Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
  • C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides

Definitions

• Rj is Cg to Ci3-alkyl, C7 to C- -alkoxy, unsubstituted or substituted phenyl-C4 to Cio-alkyl- unsubstituted or substituted phenyl-C3 to Ctp-alkoxy with substituted phenyl is substituted with bromo, chloro, trifluoromethyl, or Cj to C -alkoxy
• R is -(CH2) n ArA or ArA where n is 0-6, Ar is phenyl or substituted phenyl, and A is - (CH2) n R2- where n is 0-6.
• R2 is -COOH or CO2X where X is an alkali metal cation
• Y is R2 or -CH(R3)(CH2) m R2. and R3 is hydrogen, methyl, C ⁇ to C4 alkoxy, fluoro or hydroxy; wherein the process comprises i. preparing an aqueous alkali metal salt solution of an acid of formula A;
• phenyl or naphthyl group can be present.
• Naphthyl is represented by the use of a dotted outline with a circle in the center, that portion of formulas I and A may be absent, giving the phenyl or may be present giving the naphthyl radical.
• This invention is intended to cover both sets of compounds.
• the sulfides of formula A can be found in the literature, particularly in the patent literature.
• Compounds where R is an alkyl acid are disclosed in U.S. patent numbers 4,820,719 and 4,874,792.
• Formula A compounds where R is a 5-membered heterocyclic ring group are disclosed in U.S. patent number 5,135,938.
• Sulfides where R is a six-membered aiyl or heteroaryl group are disclosed in European Patent Application No. 90306438.4.
• Compounds where the dotted lines denotes naphthyl can be found in European Patent Application 91908637.1. All are incorporated herein by reference in full as if set out here.
• the compound of most interest in this invention is that one where R is the 4- carboxyphenyl group. How to make these sulfides is disclosed in European Patent Application 91908637.1.
• the oxidation of most interest here is that of converting the sulfide (R*,S*)- ⁇ [(4- c_-rboxyphenyl)thio)- ⁇ -methoxy-2-(8-phenyloctyl)benzene propanoic acid to its corresponding sulfone, the (R*,S*)-p ⁇ [(4-carboxyphenyl)sulfonyl)- ⁇ -methoxy-2-(8-phenyloctyl)benzene propanoic acid. Bodi of these compounds are disclosed in EP application 91908637.1. In that application the sulfone was prepared by treating the sulfide with about two equivalents of m- perchlorobenzoic acid.
• an aqueous solution of the sulfide in the form of an alkali metal salt is first prepared. This can be done by simply dissolving an existing alkali metal salt in water or by dissolving die free acid in a solution of an alkali metal base, eg. an alkali metal hydroxide. !£ the f. ⁇ re acid is being dissolved in base, at minimum two equivalents of base should be used, it is preferable to use at least one equivalent of base per acidic function in the molecule, an excess of base is preferred so that complete ionization of all acid groups is achieved. As the cation, the preferred ion is sodium. Sodium hydroxide is the preferred alkali metal hydroxide.
• a buffering agent is added to adjust die pH.
• a bicarbonate ion is preferred, particularly the bicarbonate which has the same cation as that of the sulfide salt
• sodium bicarbonate is preferred.
• Bicarbonate is added in an amount sufficient to buffer the solution to a pH between about 7.0 and 8.5, preferably 7.5 to 8.0.
• a co-solvent in the form of a water-miscible ketone is then added in an amount between 10 and 15%.
• Simple ketones such as dimethyl or diethyl ketone may be used.
• the preferred ketone is acetone.
• a preferred amount is that of about 12.5%.
• Oxone® (potassium peroxymonosulfate) is then added.
• This oxidant is commercially available from several suppliers, for example Aldrich Chemical Company, U.S.A.
• An excess of Oxone® is added. Preferably that excess will be in the range of 1.1 to 1.5 equivalents, though it will be appreciated that an amount exceeding 1.5 equivalents could be used though such added quantities likely would not achieve much in the way of a cost effective transformation of the sulfide to the sulfone.
• An optimized quantity is believed to be about 1.35 equivalent of Oxone®.
• One of the attributes of this improved process is that an elevated temperature is not required to effect the reaction. The reaction can be carried out at ambient temperature or thereabouts. An effective range is anywhere from about 10°C to 50° C.
• the reaction can be quenched by adding a reducing agent, eg. sodium bisulfite, and die sulfone recovered as the salt.
• a reducing agent eg. sodium bisulfite, and die sulfone recovered as the salt.
• die solution can be made acidic and by that means the free acid formed; it may be then recovered by any means desired.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1993
  • 1993-12-20 CN CN93120758A patent/CN1100092A/zh active Pending
  • 1993-12-20 ZA ZA939517A patent/ZA939517B/xx unknown
  • 1993-12-21 JP JP6515524A patent/JPH08505151A/ja active Pending
  • 1993-12-21 AU AU58535/94A patent/AU5853594A/en not_active Abandoned
  • 1993-12-21 EP EP94904512A patent/EP0675877A4/de not_active Withdrawn
  • 1993-12-21 WO PCT/US1993/012444 patent/WO1994021603A1/en not_active Application Discontinuation
• 1994
  • 1994-01-03 MX MX9400081A patent/MX9400081A/es unknown

Non-Patent Citations (2)

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