Carboxamides from acyl halides

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic applications, cannot be directly synthesized from amides and phosgene. Reactions of acid halides with cyanates have been suggested. Howev er, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride. Cyclic intermediates have been observed in these reactions which generally give a high yield of the desired products. 

Symmetrical A-sulfonyl sulfonamides, i.e., sulfonimides, can be prepared from the amine and two equivalents of sulfonyl chloride and base. The unsym-metrical A/-sulfonyl sulfonamides and the related A-acyl sulfonamides can be obtained by the reaction of a sulfonamide or carboxamide with an acid halide. 

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