Solubility and salting behavior of several beta-adrenergic blocking agents in liquid and supercritical carbon dioxide

摘要

The phase behavior of five beta-adrenergic blocking agents (acebutolol, atenolol, nadolol, pindolol, and propranolol) were explored in liquid and supercritical carbon dioxide at (298, 308, and 318) K and at pressures between (80 and 275) bar. The solubility of the solids in carbon dioxide was experimentally determined by observing the cloud point using a variable-volume stirred vessel with visual access. Although these compounds are very similar structurally, each containing a secondary amine, alcohol, aromatic ring, and ether group, only pindolol was soluble in carbon dioxide under the conditions explored. The other four beta blockers were observed to form yellow-brown salt complexes with carbon dioxide and did not show any appreciable solubility. It is believed that pindolol's lower basicity (having a K-b an order of magnitude lower than the other four compounds) prevented it from reacting with carbon dioxide, a Lewis acid, and salting out as the other four beta blockers did.