5-Nitro furfural

Prepd by heating furan-2,5-dioic acid with nitrosylsulfuric acid at 100° (Ref 2) hydto-lysis of 5 nitro-2-cyano-foran (Ref 5) and oxidation of 5-nitro-furfural with CrOa(Ref 4). 

The key intermediate for the synthesis of various nitrofuran drugs is 5-nitro-furfural (45, isolated as diacetate), which is obtained by careful nitration of furfural (44) with a nitric acid-acetic anhydride mixture at low temperatures [30]. Reaction of 45 with various nucleophiles gives nitrofuran drugs of the general formula 46. 

The reaction of nitric acid and furfural in acetic anhydride produces 5-nitro-furfural diacetate, an important intermediate in the production of chemotherapeutic agents, such as nitrofurazone and nitrofurantoin. 

These precursors are prepared by reaction of fuming nitric acid in excess acetic anhydride at low temperatures with 2-furancarboxaldehyde [98-01-1] (furfural) or its diacetate (16) followed by treatment of an intermediate 2-acetoxy-2,5-dihydrofuran [63848-92-0] with pyridine (17). This process has been improved by the use of concentrated nitric acid (18,19), as well as catalytic amounts of phosphoms pentoxide, trichloride, and oxychloride (20), and sulfuric acid (21). Orthophosphoric acid, -toluenesulfonic acid, arsenic acid, boric acid, and stibonic acid, among others are useful additives for the nitration of furfural with acetyl nitrate. Hydrolysis of 5-nitro-2-furancarboxyaldehyde diacetate [92-55-7] with aqueous mineral acids provides the aldehyde which is suitable for use without additional purification. 

Problem 20.47 Prepare (a) 3-aminopyridine from /3-picoline, (b) 4-aminopyridine from pyridine, (c) 8-hydroxyquinoline from quinoline, (d) 5-nitro-2-furoic acid from furfural, (e) 2-pyridylacetic acid from pyridine. 

Condensation of ferrocenecarboxyhydrazide with 5-nitro-2-fur-aldehyde or 5-nitro-2-acetylfuran gave 171, and the same hydrazide with ethyl 5-nitro-2-furimidate hydrochloride gave 172.62 The reaction of /3-ferrocenylnitroethylene and furfural with sodium methoxide gave 173.146... 

When aromatic aldehydes are condensed with nitroalkanes in the presence of a base, a, p-unsaturated nitro compounds are produced directly. For example, benzaldehyde and nitromethane in the presence of a base give a,p-unsaturated compound nitrostyrene (3.25). Similarly, the reaction of nitrobutane with furfural in the presence of a base followed by hydrolysis gives 82% yield of 2-substituted furan derivative 3.26. 

Substituted benzaldehydes and malonic acid give cinnamic acids in excellent yields. Among the common nuclear substituents are methyl, halo, " hydroxyl, methoxyl, " cyano, nitro, and diethylamino groups. Other /fi-arylacrylic acids have been made by the use of a-naphthaldehyde, phenanthraldehydes, and furfural. Phenyl-substituted aliphatic aldehydes have also been used in this condensation. ... 

A review of the literature of this reaction to 1941 has been made. The condensation is most valuable for the preparation of substituted cinnamic acids, particularly those containing halo, methyl, and nitro groups. Furfural has been condensed in good yields with acetic anhydride, butyric anhydride, and sodium phenylacetate in the... 

NB - nitro benzene AP - acetophenone IP - isophorone BL - butyl lactate CHX - cyclohexanone FF - furfural MEK - methyl ethyl ketone CA - cellosolve acetate... 

The acyloin (benzoin) condensation is applicable, not merely to benzaldehyde itself, but also to its homologs, to its alkoxy derivatives, and to furfur-aldehyde. It fails, however, with free hydroxybenzaldehydes and with halo-genated nitro and amino benzaldehydes and cinnamaldehyde gives diminutive yields. 

Thus, reaction of triethyl phosphite with furfural (31) is reported to furnish difuryleth dene as the major product. While both trimethyl and triphenyl phosphite interact with p-nitrobenzaldehyde to provide an addition product of type 26, triethyl phosphite gives instead p-nitro-benzyl p-nitrobenzoate and 27. Normal addition also occurs upon... 

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