4-Benzyl-2- -phthalazinone

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. 

Benzylidene-5-bromo-l,3-dihydro-l-isobenzofuranone (230, X = O) with hydrazine hydrate gave 4-benzyl-6-bromo-l(2//)-phthalazinone (231) (EtOH, reflux, 30 min 79%) similar treatment of 3-benzylidene-5-bromo-1,3-dihydro-1-isobenzofuranthione (230, X = S) gave the same product (231)... 

Benzylidene, 7-diiodo-l,3-dihydro-l-isobenzofuranone (232) with phenyl-hydrazine gave 4-benzyl-5,8-diiodo-2-phenyl-l(27/)-phthalazinone (233) (EtOH, reflux, 3h 41%) analogs Ukewise. ... 

Benzyl- (117) gave 4-benzoyl-l(2H)-phthalazinone (118) (Na2Cr207, AcOH 82%) analogous benzylphthalazines behaved similarly. ... 

Benzyl-2(l//)-phthalazinone (41, R = H) gave 4-benzyl-2-ethoxycarbonyl-methyl-l(2//)-phthalazinone (41, R = CH2C02Et) (ClCH2C02Et, NaOH, EtOH, 95°C, 1 h 87%) 2-ethoxycarbonyImethy 1-4-phenyl-l(2//)-phthala-... 

Benzyl-l(2/i/)-phthalazmone (44) underwent Mannich aminoalkylation by p-aminophenylacetic acid and formaldehyde to give 4-benzyl-2-[p-(carboxy-methyl)anilinomethyl]-l(2fl)-phthalazinone (45) (reactants, H2O, MeOH, reflux, 30 min then 20°C, 12 h 70% analogs likewise). 

Dimethoxyphenyl)-l(2H)-phthalazinone (49, R = H) gave 2-benzyl-4-(3,4-dimethoxyphenyl)-l(2H)-phthalazinone (49, R = CH2Ph) (substrate, NaH, MeaNCHO, 20°C, 3h then PhCHaCU, 20X, 4h 61%) analogs like 2-benzyl-4-(3,4-diniethoxyphenyl)-5,6,7,8-tetrahydro-l(2//)-phthalazinone (57%) were made likewise. 

The extranuclear phthalazinethione, 4-benzyl-2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-l(2H)-phthalazinone (7, R = H) underwent regular 5-aIkyla-tion to give, for example, 4-benzyl-2-(5-methylthio-l,3,4-oxadiazol-2-yl)-l(2H)-phthalazinone (8) but Mannich A-(aminoalkylation) to give, for example, 4-benzyl-2-(4-anilinomethyl-5-thioxo-4,5-dihydro-l,3,4-oxadiazol-... 

Amino-7-chloro-l(2//)-phthalazinone (42, R = H) gave 7-chloro-l-oxo-l, 2-dihydro-6-phthalazinesulfonyl chloride (43, R = H) (substrate, lOM HCl, 0°C NaN02 in H2OJ, dropwise, 5-10°C, 20 min this solutionj, to AcOH saturated with SO2, CuCl 68%) 2-benzyl-7-chloro- (43, R = CH2Ph) (61%) and 7-chloro-2-methyl-l-oxo-l,2-dihydro-6-phthalazinesulfonyl chloride (43, R = Me) (52%) were made similarly. " ... 

Benzyl-2-(hydrazinocarbonylmethyl)-l(2//)-phthalazinone (82) with phenyl isocyanate gave 4-benzyl-2-[(4-phenylsemicarbazido)carbonylmethyl]- (83, X = O) (reactants, PhH, reflux, 5 h 95%) or with phenyl isothiocyanate gave 4-benzyl-2- [4-phenyl(thiosemicarbazido)]carbonylmethyl -l(27f)-phthalazi-none (83, X = S) (likewise 93%). ... 

Methylamino-1,4(277,377)-phthalazinedione 4-Methylamino-1 (277)-phthalazinone Methyl 2-benzyl-1 -oxo-1,2-dihydro-... 

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