Synthesis of 5-Aryl- 1,4-benzoxazepine and 6-phenyl-2H-1,5-benzoxazocine derivatives

Abstract

Four 5-aryl-2,3-dihydro-1,4-benzoxazepines (5a-d), with electron-releasing substituents, were prepared by a Bischler-Napieralski-type reaction of N-(2-aryloxyethyl)benzamides with phosphorus oxychloride in butanenitrile or ethanenitrile. Analogous 2,3-dihydro-1,4-benzoxazepines (12a, b), with hydrogen only or a chlorine substituent in the fused aromatic ring, were prepared by C-N ring-closure reactions. Cyclization of a dilute solution of N-[3-(3-methoxyphenoxy)propyl]benzamide (21) with phosphorus oxychloride in ethanenitrile gave a 40% yield of 9-methoxy-6-phenyl-3,4-dihydro- 2H-1,5-benzoxazocine (22). The seven- and eight-membered cyclic imines were converted into their methiodide salts (6a-d), (15a,b) and (24). These were reduced with sodium tetrahydroborate to yield the 5-aryl-4-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepines (7a-d) and (l6a,b), and the 9-methoxy- 5-methyl-6-phenyl-3,4,5,6-tetrahydro-2H-1,5-benzoxazocine (25). These products were prepared for use as starting materials in ring-expansion reactions through the Meisenheimer rearrangement.