An Improved Method for the Preparation of 4,7-Dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates from 2-Acyl-1,4-benzoquinones and Mercaptoacetates

Abstract

4,thiophene-2-carboxylates (4) have been synthesized in a one-pot procedure from 2-acyl-1,4-benzoquinones (1) and mercaptoacetates (2) by using 1-trimethylsilylimidazole as a protective reagent as well as a base.Thus, reaction of 1 with 2 in THF at room temperature was followed by treatment with excess of 1-trimethylsilylimidazole at 80 ˚C.Then the cooled mixture was hydrolyzed with hydrochloric acid and oxidized with cerium(IV) ammonium nitrate (CAN) to give the expected thiophenequinone derivatives (4).4,thiophene-2-carboxylates (7) were similarly prepared from 2-acyl-1,4-naphthoquinones (5 ) and mercaptoacetates, in general, by omitting the CAN oxidation procedure.The compounds based on benzo[b]thiophene-4,7-dione or naphtho[2,3-b]thiophene-4,9-dione skeletons have received considerable attention because of their synthetic, 1 biological, 2 and industrial utilities. 3 Accordingly, a number of approaches to the construction of these systems have been developed. 4,5 Valderrama et al. have reported 6 that methyl 4,7-dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates are prepared from 2-acyl-1,4-benzoquinones and methyl mercaptoacetate in two to four step sequences.As a part of our study on the syntheses of heterocycle-fused quinone derivatives, 5,7 we investigated the possibility of modifying this method of Valderrama to a general and one-pot procedure to prepare benzo[b]thiophene-4,7-dione (4) and naphtho[2,3-b]thiophene-4,9-dione derivatives (7) as illustrated in Schemes 1 and 2, respectively.The success in our approach is attributable to the use of 1trimethylsilylimidazole, which serves as both of a protective reagent and a base and provides easyThe reactions for the preparation of 4,7-dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates (4) were carried out as depicted in Scheme 1.Thus, 2-acyl-1,4-benzoquinones (1) were treated with mercaptoacetates (2) in THF at room temperature.After removal of THF under reduced pressure, to the resulting 3-sulfenylated hydroquinone derivatives (3) was added excess 1-trimethylsilylimidazole to protect the hydroxy groups 8 and conduct thiophene ring formation, affording the 4,7bis(trimethylsiloxy)benzo[b]thiophene-2-carboxylates.The reaction mixtures were then treated with aqueous HCl to deprotect the trimethylsilyl ethers and the resulting hydroquinones were exposed with CAN to give the expected thiophenequinone derivatives (4) in good yields.All these manipulations could be carried out in one-pot.When one of the 3-sulfenylated hydroquinone derivatives (3) was treated with two equivalents of 1-trimethylsilylimidazole, no thiophene ring formation occurred.This result indicates that imidazole, generated by the protection of a hydroxy group, cannot work as a base.The use of excess 1-trimethylsilylimidazole was essential for the satisfactory formation of the desired products.This one-pot procedure was extended successfully to the preparation of 4,9-dioxo-4,9dihydronaphtho[2,3-b]thiophene-2-carboxylates (7) from 2-acyl-1,4-naphthoquinones (5) and mercaptoacetates (2) as illustrated in Scheme 2. In principle, the CAN oxidation could be omitted in the preparation of 7. Thus, deprotection of trimethylsilyl ethers and oxidation were accomplished during workup and separation procedure (preparative TLC on silica gel).However, attempts to obtain 7g in pure form by separating the reaction mixture by preparative TLC as conducted for 7a-f afforded a mixture of