Azepinones. Part 1. Synthesis of 1,2,3,7-tetrahydroazepin-4-ones and hexahydroazepin-3-ones

Abstract

2-Chloro-N-tosylprop-2-enylamine (5; R = H) was converted into methyl 3-[N-(2-chloroprop-2-enyl)-N-tosylamino]propanoate (5; R = CH₂CH₂CO₂Me) and into 3-[N-(2-chloroprop-2-enyl)-N-tosyl-amino]propanonitrile (5; R = CH₂CH₂CN). These, in turn, were converted into 4-[N-(2-chloroprop-2-enyl)-N-tosylamino]-1-methylbutan-2-ol [5; R = CH₂CH₂C(OH)Me₂], 3-[N-(2-chloroprop-2-enyl)-N-tosylamino]-1-phenylpropan-1-one (5; R = CH₂CH₂COPh), 4-[N-(2-chloroprop-2-enyl)-N-tosylamino]-2-phenylbutan-2-ol [5; R = CH₂CH₂C(OH)(Me)Ph], 3-[N-(2-chloroprop-2-enyl)-N-tosylamino]-1-phenylpropan-1-ol [5; R = CH₂CH₂CH(OH)Ph], 4-[N-(2-chloroprop-2-enyl)-N-tosylamino]butan-2-ol [5; R = CH₂CH₂CH(OH)Me] and 3-[N-(2-chloroprop-2-enyl)-N-tosylamino]propanoic acid (5; R = CH₂CH₂CO₂H). The alcohols [5; R = CH₂CH₂C(OH)Me₂] and [5; R = CH₂CH₂CH(OH)Ph] were cyclised by 90% sulfuric acid to 5,5-dimethyl-N-tosylazepan-3-one (6; R¹= R²= Me) and 5-phenyl-N-tosylazepan-3-one (6; R¹= Ph, R²= H), respectively. 6,6-Dichloro-N-tosylazepan-4-one 7 was obtained from 3-[N-(2-chloroprop-2-enyl)-N-tosylamino]propanoic acid (5; R = CH₂CH₂CO₂H)via the acid chloride and was further converted into 6-chloro-1,2,3,7-tetrahydro-N-tosylazepin-4-one (8, R = Cl) and into the 6-methoxy analogue (8; R = OMe).