Amlodipine Benzenesulfonate: A Mechanistic Investigation of Its Industrial Preparation via Detritylation of N-tritylamlodipine and Related NMR Studies
(2009) Croatica Chemica Acta — Vol. 82, n° 1, p. 299-309 (2009)
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- Abstract
- Kinetics and product analysis of detritylation of N-tritylamlodipine by benzenesulfonic acid in methanol, methanol-chloroform (volume ratio 9:1), ethanol, 2-propanol, and methanol/2-propanol (mole ratio 1:1) have been investigated by HPLC; amongst these reaction conditions are ones closely similar to those of one method of manufacturing amlodipine benzenesulfonate. Kinetics of detritylation of N-tritylamlodipine have also been investigated in methanol-d(4) by H-1 NMR spectroscopy and the agreement with the results by HPLC is good. The rate of detritylation increases with increasing concentrations of benzenesulfonic acid, and p-methoxy-substituents in the trityl group have been shown to lead to faster reactions. In methanol, the rate is hardly affected by 10 % (vol. fraction) chloroform. These studies relate to mechanistic investigations of acid-catalysed deaminations of methoxy-substituted tritylalkylamines, and Arrhenius activation parameters (E-a and A) are similar indicating a common generic mechanism. Acid-catalysed traps-esterification has been shown by HPLC to accompany detritylation in methanol, and attendant protium-deuterium exchange in the methyl at C6 by reversible acid-catalysed iminium ion formation in the 4-aryl-1,4-dihydropyridine moiety of both N-tritylamlodipine and amlodipine has been investigated in deuteriated methanol by H-1, C-13, and N-15 NMR spectroscopy.
- Affiliations
Masaryk University Department of chemistry
Citations
Furlan, B., Grdadolnik, S. G., Hocevar, S., Kocjan, D., Levec, J., Maskill, H., Navratilova, H., Pospisil, J., Potacek, M., Urleb, U., & Zmitek, J. (2009). Amlodipine Benzenesulfonate: A Mechanistic Investigation of Its Industrial Preparation via Detritylation of N-tritylamlodipine and Related NMR Studies. Croatica Chemica Acta, 82(1), 299-309. https://hdl.handle.net/2078.5/42228 (Original work published 2009)