Structural study of the solid-state ring-closure reaction of (2R,3R)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionic acid

The crystal structure of the (2R,3R)-(-)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionic acid has been determined from single-crystal X-ray diffraction data in order to study the solid state ring closure reaction between the carboxylic acid and the amino substituent. This reaction occurs only in the optically active crystals, whereas the racemate reacts only in melt or solution. (2R,3R)-(-)-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl)propionic acid (C16H17NO4S) crystallizes in the monoclinic space group P2(1) with a = 14.240(2), b = 5.3154(11), c = 19.535(6) Angstrom, beta = 91.93(2)degrees, V = 1477.8(6) Angstrom(3), Z = 4, D-x = 1.435 g cm(-3), mu = 20.63 cm(-1). The two independent molecules differ in their protonization: one is a cation and the other is an anion. A very short hydrogen bond [O ... O = 2.480(6) Angstrom] links the carboxylic acid and the carboxylate groups. The two molecules adopt different conformations: one has an extended structure whereas the other has the amino group close to the carboxylate group. The latter molecule requires only minor changes for the solid-state reaction to take place forming the seven-membered ring. From the analysis of the hydrogen-bonding pattern a reaction mechanism for the ring closure reaction is proposed.