Tetrazines Clofentezine, Diflovidazin Flutenzine

The mite ovicidal activity of ortho-halogen phenyl substituted tetrazines was discovered at Chesterford Park Research Station in 1976. In contrast to the inactive unsubstituted bis-phenyl derivative (entry 1, Table 26.2.1) the introduction of the 2-chloro-phenyl residue on one side of the tetrazine leads to an interesting ovici- 

Entry Compound no R1 R2 Relative ovicidal mite activity (0 = weak, 4 = excellent) 

Common name I UP AC name Development code Patent Launch Melting point log P 

The synthesis of clofentezine starts with a twofold acylation of hydrazine hydrate with 2-chlorobenzoyl chloride, followed by a phosphorous pentachloride mediated activation and a second reaction with hydrazine hydrate to give the 1,2-dihydrotetrazine derivative, which is finally oxidized to clofentezine using sodium nitrite [4, 11]. 

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