1.4- Dihydropyridazines, reduction with

Aryl-4,5-dihydropyridazine-3(2//)-one undergoes ring opening when submitted to Wolff-Kishner reduction, while with lithium aluminum hydride the corresponding 2,3,4,5-tetrahydro product is obtained. 

The reduction of a number of pyridazines was treated in Part I1 later electrochemical investigations296 confirmed that the initial reduction consumed two electrons and the primary product was suggested to be 1,2-dihydropyridazine, which tautomerized to the 1,4-dihydro derivative hydrolysis with ring opening followed. 

Dihydropyridazines have not been prepared by direct cycliza-tions reductions of pyridazines and oxidations of reduced pyridazines are known. 3,6-Diphenylp3n idazine is reduced with sodium and ethanol to the 1,2-dihydro derivative and the 1,2-dicarbethoxy analog is formed in a selenium dioxide oxidation of the corresponding 1,2,3,6-tetrahydro compound. 1-Carbethoxy- or 1,2-dicarbethoxy-1,2-dihydropyridazine was obtained similarly from an alkali treatment of 1,2-dicarbethoxyhexahydropyridazine. l,2-Dihydro-3,6-diphenylpyridazine is unstable and oxidizes to the parent pyridazine in the presence of air or on attempted acetylation. ... 

In a similar way, other pyridazines [306], such as 3-phenyl-6-methoxypyridazine and 3-methyl-6-chloropyridazine, are reduced, but the dihydropyridazines are in these cases rather unstable and may lose methanol or hydrogen chloride, forming the corresponding 4,5-dihydropyridazinone, which being an acylated hydrazone is cleaved with ring opening and reduction or hydrolysis of the ketimine (Chapter 11). 

Aminopyridazines are conveniently obtained from isonitroso pyrroles as shown in Eq. (1 l).The reduction can be accomplished either with aluminum in the presence of alkali or, preferably, with hydrazine.2,5-Diiminopyr-rolidine (succinimidine) or succinonitrile gives with hydrazine 3,6-dihydrazino-4,5-dihydropyridazine. ... 

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-... 

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... 

The benzyloxymethyl group has been used for the protection of the pyridazinone NH group. It is unaffected by a variety of acidic, basic, and reductive conditions and while removal by hydro-genolysis was erratic, the use of boron trichloride in DCM at — 78°C is effective <84JHC48l>. Ethyl (3-oxo-2,3-dihydropyridazin-2-yl)acetates react normally with ammonia and hydrazine to give the amides and hydrazides respectively <90CPB3009>. 

Alkenes lead to 1,4-dihydropyridazines (347) or the spiro derivatives (348). Cyclic alkenes, such as cyclopropenes give rise to diazanorcaradienes (349) or higher homologues, and reaction with alkynes yields pyridazines (350). Hetero-27r-systems such as nitriles, imines, thioketones, and N-sulflnylamines open the way to heterocyclic six-membered systems (351), (353), (357), and (356). (4-1-1) Addition reactions of isocyanides and carbenes make isopyrazoles (354) and (355) available. Reduction processes lead to 1,4- or 1,6-dihydrotetrazines (340) or (352). The reactions of 1,4-dihydrotetrazines (340) were briefly collected in Scheme 57. 

Masking of the final ketone as an alkene avoids problems in regioselective ketone reduction and avoids handling of an a-amino-ketone, with its high propensity to condense to dihydropyridazines. 

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