Patent EA-000466-B1 (EA)
Title: PROCESS FOR SYNTHESIS OF BENZO[b]THIOPHENES
Inventor: AIKINS JAMES A
IPC: C07D333/54
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 amino; which comprises cyclizing in the presence of an acid catalyst a compound of the formula   wherein: R1 and R2 are as defined above, and R3 is a thermally-labile or acid-labile C2-C10 alkyl, C4-C10 alkenyl, or aryl (C1-C10 alkyl) group. 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, ethanesulfonic acid, 4-ethylbenzenesulfonic acid, 1-hexanesulfonic acid, 1,5-naphthalenedisulfonic acid, 1-octanesulfonic acid, camphorsulfonic acid, trifluoromethanesuifonic 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 Amberlite<(RTM)>. 5. The process of Claim 4 wherein the acid catalys is selected from the group consisting of methanesulfonic acid, p-toluenesulfonic acid, Nation<(RTM)>, Amberlyst<(RTM)>, and Amberlite<(RTM)>. 6. The process of Claim 5 wherein R3 is a thermally-labile or acid-labile C2-C10 alkyl or aryl (C1-C10 alkyl) group. 7. The process of Claim 6 wherein R3 is a thermally-labile or acid-labile C2-C10 alkyl group. 8. The process of Claim 7 wherein R1 is hydrogen or C1-C4 alkoxy; and R2 is hydrogen or C1-C4 alkoxy. 9. The process of Claim 8 wherein R1 and R2 are C1-C4 alkoxy. 10. The process of Claim 9 wherein R3 is t-butyl. 11. The process of Claim 10 wherein the acid catalyst is p-toluenesulfonic acid. 12. The process of Claim 11 wherein R1 and R2 are methoxy. 13. A process for the synthesis of a compound of the formula   wherein: R8 is hydrogen, halo, amino, or hydroxyl; R9 is hydrogen, halo, amino, or hydroxyl; R5 and R6 are independently C1-C4 alkyl, or R5 and R6 together with the adjacent nitrogen atom form a heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, and morpholino; and HX is HCl 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 R3 is a thermally-labile or acid-labile C2-C10 alkyl, C4-C10 alkenyl, or aryl (C1-C10 alkyl) group; 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: R5, R6, and HX are as defined previously; and R7 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.