EP4688764A2 - Procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate - Google Patents

Procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate

Info

Publication number
EP4688764A2
EP4688764A2 EP24715486.7A EP24715486A EP4688764A2 EP 4688764 A2 EP4688764 A2 EP 4688764A2 EP 24715486 A EP24715486 A EP 24715486A EP 4688764 A2 EP4688764 A2 EP 4688764A2
Authority
EP
European Patent Office
Prior art keywords
methyl
carboxylate
xylene
formula
methylthiophene
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.)
Pending
Application number
EP24715486.7A
Other languages
German (de)
English (en)
Inventor
Alexander ARLT
Thomas Geller
Dirk Brohm
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.)
Bayer AG
Original Assignee
Bayer AG
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 Bayer AG filed Critical Bayer AG
Publication of EP4688764A2 publication Critical patent/EP4688764A2/fr
Pending legal-status Critical Current

Links

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
    • C07D333/26—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the invention relates to a novel process for the preparation of methyl 4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate, which is known as an intermediate for the synthesis of the herbicide thiencarbazone-methyl (DE 19933260).
  • methyl -4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate can be prepared starting from methyl 4-(chlorosulfonyl)-5-methylthiophene-3-carboxylate by reaction with a metal cyanate in the presence of an imidazole (WO2018/153767).
  • the sulfochloride was reacted with 1 - 2 equivalents of sodium cyanate in the presence of 1 - 1.5 equivalents of N-methylimidazole.
  • the resulting product was converted directly to thiencarbazone-methyl either in a one-pot process or in a two-step process.
  • Thiencarbazone-methyl was obtained in yields of 76% - 84%.
  • methyl -4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate can be prepared from the corresponding sulfonamide by phosgenation in the absence of an organic base and optionally in the presence of a catalyst (W02006/072376).
  • the sulfonamide was reacted with an excess of 2.4 equivalents of phosgene in the presence of n-butyl isocyanate or pentyl isocyanate. The product was obtained in 83% yield in both cases.
  • triphosgene has also been used in the literature for the synthesis of sulfonyl isocyanates.
  • the reported syntheses are disadvantageous due to various aspects. They either deliver the desired product in low yields (ChemCatChem (2020), 12(17), 4352-4372), require long reaction times (W02015/061518) or use large amounts of triphosgene (Nongyao (2015), 54(2), 83-87).
  • W02015/0615108 long reaction times
  • triphosgene Neongyao (2015), 54(2), 83-87.
  • several of the previously mentioned disadvantageous aspects apply (Journal of the American Chemical Society 2009, 131(25), 8754 - 8755).
  • Triphosgene is also toxic. However, unlike phosgene, it is a solid. Phosgene is usually only released from triphosgene in the reactor. Triphosgene can be added dropwise to a reaction solution as a solution. The phosgene is therefore released locally and in a controlled manner. The risk of gas release is therefore significantly reduced.
  • methyl 4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate obtainable by this process should preferably be obtained in high yield and in high chemical purity. Furthermore, this process should reduce the use of toxic hazardous substances (e.g. phosgene), solvents and other additives compared to the state of the art.
  • toxic hazardous substances e.g. phosgene
  • reaction can be carried out at increased concentration (less solvent) if the amount of catalyst used is simultaneously reduced. This is all the more surprising since increasing the concentration without simultaneously reducing the amount of catalyst leads to a reduced yield and reduction in product purity.
  • the present invention therefore relates to a process for the preparation of methyl 4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate of the formula (I) by reacting methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) with diphosgene or triphosgene in the presence of one or more solvents and a catalyst, wherein, with respect to diphosgene, the molar ratio of the methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of the formula (II) to diphosgene is in the range from 1.0:0.5 to 1.0:2.25; or, with respect to triphosgene, the molar ratio of the methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of the formula (II) to triphosgene is in the range from 1.0:0.333 to 1.0:1.5; and the molar ratio of
  • the molar ratio between the methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of the formula (II) and the catalyst can be selected depending on the concentration of the reactant of the formula (II) in the reaction solvent.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to catalyst is in the range of 1.0:0.5 to 1.0:2.0 and particularly preferably between 1.0:0.7 and 1.0:1.8.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to catalyst is in the range of 1.0:0.3 to 1.0:1.8 and particularly preferably between 1.0:0.5 and 1.0:1.6.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to Catalyst in the range of 1.0:0.1 to 1.0:1.6 and particularly preferably between 1.0:0.3 and 1.0:1.4.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to catalyst is in the range of 1.0:0.01 to 1.0:1.4 and particularly preferably between 1.0:0.1 and 1.0:0.8.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to catalyst is in the range of 1.0:0.01 to 1.0:1.2 and particularly preferably between 1.0:0.05 and 1.0:0.7.
  • the preferred molar ratio of methyl 4-(aminosulfonyl)-5-methylthiophene-3-carboxylate of formula (II) to catalyst is in the range of 1.0:0.01 to 1.0:1.0 and particularly preferably between 1.0:0.05 and 1.0:0.6.
  • methyl 4-isocyanatosulfonyl-5-methyl-thiophene-3-carboxylate of the formula (I) can be prepared with very good yields and in very good quality using the process according to the invention.
  • the process according to the invention overcomes further disadvantages resulting from the prior art.
  • the compounds of formula (II) can be obtained, for example, according to the process described in DE19933260.
  • alkyl stands for straight-chain, branched or cyclic hydrocarbons having preferably 1 to 8 carbon atoms, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, 2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,
  • phosgene equivalent used in the present patent application is based on the following relationship: 1 equivalent of triphosgene corresponds to 3 phosgene equivalents; 1 equivalent of diphosgene corresponds to 2 phosgene equivalents.
  • Particularly preferred solvents are chlorobenzene, toluene, o-xylene, m-xylene, p-xylene, technical xylene, ethylbenzene or mixtures thereof.
  • the reaction is generally carried out at a temperature between 20 °C and 200 °C, preferably between 80 °C and 160 °C, most preferably between 110 °C and 140 °C.
  • a 500 mL glass reactor equipped with an overhead stirrer, a gas inlet and a reflux condenser was used.

Landscapes

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

Abstract

L'invention concerne un procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate de formule (I) par réaction du méthyl-4-(aminosulfonyl)-5-méthylthiophène-3-carboxylate de formule (II) avec du diphosgène ou du triphosgène en présence d'un ou plusieurs solvants et d'un catalyseur, procédé selon lequel, pour ce qui est du disphogène, le rapport molaire du méthyl-4-(aminosulfonyl)-5-méthylthiophène-3-carboxylate de formule (II) au diphosgène est compris entre 1,0 : 0,5 et 1,0 : 2,25 ; ou, pour ce qui est du triphosgène, le rapport molaire du méthyl-4-(aminosulfonyl)-5-méthylthiophène-3-carboxylate de formule (II) au triphosgène est compris entre 1,0 : 0,333 et 1,0 : 1,5 ; et le rapport molaire du méthyl-4-(aminosulfonyl)-5-méthylthiophène-3-carboxylate de formule (II) au catalyseur est compris entre 1,0 : 0,01 et 1,0 : 2,0.
EP24715486.7A 2023-03-29 2024-03-25 Procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate Pending EP4688764A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP23165099 2023-03-29
PCT/EP2024/057902 WO2024200331A2 (fr) 2023-03-29 2024-03-25 Procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate

Publications (1)

Publication Number Publication Date
EP4688764A2 true EP4688764A2 (fr) 2026-02-11

Family

ID=85781676

Family Applications (1)

Application Number Title Priority Date Filing Date
EP24715486.7A Pending EP4688764A2 (fr) 2023-03-29 2024-03-25 Procédé de production du méthyl-4-isocyanatosulfonyl-5-méthyl-thiophène-3-carboxylate

Country Status (8)

Country Link
EP (1) EP4688764A2 (fr)
JP (1) JP2026511628A (fr)
KR (1) KR20250164206A (fr)
CN (1) CN120712257A (fr)
IL (1) IL323579A (fr)
MX (1) MX2025011158A (fr)
TW (1) TW202500015A (fr)
WO (1) WO2024200331A2 (fr)

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19933260A1 (de) 1999-07-15 2001-01-18 Bayer Ag Substituierte Thien-3-yl-sulfonylamino(thio)carbonyl-triazolin(thi)one
DE19937118A1 (de) * 1999-08-06 2001-02-08 Bayer Ag Substituierte Thienyl(amino)sulfonylharnstoffe
DE102004063192A1 (de) 2004-12-29 2006-07-13 Bayer Cropscience Ag Verfahren zur Herstellung von substituierten Thiophensulfonylisocyanaten
AU2014340110B2 (en) 2013-10-24 2018-07-12 VIIV Healthcare UK (No.5) Limited Inhibitors of human immunodeficiency virus replication
US10053419B2 (en) * 2014-12-17 2018-08-21 Sumitomo Chemical Company, Limited Isocyanate compound manufacturing method
TWI668211B (zh) 2017-02-23 2019-08-11 德商拜耳作物科學公司 製備4-[(4,5-二氫-3-甲氧基-4-甲基-5-側氧-1h-1,2,4-三唑-1-基)羰基)胺磺醯基]-5-甲基噻吩-3-羧酸甲酯之方法
CN114181120A (zh) * 2022-02-14 2022-03-15 寿光诺盟化工有限公司 一种对甲苯磺酰异氰酸酯的制备方法

Also Published As

Publication number Publication date
MX2025011158A (es) 2025-10-01
WO2024200331A3 (fr) 2024-11-21
JP2026511628A (ja) 2026-04-14
IL323579A (en) 2025-11-01
TW202500015A (zh) 2025-01-01
CN120712257A (zh) 2025-09-26
WO2024200331A2 (fr) 2024-10-03
KR20250164206A (ko) 2025-11-24

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