2.8- Dimethyl-1 -phthalazinone

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

Chemical Name 1 (2H)-Phthalazinone-(1,3-dimethyl-2-butenylidene)-hydrazone Common Name Mesityl oxide (1-phthalazinyl) hydrezone... 

Benzoylphthalazine with sodium hydroxide in dimethyl sulfoxide hydroxylates the phthalazine ring to give, after oxidation, 4-benzoyl-l(2H)phthalazinone (Scheme 16) (85CPB4193). 

Smith and Otremba138 have found that the sodium borohydride reduction of 2-methyl- and 2-ethyl-phthalazinium iodide (113) in aqueous medium results in good yields of the corresponding 1,2-dihydrophthalazines (114). The dihydrophthalazines were found to be stable to excess sodium borohydride in refluxing methanol but underwent a facile air oxidation to phthalazinones (115). The borohydride reduction of 2-benzyl-phthalazinium chloride proceeded with apparent partial debenzylation, for a 31% yield of the parent 1,2-dihydrophthalazine (114, R = H) was isolated as the 2,2-dimethyl quaternary salt. 

The electrode reactions were investigated by reducing the compound at pH 0 and 9 the reduction in acid solution produced 2-methyl-phthalimidine (2) by a six-electron reaction, whereas that at pH 9 yielded 3,4-dihydro-2,3-dimethyl-4-hydroxy-l-phthalazinone (3) in a two-electron reduction. This compound (3) was then investigated polarographically (Fig. 3) it is reduced in acid solution in 2 two-electron waves, at pH 4 in 2 one-electron waves, and not reducible in... 

Compound 3 was then reduced in hydrochloric acid at the potential of the first wave (0.7 volt vs. SCE) the product obtained is 3,4-dihydro-2,3-dimethyl-1-phthalazinone (4), this product is also obtained from 1 in a four-electron reaction at pH 5. 

Fig. 3. Dependence on pH of the limiting current (/xA), , and the halfwave potentials (SCE)0,9. (a) 3,4-Dihydro-2,3-dimethyl-4-hydroxy-l-phthala-zinone (3) and (b) 3,4-dihydro-2,3-dimethyl-1-phthalazinone (4). Concentration 2.0 x 10-4 M. From Lund.40...

Dihydroxyphthalazines40 such as 2,3-dihydro-2,3-dimethyl-l,4-phthalazinedione are reduced at low pH to a phthalimidine in a six-electron reduction in alkaline solution 4-hydroxy-3,4-dihydro-2,3-dimethyl-l-phthalazinone is formed in a two-electron reaction. In this medium it is not further reducible, but in acid solution it loses water to the reducible phthalazinonium compound. The product from this reaction is 3,4-dihydro-2,3-dimethyl-l-phthalazinone, which at low pH can be reduced to V-methylphthalimidine and its precursor V-methyl-2-(methylaminomethyl)benzamide. The reduction scheme was given in Section II, D (Scheme 1). 

Although seldom used, such substrates also give l(2//)-phthalazinones. Thus diethyl 4-formyl-2,6-dimethylisophthalate (50) with hydrazine hydrate gave ethyl 5,7-dimethyl-4-oxo-3,4-dihydro-6-phthalazmecarboxylate (51) (EtOH, reflux, 3h ... 

Acetyl-2-chlorocycloheptatrien-l-one (136) or the isomeric substrate, 2-acetyl-7-chlorocycloheptatrien-l-one (138), underwent condensation and rearrangement with hydrazine to give 4-methyl-l(27/)-phthalazinone (137) (H2NNH2 H2O, MeOH, reflux, 2h 29 or %, respectively) substrate (138) with methylhydrazine gave 2,4-dimethyl-l(2fl)-phthalazinone (139) (MeOH,... 

Methyl-5-phenylsulfonyl-3(2iJ)-pyridazinone (152, R = SOaPh) underwent Diels-Alder addition by 2,3-dimethyl-l,3-butadiene (151) to give 2,6,7-trimethyl-4a-phenylsulfonyl-4a,5,8,8a-tetrahydro-1 (2fl)-phthalazinone (153, R = S02Ph) (reactants, PhH, reflux, 10 days 90%) methyl l-methyl-6-oxo-l,6-dihydro-4-pyridazinecarboxylate (152, R = C02Me) likewise gave methyl 2,6,7-trimethyl-1 -oxo-1,2,4a,5,8,8a-hexahydro-4a-phthalazinecarbox-ylate (153, R = C02Me) (70%) such additions by an unsymmetric diene... 

Chloro-3-phenyl-l,3-dihydro-l-isobenzofuranone (210) and iVA -dimethylhy-drazine gave (via an unisolated intermediate) 4-hydroxy-2,3-dimethyl-4-phenyl-3,4-dihydro-l(2fl)-phthalazinone (211) (EtaN, PhH, 20°C, 24 h. 

Dimethyliminio-2,2-dimethyl-2,3-dihydroimidazo[2,l-fl]phthalazin-6-olate (315) underwent hydrolysis to 4-[l-(dimethylcarbamoyl)-l-methylethyl]-amino-l(2//)-phthalazinone (316) (EtaN, H2O, 20°C, 30min 96%). ... 

Dimethyl-1 (2H)-phthalazinone gave 2-bromomethyl-8-dibromomethyl-1 (2//)-phthalazinone (substrate, BZ2O2, CCLt, reflux then Br2 in CCI4J. dropwise, hv, reflux, 3 h 30% after purification). ... 

Methyl-l,4(2H,3H)-phthalazinedione (33) with the epoxide, 2,2-dimethyl-la, 7b-dihydro-2H-oxireno[c][l]benzopyran-6-carbonitrile (33a), gave 4-(6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydro-27/-[l]benzopyran-4-yloxy)-2-methyl-l(2i7)-phthalazinone (34) (pyridine, EtOH, reflux, 14 h 20%)." ... 

Pyridin-3-yl)-l(27/)-phthalazinone with dimethyl l-(2-bromopyridin-4-yl)-6,7-dimethoxy-2,3-naphthalenedicarboxylate gave 2-[4-(6,7-dimethoxy-2,3-dimethoxycarbonylnaphthalen-1 -yl)pyridin-2-yl] -4-(pyridin-3-y 1)-1 (2H)-... 

The isopropylidene ether, 4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-2-phenyl-l(277)-phthalazinone (117) gave 4-(2,3-dihydroxypropyl-2-phenyl-l(277)-... 

Note Examples have been given already for hydrolysis of the sulfones to phthalazinones (Section 11.1.1) and for their alcoholysis to alkoxyphthala-zines (Section 11.4.1). Other reactions are illustrated here. l-Phenyl-4-p-tolylsulfonylphthalazine (33) underwent cyanolysis to give 4-phenyl-l-phthalazinecarbonitrile (34) (KCN, MejNCHO, 140°C, 2h 96%). Such cyanolyses were also performed in dimethyl sulfoxide. ... 

Methyl 1 -hydroxymethyl-5,7-dimethyl-4-oxo-3, 4-dihydro-6-phthalazinecarboxylate Methyl 1 -hydroxymethyl-4-oxo-3,4-dihydro-6-phthalazinecarboxylate Methyl 2-methoxymethyl-1 -oxo-4-phenyl-1, 2-dihydro-6-phthalazinecarboxylate 4-Methyl-2-(2-methylallyl)- 1(2H)-phthalazinone... 

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