Solid state and solution structure of a commonly used peptide coupling additive

Abstract

The crystal structure of the 1-hydroxy-7-azabenzotriazole (HOAt) peptide coupling additive was determined by X-ray structure analysis. Additionally, HOAt and 1-hydroxy-benzotriazole (HOBt) were investigated by means of IR spectroscopy in the solid as well as in solution. HOAt crystallizes in the monoclinic space group C2/c with eight molecules in a unit cell of the following dimensions: a = 22.091(4) Å, b = 3.994(1) Å, c = 14.294(3) Å, β = 114.83(3)°. The structure was solved by direct methods and refined on F2 to R values of wR2 = 0.106 and R1 = 0.038, respectively, for 1344 observed unique reflections. The molecules of HOAt are associated into dimers by intermolecular hydrogen bonds between their hydroxy groups and the azanitrogen atoms of the six membered sub-ring. The molecules of the dimers are roof-like inclined towards each other. The dimers are packed in columns with an antiparallel orientation. Dimers are still present in solution. The molecular structures of HOAt and HOBt are similar, but the crystal packings differ as a result of formation of other hydrogen bonds.