3- -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. 

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. 

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]. 

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

Chemicel Neme 1 (2H)-phthalazinone hydrazone hydrochloride Common Name 1-hydrazinophthalazine hydrochloride Structural Formula ... 

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... 

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

More recently, an alternative series of 2-alkoxybenzamides was designed where an intramolecular hydrogen bond mimics the phthalazinone scaffold [19]. Gratifyingly 8 exhibited good PARP inhibition, IC50 = 18 nM. 

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. 

Phthalazinone, 19 332 o-Phthaldialdehyde-2-mercaptoethanol, chiral derivatizing reagent, 6 76t Phthalein dyes, 19 304-305 Phthalic acid, 19 332... 

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). 

One of the first examples of this type of blend was composed of SPEEK or SPES as the acidic component and diaminated PES, poly(4-vinylpyridine) (P4VP), poly(benzimidazole) (PBl), or poly(ethyleneimine) (PEI) as the basic component. " For blend lEC values of 1.0 meq/g, conductivity values were reported to be good, as was H2/O2 EC performance. Thermal stabilities for these blends was also demonstrated to be high (>270°C). Other examples of acid-base PEMs include blends of SPPO and PBI, sulfonated poly(phthalazinone ether ketone) and aminated SPES, SPIs and aminated Pls, and SPEEK with PES bearing benzimidazole side groups, ° as well as an unusual example in which the blend is composed of sulfonated, hyper-branched polyether and pyridine-functionalized polysulfone. ... 

Gao, Y., Robertson, G. R, Guiver, M. D., Jian, X. G., Mikhailenko, S. D. and Kaliaguine, S. 2005. Proton exchange membranes based on sulfonated poly(phthalazinone ether ketone)s/aminated polymer blends. Solid State Ionics 176 409-415. 

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... 

Figure 31. Synthesis of directly polymerized sulfonated poly(phthalazinone ether sulfone) ...

Sulfonated poly(arylene ether)s have shown promise for durability in fuel cell systems, while poly-(styrene)- and poly(imide)-based systems serve as model systems for studying structure-relationship properties in PEMs because their questionable oxidative or hydrolytic stability limits their potential application in real fuel cell systems. Sulfonated high performance polymer backbones, such as poly(phe-nylquinoxaline), poly(phthalazinone ether ketone)s, polybenzimidazole, and other aromatic or heteroaromatic systems, have many of the advantages of poly-(imides) and poly(arylene ether sulfone)s and may offer another route to advanced PEMs. These high performance backbones would increase the hydrated Tg of PEMs while not being as hydrolytically sensitive as poly(imides). The synthetic schemes for these more exotic macromolecules are not as well-known, but the interest in novel PEMs will surely spur developments in this area. 

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... 

Aldehyde oxidase, a non-microsomal enzyme discussed in more detail below, may also be involved in the oxidation of quinoline to give 2-hydroxyquinoline (Fig. 4.14). The heterocyclic phthalazine ring in the drug hydralazine is oxidized by the microsomal enzymes to phthalazinone. The mechanism, which may involve nitrogen oxidation, is possibly involved in the toxicity of this drug (see chap. 7). Again, other enzymes may also be involved (Fig. 4.15). 

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 polymer-supported superbase 30 was developed and used for the deprotonation and alkylation of weakly acidic nitrogen heterocycles such as indoles, phthalazinones, and pyrazoles.46 The diagram below illustrates the use of superbase 30 to alkylate a weakly basic pyrazole NH after acylation or alkylation of the more nucleophilic piperidine NH. Ami-nomethyl resin 1 was added after each step to sequester excess alkyl and/or acyl halide from the solution phase. 

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

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