Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

The reaction of 5-hydroxymethylfurfural (5-HMF) with arenes in superacidic trifluoromethanesulfonic acid (triflic acid, TfOH) as the solvent at room temperature for 1–24 h gives rise to 5-arylmethylfurfurals (yields of 17–91%) and 2-arylmethyl-5-(diarylmethyl)furans (yields of 10–37%). The formation of these two types of reaction products depends on the nucleophilicity of the arene. The same reactions under the action of acidic zeolites H-USY in high pressure tubes at 130 °C for 1 h result in the formation of only 5-arylmethylfurfurals (yields of 45–79%). 2,5-Diformylfuran (2,5-DFF) in the reaction with arenes under the action of AlBr3 at room temperature for 1 h leads to 5-(diarylmethyl)furfurals (yields of 51–90%). The reactive protonated species of 5-HMF and 2,5-DFF were characterized by NMR spectroscopy in TfOH and studied by DFT calculations. These reactions show possibilities of organic synthesis based on biomass-derived 5-HMF and 2,5-DFF.


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(standard 6-311 basis set added with polarization (d,p) and diffuse functions). Optimizations were performed on all degrees of freedom and solvent-phase optimized structures were verified as true minima with no imaginary frequencies. The Hessian matrix was calculated analytically for the optimized structures in order to prove the location of correct minima and to estimate the thermodynamic parameters. Solvent-phase calculations used the Polarizable Continuum Model (PCM). 5-Chloromethylfurfural (1b) and 5-bromomethylfurfural (1c) were obtained from D-fructose according to the literature procedure 4 .
General procedure for the reaction of furans 1a-c, 2 with arenes in TfOH (Tables 3-5). Furan 1a-c or 2 (1 mmol) was added to the mixture of TfOH (2 mL) and arene [benzene (1 mL, see Tables 3 and 5) and other arenes (1.2-10 mmol, see Table 4). The reaction mixture was stirred at room temperature for the time indicated in Tables 3-5. The mixture was poured into water (30 mL), and extracted with chloroform (3 × 30 mL). The combined extracts were washed with water, saturated aqueous solution of NaHCO 3 , water again, and dried over Na 2 SO 4 . The solvent was removed under reduced pressure, and the residue was subjected to chromatographic separation on silica gel using hexanes-ethyl acetate as an eluent.
In the same manner the reactions were carried out in H 2 SO 4 for 1a (entry 5, Table 3) and 2 (entry 3, Table 5) and quenched as described above.
Reaction of 2 with benzene was carried out in HSO 3 F (2 mL) and SO 2 (1.5 mL) at −45 °C for 2 h (entry 4, Table 5), followed by quenching with concentrated aqueous hydrochloric acid frozen down to −80 °C (30 mL), then diluted with water (50 mL). Extraction and work-up as described above.
General procedure for the reaction of furans 1a, 2 with arenes under the action of AlX 3 (X = Cl, Br) (Tables 3 and 5). Furan 1a or 2 (1 mmol) was added to the mixture of AlX 3 (X = Cl, Br) (5 mmol) and arene (5 mL). The reaction mixture was stirred at room temperature for 1 h, then poured into water (50 mL) and extracted with chloroform (3 × 30 mL). The combined extracts were washed with water, saturated aqueous solution of NaHCO 3 , water again, and dried over Na 2 SO 4 . The solvent was distilled off under reduced pressure, and the residue was subjected to chromatographic separation on silica gel using hexanes-ethyl acetate as an eluent.
Yields of the obtained compounds 5a-g are given in Table 5.
The resulting suspension was magnetically stirred at 130 °C for 1-10 h (see time in Tables 3-5).