and the a-hydroxyl group are involved, the observations on Cu(II) and Bi(III) support our notion that such complexes also play a role in the catalysis of the Pb/Pt/C catalyst. This complex formation leads

to enhanced ionization of the hydroxyl function at c2 • Due to the

juxtaposition of the lead(II) and the platinum on the catalyst,

169

and the negative charge of the oxygen on c2 , hydride transfer

from this carbon atom to the platinum is facilitated. Based on the observations that the reaction is probably first order in catalyst and D-gluconate and zero-order in oxygen (except at very low oxygen concentrations), we postulate that the hydride abstraction and the ionization of the a-hydroxyl function determine together the rate of the reaction.

170

Samenvatting

Dit proefschrift beschrijft de selectieve oxydatie van

D-glucose en D-gluconzuur tot 2-keto-D-gluconzuur met zuurstof

in neutraal of zwak alkalisch waterig milieu met behulp van een

platina op kool katalysator die gemodificeerd is door toevoeging van een onoplosbaar lood(II) zout. We berichten ook over onze

inspanningen om de bereiding van D-glucaarzuur uit D-gluconzuur

te verbeteren.

D-Glucaarzuur en 2-keto-D-gluconzuur zijn industrieel

interessanteprodukten. De eerste en 2-carboxy-D-gluconzuur, dat

gemaakt kan worden uit 2-keto-D-gluconzuur, zijn potentiele

alternatieven voor de polyfosfaten in de wasmiddel formuleringen.

Iso-vitamine C, een ander produkt dat bereid kan worden uit

2-keto-D-gluconzuur, kan dienen als ant:L-oxydant in bijv. voedsel.

Verder is een overzicht van de literatuur betreffende de berei­

ding van D-gluconzuur, D-glucaarzuur en 2-keto-D-gluconzuur gegeven.

Er is veel aandacht geschonken aan de analyse van zowel de substraten als hun produkten. Ionenwisselings-chromatografie werd met succes toegepast voor dit doel. Bij gelegenheid werden ook isotachoforese, preparatieve vloeistofchromatografie in

kombinatie met 13c-kernspin-resonantie spektroskopie en een specifieke detektie-methode voor a-keto zuren gebruikt voor het

verkrijgen van additionele informatie.

Voor het onderzoek werd een ladingsgewijs bedreven geroerde

tank reactor gebruikt. De als katalysator geteste koper(II) en

cobalt(!!} verbindingen en komplexen voor de oxidatie van

171

D-gluconzuur, resulteerden niet in de produktie van D-glucaar­

zuur, maar enkele katalyseerden wel de degradatie. van D:-glucon­

zuur. De oxidatie van boraat-gluconaat esters met een Pt/C

katalysator bij pH 8-10 en boraat/gluconaat·verhouding van 1 en

2 resulteerde niet in een industrieel interessante benadering

van de fabrikage van D-glucaarzuur. Bij de platina op kool

gekatalyseerde oxydatie van D-gluconzuur daalt de selektiviteit

voor D-glucaarzuur en de reaktiesnelheid met dalende pH. Echter

beneden pH 3,5 stijgen de selektiviteit en de reaktiesnelheid

weer. Beide verbeteringen zijn echter niet groot.

Positievere resultaten worden verkregen door het neerslaan

van een lood(II) verbinding (bijv. Pb 3 (P04 ) 2) op Pt/C. Dit levert

een katalysator waarmee aldoses en aldonzuren met een hoge selek-·

tiviteit (ongeveer 90%) met zuurstof geoxydeerd kunnen worden tot

de korresponderende a-keto-aldonzuren. De verhouding voor de oxydatie van D-gluconzuur op c2 ten opzichte van c6 is ongeveer

een faktor 150 hoger voor de gemodificeerde Pt/C katalysator dan

voor de normale Pt/C katalysator. Waarschijnlijk zijn lood­

platina ensembles de katalytisch aktieve species van de Pb/Pt/C katalysator. Deze gemodificeerde katalysator is ook aktiever dan

de gewone Pt/C katalysator. Een Pb/Pt verhouding van ongeveer 0,2

is voldoende om de maximale selektiviteit voor 2-keto-D-glucon­

zuur te verkrijgen, wat er op wijst dat. bij deze verhouding al de

optimale lood-platina oppervlakte-modifikatie is bereikt. De Pb/Pt/C deaktiveert erg snel (binnen enkele minuten) als

de zuurstofconcentratie in de vloeistoffase substantieel boven

nul stijgt. Adsorptie van bepaalde produkten, waarschijnlijk op

de lood-platina ensembles, veroorzaakt ook deaktivering van de

katalysator. Met de toevoeging van koper(II)acetaat en bismuth(III)­

hydroxyde aan een Pt/C katalysator wordt ook een verbeterde

selektiviteit voor oxydatie op het a-koolstofatoom verkregen. Daar zowel lood(II) als koper{II) als bismuth(!!!) met D-glucon­

zuur komplexeren, waarbij zowel de carboxylaat funktie als de

a-hydroxyl 'C}roep zijn betrokken, ondersteunen de waarnemingen aan

Cu(II) en Bi(III) ons denkbeeld dat zulke komplexen ook een rol

172

spelen bij de katalyse van de Pb/Pt/C katalysator. Deze komplexe­ring leidt tot sterkere dissociatie. van de hydroxyl funktie op

c2 • Door de juiste positionering. van het lood(II) en het platina op de katalys-ator, en de negatieve lading van de zuurstof op c2 ,

wordt de hydride overdracht van dit koolstofatoom naar het

platina vergemakkelijkt. Gebaseerd op de waarnemingen dat de reaktie waarschijnlijk eerste orde is in katalysator en D-gluco­naat en nulde orde in zuurstof (behalve voor erg lage zuurstof­concentraties) postuleren we dat de hydride abstraktie.en de ionisatie van de a-hydroxyl funktie samen de snelheid van de reactie bepalen.

173

Dankwoord

Bet onderzoek, beschreven in dit proefschrift, is tot stand gekomen dankzij de medewerking van velen. In het bijzonder geldt

dit voor de medewerkers en studenten van de vakgroep Chemische Technologie. Aan allen hiervoor mijn hartelijke dank.

Mijn hartelijke dank gaat uit naar mijn promotoren prof. H.S. van der Baan en prof. K. van der Wiele, alsmede naar mijn co-promotor B.F.M.Kuster, voor hun stimulerende en kritische discussies die mijn werk steeds zeer ten goede zijn gekomen.

In het bijzonder dank ik heel hartelijk de heer W.P.Th. Groenland, die met zeer grote toewijding en kennis van zaken heeft meegewerkt aan het onderzoek.

Vee! dank ben ik verschuldigd aan de afstudeerders F.X.M.G. Schiffelers, M.G.M.Wolfs, C.H.M.G.Krutzen, W.R.M.Martens, R. Reintjens en H.Naus, alsook W.Brouwer, die allen met veel inzet en enthousiasme hebben meegewerkt aan het onderzoek. Eveneens dank ik de vele praktikanten en stagiaires voor hun bijdragen.

Verder ben ik dank verschuldigd aan de heren W.Bol en L.A.Th. Verhaar van de werkgroep Koolhydraten voor hun collegialiteit en interessante discussies.

De heren D.Francois, M.P.A. van der Heyden, A.G.M.Manders, G.A. van de Put en R.J.M. van der Wey dank ik voor de goede tech­nische ondersteuning. De heer J.M.A. van Hettema voor het altijd snel afhandelen van administratieve zaken en de heer W.C.G.Heugen voor zijn behulpzaamheid die de gang van zake vaak vergemakke­lijkte.

De vakgroep Instrumentele Analyse en in het bijzonder de heren F.M.Everaerts, J.C.Reijenga en Th.P.E.M.Verheggen van de werkgroep Isotachoforese, de heer A.C.Schoots van de werkgroep Vloeistofchromatografie en de heren J.W. de Haan en L.J.M. van de Ven van de werkgroep Kernspin-resonantie spektroskopie dank ik heel hartelijk voor hun adviezen en daadwerkelijke analyses van

de monsters. De diskussies met de .heren Batelaan en de Kleyn van Akzo

hebben bijgedragen tot de praktische toepasbaarheid van het in

174

het proefschrift beschreven reaktiesysteem. Mijn hartelijke dank

hiervoor.

Prof.H. van Bekkum van de T.H.Delft en prof.E.F.Godefroi

dank ik voor het snelle en concientieuze corrigeren van het

manuscript van dit proefschrift.

Mijn dank gaat verder uit naar de heer R.J.M. van der Weij

voor het vele en uitstekende tekenwerk in dit proefschrift en de

dames A.M.A. van Bemmelen en C.Rovers voor de goede verzorging

van het vele typewerk.

Gaarne maak ik van deze gelegenheid gebruik om ook famlie,

vrienden en bekenden te danken voor hun indirekte bijdragen tot

de totstandkoming van dit proefschrift.

175

Levensbericht

Peter Carolus Cornelia Smits, .geboren op 26 april 1953 te

Urmond, began na zijn eindexamen MULO-B in 1969 met de studie

Chemische Techniek aan de Hogere Technische School te Heerlen en

behaalde zijn diploma op 28 juni 1974. Na het vervullen van de

militaire dienstplicht in de periode 1974-1975, studeerde hij

Scheikundige Technologie aan de Technische Hogeschool te Eind­

hoven, alwaar hij op 31 oktober 1979 met lof afstudeerde. Zijn

afstudeerwerk betrof het opstellen van een model voor de kirietiek

van de heterogeen alkalische isomerisatie van lactose in een

buisreaktor. Per 1 november 1979 trad hij in dienst van de Technische

Hogeschool te Eindhoven als wetenschappelijk assistent bij de

vakgroep Chemische Technologie, waar, onder leiding van prof.drs.

H.S. van der Baan, het in dit proefschrift beschreven onderzoek

werd verricht.

STELLINGEN

behorende bij het proef sohrift van

P.c.c. Smits

24 april 1984

1. Bij de interpretatie van de experimentele resultaten van Schwartz

et al. voor de radiale gassnelheidsdistributie in gepakte bedden

heeft Schlunder ten onrechte de wrijving aan de wand verwaarloosd.

Sahwa!'tz, C.E., Smith, J.M., Ind. Eng. Chem., !E_, 1209

(1953)

Sahlunde!', E.U., Chem. Reaction Engng. Rev. Houston,

ACS Symposium'Se!'ies, !.,?_, 111 (19?8)

2. Het door carugati et al. voorgestelde mechanisme van de chloor

vorming aan co 3o 4 geaktiveerde titaan anodes in waterige NaCl

oplossing is onwaarschijnlijk.

Carugati,A., Lodi, G., Trasatti, s., Extended abstraats

ISE 34th meeting, EPlangen, 31? (1983)

3. De conclusie van Hikita et al., dat bij de chemisch versnelde

absorptie van co2 in waterige monoethanolamine-oplossingen de

fysische oplosbaarheid van co2 toeneemt met de amine-concentratie,

wordt door hun experimenten niet gestaafd.

Hikita, H., Asai, S., Katsu, Y., Ikumo, S., A.I.Ch.E.

Jou!'nal, 25, ?93 (19?9)

4. De door Bajaj et al. berekende reaktiviteitsverhoudingen voor

de copolymerisatie van acrylonitril met 3-chloor-2-hydroxypropyl

methacrylaat in waterig milieu zijn niet consistent met hun

experimentele resultaten.

Bajaj, P., Padmanaban, M., J. Pol. Sai.: Pol. Chem. Ed.,

~. 2261 (1983)

5. De door Hearon et al. geclaimde resultaten van de hydrogenolyse

van methyl-a-D-glucuronide tot L-gulono-y-lacton in een 1% zwavel­

zuur oplossing (voorbeeld 3) zijn aanvechtbaar.

Hearon, W.M., Witte, J.F., U.S. Patent 4.33?.202

(29 juni 1982)

6. Door de oxidatie van D-glucono-o-lacton met behulp van een

platina op kool katalysator in een zodanig milieu uit te voeren,

dat het lacton veel langzamer gehydrolyseerd dan geoxideerd

wordt, kan een hoge selektiviteit voor D-glucaarzuur verkregen

worden.

Dit proefs~hrift, hoofdstuk 5

7. De bewering van Dautzenberg et al. dat de propagatie stap in de

Fischer Tropsch synthese over Ru/Al2o3 , snelheidsbepalend is

berust op een verkeerde veronderstelling gezien de hoge waarde

van de Schulz-Flory constarite (a= 0.95).

F.M. Dautzenberg, J.N. HeZZe, R.A. van Santen,

H. V2rbeek, J. CataZ. 8 (1977)

S. In het hedendaagse wetenschappelijk onderwijs, waarbij specia­listen door specialisten worden opgeleid is de benaming

"universiteit" niet meer op zijn plaats.

9. Om weggebruikers direkter te confronteren met de betekenis van

s.rielheid voor de verkeersveiligheid verdient het aanbeveling de eenheid "km/uur" te vervangen door "m/s".