Kinetic study on the esterification of hexanoic acid with N,N-dialkylamino alcohols: Evidence for an activation by hydrogen bonding

The pseudo-first order rate constant for the esterification of hexanoic acid (1) and five different N,N-dialkylamino alcohols (2) was determined in comparison to 1-hexanol (k = 0.67 · 10^-5 s^-1). The values range from 0.60 · 10^-5 s^-1 to 9.3 · 10^-5 s^-1. The data suggest a differing reactivity for structurally related compounds, which is directly correlated to the ability of the corresponding amino alcohol to activate the carboxylic acid by hydrogen bonding. A seven-membered transition state C≠ is postulated for reactions of 2-amino alcohols. The fastest reaction was observed for trans-2-(N,N- dimethylamino)cyclohexanol (2e), in which the amino and the hydroxyl groups are in an almost perfect synperiplanar 1,2-position. Attempts to further enhance the rate of the esterification by the addition of potential catalysts failed. Only Cu(OTf)₂ (2.5 mol-%) allowed for a moderate rate increase from 7.5 · 10^-5 s^-1 (uncatalyzed) to 14.8 · 10 ^-5 s^-1 (catalyzed) in the esterification of hexanoic acid (1) with 2-(N,N-dimethylamino)ethanol (2a).