Use of an Ionic Liquid to Aid Conversion and Reaction Work Up

The use of 1-methylimidazole as an HCl scavenger has been developed by BASF to circumvent the problematic filtration of triethylamine hydrochloride, which results if triethylamine is used as the HCl scavenger. This has been commercialised and is used in the BASIL process (BASF Ionic Liquid Process, M. Maase (BASF), C & E News, 2003, 81(13), 9) where Ph2PCl is reacted with ROH to produce Ph2POR and HCl, with the HCl being scavenged with 1-methylimidazole. 1-Methylimidazole hydrochloride is a low melting solid, which forms a separate liquid layer under the reaction conditions.

A variation on this technique has now been taken up by Schering* to drive TBDMS ether formation to completion and simplify the work up. Reaction of a secondary alcohol with TBDMS chloride under standard conditions, using imidazole in toluene, never reached completion (even after 12 hours at 50°C) because the starting material was trapped in the voluminous precipitate of imidazole HCl. Furthermore this precipitate required a tedious filtration.

Use of 1-methylimidazole as in the BASIL process gave an improved work up but still did not drive the reaction to completion. A high conversion was finally achieved using a mixture of 1-methylimidazole and imidazole with the ionic liquid mixture separating at as separate layer at the end of the reaction. There was an added benefit in that some yellow colour which had carried through from an earlier stage in the synthesis partitioned in to the ionic liquid layer leaving a clear colourless solution of the TBDMS ether in toluene which was used directly in the next stage of the synthesis.

 • Will Watson

* J. Platzek, presentation at the Scientific Update conference “Developing Chemical Processes for Active Pharmaceutical Ingredients” held at the National Chemical Laboratory, Pune, India, December 2006.

If you would like to request a copy of the complete presentation, please email Kate Laird at kate@scientificupdate.co.uk.