Patent EA-000377-B1 (EA)
Title: PROCESS FOR THE SYNTHESIS OF BENZO[b]THIOPHENES
Inventor: HOARD DAVIS W
IPC: C07D333/56
Filed: 1996-06-04
Abstract: 1. A process for preparing a compound of the formula   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or amino; and R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or aniino; which comprises cyclizing in the presence of an acid catalyst a compound of the formula   wherein: R1 and R2 are as defined above; R4 is OSi(R)3, NR5R6, or SR8; each R is independently C1-C6 alkyl, aryl, or arylalkyl; R5 and R6 are independently hydrogen, C1-C6 alkyl, arylalkyl, or aryl; or R5 and R6 together with the nitrogen atom form a ring selected from piperidine, pyrrolidine, morpholine, and hexamethylimine; and R8 is C1-C6 alkyl, aryl, or arylalkyl. 2. The process of Claim 1 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 3. The process of Claim 2 wherein the acid catalyst is selected from the group consisting of methanesulfonic acid, benzenesulfonic acid, 1-naphthalenesulfonic acid, 1-butanesulfonic acid, ethanesuifonic acid, 4-ethylbenzenesulfonic acid, 1-hexanesulfonic acid, 1.5-naphthalenedisulfonic acid, 1-octanesulfonic acid, camphorsulfonic acid, trifluorornethanesulfonic acid, p-toluenesulfonic acid. Nation(RTM), Amberlyst(RTM), and Amberlite(RTM). 4. The process of Claim 3 wherein the acid catalyst is selected form the group consisting of methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, p-toluenesulfonic acid. Nation(RTM), Amberlyst(RTM), and Amberiite(RTM). 5. The process of Claim 4 wherein the acid catalyst is selected from the group consisting of methanesulfonic acid, p-toluenesulfonic acid, Nafion(RTM), Amberlyst(RTM), and Amberlite(RTM). 6. The process of Claim 5 wherein: R4 is OSi (R)3; and each R is independently C1-C6 alkyl, aryl, or arylalkyl. 7. The process of Claim 6 wherein R4 is OTMS, OTES, OTIPS, ODMIPS, ODEIPS, OTDS, OTBDMS, OTBDPS, OTBS, DTPS, ODPMS, or OTBMPS. 8. The process of Claim 7 wherein R4 is OTMS, OTES, ODMIPS, ODEIPS, OTBDMS, OTBS, or OTPS. 9. The process of Claim 8 wherein R4 is OTMS. 10. The process of Claim 9 wherein the acid catalyst is p-toluenesulfonic acid. 11. The process of Claim 5 wherein: R4 is NR5 R6; and R5 and R6 are independently hydrogen, C1-C6 alkyi, arylalkyl, or aryl; or R5 and R6 together with l nitrogen atom form a ring selected from piperidine, pyrrolidine, morpholine, and hexamethylimine. 12. The process of Claim 11 wherein R5 and R6 are independently hydrogen, C1-C6 alkyl, or arylalkyl; or R5 and R6 together with the nitrogen atom form a ring selected from piperidine and pyrrolidine. 13. The process of Claim 12 wherein R5 and R6 are methyl, or R5 is hydrogen and R6 is benzyl. 14. The process of Claim 13 wherein the acid catalyst is p-toluenesulfonic acid. 15. The process of Claim 5 wherein: R4 is SR8; and R8 is C1-C6 alkyl, aryl, or arylalkyl. 16. The process of Claim 15 wherein R8 is C1-C6 alkyl or arylalkyl. 17. The process of Claim 16 wherein R8 is C1-C6 alkyl. 18. The process of Claim 17 wherein the acid catalyst is p-toluenesulfonic acid. 19. A process for preparing a compound of the formula   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, amino; and R2 is hydrogen, C1-C4 alkoxy, arylalkoxy. halo, amino; which comprises treating a compound of the formula   wherein R1 and R2 are as defined above, with an acid. 20. The process of Claim 19 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 21. The process of Claim 20 wherein the acid catalyst is selected form the group cocsisting of methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, p-toluenesulfonic acid. Nation(RTM), Amberlyst(RTM), and Amberlite(RTM). 22. The process of Claim 21 wherein R1 and R2 are C1-C4 alkoxy. 23. The process of Claim 22 wherein the acid catalyst is p-toluenesuifonic acid. 24. The process of Claim 23 wherein R1 and R2 are methoxy. 25. A process for preparing a compound of the formula   wherein: R9 is hydrogen, halo, amino, or hydroxyl; R10 is hydrogen, halo, amino, or hydroxyl; R11 and R12 are independently C1-C4 alkyl, or R11 and R12 together with the adjacent nitrogen atom form a heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethylenetmino, and morpholino; and HX is HC1 or HBr; comprising the steps of: (a) cyclizing in the presence of an acid catalyst a compound of the formula   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or amino; R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or amino; and R4 is OSi(R)3, NR5R6, or SR8; each R is independently C1-C6 alkyl, aryl, or arylalkyl; R5 and R6 are independently hydrogen, C1-C6 alkyl, or aryl, or R5 and R6 together with the nitrogen atom form a ring selected from piperidine, pyrrolidine, morpholine, and hexamethylimine; and R8 is C1-C6 alkyl, aryl, or arylalkyl; to prepare a benzothiophene compound of the formula   wherein R1 and R2 are as defined above; (b) acylating said benzothiophene compound with an acylating agent of the formula   wherein: R11, R12 and HX are as defined previously; and R13 is chloro, bromo, or hydroxyl; in the presence of BX'3, wherein X' is chloro or bromo; and (c) when R1 and/or R2 is C1-C4 alkoxy or arylalkoxy, dealkylating one or more phenolic groups of the acylation product of step (b) by reacting with additional BX'3, wherein X' is as defined above.