Assembly of fully substituted 2,5-dihydrothiophenes via a novel sequential multicomponent reaction

Abstract

A sequential multicomponent reaction between ketoesters, isothiocyanates and 1,2-diaza-1,3-dienes to create 2,5-dihydrothiophenes that can be converted into thiophenes.

1,2‐Diaza‐1,3‐diene‐Based Multicomponent Reactions in Sequential Protocols to Synthesize Arylamino‐5‐hydrazonothiophene‐3‐carboxylates

“…The subsequent decarboxylation promotes the aromatization of the ring (Scheme , Path A). As previously reported, the same DHT 1 , treated with Amberlyst 15H in a mixture of acetone/water, produces 5‐(arylamino)thiophene‐2,4‐dicarboxylates (ATDs) 3 (Scheme , Path B). In this latter case, to the expected hydrolysis of the hydrazone function, a retro Claisen reaction follows favoured by the acidic conditions.…”

“…Our investigations begin to tentatively transform the DHT 1a into the corresponding spiro 2,5‐dihydrothiophen‐pyrazolon‐5‐one A following the procedure previously employed for this type of cyclization (Path a, Table )…”

“…Divergent aromatization process of 2,5‐dihydrothiophenes (DHT) 1 to produce 2‐arylamino‐5‐hydrazonothiophene‐3‐carboxylates (AHTs) 2a – g by basic treatment, or 5‐(arylamino)thiophene‐2,4‐dicarboxylates (ATDs) 3 under acidic conditions …”

“…This circumstance requires an adjustment of the reactions conditions previously employed (Table ) . As described, initially in order to prepare the enamino ester intermediates 6 under solvent free conditions, to n ‐butylamine (1.0 mmol) various β‐keto ester derivatives 5a – c were added (1.1 mmol) obtaining quantitatively the corresponding enamino ester intermediates 6 in 0.5 h (Table ) .…”

“…The aromatization process probably took place through hydrolysis of the hydrazone function and subsequent retro‐Claisen reaction . Now, to further extend the scope of this sequential three component [C+CC+CS] annulation, we have developed the regioselective synthesis of new 2‐arylamino‐5‐hydrazono‐thiophene‐3‐carboxylates (AHT).…”