Phthalazinones reactions

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... 

Azelastine (107) is an antiallergic/antiasthmatic agent prepared from 4-chlorobenzyl-2 -car-boxyphenylketCHie (105) by condensation with hydrazine to give the phthalazinone (106) followed by reaction of the sodium salt of this last with 2-(2-chloroethyl)-N-methylpyrrolidine (presumably involving nucleophilic ring expansion of the bicyclic quaternary salt putatively formed as a first product) to complete the synthesis [30]. 

Phthalazinone, 355 synthesis of, 356 Phthalic anhydride, 101 Phthalic anhydride-glycerol reaction, 19 Physical properties. See also Barrier properties Dielectric properties Mechanical properties Molecular weight Optical properties Structure-property relationships Thermal properties of aliphatic polyesters, 40-44 of aromatic-aliphatic polyesters, 44-47 of aromatic polyesters, 47-53 of aromatic polymers, 273-274 of epoxy-phenol networks, 413-416 molecular weight and, 3 of PBT, PEN, and PTT, 44-46 of polyester-ether thermoplastic elastomers, 54 of polyesters, 32-60 of polyimides, 273-287 of polymers, 3... 

Poly(phthalazinone ether ketone)s (PPEKs) were synthesized by the reaction of the polymer in mixtures of 95—98% concentrated sulfuric acid and 27— 33% fuming sulfuric acid in the absence of other solvents. A general reaction scheme is given in Figure 30. The mixed solvent systems of sulfuric acid... 

Several therapeutic agents are based on phthalazinone nuclei, in which the hydrazide carbonyl group persists in unmodified form. Reaction of keto-acid (69-1) with hydrazine leads to the phthalazinone (69-2). Alkylation of the hydrazide nitrogen with 2-(chloroethyl)-A-methylpyrrolidine (69-3) surprisingly leads to the incorporation of a seven-membered azepine ring rather than the expected ethylpyrroldine. This can be explained by keeping in mind that it is likely that the... 

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-... 

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]. 

Azole approach. Like phthalazinones, which can be formed from the reaction between phthalic acids and hydrazines, the thiazole analogues can be formed from thiazole-4,5-dicarboxylic acid derivatives. Other 4,5-substituted oxo groups react similarly to give a fused thiazole (451) (71BSF1491). 

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>. 

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... 

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. 

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). 

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). 

The isolation of chloro heterocycles is not always necessary. Chlorination with POCI3 and amination can be combined in a one-pot reaction as exemplified by the reaction of 4-phenyl-1-(2//)-phthalazinone (83) with POCI3 in the presence of excess neopentylamine in boiling xylene to furnish 84 in 77% yield (85EUPI5%52). 

The reactivity of pyridazines in Pd-catalyzed reactions was of interest. For example, the Heck alkenylation at C5 of 6-phenyl-3(2//)-pyridazinones was investigated, with the aim of suppressing production of 4-phenyl-6-substituted-2-phthalazinone byproducts <04TL3459>. In another study, the reactivity of 5-iodopyridazin-3(2f/)-ones in Pd-catalyzed reactions was investigated to develop an efficient route to 2,5-disubstituted pyridazin-3(2/f)-ones <04T12177>. Other pyridazine syntheses relied on condensation approaches. Benzo[g]pyridazino[l,2-i>]-phthalazine-6,13-diones 16 and 17 related to certain anthracyclinones were obtained by cycloaddition of 1,3-dienes to benzo[g]phthalazine-l,4-dione <04H(63)1299>, and pyridazine C-nucleosides synthesized by 14-i-2 cyclocondensation of alkynyl C-nucleosides with substituted tetrazines afforded, upon extrusion of a nitrogen atom, pyrrole C-nucleosides in good yields... 

This rare type of synthesis is exemplified in the conversion of o-bromobenzo-phenone tosyfliydrazone (25) into o-lithiobenzophenone lithiotosyUiydrazone (26) (treatment with MeLi and BuLi sequentially at —78°C in THF) and subsequent treatment of the reaction mixture with oxalyl chloride (—78°C —> 20°C) to give 4-phenyl-2-tosyl-l(2F/)-phthalazinone (27) in 65% overall yield. ... 

Most of the isobenzofurans that have been used as substrates for phthalazine syntheses are in practice either l,3-dihydro-l,3-isobenzofurandiones (i.e., phthalic anhydride derivatives) or 1,3-dihydro-l-isobenzofuran-l-ones (i.e., the lactonic phthalides), both of which normally undergo ring fission and reaction with hydrazine or the like to give phthalazinones. Discussion of these syntheses is subdivided according to the type of substrate used. 

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). ° ... 

The halogenolysis of tautomeric phthalazinones has been covered in Section 10.1.1. Other recently used reactions are discussed in the following subsections. 

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. 

Several other useful reactions of tautomeric phthalazinones that have been employed in the more recent literature are illustrated by the following classified examples. 

The hydrolysis of such ethers to tautomeric phthalazinones or extranuclear hydroxyphthalazines has been covered in Sections 11.1.1 and 11.2, respectively. Other reactions are illustrated by the following classihed examples. 

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