EP0675877A1 - Procede de preparation de sulfones - Google Patents

Procede de preparation de sulfones

Info

Publication number
EP0675877A1
EP0675877A1 EP94904512A EP94904512A EP0675877A1 EP 0675877 A1 EP0675877 A1 EP 0675877A1 EP 94904512 A EP94904512 A EP 94904512A EP 94904512 A EP94904512 A EP 94904512A EP 0675877 A1 EP0675877 A1 EP 0675877A1
Authority
EP
European Patent Office
Prior art keywords
alkali metal
sulfide
formula
equivalents
sulfone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP94904512A
Other languages
German (de)
English (en)
Other versions
EP0675877A4 (fr
Inventor
Kevin Scott Webb
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Publication of EP0675877A1 publication Critical patent/EP0675877A1/fr
Publication of EP0675877A4 publication Critical patent/EP0675877A4/fr
Withdrawn legal-status Critical Current

Links

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.

Landscapes

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

Abstract

On peut transformer certains sulfures en sulfoxydes ou en sulfones à l'aide d'oxone dans de l'acétone aqueuse à 12,5 % tamponnée avec du bicarbonate de sodium de sorte que sa valeur pH soit comprise entre 7,5 et 8,0.
EP94904512A 1992-12-23 1993-12-21 Procede de preparation de sulfones. Withdrawn EP0675877A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US99634292A 1992-12-23 1992-12-23
US996342 1992-12-23
PCT/US1993/012444 WO1994021603A1 (fr) 1992-12-23 1993-12-21 Procede de preparation de sulfones

Publications (2)

Publication Number Publication Date
EP0675877A1 true EP0675877A1 (fr) 1995-10-11
EP0675877A4 EP0675877A4 (fr) 1996-07-31

Family

ID=25542798

Family Applications (1)

Application Number Title Priority Date Filing Date
EP94904512A Withdrawn EP0675877A4 (fr) 1992-12-23 1993-12-21 Procede de preparation de sulfones.

Country Status (7)

Country Link
EP (1) EP0675877A4 (fr)
JP (1) JPH08505151A (fr)
CN (1) CN1100092A (fr)
AU (1) AU5853594A (fr)
MX (1) MX9400081A (fr)
WO (1) WO1994021603A1 (fr)
ZA (1) ZA939517B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10229776A1 (de) * 2002-07-03 2004-01-22 Bayer Cropscience Ag Verfahren zum Herstellen von heterocyclischen Fluoralkenylsulfonen
ATE423764T1 (de) 2005-04-28 2009-03-15 Shiratori Pharm Verfahren zur herstellung von hydrazon-derivaten
MX2010007452A (es) 2008-01-07 2010-08-18 Biomarin Pharm Inc Metodo para sintetizar tetrahidrobiopterin.
CN102241616A (zh) * 2010-05-12 2011-11-16 利尔化学股份有限公司 砜的制备方法
CN103450058B (zh) * 2013-09-18 2015-10-14 广安凯特医药化工有限公司 一种氨磺必利酸的制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2018437A1 (fr) * 1989-06-14 1990-12-14 James Simpson Frazee Antagonistes des leukotrienes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO9421603A1 *

Also Published As

Publication number Publication date
EP0675877A4 (fr) 1996-07-31
ZA939517B (en) 1995-01-31
MX9400081A (es) 1994-07-29
JPH08505151A (ja) 1996-06-04
WO1994021603A1 (fr) 1994-09-29
CN1100092A (zh) 1995-03-15
AU5853594A (en) 1994-10-11

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