Understanding the Solvent-free Nucleophilic Substitution Reaction Performed in the High Speed Ball Mill (HSBM): Reactions of Secondary Alkyl Halides and Alkali Metal-Halogen Salts

Governments around the world continue put forth new regulations to reduce the amount of solvent emissions into the environment.^a R&D chemists must take on this challenge in order to make safer solvent choices and solvent reduction priorities in the beginning stages of product development. As the scientific community embraces the ideals of Green chemistry and moves towards more environmentally responsible research, it is necessary to understand the capacity of these new techniques on well-established reactions, e.g. S_N1 and S_N2 reactions. It has been proven that the nucleophilic substitution product of an S_N2 reaction on a primary alkyl-halogen substrate can be formed in a High Speed Ball Mill (HSBM) under solvent-free conditions.¹ The results of a nucleophilic substitution reaction performed on a secondary alkyl halide substrate in an HSBM under solvent-free conditions were previously uncharted. The mechanism of the reaction between a secondary alkyl-halogen can be considered S_N1 or S_N2 depending on a variety of factors.² The success of the S_N1 reaction, a first-order nucleophilic substitution, is largely dependent on the solvent used. This is because of the charged species formed in the first step of the reaction: bond heterolysis. By using the HSBM under solvent-free conditions, the medium which stabilizes the intermediate and transition states of the S_N1 reaction mechanism is removed.

This investigation looks at the results from the reaction of a hindered secondary alkyl halide and an alkali metal-halogen salt in a solvent-free environment in order to answer the questions: What, if any, products are formed? and How does this compare to the predicted products as seen in classic S_N1 reactions?

^a Governmental regulations on solvent emissions can be found at the websites: epa.gov, legislations.gov.uk, and Canada.gov.ca