The kinetics and mechanism of the electrophilic substitution of heteroaromatic compounds. Part XXVII. The nitration and hydrogen exchange of 1,3,5-trimethylpyrazole, 3,5-dimethylisoxazole, and 3,5-dimethylisothiazole

Abstract

The nitration and hydrogen exchange in the 4-position of the title compounds and corresponding N-methyl cations are studied kinetically. Criteria previously developed to distinguish between reaction on the free-base or conjugate-acid forms of six-membered heterocyclic aromatic compounds are applied. Both hydrogen-exchange and nitration occur on the free-base form of 3.5-dimethylisoxazole. For 1,3,5-trimethylpyrazole and 3.5-dimethylisothiazole, nitration occurs on the conjugate acids, while hydrogen-exchange undergoes a changeover from free-base to conjugate-acid reaction as the acidity is increased.The kinetic rates are compared with those for related compounds and the influence of N, 0, S. and NMe atomic groupings discussed.

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…The high reactivity of the 5-position can be due not only to the electron distribution in the ground state but also to the stabilization of the formed anion by the s-3d (sulfur) bonding. A similar study with isoxazoles provided the same conclusions [36,38].…”

Bis(1,2,3,5-tetramethyl-4-nitropyrazolium) dihydronium tris(4-methyl-3,5-dinitrobenzenesulfonate) forms C(8) chains through O—H...O bonding via the dihydronium cation

“…1,2,3,5-Tetramethylpyrazolium 4-toluenesulfonate was prepared from 1,3,5-trimethylpyrazine and methyl 4-toluenesulfonate following a similar procedure as used for 1,2,3,5-trimethyl-4-nitropyrazolium 4toluenesulfonate (Burton, et al, 1971). Nitration of 1,2,3,5-tetramethylpyrazolium 4-toluenesulfonate was carried out under similar conditions used for 4-toluenesulfonyl chloride (Schmidt et al, 1999).…”

“…Two previous reports give support to this nitration reaction. A kinetic study has indicated that the cation of 1,2,3,5-tetramethylpyrazolium bisulfate undergoes nitration to give the 1,2,3,5-tetramethyl-4-nitropyrazolium cation in a mixture of fuming nitric acid and concentrated sulfuric acid (Burton et al, 1971). In another study, 4-toluenesulfonyl chloride was reported to undergo nitration to give 4-methyl-3,5-dinitrobenzenesulfonic acid in a similar medium (Schmidt et al, 1999).…”

1H and 13C NMR study of perdeuterated pyrazoles

“…The difficulty of proton exchange with deuterium in pyrazoles increases in the order: N-H (simple agitation with D 2 O and/or CH 3 OD) > H-4 (heating in a sealed tube with D 2 O) > H-3,5 (heating in a sealed tube with D 2 O and NaOD 1N) C-CH 3 C-C 6 H 5 (supercritical deuterium exchange) [1][2][3][4][5].…”