Ring transformations in reactions of heterocyclic halogeno compounds with nucleophiles (XXXVII). A 15N study on amination and isoxazole formation in reactions of 6‐substituted 4‐chloro‐ and 4‐phenoxypyrimidine 1‐oxides with liquid ammonia and with potassium amide in liquid ammonia

Treatment of 4‐chloro‐6‐R‐[1(3)‐15N]pyrimidine 1‐oxide (RCH3, C6H5) with liquid ammonia at − 33°C yields 4‐amino‐6‐R‐pyrimidine 1‐oxide (RCH3, C6H5), which contains no 15N‐label in the amino group. The amino‐dechlorination does not take place according to an SN(ANRORC) mechanism. The same results were obtained with solutions of potassium amide in liquid ammonia at − 75°C. Furthermore, 4‐chloro‐5‐deutero‐6‐phenylpyrimidine 1‐oxide in liquid ammonia yields a 4‐amino‐5‐deutero‐6‐phenylpyrimidine 1‐oxide with the same D content as the starting material, thus excluding an SN(EA) process. It was found that the reaction of 4‐chloro‐6‐methyl‐[1(3)‐15N]pyrimidine 1‐oxide with liquid ammonia at − 33°C and with potassium amide in liquid ammonia at − 75°C, to 5‐amino‐3‐methylisoxazole is accompanied by loss of 15N. The 15N label was unequally distributed over the nitrogen of the ring and the amino group. Two concurrent mechanisms: one, involving the addition of the amide ion to C(2), the other to C(4) of the pyrimidine ring are proposed. Since the 5‐amino‐3‐methylisoxazole obtained from reaction of 6‐methyl‐4‐phenoxy‐[1(3)‐15N]pyrimidine 1‐oxide with potassium amide in liquid ammonia at − 33°C shows no lowering of the 15N content, only an initial addition of the amide ion to C(2) ‐ and not to C(4) takes place in this ring contraction.