An Experimental Study on the Effects of Solvents on the Rate and Selectivity of Organic Reactions

Abstract

In industry, solvents are an important processing aid. They often make up the bulk medium in liquid-phase reactions and have a large impact on process performance, from reaction rate to environmental impact. Traditionally solvents are chosen based on heuristics, experience and knowledge of the reaction. Recently systematic methodologies for choosing a solvent which can maximise the rate of a reaction have started to emerge (R. Gani, C. Jiménez-González and D. J. Constable, Comp. Chem. Eng., 29, 1661-1676, 2005 and M. Folić, C. S. Adjiman and E. N. Pistikopolous, Am. Inst. Chem. Eng. J., 53 (5), 1240-1256, 2007). In this work, a systematic experimental protocol for gaining insight into a specific reaction by monitoring the kinetics of this reaction in a variety of solvents using in situ 1H NMR spectroscopy and obtaining the reaction rate constants by nonlinear parameter estimation is presented. The methodology has been applied to an SN2 reaction, namely a Menschutkin reaction, in which a tertiary amine is added to a primary haloalkane to form a quaternary ammonium salt. This reaction has been chosen because it is a classic reaction to study solvent effects as this type of reaction is very sensitive to solvents and there is evidence that an empirical model of solvent effects can be developed. Reaction rate constants have been successfully determined for 10 deuterated solvents at ambient temperature (25 °C) and pressure (1 atm) using in situ 1H NMR spectroscopy. The reaction rate constants have been found to vary over two orders of magnitude depending on the solvent used. This systematic methodology has also been applied to the alkylation reaction of sodium β-naphthoxide and benzyl bromide which forms the products 1-benzyl-2-naphthyl ether and 1-benzyl-2-naphthol. It is known from the literature that depending upon the solvent used the ratio of these products vary accordingly (N. Kornblum, R. Selzer and P. Haberfield, J. Am. Chem. Soc., 85 (8) 1148-1154, 1963). In highly dipolar aprotic solvents such as DMSO and DMF the product favoured will be 1-benzyl-2-naphthyl with percentage yields as high as 95 % and 97 % respectively, whereas in polar protic solvents for example, water and 2,2,2-trifluroethanol (solvents that are capable of forming hydrogen bonds) the other product 1-benzyl-2-naphthol is more favoured in yields as high as 84 % and 85 % respectively. The kinetics and selectivity of this reaction have been studied in 9 solvents by in situ 1H NMR spectroscopy at ambient temperature (25 °C) and pressure (1 atm). This experimental study shows the strong variation of selectivity and the differences in the reaction rates, which are all dependent on the solvent.