Mechanism of Meerwein arylation of furan derivatives

Abstract

Catalytic arylation of furan-2-carbaldehyde with arenediazonium salts was studied. The yields of 5-arylfuran-2-carbaldehydes were found to depend on the solvent, catalyst, and anion in the arenediazonium salt. Redox catalysis and generation of aryl radicals are not sufficient conditions for the reaction to occur. The reaction is successful only under conditions ensuring formation of complex intermediates. A mechanism involving two Cu 2+ ↔ Cu + catalytic series and generation of furan-2-carbaldehyde was proposed.Interest in arylation of furan derivatives is largely determined by prospects in searching for biologically active substances among compounds of the furan series. Many furan derivatives are used as medicines [1,2]. Such medicines as Nitrafudan, Dantrolene, Clodanolene, and Azimilide contain an arylfuran fragment. Numerous arylfuran compounds exhibit versatile biological activity [2][3][4][5]. A convenient method for the synthesis of arylfurans is copper-catalyzed arylation of furan derivatives with arenediazonium salts according to Meerwein [4,[6][7][8][9][10][11][12]. These reactions were reported mainly for 2-substitued furans which underwent arylation at the 5-position (Scheme 1). furan derivatives follows a mechanism similar to one of the above reactions. In the first case, the reaction is redox catalytic, and it involves intermediate copper complexes [14,15], while in the second radical arylation occurs [7,13]. The ESR and polarographic data indicated generation of a radical adduct (arylfuryl radical) [16,17], and radical mechanism of the process was proposed.We performed a series of experiments on the arylation of furfurol with a view to elucidate in detail mechanism of this reaction. The following modes of generation of aryl radicals were tried: decomposition of N-nitrosoacetanilide, decomposition of diazonium salts in alkaline medium, on heating, and in the presence of potassium iodide, thermal and catalytic decomposition of diaryliodonium salts, reduction of diazonium salts with ascorbic acid, and their electrochemical reduction. The reagents and conditions were selected in such a way that the formation of intermediate complexes by the catalyst [Cu(I) or Cu(II)] with furfurol and diazonium salt be either favored or completely excluded.Using 4-nitrobenzenediazonium chloride (Ia) as an example we examined decomposition of diazonium salt in the presence of furfurol in alkaline medium (Gomberg reaction conditions) and on heating (Scheme 2). In the first case, 5-(4-nitrophenyl)furan-2-carbaldehyde (IIa) was obtained in 9% yield, and in the second case the yield of IIa was 11.5%. In both cases, the reactions were accompanied by considerable tarring. Standard Meerwein reaction conditions ensure 50-60% yield of aldehyde IIa. In the reaction of fur-

Thermodynamic properties of solubility of 2-methyl-5-arylfuran-3-carboxylic acids in organic solvents

“…One of the best approaches to the synthesis of functionalized arylfurans is Meerwein reaction [4][5][6][7][8].…”

Transition Metal‐Mediated Direct CH Arylation of Heteroarenes Involving Aryl Radicals

“…[51] The use of commercially available 4-nitrobenzenediazonium tetrafluoroborate was preferable to in situ generated 4-nitrobenzenediazonium chloride and sulScheme 14. Cu-catalyzed Meerwein arylation of coumarin with diazonium salts.…”

“…[64] In 2009, another mechanism was proposed and involved the reduction of CuCl 2 into CuCl by the olefinic substrate giving a radical cation. [65] Then copper(I) chloride reduces the arenediazonium salt and the generated aryl radical reacts with the olefin. In the same year this mechanism was criticized, since apparently nitrogen cannot be eliminated by reduction of the diazonium salt in the ground singlet state.…”

Synthesis antimicrobial and antitumor activities of 2-[5-(2-R-benzyl)thiazol-2-ylimino]thiazolidin-4-ones

“…At first stage diazonium salts 1a-e react with acroleine 2 in Meerwein reaction condition [33] to form 3-aryl-2chloropropanales 3a-e [17]. These aldehydes were converted into N-(5-R-benzyl-thiazol-2-yl)-2-chloroacetamides 6a-e in two stages according to the previously reported synthetic protocols [13].…”