Phthalazines ring opening

Nickel palladium-carbon Reductive phthalazine ring opening... 

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

Heating of 4-oxo-4//-pyrido[2,l-a]phthalazine-l-carboxylic acids or their esters (91) in methanolic potassium hydroxide or sodium methoxide yielded either 6-imino-4-oxo-6//-pyrido[2,l-a]isoindole-l-carboxylic acid (92) or ring-opened products (93) [92EUP472166 94H(37)239],... 

Pyridazine can be obtained from its benzologs by oxidation. Thus, various cinnolines, phthalazines, or other polycycles afforded the corresponding pyridazinedicarboxylic or tetracarboxylic acids (see Section IV,E). Similarly, pyridazines with a fused three- or four-membered ring readily give substituted pyridazines upon ring opening. 

LAH converts l-alkylpyridazin-6-ones (60) into the corresponding 1,6-dihydropyridazines (57 R = Me, R = H), whereas excess reagent reduces 4,5-dihydropyridazin-6-ones (61) to a mixture of 1,4,5,6-tetrahydro- (62) and hexahydro-pyrazines (63).2 Cinnolines (64) and phthalazines (66) both undergo ring opening during cathodic reduction, giving diamines (65) and (67), respectively. ... 

Many 1,2-diazines undergo N-N-bond cleavage upon electroreduction, eventually resulting either in reductive ring opening or in ring contraction, e.g. of the type pyridazine —> pyrrole [111] or phthalazine —> isoindole [112],... 

Tetramethyl pyridazine-3,4,5,6-tetracarboxylate, but not 3,6-dichloropyridazine or dimethyl phthalazine-l, 4-dicarboxylate, takes part in a Diels-Alder reaction with indole under very concentrated conditions (Scheme 31). The adduct produced after elimination of nitrogen aromatizes by ring opening and the resultant aniline attacks the adjacent ester group to give the phenanthridone... 

Although pyridine or quinoline JV-acylimines are relatively stable to alkali, quinazoline 1-benzoylimine 50 undergoes ring contraction to 3-phenylindazole, and quinoxaline 1-benzoylimine 51 and phthalazine 3-benzoylimine 54 afford 52 and 55, respectively.177 Alkaline treatment of 1-alkyl-1,2,4-triazole 4-acylimines gives a variety of products derived from the ring-opened intermediates.111... 

Indene, however, does give four-membered ring adducts with PTAD,69 and phthalazine-t,4-dione.70 The reaction with PTAD proceeds stepwise via the dipolar intermediate 43, which was trapped in the presence of water to give 44, under conditions in which the 1,2-diazetidine (45) was not opened by water to 44 (Scheme 5).69 Hydrolytic cleavage of the triazole ring in 45 using potassium rm-butoxide in wet dimethyl sulfoxide, followed by... 

Opening of the pyrimidine ring of the bicyclic system and that of the pyrimido[2,l-a]phthalazine could also be achieved by nucleophilic attack. Thus, (47) afforded the pyridazinimine (48) on heating with morpholine (Equation (5)) <85JHC1535>. 

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