Pyrazoles, 5-chloro

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

In pyrazoles the two most important effects are produced by nitro groups and by quaternization (Section 4.02.3.1.7). Both enhance considerably the reactivity of a second substituent, for example, that of a methyl group towards aldehydes or of a chloro substituent towards amines. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

Isothiazolium salts (59) react with phenylhydrazine to give pyrazoles (60) (72AHC(14)l) (see Section 4.02.1.6). When treated with hydrazine hydrate, 3-chloro-l,2-benzisothiazole gives di-(o-cyanophenyl) disulfide (73SST(2)556), but 2,1-benzisothiazole gives o-aminobenz-aldehyde azine (72AHC( 14)43). 2-Substituted saccharins give the expected o-sulfamoyl-benzohydrazides. 

Phosphetanium tetrachloroaluminum salt, 1-chloro-2,2,3-trimethyl-1-phenyl-synthesis, 1, 524 Phosphindole synthesis, 1, 517 Phosphine, pyrazol-l-yl-synthesis, 5, 236 Phosphirane, 1-phenyl-synthesis, 1, 525 Phosphirane, 1,2,3-tri-t-butyl-... 

Another type of elimination reaction is the reaction of 1 -(5-methyl-1 -phenyl- H-pyrazol-4-yl)ethanone with a Vilsmeier complex to give 3-chloro-3-(5-methyl-l-phenyl-l//-pyrazol-4-yl)propenal, which in turn undergoes dichloroformylation... 

When methylene chloride was used as a solvent, it was found that 28 are obtained in minor amounts, while the dominating product is the -coordinated chloro-carbyne species [(> -Tp )Mo(CO)2(=CCl)], whose yield increases abruptly with substitution in the pyrazol-l-yl fragments (3-methyl-, 3,4,5-trimethyl-, and 3,5-dimethyl-4-chloro derivatives) [90AX(C)59,95JCS(D) 1709]. The tungsten analog can be prepared similarly. The chlorocarbyne molybdenum complex follows also from the reaction of the parent anion with triphenylsulfonium cation but conducted in dichloromethane. The bromo- and iodocarbyne derivatives are made similarly. 

A somewhat different strategy is employed for preparation of the desoxy analogue containing the reversed pyrazole. Acylation of chloropyrazole with jfl-chloro-benzoyl chloride affords the ketone Reaction of that... 

Tricyclic pyrazolo-quinolines 239 were prepared from /1-chloro arylalde-hydes and hydrazine derivatives under microwave irradiation with an acid support [156]. The method, appHed to a series of tricyclic compounds (Scheme 89), can be used, in principle, also for the synthesis of bicycHc and even monocycHc pyrazoles. 

Ethyl 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-pyrazol-3-yl)-4-fluorophenoxyacetate... 

OsH(CO)(Hpz)2(P Pr3)2]BF4, which can be deprotonated by NaH, while treatment with HC1 gives the neutral hydride-chloro complex OsHCl(CO)(Hpz) (P Pr3)2, which can also be prepared by addition of pyrazole to OsHCl(CO) (P Pr3)2 (Scheme 37).77... 

Several interesting reactions have been described for quinolizine-3-diazonium tetrafluoroborate 121. Thus, its treatment with secondary amines gave the corresponding triazenes 122 <2004ZNB380>, while its reaction with 1,3-dicarbonyl compounds gave the corresponding hydrazones. In the case of alkyl 4-chloro-3-oxobutanoates, the intermediate hydrazone 123 furnished a pyrazole derivative 124, as shown in Scheme 17 <2002H(57)2091>. 

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