EP2766371A1 - Procédé de fabrication de dithiine-tétracarboximides - Google Patents

Procédé de fabrication de dithiine-tétracarboximides

Info

Publication number
EP2766371A1
EP2766371A1 EP12772924.2A EP12772924A EP2766371A1 EP 2766371 A1 EP2766371 A1 EP 2766371A1 EP 12772924 A EP12772924 A EP 12772924A EP 2766371 A1 EP2766371 A1 EP 2766371A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
formula
thionyl chloride
excess
stage
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Withdrawn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
EP12772924.2A
Other languages
German (de)
English (en)
Inventor
Thomas Himmler
Thomas Geller
Lars Rodefeld
Frank Volz
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 Intellectual Property GmbH
Original Assignee
Bayer Intellectual Property GmbH
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 Intellectual Property GmbH filed Critical Bayer Intellectual Property GmbH
Priority to EP12772924.2A priority Critical patent/EP2766371A1/fr
Publication of EP2766371A1 publication Critical patent/EP2766371A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
    • C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
    • C07D207/456—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 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 other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to a novel process for the preparation of dithiine tetracarboximides.
  • Dithiine tetracarboximides as such are already known. Likewise, it is known that these dithiine-tetracarboximides can be used as anthelminthicides against internal parasites of animals, in particular nematodes, and have insecticidal activity (cf US 3,364,229). In addition, it is known that certain dithiine-tetracarboximides have antibacterial activity and have some activity against human mycoses (compare II Farmaco 2005, 60, 944-947). Furthermore, it is known that dithiine-tetracarboximides can be used as pigments in electrophotographic photoreceptors or as dyes in paints and polymers (cf JP-A 10-251265, PL-B 143804). Dithiine tetracarboximides of the formula (I)
  • R 1 and R 2 are identical or different and are hydrogen, for optionally mono- or polysubstituted by halogen, -OR 3 , -COR 4- substituted Ci-Cs-alkyl, optionally mono- or polysubstituted by halogen, Ci-C i-alkyl or Ci C 1 -C 6 -haloalkyl-substituted C 3 -C 7 -cycloalkyl, in each case optionally monosubstituted or polysubstituted by halogen, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, -COR 4 or sulphonylamino, substituted aryl or aryl- (C 1 -C 4 ) alkyl),
  • R 3 represents hydrogen, Ci-C 4 alkyl, Ci-C4-alkylcarbonyl or optionally mono- or polysubstituted by halogen, Ci-C 4 alkyl or Ci-C 4 haloalkyl substituted aryl,
  • R 4 is hydroxy, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy
  • R R 1 or R :
  • This method has the disadvantage that, for example, the handling of the highly toxic hydrogen sulfide gas is technically very difficult and expensive.
  • thiourea unwanted by-products are obtained in addition to the target product, which are very difficult to remove and worsen the achievable yields (see J. Heterocycl Chem, 1988, 25, 901-906).
  • succinic anhydride of the formula (V) is reacted in a first stage with an amine of the formula (III), if appropriate in the presence of a diluent. Subsequently, the succinic monoamides of the formula (VI) thus obtained are reacted for 6 hours with a large excess of thionyl chloride in the presence of dioxane as diluent at room temperature, the dithiine-tetracarboximides of the formula (I) being finally obtained in a series of numerous reaction steps.
  • the dithiine-tetracarboximides are optionally isolated directly from the reaction mixture or after addition of water by filtration.
  • the dithiine diisoimides of the formula (VII) may possibly be isolated before they are converted into the dithiine tetracarboximides of the formula (I).
  • This preparation method of the dithiine-tetracarboximides of the formula (I) can be illustrated by the following scheme:
  • a disadvantage of this process is the long reaction time and the result that either the yields obtained usually do not exceed about 30-40% of theory or the purities of the isolated products are insufficient (see Comparative Examples).
  • the reaction mixture in an aqueous workup of the reaction mixture is disadvantageous that thereby large amounts of thionyl chloride are destroyed; The resulting gases (SO2 and HCl) must be disposed of.
  • Another disadvantage is the fact that experience shows (see Comparative Examples), the product is not obtained in a fraction. Rather, it is often the case that after a first product isolation by filtration from the filtrate after prolonged standing (for example, overnight), further product precipitates, which must be isolated again by filtration. Sometimes this process needs to be done again. This way of working is very cumbersome and time consuming.
  • dithiine-tetracarboximides are obtained by dissolving N-substituted succinic acid amides in dry 1,4-dioxane and subsequently adding thionyl chloride. Subsequently, will the reaction mixture is warmed and the solution is concentrated in vacuo and separated by column chromatography and purified (see J. Heterocycl Chem., 2010, 47, 188-193).
  • R is R 1 or R 2 ,
  • M is a cation selected from the group of alkali metals, alkaline earth metals, transition metals and metals, and
  • m is 1, 2, 3 or 4, reacted with an excess of thionyl chloride, if appropriate in the presence of a diluent, then the excess of thionyl chloride removed and the product mixture thus obtained in a second stage in an organic solvent in the dithiine-tetracarboximide of the formula ( I) transferred.
  • the dithiine-tetracarboximides of the formula (I) can be obtained in higher yield, shorter time and better purity.
  • the product mixture obtained in the first step of the process according to the invention also already contains dithiine-tetracarboximides of the formula (I), but the main components are polysulfides of the formula (IX)
  • the thiosulfonic acid derivatives of the general formula (VIII) and the polysulfides of the general formula (IX) are novel and also the subject of the present invention.
  • R is the above-mentioned meanings of R 1 or R 2 and X is chlorine or hydroxy.
  • R 1 and R 2 are as defined above and n is 0, 1, 2, 3, 4, 5, 6, 7 or 8.
  • R R or R 2
  • the succinic acid ammonium carboxylates used as starting materials in carrying out the process according to the invention are generally defined by the formula (VI).
  • R stands for the meanings of R 1 or R 2 .
  • R 1 and R 2 are preferably identical or different and are preferably hydrogen, for optionally mono- or polysubstituted by fluorine, chlorine, bromine, -OR 3 , -COR 4 -substituted Ci-C6-alkyl, optionally mono- or polysubstituted by chlorine , methyl or trifluoromethyl-substituted C3-C7 cycloalkyl, in each case optionally monosubstituted or polysubstituted by fluorine, chlorine, bromine, methyl, trifluoromethyl, -COR 4, sulphonylamino substituted phenyl or phenyl- (Ci-C4 alkyl).
  • R 1 and R 2 are more preferably identical or different and are particularly preferably hydrogen, optionally optionally mono- or polysubstituted by fluorine, chlorine, hydroxyl, methoxy, ethoxy,
  • R 1 and R 2 are very particularly preferably identical or different and are very particularly preferably hydrogen, methyl, ethyl, n-propyl, isopropyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, in each case optionally by chlorine, methyl or trifluoromethyl substituted cyclopropyl or cyclohexyl.
  • R 1 and R 2 stand at the same time for methyl.
  • R 3 is preferably hydrogen, methyl, ethyl, methylcarbonyl, ethylcarbonyl or phenyl optionally mono- or polysubstituted by fluorine, chlorine, methyl, ethyl, n-propyl, isopropyl or trifluoromethyl.
  • R 3 particularly preferably represents hydrogen, methyl, methylcarbonyl or phenyl.
  • R 4 is preferably hydroxy, methyl, ethyl, methoxy or ethoxy.
  • R 4 particularly preferably represents hydroxy or methoxy.
  • M is preferably Li, Na, K, Rb, Cs with m equal to 1, or
  • M is particularly preferably Li, Na, K, where m is 1, or Be, Mg, Ca, m is 2, or
  • Mn, Fe, Co, Al with m being 1, 2, 3 or 4.
  • M is very particularly preferably Na, K, with m being 1, or
  • Succinic acid methyl amide carboxylates are particularly preferably used as starting materials, whereby the end product is the compound (1-1) 2,6-dimethyl-1H, 5H- [1,4-dithiino [2,3-c: 5,6-c'] dipyrrole -l, 3,5,7 (2H, 6H) -tetrone.
  • succinic acid cyclohexylamide sodium carboxylate as the starting material gives the compound (1-3) 2,6-dicyclohexyl-1H, 5H- [1,4] dithiino [2,3-c: 5,6-c '] dipyrrol-l, 3,5,7 (2H, 6H) -tetrone as end product.
  • succinic acid propylamide-sodium carboxylate is used as the starting material, the compound (1-4) 2,6-dipropyl-1H, 5H- [1,4] dithiino [2,3-c: 5,6-c'] dipyrrole is obtained. l, 3,5,7 (2H, 6H) -tetrone as end product.
  • Amount of thionyl chloride in the first step of the process according to the invention is between 1 and 100 moles per mole of succinic acid monoamide carboxylate of the formula (VI). It is preferred to use between 2 and 50 mol, more preferably between 4 and 40 mol, per mole of succinic acid amido-carboxylate of the formula (VI).
  • the reaction temperature in the first step of the process according to the invention can be varied within wide limits and is between 0 ° C. and 150 ° C. To achieve satisfactory space-time yields, it is preferable to work at temperatures between 20 ° C and 120 ° C; more preferably between 30 ° C and 100 ° C.
  • the reaction time in the first step of the process according to the invention is between 10 minutes and 24 hours. Preference is given to working between 30 minutes and 6 hours, more preferably between 1 and 4 hours.
  • the first step of the process according to the invention can be carried out in the presence of a diluent which is as inert as possible under the reaction conditions.
  • a diluent which is as inert as possible under the reaction conditions.
  • diluents are aliphatic hydrocarbons such as pentane, hexane, heptane, cyclohexane, methylcyclohexane, chlorinated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, aromatic hydrocarbons such as toluene, xylene, mesitylene, chlorinated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene, Ethers such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, nitriles such as acetonitrile, propionitrile, butyronitrile, esters such as methyl
  • the removal of the thionyl chloride can be carried out in principle by hydrolysis with water.
  • the thionyl chloride is removed by distillation under reduced pressure.
  • the optionally present diluent is preferably also distilled off under reduced pressure.
  • the residue obtained after removal of the excess thionyl chloride and optionally the diluent is dissolved in a new diluent and converted into the dithiine-tetracarboximides of the formula (I) by heating in this solvent.
  • the reaction mixture is stirred here.
  • organic solvents or solvent mixtures are used.
  • Suitable diluents for the second step of the process according to the invention are in detail water, dimethyl sulfoxide, sulfolane, alcohols such as, for example, methanol, ethanol, propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, tert-butanol, 1-pentanol, cyclopentanol, cyclohexanol, Ethylene glycol, ethylene glycol monomethyl ether, hydrocarbons such as hexane, heptane, cyclohexane, methylcyclohexane, toluene, xylenes, mesitylene, ethylbenzene, cumene, chlorobenzene, dichlorobenzene, nitrobenzene, esters such as methyl acetate, ethyl acetate, amides such as formamide, ⁇ , ⁇ -dimethylform
  • the mixing ratio of water to organic solvent can be varied within wide limits from, for example, 9: 1 to 1: 9.
  • the reaction temperature in the second step of the process according to the invention can be varied within wide limits and is between 0 ° C and 200 ° C. Preference is given to working at temperatures between 20 ° C and 150 ° C, more preferably between 30 ° C and 130 ° C.
  • the reaction time in the second step of the process according to the invention is between 5 minutes and 24 hours. Preference is given to working between 30 minutes and 12 hours, more preferably between 1 and 6 hours.
  • the present invention also provides processes for preparing polysulfides of the formula
  • R 1 and R 2 are identical or different and are hydrogen, for optionally mono- or polysubstituted by halogen, -OR 3 , -COR 4- substituted Ci-Cs-alkyl, optionally mono- or polysubstituted by halogen, Ci-C i-alkyl or Ci C 1 -C 6 -haloalkyl-substituted C 3 -C 7 -cycloalkyl, in each case optionally monosubstituted or polysubstituted by halogen, C 1 -C -alkyl, C 1 -C 4 -haloalkyl, -COR 4 or sulphonylamino-substituted aryl or aryl- (C 1 -C 4 -alkyl ) stand,
  • R is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkylcarbonyl or aryl which is optionally mono- or polysubstituted by halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl,
  • R is hydroxy, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy
  • n 0, 1 or 2
  • R is R 1 or R 2 ,
  • M is a cation selected from the group of alkali metals, alkaline earth metals, transition metals and metals, and
  • n 1, 2, 3 or 4

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pyrrole Compounds (AREA)

Abstract

La présente invention concerne un nouveau procédé de production de dithiine-tétracarboximides.
EP12772924.2A 2011-10-13 2012-10-11 Procédé de fabrication de dithiine-tétracarboximides Withdrawn EP2766371A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12772924.2A EP2766371A1 (fr) 2011-10-13 2012-10-11 Procédé de fabrication de dithiine-tétracarboximides

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11185004 2011-10-13
EP12772924.2A EP2766371A1 (fr) 2011-10-13 2012-10-11 Procédé de fabrication de dithiine-tétracarboximides
PCT/EP2012/070104 WO2013053783A1 (fr) 2011-10-13 2012-10-11 Procédé de fabrication de dithiine-tétracarboximides

Publications (1)

Publication Number Publication Date
EP2766371A1 true EP2766371A1 (fr) 2014-08-20

Family

ID=47022660

Family Applications (1)

Application Number Title Priority Date Filing Date
EP12772924.2A Withdrawn EP2766371A1 (fr) 2011-10-13 2012-10-11 Procédé de fabrication de dithiine-tétracarboximides

Country Status (10)

Country Link
US (1) US20140256956A1 (fr)
EP (1) EP2766371A1 (fr)
JP (1) JP2014530228A (fr)
KR (1) KR20140088561A (fr)
CN (1) CN103987716A (fr)
BR (1) BR112014008729A2 (fr)
IL (1) IL231878A0 (fr)
IN (1) IN2014CN02645A (fr)
MX (1) MX2014004096A (fr)
WO (1) WO2013053783A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2641908A1 (fr) * 2012-03-23 2013-09-25 Bayer CropScience AG Procédé de fabrication de dithiine-tétracarboximides

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3364229A (en) * 1964-01-30 1968-01-16 Shell Oil Co 1, 4 dithiin-2, 3, 5, 6-tetracarboximides and process for their preparation
PL143804B2 (en) 1985-10-15 1988-03-31 Univ Lodzki Process for preparing novel derivatives of 2,6-diphenyl-2,3,6,7-tetrahydro-1h,5h-1,4-dithiin-/2,3-c:5,6-c/-diprolo-1,3,5,7-tetraon substituted in phenyl ring
JP3530702B2 (ja) 1997-03-06 2004-05-24 京セラミタ株式会社 ジチオマレイン酸イミド誘導体を用いた電子写真感光体
PT2386203E (pt) * 2008-10-15 2014-02-17 Bayer Cropscience Ag Utilização de ditiina-tetracarboximidas para combater fungos fitopatogénicos
CN103003284B (zh) * 2010-04-14 2016-01-20 拜耳知识产权有限责任公司 制备二噻烯-四甲酰亚胺的方法
KR101746023B1 (ko) * 2010-04-14 2017-06-12 바이엘 인텔렉쳐 프로퍼티 게엠베하 디티인 테트라카복시-디이미드의 제조방법
DK2611814T3 (en) * 2010-09-03 2014-12-08 Bayer Ip Gmbh METHOD OF PREPARING DITHIIN-TETRACARBOXIMIDES
EP2611813B1 (fr) * 2010-09-03 2015-01-21 Bayer Intellectual Property GmbH Dithiine-tétra(thio)carboximides pour lutter contre des champignons phytopathogènes
EP2766372A1 (fr) * 2011-10-13 2014-08-20 Bayer Intellectual Property GmbH Procédé de fabrication de dithiine-tétracarboximides
EP2641908A1 (fr) * 2012-03-23 2013-09-25 Bayer CropScience AG Procédé de fabrication de dithiine-tétracarboximides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2013053783A1 *

Also Published As

Publication number Publication date
BR112014008729A2 (pt) 2017-04-18
WO2013053783A1 (fr) 2013-04-18
IL231878A0 (en) 2014-05-28
US20140256956A1 (en) 2014-09-11
KR20140088561A (ko) 2014-07-10
MX2014004096A (es) 2014-07-09
IN2014CN02645A (fr) 2015-08-07
JP2014530228A (ja) 2014-11-17
CN103987716A (zh) 2014-08-13

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