Interaction of thiophene enamino ester 1a,b with the acid chloride of p-tolyl sulphonamido-N-acetic acid derivatives 2a-cafforded the corresponding amide derivatives respectively 3a-f. Hydrazinolysis of 3a-f with hydrazine hydrate yielded 4a-f. Diazotization of 1a then coupling with different amines gave 6a,b. compounds 7a,b was afforded when diazonium chloride of p-toludin or enamino thiophene 3-carboxylate (5) was reacted with compound 1a. Air oxidation of 6a yielded 8. Coupling was carried out with different amines compounds where 5 yielded 9a,b. According to Gewald method 11a-b was prepared from reaction of 10a,bwith malononitrile, From 11a,bwe can prepare compounds 13, 14a-c, 15a-c 16a,b, 17a,b, 18, 19 and 20. The structure of these compounds was confirmed by infrared, mass, H-NMR spectra the biological activity of some compounds were discussed and found to be active.