Synthesis of 4(5)-nitroimidazole - the convenient synthon for the selective production of dinitroimidazoles

The results of investigation of imidazole and its derivative 4(5)-nitroimidazole nitration by sodium nitrate as nitration agent are represented. The conditions for selective preparation of 4(5)-nitroimidazole, 4,5- and 1,4-dinitroimidazole are determined. Reactions of nitration were carried out with sulfuric acid solution in the case synthesis of mononitroimidazole and 4,5-dinitroimidazole, while acetate solution was used for synthesis the 1,4-dinitroimidazole. In this paper sodium nitrate is proposed for the first time as a nitration reagent to obtain the dinitroimidazoles. This makes the method more technological as compared with the known methods of nitration of imidazoles using concentrated nitric acid and acetic anhydride. It was determined that synthesis of 4(5)-nitroimidazole and 4,5-dinitroimidazole occurs advantageously at high temperatures (100-160°C), while the obtaining of 1,4-dinitroimidazole occurs at a temperature near 50°C. The influence of the reaction time of imidazoles nitration, the temperature conditions of the reaction and the amount of nitrating agent on yield of base mono- and dinitroimidazoles were investigated. Optimal conditions of nitration processes to corresponding nitroimidazole maximum yield were determined. The graphs of dependence of yields the base products from conditions are constructed. It was founded that the dependence of the yield of 4,5-dinitroimidazole from amount of sodium nitrate in certain interval of the graph has pronounced linear character. Deviation from optimal conditions leads to decreasing of main product yield which induced by oxidative processes to produce different substances with unascertained structure. Synthetic methods proposed in the present work does not require special additional equipment, simply reproduce in preparative practice and are characterized by good selectivity. In the experimental part of this paper the detailed methods of synthesis of 4(5)-nitroimidazole, 4,5- dinitroimidazole and 1,4-dinitroimidazole are described. The characteristics of the synthesized compounds reported in the experimental part have agreement with literature data. The resulting products were identified by physical-chemical methods such as IR-spectroscopy, NMR-spectroscopy, elemental analysis, melting point measurement. The effect of temperature conditions, the time of the reaction, the amount of added components to yield the appropriate mono- and dinitroimidazoles were studied. Preparative methods of synthesis of nitroimidazoles suggested in this work can be used to develop technologies for their production, which are attractive for a potential industrial partner. Moreover, designed methods C- and N-nitration of imidazoles can be used for obtaining another nitroderivatives diazaheterocycles.

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