Acid Derivatives

O O R C Cl Acid chloride R C O Acid anhydride Ester Acid amide R C O R C OR' O R C NH2 O

Acid Derivatives
All of them undergo nucleophilic reactions: Nucleophilic addition followed by elimination. Mechanism:
O R Nu C G R O C Nu G R C Nu O

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.

Acid Derivatives
b. Mesomeric effect of G exert on the carbonyl carbon From the orbital approach, resonance energy is higher in acid amide, ester and acid anhydride due to the better interaction of the 2p orbitals of N and O with 2p orbital of C.
O R C N

Acid Derivatives
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.
O R
2p orbital

C Cl 3p orbital

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

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 decrease in the order: Acid chloride > Acid anhydride > Ester > Acid amide

Acid Derivatives Acid Chloride

1. Preparation
O R C OH O R C OH O R C OH PCl5 O R C Cl O R C Cl O R C Cl + SO2 + HCl + H3PO3 + POCl3 + HCl

PCl3

SOCl2

Acid Derivatives Acid Chloride

2. Physical properties a. Lower members are colourless liquid. b. It has a pungent and irritating smell.

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 acid derivatives. c. Cl- is a weak base and thus a good leaving group.

Acid Derivatives Acid Chloride

3. Chemical properties
O R C Cl O R C Cl O R C Cl NH3 / R'NH2 R'OH / phenol R C OH2 O R C OH O OR' O R C NH2 R C Cl R C Cl R' C O O OH LiAlH4 R C H H O R'COONa R C O O

Acid Derivatives Acid Chloride

3. Chemical properties Reduction a. With LiAlH4
O OH C H R C Cl 1. LiAlH4 /dry ether 2. water R H

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

Acid Derivatives Acid Chloride

3. Chemical properties Reduction b. To aldehyde
O R C Cl + H2 Pd / BaSO4 R C H O + HCl

It is a very good method to prepare aldehyde.

Acid Derivatives Acid Anhydride

O R R C O C O Simple anhydride R' C O Mixed anhydride R C O O

Acid Derivatives Acid Anhydride

1. Preparation a. Dehydration of acid (for simple anhydride only) O
2 RCOOH ZnO o 250 C OR P2O5 R R C O C O

Acid Derivatives Acid Anhydride

1. Preparation b. From acid chloride
O O R C Cl R' C O R'COONa R C O

Acid Derivatives Acid Anhydride

2. a. b. c. Physical properties Lower members are colourless liquid. It is slightly soluble in water. It has a pungent odour.

Acid Derivatives Acid Anhydride

3. Chemical properties Also undergo nucleophilic addition followed by eliminated. Carboxylate anion is a good leaving group and reaction 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 group increase steric crowding in forming the intermediate, so the anhydride are generally less reactive than acid chloride.

Acid Derivatives Acid Anhydride

3. Chemical properties a. Hydrolysis
O R R C O C O + H2O 2R C OH O

Acid Derivatives Acid Anhydride

3. Chemical properties b. Ammonolysis
O R R C O C O O R R C O + R'NH2 C O R C NH R' O + RCOOH R'NH2 -+ RCOO NH3R' + NH3 R C NH2 O + RCOO NH4+

Acid Derivatives Acid Anhydride

3. Chemical properties c. Alcoholysis
O R R C O + 2 R'OH C O 2 RCOOR' + H2O

Acid Derivatives Ester

O CH3CHC O CH3 Br

Methyl 2-bromopropanoate
O CH2=CHCH2C OCH2 Cl

Chloromethyl but-3-enoate

Acid Derivatives Ester

1. Preparation a. Esterification
O R C OH + R'OH R C OR' O + H2O

Acid Derivatives Ester

1. Preparation b. Acylation of alcohol / phenol
O R C Cl O R C Cl + OH R C OR' + R'OH R C OR' O O

Acid Derivatives Ester

1. Preparation c. From alkyl iodide
O R C O Ag + + R'I R C OR' O

Acid Derivatives Ester

2. a. b. c. Physical properties It is oily liquid solid. It has a fragrant fruity smell. It is insoluble in water.

Acid Derivatives Ester

3. Chemical properties a. Hydrolysis
O R C OR' + H2O R C OH O + R'OH

Acid Derivatives Ester

3. Chemical properties
Saponification
O R O R1 C O R2 C O R3 C C O R C O O O CH2 O CH + 3NaOH R1 C O R C 2 O R C 3 OOOHO CH2 + HO CH + R'OH + OH OR'

O CH2

HO CH2

(And preparation of soapy detergent)

Acid Derivatives Ester

3. Chemical properties b. Ammonolysis
O R C + NH3 OR' O R C + R"NH2 OR' R C R C O + R'OH NH2 O + R'OH NHR"

Acid Derivatives Ester

3. Chemical properties c. Alcoholysis / trans-esterification
O n HOCH2CH2OH + n CH3O C O C OCH3

O OCH2CH2 O C

O C n + nCH3OH

Acid Derivatives Ester

3. Chemical properties d. Reduction
O R C OR' RCH2OH + R'OH

Reducing agents may be: 1. LiAlH4 / ether followed by H+ 2. Na / alcohol

Acid Derivatives Acid Amide

O R C NH2 primary R C NHR' secondary O R C NR'R" tertiary O

Acid Derivatives Acid Amide

1. Preparation a. Ammonolysis
O R C Cl O R O C R O C + NH3 OR' O C R + NH3 R C R C NH2 O + NH2 R C O O NH4+ + NH3 R C NH2 O + R'OH O + HCl

Acid Derivatives Acid Amide

1. Preparation b. From acid
RCOOH + NH3 RCOO NH4+ RCOO NH4 O R C + H2O NH2

Acid Derivatives Acid Amide

1. Preparation c. From acid nitrile
alcoholic NaOH O R C NH2

RCN

Acid Derivatives Acid Amide

2. Physical properties a. All 1o and 2o acid amides except methanamide are colourless solides because of the strong intermolecular Hbond. 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.

Acid Derivatives Acid Amide

3. Chemical properties a. Hydrolysis
O R C NH2 O R C + H3O+ NH2 R C OH + OH R C OO + NH4+ O + NH3

Acid Derivatives Acid Amide

3. Chemical properties b. Dehydration
O R C NH2 P2O5 heat R C N

Acid Derivatives Acid Amide

3. Chemical properties c. Reduction
O R C NH2 LiAlH4 / dry ether (or Na / ethanol) RCH2NH2

Acid Derivatives Acid Amide

3. Chemical properties d. Hofmann Degradation (Reduce one carbon atom)
O R C + Br2 + 4 KOH NH2 RNH2 + 2 KBr + K2CO3