Abstract
The solvent effect on the Grignard reaction of benzyl, aryl and heteroaromatic substrates has been systematically evaluated based on reaction efficiency, ease of subsequent work-up, safety and greenness. 2-Methyltetrahydrofuran (2-MeTHF), which can be derived from renewable resources, had at least an equal if not a superior overall process most notably in suppressing the Wurtz coupling by-product from the benzyl Grignard reactions. It is therefore a recommended alternative solvent to Et2O and THF for the preparation of most Grignard reagents and their subsequent reactions.
Highlights
The American Chemical Society’s Green Chemistry Institute Pharmaceutical Roundtable (GCIPR) was developed in 2005 to encourage the integration of green chemistry and engineering into the pharmaceutical industry and to promote sustainable manufacturing
The Grignard reagents were generated by reacting the alkyl- or aryl-halides with commercial grade magnesium turnings
It is important to note in these systems that the reaction of the magnesium metal with the aryl or alkyl halide forms the Grignard reagent, and is not classified as the actual Grignard reaction, though both processes are often carried out sequentially and impurities generated from the Grignard reagent formation step are carried into the Grignard reaction
Summary
Victor Grignard and Paul Sabatier received the Nobel Prize in 1912 for the discovery of what was later called the Grignard reaction.[2]. In some instances research scale chemistry has been recently carried out using continuous flow methods to alleviate the exotherm hazards of the Grignard reaction.[10] the solvents typically employed such as Et2O and THF have low boiling points, and are capable of forming peroxides, which are both hazardous as well as detrimental to the reaction. The optimal solvent would be one with a better safety profile, and ideally available from renewable sources.[13] Aycock[14] has presented initial data showing the promising nature of 2-MeTHF for Grignard reactions, and Clarke[15] has employed Grignard reagents of significantly enhanced concentrations (up to 5 M) in cross-coupling chemistry using this solvent. It has long been recognized that the solvent in which a Grignard reagent is formed has a significant effect on its reactivity due to the formation of potential aggregates with a chelating solvent, and a redistribution of organomagnesium species in the Schlenk
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
