Interaction of triols with formaldehyde and acetone: Experimental and theoretical study

Experimental and theoretical aspects of the condensation of glycerol and its homologs (1,2,3‐ and 1,2,4‐butanetriols) with formaldehyde and acetone are studied under conditions of acid catalysis. Calculation of the thermodynamic parameters of the resulting products by the composite method CBS‐QB3 shows that the six‐membered heterocycles, the products of the interaction of triols with formaldehyde, are thermodynamically more stable than the five‐membered acetals, while the reaction of the same triols with acetone is preferable for the formation of the five‐membered acetals. This is due to the fact that the regioselectivity of the studied reactions is determined by the structural features and reactivity of the carbocations formed in a condensed medium during the course of the reaction. According to the theoretical data obtained experimentally, during the condensation of glycerol and 1,2,4‐butanetriol with formaldehyde in the most stable form of the six‐membered cyclic carbocation, intramolecular hydrogen bonding and anomeric stabilization due to the axially oriented hydroxyl group take place. As a result, cation 1b–1 is 1.2–1.6 kJ/mol more stable than its five‐membered isomers (1a–1 and 1b–2). It leads to the predominant formation of 1,3‐dioxane (3b). However, upon condensation of butanetriol‐1,2,3 with formaldehyde, the intermediate cation 4a–1 turns out to be significantly more stable than the other isomers due to the strong intramolecular hydrogen bond in the six‐membered ring with the participation of the hydroxyl group of the substituent and the hydroxyl group of the cationic center, leading to the predominant formation of the dioxolane 6a. The experimental and theoretical aspects of the condensation of glycerol and its homologs (1,2,3‐ and 1,2,4‐butanetriols) with formaldehyde and acetone are studied under conditions of acid catalysis. It is shown that the regioselectivity of the reaction is determined by the stability of the intermediate cation.