Effect of ultrasound-assisted crystallization in the diastereomeric salt resolution of tetramisole enantiomers in ternary system with O,O'-dibenzoyl-(2R,3R)-tartaric acid

Zsolt Szeleczky; Erzsébet Kis-Mihály; Sándor Semsey; Hajnalka Pataki; Péter Bagi; Emese Pálovics; György Marosi; György Pokol; Elemér Fogassy; János Madarász

doi:10.1016/j.ultsonch.2016.02.015

Effect of ultrasound-assisted crystallization in the diastereomeric salt resolution of tetramisole enantiomers in ternary system with O,O'-dibenzoyl-(2R,3R)-tartaric acid

Ultrason Sonochem. 2016 Sep:32:8-17. doi: 10.1016/j.ultsonch.2016.02.015. Epub 2016 Feb 13.

Affiliations

¹ Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary. Electronic address: szeleczky@mail.bme.hu.
² Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary.
³ Research Group for Organic Chemical Technology, Hungarian Academy of Sciences, 1521 Budapest, Hungary.
⁴ Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, 1521 Budapest, Hungary.

PMID: 27150740
DOI: 10.1016/j.ultsonch.2016.02.015

Abstract

The diastereomeric salt resolution of racemic tetramisole was studied using ultrasound irradiation. We examined the effect of power and duration of ultrasonic irradiation on the properties of the crystalline phase formed by ultrasound-assisted crystallization and the result of the whole optical resolution. The results were compared with reference experiment without using ultrasound. The US time (5-30min) caused higher enantiomeric excess. Although yield was lower continuously high resolving efficiency could have been reached through ultrasound. We had the best results with 4.3W ultrasound power when resolvability was even higher than the best of reference. Furthermore, we accomplished a deep and thorough examination of the salts that possibly could form in this resolution. One of the four diastereomeric salts, which have been identified by powder X-ray diffraction, FTIR-spectroscopy, and differential scanning calorimetry (DSC) in the ternary system of the two tetramisole enantiomers and the resolving agent, namely the bis[(S)-tetramisole]-dibenzoyl-(R,R)-tartrate salt have been proven the key compound in the resolution process, and presented the highest melting point of 166°C (dec.) among the four salts. The originally expected diastereomeric bitartrate salts with 1:1M base:acid ratio [(S)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt and (R)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt] and their 'racemic' co-crystal [(RS)-tetramisole-dibenzoyl-(R,R)-hydrogen-tartrate salt] showed somewhat lower melting points (152, 145, and 150°C, respectively) and their crystallization was also prevented by application of ultrasound. Based on the melting points and enthalpies of fusion measured by DSC, all the binary and ternary phase diagrams have been newly established and calculated in the system with help of classical modelling equations of liquidus curves.

Keywords: Diastereomeric salt; Optical resolution; Sonocrystallization; Ternary and binary phase diagrams; Tetramisole (Levamisole).

Publication types

Research Support, Non-U.S. Gov't