Pyrazoles bromination

Reactions of Pyrazoles. Bromination of 3,5-dimethylpyrazole yields the dibromo-... 

A -Pyrazolines are converted into pyrazoles by oxidation with bromine or Pb(OAc)4 and... 

A-Halogenated pyrazoles are unstable compounds (Cl>Br>I) that are seldom isolated. 1-Bromopyrazoles resemble NBS and may be important in the process of C-bromination, not because of an A to C rearrangement but by acting as a source of the powerfully electrophilic brominium ion (Section 4.04.2.1.4(v)). 4-Substituted pyrazoles can form... 

Pyrazole is very stable in acid media and even under more vigorous nitration conditions neither ring opening nor ring oxidation was observed (for oxidation to pyrazolones with a mixture of bromine and nitric acid see Section 4.04.2.1.4(v)). 

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

Halogenation is one of the most studied electrophilic substitutions in the pyrazole series (67HC(22)1, B-76MI40402). The results concern chlorination, bromination and iodination since there is no report on direct fiuorination of pyrazoles (fiuoropyrazoles are prepared by other... 

Bromine in chloroform and bromine in acetic acid are the reagents used most often to brominate pyrazole. When nitric acid is used as a solvent, both bromine and chlorine transform pyrazoles into pyrazolones (Scheme 24). Thus 3-methyl-l-(2,4-dinitrophe-nyOpyrazole is brominated at the 4-position (309). The product reacts with chlorine and nitric acid to give the pyrazolone (310). The same product results from the action of bromine and nitric acid on (311). The electrophilic attack of halogen at C-4 is followed by the nucleophilic attack of water at C-5 and subsequent oxidation by nitric acid. 

Pyrazolesulfonic acids, like (493), have high melting points (Table 24) and probably exist as the zwitterions (497). They are very stable to hydrolysis and only afford pyrazolones at high temperatures. The replacement of the SO3H group by bromine has also been reported (B-76MI40402). Pyrazole-3-, -4- and -5-sulfonic acids react with phosphorus pentachloride to form sulfonyl chlorides. 

The seeond problem is the relationship between the position of the substituent in the pyrazole nueleus and its mobility. In the 1-phenylpyrazole series in their reaetions with Grignard reagents, the bromine reaetivity deereases in the order 5-Br>4-Br>3-Br (B-76MI40402). When an eleetron-withdrawing group is present at the 4-position, the 5-ehloropyrazole is more reaetive than 3-ehloropyrazole, but this has been attributed to bond fixation (Seetion 4.02.3.9). Thus, this problem needs further elarifieation. 

Pyrazole, 1 -(2,4-dinitrophenyl)-3-methyl-bromination, S, 240 Pyrazole, 2,3-diphenyl-synthesis... 

Pyrazole, 3-(trifluoromethyl)-4,5-trimethylene as amebicide, 5, 291 Pyrazole, 3-triflyl-4-phenyl-synthesis, 5, 282 Pyrazole, 1,3,4-triiodo-synthesis, 5, 234 Pyrazole, 1,3,5-trimethyl-isomerization, 5, 221 Pyrazole, 3,4,5-trimethyl-bromination, 5, 240 halogenation, 5, 89 reactions... 

Several 3-(perfluoroalkyl)pyrazoles can be brominated at position 4 under mild conditions, however, 5-(perfluoroalkyl)pyrazoles are unreactive [37] (equation 19). 

The reaction of pyrazole acetic acids 269a-c with two equivalents of bromine in water gave the corresponding monobromopyrazol-3-ones 270a-c. When acids 269d,e were reacted with three equivalents of bromine, the respective dibromo-pyrazol-3-ones 271d,e were isolated (98JPR437) (Scheme 66). 

However, addition of bromine is accompanied by bromination of 3,5-dimethyl-pyrazolate and pyrazolate ligands at position 4, which is blocked in 4-methyl-pyrazolate. The product of electrochemical oxidation of 175 (R -- R = Me, R = Br) is 177 (R = R = Me, R = Br, X = CIO4). Chlorination proceeds similarly to bromination. 

The reaction of bromine with (pyrazol-4-yl)acrylic acid and its esters and the subsequent dehydrobromination of the products have been investigated by Finar and Okoh [73JCS(P1)2008]. Attempts to dehydrobrominate bromoacrylic acids (20) to 3-( 1 -phenylpyrazol-4-yl)propiolic acids 22 failed, but were successful when bromoesters 21 were used (Scheme 32). 

Partial rate factors calculated for indazole bromination indicate that the benzo derivative is less reactive than pyrazole a positional reactivity order of 5 > 3 > 7 (in the ratio 10.7 6.9 I) was obtained [78JCS(P2)865]. 

The 5-position was the most reactive in bromination of 1,3-disubstituted l//-thieno- and -seleno-[3,2-c/]pyrazoles (59), whereas the isomeric 2H-[3,2-c] derivatives (60) reacted at the 6-position [73JOU2216 77CS( 12)1 ]. 

Most references involve studies of pyrazoloimidazoles. Bromine entered l//-imidazo[l,2-6]pyrazole at the 7-position (equivalent to the 4-position in pyrazole) (78MI1). Similar regiochemistry was observed when... 

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). 

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