Crystallization of R-(+)-atenolol hydrochloride from racemic ionic liquid - A selective double decomposition green reaction

Atenolol is a cardioselective antihypertensive drug. It is classified under arylethanolamine β adrenergic receptor antagonists. Hypotensive action for this racemic drug was found to be selective for the S-(−)- β receptor blocking stereoisomer as this enantiomer was found to have 20 fold greater affinity for β1 adrenoreceptors when compared to β2 adrenoreceptors of human heart muscle. Albeit the action of the drug was mentioned as stereoselective, atenolol is always administered as racemic mixture only. Recently several adverse drug reports were published on atenolol treatment and the study suggested for intensive research on structure activity relationship of R-(+)-stereoisomer. In this study, we report the solid state structure of R-(+)-atenolol for the first time as hydrochloride salt. We also report a unique resolution process based on ionic liquid formation for obtaining this stereoisomer. The process is first of its kind for a pharmaceutical ionic liquid material. We believe that the atomic structure of R-(+)-stereoisomer will significantly contribute for understanding its biological activity when compared to its counter enantiomer.