Thiazoles and thiadiazines. The condensation of ethyl 4‐chloroacetoacetate with thiosemicarbazide

By varying the acidity, solvent polarity, and temperature when thiosemicarbazide reacted with ethyl 4‐chloroacetoacetate, ethyl 2‐amino‐6 H ‐1,3,4‐thiadiazine‐5‐acetate hydrochloride, ethyl 2‐hydrazinothiazole‐4‐acetate, and ethyl 2‐imino‐3‐aminothiazoline‐4‐acetate hydrochloride were prepared selectively. Double bond migration occurred after neutralizing the thiadiazine and thiazoline hydrochlorides to form the α,β‐unsaturated esters: 2‐amino‐5‐carbethoxymethylidene‐4,5‐dihydro‐6 H ‐1,3,4‐thiadiazine and 2‐imino‐3‐amino‐4‐carbethoxymethylidenethiazolidine. Pmr studies revealed that an equilibrium existed in solution between the imine and enamine tautomers of the thiadiazine free base. In the enamine structure, a 6‐membered hydrogen bonded ring system promotes stability. The thiadiazine contracted in acidic aqueous acetone to ethyl 2‐isopropylidenehydrazonothiazole‐4‐acetate. Monobenzoylation at the primary amine of the thiadiazine yielded ethyl 2‐benzamido‐6 H ‐1,3,4‐thiadiazine‐5‐acetate without disruption of the hydrogen bonded ring, but benzoylating the imino functionality of the thiazolidine caused deconjugation of the α,β‐unsaturated ester by double bond migration back into the ring, and ethyl 2‐benzimido‐3‐aminothiazoline‐4‐acetate was produced, dehydration yielded ethyl 2‐phenylthiazolo[3,2‐ b ]‐ s ‐triazole‐5‐acetate. This compound was also obtained by reacting 3‐phenyl‐1,2,4‐triazole‐5‐thiol with ethyl 4‐chloroacetoacetate, while the monobenzoylated derivative of the hydrazinothiazole, ethyl 2‐(2‐benzoylhydrazino)thiazole‐4‐acetate underwent a dehydrative cyclization to ethyl 3‐phenyl‐thiazolo [2,3‐ c ]‐ s ‐triazole‐5‐acetate. In chloroform solvent, the second site of benzoylation on the thiadiazine was ring nitrogen 3 while in ethanol or acetonitrile‐pyridine ring nitrogen 4 was benzoylated instead. Benzoylation at ring nitrogen 3 resulted in deconjugation of the α,β‐unsaturated ester moiety and formed the endocyclic imine, ethyl 2‐benzimido‐3‐benzoyl‐2,3‐dihydro‐6 H ‐1,3,4‐thiadiazine‐5‐acetate. However, deconjugation of the unsaturated ester did not occur after benzoylation at ring nitrogen 4; the product was trans ‐2‐benzamido‐4‐benzoyl‐5‐carbethoxymethylidene‐4,5‐dihydro‐6 H ‐1,3,4‐thiadiazine. The hydrogen bonded oximes, syn ‐2‐amino‐5‐ethyloxalyl‐6 H ‐1,3,4‐thiadiazine oxime, 3,3‐dimethyl‐5‐ethyloxalyl‐2 H ‐1,2,4‐triazolo[3,4‐ b ]thiazole oxime, and 2‐(2‐benzoylhydrazino)‐4‐ethyloxalylthiazole oxime were synthesized by nitrosation. 2‐Amino‐5‐ethyloxalyl‐6 H ‐1,3,4‐thiadiazine oxime benzoate, 2‐benzamido‐5‐ethyloxalyl‐6 H ‐1,3,4‐thiadiazine oxime dibenzoate, and the tribenzoylated derivatives, 2‐benzimido‐3‐benzoyl‐5‐ethyloxalyl‐2,3‐dihydro‐6 H ‐1,3,4‐thiadiazine oxime benzoate and 2‐benzamido‐4‐benzoyl‐5‐ethyl‐oxalyl‐4 H ‐1,3,4‐thiadiazine oxime benzoate, of the thiadiazine oxime werè prepared. The oxime benzoylated first, the primary amine second, and the number 3 and 4 ring nitrogens last.