Side Reaction of DMF

W R Jackson et al (SYNLETT, 2011, (6), 831) describe an unexpected reaction of DMF to form tetramethylguanidines.  The intended chemistry was the base-mediated removal of an fmoc protecting group in DMF as solvent, but the group found considerable extent of the by-product, as illustrated below.  Based on the limited range of examples in the paper, it appears as though piperidine in DMF favoured the tetramethylguanidine by-product whilst triethylamine in DMF favoured the desired fmoc deprotection.

In retrospect this perhaps does not come as a surprise.  But it does serve as a useful reminder to those of us investigating or developing new processes that the solvent not only plays an important role in the chemistry, such as influencing selectivity, but can of course be very disruptive as a result of reactivity in its own right.