Synthesis of nitrofurans

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

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. 

At present there are six nitrofuran azomethine compounds which are used clinically. These are synthesized by replacing semicarbazide in the preparation of nitrofiirazonc by hydroxylamine, aminoguanidine, 1-aminohydan-toin, 3-amino-2-oxazolidinone and 3-amino-5-morpholinomethyl-2-oxazo-lidinone to give respectively nifuroximei , guanofuracin , nitrofurantoin , furazolidone and furaltadonc .  

The early synthetic work on some of these azomethine nitrofuran compounds has been reviewed . The nitrofurans have been discussed in a monograph on furan compounds in general. 

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Both 2- and 3-nitrofurans with additional substituents on the available positions of the furan ring have been synthesized by cyclization procedures. The nitro-containing reagents are of type 1 or 2. No type 3 reagent seems to have been used for the synthesis of nitrofurans or condensed nitrofurans. 

The synthesis of nitrofuran and nitroimidazole drugs will be discussed in Chapter 17. In this chapter the synthesis of only those nitroaryls will be described, which are of sigirificance in the chemotherapy of helminthiasis. 

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