Phthalazinones cyclization

The reaction of azines 107, prepared in situ from aldehydes or ketones and hydrazine, afforded the Ugi adducts 108. The acid treatment of 108 resulted in the hydrolytic cleavage of the imino group with formation of the hydrazides, which immediately cyclized to phthalazinone amides 109 (Scheme 2.39) [70]. 

Competition between the two carboxy residues in the cyclization of alkyl 1,3-dihydro-l-hydroxy-a,a-disubstituted-3-oxo-l-benzoisofuranacetates with hydrazines can lead to phthalazinones and/or pyrazolones (Equation (39)). With ethyl esters a mixture of both products may be obtained, and while increased bulk at the a-position leads to the pyrazolone as the sole product, phthalazinones are the exclusive products from /-butyl esters <9lJOC2587). 

Hydroxybutyl)-4-(2-hydroxyethylamino)-l(2 0-phthalazinone (30) gave 2-(4-bromobutyl)-4-(2-hydroxyethylamino)-1 (2fl)-phthalazinone (31) (48 % HBr, reflux, 5 min 78% longer reaction times induced a second halogen-olysis and subsequent cyclization). ° ... 

Methyl-2-[2-nitro-5-(pyrrolidin-l-yl)phenyl]-l(2//)-phthalazinone (14, R = NO2) underwent a one-pot reduction to the corresponding amino analog (14, R = NH2) and dehydrative cyclization to give 5-methyl-9-(pyrrolidin-l-yl)benzimidazo[2,l-fl]phthalazine (15) (substrate, polyphosphoric acid, 100°C Fe powderj, portionwise then 140°C briefly 25%). ... 

Hydrazinocarbonylmethyl-4-phenyl-l(2//)-phthalazinone (84) with triethyl orthoformate gave 2-(5-oxo-2-pyrazolin-4-yl)-4-phenyl-l(2f/)-phthalazinnne. (85) (neat reactants, reflux, 4h 80%), with carbon disulfide/potassium hydroxide gave 2-(3-oxo-5-thioxopyrazolin-4-yl)-4-phenyl-1 (2//)-phthalazi-none (86) (reactants, EtOH, reflux, 4 h 75%), or simply on fusion gave 3,4-dihydro-2H-[l,2,4]triazino[3,4-a]phthalazin-3-one (87) (200°C, 1 h 75%) ° also analogous cyclizations. ° ° ... 

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