Study On Chiral Resolution Of Citalopram Intermediate

Adsorbents were synthesized and the separation performance of intermediate enantiomers of antidepressant drug Citalopram was characterized. Adsorbents were perpaerd through the reaction of microcrystalline cellulose(MCC) with an excess of benzoyl chloride and isocyanates respectively. Structures of the synthesized adsorbents were analyzed using Elementary Aanlysis, Fourier transform infared, and the separation performance of Citalopram intermediate(CITI) enantiomers was evaluated using Circular Dichroism. Major conclusions were obtained as below.1) It is indicated that the synthesized cellulose benzoate is not capable of separating the intermediate CITI enantiomers, while the cellulose phenylcarbamate shows good chiral separation of the CITI enantiomers.2) Based on orthogonal design experiments, the optimal reaction conditions for synthesis of cellulose phenylcarbamate are: the swelling time in pyridine = 1 h, reaction temperature = 105℃, and the molar ratio of isocyanates to MCC = 4.0, the precipitation period in methanol = 10 min.3) Solvents greatly affects the separation performance of the adsorbent. Using anhydrous ethanol as the solvent, the circular dichroismΔεmin of the CITI solution is changed from the initial zero to -18.4 after being adsorbed by cellulose phenylcarbamate for 1 h. When using organic mixture as the solvent, the chiral separation performance is depend on the composition of the mixed solvent. Taking the mixed n-hexane and ethanol(3:17,V/V) as the solvent, the adsorbed CITI solution shows a circular dichroism up to -25.3.