Iodination of pyrazoles

Rate data for the iodination of pyrazole in aqueous solution showed the reaction to be first-order in both iodine and heterocycle and an inverse first-order [H+] dependence was found over the pH range 5.96-6.74 (64JA2857). A kinetic study of the aqueous iodination of pyrazole coordinated to Ni2+ showed the coordinated ligand to react more rapidly, and a [H+] dependence that differed from that of the free ligand (82JA2460). However, the results of this study should be viewed with caution, as the presence of several nickel-pyrazole complexes in solution necessarily leads to uncertainties about the exact nature of the reactive species. 

Vaughan and co-workers104 have studied the iodination of pyrazole. The kinetic features are similar to those of the iodination of imidazole. Also in this case, the rate could be separated into parallel uncatalyzed and base-catalyzed reactions and the mechanism proposed... 

A study of the iodination of pyrazole and 1-alkylpyrazoles has led to the conclusion that the reactivity of the anion (conjugate base) is enhanced relative to the neutral species by io9 5-12 8 (67JA6218). The reactivity of the 4(5)-positions of imidazole (statistically corrected) to that of the 4-position of pyrazole has been determined as 1.3 (64JA2857), which agrees with the localization energy calculated for these positions of -2.103 and -2.13(3, respectively (55AJC100). 

Cobalt, cyclopentadienyl complexes with thioformaldehyde, 55, 14 Cocaine analogs, isoxazolines, 60, 297 Coenzyme factor 420, synthesis, 55, 192 Colloidal media, iodination of pyrazoles in. 57, 344... 

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... 

Pyrazole does not react with iodine although pyrazolylsilver is converted into 4-iodopyrazole. 3-Iodoindazole can be obtained by the reaction of iodine with the silver salt of indazole. Kinetic studies on pyrazole iodination have been carried out by Vaughan et al. (71PMH(4)55, B-76MI40402). Coordination of pyrazole by nickel(II) in aqueous solution increases the rate of iodination by factors of two at pH 6 and eight at pH 7.2 (72JA2460). 

The 3,5-bis(trifluoromethyl)pyrazolate analog [Ir(cod)(/x-3,5-(CF3)2pz)]2 does not enter into oxidative addition with iodine, methyl iodide, or acetylenes. The mixture of pyrazolate and 3,5-bis(trifluoromethyl)pyrazolate gives [(rj -codllrf/x-pz)(/L-3,5-(CF3)2pz)Ir(rj -cod)], which reacts with bis(trifluoromethyl)acetylene in a peculiar manner [83JCS(CC)580], producing 145, where 3,5-bis(trifluoromethyl) pyrazolate is replaced by the ethylene bridge and the rj -coordination mode of one of the cod ligands is converted into the rj -allylic mode. 

Another situation is observed in the case of oxidative cyclization of unsaturated ketones 58 with phenylhydrazine 33 in the presence of iodine [61]. The reaction passes through the initial formation of pyrazoline 59, which is oxidized in the presence of iodine to pyrazole 60 (Scheme 2.14). 

The reactivities of 1-methyl-, 1-ethyl-, and 1-isopropylpyrazoles follow the inductive order of the alkyl group. The rate of iodination of the pyrazole neutral molecule was estimated from those of the 1-alkyl derivatives and the relative rate kP lkP for the uncatalyzed reaction was estimated to be in the range 3 x 109 to 7 x 1012, or even larger if it is assumed that the anionic substrate undergoes attack by molecular iodine (the probability of encounter between the anion and IOH2+ is very small) and the neutral substrate by either I, or IOHo+. 

Buchner and Fritsche initially considered that the hydrogen atoms of pyrazole could not be replaced by iodine.64 Buchner himself, however, later obtained 4-iodopyrazole by the action of iodine solution on the silver salt of pyrazole.555... 

Iodination has been used to assess the effect of Ni(II) complexa-tion upon the reactivities of pyrazole and imidazole (66JA5537 72JA-2460), which curiously are opposite in effect. Iodination has been used to determine the relative reactivities of pyrazole and its anion (conjugate base) (67JA6218). Under alkaline conditions, pyrazole reacts as the anion which is so reactive that it may be tribrominated [55LA(593)179 ... 

Synthesis of l-iodo-3,4,5-trisubstituted pyrazoles 25 (R=Me, X=C1, Br, I, Me) may be carried out by the reaction of the corresponding silver salts of pyrazole with iodine (70CB1949). 

By far the most frequently encountered reactions of pyrazol-3-ones with halogens are chlorination and bromination. Only one reference refers to the introduction of a fluorine atom whereas two references describe iodinated products. 

Afterwards, the kinetics of iodination of some 1-alkyl-substituted pyrazoles in buffered solutions have been studied by the same research group. In these cases dissociation is, of course, not pos.sible and the rate law observed is the same as that of iodination of aniline. ... 

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