Patent EA-000405-B1 (EA)
Title: Vinyl sulfoxides and a process for their synthesis
Inventor: AIKINS JAMES A
IPC: C07D333/56
Filed: 1996-06-04
Abstract: 1. 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.provided R1 and R2 are not both hydrogen when R3 is C2-C10 alkyl or aryl (C1-C10 alkyl), and R1 is not C1-C4 alkoxy when R2 is hydrogen and R3 ia C2-C10 alkyl. 2. A compound as claimed in Claim 1 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 3. A compound as claimed in Claim 2 wherein R3 is thermally-labile or acid-labile C2-C10 alkyl or aryl (C1-C10 alkyl) group. 4. A compound as claimed in Claim 3 wherein R3 is thermally-labile or acid-labile C2-C10 alkyl group. 5. A compound as claimed in Claim 4 wherein: R1 is hydrogen or C1-C4 alkoxy; and R2 is hydrogen or C1-C4 alkoxy. 6. A compound as claimed in Claim 5 wherein R1 and R2 are C1-C4 alkoxy. 7. A compound as claimed in Claim 6 wherein R3 is t-butyl. 8. A compound as claimed in Claim 5 wherein R1 and R2 are methoxy. 9. A compound as claimed in Claim 1 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 provided R1 and R2, are not both hydrogen when R3 is C2-C10 alkvl or aryl (C1-C10 alIkyl), and R1 is not C1-C4. allkoxy when R2 is hydrogen and R3 is C2-C10 alkyl. 10. A compound as claimed in Claim 9 wherein R1 and R2 are methoxy, and R3 is t-butyl. 11. A compound as claimed in Claim 1 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, provided R1 and R2 are not both hydrogen when R3 is C2-C10 alkyl or aryl (C1-C10 alkvl). and R1 is not C1-C4 alkoxv when R2 is hydrogen and R3 is C2-C10 alkyl. 12. A compound as claimed in Claim 11 wherein R1 and R2 are methoxy, and R3 is t-butyl. 13. A process for preparing 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 a thermally-labile or acid-labile C4-C10 alkyl, C4.-C10 alkenyl, or ary (C1-C10 alkyl) group all having a tertiary carbon atom adjacent to the sulfur atom; comprising the steps of: 1) oxidizing a benzyl sulfide of the formula:   wherein R2 and R3 are as defined above; with an oxidizing agent to produce a benzyl sulfoxide of the formula:   wherein R2 and R3 are as defined above; 2) reacting said benzyl sulfoxide with a first strong base to form a benzylic anion; 3) condensing said benzylic anion with a benzaldehyde of the formula   wherein R1 is as defined above; 4)- reacting the condensation product from step 3 with an acid chloride to produce an ester of the formula   wherein: R1, R2, and R3 are as defined above; and R4 is CO(C1-C6 alkyl), CO(aryl), CO(arylalkyl), S02(C1-C6 alkyl), S02(aryl), SO2(arylalkyl), CO2(C1-C6 alkyl), C02(aryl), C02(arylalkyl), or CON(C1-C6 alkyl)2; and 5) treating said ester with a second strong base. 14. The process of Claim 13 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 15. The process of Claim 14 wherein R3 is a thermally-labile or acid-labile C4-C10 alkyl or aryl (C1-C10 alkyl) group, all having a tertiary carbon atom adjacent to the sulfur atom. 16. The process of Claim 15 wherein the oxidizing agent is peracetic acid. 17. The process of Claim 16 wherein the first stong base is an alkyllithium. 18. The process of Claim 17 wherein the first strong base is n-butyllithium. 19. The process of Claim 17 wherein the acid chloride is a sulfonyl chloride, and R4 is SO2(C1-C6 alkyl), SO2(aryl), or SO2 (arylalkyl). 20. The process of Claim 19 wherein the sulfonyl chloride is methanesulfonyl chloride. 21. The process of Claim 17 wherein the second strong base is a metal alkoxide. 22. The process of Claim 19 wherein the metal alkoxide is potassium t-butoxide. 23. The process of Claim 22 wherein R3 is a thermally-labile or acid-labile C4-C10 alkyl group, having a tertiary carbon atom adjacent to the sulfur atom. 24. The process of Claim 17 wherein R1 and R2 are methoxy, and R3 is t-butyl. 25. A process for preparing 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 C4-C10 alkyl, C4-C10 alkenyl, or aryl (C1-C10 alkyl) group all having a tertiary carbon atom adjacent to the sulfur atom; comprising the steps of: 1) reacting a benzyl sulfide of the formula:   wherein R2 and r3 are as defined above; with a first strong base to form a benzylic anion; 2) condensing said benzylic anion with a benzaldehyde of the formula   wherein R1 is as defined above; 3) reacting the condensation product from step 2 with an acid chloride to produce an ester of the formula   wherein: R1, R2, and R3 are as defined above; and R4 is CO(C1-C6 alkyl), CO(aryl), CO (arylalkyl), SO2 (C1-C6 alkyl), S02(aryl), S02(arylalkyl), CO2(C1-C6 alkyl), CO2(aryl), CO2(arylalkyl), or CON(C1-C6 alky)2; 4) treating said ester with a second strong base to produce a styryl sulfide of the formula;   wherein R1, R2, and R3 are as defined above; and 5) oxidizing said styryl suifide with an oxidizing agent. 26. The process of Claim 25 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 27. The process of Claim 26 wherein R3 is a thermally-labile or acid-labile C4-C10. alkyl or aryl(C1-C10 alkyl) group, all having a tertiary carbon atom adjacent to the sulfur atom. 28. The process of Claim 26 wherein the oxidizing agent is peracetic acid. 29. The process of Claim 28 wherein the first stong base is an alkyllithium. 30. The process of Claim 29 wherein the first strong base is n-butyllithium. 31. The process of Claim 29 wherein the acid chloride is a sulfonyl chloride, and R4 is S02(C1-C6 alkyl), SO2(aryl), or SO2(arylalkyl). 32. The process of Claim 31 wherein the sulfonyl chloride is me thanesulfonyl chloride. 33. The process of Claim 29 wherein the second strong base is a metal alkoxide. 34. The process of Claim 33 wherein the metal alkoxide is potassium t-butoxide. 35. The process of Claim 34 wherein R3, is a thermally-labile or acid-labile C2-C10 alkyl group, having a tertiary carbon atom adjacent to the sulfur atom. 36. The process of Claim 29 wherein R1 and R2 are methoxy, and R3 is t-butyl. 37. A process for preparing 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; 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; and d) optionally isolating the compound of formula XII.