Chromate Oxidation of α-Nitro Alcohols to α-Nitro Ketones: Significant Improvements to a Classic Method

A series of eight alkyl and aryl α-nitro ketones were prepared by the potassium dichromate oxidation of the corresponding nitro alcohols. Short reaction times allowed for the easy isolation of pure nitro ketones that are devoid of starting materials and/or other oxidation side products.


Introduction
Our interest in α-nitro ketones stems from their usefulness in the synthesis of alkyl substituted pyrazines [1]. A literature search revealed a limited number of procedures for their preparation. α-Nitro ketones have been prepared in a one pot procedure by a solvent free nitroaldol (Henry reaction) reaction followed by oxidation to the corresponding ketone using wet-alumina supported chromium(VI) oxide [2], by the base catalyzed nitroaldol reaction using alumina supported potassium fluoride, followed by oxidation using CrO 3 along with the addition of montmorillonite K 10 [3] , or by the sodium dichromate oxidation of α-nitro alcohols [4] formed from the Henry reaction [5]. Other general methods for the oxidation of primary and secondary alcohols have been reported and these include the use of PCC [6] and the Swern [7] oxidation reactions. Finally α-nitro ketones can be prepared through the reaction of acyl imidazoles with nitroalkanes in the presence of lithium hydride in dimethyl sulfoxide [8].

Results and Discussion
This series of compounds reported here was prepared by a modified version of the sodium dichromate oxidation [4]. In the method used by Hurd and Nilson [4] the sulfuric acid solution was added to a mixture of the alcohols and sodium dichromate over a period of six hours, followed by long mixing periods (2-72 hours), depending on the nitro ketone prepared. In our modification of the procedure (given below), the nitro alcohol was gradually added to the potassium dichromate solution followed by a ten-minute stirring period, then the drop-wise addition of the sulfuric acid solution over a period of one hour. After the sulfuric acid addition is complete, the reaction is terminated by the addition of water, followed by extraction and purification.
This method led to yields between 85-95%, with minimal purification, as compared to literature yields of 68-86% [2], 76-90% [3] and 39-74% [4], which required more time and, in some cases, complex methods. It should be noted that NMR spectral analysis of the crude material (prior to Kugelrohr distillation) showed the compounds to be very pure, and thus they can be used directly in most applications.

Conclusions
We have presented a facile route for the formation of α-nitroketones, useful intermediates in heterocyclic synthesis.
All 1 H-and 13 C-NMR spectra were recorded in CDCl 3 on a Varian Mercury NMR spectrometer operating at 300 and 100 MHz, respectively. Chemical shifts are expressed in ppm relative to TMS as an internal standard. J values are given in hertz. Final products were purified by Kugelrohr distillation using a Büchi B-580 Glass Oven. Starting materials were purchased from Aldrich and used without further purification.