Furane-3,4-dialdehyde

A benz-analog of 353, namely 360, has been obtained in a Wittig reaction with either o-phthalaldehyde or furan-3,4-dialdehyde as expected, 360 was found to be more stable than 353. Diels-Alder reaction with dimethyl fumarate resulted in cycloaddition to the furan ring. ... 

Furan dialdehyde may be the closest relative of furfural, but strangely enough it is not made from furfural but from fructose. Furan dialdehyde is an obvious competitor of difurfural as a building block for high-temperature polymers based on the thermal stability of the furan ring. 

The furan dialdehyde is a stable colorless compound having a melting point of 110 °C. Contrary to furfural, even in the liquid state the furan dialdehyde does not undergo discoloration as it does not have the highly reactive hydrogen by which furfural polymerizes. At room temperature, furan dialdehyde is slightly soluble in water (10 g per liter at 17 °C) as well as in cyclohexane, hexane, ligroin, carbon tetrachloride, diethyl ether, and benzene. It is well soluble in ethanol, ethyl acetate, acetone, dimethylsulfoxide, and methylisobutyl ketone, as well as in hot water. 

Figure 134. Derivatives of Furan Dialdehyde by Linkages via Nitrogen.

Figure 137. Macrocycles obtained from Furan Dialdehyde.

Furan-dialdehyd-(8.6)-dianil 17 1240. 2-Phenyl-5-benzoyl pyridin-oxim 21II 294. 2FhenyI-pyrldin oarbon8fture-(5)-aniIid 22 II 63. 

Furan can be catalyticaHy oxidized in the vapor phase with oxygen-containing gases to maleic anhydride (93). Oxidation with bromine or in an electrochemical process using bromide ion gives 2,5-dimethoxy-2,5-dihydrofuran [332-77-4] (19) which is a cycHc acetal of maleic dialdehyde (94—96). 

The hydrogenation of HMF in the presence of metal catalysts (Raney nickel, supported platinum metals, copper chromite) leads to quantitative amounts of 2,5-bis(hydroxymethyl)furan used in the manufacture of polyurethanes, or 2,5-bis(hydroxymethyl)tetrahydrofuran that can be used in the preparation of polyesters [30]. The oxidation of HMF is used to prepare 5-formylfuran-2-carboxylic acid, and furan-2,5-dicarboxylic acid (a potential substitute of terephthalic acid). Oxidation by air on platinum catalysts leads quantitatively to the diacid. [32], The oxidation of HMF to dialdehyde was achieved at 90 °C with air as oxidizing in the presence of V205/Ti02 catalysts with a selectivity up to 95% at 90% conversion [33]. 

No studies were located regarding metabolism of 2,3-benzofuran in humans or animals. However, the metabolism of several other substituted furans has been shown to involve oxidation by P-450, with the unsubstituted double bond of the furan ring converted either to an epoxide (Boyd 1981) or to a dialdehyde (Ravindranath et al. 1984). Pretreatment with inducers and inhibitors of P-450 modified the toxicity of a single intraperitoneal injection of 2,3-benzofuran to male mice (McMurtry and Mitchell 1977). Oral exposure to 2,3-benzofuran altered the activity of P-450 and other enzymes in the livers of female mice (Heine et al. 1986). These experiments indicate that cytochrome P-450 may be involved in the toxicity of 2,3-benzofuran, but do not provide a clear picture of 2,3-benzofuran metabolism. 

In conclusion, the pulmonary toxicity of 4-ipomeanol seems to be due to metabolic activation probably by formation of an unstable epoxide on the furan ring catalyzed by CYP4B1 in the Clara cell. The epoxide can rearrange to an a, 3 unsaturated dialdehyde (Fig. 7.37), which can interact with macromolecules and covalently bind, leading to cellular necrosis and edema. 

Preparation the linear tropone-annelated benzo [c] furans 371 (X = O) by direct condensation of dialdehyde 370 (X = O) with acetone, 1-phenyl-acetone, and 1,3-diphenylacetone, in alkaline medium was—in contrast to the corresponding benzo [c]thiophene (X = S)—unsuccessful. Interestingly, this condensation has been brought about with the Diels-Alder adduct 372 subsequent heat yields 371 (X = O), a rare case where V-phenylmaleimide is used as a protective group. Compounds 371 react with V-phenylmaleimide even at room temperature to give adducts 373. 

A novel synthesis of the sesquiterpene ( )-cinnamodial (148) utilizes the furan ring as a latent 1,4-dialdehyde synthon (81JA3226). The triol (141) was thus oxidized to the ketofuran (142). Oxidation of the furan moiety with lead tetraacetate afforded a 90% yield of epimeric diacetates (143) which when exposed briefly to DBU gave dienone (144). Epoxidation of (144) and exposure of the epoxide (145) to p-toluenesulfonic acid gave the bis-acetal (146). Reduction of this intermediate to a diol and hydrolysis of the bis-acetal furnished dialdehyde (147). Acetylation of the secondary hydroxyl group completed the synthesis of cinnamodial (Scheme 32). 

Furans have been prepared from 1,4-dialdehydes, usually in the more accessible acetal form by acid catalyzed ring closure. Using this approach, furan-3,4-dicarboxyIic acid has been obtained in 70% yield as the ester from 2-(dialkoxymethyl)-l-formyl succinic ester (54JOC1671). c/s-2-Butene-l,4-diol on oxidation to the monoaldehyde is cyclized to furan (61 ACSll77). The acetals (83) and (84) have been converted to the corresponding furan... 

The oxidative reaction of furan with bromine in methanol solution or an electrochemical process using sodium bromide produces 2,5-dimethoxy-2,5-dihydrofuran (19), which is a cyclic acetal of maleic dialdehyde. The double bond in (19) can be easily hydrogenated to produce the corresponding succindialdehyde derivative. Both products find application in photography and as embalming materials, as well as other uses. 

Furan-2,5-dicarboxylic add also has tremendous industrial potential, because it could replace oil-derived diadds such as adipic or terephthalic acid as monomers for polyesters and polyamides [98, 99]. This diadd can be synthesized by Pt-catalyzed oxidation with 02 of 5-hydroxymethylfurfural the latter is obtained by acid-catalyzed dehydration of D-frudose or frudosans (inulin) the latter, however, are too expensive as starting materials, and yields from glucose-based waste raw materials are no higher than 40%. Therefore, the potential attractive option of furan-2,5-dicarboxylic acid will develop only after an effident generation of 5-hydroxymethylfurfural from forestry waste materials has been developed. The same compound is also the starting material for the synthesis of other interesting chemicals obtained by oxidative processes, such as 5-hydroxymethylfuroic add, 5-formylfuran-2-carboxylic add and the 1,6-dialdehyde. 

The direct electrochemical methoxylation of furan derivatives represents another technically relevant alkoxylation process. Anodic treatment of furan (14) in an undivided cell provides 2,5-dimethoxy-2,5-dihydrofuran (15). This particular product represents a twofold protected 1,4-dialdehyde and is commonly used as a C4 building block for the synthesis of N-heterocycles in life and material science. The industrial electroorganic processes employ graphite electrodes and sodium bromide which acts both as supporting electrolyte and mediator [60]. The same electrolysis of 14 can be carried out on BDD electrodes, but no mediator is required The conversion is performed with 8% furan in MeOH, 3% Bu4N+BF4, at 15 °C and 10 A/dm2. When 1.5 F/mol were applied, 15 is obtained in 75% yield with more or less quantitative current efficiency. Treatment with 2.3 F/mol is rendered by 84% chemical yield for 15 and a current efficiency of 84% [61, 62]. In contrast to the mediated process, furan is anodically oxidized in the initial step and subsequently methanol enters the scene (Scheme 7). 

A condensation occurs between 5-hydroxymethylfurfural and malonic ester20 and in a similar way, two molecules of malonic ester react with furan 2,5-dialdehyde.88 A condensation product, XXXV, has also been obtained with hydantoin.89 5-Hydroxymethylfurfural and its acetyl derivative undergo the Perkin reaction with sodium acetate and acetic anhydride giving 5-acetoxymethylfuran 2-acrylic acid (XXXVI).70 Similar products of the same reaction are obtained from 5-methyl-furfural71 and 5,5 -diformyl-l,l -furylmethyl ether (XXVII).61,72... 

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