Solvent Effects on the Menshutkin Reaction

Abstract

The Menshutkin reaction is a methyl transfer reaction relevant in fields ranging from biochemistry to chemical synthesis. In the present work, the energetics and solvent distributions for NH3+MeCl and Pyr+MeBr reactions were investigated in explicit solvent (water, methanol, acetonitrile, benzene, cyclohexane) by means of reactive molecular dynamics simulations. For polar solvents (water, methanol, and acetonitrile) and benzene, strong to moderate catalytic effects for both reactions were found, whereas apolar and bulky cyclohexane interacts weakly with the solute and does not show pronounced barrier reduction. The calculated barrier heights for the Pyr+MeBr reaction in acetonitrile and cyclohexane are 23.2 and 28.1 kcal/mol compared with experimentally measured barriers of 22.5 and 27.6 kcal/mol, respectively. The solvent distributions change considerably between reactant and TS but comparatively little between TS and product conformations of the solute. As the system approaches the transition state, correlated solvent motions occur which destabilize the solvent–solvent interactions. This is required for the system to surmount the barrier. Finally, it is found that the average solvent–solvent interaction energies in the reactant, TS, and product state geometries are correlated with changes in the solvent structure around the solute.

Atomistic Simulations for Reactions and Vibrational Spectroscopy in the Era of Machine Learning─Quo Vadis?

“…Reactive dynamics simulations can also been carried out in solution. MS-ARMD treatments have been applied to the Claisen rearrangement in solution and in chorismate and for two Menshutkin-type methyl transfer reactions in different solvents . Another example is the F + CD 3 CN abstraction reaction to form DF + CD 2 CN in CD 3 CN, which was treated with a multistate empirical valence bond (EVB) approach .…”

“…MS-ARMD treatments have been applied to the Claisen rearrangement in solution and in chorismate 149 and for two Menshutkin-type methyl transfer reactions in different solvents. 42 Another example is the F + CD 3 CN abstraction reaction to form DF + CD 2 CN in CD 3 CN, which was treated with a multistate empirical valence bond (EVB) approach. 150 This work reproduced the experimentally observed 151 solvatochromic shift of the DF product in CD 3 CN and reported that the DF product contains a significant amount of vibrational energy (v = 2−3).…”

“…Typical question arising in this context are A) whether reactions proceed stepwise or concerted, e.g. for phosphate transfer, − Menshutkin-type, − or Diels–Alder reactions, − or (B) for unimolecular reactions whether (I) decomposition involves one or several competing routes, (II) a potential barrier is involved, (III) it simply progresses by stretching a chemical bond until it breaks, or (IV) a combination of points II and III is at play which was coined “roaming” and was first discussed for formaldehyde some 15 years ago . Also, competing pathways can occur and have been found from atomistic simulations. − …”

Quantitative molecular simulations

“…For one of the systems, Pyr + MeBr experimentally determined barrier heights for acetonitrile and hexane as the solvent were 22.5 kcal mol −1 and 27.6 kcal mol −1 which compare with 23.2 kcal mol −1 and 28.1 kcal mol −1 from MS-ARMD simulations. 221 …”

Solvent and solvation effects on reactivities and mechanisms of phospho group transfers from phosphate and phosphinate esters to nucleophiles

“…On the other hand, there is another group of solvent effects, termed specific solvent (or solvation) effects , which depend on solute-solvent interactions of the ion-dipole and acid-base types in mainly dipolar aprotic solvents ( Parker, 1962 ; Epley and Drago, 1967 ; Parker, 1969 ) which affect the rates and mechanisms of chemical reactions executed in them. Considerable work has been achieved in determining solvent effects in nucleophilic substitution and a great variety of other reactions ( Ritchie, et al, 1967 ; Abraham, 1986 ; Reichardt, 2007 ; Cainelli et al, 2009 ; Turan et al, 2022 ). The predictions of the effect of solvent change on such reactions have generally been borne out by published experimental results.…”