Synthesis of a novel 8‐thia‐1,4‐diazacycl[3.3.2] azine

Abstract

AbstractA unique covalently hydrated cyclazine adduct, 2‐imino‐6a‐hydroxy‐4,5,6,6a‐tetrahydro‐7H‐8‐thia‐J, 4‐diazacycl[3.3.2]azin‐5‐one hydrochloride was prepared by reacting ethyl 4‐chloro‐acetoacetate with 4,6‐diamino‐2‐thiopyrimidine in neutral alcohol. Neutralization gave 2‐imino‐5,6a‐dihydroxy‐6,6a‐dihydro‐7H‐8‐thia‐1,4‐diazacycl[3.3.2]azine which decomposed to 4,6‐diamino‐2‐acetonylthiopyrimidine upon heating in water. Warming the hydrated hydrochloride in concentrated hydrochloric acid caused dehydration to yield 2‐imino‐5‐hydroxy‐6H‐8‐thia‐1,4‐diazacycl[3.3.2]azine hydrochloride. Partial isomerization (20%) to 2‐imino‐5‐hydroxy‐7H‐8‐thia‐1,4‐diazacycl[3.3.2]azine hydrochloride occurred during recrystallization from aqueous acidic methanol. The free base, 2‐imino‐5‐hydroxy‐7H‐8‐thia‐1,4‐diazacycl[3.3.2]azine was obtained after neutralizing either of the tautomeric hydrochlorides. Treating the free base with trifluoroacetic acid produced a mixture of the trifluoroacetate salts of the two tautomeric bases. Isomerization of one trifluoroacetate salt into the other in trifluoroacetic acid was observed by pmr at room temperature. Both 2‐amino‐5‐hydroxy‐7‐nitroso‐8‐thia‐1,4‐diazacycl[3.3.2]azine and 2‐amino‐5‐hydroxy‐6‐nitroso‐8‐thia‐1,4‐diazacycl[3.3.2]azine were isolated after nitrosation of the hydrochloride mixture.