P Chlorobenzoyl chloride

This modification is illustrated by the preparation of p-chlorobenzoic anhydride from p-chlorobenzoyl chloride. 

Place a mixture of 17 -5 g. p-chlorobenzoyl chloride (1) and 50 ml. of dry pyridine (Section 11,47,22) in a loosely-stoppered 250 ml. flask and warm on a steam hath for 5 minutes. Pour the reaction mixture upon 100 g. of crushed ice and 50 ml. of concentrated hydrochloric acid. The anhydride separates out at once. When the ice has melted sufficiently, filter the mixture by suction. Wash the sohd with 15 ml. of methanol and then with 15 ml. of dry benzene. The yield of crude p-chlorobenzoic anhydride is 14 5 g. Recrystalhse from 250 ml. of dry benzene 13 g. of the pure anhydride, m.p. 192-193°, are obtained. 

Prepare p-chlorobenzoyl chloride by refluxing and stirring 78 g. of p-chloro-benzoic acid (Section IV,157) and 100 g. of redistilled thionyl chloride until solution is complete. Distil off the excess of thionyl chloride at atmospheric pressure and then the acid chloride under reduced pressure 70 g. of product, b.p. 119-120°/ 22 mm., m.p. 14-15°. are obtained. 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

Yet another nontricyclic antidepressant consists of a relatively simple morpholine derivative. Acylation of aziridine with p-chlorobenzoyl chloride gives the amide 130. This intermediate is. sufficiently reactive to undergo ring opening on treatment with morpholine. The product is the antidepressant agent moclobemide (131) 33J. 

Ethyl-2-(3-hydroxy-4-amlnophenyl)propionate p-Chlorobenzoyl Chloride... 

N-p-Chlorobenzohydryl piperazine Hydroxyzine HCI o-Chlorobenzo nitrile Ketamine HCI o-Chlorobenzophenone Chlophedianol 4-Chlorobenzophenone Chlorphenoxamine HCI p-Chlorobenzoyl chloride Benoxaprofen... 

For (313), he began with the intact nucleoside 5-ethoxymethyl-2 -deoxyuridine (307) [160], After protection of the 3 - and 5 -hydroxy groups with p-chlorobenzoyl chloride, the resulting diester (308) was converted into a separable mixture of (309) (major) and (310) (minor). Alkylation of (35) with crude (309) gave (311) together with small amounts of unreacted (35) and a product tentatively identified as (310). Cleavage of the p-chlorobenzoates with methanolic sodium methoxide with concomitant transesterification yielded (312), which was saponified and then treated with barium acetate to afford the barium salt of (313). 

Azaindoles are readily acylated on the pyrrole nitrogen by warming on a water bath with acid anhydrides or with acid chlorides in the presence of carbonate or pyridine. Good yields were obtained by this procedure for the following compounds l-acetyl-7-azaindole, 1-benzoyl- and l-benzenesulfonyl-7-azaindole, l-benzoyl-2-methyl-7-azaindole, 1-ethoxycarbonyl- and l-chloroacetyl-7-azaindole, l-acetyl-3-cyano-7-azaindole, 1-benzoyl-4-azindole, and 1-acetyl- and l-benzoyl-2,5-dimethyl-4-azaindole. The only reported failure was with 5-methyl-2-phenyl-4-azaindole, which failed to react with acetic anhydride or benzoyl chloride. 2-Methyl-7-azaindole-3-acetic acid was acylated by treatment of its ierGbutyl ester with sodium hydride in dimethylformamide, followed by p-chlorobenzoyl chloride. ... 

Table 14.6 Benzoylation of phenetole with p-chlorobenzoyl chloride over different zeolites.

Yield relative to p-chlorobenzoyl chloride (molar ratio phenetole p-chlorobenzoyl chloride = 4). 

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