Elucidation of the Vicarious Nucleophilic Substitution of Hydrogen Mechanism via Studies of Competition between Substitution of Hydrogen, Deuterium, and Fluorine

Abstract

Relations of rates of the vicarious nucleophilic substitution of hydrogen (VNS) and S(N)Ar substitution of fluorine in 2-fluoronitrobenzenes with chloroalkyl aryl sulfone carbanions were determined from competitive experiments carried out at various concentrations of base. The observed dependence of the VNS/S(N)Ar rate ratio on the base concentration confirmed the two-step mechanism of the VNS, which consists of reversible formation of sigma(H) adducts of the alpha-chlorocarbanion to nitroarene, followed by base-induced beta-elimination of HCl. It was also evidenced that both of these processes can be the rate-limiting steps: the beta-elimination at low base concentration and the nucleophilic addition at high base concentration. Consistent with that conclusion is the finding that the kinetic isotope effect in the VNS reaction decreases from 4.2 (a value typical of a primary KIE) to 0.8 (a value typical of a secondary KIE) with increasing base concentration. Also reported is our discovery that the S(N)Ar substitution of the 2-fluoronitrobenzenes studied in this work was subject to base catalysis under some of the experimental conditions employed in our competitive experiments.

Reactions of Nitroheteroarenes with Carbanions: Bridging Aromatic, Heteroaromatic, and Vinylic Electrophilicity

“…After final protonation, the substituted nitroarene or -heteroarene is obtained (Scheme 1). [7][8][9][10] It has been reported that the solvent, the nature and concentration of the base, and the steric demand of the carbanion have a considerable influence on the ratio of isomeric products. [11] When there is a high excess of the base, H À X elimination is faster than the retroaddition of the s H -adduct, and the formation of the s H -adducts becomes irreversible.…”

Vicarious Nucleophilic C-Amination of Nitrobenzene and 5- and 6-Nitro-1-methylbenzimidazoles

“…These findings prompted us to examine the process by ESR spectroscopy. Despite numerous previous attempts to study the mechanism of vicarious nucleophilic substitution of hydrogen [35][36][37], the problem concerning elementary steps of this process remains unclear. There is a concept according to which the reaction follows a polar mechanism involving intermediate formation of σ H complex [1,4,6,8,11,12].…”

Direct Nucleophilic Addition versus a Single‐Electron Transfer Pathway of σH Adduct Formation in Vicarious Nucleophilic Substitution of Hydrogen

“…[18] Much less attention has been paid to the question of how the σ H adducts are formed. Formation of the anionic σ adducts of carbanions to nitroarenes is a common initial step for the VNS reaction, the S N Ar reaction of halogens or other leaving groups in nitroaromatic rings and some other processes.…”