The stability and the reactivity of mono- and diprotonated 4-heterocyclohexanones as well as cyclohexanone in triflic acid have been studied at the PBE0/aug-cc-pvtz//PBE0/6-31+G** level of theory. In all cases the first protonation is an exergonic process occurring at a carbonyl oxygen except for 4-piperidone where a nitrogen atom is protonated fist. Second protonation is only slightly endergonic for all studied molecules except for cyclohexanone where the second protonation is very unfavorable thermodynamically. According to calculations, diprotonated 4-heterocyclohexanones are much more active in the reactions of triflic acid mediated polyalkoxyalkylation with aromatic hydrocarbons compared to monoprotonated ones. The increase of the reactivity of diprotonated 4-heterocyclohexanones is due to inductive effect rather than through space electrostatic influence as follows from the electronic structure analysis of dications. Moreover, the second protonation reduces the possibility of an aldol condensation side reaction, reducing the enol electrophilicity rendering heterocyclohexanones as promising monomers for superacid mediated polyhydroxyalkylation.

Mono‐ and diprotonated reaction intermediates involved in the acid‐catalyzed polyhydroxyalkylation of aldehydes and ketones of the general formula R1COR2, (R1 = H, CH3, CF3 and R2 = Ph, CH3, CF3) with benzene and biphenyl, were studied theoretically at PBE0/aug‐cc‐PVTZ//PBE0/6‐31 + G** level of theory. The calculations performed for sulfuric acid and TFSA‐catalyzed reactions showed that for all studied reactions the enhancement of the reactivity of diprotonated species is not sufficient to compensate for the large positive Gibbs energy of second protonation. An alternative mechanism has been proposed for the reaction between benzene and benzaldehyde in TFSA involving only monoprotonated species. The low reactivity of carbonyl compounds with electron donating substituents is due to excessive stabilization of monoprotonated species rendering the reaction thermodynamically impossible.magnified image

Cover: The picture shows that diprotonation of carbonyl compounds does not occur in triflic acid. The triflic acid mediated reaction of polyhydroxyalkylation of aromatic hydrocarbons involves only monoprotonated species. The reactivity of carbonyl molecules is governed by electronic effects of the groups linked directly to the carbonyl. Strong donor and strong electron withdrawing groups reduce the reactivity of carbonyl group as electrophile; in the first case the protonation leads to the formation of excessively stable cation, in the second one monoprotonation is impossible thermodynamically.