WO2001021617A1 - Procede de preparation de composes de sulfoxyde - Google Patents

Procede de preparation de composes de sulfoxyde Download PDF

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Publication number
WO2001021617A1
WO2001021617A1 PCT/KR2000/001019 KR0001019W WO0121617A1 WO 2001021617 A1 WO2001021617 A1 WO 2001021617A1 KR 0001019 W KR0001019 W KR 0001019W WO 0121617 A1 WO0121617 A1 WO 0121617A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
sulfoxide
yield
hydrogen peroxide
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Application number
PCT/KR2000/001019
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English (en)
Inventor
Soo Jin Choi
Seong Cheol Moon
Young Seok Byun
Original Assignee
Daewoong Pharm Co., Ltd.
Daewoong Chemical Co., Ltd.
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 Daewoong Pharm Co., Ltd., Daewoong Chemical Co., Ltd. filed Critical Daewoong Pharm Co., Ltd.
Priority to AU70407/00A priority Critical patent/AU7040700A/en
Publication of WO2001021617A1 publication Critical patent/WO2001021617A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a process for preparing sulfoxide compounds useful as anti -ulcer agents having a gastric acid secretion inhibiting action. More particularly, the present invention relates to a process for preparing a sulfoxide compound of the formula I, which comprises the step of oxidizing a sulfide compound of the formula II with hydrogen peroxide in the presence of a rhenium compound acting as a catalyst. Unlike the prior art, the process of the present invention minimizes a production of an N-oxide by-product of the formula III and an sulfone by-product of the formula IV and thus produces the sulfoxide compound of the formula I at high yield and purity using a simple isolation procedure.
  • the sulfoxide compound represented by the formula I is useful as an anti-ulcer agent having a gastric acid secretion inhibiting action.
  • the sulfoxide compound of the formula I is prepared by oxidizing the sulfoxide compound of the formula II with an oxidizing agent, as indicated in the following Scheme 1:
  • Oxidizing agents previously disclosed in the art for the oxidation of the sulfide compound include iodosobenzene (Spanish Patent No. 539,793 (1985)), iodosomethylbenzene (Spanish Patent No. 540,147 (1985)), m-chloroperbenzoic acid (US Patent No. 4,628,098 (1986) and 4,255,431 (1981)), peracetic acid (WO 98/09962
  • Korean Patent No. 052837 (1992) describes only a melting point of the compound I without descriptions of a purity and yield of the compound I.
  • Example of Korean Patent No. 100796 (1996) describes preparing the compound I at a relatively low yield of 74.9%.
  • the produced byproducts are very similar in physical and chemical properties, such as solubility, to those of the sulfoxide compound I and thus is not easily removed by a usual purification method such as recrystallization.
  • the oxidation with m-chloroperbenzoic acid is disadvantageous in that m-chloroperbenzoic acid is an expensive reagent and is a dangerous substance requiring cautions during its use and storage so that it is difficult to be handled in large quantities.
  • the oxidation with m-chloroperbenzoic acid has a drawback when being applied for industrial purpose, because it utilizes environmentally harmful halogenated solvents such as chloroform, methylene chloride and the like.
  • Japanese Patent Application Laid Open No. Heisei 11-71370 (1999) discloses a process of preparing the sulfoxide compound I by oxidizing the sulfide compound II in a mixed solvent of nonpolar solvent and lower alcohol. However, this process is reported as producing the sulfoxide compound I at a low yield of 71.6%.
  • WO 99/02521 (1999) describes oxidizing the sulfide compound II with sodium perborate tetrahydrate (NaB0 3 .4H 2 0) in the presence of anhydrous acetic acid and water to produce the sulfoxide compound I at a yield of 78.4%.
  • An alternative process in the latter publication includes oxidizing the sulfide compound II with N-chlorosuccinic acid in the presence of an inorganic base to produce the sulfoxide compound I at a yield of 84.1%.
  • Korean Patent No. 100796 discloses a process for preparing the sulfoxide compound of the formula I by oxidizing the sulfide compound of the formula II with hydrogen peroxide in the presence of a vanadium catalyst. This process is described as producing the end compound at a high yield of 89.5 to 93.2 while inhibiting a production of the N-oxide byproduct at a low level .
  • the process according to the latter patent involves several problems when being applied for the industrial purpose.
  • the specification of the disclosed patent mentions only the N-oxide by-product III, but includes no mention of whether the sulfone by- product IV as indicated in Scheme 2 is produced. Also, the specification does not mention a method of removing the sulfone by-product IV.
  • the vanadium compound used as a catalyst is highly poisonous to a human body and is not easy to handle, so that it is not suitable for use in mass production (US Patent No. 5,391,752).
  • the above described prior processes employs a complex purification procedure to remove byproducts. Namely, the purification procedure according to the prior processes comprises heating a crude crystal obtained after a reaction for obtaining the end compound to 60-70 °C to dissolve the crude crystal, filtering the solution to remove insoluble material, and recrystallizing the solution. Thus, it is difficult for the prior processes to be applied for mass production due to an increase in working processes and a rising in manufacturing-costs .
  • the prior processes disadvantageously results in the formation of a colored reaction mixture during the oxidation procedure, and thus further require a decoloring step of the reaction mixture, additionally to the purification procedure. It is generally well known that benzimidazole compounds are instable under acidic conditions so that they are discolored under oxidation conditions. For this reason, the prior processes additionally require the decoloring step (WO 98/40377 and 98/40378, and US Patent No. 5,374,730) .
  • Spainish Patent No. 2,036,948 (1993) discloses a process which comprises oxidizing the sulfide compound with hydrogen peroxide in the presence of ammonium molybdate [ (NH 4 ) 2 Mo0 4 ] , a molybdenum compound, which is substituted for the vanadium compound catalyst.
  • this process produces a sulfoxide compound at a low yield of 75% and thus is disadvantageous in view of the economical efficiency.
  • the prior processes for preparing the sulfoxide compound disadvantageously produce the N-oxide by-product III and the sulfone by- product IV during the oxidation step. This makes the isolation and purification of a pure sulfoxide compound difficult.
  • Another drawback with the prior processes is that they require the complex purification procedure including an additional decoloring step which is required due to the formation of the colored product.
  • the prior processes are problematic in that they employ an environmentally harmful catalyst, or a catalyst or oxidizing agent poisonous to a human body, thereby involving a difficult when being applied for mass production.
  • the present invention is directed to a process for preparing a sulfoxide compound of the formula I, which comprises the step of oxidizing a sulfide compound of the formula II with hydrogen peroxide as an oxidizing agent, in an ethanol solvent, in the presence of a rhenium compound as a catalyst .
  • the process of the present invention is illustrated in the following Scheme 6.
  • the process according to the present invention minimizes a production of the N-oxide by-product III and the sulfone by-product IV while removing the by-products by only a simple isolation step, i.e., a filtration step, thereby producing the sulfoxide compound I at a high purity and yield.
  • rhenium compound used as the catalyst in the practice of the present invention examples include methyltrioxorhenium, ethyltrioxorhenium, Re (PPh 3 ) 2 OCl 3 and the like.
  • the most preferred catalyst is methyltrioxorhenium (CH 3 Re0 3 ; commercially available from CAS Corp., Korea) .
  • Methyltrioxorhenium was first reported by Hermann et al . to be a catalyst efficient for epoxidation of olefinic compounds with hydrogen peroxide (Angew, Chem. , Int. Ed. Engl., 30, 1636 (1991)). This methyltrioxorhenium is known as activating hydrogen peroxide, an oxygen source for an oxidizing agent, by an electrophilic reaction mechanism. In particular, unlike oxidizing agents used at approximately one equivalent amount or excess equivalent amounts, the methyltrioxorhenium catalyst has a significant advantage in that it is used for oxidation of a reactant without producing by-products.
  • the rhenium compound has advantages in that it is non-toxic to a human body and also shows a very high stability in air so that it is easy to store, handle and weigh.
  • the rhenium compound is used at the amount of 0.1 to 10 mole %, and preferably 1 to 5 mole % relative to the compound of the formula II.
  • Hydrogen peroxide as an oxygen source for an oxidizing agent is generally used in aqueous solution.
  • hydrogen peroxide is preferably used at a concentration converted by a titration method. Also, hydrogen peroxide is used at the amount of 0.9 to 2 equivalents, and preferably 1 to 1.3 equivalents per one equivalent of the compound II.
  • the organic solvents used in the practice of the present invention include alcoholic solvents such as methanol , ethanol, isopropanol, butanol, and the like. The preferred solvents are methanol and ethanol. These alcoholic solvents may be used alone or in admixture with water. In the latter case, the volume ratio of water to alcoholic solvent is in the range of 1:5 to 1:15, and preferably 1:8 to 1:10.
  • the oxidation according to the present invention is carried out at a temperature of -40 °C to 0 °C and preferably -30°C to -15 °C, for 1 to 10 hours and preferably 3 to 7 hours .
  • the reaction mixture produced under the oxidation conditions as described above contains the N-oxide compound III at the amount of less than 0.06% (by HPLC area percent) and the sulfone compound IV at the amount of less than 0.06% (by HPLC area percent) , additionally to the sulfoxide compound of the formula I.
  • the prior art Kerean Patent No. 100796
  • the oxidation conditions of the present invention were excellent as compared to those of the prior art.
  • the sulfoxide compound I is mostly deposited in the form of crystal.
  • the conventional isolation procedures for example, extraction, decoloration and recrystallization are not required to isolate the end compound.
  • aqueous sodium thiosulfate solution is added to the deposited crystal to decompose the remaining hydrogen peroxide. After this, the resulting mixture is filtered and washed with the appropriate alcoholic solvent as described above to give the sulfoxide compound of the formula I at a high purity and yield.
  • the preparing process of the present invention inhibits a production of the N-oxide compound II to less than 0.05% (by HPLC area percent) and a production of the sulfone compound IV to 0% (by HPLC area percent) .
  • the process of the present invention can prepare the sulfoxide compound at a high purity of more than 99.95% (by HPLC area percent) and a high yield of more than 90%.
  • the process of the present invention can be summarized as follows: First, the prior art employs a dangerous material, or an oxidizing agent and catalyst poisonous to a human body, whereas the process of the present invention utilizes the rhenium compound which is harmless to a human body and easy to store and handle. Thus, the process of the present invention can be easily applied for mass production. Second, the process of the present invention minimizes a production of the N-oxide and sulfone by-products as compared to that of the prior art , and thus can produce the end compound at a high purity of 99.95 % or more (by HPLC area percent) and a high yield of 90% or more.
  • the process of the present invention eliminates the use of the environmentally harmful halogenated solvent while employing the environmentally harmless ethanol solvent.
  • the prior art requires a complex purification procedure, such as extraction, decoloration, recrystallization and the like, whereas the present invention allows the end compound to be obtained at a high purity by simply filtering and washing a crystal produced after the reaction. This ensures that the present invention is easily applied for mass production and economically carried out.
  • Example 1 Preparation of 2- [ [3 -methyl -4- (2 , 2 , 2- trifluoroethoxy) yrid-2-yl] methylsulfinyl] benzimidazole 1.0 g (2.7 mmol) of 2- [ [3-methyl-4- trifluoroethoxy] pyrid-2-yl] methylthio] benzimidazole monohydrate was dissolved in 20 ml of 95% ethanol and cooled to a temperature of -20 to -30 °C . Then, 26.4 mg of methyltrioxorhenium and 0.31 g (2.7 mmol) of a 30% aqueous hydrogen peroxide solution were added, and stirred for 5 hours at the same temperature.
  • Comparative Example 1 Preparation of 2-[[3- methyl-4- (2,2, 2 -trifluoroethoxy) pyrid-2- yl] methylsulfinyl] benzimidazole 1.0 g (2.7 mmol) of 2- [ [3 -methyl -4- trifluoroethoxy] pyrid-2-yl] methylthio] benzimidazole monohydrate was dissolved in 10 ml of 95% methanol and cooled to a temperature of -20 to -30 °C. Then, 26.4 mg of methyltrioxorhenium and 0.31 g (2.7 mmol) of an aqueous 30% hydrogen peroxide solution were added, and stirred for 5 hours at the same temperature.
  • Table 1 shows a comparison of products from Example 1, Comparatives 1-3 and the prior art (Korean
  • Patent No. 100796 in terms of yield and purity (by HPLC area percent) .
  • HPLC conditions used for the purity analysis are as follows:
  • Example 1 using ethanol as a solvent showed an excellent yield compared to Comparative Examples 1-3 using methanol or a mixture of ethanol and water as the solvent. Also, it could be found that, when the methyltrioxorhenium catalyst was used at the amount of 1 mole% or less, yield was decreased.
  • Example 1 of the present invention when comparing Example 1 of the present invention and Example 4 of Korean Patent No. 100796 in terms of the by-product production percent and the end compound purity, it could be found that Example 1 showed a higher purity than Example 4 of the prior art (Korean Patent No. 100796) .
  • Example 1 showed a sulfone compound area percent of 0 %, it can be found that the process of the present invention produced no sulfone by-product and thus produced the sulfoxide compound I at a higher yield compared to Comparative Examples 1-3 and the prior art.
  • the process of the present invention could be found to be an excellent process capable of basically preventing the sulfone by-product production.
  • the process according to the present invention minimizes a production of by-products by conducting the oxidation of the sulfide compound with hydrogen peroxide in the presence of the methyltrioxorhenium catalyst which is harmless to a human body and is easy to store and handle.
  • the process of the present invention can produce the sulfoxide compound useful as anti-ulcer agents at a high yield and purity by only a simple filtration without a need of the complex procedure or the decoloring step.
  • the process of the present invention is easily applied for mass production and thus is useful in the industrial and economical views .

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

Abstract

L'invention concerne un procédé de préparation d'un composé de sulfoxyde de formule (I) utilisé comme agent antiulcéreux avec un rendement et un degré de pureté élevés. Ce procédé consiste à faire réagir un composé de soufre de formule (II) avec du peroxyde d'hydrogène dans un solvant à base d'éthanol en présence d'un catalyseur de rhénium variant entre 1 et 5 en pourcentage molaire par rapport au composé de soufre (II).
PCT/KR2000/001019 1999-09-21 2000-09-07 Procede de preparation de composes de sulfoxyde WO2001021617A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU70407/00A AU7040700A (en) 1999-09-21 2000-09-07 Process for preparing sulfoxide compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1999/40831 1999-09-21
KR1019990040831A KR100362947B1 (ko) 1999-09-21 1999-09-21 설폭시드 화합물의 제조방법

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004056803A1 (fr) * 2002-12-23 2004-07-08 Chemi Spa Procede de preparation de derives sulfinyle par oxydation des sulfures correspondants
US6909004B2 (en) 2002-08-21 2005-06-21 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
WO2005077936A1 (fr) * 2004-02-11 2005-08-25 Ulkar Kimya Sanayii Ve Ticaret A.S. Sulfoxydes pyridine benzimidazole d'une grande purete
EP2030973A1 (fr) * 2007-08-31 2009-03-04 KRKA, tovarna zdravil, d.d., Novo mesto Procédé pour la préparation de 2-sulfinyl-1H-benzimidazoles
US7678816B2 (en) * 2003-02-05 2010-03-16 Teva Pharmaceutical Industries Ltd. Method of stabilizing lansoprazole
US7683177B2 (en) 2003-06-10 2010-03-23 Teva Pharmaceutical Industries Ltd Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
US7683080B2 (en) * 2002-11-18 2010-03-23 Teva Pharmaceutical Industries Ltd. Stable iansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol
US7915423B2 (en) 2002-12-19 2011-03-29 Teva Pharmaceutical Industries, Ltd. Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
CN102628110A (zh) * 2012-04-06 2012-08-08 阳谷祥光铜业有限公司 一种从铜冶炼废酸中回收铼的方法
CN106011487A (zh) * 2016-06-28 2016-10-12 阳谷祥光铜业有限公司 一种铜冶炼烟尘洗涤废酸中铼的回收方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0302720A1 (fr) * 1987-08-04 1989-02-08 Takeda Chemical Industries, Ltd. Préparation de composés 2-(2-pyridylméthylsulfinyl)-benzimidazoliques
US5374730A (en) * 1993-11-04 1994-12-20 Torcan Chemical Ltd. Preparation of omeprazole and lansoprazole

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0302720A1 (fr) * 1987-08-04 1989-02-08 Takeda Chemical Industries, Ltd. Préparation de composés 2-(2-pyridylméthylsulfinyl)-benzimidazoliques
US5374730A (en) * 1993-11-04 1994-12-20 Torcan Chemical Ltd. Preparation of omeprazole and lansoprazole

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ARTERBURN J.B. AND NELSON S.L.: "Rhenium-catalyzed oxidation of sulfides with phenyl sulfoxide", J. ORG. CHEM., vol. 61, no. 7, 1996, pages 2260 - 2261 *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7622588B2 (en) 2002-08-21 2009-11-24 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7022859B2 (en) 2002-08-21 2006-04-04 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US6909004B2 (en) 2002-08-21 2005-06-21 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7060837B2 (en) 2002-08-21 2006-06-13 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7683080B2 (en) * 2002-11-18 2010-03-23 Teva Pharmaceutical Industries Ltd. Stable iansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol
US7915423B2 (en) 2002-12-19 2011-03-29 Teva Pharmaceutical Industries, Ltd. Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
WO2004056803A1 (fr) * 2002-12-23 2004-07-08 Chemi Spa Procede de preparation de derives sulfinyle par oxydation des sulfures correspondants
US7105681B2 (en) 2002-12-23 2006-09-12 Chemi Spa Process for the preparation of sulphinyl derivatives by oxidation of the corresponding sulfides
US7678816B2 (en) * 2003-02-05 2010-03-16 Teva Pharmaceutical Industries Ltd. Method of stabilizing lansoprazole
US7683177B2 (en) 2003-06-10 2010-03-23 Teva Pharmaceutical Industries Ltd Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
WO2005077936A1 (fr) * 2004-02-11 2005-08-25 Ulkar Kimya Sanayii Ve Ticaret A.S. Sulfoxydes pyridine benzimidazole d'une grande purete
WO2009027533A1 (fr) * 2007-08-31 2009-03-05 Krka, Tovarna Zdravil, D.D., Novo Mesto Procede de preparation de 2-sulfinyl-1h-benzimidazoles
EP2030973A1 (fr) * 2007-08-31 2009-03-04 KRKA, tovarna zdravil, d.d., Novo mesto Procédé pour la préparation de 2-sulfinyl-1H-benzimidazoles
EA018796B1 (ru) * 2007-08-31 2013-10-30 Крка, Товарна Здравил, Д. Д., Ново Место Способ получения 2-(2-пиридинилметилсульфинил)-1н-бензимидазолов
CN102628110A (zh) * 2012-04-06 2012-08-08 阳谷祥光铜业有限公司 一种从铜冶炼废酸中回收铼的方法
CN106011487A (zh) * 2016-06-28 2016-10-12 阳谷祥光铜业有限公司 一种铜冶炼烟尘洗涤废酸中铼的回收方法

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AU7040700A (en) 2001-04-24
KR100362947B1 (ko) 2002-11-30
KR20010028547A (ko) 2001-04-06

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