acid derivatives correct

8/3/2019 Acid Derivatives Correct

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Acid Derivatives

CR

O

Cl

CR

O

CR

O

OCR

O

OR'CR

O

NH2

Acid

chloride

Acid

anhydride

Ester Acid

amide


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Acid Derivatives

All of them undergo nucleophilic reactions:

Nucleophilic addition followed by

elimination.

Mechanism:

CR

O

GNu

CR G

Nu

O

CR

O

Nu


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Acid Derivatives

Reactivity depends on:

1. Structure of acid derivatives

a. Inductive effect of G exert on the

carbonyl carbon

The more negative the inductive

effect, the more reactive the

compound.However, the effect is small since

difference of electronegativity between

Cl, N and O is small.


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Acid Derivatives

b. Mesomeric effect of G exert on thecarbonyl carbon

From the orbital approach, resonanceenergy is higher in acid amide, ester

and acid anhydride due to the betterinteraction of the 2p orbitals of N andO with 2p orbital of C.

C

O

RN


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While in acid chloride, resonance energy

is least as 3p-2p interaction is weaker.

Also, if the overlapping is more effective,

the carbonyl carbon will be less positive,

i.e. less reactive.

Acid Derivatives

CO

RCl

3p orbital

2p orbital


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Acid Derivatives

Reactivity depends on:

2. Leaving group ability of G

Less basic the anion, the better it acts

as a leaving group.Basic strength:

NH2- > OR- > OH- > RCOO- > Cl-

Leaving ability:Cl- > RCOO- > OH- > OR- > NH2-


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Acid Derivatives

From the 2 factors above (Structure of

acid derivatives and Leaving group

ability of G), the reactivity of the acid

derivatives towards nucleophile decreasein the order:

Acid chloride > Acid anhydride > Ester >

Acid amide


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Acid Derivatives

Acid Chloride

1. Preparation

CR

O

ClCR

O

OH

PCl5

+ POCl3 + HCl

CR

O

Cl

CR

O

OH

PCl3

CR

O

Cl

CR

O

OH

SOCl2

+ H3PO

3

+ SO2

+ HCl


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Acid Derivatives

Acid Chloride

2. Physical properties

a. Lower members are colourless liquid.

b. It has a pungent and irritating smell.


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Acid Derivatives

Acid Chloride

3. Chemical properties

Nucleophilic reaction occurs easily because

a. Carbonyl carbon is more positive since it

attaches to 2 electronegative atoms (O &

Cl).

b. The lateral overlapping of Cl with carbonyl

carbon is the least among the acidderivatives.

c. Cl- is a weak base and thus a good

leaving group.


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Acid Derivatives

Acid Chloride


CR

O

Cl

CR

O

OH

CR

O

Cl

CR

O

Cl

CR

O

Cl

CR

O

Cl

CR

O

OR'

CR

O

NH2

OH2

R'OH / phenol

NH3

/ R'NH2

R'COONa CR

O

CR'

O

O

LiAlH4 CR H

H

OH


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Acid Derivatives

Acid Chloride

3. Chemical propertiesReduction

a. With LiAlH4

CR

O

Cl

LiAlH4 /dry etherCR H

H

OH

1.

2. water

LiAlH4 is a very strong reducing agent,so it will reduce acid chloride to alcohol.

Another reducing agent has the same result:

H2, Pd / Pt


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Acid Derivatives

Acid Chloride

3. Chemical propertiesReduction

b. To aldehyde

CR

O

Cl

+ H2

Pd / BaSO4

CR

O

H

+ HCl

It is a very good method to prepare aldehyde.


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Acid Derivatives

Acid Anhydride

CR

O

CR

O

O

Simpleanhydride

CR

O

CR'

O

O

Mixedanhydride


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Acid Derivatives

Acid Anhydride

1. Preparation

a. Dehydration of acid (for simple

anhydride only)

CR

O

CR

O

ORCOOHZnO

250 Co

2

OR P2O

5


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Acid Derivatives

Acid Anhydride

1. Preparation

b. From acid chloride

CR

O

Cl

CRO

CR'

O

O

R'COONa


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Acid Derivatives

Acid Anhydride


a. Lower members are colourless liquid.

b. It is slightly soluble in water.c. It has a pungent odour.


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Acid Derivatives

Acid Anhydride


Also undergo nucleophilic addition

followed by eliminated. Carboxylate

anion is a good leaving group andreaction of anhydride parallel those of the

acid chloride. However, the lateral overlap

of O with carbonyl carbon is more effective,

and that the large carboxylate groupincrease steric crowding in forming the

intermediate, so the anhydride are generally

less reactive than acid chloride.


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Acid Derivatives

Acid Anhydride


a. Hydrolysis

CRO

CR

O

O + H2O CR

O

OH

2


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Acid Derivatives

Acid Anhydride


b. Ammonolysis

CR

O

CR

O

O CR

O

NH2

+ NH3 + RCOO NH4

+-

CRO

CR

O

O + R'NH2 CR

O

NH

R'

+ RCOOH

R'NH2

RCOO NH3R'

+-


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Acid Derivatives

Acid Anhydride


c. Alcoholysis

CR

O

CR

O

O + R'OH2 RCOOR' + H2O2


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Acid Derivatives

Ester

Chloromethyl but-3-enoate

Methyl 2-bromopropanoate

CH3CHC OCH3

O

Br

CH2=CHCH

2C OCH

2

O

Cl


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Acid Derivatives

Ester

1. Preparation

a. Esterification

CR

O

OH

+ R'OH CR

O

OR'

+ H2O


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Acid Derivatives

Ester

1. Preparation

b. Acylation of alcohol / phenol

CRO

Cl

+ R'OH CRO

OR'

CR

O

Cl+

OH

CR

O

OR'


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Acid Derivatives

Ester

1. Preparation

c. From alkyl iodide

CR

O

O Ag

CR

O

OR'+-

+ R'I


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Acid Derivatives

Ester


a. It is oily liquid solid.

b. It has a fragrant fruity smell.c. It is insoluble in water.


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Acid Derivatives

Ester


a. Hydrolysis

CR

O

OR'

+ H2O CR

O

OH

+ R'OH


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Acid Derivatives

Ester


CR

O

OR'

CR

O

O + R'OH+ OH

-

-

CR

O

O CH21

CR

O

O CH2

CR

O

O CH23

+ NaOH3

CR

O

O-

CR

O

O-

CR

O

O-

1

2

3

+

OH CH2

OH CH

OH CH2

Saponification

(And preparation of soapy detergent)


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Acid Derivatives

Ester


b. Ammonolysis

CRO

OR'

+ R'OH+ NH3

CRO

NH2

CR

O

OR'

+ R'OHCR

O

NHR"

+ R"NH2


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Acid Derivatives

Ester


c. Alcoholysis / trans-esterification

n HOCH2CH

2OH + n C C OO

O O

CH3

CH3

C CO

O O

OCH2CH

2+ nCH

3OH

n


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Acid Derivatives

Ester


d. Reduction

CR

O

OR'

RCH2OH + R'OH

Reducing agents may be:

1. LiAlH4 / ether followed by H+

2. Na / alcohol


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Acid Derivatives

Acid Amide

CR

O

NH2

CR

O

NHR'CR

O

NR'R"

primary secondary tertiary


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Acid Derivatives

Acid Amide

1. Preparation

a. Ammonolysis

CR

O

Cl

+ NH3

CR

O

NH2

+ HCl

CR

O

OR'

+ NH3

CR

O

NH2

+ R'OH

C

ORC

R

O O

+ NH3 CR

O

NH2

CR

O

O NH4

++-


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Acid Derivatives

Acid Amide

1. Preparation

b. From acid

RCOOH + NH3 RCOO NH4-

RCOO NH4+-

CR

O

NH2

+ H2O


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Acid Derivatives

Acid Amide

1. Preparation

c. From acid nitrile

RCNalcoholic NaOH

CR

O

NH2


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Acid Derivatives

Acid Amide


a. All 1o and 2o acid amides except

methanamide are colourless solides

because of the strong intermolecular H-bond. They have high m.p. and b.p.

But 3o amides have normal m.p. and b.p..

(Why?)

b. Lower members are soluble in water due to

the formation of extensive H-bond with

water.


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Acid Derivatives

Acid Amide


a. Hydrolysis

CRO

NH2

+ OH-

CRO

O

+ NH3

-

CR

O

NH2

CR

O

OH

+ H3O+ + NH

4+


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Acid Derivatives

Acid Amide


b. Dehydration

CRO

NH2

P2O

5

heatCR N


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Acid Derivatives

Acid Amide


c. Reduction

CR

O

NH2

LiAlH4

/ dry ether

(or Na / ethanol)RCH

2NH

2


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Acid Derivatives

Acid Amide


d. Hofmann Degradation

(Reduce one carbon atom)

CR

O

NH2

+ Br2

+ KOH RNH2

+ KBr + K2CO

34 2

acid derivatives correct

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