Selective catalytic dehydration of furfuryl alcohol to 2, 2′-difurfuryl ether using a polyoxometalate catalyst

The spice flavour compound 2, 2′-difurfuryl ether (DFE) is widely utilised in the food industry as it has a coffee-like, nutty, earthy, mushroom-like odour. However, despite intensive research efforts, to date, an environmentally friendly and practical synthetic preparation technique for 2, 2′-difurfuryl ether is still unavailable. Here, we investigate a new approach using polyoxometalate catalysts to selectively catalytically dehydrate furfuryl alcohol to 2, 2′-difurfuryl ether. We have successfully applied this methodology using the polyoxometalate (POMs) catalyst {[(CH3CH2CH2CH2)4N]2[SMo12O40]} to produce 2,2′-difurfuryl ether in a 30.86% isolated yield.

in this study, we investigate the feasibility of using selective catalytic dehydration of furfuryl alcohol in the presence of various POM catalysts to produce 2, 2′-difurfuryl ether -thus producing a more environmentally friendly synthetic approach.
As with all catalysis, the first step in utilising POMs for the selective catalytic dehydration of furfuryl alcohol to 2, 2′-difurfuryl ether, will be to choose an appropriate POM catalyst. For thus, a series of POMs catalysts were prepared as summarised in Table 1 [27][28][29][30][31] . In order to relatively assess the utility of these synthetic catalysts a set of standard experimental conditions was employed (i.e., in toluene at 100 °C for 7 h). The results are given in Table 2, revealing catalytic activities in the following order: sulfo-polyoxometalates > quaternary ammonium phosphomolybdates > quaternary ammonium phosphotungstates and heteropolyacid salts. With respect to the heteropolyacid salts, the catalysts 4 d and 4 h showed greater yields (entry 4, 8 Table 2) than the other heteropolyacid salt catalysts (entry 1-8 Table 2). We also found that the heteropolyacid Al 3+ salts showed a much better catalytic ability than the Na + , K + and Fe 3+ salts. Furthermore, of the quaternary ammonium phosphomolybdates with the same phosphomolybdic group, we found that the character of the quaternary ammonium cation groups have a very limited influence on the catalytic activity (entries 13-17, Table 2). Moreover, although Mo and W belong to the same main group, they display difference catalytic activities in this reaction. We also found that the quaternary ammonium phosphomolybdates usually displayed better catalytic ability (entries 13-17, Table 2) than the quaternary ammonium phosphotungstates (entries 9-12,  Table 2), and the product was readily isolated and purified.
Whilst POMs were known as effective catalysts, reports generally focus on their chemical oxidation, electrochemical oxidation, reduction reactions, photochemical oxidation, base catalysed reactions, acid catalysis and  other reaction potential 32 . In this study, the reasons these different POMs catalysts showed different activities on this selective catalytic dehydration reaction were unclear. In order to optimise the synthetic conditions for DFE using the 4r POMs catalyst, we systematically varied the parameters of catalyst quantity and reaction time. The amount of catalyst 4r in the reaction was optimised firstly (entries 1-10, Table 3). We found that DFE was produced in the highest yield (26.90%) when 1% equivalent of the catalyst was used (entry 6, Table 3). The yield decreased significantly, from 26.90% to 8.29%, when the catalyst loading was lowered from 1% to 0.1% equivalents, whereas the yield did not increase with incremental catalyst loading from 1% to 5% equivalents. We subsequently optimised the reaction time, the results were shown in Table 3 (entries [11][12][13][14][15][16][17][18][19][20]. We found that the DFE yield increased gradually with extended reaction times from 1 h to 9 h (entries 11-19, Table 3), however, the yield did not increase furthermore up to 10 h (entries 19, 20, Table 3). Overall, the optimised conditions for DFE synthesis are a reation time of 9 h at 100 °C with a 1% equivalent of 4r catalyst, resulting in a yield of 34.50% (entries 19, Table 3). The reaction was repeated under the above optimised conditions and 2,2′-difurfuryl ether (DFE) was obtained in an average isolated yield of 30.86% 16,17 .
As per previous literature preparations of DFE 25 , other compounds appear in the oligomerization reaction (Fig. 2, Figure S1), as determined by GC/MS. As shown in Table 4, these include: compound 5 (5-furfuryl-furfuryl alcohol, Figure S5); compound 6 (2, 2′-difurylmethane, Figure S6) and compound 7 (2, 5-difurfurylfuran,    Figure S7). Although other compounds have been proposed as side-products in such reactions, we found no evidence of them under our experimental and equipment conditions. As shown in Tables 3 and 4, the reaction time has an obvious influence on the yields of compound 4 (DFE), compound 5, compound 6 and compound 7. As expected, the yields of compound 5, compound 6 and compound 7 decrease and yields of compound 4 increases with reaction time. The yield of compound 5 increased gradually with extended reaction times from 1 h to 7 h (entries 1-7, Table 4), but decreased with reaction time from 7 h to 10 h (entries 7-10, Table 4). Compound 5 was obtained in the highest yield of 20.30% after 7 h (entries 7, Table 4). The yield of compound 6 increased gradually with extended reaction times from 1 h to 6 h (entries 1-6, Table 4), but the yield decreased with reaction time from 6 h to 10 h (entries 6-10, Table 4). Compound 6 has the highest yield of 23.20% after 6 h (entries 6, Table 4). The yield of compound 7 increased gradually with extended reaction times from 1 h to 7 h (entries 1-7, Table 4), but the yield decreased with the increment of reaction time from 7 h to 10 h (entries 7-10, Table 4). Compound 7 has highest yield of 10.86% after 7 h (entries 7, Table 4). Therefore, it was fortunate that compound 4 (DFE) was obtained in the highest yield of 34.50% after 9 h (entries 19, Table 3). These results clearly illustrate that catalyst 4r was a strong candidate as a heterogeneous catalyst for the selective catalytic dehydration of FA to DFE.

Conclusions
In this paper, a comprehensive study on the utility of POMs catalysts for the selective catalytic dehydration of furfuryl alcohol to 2, 2′-difurfuryl ether has successfully been carried out. Through assessing a range of potential POMs catalysts, we found that {[(CH 3 CH 2 CH 2 CH 2 ) 4 N] 2 [SMo 12 O 40 ]} was the most effective, accomplishing the reaction in an overall 30.86% yield. Thus, we have present a novel synthetic avenue for the efficient and environmentally benign synthesis of 2, 2′-difurfuryl ether, which employs a inexpensive and simple POMs catalyst. Further studies are underway to further improve the yield of 2, 2′-difurfuryl ether using other POMs catalysts and various synthetic conditions.

Synthesis of the catalysts a-h.
All of the catalysts a-h were synthesised by the same approach. This method is illustrated following for catalyst 4a as an example.
A solution of H 3 PW 12 O 40 (2.88 g, 1 mmol) in deionized water (10 mL) was added into a 50 mL beaker. The reaction mixture was stir for 5 min at 25 °C, and Na 2 CO 3 (1.06 g, 10 mmol) in deionized water (10 mL) was added over 5 min. After addition, the mixture was stir for 1 h at 25 °C, then filtered and washed with deionized water and dried in vacuo and subsequently calcined at 450 °C for 2 h to afford 4a as a white solid (2.38 g, 81%) 33 . The elemental analysis data for the purified salts were as follows.  12 O 40 (1.82 g, 1 mmol) and deionized water (10 mL) were combined in a 50 mL three-neck flask. The mixture was stirred for 5 min at 25 °C and further cetylpyridinium chloride (0.36 g, 1 mmol) in deionized water (10 mL) was added after 5 min, then the mixture was stirred for 3 h at 25 °C. When filtered, the filtrate cake was washed with liquid and dried by vacuum to produce 4n (1.76 g, 82%) as a dark green solid. The elemental analysis data for the purified salts were as follows.   Table 4. The yields for the oligomerization reaction using the 4r catalyst. * Reaction conditions: FA (10 mmol), catalyst 4r (0.01 equiv.), toluene (10 mL) and 100 °C. GC yield.
Synthesis of the DFE. Each of the catalysts were employed, respectively, for this reaction and the overall synthetic conditions are illustrated following using 4r as an example (Fig. 3). FA (0.98 g, 10 mmol), 4r (0.23 g, 0.1 mmol, 1% equiv.) and toluene (10 mL) were added into a 50 mL three-neck flask. The mixture was stirred for 9 h at 100 °C. The toluene was subsequently removed under reduced pressure. The residue was extracted with ether, the organic phases were then washed with a saturated solution of Na 2 CO 3 and brine and then dried over MgSO 4 . After solvent removal, the residue was purified by flash chromatography on silica gel (petroleum/EtOAc, 40:1) to afford DFE as a colourless liquid (0.55 g, 30.86%). 1 Figure S4).