2-Furaldehyde derivatives

A number of 5-nitro-2-furaldehyde derivatives, called nitrofurans, are used in the treatment and/or prophylaxis of microbial infections, primarily in the urinary tract. Recent evidence suggests that the reduction of the 5-nitro group to the nitro anion results in bacterial toxicity. Intermediate metabolites modify various bacterial macromolecules that affect a variety of biochemical processes (e.g., DNA and RNA synthesis, protein synthesis) this observation may explain the lack of resistance development to these drugs. Evidence also indicates that the nitro anion undergoes recycling with the production of superoxide and other toxic oxygen compounds. It is presumed that the nitrofurans are selectively toxic to microbial cells because in humans, the slower reduction by mammalian cells prevents high serum concentrations. 

During the formation of colorant from D-fructose at pH 7.0,73 the first changes in the absorption spectrum occur at 210-240 mu and at 270-290 m/x. Judging by the data in Table II, these peaks are occasioned by a 2-furaldehyde derivative, possibly 5-(hydroxymethyl)-2-furaldehyde, or a compound of equivalent conjugation. Later, the absorption at 350-400 m/x increases. With further reaction, these peaks tend to be smoothed out to a hyperbolic curve, and absorption in the visible range appears and, still later, the solution becomes turbid as well as colored. If the process is continued, brown-to-black material is precipitated. 

Modern methods of estimation of D-fructose largely depend upon the spectrophotometric determination of a color produced by the interaction of amines or phenols with D-fructose in the presence of a mineral acid. Usually, little specificity is shown by these methods, for aldoses also react to give the final 5-(hydroxymethyI)-2-furaldehyde derivative, but always at a lower rate. 

The 2-methyl ethers of the enol form of 3-deoxyhexosuloses are difficult to separate, by chromatography, from the parent 2-methylaldose and from the derived a s-3,4-dideoxyhexosu]os-3-ene. They react with dilute acid to give a peak in the ultraviolet spectra, first at about 230 m/x (cis-hexosulos-3-ene), and later at about 280-285 m/x (2-furaldehyde derivative). With larger amounts, in deuterium oxide, the successive presence of the distinctive, nuclear magnetic resonance spectra of these three types of compound can readily be seen. ... 

The formation of 2-furaldehyde on acid-catalysed dehydration, etc., of 1-benzyl-amino-l-deoxy-D-f/ireo-pentulose and l-benzylamino-l-deoxy-o-fructuronic acid has been studied in isotopically labelled water (either acidified deuterium oxide or tritiated water).The pattern of labelling of the 2-furaldehyde derived from the latter compound is consistent with a mechanism involving the decarboxylation of a Py-unsaturated carboxylic acid intermediate (see also p. 136). 

Most studies on sulfur ylide-mediated asymmetric epoxidation have concentrated on the development of the methodology. The usefulness of this approach has been demonstrated in the synthesis of a number of biologically interesting compounds. Furaldehyde-derived epoxides can be oxidized to produce glycidic esters that are versatile intermediates in several syntheses (see Scheme 10.9) [46]. The... 

If on the other hand the polymerization of a furan derivative takes place through a substituent containing an adequate functionality, such as C=C or C=0, the furan ring should in principle conserve its structure and the polymers obtained will bear it as a side group. It has been found, however, that in some of these systems the normal propagation is accompanied by other reactions which involve participation of the ring and which therefore alter the normal structure of the macromolecule. The second section of this chapter deals with monomers, such as 2-vinylfuran and 2-furaldehyde, which exhibit this general behaviour. 

While the products of 2-furaldehyde polymerization by heat are branched polycondensates with highly conjugated structures (see Section Il-C), the photopolymerization of this furan derivative gives a linear polyaddition product 24>7S). 

The well-known condensation between 2-furaldehyde and acetone in a basic medium yields what is usually called furfurylidene acetone monomer composed of a mixture of 2-furfurylidene methyl ketone, di-2-furfurylidene ketone, mesityl oxide and other oligomers derived from further condensation reactions135. This mixture is then polymerized by the action of an acidic catalyst in the first phase of the reaction a polymer of low molecular weight is produced which on further treatment cross-links to a black insoluble and heat-resistant material136. ... 

Both anionic147-148 and cationic catalysts148,149 have failed to promote the homopolymerization of 2-furaldehyde and some of its derivatives. Recently, Gandini and Rieumont148 also experimented with the Kargin apparatus, but the results were negative. 

The well-known acid-catalyzed conversion of sugars into furan derivatives obviously consists of a complex sequence of reactions, and the industrial heterophasic conversion of pentosans in plant tissues has been discussed in detail.11 The reactions themselves are still not well understood, although xylose and glucuronic acid in deuterium oxide afford 2-furaldehyde without uptake of isotope thus limiting the mechanistic possibilities to those not permitting reversible enolization.12 The bacterial sugar streptose yields... 

A more general reaction between kojic acid and aldehydes is a trimolecu-lar condensation discovered by Barham and Reed." By a process of elimination, they arrived at the conclusion that C6 of kojic acid was most probably the point of attack two molecules of kojic acid reacted with one molecule of the aldehyde, with the elimination of one molecule of water, giving a product of structure LXXV. Such compounds were prepared from kojic acid and the following aldehydes the normal alkanals from formaldehyde to heptanal, benzaldehyde, cinnamaldehyde, hydrocinnamaldehyde, 2-furaldehyde, and acrolein. The compound derived from kojic acid and benzaldehyde (LXXV, R = phenyl) was also obtained by treating LXXII (R = phenyl) with hot, aqueous sodium carbonate.92... 

The synthesis of the furan-imidazole derivatives, shown in Scheme 2, were also described by Wang et al. [34]. Reaction of 4-(dimethylamino)benzalde-hyde (20) with trimethylsilylcyanide (TMS)-CN in the presence of Znl2 produced the TMS cyanohydrin 21. Compound 21 was treated with LDA followed by the addition of 3,4,5-trimethoxybenzaldehyde to give the benzoin intermediate 22. Oxidation with CUSO4 in aqueous pyridine, followed by reaction with 3-furaldehyde in acetic acid, produced the substituted imidazole 23. 

The three acid-derived components of the hexuronic acids, namely, 5, 47, and 48, are essentially end products in the reaction. This is quite surprising, as 48 required only decarboxylation to form 2-furaldehyde. However, the rate of decarboxylation of the furoic acid was <2% of that of D-galacturonic acid under similar conditions. Furthermore, no trace of pentoses was noted in any of the reaction mixtures, which eliminates previous suggestions of their role in the mechanism of 2-furaldehyde for-... 

The formation of such chromones as 3,8-dihydroxy-2-methyl-chromone by treating uronic acids or pentoses with dilute acid was reported by Aso,119 and studied by Popoff and Theander,120 who obtained a number of these compounds in 3.5% yield, as well as some catechols. Although nothing is yet known about the mechanism of formation of these compounds, the fact that the chromones contain 10 carbon atoms and are produced both from pentoses and uronic acids suggests that they may be derived from 2-furaldehyde or re-ductic acid, or produced from a decarboxylated intermediate. 

In concentrated sulfuric acid, D-glucuronic acid is dehydrated more slowly than either its 4-O-methyl derivative or D-glucose, probably because of the stability of its lactone. All hexuronic acids, however, eventually produce the same characteristic absorbance that corresponds roughly to a composite of 5-formyl-2-furoic acid, 2-furaldehyde, and reductic acid. It is interesting that a thin-layer chromatographic examination of the reaction products of D-glucuronic acid with 89% sulfuric acid at 70° revealed 5-formyl-2-furoic acid as a major product, but no evidence was obtained for the presence of reductic acid. This result is in distinct contrast to the products obtained in dilute acid solutions, in which 5-formyl-2-furoic acid is produced in very low yield, whereas reductic acid is formed in yields in excess of 10%. 

The formation of furan derivatives in acid-catalyzed dehydrations of carbohydrate substrates is a well known reaction, first reported by Dobereiner186 in 1832. Among the plethora of compounds formed, 2-furaldehyde is the main product obtained from all of the pentoses, whereas 5-(hydroxymethyl)-2-furaldehyde is the major product... 

On consecutive treatment with base and acid, the disaccharide derivative 48 yielded the /8-D-xylopyranoside of 5-(hydroxymethyl)-2-furaldehyde (49) (see Scheme 6).108 S. A. Barker and coworkers... 

Many heterocyclic nitro compounds have been used in the treatment of bacterial, protozoal or other infections. The first of these were derivatives of 5-nitro-2-furaldehyde... 

The transformation of pentoses and hexoses into 2-furaldehyde and 5-(hydroxymethyl)-2-furaldehyde, respectively, by the action of acids is a well-known reaction. Professor Bognar was long interested in ascertaining whether this reaction is reversible. With both a theoretical and a practical goal, the Bogn r group then synthesized the dl forms of several important monosaccharides (xylose, ribose, and arabinose) from the aforementioned furan derivatives. 

Toward this goal, a furane ring was included in the carbonyl or amine component, since this moiety will furnish a highly reactive diene for the following IMDA. In most cases 2-furaldehyde (or the corresponding 5-methyl derivative) was employed. The acid component was chosen in order to introduce an activated dienophile suited for the IMDA and was in turn a fumaric acid monocarboxyamide [82, 84], a maleic or fumaric acid monoester [84] or a 3-substituted propynoic acid [83]. Benzylamine (or a para-substituted derivative) [81-83] or t-butylamine [83] have been chosen as amine component for the Ugi reactions. 

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