Patent EA-000606-B1 (EA)
Title: Vinyl sulfenic acid derivatives and process for their synthesis
Inventor: HOARD DAVID W
IPC: C07C317/18
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; 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, or hexamethylimine; and R8 is C1-C6 alkyl, aryl, or arylalkyl. 2. The compound of Claim 1 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 3. The compound of Claim 2 wherein: R4 is OSi(R)3; and each R is independently C1-C6 alkyl, aryl, or arylalkyl. 4. The compound of Claim 3 wherein R4 is OTMS, OTES, OTIPS, ODMIPS, ODEIPS, OTDS, OTBDMS, OTBDPS, OTBS, OTPS, ODPMS or OTBMPS. 5. The compound of Claim 4 wherein R4 is OTMS, OTES, ODMIPS, ODEIPS, OTBDMS, OTBS or OTPS. 6. The compound, of Claim 5 wherein R1 and R2 are C1-C4 alkoxy. 7. The compound of Claim 6 wherein R1 and R2 are methoxy and R4 is OTMS. 8. The compound of Claim 2 wherein: R4 is NR5R6; and 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. 9. The compound of Claim 8 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. 10. The compound of Claim 9 wherein R1 and R2 are C1-C4 alkoxy. 11. The compound of Claim 10 wherein R1 and R2 are methoxy, and R5 and R6 are methyl. 12. The compound of Claim 10 wherein R1 and R2 are methoxy, R5 is hydrogen, and R6 is benzyl. 13. The compound of Claim 2 wherein: R4 is SR8; and R8 is C1-C6 alkyl, aryl, or arylalkyl. 14. The compound of Claim 13 wherein R8 is C1-C6 alkyl or arylalkyl. 15. The compound of Claim 14 wherein R8 is C1-C6 alkyl. 16. The compound of Claim 15 wherein R1 and R2 are C1-C4 alkoxy. 17. The compound of Claim 16 wherein R1 and R2 are methoxy, and R8 is ethyl. 18. A process for preparing a compound of the formula III   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo or amino; R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo or amino; 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, pyrroimidine, morpholine, or hexamethylimine; and R8 is C1-C6 alkyl, aryl or arylalkyl; which comprises: (1) reacting a compound of the formula II   wherein: R1 and R2 are as defined above, and R3 is a thermally-labile or acid-labile C2-C10 alkyl, C4-C10 alkenyl or ary (C1-C10) alkyl group; with a silylating reagent to produce a sulfenate silyl ester of the formula IV   wherein: R1 and R2 are as defined above; R7 is OSi(R)3; and each R is independently C1-C6 alkyl, aryl or arylalkyl; (2) optionally reacting said sulfenate silyl ester with an amine of the formula HNR5R6 wherein R5 and R6 are as defined above; or (3) optionally reacting said sulfenate silyl ester with a mercaptan of the formula HSR8, wherein R8 is as defined above, in the presence of an amine base. 19. The process of Claim 1 for preparing a compound of the formula IV   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or amino; R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, or amino; R7 is OSi(R)3; and each R is independently C1-C6 alkyl, aryl, or arylalkyl; which comprises reacting 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; with a silylating reagent. 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: R7 is OTMS, OTES, OTIPS, ODMIPS, ODEIPS, OTDS, OTBDMS, OTBDPS, OTBS, OTPS, ODPMS or OTBMPS. 22. The process of Claim 21 wherein the silylating reagent is a bis(trialkylsilyl)urea or a combination of a hexaalkyl-disilylzane and a catalytic amount of a chlorotrialkylsilane, and R is C1-C6 alkyl. 23. The process of Claim 22 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl. 24. The process of Claim 23 wherein R3 is a thermally-labile or acid-labile C2-C10 alkyl group. 25 The process of Claim 24 wherein R1 and R2 are raethoxy, and R3 is t-butyl. 26. The process of Claim 18 for preparing a compound of the formula   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, amino; R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, amino; and 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, or hexamethylimine; comprising the steps of: (1) reacting 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; with a silylating reagent to produce a sulfenate silyl ester of the formula   wherein: R1 and R2 are as defined above; R7 is OSi(R)3; and each R is independently C1-C6 alkyl, aryl or arylalkyl; and (2) reacting said sulfenate silyl ester with an amine of the formula HNR5R6 wherein R<5> and R6 are as defined above. 27. The process of Claim 26 wherein: R1 is hydrogen, C1-C4 alkoxy or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy or arylalkoxy. 28. The process of Claim 27 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl. 29. The process of Claim 28 wherein R3 is a thermally-labile or acid-labile C2-C10 alkyl group. 30. The process of Claim 29 wherein R1 and R2 are methoxy, and R3 is t-butyl. 31. The process of Claim 30 wherein R5 and R6 are independently hydrogen, C1-C6 alkyl or aryl. 32. The process of Claim 31 wherein R5 and R6 are methyl, or R5 is hydrogen and R6 is benzyl. 33. The process of Claim 18 for preparing a compound of the formula   wherein: R1 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, amino; R2 is hydrogen, C1-C4 alkoxy, arylalkoxy, halo, amino; and R8 is C1-C6 alkyl, aryl, or arylalkyl comprising the steps of (1) :reacting a compound of the formula II   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; with a silylating reagent to produce a sulfenate silyl ester of the formula   wherein: R1 and R2 are as defined above; R7 is OSi(R)3; and each R is independently C1-C6 alkyl, aryl or arylalkyl; and (2) reacting said sulfenace silyl ester with a mercaptan of the formula HSR8, where R8 is as defined above, in the presence of an amine base. 34. The process of Claim 33 wherein: R1 is hydrogen, C1-C4 alkoxy, or arylalkoxy; and R2 is hydrogen, C1-C4 alkoxy, or arylalkoxy. 35. The process of Claim 34 wherein the amine base is triethylamine, diisopropylethylamine or pyridine. 36. The process of Claim 35 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl. 37. The process of Claim 36 wherein R3 is a thermally-labile or acid-labile C2-C10 alkyl group. 38. The process of Claim 37 wherein the amine base is triethylamine. 39 The process of Claim 38 wherein R1 and R2 are methoxy and R3 is t-butyl. 40. The process of Claim 39 wherein R8 is C1-C6 alkyl. 41. The process of Claim 40 wherein R8 is ethyl. 42. The process for the synthesis of a compound of the formula XIII   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, 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 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 lform a ring selected from piperidine, pyrrolidine, morpholine, and hexaniethylimine; and R8 is C1-C6 alkyl, aryl, or arylalkyl; to prepare a benzothiophene compound of the formula I   wherein R1 and R2 as defined above; (b) acylating said benzothiophene compound with an acylating agent of the formula XII   wherein: R11, R12' and HX are as defined above; and R13 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, optionally, (d) isolating the formula XIII compound.