Tresyl-mediated synthesis: Kinetics of competing coupling and hydrolysis reactions as a function of pH, temperature, and steric factors

Kinetic parameters have been measured for coupled nucleophilic and solvolyt ic reactions of 2,2,2-trifluoroethanesulfonyl (tresyl)-modified poly(ethyle ne glycol) based on a system of coupled differential equations implied by r ecently proposed elementary reaction mechanisms. Fitted kinetic parameters were found to be strong functions of pH, temperature, and steric factors. T o maximize the total yield of coupled amine as well as the fraction of seco ndary amine linkages, our model predicts that it is desirable to run tresyl coupling reactions at low temperatures at pH similar to 8.0, depending on the amine pK(a) for primary, unhindered amines. For branched primary amines , our data favor room temperature at a slightly higher pH.