4- 1- -phthalazinone reduction

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-... 

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... 

The fact that the polarographic data for 1 at pH 5 suggests a two-electron reaction, whereas the preparative results prove a four-electron reduction, means that a slow chemical step occurs after the uptake of two electrons. The partly reduced molecule diffuses from the microelectrode before the chemical follow-up reaction has occurred, but this does not matter in an exhaustive, preparative reaction. The rate of the slow step is pH-dependent and this step is not apparent at low pH where it is sufficiently fast. The slow step is suggested to be the acid-catalyzed dehydration of 2 to the quaternary phthalazinone (5). 

The reduction of phthalazinones is apparently the only observed example of a reduction of a protonated compound containing > C=N—N < in which the C=N double bond proves to be easier to reduce than the N-N bond. The differences in reduction potential between the azomethine double bond and the nitrogen-nitrogen bond are not great in acyclic compounds and the presence of a phenyl group fused to the heterocyclic ring may alter several parameters. The phenyl group acts as a nonreducible, nondisplaceable unsaturated center, and its presence may influence the orientation of the molecule and the adsorption of the compound at the electrode. 

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). 

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). ... 

Su et al. [138] prepared composite PEMs from sulfonated poly(phthalazinone ether ketone) (sPPEK) and various amounts of sulfonated silica nanoparticles (silica-SO3H). The use of silica-SO H was seen to compensate for the reduction in the lEC of the membrane, while the strong -SO3H/-SO3H interaction between sPPEK chains and silica-SO3H particles led to ionic crosslinking in the membrane structure, which improved not only the thermal stability but also the methanol resistance. 

Tautomeric phthalazinones undergo several reductive or oxidative reactions, the most important of which is the production of phthalazinequinones or semiquinones. The following examples illustrate such reactions. 

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%). ... 

Most aminophthalazines have been made by primary synthesis (see Chapter 8), by the addition of amines to alkylphthalazines (Section 9.3.2), by aminolysis of halogenophthalazines (Section 10.3.2), by aminolysis of phthalazinones (Section 11.1.2.4), by aminolysis of alkoxyphthalazines (Section 11.4.2), by aminolysis of alkylthiophthalazines (Section 12.2), or by reduction of nitrophthalazines... 

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