lecture 13 aldehydes ketones 2009 print this

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Chapter 13Chapter 13Aldehydes and KetonesAldehydes and Ketones


The Carbonyl GroupThe Carbonyl Group• In this and several following chapters, we study

the physical and chemical properties of classes of compounds containing the carbonyl group

•

C=O• aldehydes and ketones (Chapter 13)• carboxylic acids (Chapter 14)• acid halides, acid anhydrides, esters, amides (Chapter 15)• enolate anions (Chapter 16)


StructureStructure• the functional group of an aldehyde is a carbonyl group

bonded to a H atom • the functional group of a ketone is a carbonyl group

bonded to two carbon atoms

Propanone(Acetone)

Ethanal(Acetaldehyde)

Methanal(Formaldehyde)

O O O

CH3CHHCH CH3CCH3


Aldehydes and KetonesAldehydes and Ketones

In an aldehyde, an H atom is attached to a carbonyl group O carbonyl group

CH3-C-H

In a ketone, two carbon groups are attached to a carbonyl group

O carbonyl group CH3-C-CH3


Naming AldehydesNaming Aldehydes

IUPAC Replace the -e in the alkane name -al Common Add aldehyde to the prefixes form (1C), acet

(2C), propion(3), and butry(4C)

O O O

H-C-H CH3-C-H CH3CH2C-H methanal ethanal propanal (formaldehyde) (acetaldehyde) (propionaldehyde)


Aldehydes as FlavoringsAldehydes as Flavorings

Benzaldehyde Vanillin Cinnamaldehyde(almonds) (vanilla beans) (cinnamon)

CH=CH CH

OCH

O

HO

OCH3

CH

O


Aldehydes: Common ExamplesAldehydes: Common Examples

glucose

C

OH

C

CHO H

CH OH

C

CH2OH

OH

OHH

H

H H

O

O

H

H

O

H

O

H

O

methanal (formaldehyde)

ethanal (acetaldehyde)

propanal (propionaldehyde)

butanal (butyraldehyde)

2-methylpropanal (isobutyraldehyde)


Naming KetonesNaming Ketones

In the IUPAC name, the -e in the alkane name is replaced with -one

In the common name, add the word ketone after naming the alkyl groups attached to the carbonyl group O O

CH3 -C-CH3 CH3-C-CH2-CH3

Propanone 2-Butanone (Dimethyl ketone) (Ethyl methyl ketone)

Cyclohexanone

O


Ketones: common examplesKetones: common examples

O O

Butter flavor CH3-C-C-CH3

O Clove flavor CH3-C-CH2CH2CH2CH2CH3

2-heptanone

Butanedione

D-Fructose

H2OHC

C

CHO H

C

O

H OH

C

CH2OH

OHH


Ketones as HormonesKetones as Hormones

Cortisone

O

CH2OH

OCH3

CH3

O OH


NomenclatureNomenclature• IUPAC names:

• the parent chain is the longest chain that contains the carbonyl group

• for an aldehyde, change the suffix from -e to -al• for an unsaturated aldehyde, show the carbon-carbon

double bond by changing the infix from -an--an- to -en--en-; the location of the suffix determines the numbering pattern

• for a cyclic molecule with –CHO bonded to the ring,

use suffix -carbaldehyde


NomenclatureNomenclature

CHO HO CHO

Cyclopentane-carbaldehyde

trans-4-Hydroxycyclo-hexanecarbaldehyde

14

3-Methylbutanal 2-Propenal(Acrolein)

H

O

(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)

1

2

3

4

5

6

7

8

11

223

3

4H

O

H

O

2-Methyl-cyclohexanone

5-Methyl-3-hexanone

Benzophenone Acetophenone

OO

O O


NomenclatureNomenclature

HCOOH

O

COOHO

COOHHO

OHHS

COOHNH2

-al oxo-

Ketone -one oxo-

Alcohol -ol hydroxy-

Amino -amine amino-

3-Oxopropanoic acid

3-Oxobutanoic acid

4-Hydroxybutanoic acid

3-Aminobutanoic acid

Example of When the FunctionalGroup Has a Lower Priority

Sulfhydryl -thiol mercapto- 2-Mercaptoethanol

Functional Group Suffix Prefix

Carboxyl -oic acid

Aldehyde


NomenclatureNomenclature• Common names

• for an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid

• for a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone

FormaldehydeFormic acid Acetaldehyde Acetic acid

Ethyl isopropyl ketoneDiethyl ketoneDicyclohexyl ketone

O OO

H H

O

H OH

O

H

O

OH

O


Physical PropertiesPhysical Properties• Oxygen is more electronegative than carbon (3.5

vs 2.5) and, therefore, a C=O group is polar

• aldehydes /ketones are polar compounds (interact by dipole-dipole interactions)

• they have higher boiling points • more soluble in water than nonpolar compounds of

comparable molecular weight

C O C O –

Polarity of acarbonyl group

-+C O

+

More importantcontributing

structure

::: : :


ReactionsReactions

• The most common reaction theme of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound

Tetrahedral carbonyl addition compound

+ CR

R

O CNu

O -

RR

Nu -: :

:::

:


ReactionsReactions

Tetrahedral carbonyl addition compound

+ CR

R

O CNu

O -

RR

Nu -: :

::

:

:

1. Grignard Reaction

2. Hemiacetal Formation

3. Imine Formation

4. Reductive Amination

5. Keto-enol Tautomerism

6. Alpha-halogenation

7. Oxidation/ Reduction

8. Oximes & Hydrazones

8. Formation of Oximes/ Hydrazones8. Formation of Oximes/ Hydrazones


1. Grignard1. Grignard ReagentsReagents

•Grignard reagents RMgX where R is an alkl or aryl group and X is a halogen

Br Mg MgBr+1-Bromobutane Butylmagnesium bromide

ether

Br Mg MgBr+ ether

Bromobenzene Phenylmagnesium bromide

Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent,

with C- and Mg+


• Hemiacetal: a molecule containing an -OH goup and an -OR group bonded to the same carbon

• hemiacetals are minor components of an equilibrium mixture except where a 5- or 6-membered ring can form

CH3CCH3

O H

OCH2CH3H+

CH3C-OCH2CH3

CH3

OH

A hemiacetal

+

4-Hydroxypentanal A cyclic hemiacetal(major form present at equilibrium)

OHH

O

OH

O

Hredraw to showthe OH close tothe CHO group O OH1

23

45

1

23

451

23

45

2. Hemiacetal Formation2. Hemiacetal Formation


• Acetal: a molecule containing two -OR groups bonded to the same carbon

CH3C-OCH2CH3

CH3

OH

CH3CH2OHH

+CH3C-OCH2CH3

CH3

OCH2CH3

H2O

A diethyl acetal

++

A hemiacetal

OHH

O

O OHCH3OH

H+ O OCH3H2O

4-Hydroxypentanal

+

A cy clic acetal

2. Hemiacetal Formation2. Hemiacetal Formation


1. Proton transfer from HA to the hemiacetal oxygen

2. Loss of H2O gives a cation

HO

H

R-C-OCH3 H A

H

H

O

R-C-OCH3

H

A -+

+

An oxonium ion

+

H O

R-C-OCH3

H

H

R-C

H

OCH3

H

R-C OCH3 H2O+

+

A resonance-stabilized cation

+

+

2. Acetal Formation2. Acetal Formation


3. reaction of the cation (an electrophile) with an alcohol (a nucleophile)

4. proton transfer to A- gives the acetal and regenerates the acid catalyst

CH3-O

H

R-C OCH3

H

H

H

O

R-C-OCH3

CH3+

+

A protonated acetal

+

A

H O

R-C-OCH3

CH3

H

HAH

O

R-C-OCH3

CH3

A protonated acetal An acetal

++

+



• Draw a structural formula for the acetal formed in each reaction

O HOOH H2SO4+

Ethyleneglycol

(a)

OH

OH

O H2SO4(b) +



Acetals as Protecting GroupsAcetals as Protecting Groups

• one way to synthesize the ketoalcohol on the right is by a Grignard reaction

• but first the aldehyde of the bromoaldehyde must be protected; one possibility is as a cyclic acetal

Ph H

O

H

OBr

Ph H

OH O

5-Hydroxy-5-phenylpentanal4-BromobutanalBenzaldehyde+

??

H

OBr

A cyclic acetal

+H

+

H2OHOOH+ Br O

O

Ethylene glycol



• Imine: a compound containing a C=N bond; also called a Schiff base• formed by the reaction of an aldehyde or ketone with

ammonia or a 1° amine

An imineAmmoniaCyclohexanone

++ NH3 H2OO NHH+

CH3CH

O

H2N CH3CH=N H2O+ +

Ethanal Aniline An imine

H+

3. Imine Formation3. Imine Formation


1. addition of the amine to the carbonyl carbon followed by proton transfer

2. two proton-transfer reactions and loss of H2O

C

O

H2N-R C

O

HN-R

H

C

OH

N-RH

-

+

A tetrahedral carbonyladdition intermediate

+

H

O H

H

C

OH

N-RH

C

OHH

N-R

H

H

OH

C N-R H2O H OH

H

An imine

+

+

+ ++

3. Imine Formation3. Imine Formation


HH22NN

RR

CC OO••••

++•••• •••• HH

a carbinolaminea carbinolamine

CC OOHNHN

RR

••••

••••

••••

NN

RR

CC + H+ H22OO(imine)(imine)••••

Imine (Schiff's Base) Formation


CHCH33NNHH22CHCH

OO

++

CH=CH=NNCHCH33 + + HH22OO

N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)

ExampleExample


CHCH33NNHH22CHCH

OO

++

CH=CH=NNCHCH33 + + HH22OO

N-N-Benzylidenemethylamine (70%)Benzylidenemethylamine (70%)

ExampleExample CHCH

OOHH

NNHHCHCH33


(CH(CH33))22CHCHCHCH22NNHH22OO ++

+ + HH22OO

N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)

NNCHCH22CH(CHCH(CH33))22

ExampleExample


(CH(CH33))22CHCHCHCH22NNHH22OO ++

+ + HH22OO

N-N-Cyclohexylideneisobutylamine Cyclohexylideneisobutylamine (79%)(79%)

NNCHCH22CH(CHCH(CH33))22

OOHH

NNHHCHCH22CH(CHCH(CH33))22

ExampleExample


RhodopsinRhodopsin

• reaction of vitamin A aldehyde (retinal) with an amino group on the protein opsin gives rhodopsin

C=OH

H2N-Opsin+

C=H

N-Opsin

1112

11-cis-Retinal

Rhodopsin(Visual purple)


• Reductive amination: the formation of an imine followed by its reduction to an amine

• reductive amination is a valuable method for the conversion of ammonia to a 1° amine, and a 1° amine to a 2° amine

+

Cyclohex-anone

Cyclohexyl-amine

(a 1° amine)

O-H2OH+

H2N

Dicyclohexylamine(a 2° amine)

An imine(not isolated)

NH2/Ni

NH

4. Reductive Amination4. Reductive Amination


• Enol: molecule with -OH on a C=C of an alkene

• the keto form predominates

for most

simple

aldehydes and

ketones

CH3-C-CH3

O OHCH3-C=CH2

Acetone(keto form)

Acetone(enol form)

CH2=CHOH

CH3C=CH2

OH

OH

CH3CHO

O

CH3CCH3

O

Keto form Enol form% Enol atEquilibrium

6 x 10-5

6 x 10-7

4 x 10-5

5. Keto-enol Tautomerism5. Keto-enol Tautomerism


• Problem: draw two enol forms for each ketone

• Problem: draw the keto form of each enol

(a) (b)

OO

OCHOH OH

OH

OH(c)(b)(a)



• Mechanism (acid catalysed)

1. proton transfer to the carbonyl oxygen

2. proton transfer from the -carbon to A:-

CH3-C-CH3

O

H-A CH3-C-CH3

OH

A-+

+

fast+

Keto form

• •

• • ••••

The conjugate acidof the ketone

CH3-C-CH2-H

OH

A-CH3-C=CH2

OHH-A

Enol form+

+

slow+

• •

• • ••••



• Aldehydes and ketones with an -hydrogen react with Br2 and Cl2 to give an -haloaldehyde or an -haloketone

O

Br2CH3COOH

OBr

HBr+ +

Acetophenone -Bromoacetophenone

6. 6. -Halogenation-Halogenation


• the key intermediate in -halogenation is an enol1. formation of the enol

2. nucleophilic attack of the enol on the halogen

O OH

Keto form Enol form

H+

OH

Br Br

OBr

H-Br+ +

6. 6. -Halogenation-Halogenation


• Aldehydes are one of the most easily oxidized of all functional groups

CHO

HO

MeOAg2O

THF, H2O

NaOHHClH2O

COOHMeO

HOAg

Vanillic acidVanillin

++

CHO H2CrO4 COOH

Hexanal Hexanoic acid

2 CHO O2 2 COOH

Benzoic acidBenzaldehyde

+

7. Oxidation-Reduction7. Oxidation-Reduction


• Ketones are not normally oxidized by H2CrO4; in fact this reagent is used to oxidize 2° alcohols to ketones• they are oxidized by HNO3 at higher temperatures

• oxidation is via the enol

• adipic acid is one of the starting materials for the synthesis of nylon 66

O OH

HNO3

O

HOOH

O

Hexanedioic acid(Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)



• aldehydes can be reduced to 1° alcohols• ketones can be reduced to 2° alcohols

R-CH

O

R-C-R'O

R-CH-R'OH

R-CH2OHA primaryalcohol

A secondaryalcohol

An aldehyde

reduction

A ketone

reduction



• Catalytic reductions are generally carried out from 25° to 100°C and 1 to 5 atm H2

• a carbon-carbon double bond may also be reduced under these conditions

+25oC, 2 atm

Pt

Cyclohexanone Cyclohexanol

O OH

H2

1-Butanol trans-2-Butenal(Crotonaldehyde)

2H2

NiH

O

OH



Metal Hydride ReductionsMetal Hydride Reductions• The most common laboratory reagents for the

reduction of aldehydes and ketones are NaBH4 and LiAlH4

• both reagents are sources of hydride ionhydride ion, H:H:--, a very strong nucleophile

Hydride ionLithium aluminum hydride (LAH)

Sodium borohydride

H

H H

H

H-B-H H-Al-HLi +Na+

H:



NaBHNaBH44 Reductions Reductions

• reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol

• one mole of NaBH4 reduces four moles of aldehyde or ketone

4RCHO

NaBH4

(RCH2O)4B- Na

+ H2O4RCH2OH

A tetraalkyl borateborate salts

+

+ methanol



NaBHNaBH44 Reductions Reductions

• the key step in metal hydride reductions is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound

Na+H-B-H

H

R-C-R'

O

H

R-C-R'

H

O BH3 Na+

H2O

R-C-R'

H

O-H

from water

from the hydride reducing agent

+



Metal Hydride ReductionsMetal Hydride Reductions

• metal hydride reducing agents do not normally reduce carbon-carbon double bonds, and selective reduction of C=O or C=C is often possible

O OH

RCH=CHCR' RCH=CHCHR'1. NaBH4

2. H2O

+Rh

O

RCH=CHCR' RCH2 CH2CR'H2

O



W W U W W U - -- - C h e m i s t r yC h e m i s t r y

A l d e h y d e sA l d e h y d e s c a n b e p r e p a r e d c a n b e p r e p a r e d b yb y r e d u c t i o nr e d u c t i o n ..

• T h i s w o u l d b e d e s i r a b l e t o d o :

• T h e p r o b l e m i s , h o w t o s t o p t h e r e d u c t i o n a t t h e a l d e h y d e s t a t e , w i t h o u t r e d u c i n g a l l t h e w a y t o a p r i m a r y a l c o h o l ?

R C Cl

O

R C H

O

[H]

[ H ] r e p r e s e n t s a n y g e n e r a l r e d u c t i o n


Among the most useful modified aluminum

hydride (LiAlH4) reducing agents is

Diisobutylaluminum Hydride, also known as DIBALH.

CH3 CH CH2 Al CH2 CH CH3

CH3CH3 H


Nitriles can also be reduced to Nitriles can also be reduced to aldehydes, using DIBALHaldehydes, using DIBALH

C N

DIBALH

toluene -78°C

H2O

HCl

C

H

O

Benzaldehyde (90% yield)


+ + H2OC O

R

R

NH2 OH C

R

R

N OH..

an oxime

acid

•Aldehydes and ketones react with hydroxylamine to yield oximes.

•Oximes are important derivatives in qualitative organic analysis.



+ + H2O..

a hydrazone

C O

R

R

NH2 NH R C

R

R

N NH Racid

•Aldehydes and ketones react with substituted hydrazines to yield substituted hydrazones.

•The equilibrium is generally unfavorable.

•Exception: when R is an aromatic ring.



2,4-Dinitrophenylhydrazones2,4-Dinitrophenylhydrazones

+

+ H2O

C O

R

R

NH2 NH NO2

NO2

C

R

R

N NH

NO2

NO2

..

a 2,4-dinitrophenylhydrazone

a 2,4-DNP

acid

2,4-DNP’s are the most important of all derivatives for aldehydes and ketones.



Aldehydes andAldehydes andKetonesKetones

End Chapter 13End Chapter 13

lecture 13 aldehydes ketones 2009 print this

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