Furfural 2-arylation

Installation of a different side chain completely alters the pharmacological profile leading to a new class of muscle relaxants. The synthesis begins with copper(II)-promoted di-azonium coupling between furfural (j ) and 3,4-dichlorobenzene-diazonium chloride (15) to give bi aryl aldehyde Next, condensation with 1-aminohydantoin produces the muscle relaxant clodanolene (17). ... 

The furan ring undergoes arylation with diazo compounds, but the yield is poor. Thus, furfural,23 2-furoic acid,158 and furylacrylic acid can be converted into 5-substituted arylfuran derivatives by diazo-nium salts (see further references in Ref. 159) ... 

Aldehydes. Formaldehyde, paraformaldehyde, furfural, acrolein, alkyl aldehydes, and aryl aldehydes can be used as aldehydes, but formaldehyde is popularly used. An aqueous solution of formaldehyde is called formalin, and in almost all cases formalin is used industrially. When 1 mol of formaldehyde is dissolved in water, about 15 kcal of heat is generated. This heat generation results because methylene glycol is produced by solvation. 

Friedel-Crafts reactions, 20, i, 29 Fries rearrangement, 21, 23 Froth dissipation, 20, 3 Fusiaryl chloride, 20, 29, 51 z-Furanacrylic acid, 20, 55 Furfural, 20, 35 Fdrylacrylic acid, 20, 55 Fusion, alkaline, of an aryl sulfonate, 21,... 

With derivatives of benzaldehyde, the reaction proceeded regardless of electron-donating or electron-withdrawing properties of the substituents. A diverse range of aldehydes was employed, extending to heterocyclic compounds such as furfural and aryl dialdehydes. Benzene-1,3-dicarboxaldehyde, with cyclohexenone and benzylamine, reacted to produce a bis-anilino derivative, 2,2 -[l,3-phenylenebis(methylene)bis(A-benzylaniline)]. The yield (65%) was... 

Further, 1,2,4-triazinones, 1,2,4-triazine thiones, and their numerous derivatives are of interest for the synthesis of biologically active compounds. For instance, 4-amino-6-arylmethyl-3-mercapto-l,2,4-triazin-5(4//)-ones were condensed with suitably substituted 5-aryl-2-furfurals or 5-aryl-2-furoic acids to obtain biologically active derivatives 201 and 202 which exhibit antibacterial activities compared to furacin (Figure 11) <2003IJH85>. 

Among the intermolecular arylations, specially useful are those with thiophenes and furans. The latter electron-rich heterocycles bearing an electron-withdrawing group readily undergo the arylation with aryl iodides and bromides to give the respective biaryls in good to excellent yields. In this fashion, 4-nitro-iodobenzene (225) reacts with furfural (478) to produce the biaryl 479 in 88% yield, respectively. Scheme 28. 

In general it is not advisable to have the palladium-catalysed coupling reaction as last or penultimate step in view of the need to reduce palladium levels in the final product to below 10 ppm. Based on this reasoning, Taiwanese chemists patented an alternative route towards Lapatinib in which the furan ring is coupled to the quinazoline moiety before attachment of the substimted aniline (Scheme 23) [69]. Thus, coupling between the furfural-boronic acid 99 and aryl halide 103 catalysed by a catalyst prepared in situ from palladium acetate and one equivalent of tri-t-butylphosphine (2 mol%) gave the biaryl compound 104 in 98% HPLC yield. 

A variety of 2-acyloxylquinoline N-oxides, which is a valuable template for psychiatric medications, were prepared by condensation of quinoline N-oxides with aldehydes in the presence ofTBHP as an oxidant and a copper catalyst (Scheme 72) (13CC6900). Acetoxylation occurred regioselec-tively at C-2. A number of electron-rich aldehydes could be added to the quinoline N-oxides. Quinoline N-oxides with methyl or methoxy groups also worked well under these conditions. Other aryl aldehydes (pyridinecar-boxyaldehde and furfural) failed to provide the desired product. 

Oxidation of benzoquinones and naphthoquinones by palladium diacetate in arene-containing acetic acid gave the corresponding aryl-substituted quinones (eq 70). Treatment of 1,4-naphthoquinone with aromatic heterocycles, for example furfural, 2-acetylfuran, 2-acetylthiophene, and 4-pyrone, yielded the corresponding 2-heteroaryl-substituted 1,4-naphthoquinones. 

A number of well-known color reactions that are specific for carbohydrates depend on the formation of furfural derivatives by the action of strong acid. The furfural that is produced is condensed with a phenolic compound or an aryl amine. 

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