3,6-dihydropyridazine 1,2,3,6-tetrahydropyridazine

Pyridazines,pyridaziniumsalts, dihydropyridazines, tetrahydropyridazines, cinnolines andphthalazines... 

Aryl-2-phenyl-4,5-dihydropyridazin-3(2//)-ones react either with phenylmagnesium bromide or with phenyllithium to give 6-aryl-2,6-diphenyl-l,4,5,6-tetrahydropyridazin-3(2//)-ones (135) (products of 1,2-addition to the azomethine bond), while 2-methyl-6-phenyl-4,5-dihydropyridazine-3(2//)-one reacts with two equivalents of phenylmagnesium bromide at the carbonyl and azomethine group to produce 2-methyl-3,3,6,6-tetraphenyl-hexahydropyridazine (136) (Scheme 53) (80JPR617). 

The cathodic reduction in acidic medium, of 4,5-dihydropyridazine-3-ones unsubstituted at the N-2 position gives 1-aminopyrrohdin-2-ones via the corresponding tetrahydropyridazine-3-ones. 

Intramolecular nucleophilic aromatic substitution on 243 allowed l,4-dihydropyridazin-3(2//)-one ring construction (Equation 58) . Similarly, a tetrahydropyridazine unit could be constructed starting from 244 (Equation 59) . 

Dihydropyridazines are obtained from 1,4-dicarbonyl compounds and hydrazine (Section III,B) or from the reaction of sym-tetrazines and simple ethylenic compounds (Section III,H). There are also a few special reactions, such as that between a tetrahydrofuran and phenylhydrazine, or from a 1,4,5,6-tetrahydropyridazine derivative. The 1,4-dihydro structure has been found to be correct, rather than the 1,6-dihydro structure, postulated earlier for some of these reduced pyridazines (Section III,H). 1,4-Dihydropyridazines can be reduced or oxidized easily and acid treatment of l-tosyl-1,4-dihydropyridazine causes rearrangement to 1-tosylaminopyrrole. ... 

Pyridazines (56) are reduced by treatment with a mixture of dimethyl sulfate (which forms the corresponding salts in situ) and sodium borohydride to yield 1,6-dihydropyridazines (57 R = Me), together with minor amounts of 1,4,5,6-tetrahydropyridazines (58 R = Me). Normally 1,6-dihydropyrazines are unstable and decompose in air, but N-acylated derivatives are more stable. Thus if methyl chloroformate replaces dimethyl sulfate in the reaction mixture both 1,4-dihydro- (59 R = C02Me) and 1,6-dihydro-pyridazines (57 R = COjMe) can be isolated, the latter predominating if there is an electron-withdraw-ing group at C-6 in the starting material (Scheme 2)f ... 

Cycloadditions of l,r-bicyclohexenyl (34) with acylazo compounds have given high yields of the tetrahydropyridazines 35 and 36. - ° No attempts have been made to aromatize such compounds, but it is found that alkaline hydrolysis of 36 is accompanied by decarboxyation to the unstable 37, which is oxidized by air back to l.l -bicyclohexenyl with loss of nitrogen, presumably via the dihydropyridazine 38. ... 

Study of the reduction of 2,3,4,5-tetrahydropyridazine-3-ones, which can be regarded as cyclic acylhydrazines, with lithium aluminum hydride revealed that, in proportions varying with conditions, 1,4,5,6-tetrahydropyridazines, hexahydropyridazines, and/or 1,4-dihydropyridazines are formed. Although 3,6-diphenyl-4,5-dihydropyridazine has been isolated and is reasonably stable, related 4,5-dihydro analogs readily dimerize or trim-... 

Electroreduction of pyridazines in the presence of acetic anhydride gives the acylated open-chain diamines (cf. 117 -> 222). In aqueous solution a 1,2-dihydropyridazine is formed, which decomposes to nitrogen and an unsaturated hydrazino-aldehyde that polymerizes. Allylic bromi-nation of l,2-dicarbomethoxy-l,2,3,6-tetrahydropyridazine followed by de-hydrobromination gives l,2-dicarbomethoxy-l,2-dihydropyridazine. Catalytic hydrogenation gives the hexahydro compound." ... 

For example, mixing 6-oxo-3-styryl-l,4,5,6-tetrahydropyridazine with a three- to fourfold molar excess of certain aryl and a-naphthylmagne-sium bromides has been reported to yield the 4,5-dihydropyridazine 68... 

Eq. (14)].122 Similarly, the addition of phenyl Grignard to 6-oxo-3-phenyl-1,4,5,6-tetrahydropyridazine gives the aromatic 3,6-diphenylpyridazine, presumably through the intermediacy of the dihydropyridazine.123,124... 

Aubagnac et al. reported the isolation of 1,4-dihydropyridazines 70 among the products of the reduction of 6-oxo-l,4,5,6-tetrahydropyridazines with LiAlH4[Eq. (16)].126... 

Conformational studies using C NMR show that the 1,2-dihydropyridazine (24) is planar, while the 1,2,3,6-tetrahydropyridazines (25) and (26) have a half chair or boat conformation, respectively, as a consequence of the position of ring substituents. The hexahydropyridazine (27) probably exists as a mixture of three conformers due either to restricted rotation or inversion of the N-substituents with the bromines d -axial. In the absence of the 4,5-methyl groups the situation is made more complex by the additional presence of di-equatorial bromines <8772443). 

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