Abstract: Continuous-flow upgrading of pentaerythritol synthesis technology via base-catalyzed aldol and Cannizzaro reactions of formaldehyde and acetaldehyde faces the challenge of effectively controlling the critical side reaction of hydroxymethyl acetaldehyde (HA) to the acrolein intermediate. Here, we first identified the forms of industrial formaldehyde as methane diol that easily converts to the alkaline formaldehyde under alkaline (NaOH) environment. The carbonyl group of alkaline formaldehyde induces deprotonation of acetaldehyde instead of the recognized base-hydroxyl group-induced deprotonation, and it needs to overcome only 18.31 kcal·mol^-1 (1 kcal = 4.186 kJ) energy barrier to form key intermediates of HA. The sodium solvation cage formed by NaOH hexa-coordinated formaldehyde effectively inhibits the alkalinity, thus contributing to a high energy barrier (46.21 kcal·mol^-1) to unwanted acrolein formation. In addition, the solvation cage gradually opens to increase the alkalinity with the consumption of formaldehyde, thus facilitating the subsequent Cannizzaro reaction (to overcome 11.77 kcal·mol^-1). In comparison, strong alkalinity promotes the formation of acrolein (36.65 kcal·mol^-1) to initiate the acetal side reaction, while weak alkalinity reduces the possibility of the Cannizzaro reaction (to overcome 20.44 kcal·mol^-1). This theoretically reveals the importance of the segmented feeding of weak and strong bases to successively control the aldol reaction and Cannizzaro reaction, and the combination of Na₂CO₃ or HCOONa with NaOH improves the pentaerythritol yield by 7% to 13% compared to that of NaOH alone (70% yield) within 1 min at a throughput of 155.7 ml·min^-1.

Key words: Alkaline formaldehyde, Sodium solvation cage, Aldol reaction, Cannizzaro reaction, Continuous-flow, Pentaerythritol

摘要： Continuous-flow upgrading of pentaerythritol synthesis technology via base-catalyzed aldol and Cannizzaro reactions of formaldehyde and acetaldehyde faces the challenge of effectively controlling the critical side reaction of hydroxymethyl acetaldehyde (HA) to the acrolein intermediate. Here, we first identified the forms of industrial formaldehyde as methane diol that easily converts to the alkaline formaldehyde under alkaline (NaOH) environment. The carbonyl group of alkaline formaldehyde induces deprotonation of acetaldehyde instead of the recognized base-hydroxyl group-induced deprotonation, and it needs to overcome only 18.31 kcal·mol^-1 (1 kcal = 4.186 kJ) energy barrier to form key intermediates of HA. The sodium solvation cage formed by NaOH hexa-coordinated formaldehyde effectively inhibits the alkalinity, thus contributing to a high energy barrier (46.21 kcal·mol^-1) to unwanted acrolein formation. In addition, the solvation cage gradually opens to increase the alkalinity with the consumption of formaldehyde, thus facilitating the subsequent Cannizzaro reaction (to overcome 11.77 kcal·mol^-1). In comparison, strong alkalinity promotes the formation of acrolein (36.65 kcal·mol^-1) to initiate the acetal side reaction, while weak alkalinity reduces the possibility of the Cannizzaro reaction (to overcome 20.44 kcal·mol^-1). This theoretically reveals the importance of the segmented feeding of weak and strong bases to successively control the aldol reaction and Cannizzaro reaction, and the combination of Na₂CO₃ or HCOONa with NaOH improves the pentaerythritol yield by 7% to 13% compared to that of NaOH alone (70% yield) within 1 min at a throughput of 155.7 ml·min^-1.

关键词: Alkaline formaldehyde, Sodium solvation cage, Aldol reaction, Cannizzaro reaction, Continuous-flow, Pentaerythritol