Reduction of 1,2-pyridazines

Ring contractions may occur during reductions or oxidations. In Part I1 the ring contractions that were described included reductions of pyridazines... 

Reduction of pyridazin-4-ones seems not to have been reported, f. Derivatives of Cinnoline. 3-Hydroxycinnoline (222)44 is reduced in a two-electron wave from pH 0 to 11. In strongly acid solution the main product is 1-aminooxindole (223), which is also obtained on reduction with zinc and sulfuric acid.232 Reduction in an emulsion of an aqueous phosphate buffer (pH 6.5) and n-butanol produced a nearly quantitative yield of 3-keto-l,2,3,4-tetrahydrocinnoline (224) this compound was easily reoxidized to 3-hydroxycinnoline. 

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. ... 

Polarographic reduction of pyridazines and pyridazine 1,2-dioxide has been studied. " The polarographic behavior of pyridazine is typical of an overall two-electron reduction process. In alkaline solution it is reduced polarographically to 1,4-dihydropyridazine, but in acid solutions this compound gives an open-chain aminoimine. ... 

Selective reduction and ring contraction of pyridazin-3-ones provide access to 3-pyrroUn-2-ones. Brown and coworkers explored the reduction of pyridazin-3-ones with zinc dust and acetic acid to give reduced products which underwent ring contractions, thus offering 3-pyrrolin-2-ones and... 

Reduction of nitroaminopyridazines yields the corresponding aminopyridazines. Reductive cleavage of hydrazinopyridazines to give amino compounds is of practical significance in cases when halogen atoms are resistant to ammonolysis. Many substituted 3,4-diamino-, 4,5-diamino- and 3,5-diamino-pyridazines can be prepared in this way. 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

The electroreductive hydrogenation of pyridazine-3-ones performed at the first wave, in acidic or basic medium, takes place at the 4,5-double bond. A further reduction of 4,5- dihydropyridazin-3-ones in basic media, affords the corresponding tetrahydro derivatives (Scheme 139) [252]. 

When the hydrochloride salt of 2,3,4,4a,5,6-hexahydro-l//-pyridazino [1,6-a]quinoline was subjected to catalytic hydrogenation in ethanol over Pt02, 3-[2-(l,2,3,4-tetrahydroquinolyl)]propylamine was obtained (66YZ608). Catalytic reduction of perhydropyrido[l,2-ft]pyridazine over a skeletal nickel catalyst in ethanol at 30 atm gave ring-opened 2-(3-aminopropyl)piperidine (66KGS91). 

Reduction of 2-methyl-4-phenyl-3//-pyrido[l,2-Z)]pyridazin-3-one (44) with NaBH4 in ethanol afforded the 5,6,7,8-tetrahydro derivative [76JCS(CC)275 78JOC2892],... 

Guy Lemiere was born in Antwerp, Belgium, and studied chemistry at the Universities of Antwerp and Ghent. In 1975 he obtained a PhD in organic chemistry from the University of Antwerp on the subject Study on enzymatic in vivo and in vitro reductions of cyclic ketones . He built up all his academic career at the University of Antwerp. His scientific interests evolved from the stereochemistry of enzymatic reactions to natural products and further to heterocyclic chemistry, especially the chemistry of pyridazines. In 2004 he organized together with Bert Maes the 9th International Symposium on the Chemistry and Pharmacology of Pyridazines in Antwerp. He is an author of around 80 scientific papers. 

Yutilov et al. reported the formation of the [l,2,3]triazolo[4,5- / pyridazin-4-one ring system with simultaneous conversion of the 7-nitro into a methyl substituent, and reduction of the aryl nitro group to an amino substituent on... 

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. 

Reduction of tetrazolo[ 1,5- >]pyridazine (274) by sodium borohydride results in the partial reduction of the pyridazine moiety (tetrahydro compound 275 was formed) (76JHC835). The catalytic reduction of the substituted tetrazolo[ 1,5- >]pyrimidine (276) afforded the diaminopyrimidine derivative (277) (85MIP155606). 

Diazoninones 64 were synthesized by reduction of hexahydro-l//-pyrazolo[l,2-tf]pyridazin-l-ones with sodium in liquid ammonia (Scheme 7, Section 14.10.5.2.1) <2000CL1104, 2002T7177>. One of the synthetic routes for the preparation of diazoninone 291 includes reduction of dihydropyrimidinone 292 (Scheme 53) <2002T7177>. 

---