Effect of acids on isomer formation of tricyclic antidepresant drugs

Doxepin and Dothiepin belonging to tricyclic antidepressants exists as a mixture of E & Z isomers; whereas the activity of Doxepin and Dothiepin is attributed to there E-isomers. Therefore in the present study doxepin and dothiepin have been synthesized and separation of E and Z isomers was achieved by HPLC to know the percentage of E isomer in doxepin and Dothiepin. Since the activity of doxepin and dothipin is dependent on the E isomer effects of various acids in the formation of E isomer is dealt with. Doxepin and dothiepin synthesis in the penultimate step involves the dehydration of (11RS)-11[3-(dimethylamino)propyl]-611- dihydrodibenzo[be]oxepin-11-ol and (11RS)-11[3-(dimethylamino)propyl]-611-dihydrodibenzo[be]thiepin-11-ol by acid leading to formation E and Z isomers. In this study attempts have been made to study the effects of various acids such as oxalic acid maleic acid phosphoric acid p-toluyl sulphonic acid Indian resin-220 and tartaric acid in improving the formation E isomer and reduction in the formation of Z-isomer. E -isomer formation was found to be optimum with the use of tartaric acid Indian resin-220 and p-toluyl sulphonic acid.