6-Phenyl-4,5-dihydropyridazin-3-ones

Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. Thus, bicyclic lactams 112 with hydrazine dichloride in a dioxan/water mixture produced the desired 6-phenyl-4,5-dihydropyridazin-3-ones 113. However, reacting the bicyclic lactam with phenylhydrazine hydrochloride yields 2,6-diphenyl-4,5-dihydropyridazin-3-one 115 as a sole product (2004TL7799 Scheme 20). 

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). 

Ring transformation involving the intramolecular reaction of a hydrazone or in situ formed hydrazone also appeared. The transformation of 6-methyl-2//-pyran-2,3,4-trione 3-arylhydrazones 332 into l-aryl-6-methyl-4-oxo-l,4-dihydropyridazine-3-carboxylic acids 333 is an example of the former (Scheme 82). Compound 332 are formed via reaction of 4-hydroxy-6-methyl-27/-pyran-2-one 331 with substituted benzenediazonium chlorides. These are normally not isolated and immediately used further <2005EJM1325>. An example where a hydrazone is formed in situ is the reaction of 2-amino-5-aryldiazenyl-4-oxo-6-phenyl-4//-pyran-3-carbonitriles 334 with H2SO4 in glacial acetic acid, yielding 2-aryl-6-benzoyl-3-hydroxy-5-oxo-2,5-dihydropyridazine -carbonitriles 335 (Scheme 83) <2001T6787>. 

A combination EIMS and X-ray study of [l,2,4]triazolo[l,2-b]- and [l,3,4]thiadiazolo[3,4-i>]phthalazines was undertaken [95JHC283], and X-ray crystal structure determinations of 5-(2-chlorobenzyl)-6-methyl-3(2W)-pyridazinone [95AX(C)1834], and on 6-benzyloxy-7,8-dihydro-8-phenyl-3-trifluoromethyl-r-triazolo[4,3-i>]pyridazine and its 5,6-dihydro-6-one derivative [95AX(C)1829] have been performed. Structures of some pharmacologically-active pyridazines previously reported as arylidene-4,5-dihydropyridazines need to be revised to those of aromatic pyridazine tautomers 6-8 based on a combination H NMR nOe and X-ray study [95AJC1601],... 

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