Cleavage of tert-Butyl Benzoates with NaH in DMF: Comments on the Mechanism and a Simple and Safe Alternative Procedure

Emane Filali, Guy C. Lloyd-Jones*, David A. Sale

*School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK, Email: guy.lloyd-jonesbris.ac.uk

E. Filali, G. C. Lloyd-Jones, D. A. Sale, Synlett, 2009, 205-208.

DOI: 10.1055/s-0028-1087668

Abstract

The hazardous Schmidt procedure for tert-butyl benzoate ester cleavage using NaH in DMF involves B_AC2 ester cleavage by NaH-derived NaOH, rather than the proposed E₂ elimination of isobutylene by DMF-derived NaNMe₂. Powdered KOH in THF is a significantly safer and simpler alternative that effects cleavage of tert-butyl benozoates at ambient temperature in excellent yield.

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proposed mechanisms

Note

Schmidt's conditions involved RT or heating to 70 - 80°C. It is this heating part that potentially makes it very hazardous, as NaH and DMF can undergo uncontrollable exothermic decomposition even at 26°C. In some cases these exothermic reactions have resulted in violent eruptions of the mixture from the reaction vessel, in particular when conducted at scale. See: L. Bretherick, Handbook of Reactive Chemical Hazards, 4th ed.; Butterworth-Heinemann: Oxford, 1990, 1181.

Guy C. Lloyd-Jones, April 17, 2010

Key Words

tert-butyl esters, cleavage, hydrides, DMF, hazard

ID: J60-Y2009-0250