L -Phthalazinone

The disproportionation of heteroaromatic cations in aqueous base has been known for many years.277 279 For example, fresh organic extracts of basic aqueous solutions of the 2-methylphthalazinium cation (119) contain26,277,280 a mixture of 2-methyl-l,2-dihydrophthalazine (120) and 2-methyl-l-phthalazinone (121). Similar reactions have been reported for... 

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... 

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). 

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-... 

Phenyl-2(l//)-phthalazinone (42, R = Ph) with acrylonitrile gave 2-(2-cya-noethyl)-4-phenyl-l(2//)-phthalazinone (43, R = Ph) (reactants, trace Triton B, MeOH, dioxane, reflux, 3h 65%) ° somewhat similarly, 4-(p,p -dibro-mobenzhydryl)-l(2//)-phthalazinone [42, R = CH(CeH4Br- )2] gave 2-(2-cyanoethyl)-4-(p,p -dibromobenzhydryl)-l(277)-phthalazinone [43, R = CH (CeH4Br-p)2] (H2C = CHCN, pyridine, reflux, 2h 90% structure confirmed by X-ray analysis analogs likewise)... 

In much the same way, 4,4-bis(p-dimethylaminophenyl)-3,4-dihydro-l(2//)-phthalazinone (81) gave the unstable semiquinone ( ), 4,4-bis(p-dimethyla-minophenyl)-l,4-dihydro-l-phthalazinone (82) [substrate, Et3N, CH2CI2, -80°C Pb(OAc)4 in CH2Cl2i slowly 80°C, 3h) (see also Section 11.5.2)7 ... 

Ethyl 4-oxo-3-phenyl-3,4-dihydro-6-phthalazmecarboxylate (102, R = C02Et) gave 7-hydroxymethyl-2-phenyl-l(2/l)-phthalazinone (102, R = CH2OH) (NaBH4, EtOH, 20°C reflux, 2h 76%) analogs Ukewise." ... 

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. 

Phthalazin-1 (2H)-one, 4-hydroxy-2-methyl-methylation, 3, 17 Phthalazin-l(2H)-one, 4-methoxy-methylation, 3, 17 Phthalazinones in thermography, 1, 392 Phthalazin-l(2H)-ones alkylation, 3, 17 reaction... 

Chlorophthalazine is quite reactive to many basic nucleophiles but reacts sluggishly with aqueous or alcoholic alkali. In contrast, it is very rapidly hydrolyzed by warm, concentrated hydrochloric acid as are its diazine isomers. In hydrolysis with very dilute acid or with water, it forms some phthalazinone but mostly the self-con-densation product which hydrolyses to give 2-(l -phthalazinyl)-phthalazin-l-one (70% yield). Such self-condensations in diazanaph-thalenes and in monocyclic azines are always acid-catalyzed (Sections II, C and III,B). With methanolic methoxide, 1-chlorophthalazine (65°, few mins), its 7-methoxy analog (20°), and 1,6- and 1,7-dichlorophthalazines (20°) readily undergo mono-substitution. 

CN 4-[(4-chlorophenyl)methyl]-2-(hexahydro-l-methyl-l/f-azepin-4-yl)-l(2//) phthalazinone hydrochloride... 

The Chemical Abstracts name for hydralazine hydrochloride is l(2H)-phthalazinone hydrazone monohydrochloride, starting with volume 80 previously the name 1-hydrazino-phthalazine monohydrochloride was used. The CAS Registry No. is [304-20-1] for the hydrochloride salt, [86-54-4] for the base. 

AO is also effective in metabolizing a wide range of nitrogen-containing heterocycles such as purines, pyrimidines, pteridines, quinolines, and diazanaphthalenes (95). For example, phthalazine is rapidly converted to 1-phthalazinone by AO and the prodrug, 5-ethynyl-2-(l//)-pyrimidone, is oxidized to the dihydropyrimidine dehydrogenase mechanism-based inhibitor, 5-ethynyluracil, by AO (Fig. 4.40) (96). 

Phthalazinium-1-dates (196) are stable, yellow or colorless crystalline compounds that undergo an interesting variety of reactions. Reduction of aryl derivatives with zinc and dilute hydrochloric acid gives phthalimidines (210) whereas reduction with alkaline sodium hyposulfite gives 3-aryl-3,4-dihydro-l(2A)-phthalazinones (211)." 6.118-120,137 3 Mcthylphthal-... 

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

Nl - 1(2H)-PHTHALAZINONE, 4-C C4-CHL0R0PHENYL)METHYl)-2-(HEXAHYDR0-l-METHYL-lH-AZEPIN-4-YL)-, HYOROCHLORIOE... 

Chemical Name l(2FI)-Phthalazinone-(l,3-dimethyl-2-butenylidene)-hydrazone... 

Chemical Name l(2H)-Phthalazinone hydrazone hydrochloride Common Name 1-Hydrazinophthalazine hydrochloride Structural Formula ... 

Quinolyl)pyrazoIo[3,4-i7]pyridazincs were prepared by cyclocondensation reactions of an anilino-pyrazole acid with acetaldehyde <02JHC869>. Cyclopentadienyl-derived y-diketones and arylhydrazines condensed to 4-(l,4-diaryl-2//-cyclopent[d]pyridazin-2-yl)-benzenesulfonamides <02H(57)2383>. Sulfonated polyfphthalazinone ether sulfone)s 37 were prepared by polycondensation of 4-(4-hydroxyphenyl)phthalazinone 36 with various ratios of disodium 5,5 -sulfonylbis(2-fluorobenzenesulfonate) and bis(4-fluorophenyl)sulfone <02P5335>. 

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...

An alternative route that also gives good yields of 3-arylphthalazinium-l-olates (e.g., 205 Ar = Ph) has been described by Lund and involves thermolysis (100-120 C) of A-arylamino-3-hydroxyphthalimidines (197). This transformation (197 - 196) probably proceeds by formation of a hydrazide (198) prior to cyclodehydration (198 - 1%). Compound 205 (Ar = Ph) is obtained in low yields by lithium aluminum hydride reduction of 4-hydroxy-2-phenyl-l(2//)-phthalazinone 207 (R = OH, = Ph). ... 

MONOHYDROCHLORIDE HYDRALLAZINE HYDROCHLORIDE HYDRAPRESS 1-HYDRA-ZINOPHTHAL ZINE HYDROCHLORIDE 1-HYDRAZINOPHTHALAZINE MONOHYDROCHLORIDE HYPERAZIN HYPOPHTHALIN HYPOS IPOLINA LOPRESS NOR-PRESS 25 1 (2H)-PHTHALAZINONE HYDRAZONE HYDROCHLORIDE l(2H)-PHTR5LAZINONE, HYDRAZONE, MONOHYDROCHLORIDE PRAPARAT 5968 ROLAZINE SERPASIL APRESOLINE No. 2... 

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