ch16 aldehydes and ketones

7/27/2019 CH16 Aldehydes and Ketones

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Organic Chemistry II

Aldehydes

Ketones

7th

March, 2012


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Aldehydes&

Ketones

Chapter 16 Rod cells in the humaneye. Inset: a model of 11-c is-retinal, an oxidizedform of vitamin A.


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The Carbonyl Group

In this and several following chapters, we study

the physical and chemical properties of classesof compounds containing the carbonyl group,C=O

aldehydes and ketones (Chapter 16)

carboxylic acids (Chapter 17)

acid halides, acid anhydrides, esters, amides (Chapter18)

enolate anions (Chapter 19)


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Structure

the functional group of an aldehyde is a carbonyl

group bonded to a H atom and a carbon 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


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Nomenclature

IUPAC names:

the parent chain is the longest chain that contains thefunctional group

for an aldehyde, change the suffix from -e to -al

for an unsaturated aldehyde, change the infix from -an-

to -en-; the location of the suffix determines thenumbering pattern

for a cyclic molecule in which -CHO is bonded to thering, add the suffix -carbaldehyde


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Nomenclature: Aldehydes

H

O

3-Methylbutanal 2-Propenal(Acrolein) (2E

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

1

2

3

4

5

6

7

8H

O

H

O


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CHO HO CHO

Cyclopentane-carbaldehyde

trans-4-Hydroxycyclo-

hexanecarbaldehyde

14


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the IUPAC retains the common names benzaldehyde

and cinnamaldehyde, as well formaldehyde andacetaldehyde

CHOC6 H5CHO

t rans -3-Phenyl-2-propenal

(Cinnamaldehyde)

Benzaldehyde


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Benzaldehyde is found in the kernels of bitter almonds.

Cinnamaldehyde is found in Ceylon and Chinese cinnamon oils.

Benzaldehyde

Cinnamaldehyde


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Nomenclature: Ketones

IUPAC names

the parent alkane is the longest chain that contains thecarbonyl group

indicate the ketone by changing the suffix -e to -one

number the chain to give C=O the smaller number

the IUPAC retains the common names acetone,acetophenone, and benzophenone

Propanone(Acetone)

Benzophenone 1-Phenyl-1-pentanoneAcetophenone

O O OO


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Order of Precedence

For compounds that contain more than one

functional group indicated by a suffix

HCOOH

O

COOH

O

COOHHO

OHHS

COOH

NH2

FunctionalGroup

Carb oxyl -oic acidAldehyde -al oxo-

Ketone -one oxo-

Alcohol -ol hydroxy-

Amino -amine amino-

3-Oxopropanoicacid

3-Oxobutanoic acid

4-Hydroxybutanoicacid

3-Aminobutanoicacid

Example when thefunctional group h as

a lower priority

Sulfhydryl -thiol mercapto 2-Mercaptoethanol

Suffix if

higherpriority

Pref ix iflowerpriority

Increasing precedence


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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

HCH

O

HCOH

O

CH3 CH

O

CH3COH

O

Formaldehyde Formic acid Acetaldehyde Acetic acid

Ethyl isopropyl ketone Diethyl ketone Dicyclohexyl ketone

O O

O


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Physical Properties

Oxygen is more electronegative than carbon (3.5

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

aldehydes and ketones are polar compounds and

interact in the pure state by dipole-dipole interaction they have higher boiling points and are more soluble

in water than nonpolar compounds of comparablemolecular weight


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Reaction Themes

One of the most common reaction themes of a

carbonyl group is addition of a nucleophile toform a tetrahedral carbonyl addition compound

Tetrahedral carbonyladdition compound

+ C

R

R

O CNu

O-

RR

Nu-


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Reaction Themes

A second common theme is reaction with a

proton or other Lewis acid to form a resonance-stabilized cation

protonation increases the electron deficiency of thecarbonyl carbon and makes it more reactive toward

nucleophiles

B-

C OR

R

H-Nu

H-B

C O

R

RH

B-

C O

R

RH

CNu

O-H

RR

C O

R

RH

H-B

+fast +

++

+slow

Tetrahedral carbonyladdition compound

++ +


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Reaction Themes

often the tetrahedral product of addition to a carbonyl

is a new chiral center if none of the starting materials is chiral and the

reaction takes place in an achiral environment, thenenantiomers will be formed as a racemic mixture

Nu-

C OR

R'

Nu

OR'

R

Nu

OR

R'+

H3 O+

Nu

OHR

R'

Nu

OHR'

R

+

A racemic mixtureA new chiralcen ter is created

Approach fromthe bottom face

Approach fromthe top face


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Addition of C Nucleophiles

Addition of carbon nucleophiles is one of the

most important types of nucleophilic additions toa C=O group

a new carbon-carbon bond is formed in the process

we study addition of these carbon nucleophiles

RMgX RLi-

CRC C-

N

A Grignardreagent

An organolithiumreagent

An alkyneanion

Cyanide ion


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Grignard Reagents

Given the difference in electronegativity between

carbon and magnesium (2.5 - 1.3), the C-Mg bondis polar covalent, with C- and Mg+ in its reactions, a Grignard reagent behaves as a

carbanion

Carbanion:an anion in which carbon has anunshared pair of electrons and bears a negativecharge

a carbanion is a good nucleophile and adds to thecarbonyl group of aldehydes and ketones


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Grignard Reagents

addition of a Grignard reagent to formaldehyde

followed by H3O+ gives a 1 alcohol

CH3CH2 -MgBr

O

H-C-H

O-[ MgBr]

+

CH3CH2 -CH2HCl

H2O

OH

CH3CH2 -CH2 Mg2+

ether

1-Propanol

(a 1 alcohol)

Formaldehyde

+

+

A magnesium

alkoxide


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Grignard Reagents

addition to any other RCHO gives a 2 alcohol

MgBr

H

O

O-[ MgBr]

+

HCl

H2O

OH

Mg2+

+ether

Acetaldehyde(an aldehyde)

+

A magnesiumalkoxide 1-Cyclohexylethanol(a 2 alcohol;(racemic)


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Grignard Reagents

addition to a ketone gives a 3 alcohol

Ph-MgBrO

Ph

O-[ MgBr]

+HCl

H2O Ph

OHMg2+

+

Acetone(a ketone)

ether

+

A magnes iumalkoxide

2-Phenyl-2-propanol(a 3 alcohol)

Phenyl-magnesium

bromide


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Grignard Reagents

Problem:2-phenyl-2-butanol can be synthesized by three

different combinations of a Grignard reagent and aketone. Show each combination.

C-CH2 CH3

CH3

OH


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Organolithium Compounds

Organolithium compounds are generally more

reactive in C=O addition reactions than RMgX,and typically give higher yields

LiO

O-

Li+

HCl

H2O

OH

3,3-Dimethyl-2-butanone

3,3-Dimethyl-2-phenyl-2-butanol(racemic)

+

Phenyl-lithium

A li thium alkoxide(racemic)


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Salts of Terminal Alkynes

Addition of an alkyne anion followed by H3O+

gives an -acetylenic alcohol

C:-

Na+

HC

OC O

-Na

+HC

HCl

H2 O

C OHHC

1-Ethynyl-cyclohexanol

A sodiumalkoxide

+

CyclohexanoneSodiumacetylide


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Salts of Terminal Alkynes

H2 O

HO C CHH2 SO4 , HgSO4

1. (sia)2 BH

2. H2O2 , NaOH

O

HO CCH3

HO CH2CHO

An -hydroxyketone

A -hydroxyaldehyde


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Addition of HCN

HCN adds to the C=O group of an aldehyde or

ketone to give a cyanohydrin Cyanohydrin:a molecule containing an -OH

group and a -CN group bonded to the samecarbon

2-Hydroxypropanenitrile

(Acetaldehyde cyanohydrin)

+ HC N CH3C-C NCH3CH

OH

H

O


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Addition of HCN

Mechanism of cyanohydrin formation

Step 1: nucleophilic addition of cyanide to thecarbonyl carbon

Step 2: proton transfer from HCN gives thecyanohydrin and regenerates cyanide ion

- +

H3 CC

H3 C

O C

O-

H3 C

H3 C

C

N

N

C

C

O -

H3 C

H3 C

C N

NH C C

C

H3 C

H3 C

O-H

NC N++

-


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Wittig Reaction

The Wittig reaction is a very versatile synthetic

method for the synthesis of alkenes fromaldehydes and ketones

Triphenyl-phosphine oxide

Methylene-cyclohexane

A phosphoniumylide

++

-+

CH2 Ph3P=OPh3 P-CH2

Cyclohexanone

O


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Phosphonium Ylides

Phosphonium ylidesare formed in two steps:

Step 1: nucleophilic displacement of iodine bytriphenylphosphine

Step 2: treatment of the phosphonium salt with a verystrong base, most commonly BuLi, NaH, or NaNH

2

Ph3P CH3 -I Ph3P-CH3 I

Triphenylphosphine

++

SN2

Methyltriphenylphosphonium iodide(an alkyltriphenylphosphine salt)

CH3 CH2 CH2 CH2 -Li

+H-CH2 -PPh3 I

-

-CH2 -PPh3CH3 CH2 CH2 CH3 LiI

A phosphonium

ylide

Butane

Butyllithium

+++

++


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Wittig Reaction

Phosphonium ylides react with the C=O group of

an aldehyde or ketone to give an alkene Step 1: nucleophilic addition of the ylide to the

electrophilic carbonyl carbon

Step 2: decomposition of the oxaphosphatane

CR2

O

CH2Ph3PCH2

-

:O CR2

Ph3P

O CR2

Ph3P CH2-+

An oxaphosph etane

+

A betaine

CH2

O CR2

Ph3 PPh3P=O R2 C=CH2

An alkene

+

Triphenylphosphineoxide

Wi i R i


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Wittig Reaction

Examples:

O Ph3 P+ Ph3P=O

2-Methyl-2-heptene

+

Acetone

Ph O

H

Ph3 P Ph Ph Ph3P=O

Phenyl-acetaldehyde

+ ++

(Z)-1-Phenyl-2-butene

(87%)

(E)-1-Phenyl-2-butene

(13%)

PhO

H

OEtPh3 P

O

PhOEt

O

Ph3P=O

Ethyl (E)-4-phenyl-2-butenoate

(only the E is omer is formed)

++

Phenyl-acetaldehyde

Wi i R i


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Wittig Reaction

some Wittig reactions are Zselective, others are E

selective Wittig reagents with an anion-stabilizing group, such

as a carbonyl group, adjacent to the negative chargeare generally Eselective

Wittig reagents without an anion-stabilizing group aregenerally Zselective

OEtPh3 P

O

OEtPh3 P

O

Resonance contributing structures for anylide stabilized by an adjacent carbonyl group

Wi i R i


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Wittig Reaction

Horner-Emmons-Wadsworth modification

uses a phosphonoester

Br-CH2 -C-OEt

O

( MeO)3 PBr-CH2 -C-R

O

(MeO) 2 P-CH2-C-R

OO

( MeO)2 P-CH2 -C-OEt

OO

MeBr

MeBran -bromoester

an -bromoketone

+

+

An -phosphonoester

An -phosphonoketoneTrimethyl-phosphite

Witti R ti


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Wittig Reaction

phosphonoesters are prepared by successive SN2

reactions

( MeO)3 P CH2 -C-OEt

O

Br

CH3 -O-P-CH2 -C-OEt

O

OMe

OMe

Br

( MeO)2 P-CH2 -C-OEt

OO

MeBr

+

+

SN 2

SN 2

An -phosphonoester


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Additi f H O


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Addition of H2O

Addition of water (hydration) to the carbonyl

group of an aldehyde or ketone gives a geminaldiol, commonly referred to a gem-diol

gem-diols are also referred to as hydrates

C O + H2 O C

OH

OH

Carbonyl groupof an aldehyde

or ketone

A hydrate(a gem-diol)

acid orbase

Additi f H O


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Addition of H2O

when formaldehyde is dissolved in water at 20C, the

carbonyl group is more than 99% hydrated

the equilibrium concentration of a hydrated ketone isconsiderably smaller

H

H

O H2 O+

Formaldehyde

H

HOH

OH

Formaldehyde hydrate

(>99%)

O H2 O+

2,2-Propanediol(0.1%)

Acetone(99.9%)

OH

OH


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Continue next week

Additi f Al h l


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Addition of Alcohols

Addition of one molecule of alcohol to the C=O

group of an aldehyde or ketone gives ahemiacetal

Hemiacetal:a molecule containing an -OH and an-OR or -OAr bonded to the same carbon

O H-OEtOH

OEt+

acid orbase

A hemiacetal

Ar = aryl group



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hemiacetals are only minor components of an

equilibrium mixture, except where a five- or six-membered ring can form

(S)-4-Hydroxypentanal Cyclic hemiacetals(major forms present at equilibriu m)

OH

H

O

O OH O OH+

41 14 14

OH

OH

OH

HO

H

OOH

O

OH

HO

HO

CH2OH

OH

HO

CH2OH

O

OH

HO OH1

2

3

6

6

12

anomericcarbon

Anomer ofD -glucosecyclic hemiacetal

(predominates

at equ ilibrium)

Anomer ofD -glucose cyclic

hemiacetal

+

4

5

D-Glucose(open chain form)

123

4 5

3

4 5

6



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at equilibrium, the anomer of glucose predominatesbecause the -OH group on the anomeric carbon isequatorial

O

OH

HO

OHHO

O

OH

OH

HO

HO

CH2 OH

OHO

HO

HO

OH

O

OH

HO

HOCH2 OH

OH

1

234 5

6

anomericcarbon

Anomer

anomericcarbon

132

4 56

(equatorial)

123

4 5

6

anomericcarbon

Anomer of

anomericcarbon

13

2

4 56

(axial)

redraw asa chair

conformation

redraw asa chair

conformation

OH

OH



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Formation of a hemiacetal is base catalyzed

Step 1: proton transfer from HOR gives an alkoxide

Step 2: attack of RO-on the carbonyl carbon

Step 3: proton transfer from the alcohol to O-gives thehemiacetal and generates a new base catalyst

B - H OR B H- OR+ +

fast andreversible

CH3 -C-CH3

O

:O-R

O:

CH3 -C-CH3

OR

+

O:

CH3 -C-CH3

OR

H OR

OR

OH

CH3 -C-CH3-

OR++



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Formation of a hemiacetal is also acid catalyzed

Step 1: proton transfer to the carbonyl oxygen

Step 2: attack of ROH on the carbonyl carbon

Step 3: proton transfer from the oxonium ion to A-

givesthe hemiacetal and generates a new acid catalyst

O

CH3 -C-CH3 H-A

O

CH3 -C-CH3

H

A-

+

+ +

fast andreversible

O

CH3 -C-CH3

H

H-O-R CH3 -C-CH3

O-H

ORH

++

+

RH

CH3 -C-CH3

O

OH

OR

OH

CH3 -C-CH3 H-A

A -

+

+



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Hemiacetals react with alcohols to form acetals

Acetal:a molecule containing two -OR or -OAr groupsbonded to the same carbon

OH

OEtH-OEt

H+

OEt

OEtH2O

A diethyl acetal

+

A h emiacetal

+



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Step 1: proton transfer from HA gives an oxonium ion

Step 2: loss of water gives a resonance-stabilized cation

HO

R-C-OCH3

H

H A

HHO

H

R-C-OCH3 A:-

+

An oxonium ion

+

+

R-C OCH3

H

OHH

H

R-C OCH3 R-C

H

OCH3 H2 O+

A resonance-stabilized cation

++

+



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Step 3: reaction of the cation (an electrophile) with

methanol (a nucleophile) gives the conjugate acid ofthe acetal

Step 4: proton transfer to A- gives the acetal andgenerates a new acid catalyst

CH3 -OH

H

R-C OCH3 R-C OCH3

H

OCH3H

A protonated acetal

++

+

A:-

R-C OCH3

H

OCH3H OCH3

H

R-C-OCH3 H-A+(4)

An acetal

+

+


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Dean Stark Trap


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Dean-Stark Trap

Acetals as Protecting Grps


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Acetals as Protecting Grps

Suppose you wish to bring about a Grignard

reaction between these compounds

5-Hydroxy-5-phenylpentanal(racemic)

4-BromobutanalBenzaldehyde

??+

H

O

H

O

H

OH O

Br

Acetals as Protecting Groups


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Acetals as Protecting Groups

a Grignard reagent prepared from 4-

bromobutanal will self-destruct! first protect the -CHO group as an acetal

then do the Grignard reaction

hydrolysis (not shown) gives the target molecule

H

O

Br

A cyclic acetal

+H

+

H2OHO

OH+Br

O

O

Br O

O1. Mg, ether

2. C6H5 CHO

O

OO-MgBr

+

A chiral magnesiu m alkoxide(produced as a racemic mixture)


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Addition of Nitrogen Nucleophiles


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Ammonia, 1 aliphatic amines, and 1 aromatic

amines react with the C=O group of aldehydesand ketones to give imines (Schiff bases)

CH3 CH H2 NH

+

CH3 CH=N H2 O+ +

Acetaldehyde Aniline An imine(a Schiff base)

O

An imine(a Schiff base)

AmmoniaCyclohexanone

++ NH3 H2 OO NHH

+



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Formation of an imine occurs in two steps

Step 1: carbonyl addition followed by proton transfer

Step 2: loss of H2O and proton transfer to solvent

C

O

H2N-R

H

H

C

O:-

N-R

OH

N-R

H

C++

O H

H

H H

C

OH

N-R N-R

H

C

OHH

OH

H

C N-R OH

H

HAn imine

+

+

+ +

+

+ H2 O



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a value of imines is that the carbon-nitrogen double

bond can be reduced to a carbon-nitrogen single bond

+

Dicyclohexylamine

Cyclohexanone

(An imine)

Cyclohexylamine

O

N N

H

-H2O

H2/Ni

H+

H2N



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Rhodopsin (visual purple) is the imine formed

between 11-c is-retinal (vitamin A aldehyde) andthe protein opsin

11

12

11-ci s-RetinalRhodopsin

(Visual purple)

H2

N-opsin

H N-opsinH O

+



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Secondary amines react with the C=O group of

aldehydes and ketones to form enamines

the mechanism of enamine formation involvesformation of a tetrahedral carbonyl addition compoundfollowed by its acid-catalyzed dehydration

we discuss the chemistry of enamines in more detail inChapter 19

O H-NH

+

N H2 O

An enaminePiperidine(a secondary amine)

++

Cyclohexanone



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Addition of Nitrogen Nucleophiles the carbonyl group of aldehydes and ketones reacts

with hydrazine and its derivatives in a manner similar

to its reactions with 1 amines

O H2 NNH2 NNH2 H2 O+

Hydrazine

+

A hydrazone

H2

N-NHCNH2

H2N-OH

H2 N-NH

H2 N-NH NO2

O2 N

Reagent, H2N-R

Hydroxylamine Oxime

Phenylhydrazine

2,4-Dinitrophenyl-hydrazine

Semicarbazide

2,4-Dinitrophenylhydrazone

Semicarbazone

Name of Derivative FormedName of Reagent

Phenylhydrazone

O

Acidity of -Hydrogens


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Acidity of Hydrogens Hydrogens alpha to a

carbonyl group are moreacidic than hydrogens ofalkanes, alkenes, andalkynes but less acidic than

the hydroxyl hydrogen ofalcohols

CH3 CH2O-HO

CH3 CCH2 -H

CH2 =CH-H

CH3 CH2 -H

CH3C C-H

T yp e of Bond p K a

16

20

25

44

51

Acidity of -Hydrogens


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Acidity of Hydrogens -Hydrogens are more acidic because the

enolate anion is stabilized by1. delocalization of its negative charge

2. the electron-withdrawing inductive effect of theadjacent electronegative oxygen

CH3 -C-CH2-H

O

:A-

O

CH3 -C CH2

O-

CH3 -C=CH2 H-A

Resonance-stabilized enolate anion

+ +

Keto-Enol Tautomerism


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Keto Enol Tautomerism

protonation of the enolate anion on oxygen gives the

enol form; protonation on carbon gives the keto form

Enolate anion

Enol formKeto form

-O

CH3 -C-CH2 CH3 -C=CH2

CH3 -C=CH2

H- A

CH3 -C-CH3 + A-

-

+

H- AOH

O-

O

To be continued



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acid-catalyzed equilibration of keto and enol tautomers

occurs in two stepsStep 1: proton transfer to the carbonyl oxygen

Step 2: proton transfer to the base A-

O

CH3 -C-CH3 H-A

O

CH3 -C-CH3

H

A-

+

+

+

Keto form

The conjugate acidof the ketone

fast andreversible

OCH3 -C-CH2 -H

H

:A-

OHCH3 -C=CH2 H-A

Enol form

+

+

slow+



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Keto-enol

equilibria forsimplealdehydesand ketones

lie far towardthe keto form

OH

O

O

CH3 CH CH2 = CH

CH3 CCH3

Keto form Enol form

% Enol at

Equilibrium

6 x 10-5

OH

CH3 C=CH2 6 x 10-7

O

O OH

OH

1 x 10-6

4 x 10-5



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For certain types of molecules, however, the enol

is the major form present at equilibrium for -diketones, the enol is stabilized by conjugation of

the pi system of the carbon-carbon double bond andthe carbonyl group

for acyclic -diketones, the enol is further stabilized byhydrogen bonding

Oxidation of Aldehydes


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Aldehydes are oxidized to carboxylic acids by a

variety of oxidizing agents, including H2CrO4

They are also oxidized by Ag(I) in one method, a solution of the aldehyde in aqueous

ethanol or THF is shaken with a slurry of silver oxide

CHO H2 CrO4 COOH

Hexanal Hexanoic acid

Vanillic acidVanillin

++CH

HO

CH3 O

O O

CH3 O

HO

COHAg2 O

THF, H2 O

NaOHAgHCl

H2 O



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Aldehydes are oxidized by O2 in a radical chain

reaction liquid aldehydes are so sensitive to air that they must

be stored under N2

Benzoic acidBenzaldehyde

+CH

O O

COH2O22

Oxidation of Ketones


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Oxidation of Ketones

ketones are not normally oxidized by chromic acid

they are oxidized by powerful oxidants at hightemperature and high concentrations of acid or base

Hexanedioic acid(Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)

HNO3

O

HOOH

OO OH

Reduction


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Reduction

aldehydes can be reduced to 1 alcohols

ketones can be reduced to 2 alcohols the C=O group of an aldehyde or ketone can be

reduced to a -CH2- group

Aldehydes

Can Be

Reduced to Ketones

Can Be

Reduced to

O OOH

RCH

RCH2OH

RCH3

RCR'RCHR'

RCH2R'

Metal Hydride Reduction


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Metal Hydride Reduction

The most common laboratory reagents for the

reduction of aldehydes and ketones are NaBH4and LiAlH4 both reagents are sources of hydride ion, H:-, a very

powerful nucleophile

Hydride ionLithium aluminum

hydride (LAH)

Sodium

borohydride

H

H H

H

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

H:

NaBH4 Reduction


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a 4 educt o

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

4RCH

O

NaBH4

( RCH2O) 4B-

Na+ H2O

4RCH2OH

A tetraalkyl borate

boratesalts

+

+ methanol

NaBH4 Reduction


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a 4 educt o

The key step in metal hydride reduction is

transfer of a hydride ion to the C=O group toform a tetrahedral carbonyl addition compound

Na+

H

H

H-B-H

O

R-C-R'

O BH3

H

R-C-R'

Na+H2O

O-H

H

R-C-R'

This H comes from waterduring hydrolysis

This H comes from the

hydride reducing agent

+

LiAlH4 Reduction


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4

unlike NaBH4, LiAlH4 reacts violently with water,

methanol, and other protic solvents reductions using it are carried out in diethyl ether or

tetrahydrofuran (THF)

4RCR LiAlH4 ( R2 CHO)4Al-

Li+ H2O

H

+

or OH

-

OH

4RCHR+ + aluminum

saltsA tetraalkylaluminate

etherO

Catalytic Reduction


74/84

y

Catalytic reductions are generally carried out at

from 25 to 100C and 1 to 5 atm H2

+25oC, 2 atm

Pt

Cyclohexanone Cyclohexanol

O OH

H2

1-Butanolt rans-2-Butenal(Crotonaldehyde)

2H2

NiH

O

OH

Catalytic Reduction


75/84

y

A carbon-carbon double bond may also be

reduced under these conditions

by careful choice of experimental conditions, it is oftenpossible to selectively reduce a carbon-carbon doublein the presence of an aldehyde or ketone

1-Butanolt rans-2-Butenal

(Crotonaldehyde)

2H2

NiH

O

OH

O OHRCH=CHCR' RCH=CHCHR'

1. NaBH4

2. H2O

O

RCH=CHCR' H2Rh

RCH2 CH2CR'

O

+

Clemmensen Reduction


76/84

refluxing an aldehyde or ketone with amalgamated zinc

in concentrated HCl converts the carbonyl group to amethylene group

Zn(Hg), HCl

OH O OH

Wolff-Kishner Reduction


77/84

in the original procedure, the aldehyde or ketone and

hydrazine are refluxed with KOH in a high-boilingsolvent

the same reaction can be brought about usinghydrazine and potassium tert-butoxide in DMSO

+

diethylene glycol(reflux)

KOH

N2

Hydrazine

+ H2 NNH2

+ H2 O

O

Racemization


78/84

Racemization at an -carbon may be catalyzedby either acid or base

O

Ph

OH

Ph

O

Ph

An achiralenol

(R)-3-Phenyl-2-butanone

(S)-3-Phenyl-2-butanone

omit

Deuterium Exchange


79/84

g

Deuterium exchange at an -carbon may becatalyzed by either acid or base

+

Acetone-d 6Acetone

+

O O

CH3 CCH 3 6 D2 O CD3 CCD 3 6 HODD

+

or OD-

omit

-Halogenation


80/84

g

-Halogenation: aldehydes and ketones with atleast one -hydrogen react at an -carbon withBr2 and Cl2

reaction is catalyzed by both acid and base

O

Br2CH3COOH

O

BrHBr

Acetophenone

++

-Bromo-acetophenone

omit

-Halogenation


81/84

g

Acid-catalyzed -halogenationStep 1: acid-catalyzed enolization

Step 2: nucleophilic attack of the enol on halogen

Step 3: (not shown) proton transfer to solvent completesthe reaction

H

R

R'-C-C-R

O

R'

C C

H-O R

R

slow

C

R

RH-O

C

R'

Br BrR'

C C

O Br

R

R

H

Br:-

+fast

+

omit

-Halogenation


82/84

g

Base-promoted -halogenationStep 1: formation of an enolate anion

Step 2: nucleophilic attack of the enolate anion onhalogen

+-

-

Res onance-stabilized enolate anion

+slow

O H

R

O

C C

R'R'

C C

O:

R'-C-C-R-:OH H2O

R

R

R

R

+fast

R'

C CO Br

R

R BrBr Br +

-

R'

C CO: R

Romit

-Halogenation


83/84

Acid-catalyzed halogenation:

introduction of a second halogen is slower than thefirst

introduction of the electronegative halogen on the -carbon decreases the basicity of the carbonyl oxygen

toward protonation Base-promoted -halogenation:

each successive halogenation is more rapid than theprevious one

the introduction of the electronegative halogen on the-carbon increases the acidity of the remaining -hydrogens and, thus, each successive -hydrogen isremoved more rapidly than the previous one

omit


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End

ch16 aldehydes and ketones

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