Issue 11, 2012

Methylation using dimethylcarbonate catalysed by ionic liquids under continuous flow conditions

Abstract

The ionic liquid, tributylmethylammonium methylcarbonate, has been employed as a catalytic base for clean N-methylation of indole with dimethylcarbonate. The reaction conditions were optimised under microwave heating to give 100% conversion and 100% selectivity to N-methylindole, and subsequently transferred to a high temperature/high pressure (285 °C/150 bar) continuous flow process using a short (3 min) residence time and 2 mol% of the catalyst to efficiently methylate a variety of different amines, phenols, thiophenols and carboxylic acid substrates. The extremely short residence times, versatility, and high selectivity have significant implications for the synthesis of a wide range of pharmaceutical intermediates, as high product throughputs can be obtained via this scalable continuous flow protocol. It has also been shown that the ionic liquid can be generated in situ from tributylamine, which has the net effect of transforming an ineffective stoichiometric base into a highly efficient catalyst for this broad class of reactions.

Graphical abstract: Methylation using dimethylcarbonate catalysed by ionic liquids under continuous flow conditions

Article information

Article type
Paper
Submitted
03 Aug 2012
Accepted
19 Sep 2012
First published
20 Sep 2012
This article is Open Access
Creative Commons BY license

Green Chem., 2012,14, 3071-3076

Methylation using dimethylcarbonate catalysed by ionic liquids under continuous flow conditions

T. N. Glasnov, J. D. Holbrey, C. O. Kappe, K. R. Seddon and T. Yan, Green Chem., 2012, 14, 3071 DOI: 10.1039/C2GC36226K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements