Pyrimido[1,4]benzothiazines and pyrimido[1,5]benzothiazepines. Part 3. Novel ring-contraction and ring-opening of pyrimido[1,5]benzothiazepines

Abstract

Pyrimido[1,5]benzothiazepine (1a) undergoes ready ring-contraction leading to 4a-alkoxymethylpyrimido[1,4]-benzothiazines (2a and b) upon treatment with iodine in alcohols. The reaction of (1a) with iodine in morpholine, however, results in the formation of pyrimido[1,4]benzothiazine (3) accompanied by loss of a methylene group. Ring-contraction of (1) to 4a-halogenoalkylpyrimido[1,4]benzothiazines (2c–f) is observed upon treatment with N-halogenosuccinimides or iodide in chloroform. When (1a—c) are allowed to react with alkyl halides in hot dimethylformamide, bispyrimidylmethane derivatives (4a—e) are obtained in moderate yields. Treatment of thiazepine S-oxide (10) with triethylamine in alcohols leads to the formation of the ring-contracted product, bis-(pyrimidobenzothiazinyl)methane (11). Additionally, pyrolysis of the bispyrimidylmethane derivative (4a) caused carbon–carbon bond cleavage to give the uracil derivatives (5) and (6) and the pyrimidoquinoline derivative (7). The mechanisms of the observed reactions are also discussed on the basis of available data.