A theoretical investigation to understand the difference in reactivities of secondary and tertiary propargylic alcohols with 1,3,5-trimethoxybenzene in presence of Brnøsted acid

The work presented here establishes the experimental findings of the reaction between secondary/tertiary propargylic alcohol (PA) and 1,3,5-trimethoxybenzene (TMB) in the presence of acetonitrile solvent (MeCN) based on theoretical calculations. When secondary PA reacts, the reaction goes via S_N2 pathway, where the reaction barrier is about 14.32 kcal/mol. On the other hand, tertiary PA reacts with TMB via S_N2′ and S_N1′ pathway, and the corresponding reaction barriers are 17.59 and 17.86 kcal/mol. Other possible pathways, namely, S_N1, S_N1′, etc. for secondary PA, and S_N2, S_N1 pathways for tertiary PA are also investigated and the associated barrier heights are found higher. Rates of those reactions are also calculated considering the rate-determining steps only. Reaction of secondary PA with TMB is found to be much faster than the reaction of tertiary PA and the results are in accordance with the experimental findings.