Quantum-chemical investigation of the effect of solvent polarity on the direction of sulfonation of pyrrole

Abstract

The relative stability of the isomeric σ-complexes formed in the sulfonation of pyrrole at the α-or β− position (the α-isomer is energetically more favorable) does not agree with the experimentally established positional selectivity of substitution (the formation of β-pyrrolesulfonic acid). However, quantum-chemical calculations of the energy parameters for the reaction of pyrrole and SO 3 with due regard to the solvation effect in the model solvent methylene chloride (ε = 8.93) lead to the conclusion that the calculated activation energy of the rearrangement to the more favorable β-pyrrolesulfonic acid for the less favorable β-isomer of the σ-complex is lower than on the path to the formation of the α-pyrrolesulfonic acid. It was shown that the significant increase in the polarity of the model medium in the transition to DMSO (ε = 46.7) does not lead to substantial change in the energy parameters of the reaction. The explanation for the positional selectivity during the sulfonation of pyrrole using Py⋅SO 3 , according to previous data, involves the participation of the pyridine in the transformation of the σ-complexes into the products. The calculations were made by the B3LYP/6-31G(d) and HF/3-21+G methods using the model of overlapping spheres to take account of solvation.Keywords: quantum-chemical calculations, B3LYP/6-31G(d) method, positional selectivity of substitution, sulfonation of pyrrole.Earlier [1] we undertook quantum-chemical calculations for the molecules of pyrrole, furan, thiophene, selenophene, and the corresponding benzannelated systems and hetarenium ions formed during their C-protonation by ab initio methods [MP2/6-31G(d)//RHF/6-31G(d)] and by density functional theory [B3LYP/6-31G(d)]. On the whole the results of these calculations agree with existing experimental data on the positional selectivity not only for the acid-catalyzed isotope exchange of hydrogen but also for other electrophilic substitution reactions of five-membered heterocycles with one heteroatom and their various derivatives. Only for the most active and least selective compounds (pyrrole and its N-substituted derivatives) are there discrepancies with experiment; calculations by these methods for the molecules of N-substituted pyrroles (substituents at the nitrogen atom R = Me, Et, i-Pr, t-Bu, CH═CH 2 , C≡CH, Ph, PhSO 2 , 4-O 2 NC 6 H 4 ) and the hetarenium ions formed during their -and -protonation predict a preference for -substitution [2], although cases of preferred or even exclusive -protonation are known for a series of reactions of similar _______ * Dedicated to E. J. Lukevics on his 70th birthday __________________________________________________________________________________________

Development of quantum-chemical investigations of heterocycles at the Institute of Organic Chemistry, Russian Academy of Sciences (review)

“…It was suggested in [46,47] that the stability of the 3H-hetarenium ions B corresponding to β-substitution, where the positive charge is distributed between two atoms (the heteroatom and atom C(2)), depends on the effect of the heteroatom to a larger degree than in the case of α substitution (cation A) where three ring atoms formally participate in delocalization of the positive charge; here the variation of the relative stability of the 3H-hetarenium ions in relation to the nature of the heteroatom must be similar to the variations found in onium compounds (N + > S + > O + ) and must correspond to the observed decrease in the content of the β-isomers in the order: pyrrole > thiophene >furan Subsequently, the ratio of the activity and selectivity in the electrophilic substitution reactions of fivemembered heteroaromatic compounds has been the subject of extensive quantum-chemical investigations by the CNDO/2 method [48][49][50][51] and in later years by the B3LYP/6-31G(d) method of density functional theory and the nonempirical RHF/6-31G(d) and PM2/6-31G(D) methods [52][53][54][55][56][57][58][59][60][61]. The calculations by the semiempirical CNDO/2 method [48] gave values for the differences in the energies of the cations formed during protonation at the α-and β-positions (ΔE α-β ) that corresponded to existing experimental data on the order of variation of the positional selectivity: furan > thiophene > pyrrole.…”

“…The results of B3LYP6-31G(d) investigation of the sulfonation of pyrrole [55][56][57] and N-methyl-and N-(tert-butyl)pyrrole [55] with sulfur trioxide were not entirely unequivocal; the σ-complexes formed during attack at the α-positions are preferred thermodynamically to their β-isomers, but the β-sulfonic acids are thermodynamically more favorable than the α-sulfonic acids, and the thermodynamic favorability of the β-sulfonic acids increases from pyrrole to N-methylpyrrole and then to N-(tert-butyl)pyrrole. The formation of the β-sulfonic acids can be explained in terms of the reversibility of the first stage of sulfonation and the increased stability of the σ-complexes of the type formed during attack at the α-position [55].…”