Oct 2016 - Article in Organic Syntheses Published

James Murray's procedure for making N-methylimidazole-N-oxide, a potent Lewis base catalyst e.g. for silylation of tert-alcohols, is published.

James I. Murray, Alan C. Spivey, 'Preparation of 1-methylimidazole-N-oxide (NMI-O)', Org. Synth. 2016, 93, 331; DOI: 10.15227/orgsyn.093.0331 

1-Methylimidazole-N-oxide (NMI-O) has been an underused member of the aryl-N-oxides, primarily due to its problematic synthesis. Tsai et al. mistakenly reported the use of NMI-O as an efficient catalyst in the Morita-Baylis-Hillman reaction. However, these authors were subsequently shown by Laus et al. to have employed the N-methylimidazole (NMI) semiperhydrate (NMI.½H₂O₂) for these studies. The error resulted from the use of hydrogen peroxide (H₂O₂) for the direct oxidation of NMI, which has been repeatedly reported not to yield the desired N-oxide. It is likely that NMI-O is concomitantly deoxygenated by H₂O₂ and by peracids during attempted preparation in this fashion. Laus et al. demonstrated the first synthesis of authentic NMI-O, requiring an 8 step synthesis from glyoxal. Here, we repotr a convenient three-step, one pot preparation of this previously elusive molecule.

The efficiency of NMI-O as a highly active catalyst for the sulfonylation and silylation of alcohols (e.g. see: Murray, J. I.; Spivey, A. C. Adv. Syn. Catal. 2015, 357, 3825-3830 - DOI: 10.1002/adsc.201500773) should mean that it becomes widely used in synthesis. The operationally facile synthesis presented in this Org. Synth. preparation allows for multi gram-scale preparation of this highly active Lewis-basic catalyst and so should enable its widespread use and the development of novel derivatives.