The preparation of 3-benzyl-6-(α-methylbenzyl)- and 3,6-bis(α-methylbenzyl)-s-tetrazines by alkylation of 3,6-dibenzyl-s-tetrazine and a study of their rearrangements to imidazo[1,2-b]-s-tetrazines in alkali

Abstract

3,6-Dibenzyl-s-tetrazine (1a) can be alkylated with methyl iodide after treatment with LDA in tetrahydrofuran to give a mixture of 3-benzyl-6-(α-methylbenzyl)- and 3,6-bis(α-methylbenzyl)-s-tetrazines (1c) and (18) separable by chromatography. 3,6-Dibenzyl-s-tetrazine on treatment with potassium hydroxide in benzyl alcohol yields, among other products, 3-benzyl-7-benzyloxy- and 3,7-dibenzyl-6-phenylimidazo[1,2-b]-s-tetrazines (8b) and (5a), the 7-benzyloxy group being generated from the solvent but the 7-benzyl group having the parent tetrazine (1a) as its precursor. Similar treatment of 3-benzyl-6-(α-methylbenzyl)-s-tetrazine (1c) but with methanol as solvent yields the related 7-methoxy-3-(α-methylbenzyl)-6-phenylimidazo[1,2-b]-s-tetrazine (8c) along with a novel compound assigned the structure of a substituted 1,2,4-triazolo[1′,5′ : 4,5]pyrazino[1,2-b]-s-tetrazine (15). 3,6-Bis(α-methylbenzyl)-s-tetrazine (18) is stable to alkali except when prolonged reaction times are employed when it breaks down to acetophenone, by way of an alkylidene hydrazide intermediate (19). Mechanisms are proposed for each of these reactions.