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DK151904B - METHOD OF ELECTROCHEMICAL PREPARATION OF 2- (2-AMINOETHYL) THIOPHEN - Google Patents

METHOD OF ELECTROCHEMICAL PREPARATION OF 2- (2-AMINOETHYL) THIOPHEN Download PDF

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DK151904B
DK151904B DK013879AA DK13879A DK151904B DK 151904 B DK151904 B DK 151904B DK 013879A A DK013879A A DK 013879AA DK 13879 A DK13879 A DK 13879A DK 151904 B DK151904 B DK 151904B
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process according
organic
thiophene
aminoethyl
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DK13879A (en
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Emile Henri Urbain Braye
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Parcor
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04Heterocyclic 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
    • C07D333/06Heterocyclic 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
    • C07D333/14Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C25ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25BELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00Electrolytic production of organic compounds
    • C25B3/20Processes
    • C25B3/25Reduction

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Materials Engineering (AREA)
  • Metallurgy (AREA)
  • Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

iin

DK 151904 BDK 151904 B

Den foreliggende opfindelse angår en fremgangsmåde til elektrokemisk fremstilling af 2-(2-aminoethyl)-thiophen.The present invention relates to a process for the electrochemical preparation of 2- (2-aminoethyl) thiophene.

2-(2-aminoethyl)-thiophen er et mellemprodukt, der benyttes 5 til syntese af thienopyridinderivater, som især har inhibe-rende virkning på blodpladeaggregationen samt antiinflamma-toriske og vasodilatoriske virkninger, og som er omhandlet i fransk patentskrift nr. 2.215.948 og beskrivelsen til det dertil hørende tillægspatent nr. 2.345.150.2- (2-Aminoethyl) -thiophene is an intermediate used for the synthesis of thienopyridine derivatives, which have especially inhibitory action on platelet aggregation as well as anti-inflammatory and vasodilatory effects, and are disclosed in French Patent No. 2,215,948. and the description of the accompanying supplemental patent No. 2,345,150.

1010

Pra S. Gronovitz og F. Sandberg: "Arkiv, for Kemi, 1970, 32, 217" er det kendt at fremstille 2-(2-aminoethyl)-thiophen ved reduktion af 3-nitrovinyl-2-thiophen med lithiumaluminium-hydrid, men dette reagens er dyrt og vanskeligt at håndtere 15 i industriel skala, så at mange forholdsregler må træffes ved dets anvendelse. Fremgangsmåden ifølge fransk patentskrift nr. 2.299.332, ved hvilken 2-(2-aminoethyl)-thiophen eller 2-(2-thienyl)-ethylamin blev fremstillet i to trin ud fra 2-(2-thienyl)-ethyl-p-toluensulfonat med'et udbytte på 34%, 20 repræsenterer en forbedring i forhold til den nævnte kendte reduktionsproces, men p-toluensulfonatderivatet skal være fremstillet i forvejen, f.eks. ved fremgangsmåden ifølge fransk patentskrift nr. 2.300.090, der resulterer i et udbytte på 72%. Det samlede udbytte ved den forbedrede fremgangsmåde 25 er derfor under 30%.Pra S. Gronovitz and F. Sandberg: "Archives, for Chemistry, 1970, 32, 217" it is known to prepare 2- (2-aminoethyl) thiophene by reduction of 3-nitrovinyl-2-thiophene with lithium aluminum hydride, but this reagent is expensive and difficult to handle on an industrial scale, so that many precautions must be taken in its use. The process of French Patent No. 2,299,332 in which 2- (2-aminoethyl) thiophene or 2- (2-thienyl) ethylamine was prepared in two steps from 2- (2-thienyl) ethyl-p toluene sulfonate with the yield of 34%, 20 represents an improvement over the known reduction process, but the p-toluenesulfonate derivative must be prepared in advance, e.g. by the method of French Patent No. 2,300,090 resulting in a yield of 72%. Therefore, the overall yield of the improved process 25 is below 30%.

Det har nu vist sig, at man ved fremgangsmåden ifølge opfindelsen kan fremstille 2-(2-aminoethyl)-thiophen ud fra 2-(2-nitro-vinyl)-thiophen i et udbytte på 47% i et trin ved anvendelse 30 af elektrokemisk reduktion af udgangsmaterialet.It has now been found that in the process of the invention, 2- (2-aminoethyl) thiophene can be prepared from 2- (2-nitro-vinyl) thiophene in 47% yield in one step using electrochemical 30 reduction of the starting material.

Den foreliggende opfindelse angår således en fremgangsmåde til fremstilling af 2-(2-aminoethyl)-thiophen med formlen I ch2-ch2-nh2 35 2Thus, the present invention relates to a process for the preparation of 2- (2-aminoethyl) thiophene of formula I ch2-ch2-nh2

DK 151904 BDK 151904 B

hvilken fremgangsmåde er ejendommelig ved, at man elektrokemisk reducerer 2-(2-nitrovinyl)-thiophen med formlen ^ S\ - [ ]τ- ch=ch-no9 i_I! ved et potentiale på 1,10-1,30 volt, målt i forhold til en mættet kalomel-referenceelektrode, fortrinsvis ved 1,15 volt, i et organisk eller organisk-vandigt medium i nærværelse af j^Q et alkalimetalchlorid i en koncentration på 0,2-0,7 mol/1, fortrinsvis 0,5 mol/1, som elektrolyt ved en sur pH-værdi og ved en temperatur mellem 5°C og 40°C, og at man udvinder det ønskede produkt fra reaktionsmediet. Udvinding af produktet foretages fordelagtigt ved hjælp af et organisk opløsnings-15 middel efter neutralisation af elektrolytten.which method is characterized by electrochemically reducing 2- (2-nitrovinyl) -thiophene of the formula ^ S \ - [] τ- ch = ch-no9 i_I! at a potential of 1.10-1.30 volts, measured relative to a saturated calomel reference electrode, preferably at 1.15 volts, in an organic or organic aqueous medium in the presence of 1 M a alkali metal chloride at a concentration of 0.2-0.7 mol / l, preferably 0.5 mol / l, as electrolyte at an acidic pH and at a temperature between 5 ° C and 40 ° C and recovering the desired product from the reaction medium. Advantageous extraction of the product is carried out by means of an organic solvent after neutralization of the electrolyte.

Det organiske medium bør være et sådant, som muliggør solubili-sering af udgangsmaterialet, dvs. 2-(2-nitrovinyl)-thiophen, og det kan eksempelvis være eddikesyre, dioxan eller methanol.The organic medium should be one which allows solubilization of the starting material, i.e. 2- (2-nitrovinyl) -thiophene, and it may be, for example, acetic acid, dioxane or methanol.

2020

Ifølge en foretrukken udførelsesform for opfindelsen gøres der brug af et vandigt-alkoholisk medium omfattende 20-70 vægt% organisk opløsningsmiddel, fortrinsvis en blanding omfattende 50% organisk opløsningsmiddel, såsom en vand-eddike-25 syreblanding (50:50). jAccording to a preferred embodiment of the invention, an aqueous-alcoholic medium comprising 20-70% by weight of organic solvent is used, preferably a mixture comprising 50% organic solvent, such as a water-acetic acid mixture (50:50). j

Reaktionsmediets pH-værdi skal ligge i det sure område og fortrinsvis ved pH ca. 2. Denne pH-værdi kan opnås ved tilsætning af en stærk uorganisk syre, såsom saltsyre, eller ved 3Q hjælp af en pasende puffer (citrat-HCl, f.eks.).The pH of the reaction medium should be in the acidic range and preferably at pH ca. 2. This pH can be obtained by the addition of a strong inorganic acid such as hydrochloric acid or by a suitable buffer (citrate-HCl, for example).

Elektrolytten sættes til det organiske eller vandigt-organiske medium til gennemførelse af den elektrokemiske reak- 35 3The electrolyte is added to the organic or aqueous-organic medium to carry out the electrochemical reaction.

DK 151904BDK 151904B

tion og er et alkalimetalchlorid, såsom natrium- eller lithium-chlorid, til en passende koncentration, som en 0,2-0,7 mol/1, og fortrinsvis 0,5 mol/1.is an alkali metal chloride, such as sodium or lithium chloride, to an appropriate concentration, such as 0.2-0.7 mol / l, and preferably 0.5 mol / l.

g En passende temperatur i reaktionsmediet ligger mellem 5°C og 40°C, og det foretrækkes at anvende stuetemperatur.g An appropriate temperature in the reaction medium is between 5 ° C and 40 ° C, and room temperature is preferred.

Koncentrationen af 2-nitro-2-vinyl-thiophen i reaktionsmediet ligger fordelagtigt mellem 1 g/1 og 10 g/1, fortrinsvis mellem 1Q 1 g/1 og 3 g/1.The concentration of 2-nitro-2-vinyl-thiophene in the reaction medium is advantageously between 1 g / l and 10 g / l, preferably between 1 and 1 g / l and 3 g / l.

Som arbejdselektrode for den elektrokemiske celle benyttes et materiale med en høj hydrogenoverspænding, såsom kviksølv, zink eller bly, idet et kviksølvlag foretrækkes.As the working electrode of the electrochemical cell, a material with a high hydrogen overvoltage such as mercury, zinc or lead is used, with a mercury layer being preferred.

1515

Opfindelsen forklares nærmere i den efterfølgende beskrivelse i forbindelse med figuren på tegningen.The invention is explained in more detail in the following description in connection with the figure in the drawing.

Den elektrokemiske reduktion af 2-(2-nitrovinyl)-thiophen 20 kan udføres i en celle, som den på tegningen viste.The electrochemical reduction of 2- (2-nitrovinyl) -thiophene 20 can be carried out in a cell as shown in the drawing.

Denne celle 1 er delt i et elektrolysekammer 2 og et anodekammer 3, hvilke kamre er adskilt ved hjælp af en porøs væg 4 af eksempelvis sintret glas til sikring af elektrisk led-25 ning. En platin- eller grafitelektrode 5 fungerer som anode, medens en elektrode 6 (eller arbejdselektrode) er placeret ved bunden eller nær ved bunden af elektrolysekammeret. Cellen 1 er i kammeret 2 udstyret med et omrørerorgan for reaktionsmediet, og i den viste udførelsesform er en magnetstang 30 7 placeret i nærheden af cellebunden.This cell 1 is divided into an electrolysis chamber 2 and anode chamber 3, which chambers are separated by a porous wall 4 of, for example, sintered glass to secure electrical conduction. A platinum or graphite electrode 5 acts as an anode while an electrode 6 (or working electrode) is located at the bottom or near the bottom of the electrolytic chamber. The cell 1 is provided in the chamber 2 with a stirring means for the reaction medium, and in the embodiment shown, a magnetic rod 30 7 is located near the cell bottom.

Cellen er også indrettet med et indløb 8 for indifferent gas under elektrolytopløsningens overflade og har et udløb 9 for denne gas i cellelåget 10.The cell is also provided with an inert gas inlet 8 below the surface of the electrolyte solution and has an outlet 9 for this gas in the cell lid 10.

En referenceelektrode 11 er placeret uden for cellen med henblik på hindring af forurening med reduktionsprodukterne, i- 35A reference electrode 11 is located outside the cell to prevent contamination with the reduction products, e.g.

DK 151904BDK 151904B

4 det den elektriske ledning foregår via en bro 12 omfattende en trevejsventil 13 og et rør 14, som er lukket med sintret glas, og som rager ned i katodefcammeret 2.4, the electrical conduit is conducted via a bridge 12 comprising a three-way valve 13 and a tube 14, which is closed with sintered glass, which projects into the cathode chamber 2.

Det efterfølgende eksempel tjener til illustration af 5 opfindelsen.The following example serves to illustrate the invention.

Eksempel.Example.

^ Den elektrokemiske reduktion af 2-(2-nitrovinyl)-thiophen foretages i en celle indeholdende en platinanode, og cellens ar-bejdselektrode eller katode er et kviksølvlag.The electrochemical reduction of 2- (2-nitrovinyl) thiophene is made in a cell containing a platinum anode and the working electrode or cathode of the cell is a mercury layer.

Reaktionsmediet er en eddikesyre-vand-blanding (50:50), og ^ 0,5 molær lithiumchlorid anvendes som elektrolyt.The reaction medium is an acetic acid-water mixture (50:50) and 0.5 molar lithium chloride is used as the electrolyte.

Reduktionspotentialet holdes ved 1,150 volt i forhold til en mættet kalomelelektrode, og reaktionen udføres ved stuetemperatur .The reduction potential is maintained at 1,150 volts relative to a saturated calomel electrode and the reaction is carried out at room temperature.

20 2-(2-nitrovinyl)-thiophensættes til det vandigt-organiske medium til en begyndelseskoncentration på 2,5 g/1.2- (2-Nitrovinyl) thiophenate is added to the aqueous-organic medium to an initial concentration of 2.5 g / L.

Cellen holdes under en nitrogenatmosfære, og reduktionen udføres under omrøring ved hjælp af strømgennemgang ved den forudbestemte spænding.The cell is kept under a nitrogen atmosphere and the reduction is carried out with stirring by means of current flow at the predetermined voltage.

Efter afslutning af elektrolysen (efter gennemgang af 2500 coulomb), neutraliseres katodekammerets elektrolyt, ekstra-heres med chloroform og vaskes derpå med vand samt tørres over vandfrit I^CO^. Den ønskede amin udvindes som hydrochlo= ridet eller oxalatet i ethanol.After completion of the electrolysis (after reviewing 2500 coulomb), the cathode chamber electrolyte is neutralized, extracted with chloroform and then washed with water and dried over anhydrous 1 CO 2. The desired amine is recovered as the hydrochloride or the oxalate in ethanol.

Udbyttet af 2-(2-aminoethyl)-thiophen er 47%, regnet i forhold 35 til udgangsmaterialet Dette udbytte svarer også til det fara-diske udbytte, eftersom den elektricitetsmængde, som er passeret gennem cellen, svarer til en 100% omdannelse.The yield of 2- (2-aminoethyl) thiophene is 47%, calculated in relation to the starting material. This yield also corresponds to the hazardous yield since the amount of electricity passed through the cell corresponds to a 100% conversion.

Claims (6)

1. Fremgangsmåde til fremstilling af 2-(2-aminoethyl)-thio-5 phen med formlen -^1 2\ 11 ||- ch2-ch2-nh2 kendetegnet ved/ at man elektrokemisk reducerer 10 2-(2-nitrovinyl)-thiophen med formlen S j/ /·—CH=CH-N0o Ij_II 2 15 ved et potentiale på 1,10-1,30 volt, målt i forhold til en mættet kalomel-referenceelektrode, fortrinsvis ved 1,15 volt, i et organisk eller organisk-vandigt medium i nærværelse af et alkalimetalchlorid i en koncentration på 0,2-0,7 mol/1, fortrinsvis 0,5 mol/1, som elektrolyt ved en sur pH-værdi 20 og ved en temperatur mellem 5°C og 40°C, og at man udvinder det ønskede produkt fra reaktionsmediet.A process for the preparation of 2- (2-aminoethyl) -thiophenyl of the formula - (CH2-CH2-NH2) characterized by electrochemically reducing 2- (2-nitrovinyl) - thiophene of the formula S₂ / CH -CH = CH-NOo I₂-II 2 at a potential of 1.10-1.30 volts, measured relative to a saturated calomel reference electrode, preferably at 1.15 volts, in an organic or organic aqueous medium in the presence of an alkali metal chloride at a concentration of 0.2-0.7 mol / l, preferably 0.5 mol / l, as electrolyte at an acidic pH of 20 and at a temperature between 5 ° C and 40 ° C, and recovering the desired product from the reaction medium. 2. Fremgangsmåde ifølge krav 1, kendetegnet ved, at 2-(2-aminoethyl)-thiophenen udvindes fra reaktionsmediet 25 ved hjælp af et organisk opløsningsmiddel efter neutralisation af elektrolytten.Process according to claim 1, characterized in that the 2- (2-aminoethyl) thiophene is recovered from the reaction medium 25 by means of an organic solvent after neutralization of the electrolyte. 3. Fremgangsmåde ifølge krav 1 eller 2, kendetegnet ved, at det organiske eller vandigt-organiske medium 30 er valgt blandt eddikesyre, methanol, dioxan eller blandinger deraf med vand i en mængde på 20-70 vægt%. Fremgangsmåde ifølge krav 3, kendetegnet ved, at en vand-eddikesyreblanding (50:50) anvendes som medium. 35 2 Fremgangsmåde ifølge ethvert af de foregående krav, kendetegnet ved, at en kviksølv-, zink- eller blykatode og en platin- eller grafitanode anvendes som elektroder. DK 151904 BProcess according to claim 1 or 2, characterized in that the organic or aqueous-organic medium 30 is selected from acetic acid, methanol, dioxane or mixtures thereof with water in an amount of 20-70% by weight. Process according to claim 3, characterized in that a water-acetic acid mixture (50:50) is used as the medium. A method according to any one of the preceding claims, characterized in that a mercury, zinc or lead cathode and a platinum or graphite anode are used as electrodes. DK 151904 B 6. Fremgangsmåde ifølge ethvert af de foregående krav, kendetegnet ved, at ekstraktionsopløsningsmidlet er chloroform.Process according to any one of the preceding claims, characterized in that the extraction solvent is chloroform. 7. Fremgangsmåde ifølge krav 1, kendetegnet ved, 5 at reaktionstemperaturen er stuetemperatur.Process according to claim 1, characterized in that the reaction temperature is room temperature. 8. Fremgangsmåde ifølge krav 1, kendetegnet ved, at begyndelseskoncentrationen af 2-( 2-nitrovinyl )‘-thiophen er 1-10 g/1. i iProcess according to claim 1, characterized in that the initial concentration of 2- (2-nitrovinyl) - thiophene is 1-10 g / l. i i
DK013879A 1978-01-25 1979-01-12 METHOD OF ELECTROCHEMICAL PREPARATION OF 2- (2-AMINOETHYL) THIOPHEN DK151904C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR7801992A FR2415671A1 (en) 1978-01-25 1978-01-25 PROCESS FOR PREPARING 2-AMINO 2-ETHYL-2-THIOPHENE BY ELECTROCHEMICAL METHOD
FR7801992 1978-01-25

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DK13879A DK13879A (en) 1979-07-26
DK151904B true DK151904B (en) 1988-01-11
DK151904C DK151904C (en) 1988-06-06

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EP (1) EP0003446B1 (en)
JP (1) JPS6046190B2 (en)
AR (1) AR220736A1 (en)
AT (1) AT364839B (en)
BE (1) BE873677A (en)
CH (1) CH635618A5 (en)
DE (1) DE2960070D1 (en)
DK (1) DK151904C (en)
ES (1) ES476659A1 (en)
FI (1) FI62684C (en)
FR (1) FR2415671A1 (en)
GB (1) GB2013196B (en)
GR (1) GR65325B (en)
IE (1) IE47783B1 (en)
IT (1) IT1115135B (en)
LU (1) LU80772A1 (en)
MX (1) MX5460E (en)
NO (1) NO151715C (en)
PT (1) PT69105A (en)

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US5191090A (en) * 1990-01-25 1993-03-02 Syntex (U.S.A.) Inc. Preparation of 2-(2'-thienyl)ethylamine derivatives and synthesis of thieno[3,2-c]pyridine derivatives therefrom
JP7229710B2 (en) 2018-09-26 2023-02-28 本田技研工業株式会社 VEHICLE CONTROL DEVICE, VEHICLE CONTROL METHOD, AND PROGRAM

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DE2960070D1 (en) 1981-02-12
IE790112L (en) 1979-07-25
ES476659A1 (en) 1979-05-16
JPS6046190B2 (en) 1985-10-15
FI62684C (en) 1983-02-10
GR65325B (en) 1980-08-11
DK13879A (en) 1979-07-26
NO790231L (en) 1979-07-26
FR2415671A1 (en) 1979-08-24
GB2013196B (en) 1982-06-23
DK151904C (en) 1988-06-06
ATA38379A (en) 1981-04-15
AT364839B (en) 1981-11-25
LU80772A1 (en) 1979-05-16
JPS54117462A (en) 1979-09-12
AR220736A1 (en) 1980-11-28
CH635618A5 (en) 1983-04-15
PT69105A (en) 1979-02-01
NO151715C (en) 1985-05-22
EP0003446B1 (en) 1980-11-26
GB2013196A (en) 1979-08-08
FR2415671B1 (en) 1981-11-20
FI790121A7 (en) 1979-07-26
BE873677A (en) 1979-07-24
IE47783B1 (en) 1984-06-13
FI62684B (en) 1982-10-29
MX5460E (en) 1983-08-11
EP0003446A1 (en) 1979-08-08
IT7947735A0 (en) 1979-01-23
IT1115135B (en) 1986-02-03
NO151715B (en) 1985-02-11

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