Pyridazine 1,2-dioxides synthesis

Only two examples of the synthesis of pyrrolo[3,4-r-]pyridazines that begin with a pyridazine have been reported. The first involves a Diels-Alder reaction. Thus pyridazine 88 under thermal conditions provides the heterodiene 89 intermediate with loss of CO2, which is trapped / situ with A -phenyldiazamaleimide to form 90 in the yields shown (Scheme 8) <20010L3647>. Alternatively, the thiadiazole 1,1-dioxide 91 can produce 89 by loss of SO2. 

The primary adducts, cyclohexadiene derivatives, formed by [4+2] cycloaddition of thiophene dioxides with dienophiles, may further undergo [4+2] cycloaddition with the dienophiles. Thus, the adducts 84 of 3,4-di-ferf-butylthiophene dioxide 83 with maleic anhydride and AT-phenylmaleimide further react with these dienophiles to give excellent yields of bis-adducts, which are composed of the endo-endo and endo-exo isomers, 85a and 85b (Scheme 49) [160]. A similar reaction was also observed with 3,4-dichlorothiophene 1,1-dioxide with N-butyl- and A-p-nitrophenylmaleimides (Scheme 50) [133]. The reaction of highly congested thiophene dioxides 87 with 4-phenyl-1,2,4-triazoline-3,5-dione provides a unique pyridazine synthesis since the bis-adducts 88 are converted into the corresponding pyridazines 89 in one pot and in good yields by treatment with KOH in methanol (Scheme 51) [174]. 

Homolytic substitution of pyridazines by N-acyl-pyrrolidines under Minisci conditions i.e. ammonium persulphate, and ferrous sulphate in sulphuric acid), has proved useful for the synthesis of azanicotine analogues, e.g. (198). Measurements of ionization constants and u.v. spectra of the N- and 5-methyl derivatives of 3,4,5-trimercaptopyridazine indicate that it exists as the N(2)-H tautomer (199).On the basis of X-ray and chemical data, the photo-isomers of pyridazine 1,2-dioxides, reported last year, have been re-formulated as 3a,6a-dihydroisoxazolo[5,4-ii]isoxazoles (200). 

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