[New findings on the synthesis of the centrally acting muscle relaxant chlormezanone and its resolution of a gram scale using a Chiralcel OD column].
2-(4-Chlorophenyl)-4-metathiazanone (2) is the intermediate product for the two step-synthesis of chlormezanone (1), a centrally acting muscle relaxant. The second step includes the oxidation of its sulfur atom. It has been found that the foregoing reaction of 4-chlorobenzaldehyde with methylamine forming the hemiaminale and the subsequent addition of beta-mercaptopropionic acid leads to a remarkable better yield (67% of th.) than the route via the hemimercaptale (42% of th.). 2 could be oxidized with sodium perborate superior to potassium permanganate. The racemic chlormezanone (1) is resolved quickly on a gram scale by preparative column chromatography on a Chiralcel OD column (tris(3,5-dimethyl-phenyl-carbamoyl)cellulose on silicagel). The resolution needed only 40 min, if flow rate, composition of the mobile phase and temperature as the most important factors are determined prior with an analytical column. Both dissociation constants could be determined for the first time with the aid of a log pKa-Titrator of the Sirius Co., which needs for the registration of the curves only 15-17 min in the pH range of 2-12. This speed outplayed the disturbing cleavage of the S-C bond of chlormezanone at strong acidic and alkaline pH values.
Oelschläger
H
H
Institut für Pharmazie der Friedrich-Schiller-Universität Jena, Germany. b8oehe@rz-uni-jena.de
Wange
J
J
Letsch
J
J
Seeling
A
A
D002720:Chlormezanone / Q000138:chemical synthesis* / Q000737:chemistry; D002852:Chromatography, Ion Exchange; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013696:Temperature
D007202:Indicators and Reagents; D009125:Muscle Relaxants, Central; D002720:Chlormezanone