Mechanism of reaction of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) with nucleophiles and its crystal structure
Abstract
Hydrolysis of the title compound (1) occurs via reaction of the protonated species (16) with H2O or HO–. The high basicity of (1)[pKa of (1H+) is 4.22], which is necessary for high reactivity, is shown by analogues with 2-aryloxy- or 2-alkoxy-substituents, but not by 2-cyano-compounds [Reissert compounds (11)] or by 3,4-dihydroquinolines (10). 1-Aryl- or 1-alkyl-oxycarbonyl-substituents have the largest effect on reactivity [e.g. the pKa of (14H+) is 2.3 and its rate of reaction is increased 160-fold relative to (1H+)] suggesting that reaction of nucleophile initially occurs at this site. Both acetate and amine (trifluoroethylamine) buffers react with (1) by similar mechanisms involving reaction between (1H+) and either AcO– or free amine; the reaction-rate–pH profiles are ‘bell-shaped.’ A new mechanism for the reaction of (1) as a reagent to promote peptide synthesis is suggested. Crystals of (1) are monoclinic, space group P21/n, with Z= 4 in a unit cell of dimensions a= 12.608(2), b= 7.644(1), c= 13.374(2)Å, β= 99.06(2)°. The structure was determined by direct methods from four-circle diffractometer data and refined to a final R value of 5.47% from 1 490 observed reflections.