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...