Pyrazole, bromo

Bromo-l-(2,4-dinitrophenyl)pyrazole (101) 4-Chloro-l-(2,4-dinitrophenyl)pyrazole 4-Bromo-3-methyl-l-(4-nitrophenyl)pyrazole... 

Pyrazoles can undergo nitration at several positions 4-bromo-l-methylpyrazole yields the 3,5-dinitro product. 1-Methylpyrazole 2-oxide yields the 5-nitro derivative. 

Owing to their particular interest two individual reactions will now be discussed separately. The reaction of methoxycarbonylhydrazine and 3-bromo-2,4-pentanedione affords, in addition to the expected pyrazole (608), a pyrazolium salt (609), the structure of which was established by X-ray crystallography (74TL1987). Aryldiazonium salts have been used instead of arylhydrazines in the synthesis of pyrazolines (610) and pyrazoles (611) (82JOC81). These compounds are formed by free radical decomposition of diazonium salts by titanium(n) chloride in the presence of a,/3-ethylenic ketones. 

Examples of dehydrobromination leading to bromoethynylpyrazoles as illustrated by Scheme 36 are described in a patent (99USP5925769). Treatment of 1,1-dibromooleflns with tetrabutylammonium fluoride in THE at room temperature for about 24 h under N2 gives the l-bromo-2-(pyrazol-3-yl)acetylenes where R, R, R, and R" are independently selected from H and alkyl, alkoxy. 

It is neeessary to emphasize that the direet amination of the methyl group at position 5 of pyrazoles is impossible. Neither 1,3,5-tiimethyl- nor4-ethynyl-l,3,5-trimethylpyrazole undergoes sueh transformations under the reaetion eonditions and starting materials are reeovered nearly quantitatively. Moreover, 4-bromo-ethynyl-l,3,5-trlmethyl- and 4-iodoethynyl-l,3,5-trimethylpyrazole with sodium amide in ammonia exehange the halogen for metal almost quantitatively and in this respeet are similar to phenylehloroaeetylene (Seheme 102). 

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. 

Pyrazolo[l,2-a]pyrazoles give 3-bromo products unless the 3-position is blocked by a methyl when bromomethyl products arise (80JA4983 81JOC1666, 87JOCI673). When all of the pyrazole ring positions are filled by phenyl groups, chlorination and bromination occur in thepara-positions (74BCJ946) (see also B, 1,2). 

An analogous approach has been utilized to generate the central piperazine ring of 337 via dimerization of 5-amino-4-bromo-2-phenyl-2,4-dihydro-pyrazol-3-one 336 under basic conditions in good yield (Equation 91) <2003HAC211>. 

Only a few reports have dealt with the behavior of tetra-azaindenes toward electrophiles, and the reactions reported involved the pyrazole ring. Thus, alkylation of 336 with alkyl halides affords a mixture of the A-alkylated derivatives 337 and 338. Compound 336 is produced by alkylation of 339. Bromination of 339 (R = H) affords the 7-bromo derivative 340 (82JHC817) (Scheme 34). Nitration of 2-methylpyrazolo[3,4-c] pyridazine occured at pyrazole C-3 (73JAP76893). Bromination of 341 with bromine in acetic acid gives 342 (83AP697). 

Less success has been obtained with removable N-substituents, however, the trityl and THP derivatives of 4-bromopyrazole both giving low yields of products derived from reaction of the lithio derivatives with carbonyl compounds [62CB222 82ACS(B)101]. Magnesium metal has also been used to produce l-methyl-4-(trimethylsilyl)pyrazole by an in situ Grignard reaction on the analogous 4-bromo compound in HMPT (84JOC4687). 

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