Nucleophilic Substitution in Acyl Chlorides 3

General Mechanism for Nucleophilic Acyl Substitution involves formation and dissociation of a tetrahedral intermediate O •• • • C R X C R OH X Y O •• • • C R Y HY -HX 1 4

Preparation of Acyl Chlorides from carboxylic acids and thionyl chloride (CH3)2CHCOH O (CH3)2CHCCl O SOCl2 + SO2 + HCl heat (90%) 1 7

Reactions of Acyl Chlorides RCCl O RCOCR' O RCOR' O RCNR'2 O RCO– O 4

Reactions of Acyl Chlorides Acyl chlorides react with carboxylic acids to give acid anhydrides: RCCl O R'COH O RCOCR' O + + HCl 4

Reactions of Acyl Chlorides Acyl chlorides react with carboxylic acids to give acid anhydrides: RCCl O R'COH O RCOCR' O + + HCl C R O Cl OCR' H via: 4

Example CH3(CH2)5CCl O CH3(CH2)5COH O + pyridine CH3(CH2)5COC(CH2)5CH3 (78-83%) 4

Reactions of Acyl Chlorides Acyl chlorides react with alcohols to give esters: RCCl O RCOR' O + R'OH + HCl 4

Reactions of Acyl Chlorides Acyl chlorides react with alcohols to give esters: RCCl O RCOR' O + R'OH + HCl C R O Cl OR' H via: 4

Example C6H5CCl O C6H5COC(CH3)3 O pyridine + (CH3)3COH (80%) 4

Reactions of Acyl Chlorides Acyl chlorides react with ammonia and amines to give amides: RCCl O RCNR'2 O + R'2NH + HO– + H2O + Cl– 4

Reactions of Acyl Chlorides Acyl chlorides react with ammonia and amines to give amides: RCCl O RCNR'2 O + R'2NH + HO– + H2O C R O Cl NR'2 H + Cl– via: 4

Example C6H5CCl O C6H5CN O HN NaOH + H2O (87-91%) 4

Reactions of Acyl Chlorides Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): RCCl O RCOH O + H2O + HCl RCCl O RCO– O + 2HO– + Cl– + H2O 4

Reactions of Acyl Chlorides Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): RCCl O RCOH O + H2O + HCl C R O Cl OH H via: 4

Example C6H5CH2CCl O C6H5CH2COH O + H2O + HCl 4

Relative rates of hydrolysis (25°C) 1,000 1 Reactivity Acyl chlorides undergo nucleophilic substitution much faster than alkyl chlorides. C6H5CCl O C6H5CH2Cl Relative rates of hydrolysis (25°C) 1,000 1 4

Preparation of Carboxylic Acid Anhydrides Anhydrides can be prepared from acyl chlorides 3

Some anhydrides are industrial chemicals CH3COCCH3 O Acetic anhydride Phthalic anhydride Maleic anhydride 4

From dicarboxylic acids Cyclic anhydrides with 5- and 6-membered rings can be prepared by dehydration of dicarboxylic acids C H COH O O H tetrachloroethane 130°C + H2O (89%) 4

Reactions of Carboxylic Acid Anhydrides 3

Reactions of Anhydrides RCOCR' O RCOR' O RCNR'2 O RCO– O 4

Reactions of Acid Anhydrides Carboxylic acid anhydrides react with alcohols to give esters: RCOCR O RCOR' O RCOH O + R'OH + normally, symmetrical anhydrides are used (both R groups the same) reaction can be carried out in presence of pyridine (a base) or it can be catalyzed by acids 4

Reactions of Acid Anhydrides Carboxylic acid anhydrides react with alcohols to give esters: RCOCR O RCOR' O RCOH O + R'OH + C R O OCR OR' H via: 4

Example + CH3COCCH3 O CH3CHCH2CH3 OH H2SO4 CH3COCHCH2CH3 O CH3 (60%) 4

Reactions of Acid Anhydrides Acid anhydrides react with ammonia and amines to give amides: RCOCR O RCNR'2 O RCO– O + 2R'2NH + R'2NH2 + 4

Reactions of Acid Anhydrides Acid anhydrides react with ammonia and amines to give amides: RCOCR O RCNR'2 O RCO– O + 2R'2NH + C R O OCR NR'2 H R'2NH2 + via: 4

Example CH3COCCH3 O H2N CH(CH3)2 + O CH3CNH CH(CH3)2 (98%) 4

Reactions of Acid Anhydrides Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): RCOCR O O + H2O 2RCOH RCOCR O O + 2HO– 2RCO– + H2O 4

Reactions of Acid Anhydrides Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): RCOCR O O + H2O 2RCOH C R O OCR OH H 4

Example COH O O + H2O 4