N-Alkylation of Unsymmetrical 1,6-Dihydro-1,2,4,5-tetrazine Under Alkali Condition

Abstract

6-Methyl-3-phenyl-1,6-dihydro-1,2,4,5-tetrazine was stable in alkali solution at room temperature and decomposed gradually to form 1,2-dibenzylidenehydrazine. The plausible mechanism of the reaction is discussed. Because it was stable for a period of time, a convenient and effective method for synthesis of 1-alkyl-1,6-dihydro-1,2,4,5-tetrazines has been developed. The starting 1,6-dihydro-1,2,4,5-tetrazine can be alkylated with alkyl halides in methanol and lithium hydroxide monohydrate as a base at room temperature.

Keywords:

• Alkyl halides
• N-alkylation
• 1,6-dihydro-1,2,4,5-tetrazine
• lithium hydroxide
• unsymmetrical

ACKNOWLEDGMENTS

We are indebted to the Science Foundation for Excellent Youth Scholars of the Department of Education of Zhejiang Province and the Educational Commission of Zhejiang Province for financial support (Y201018289).

Notes

^a Reactions conditions: 3-phenyl-6-methyl-1,6-dihydro-1,2,4,5-tetrazine 3 (1.0 mmol, 1.0 equiv), benzyl bromide 4a (1.0 equiv), base in corresponding solvent (20 ml) at room temperature.

^b Isolated yields.

^c These reactions retrieved 3 with yields of 50% (entry 1), 32% (entry 2), 35% (entry 3), 42% (entry 7), and 85% (entry 10), respectively.

^a Reactions conditions: 3-phenyl-6-methyl-1,6-dihydro-1,2,4,5-tetrazine 3 (1.0 mmol, 1.0 equiv), alkyl halides (1.0 equiv), and base (1.0 equiv) in methanol (20 ml) at room temperature.

^b Isolated yields.

^c These reactions retrieved 3 with yields of 65% (entry 12) and 85% (entry 13), respectively.