Chemistry Reference
In-Depth Information
4.4.2
Acid Chlorides. Chlorination of Carboxylic Acids
Phosgene and its equivalents (triphosgene, for example) react with carboxylic acids
1325 to give an acyl haloalkyl carbonate 1326 or acyl chloroformate 1327. Depend-
ing on the reaction conditions, the predicted intermediates, which are of limited
stability, readily lose carbon dioxide to give an acid chloride 1328 as a more stable
carbonic acid derivative, or react with a nucleophile (for example, the acid carboxy-
late) to give the corresponding product of nucleophilic substitution 1329.
O
R
Cl
- CO
2
O
O
O
l
Cl
Cl
O
O
(CCl
3
O)
2
CO
1328
R
H
R
O
Cl
R
O
O
O
NuY
+
YCl
1325
1326
1327
R
Nu
- CO
2
1329
Various chlorinating agents have been used to convert carboxylic acids or their an-
hydrides into acid chlorides. The most commonly reported methods employ thi-
onyl chloride, phosphorus trichloride,orphosphorus pentachloride. However, the
unsatisfactory degree of purity of the final acid chlorides, due to inherent contam-
ination with sulfur or phosphorus by-products, has stimulated a search for new
reagents and catalysts.
4.4.2.1
Phosgene
Phosgene as a chlorinating agent, together with N,N-dialkyl carboxamides, amidi-
nium salts, or tetralkyl ureas as catalysts, has proved to be an economical alterna-
tive to the large-scale manufacture of acid chlorides [998-1001]. Comprehensive
catalyst screening studies to achieve high reaction rates and conversions have been
reported [1002-1004].
CO
2
H
1330
COCl
2
cat. imidazole
90-99°C
30-60 min
- HCl
- CO
2
COCl
94.5 %
1331
Typical procedure. Lauroyl chloride 1331 [1002].
Equipment: A 500-mL, round-
bottomed flask was fitted with a paddle stirrer, a gas inlet tube, a thermowell, and a
