Acyl benzoic acids, hydrogenation

Initial efforts to prepare benzoic acid 28 from methyl or ethyl 4-aminobenzoate and biphenyl-2-carboxylic acid (27) afforded poor yields of 28 (48% and 7%, respectively). However, acylation of 4-aminobenzoic acid with biphenyl-2-carbonyl chloride was found to provide 28 in excellent yield (95%) when DMAP was employed as a base. Selective acylation of the anilinic nitrogen of 26 with benzoic acid 28 was accomplished in analogy with the first-generation process synthesis by conversion of 28 to the corresponding acid chloride (SOCl2, CH3CN) followed by acylation of 26 in acetonitrile. Subsequent addition of ethanolic hydrogen chloride to the reaction mixture resulted in the precipitation of conivaptan HCl (1), which was isolated in 90% yield. 

Intramolecular if>so-acylationst Grisadienediones such as 2 can be obtained by treatment of a substituted o-phenoxy benzoic acid ester (1) with dry hydrogen chloride and an excess of TiCl4 at 0-25°. The synthesis involves an intramolecular (pro-acylation.1... 

The reaction of acyl halides with carboxylic acids affords good yields of simple and mixed anhydrides. The use of pyridine or triethylamine helps to remove the hydrogen chloride by-product. However, the preparation of benzoic anhydride from benzoic acid and benzoyl chloride has also been carried out in the absence of trialkylamines by heating under reduced pressure, in the presence of zinc chloride or by refluxing in chlorohydrocarbons such as methylene chloride. 

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