Nitrofurfural

Aminothiazole present in urine or blood plasma forms a colored Schiff base when 5-nitrofurfural is added the colorimetric analysis of the Schiff base allows the quantitative determination of this thiazole (1571). The Schiff base may also be dosed by polarographic of spectro-photometric methods (1572). 

The first drugs in this class to be introduced into clinical practice are simple derivatives of 5-nitrofurfural (18). Thus, the oxime is known as nitrofuroxime (19) while the semicarbazone is called nitrofurazone (20). In order to maintain better control over the distribution and metabolism of these antibacterial agents, increasingly complex side chains and rings have been grafted onto the hydrazone. 

The extensive series of antibacterial agents consisting of derivatives of 5-nitrofurfural has been discussed in Chapter 8. It is of interest that a... 

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

Antibacterial activity has also been observed with a variety of sulphameth-oxypyridazine derivatives like the imine obtained upon reaction of (95, R1 = MeO R2 = H) with 5-nitrofurfural [312], 2-aryl-3-nitrofurylacrylamides (105) [313], quinazoline-2,4-diones (106) [314], thiazolin-4-ones of type (107) [315] and with aldol condensation products of the latter [316], Sulpnonylpyridazmones (108, R1, R3 = alkyl, Ph R2 = substituted NH2, HO, RO) [273,274], trichloromethylchloropyridazines (109) [317] and 3-mer-captopyridazine 2-oxide derivatives [318, 319] have been claimed as antibacterial agents. 

Neurotransmitters, in regulation of blood pressure, 55 Nialamide, 254 Nicotinic acid, 253 Nicotinyl alcohol, 253 Nidroxyzone, 228 Nifenazone, 234 Niflvminic acid, 256 Nifurprazine, 231 Nikethamide, 253 Nitrazepam, 366 Nitrimidazine, 240 Nitrofurantoin, 230 Nitrofuratel, 229 Nitrofurazone, 228 5-Nitrofurfural, 228 Nitrofuroxime, 228 Nitrosation... 

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

NITROFURFURAL SEMICARBAZONE (5-NITRO-2-FCRFURYLIDENEAMINO)UREA NITROZONE NSC-2100 OTOFURAN SANFURAN SPRAY-DERMIS SPRAY-FORAL U-6421 USAF EA-4 VABROCID DVADROCID VETERINARY NITROFURAZONE YATROCIN... 

NITROFURFURAL SEMICARBAZONE see NGE500 l-((5-NITROFURFURYLIDENE)A. nNO)HYDANTOIN see NGEOOO... 

Fig. 10.20 A, Furan B, 5-nitrofurfural C-F, nitrofuran drugs respectively C, nitrofurazone, D, nitrofurantoin, E, furazolidone and F, furaltadone.

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. 

Table 6.3. JV-Alkyl derivatives of 5-nitrofurfural hydrazone 5-OaN Fur CH=N NRRi...

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. 

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