US3412103A - Process for the reduction of thiophenesubstituted ketoacids - Google Patents

Process for the reduction of thiophenesubstituted ketoacids Download PDF

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Publication number
US3412103A
US3412103A US436922A US43692265A US3412103A US 3412103 A US3412103 A US 3412103A US 436922 A US436922 A US 436922A US 43692265 A US43692265 A US 43692265A US 3412103 A US3412103 A US 3412103A
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United States
Prior art keywords
sulfide
hydrogen
reduction
ketoacid
parts
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Expired - Lifetime
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US436922A
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English (en)
Inventor
Chibnik Sheldon
Harold M Foster
Laverne A Glick
Harold A Kaufman
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Bayer CropScience Inc USA
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Mobil Oil AS
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Publication date
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Priority to US436922A priority Critical patent/US3412103A/en
Priority to NL6601413A priority patent/NL6601413A/xx
Priority to GB9170/66A priority patent/GB1086375A/en
Priority to FR51910A priority patent/FR1482037A/fr
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Publication of US3412103A publication Critical patent/US3412103A/en
Assigned to RHONE-POULENC, INC., A COP. OF NY reassignment RHONE-POULENC, INC., A COP. OF NY ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: MOBIL OIL CORPORATION, A NY CORP.
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • This invention relates to the reduction of keto groups. It is more particularly concerned with the reduction of keto groups in ketoacids attached to heterocyclic sulfur ring systems.
  • a ketoacid contains a sulfur substituent, such as a thienyl group, however, the sulfur atom poisons the catalyst or is removed by.hydrodesulfurization.
  • a sulfur-containing ketoacid e.g., 3-(2- thenoyl)propionic acid to 4-(2-thienyl)butyric acid
  • the Clemmenson reduction has been used. Results were erratic and yields were low.
  • ketoacids having heterocyclic sulfur group substituents can be reduced to the corresponding alkanoic acid by a process that is relatively. simpleand which can be operated at elevated temperatures with little or no corrosion problems to effect commercially feasible yields.
  • this invention provides a method for reducing an aliphatic ketoacid, which is attached to a heterocyclic sulfur ring system, to the corresponding heterocyclic substituted alkanoic acid that comprises contacting an aqueous solution of a water-soluble alkali or alkaline earth metal salt of said ketoacid and hydrogen with a catalyst comprising an aqueous sodium hydroxide insoluble sulfide of a transitional metal, and in the presence of hydrogen sulfide.
  • the ketoacid reactants that are reduced in accordance with this invention are aliphatic ketoacids containing 2 to 14 carbon atoms and having substituted thereon a heterocyclic sufur ring system.
  • the ketoacid, exclusive of the heterocyclic sulfur ring substituent can be straightchain or branched chain, saturated or unsaturated.
  • the heterocyclic sulfur ring substituent (which interferes with the reduction of a keto group by ordinary methods of reduction) can contain other heterocyclic atoms along with heterocyclic sulfur.
  • Typical substituents include thienyl, benzothienyl, thiazolyl, benzothiazolyl, and thiapyranyl.
  • the ketoacid reactant can have, on the chain portion or on the heterocyclic group substituent, other substituents which in general are not readily reduced, such as alkyl, aryl, amino, dialkylamino, methylmercapto, alkoxy, and halogen.
  • the ketoacid reactant is used in the form of its watersoluble salt in aqueous solution.
  • Either alkali metal or alkaline earth metal water-soluble salts can be employed.
  • the sodium salt is preferred, based on the ready availability of sodium hydroxide.
  • Other salts, however, are utilizatlble, such as lithium, potassium, and calcium, provided they are water-soluble.
  • the ketoacid must be completely neutralized, i.e., at least stoichiometric amounts of base and acid must be used. When the ketoacid is incompletely neutralized, undesirable by-products are formed. A slight excess of base is not detrimental but a large excess will react with hydrogen sulfide to form metal sulfide which will increase the problem of subsequent product recovery.
  • the catalysts used in the reduction process of this invention are sulfides or mixtures of sulfides of transitional metals that are insoluble in aqueous alkali-metal hydroxide.
  • the preferred catalysts are the sulfides of metals of Groups 6a and 8 of the Periodic Arrangement of the Elements Based on Atomic Numbers [1. Chem. Educ., 16, 409 (1939)].
  • Some transitional metal sulfides are known to be soluble in aqueous caustic (e.g. aqueous solution of sodium hydroxide) when the metal is present in its higher valence state, such as molybdenum trisulfide and tungsten trisulfide.
  • Such soluble sulfides are not per se catalysts for the process of this invention, but they are utilizable when reduced to a lower valence state metal sulfide that is insoluble in aqueous sodium hydroxide solution.
  • the reduced valence state transitional metal sulfide can be prepared by reducing, with hydrogen, a solution of the soluble metal sulfide (e.g. M08 in aqueous sodium hydroxide and collecting, as the catalyst, precipitated metal sulfide in which the metal is in a reduced valence state.
  • a solution of the corresponding oxide e.g.
  • M00 in aqueous sodium hydroxide can be reacted with hydrogen and hydrogen sulfide to produce a metal sulfide catalyst precipitate.
  • the conditions utilizable to produce the catalytic metal sulfide of reduced valence state are those used in the process of this invention. Accordingly, a soluble metal sulfide, such as M05 can be dissolved in aqueous caustic (NaOH) and added to the reactor along with the solution of the ketoacid salt. In this case, when hydrogen is charged under reaction conditions of the process of this invention, catalytic metal sulfide will be formed in situ. Cobalt polysulfide and a molybdenum sulfide of reduced valence state are particularly preferred.
  • catalysts that are utilizable are iron sulfide, nickel sulfide, platinum sulfide, palladium sulfide, vanadium sulfide, titanium sulfide, manganese sulfide, tungsten sulfide, and mixtures of cobalt sulfide and nickel sulfide, cobalt sulfide and manganese sulfide, nickel sulfide and tungsten sulfide, and cobalt sulfide and iron sulfide.
  • the transitional metal sulfide can be used as a slurry of finely divided particles in the aqueous reaction medium.
  • the reduction of the ketoacid reactant with hydrogen takes place in the pres ence of hydrogen sulfide.
  • Hydrogen sulfide itself can be used, but it is also contemplated to use sulfur-containing materials that form hydrogen sulfide in situ under the conditions of the reduction reaction.
  • sulfur-containing materials include elemental sulfur, mercaptans, thioacetamides, alkyl sulfides, disulfides and polysulfides, carbon disulfide, carbonyl sulfide, and metal sulfides, such as ferric sulfide.
  • hydrogen sulfide in the presence of hydrogen sulfide, as used herein and in the claims, includes hydrogen sulfide added per se and also hydrogen sulfide produced in situ from the aforedescribed sulfur-containing materials. Although hydrogen sulfide is preferred, hydrogen selenide, hydrogen telluride and corresponding compounds that can form hydrogen selenide and hydrogen telluride can be used.
  • the reduction is carried out at temperatures of between about 225 C. and about 280 C., for reaction times of between about 15 minutes and about 3 hours varying inversely with temperature; although higher and lower temperatures and longer and shorter times can be used. Longer reaction times would not appear to be detrimental, but are not necessary. Shorter times result in incomplete conversion. At higher temperatures, by-product formation increases.
  • the particularly preferred time and temperature range is from about 240 C. for about 3 hours to about 260 C. for about 40 minutes.
  • the process of this invention is carried out batchwise or continuously, under pressure in suitable pressure equipment.
  • the hydrogen partial pressure will be between about 1000 p.s.i.g. and about 2300 p.s.i.g. Practical, effective molar ratios of hydrogen were found to be between about 7 and about 22 moles per mole ketoacid reactant.
  • the product, reduced ketoacid can be recovered by conventional means for isolating carboxylic acids from solutions of their water-soluble salts.
  • the aqueous solution is acidified with hydrochloric acid or sulfuric acid.
  • the freed carboxylic acid is dissolved in a suitable solvent, such as ether or a low-boiling liquid paraffinic hydrocarbon.
  • the resultant solution is separated, dried, and freed of solvent, as by evaporation or by distillation, to obtain the product acid.
  • EXAMPLE 1 A solution of 25 parts 3-(2-thenoyl)propionic acid in 5.8 parts sodium hydroxide and 200 parts water is charged in an autoclave with 8 parts sulfur, 10 parts moist cobalt polysulfide catalyst and 1000p.s.i.g. hydrogen. The autoclave is heated to 260 C. while stirring and held at the temperature for 40 minutes. The autoclave is cooled and the filtered solution is treated with 100 parts diethyl ether to remove 0.4 part neutral materials. Acidification of the remaining aqueous solution followed by extraction with ether and removal of ether gives 21.7 parts (91% yield) of 4-(2-thienyl)butyric acid of high purity (98%).
  • EXAMPLE 2 A solution of 25 parts 3-(2-thenoyl)propionic acid in 5.8 parts sodium hydroxide and 200 parts water is charged into the autoclave with 10 parts moist cobalt polysulfide catalyst. Hydrogen sulfide gas, equivalent to 8 parts sulfur, and 1000 p.s.i.g. hydrogen are charged. The autoclave is heated to 260 during stirring and is held at this tem perature for 60 minutes. After cooling and venting, the mixture is worked-up as described in Example 1 to give 21.7 parts (91% yield, 100% conversion) of 4-(2-thienyl) butyric acid.
  • EXAMPLE 4 An example of the preparation of a catalyst suitable for the present invention is as follows: 30 parts molybdic oxide is dissolved in 16.8 parts sodium hydroxide and 300 parts water and charged to the autoclave and hydrogen sulfide equivalent to 8 moles hydrogen sulfide to 1 mole molybdic oxide is charged. After stirring one hour, 1000 p.s.i.g. hydrogen is charged and the autoclave is heated to 225 C. and held at this temperature for an additional hour. After cooling, the fine black powder is filtered and bottled for use as a reduction catalyst.
  • molybdenum trisulfide is dissolved in aqueous sodium hydroxide solution and reduced with 1000 p.s.i.g. hydrogen at 225 C. for one hour. After cooling a fine black powder is filtered and bottled for use as a reduction catalyst.
  • a method for reducing a ketoacid, 3-(2-thenoyl) propionic acid to 4-(2-thienyl) butyric acid that comprises contacting an aqueous solution of a water-soluble salt, selected from the group consisting of alkali metals and alkaline earth metals, of said ketoacid and hydrogen at a pressure of about 1000 p.s.i.g. to about 2300 p.s.i.g. with a catalyst consisting essentially of an aqueous sodium hydroxide-insoluble sulfide of a transitional metal of Groups 6a and 8 of the Periodic Arrangement of the Elements Based on Atomic Numbers, at a temperature of about 225 C. to about 280 C. and in the presence of hydrogen sulfide.
  • a water-soluble salt selected from the group consisting of alkali metals and alkaline earth metals
  • cata- 6 lyst is a molybdenum sulfide, in which the molybdenum is in a reduced valence state.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Catalysts (AREA)
  • Inorganic Compounds Of Heavy Metals (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US436922A 1965-03-03 1965-03-03 Process for the reduction of thiophenesubstituted ketoacids Expired - Lifetime US3412103A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US436922A US3412103A (en) 1965-03-03 1965-03-03 Process for the reduction of thiophenesubstituted ketoacids
NL6601413A NL6601413A (en:Method) 1965-03-03 1966-02-03
GB9170/66A GB1086375A (en) 1965-03-03 1966-03-02 Process for the reduction of heterocyclic sulphur group-substituted ketoacids
FR51910A FR1482037A (fr) 1965-03-03 1966-03-03 Procédé perfectionné pour réduire les groupes céto des cétoacides reliés à des structures hétérocycliques sulfurées

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US436922A US3412103A (en) 1965-03-03 1965-03-03 Process for the reduction of thiophenesubstituted ketoacids

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US3412103A true US3412103A (en) 1968-11-19

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GB (1) GB1086375A (en:Method)
NL (1) NL6601413A (en:Method)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2909657A1 (fr) * 2006-12-12 2008-06-13 Commissariat Energie Atomique Composition minerale apte a pieger l'hydrogene, procede de preparation et utilisations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2909657A1 (fr) * 2006-12-12 2008-06-13 Commissariat Energie Atomique Composition minerale apte a pieger l'hydrogene, procede de preparation et utilisations
WO2008071716A3 (fr) * 2006-12-12 2008-07-31 Commissariat Energie Atomique Composition minerale apte a pieger l'hydrogene, procede de preparation et utilisations
US20100105550A1 (en) * 2006-12-12 2010-04-29 Chantal Riglet-Martial Mineral Composition Capable of Trapping Hydrogen, Preparation Method and Uses
CN101563289B (zh) * 2006-12-12 2011-06-22 原子能委员会 能俘获氢的无机组合物、其制备方法和用途
US8093175B2 (en) 2006-12-12 2012-01-10 Commissariat A L'energie Atomique Mineral composition capable of trapping hydrogen, preparation method and uses

Also Published As

Publication number Publication date
GB1086375A (en) 1967-10-11
NL6601413A (en:Method) 1966-09-05

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AS Assignment

Owner name: RHONE-POULENC, INC. BLACK HORSE LANE, MONMOUTH JUN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST. AS OF JULY 31, 1981.;ASSIGNOR:MOBIL OIL CORPORATION, A NY CORP.;REEL/FRAME:003996/0522

Effective date: 19810731