Chapter 21.

Carboxylic Acid

Derivatives: Esters and Amides

Based on McMurrys Organic Chemistry, 7th edition

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Preparation of Esters[1]
Esters are usually prepared from carboxylic acids

Ester from carboxylic acid with alkyl halide [2]

O H H3C O Na OH H3C O H H3C O Br OH

Na
O

-H2O

H3C

O- Na+

Asam asetat

NaBr

H3C

Metil asetat

Acid catalysist esterification : carboxylic acid with alcohol [3]

O OH OH OH O H3C H H3C O H OCH3 O H

H
OH

asam benzoat

-H2O

H O O

OCH3

-H+

OCH3

4
metil benzoat

Conversion of An Acyl Chloride Into An Ester [2]

Preparation of Acyl Chloride
O O S OH Cl H Cl Cl O S Cl O O

Asam asetat

-H+ -ClN O O

-SO2
Cl O

5
S Cl

Asetil Klorida

Conversion of An Acyl Chloride Into An Ester [2]

O H3C Cl OH OCH3 H O Cl

Asetil Klorida

-Cl

+
OCH3

6
Cl OCH3

Metil Asetat

Reactions of Esters [1]

Less reactive toward nucleophiles than are acid chlorides or anhydrides Cyclic esters are called lactones and react similarly to acyclic esters

Hydrolysis: Conversion of Esters into Carboxylic Acids [1]

An ester is hydrolyzed by aqueous base or aqueous acid to yield a carboxylic acid plus an alcohol
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Mechanism of Ester Hydrolysis [1]

Hydroxide catalysis via an addition intermediate

Conversion of metyl acetate into acetic acid [3]

H O H B+ O OH OCH3 O H H OH OH OH OCH3 OCH3 OCH3

Metil Asetat

B
H

B+

B
O

HB

H O

OH OCH3

CH3OH
OH

+
OH OH

Asam asetat

10

Aminolysis of Esters [1]

Ammonia reacts with esters to form amides

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Mechanism of Ester [2] Aminolysis

O O O OCH3 NH3 Ph NH2 H

eter
Ph OCH3

Ph

NH3 -OCH3

Metyl benzoate

CH3OH metanol

+
Ph NH2

benzamide

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Mechanism of Reaction
O O O OEt NH2CH3 Et NHCH3 H

eter
Et O

CH3NH2 -OEt

Etyl propionate

O OH

+
N H

ethanol

13

N-methylpropionamide

Reduction: Conversion of Esters into Alcohols [1]

Reaction with LiAlH4 yields primary alcohols
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Mechanism of Reaction 1
O
H OEt H AlH3 Li+ O
+

LiAlH3
OEt

eter
H3CH2C(HC)2

ethyl 2-pentenoate -+LiAlH3

H H O H H3CH2C(HC)2

O +LiAlH3 H H H

Et

O-

-EtOH -H2O
H H AlH3 Li+ H O H

-+LiAlH3

15
H2O +
OH

2-penten-1-ol

Mechanism of Reaction 2
O H O O O

eter
H AlH3 Li+

-+LiAlH3
H

lactone
O

Li H3Al

H H

H O H

-H2O

OH

O Li+ AlH3

-+LiAlH3 -H2O
OH H

H O H H

16
OH

1,4-pentanediol

Mechanism of Reduction of Esters [1]

Hydride ion adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde Reduction of the aldehyde gives the primary alcohol

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Conversion of methyl propionate into propanol [3]

H3C OO

O
H O AlH3 Li
+

O Et H

LiAlH3 -+LiAlH3
OCH3

methyl propionate

AlH3 Li+

O +LiAlH3 H Et H H

H2O

+ propanol

OH

-+LiAlH3
H O

18

Reaction of Esters with Grignard Reagents [1]

React with 2 equivalents of a Grignard reagent to yield a tertiary alcohol
19

19

Mechanism of Reaction
MgBr O Ph O Ph Ph MgBr

MgBr
O O

-OCH3
OCH3 Ph Ph

methyl benzoat
H OH H O H Ph Ph Ph O Ph Ph

MgBr

H2O

Ph

triphenylmethanol

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Conversion of an ester into a tertiary alcohol [3]

MgBr
O Et O H3C MgBr CH3 H3C MgBr O O

-OCH3
OCH3

an ester

H OH H O H Et CH3 CH3 O CH3 CH3

MgBr

H2O

Et

a tertiary alcohol

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21.7 Chemistry of Amides [1]

Amides are abundant in all living organismsproteins, nucleic acids, and other pharmaceuticals have amid functional groups

22

Preparation of Amides [1]

Prepared by reaction of an acid chloride with ammonia, monosubstituted amines, or disubstituted amines

23

Mechanism Reaction 1[2]

O O Ph H N H Cl H O H N H H

-Cl

NH3

Ph

Cl

Ph

NH3

-H+

Ph

NH2

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Mechanism Reaction 2[2]

O O Et H N H Cl CH3 O H N H

-Cl

H2NCH3
CH3

Et

Cl

Et

H2NCH3

-H+

Et

NHCH3

25

Mechanism Reaction 3[2]

O O H3C H3C N CH3 Cl H

H N CH3 CH3

-Cl

N(CH3)2

H3C

Cl

H3C

N(CH3)2

-H+

26

Reactions of Amides [1]

Heating in either aqueous acid or aqueous base produces a carboxylic acid and amine Acidic hydrolysis by nucleophilic addition of water to the protonated amide, followed by loss of ammonia

27

Basic Hydrolysis

[1] of Amides

Addition of hydroxide and loss of amide ion

28

28

Mechanism for acid-catalyzed hydrolysis of an amide [3]

29

Reduction: Conversion of Amides into Amines [1]

Reduced by LiAlH4 to an amine rather than an alcohol Converts C=O CH2

30

Mechanism of Reduction [1]

Addition of hydride to carbonyl group Loss of the oxygen as an aluminate anion to give an iminium ion intermediate which is reduced to the amine

31

Conversion of amide into amine [3]

O H H3C(H2C)10 NCH3 H AlH3 H3C(H2C)10 NCH3 H3C(H2C)10 NCH3 O

AlH3

H Al O

H H

N-Methyldodecanamide

H H3C(H2C)10 N

AlH3 H3C(H2C)10 C H NCH3 H3C(H2C)10

AlH2 NCH3

H2O

AlH2O-

H3C(H2C)10

N H

-OH

Dodecylmethylamine

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Mechanism for the reaction of an N-subtituted amide with hydride ion [3]
O H H3C NCH3 H AlH3 H3C NCH3 H3C NCH3 O

AlH3

H Al O

H H

an amide

AlH3 H3C C H NCH3 H3C

-

AlH2 NCH3

H2O

AlH2O

33
N H

-OH

an amine

Conversion of amide into amine [3]

34

Reference
[1] McMurry, J., 2008, Organic Chemistry, Seventh Edition, Thomson Learning, Inc., USA [2] Hart, H., Leslie E.C., David J.H., 2003,Kimia Organik : Suatu Kuliah Singkat, Edisi Kesebelas, diterjemahkan oleh : Suminar S.A., Penerbit Erlangga, Jakarta [3]Bruice, P.Y., 2004, Organic Chemistry, Fourth Edition, Pearson Prentice Hall, New Jersey

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