Pyridazines ring rearrangements

The reaction of several substituted imidazo[4,5-c/]-, pyrazolo[3,4-r/]- and triazolo[4,5-zf]pyrid-azines 3 with ynamines, in competition with [4 + 2] cycloaddition, leads to [2 + 2] derivatives 4, which rearrange to l,2-diazocines5.7 8 The reaction seems to be sensitive to the substituents, as replacement of the electron-withdrawing group R on the pyridazine ring of the pyrazolo compound (A = N, B = CH) by chlorine completely inhibits both the [4 + 2] and [2 + 2] cycloaddition reactions. The X-ray structure of the imidazo derivative 5 (R = Ms, A = CH, B = N) reveals a tub conformation of the eight-membered ring. 

Dipolar cycloadditions lead to six-membered rings. Rearrangements may be encountered. Thiazole or 2-methylthiazole (129 R = H and Me) with DMAD forms an initial 1,4-dipolar species (130). Reaction of (130) with a second DMAD gives a 1 2 adduct, presumably (131). Ring opening to (132), followed by cyclization in the alternative mode, resulted in (133) (78AHC(23)263) (see also CHEC 4.19). For the similar reactions of pyridine with DMAD and pyridazine with maleic anhydride see Section 3.2.1.3.7. 

The cyclization reaction of 39 under basic conditions furnished a 1 1 mixture of diazepines 40 and 43. The unexpected formation of 43 has been rationalized by a Smiles rearrangement involving a nucleophilic attack of the deprotonated 3 -nitrogen at position 4 of the second pyridazine ring resulting in the displacement of a carboxamide anion followed by cyclization to afford 43. ... 

Photolysis of pyridazine IV-ethoxycarbonylimide results in the formation of the pyrrole derivative (56). The rearrangement is postulated to proceed via a diaziridine, followed by ring expansion to the corresponding 1,2,3-triazepine derivative and rearrangement to a triazabicycloheptadiene, from which finally a molecule of nitrogen is eliminated (Scheme 19) (80CPB2676). 

In this work the possibility of the existence of 1,2-dihydro isomer with the core structure 42 was not considered. Recently, however, it was shown that 1,2-dihydropyridazines could be prepared by careful electroreduction of the corresponding pyridazines, and that their stability depends significantly on the ring substitutions. Thus, dimethyl l,2-dihydropyridazine-3,6-dicarboxylate 43a (R = H) is reasonably stable and rearranges into the 1,4-dihydro tautomer 43b only at a more negative potential, while the tautomerization in its tetrasubstituted analog 43a (R = COOMe) occurs more readily (Scheme 14) [00TL647]. 

The reaction of oxime 323 with concentrated aqueous HCl proceeded with a ring contraction and afforded pyridazine 324 as a single product (equation 140) . On the contrary, the rearrangement of pyrrol-3-one oxime in the presence of hydrazine proceeded with ring enlargement and led to l//-pyridazin-4-one oxime . ... 

Nitration of l,4-diaminopyridazino[4,5-d]pyridazine (68) resulted in the isolation of the nitramine (69). This nitro group could not be rearranged on to the other heterocyclic ring (68JHC53). 

Rearrangement of a pyridazine into a pyrrole has been found when 3-anilinopyridazine is heated in the presence of Raney nickel 2-anilino-2-pyrroline is formed in this reductive ring contraction. Similarly, 2,3,4-triphenylpyrrole is obtained from 4,5,6-triphenyl-3(2H)-pyridazinethione by reductive desulfurization with Raney nickel. A mechanism suggested for similar ring contractions of cinno-lines into indoles may be operating also in this case. Another... 

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