Preferential formation of specific hexose and heptose in the formose reaction under microwave irradiation

Abstract

To realize sustainable societies, the production of organic compounds not based on fossil resources should be developed. Thus, C1 chemistry, utilizing one-carbon compounds as starting materials, has been of increasing importance. In particular, the formose reaction is promising because the reaction produces sugars (monosaccharides) from formaldehyde under basic conditions. On the other hand, since microwave (MW) induces the rotational motion of molecules, MW irradiation often improves the selectivity and efficiency of reactions. In this study, the formose reaction under MW irradiation was thus investigated under various conditions. The formose reaction proceeded very fast using 1.0 mol per kg formaldehyde and 55 mmol per kg calcium hydroxide (Ca(OH)₂) as a catalyst at a high set temperature (150 °C) for a short time (1 min) to form preferentially specific hexose and heptose. The major products were isolated by thin layer chromatography and characterized by mass spectroscopy and NMR. These characterization data elucidated that the hexose and heptose were 2-hydroxymethyl-1,2,4,5-tetrahydroxy-3-pentanone (C6*) and 2,4-bis(hydroxymethyl)-1,2,4,5-tetrahydroxy-3-pentanone (C7*), respectively. On the basis of these observations, as well as density functional theory calculations, a plausible reaction pathway was also discussed; once 1,3-dihydroxyacetone is formed, consecutive aldol reactions favorably occur to form C6* and C7*.

Fig. 1. Formose reaction under MW irradiation using 1.0 mol per kg formaldehyde and Ca(OH)₂ under various conditions. (A) The conversion of formose reaction carried out at a set temperature of 150 °C for 1 (red circle), 3 (green square), and 5 min (blue triangle) using varying concentrations of Ca(OH)₂. (B) Time-conversion plots for formose reaction carried out using 55 mmol per kg Ca(OH)₂ at set temperatures of 150 (red circle), 100 (orange square), and 60 °C (dark yellow triangle). (C) HPLC charts for the products of formose reaction carried out at a set temperature of 150 °C for 1 min using (a) 47, (b) 54, (c) 55, (d) 57, and (e) 94 mmol per kg Ca(OH)₂. (D) HPLC charts for the products of formose reaction carried out using 55 mmol per kg Ca(OH)₂ at set temperatures of (a) 150, (b) 100, and (c) 60 °C for 1, 20, and 360 min, respectively.

Fig. 2. Purification and characterization of the major products (heptose C7* and hexose C6*) of formose reaction under MW irradiation using 1.0 mol per kg formaldehyde and 55 mmol per kg Ca(OH)₂ at a set temperature of 150 °C for 1 min. (A) A photograph of a TLC plate for separation of the major products. (B) MS for C7* (upper) and C6* (lower). (C) ¹H NMR spectra for C7* (upper) and C6* (lower) (D₂O). (D) ¹³C NMR spectra for C7* (upper) and C6* (lower) (D₂O).

Fig. 3. Plausible reaction pathways for the preferential formation of C6* and C7* in the formose reaction under MW irradiation.