From 1,2,4,5-Tetrazines as Substrates

Although not used to make phthalazines, fused phthalazines have been prepared from pyridazine substrates by completing the C6-C7 bond of the phthalazine system therein for example, 2-benzyl-5-o-bromophenyl-6-phenyl-l(27/)-pyridazi-none (155) gave 2-benzyldibenzo[/,/i]phthalazin-l(2/l)-one (155a) [AcNMe2, AcONa, Pd(PPh3)2Cl2, N2, 130°C, 64 h 56%]. Such a reaction should also be useful to make unfused phthalazines. 

The only heteromonocyclic system (other than pyridazine) that has been used as a substrate for the primary synthesis of phthalazines is 1,2,4,5-tetrazine. It undergoes Diels-Alder condensation with a variety of appropriate cyclic synthons (with loss of nitrogen) to afford phthalazines or reduced phthalazines. The following examples illustrate such syntheses. 

6-Bis(triiluoromethyl)-l,2,4,5-tetrazine (157) and anisole (156) gave 6-meth-oxy-l,4-bis(trifluoromethyl)phthalazine (158) by a Diels-Alder condensation, loss of N2, and spontaneous oxidation (neat reactants. Teflon-lined autoclave, 140°C, 12h 68% after separation from minor products thioani-sole likewise afforded 6-methylthio-l,4-bis(trifluoromethyl)phthalazine (56%). i i 

Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (160) and benzyne (159) gave dimethyl 1,4-phthalazinedicarboxylate (161) [substrate (160), dioxane o-H2NC6H4C02H/dioxane and PrCHMeONO/dioxane both), dropwise, gentle 

6-Diphenyl-1,2,4,5-tetrazme (170) with A(-(cyclohex-l-enyl)morpholine (169) gave either 4a-morpholino-l,4-diphenyl-4a,5,6,7,8,8a-hexahydrophthalazine (171) (reactants, MeCN, reflux, 7h 90%) or l,4-diphenyl-5,6,7,8-tetrahy- 

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