20.3 Nucleophilic Substitution in Acyl Chlorides

General Mechanism for Nucleophilic Acyl Substitution involves formation and dissociation of a tetrahedral intermediate O C R X HYHYHYHY C ROHX Y O C R Y -HX

Preparation of Acyl Chlorides from carboxylic acids and thionyl chloride (Section 12.7) (CH 3 ) 2 CHCOH O SOCl 2 heat (CH 3 ) 2 CHCCl O+ SO 2 + HCl (90%)

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

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

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

CH 3 (CH 2 ) 5 CCl OExample + CH 3 (CH 2 ) 5 COH Opyridine CH 3 (CH 2 ) 5 COC(CH 2 ) 5 CH 3 OO(78-83%)

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

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

Example C 6 H 5 CCl O+ (CH 3 ) 3 COH pyridine (80%) C 6 H 5 COC(CH 3 ) 3 O

RCCl O Reactions of Acyl Chlorides + RCNR' 2 O+ H2OH2OH2OH2O Acyl chlorides react with ammonia and amines to give amides: R' 2 NH + HO – + Cl –

RCClO Reactions of Acyl Chlorides + RCNR' 2 O+ H2OH2OH2OH2O Acyl chlorides react with ammonia and amines to give amides: R' 2 NH + HO – + Cl – via: C R O Cl NR' 2 H

Example C 6 H 5 CCl O+ NaOH (87-91%) H2OH2OH2OH2O HNHNHNHN C6H5CNC6H5CNC6H5CNC6H5CNO

RCCl O Reactions of Acyl Chlorides + RCOH O+ HCl Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): H2OH2OH2OH2O RCCl O+ RCO – O+ Cl – 2HO – + H2OH2OH2OH2O

RCCl O Reactions of Acyl Chlorides + RCOH O+ HCl Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base): H2OH2OH2OH2O via: C R O Cl OHOHOHOHH

Example C 6 H 5 CH 2 CCl O+ H2OH2OH2OH2O C 6 H 5 CH 2 COH O+ HCl

Reactivity C 6 H 5 CCl O C 6 H 5 CH 2 Cl Acyl chlorides undergo nucleophilic substitution much faster than alkyl chlorides. Relative rates of hydrolysis (25°C) 1,0001

20.4 Preparation of Carboxylic Acid Anhydrides Anhydrides can be prepared from acyl chlorides as described in Table 20.2

Some anhydrides are industrial chemicals CH 3 COCCH 3 OO Acetic anhydride OO OOO O Phthalic anhydride Maleic anhydride

From dicarboxylic acids Cyclic anhydrides with 5- and 6-membered rings can be prepared by dehydration of dicarboxylic acids C C H HCOH COHOO OO O H H tetrachloroethane130°C (89%) + H 2 O

20.5 Reactions of Carboxylic Acid Anhydrides Table 20.3

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

Reactions of Acid Anhydrides + RCOR' O+ Carboxylic acid anhydrides react with alcohols to give esters: R'OH RCOCR OORCOHO 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

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

Example (60%) H 2 SO 4 + CH 3 COCCH 3 OO CH 3 CHCH 2 CH 3 OHOHOHOH CH 3 COCHCH 2 CH 3 O CH 3

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

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

Example (98%) + CH 3 COCCH 3 OO H2NH2NH2NH2N CH(CH 3 ) 2 O CH 3 CNH CH(CH 3 ) 2

Reactions of Acid Anhydrides + 2RCOH O Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): H2OH2OH2OH2O + 2RCO – O+ 2HO – H2OH2OH2OH2O RCOCR OO OO

Reactions of Acid Anhydrides + 2RCOH O Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base): H2OH2OH2OH2O RCOCR OO C R O OCR OHHO

Example + H2OH2OH2OH2OOO O COHOCOH O