5-nitrofurfural diacetate

A safe method of nitrating furfuraldehyde or its 0,0-diacetate to 5-nitrofurfural diacetate is described which minimises the formation of acetyl nitrate. 

The nitration of furfural in the presence of acetic anhydride gave 5-nitrofurfural diacetate (74%). 

The azomethine derivative is generally prepared by the condensation of a substituted hydrazine with nitrofurfural in the presence of acid. For example, nitrofurazone(.E) is formed by the interaction of 5-nitrofurfural diacetate which is hydrolysed to the active 5-nitrofurfural and semicarbazide in the presence of sulphuric acid and water. This reaction proceeds by heating at about 100°C for 5 hours. 

A mixture of 5-nitrofurfural diacetate, abs. ethanol, some coned. H2SO4, and benzene refluxed 30 hrs. with azeotropic water entrainment -> 5-nitrofurfural diethyl acetal. Y 82%. F. e. s. W. Weuffen and H. Tiedt, Arch. Exp. Veterinaermed. 21 (1), 267 (1967) C. A. 68, 21758. 

Nitrofurfural diacetate added portionwise with stirring at 65 to a mixture of finely powdered 3-amino-4-quinazolone, acetic acid, aq. 50%-H2SO4, and alcohol, stirred for an additional 5 hrs. at 65° o-(5-nitrofurfurylideneamino)-benzoic acid 5-nitrofurfurylidenehydrazide. Y 88%. C. Casagrande, M. Canova, and G. Ferrari, Farmaco, Ed. Sci. 20, 544 (1965). 

Nitrofurfural and its diacetate are the commonest starting materials for the preparation of many of the therapeutically active compounds. Nitrofurfural diacetate is easily obtained by the action of acetyl nitrate on furfural ( ) or its acetate ( ) if acetic anhydride is in excess, a yield of 40-70 per cent can be expected. The use of strong catalysts such as sulphuric acid enhances the yield. Marquis first tried to nitrate furfural and later Gilman and Wright succeeded in preparing the pure 5-nitrofurfural. 

The 5-nitrofuran derivatives were the first nitroheterocycles of therapeutic value (Fig. 7-3). They are all synthesized from 5-nitro-2-furancarboxyaldehyde (5-nitrofurfural) or its diacetate by azomethine (Schiff base) formation with the appropriate amino compound (Eq. 7.1). The important nitrofurans in use today are shown in Figure 7-4. Since the first report of their antibacterial activity about 4,000 nitrofuran compounds have been synthesized and tested. Those that reached commercial use in human and veterinary medicine, including farm animal husbandry, did so because of their broad spectrum of activity including Gm+ and Gm- bacteria (except P. aeruginosa and some Klebsiella and Proteus strains), relatively low toxicity, and infrequent development of resistance. 

The intermediate product, (C), when treated with a base such as trisodium phosphate or pyridine, gives the diacetate ( )) of 5-nitrofurfural ... 

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