CH395967A - Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acid - Google Patents
Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acidInfo
- Publication number
- CH395967A CH395967A CH215160A CH215160A CH395967A CH 395967 A CH395967 A CH 395967A CH 215160 A CH215160 A CH 215160A CH 215160 A CH215160 A CH 215160A CH 395967 A CH395967 A CH 395967A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- racemic
- dimercapto
- succinic acid
- addition
- Prior art date
Links
- ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 title claims description 18
- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- DUFSSPJKXPKOIZ-UHFFFAOYSA-N 2-acetyl-4-oxo-3-sulfanylcarbonylpentanoic acid Chemical compound C(C)(=O)C(C(=S)O)C(C(=O)O)C(C)=O DUFSSPJKXPKOIZ-UHFFFAOYSA-N 0.000 claims description 3
- YTIVTFGABIZHHX-UHFFFAOYSA-N butynedioic acid Chemical compound OC(=O)C#CC(O)=O YTIVTFGABIZHHX-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001640 fractional crystallisation Methods 0.000 claims description 2
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 2
- 238000000926 separation method Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ACTRVOBWPAIOHC-LWMBPPNESA-N (2r,3r)-2,3-bis(sulfanyl)butanedioic acid Chemical compound OC(=O)[C@@H](S)[C@H](S)C(O)=O ACTRVOBWPAIOHC-LWMBPPNESA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 239000002253 acid Substances 0.000 description 5
- 229910052787 antimony Inorganic materials 0.000 description 5
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 5
- 238000007259 addition reaction Methods 0.000 description 4
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- FAWGZAFXDJGWBB-UHFFFAOYSA-N antimony(3+) Chemical compound [Sb+3] FAWGZAFXDJGWBB-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- -1 ethyl acetate Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- KLLYWRUTRAFSJT-UHFFFAOYSA-M potassium;4-hydroxy-4-oxobut-2-ynoate Chemical compound [K+].OC(=O)C#CC([O-])=O KLLYWRUTRAFSJT-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/90—Antimony compounds
- C07F9/902—Compounds without antimony-carbon linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/06—Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von racemischer und optisch aktiver 2,3-Dimercapto bernsteinsÏure
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von 2, 3-Dimercapto-bernsteinsäure der Formel
EMI1.1
welches dadurch gekennzeichnet ist, dass Acetylendicarbonsäure durch Anlagerung von Thiaessigsame in 2, 3-Diacetyl-thiobernsteinsäure und diese durch Hydrolyse in die 2, 3-Dimercapto-bernsteinsäure über- geführt wird, wobei zu einem beliebigen Zeitpunkt nach erfolgter Anlagerung die racemische Form des Reaktionsproduktes von der meso-Form isoliert wird.
Die so erhaltene 2, 3-Dimercapto-bernsteinsäure kann hierauf in einen Dialkylester der Formel
EMI1.2
übergeführt werden, worin R eine niedere Alkylgruppe, insbesondere die Methylgruppe, bedeutet.
Ferner kann das in racemischer Form erhaltene Reaktionsprodukt in die optischen Antipoden aufgespalten werden.
Die Anlagerungsreaktion wird vorteilhafterweise unter Anwendung von mindestens 2 Mol Thioessigsäure auf 1 Mol Acetylendicarbonsäure und in einem Lösungsmittel, z. B. einem Ester, wie Essigester, oder einem cyclischen Ather, wie Dioxan oder Tetra hydrofuran, zweckmässig bei einer Temperatur unterhalb 50 durchgeführt.
Die Hydrolyse der durch die Anlagerungsreaktion erhaltenen 2, 3-Diacetylthio-bernsteinsäure zur 2, 3 Dimercapto-bernsteinsäure kann in saurem oder in basischem Medium, z. B. in wässriger Salzsäure oder in Natronlauge zweckmässig bei Raumtemperatur durchgeführt werden.
Die Veresterung der erhaltenen 2, 3-Dimercapto bemsteinsäure kann in an sich bekannter Weise, z. B. durch Reaktion mit einem Alkanol oder einem Alkylierungsmittel, wie Diazomethan, erfolgen. So erhält man durch Umsetzung der 2, 3-Dimercaptobernsteinsäure mit 2 Mol Diazomethan den Dimethylester der Säure.
Die Isolierung der racemischen Form wird zweckmässigerweise direkt nach der Anlagerungsreaktion vorgenommen, indem z. B. das nach dem Einengen der Reaktionslösung erhaltene rohe Anlagerungsprodukt nach an sich bekannten Methoden, z. B. durch fraktionierte Kristallisation, in die mesound die racemische dl-Form aufgetrennt wird. Die Isolierung des Racemates kann aber auch nach erfolgter Hydrolyse des Anlagerungsproduktes stattfinden.
Die Zerlegung in die optisch aktiven Formen des erfindungsgemäss erhaltenen Racemates kann nach an sich bekannten Methoden erfolgen, z. B. durch Salzbildung mit einer optisch aktiven Base, wie Brucin, Chinin usw.
Die Zerlegung kann zu beliebigem Zeitpunkt vorgenommen werden, vorteilhafterweise aber nach erfolgter Anlagerungsreaktion oder nach erfolgter Hydrolyse des Anlagerungsproduktes.
Die nach dem erfindungsgemässen Verfahren er hältlichen racemischen und optisch aktiven Verbin dungen sind interessante, gewerblich verwertbare Produkte, die sich insbesondere durch ihre fungizide Wirkung auszeichnen.
Die erfindungsgemäss erhältlichen Verbindungen können auch zur Herstellung von Metallkomplexsn Verwendung finden. Letztere, insbesondere in Verbindung mit Antimon, zeigen im Tierexperiment hervorragende Wirkung bei Infektionen mit Schistosoma mansoni. Ein bevorzugter Metallkomplex ist derjenige zwischen dl-2, 3-Dimercapto-bernsteinsäure und Antimon. Er kann z. B. durch Reaktion von dl-2, 3 Dimercapto-bernsteinsäure mit einer dreiwertigen Antimonverbindung, wie Antimon-III-oxyd, Antimon III-hydroxyd oder Antimon-III-acetat, erhalten werden.
Beispiel 1
Zu 500 mi einer 5n Lösung von Chlorwasserstoff in Essigester werden unter Eiskühlung 380 g Acetylendicarbonsäuremonokaliumsalz innert 30 Minuten zugerührt. Nach einer Stunde werden 380 g Thio essigsäure unter Rühren und mässigem Kühlen innert ; 21/2 bis 3 Stunden so zugetropft, dass die Reaktionstemperatur nicht über 35 steigt. Man rührt noch 15 Stunden bei Raumtemperatur weiter. Das Reaktionsgemisch wird sodann zwischen Wasser und Essigester verteilt. Durch Einengen der Essigesterlösung auf etwa 1 Liter fallen zunächst 260 g einer kristallisierten Substanz aus, von welcher abfiltriert wird.
Sie besteht vorwiegend aus meso-2, 3-Diacetylthio-bern- steinsäure, die durch Umlösen aus Essigester gereinigt werden kann. Durch Einengen des Filtrates und Zugabe von Petroläther wird die dl-2, 3-Diacetylthiobernsteinsäure gewonnen. Zur Reinigung wird sie mit Dibutyläther ausgekocht und dann aus Essigester Petroläther umgelöst. Man erhält 75 g reine Verbindung vom Schmelzpunkt 150-152 .
19 g dl-2, 3-Diacetylthio-bernsteinsäure werden in 190 ml 3n Natronlauge gelöst und während 2 Minuten bei Raumtemperatur belassen. Dann kühlt man auf 0 ab, sättigt mit Kochsalz, stellt mit Salzsäure kongosauer und extrahiert mit Ather. Der nach dem Einengen der ätherischen Lösung erhaltene Rück- stand wird aus Isopropyläther umgelöst. Man erhält 10, 5 g dl-2, 3-Dimercapto-bernsteinsäure vom Schmelz- punkt 126-127 .
Beispiel 2
2, 6 g gemäss Beispiel 1 erhaltener dl-2, 3-Di mercapto-bernsteinsäure werden in 150 ml Ather gelöst und mit der zur Methylierung von 2 Carboxylgruppen berechneten Menge einer ätherischen Diazomethanlösung versetzt. Man wäscht anschliessend mit Bicarbonatlösung und Wasser, trocknet die ätherische Lösung über Natriumsulfat, engt ein und reinigt den erhaltenen dl-2, 3-Dimercapto-bernsteinsäure-dimethyl- ester durch Destillation im Hochvakuum, wobei ein farbloses ÖI übergeht. Siedepunkt 80 /0, 01 mm Hg.
Der Dimethylester kann auch wie folgt hergestellt werden :
40 g dl-2, 3-Dimercapto-bernsteinsäure werden in einer Lösung von 20 ml konz. Schwefelsäure in 300 ml Methanol 5 Stunden unter Rückfluss gekocht.
Nach dem Erkalten wird die Lösung im Vakuum auf etwa 100 ml eingeengt, mit 400 ml Ather verdünnt und neutral gewaschen. Nach Trocknen über Natriumsulfat wird die ätherische Lösung eingeengt und der erhaltene dl-2, 3-Dimercapto-bernsteinsäure- dimethylester im Hochvakuum destilliert. Man erhält 35 g farbloses 01 vom Siedepunkt 80¯/0, 01 mm Hg.
Beispiel 3
4, 5 g gemmas Beispiel 1 erhaltener dl-2, 3-Di mercapto-bernsteinsäure werden in 250 ml Methanol gelöst und mit einer Lösung von 20 g Brucin in 250ml Methanol versetzt. Das Brucinsalz der dl-2, 3 Dimercapto-bernsteinsäure kristallisiert spontan aus (23 g, Schmelzpunkt 156-158 ). Zur optischen Spaltung wird es mit 240 ml In Salzsäure übergossen und während 2 Stunden gut geschüttelt. Man erhält dabei 9, 4 g unlösliche Anteile, die weiter unten auf (+)-2, 3-Dimercapto-bernsteinsäure verarbeitet werden.
Zur Gewinnung der (-)-drehenden Säure sättigt man die salzsaure Lösung mit Kochsalz und extrahiert dreimal mit ¯ther. Der nach dem Trocknen und Einengen der Ätherextrakte erhaltene Rückstand liefert nach dem Umlösen aus Benzol 600 mg Kristalle vom Schmelzpunkt 110-115 ; [a] 22D = -50¯ (c = 1 in Ather). Durch mehrmaliges Umlösen aus Essigester-Petroläther kann eine (-)-2, 3-Dimercaptobernsteinsäure vom Schmelzpunkt 125-126 erhalten werden, [a] 2D =-130 (c = 1 in ¯ther).
Zur Gewinnung des (+)-drehenden Antipoden kristallisiert man die 9, 4 g des in Salzsäure unlöslichen Brucinsalzes einmal aus Methanol um, wobei man ein Brucinsalz vom Schmelzpunkt 275-280 erhält, das nach Lösen in wenig Wasser, Ansäuern mit Salzsäure, SÏttigen mit Kochsalz und Extrahieren mit ¯ther 300 mg einer (+)-2, 3-Dimercapto-bernstein- säure vom Schmelzpunkt 125 liefert ; [a] D = + 116 (c = 1 in Äther). Nach zweimaligem Umlösen aus Essigester-Petroläther erhält man 100 mg reine (+)-2, 3-Dimercapto-bernsteinsäure vom Schmelzpunkt 125-126 ; [a] 2D = + 128 (c = 1 in Äther).
Die analoge Behandlung von dl-2, 3-Diacetylthiobernsteinsäure mit Brucin in Methanol ergibt ein Brucinsalz vom Schmelzpunkt 130-131 ; [α] 21D = -67 (c = 0, 7 in Dimethylformamid). Zur Gewinnung der optisch aktiven 2, 3-Dimercapto-bernsteinsäure wird das Brucinsalz der Diacetylthioverbindung in verdünnter Natronlauge suspendiert und während 5 Minuten gesch ttelt. Nach Filtration des ausgeschiedenen Brucins wird mit Salzsäure kongosauer gestellt und mit Äther extrahiert. Der nach dem Trocknen der ätherischen Lösung über Natriumsulfat und Einengen erhaltene Rückstand besteht aus (-)-2, 3-Dimercapto-bernsteinsäure.
Process for the preparation of racemic and optically active 2,3-dimercapto succinic acid
The present invention relates to a process for the preparation of 2,3-dimercapto-succinic acid of the formula
EMI1.1
which is characterized in that acetylenedicarboxylic acid is converted into 2,3-diacetyl-thiosuccinic acid by addition of thiaacetic acid and this is converted into 2,3-dimercapto-succinic acid by hydrolysis, the racemic form of the reaction product at any point after the addition is isolated from the meso form.
The 2,3-dimercapto-succinic acid thus obtained can then be converted into a dialkyl ester of the formula
EMI1.2
be converted, where R is a lower alkyl group, in particular the methyl group.
Furthermore, the reaction product obtained in racemic form can be split into the optical antipodes.
The addition reaction is advantageously carried out using at least 2 moles of thioacetic acid to 1 mole of acetylenedicarboxylic acid and in a solvent, e.g. B. an ester such as ethyl acetate, or a cyclic ether such as dioxane or tetrahydrofuran, conveniently carried out at a temperature below 50.
The hydrolysis of the 2,3-diacetylthio-succinic acid obtained by the addition reaction to give 2,3-dimercapto-succinic acid can be carried out in an acidic or in a basic medium, e.g. B. in aqueous hydrochloric acid or in sodium hydroxide solution are conveniently carried out at room temperature.
The esterification of the resulting 2,3-dimercapto succinic acid can be carried out in a manner known per se, for. B. by reaction with an alkanol or an alkylating agent such as diazomethane. Thus, by reacting the 2,3-dimercaptosuccinic acid with 2 mol of diazomethane, the dimethyl ester of the acid is obtained.
The isolation of the racemic form is conveniently carried out directly after the addition reaction by z. B. the crude addition product obtained after concentrating the reaction solution by methods known per se, for. B. by fractional crystallization, in the mesound the racemic dl form is separated. However, the racemate can also be isolated after the addition product has been hydrolyzed.
The breakdown into the optically active forms of the racemate obtained according to the invention can be carried out by methods known per se, e.g. B. by salt formation with an optically active base such as brucine, quinine, etc.
The decomposition can be carried out at any point in time, but advantageously after the addition reaction or after hydrolysis of the addition product has taken place.
The racemic and optically active compounds obtainable by the process according to the invention are interesting, commercially utilizable products which are distinguished in particular by their fungicidal action.
The compounds obtainable according to the invention can also be used for the production of metal complexes. The latter, especially in connection with antimony, show an excellent effect in animal experiments on infections with Schistosoma mansoni. A preferred metal complex is that between dl-2,3-dimercapto-succinic acid and antimony. He can z. B. by reaction of dl-2, 3 dimercapto-succinic acid with a trivalent antimony compound, such as antimony III oxide, antimony III hydroxide or antimony III acetate.
example 1
To 500 ml of a 5N solution of hydrogen chloride in ethyl acetate, 380 g of acetylenedicarboxylic acid monopotassium salt are stirred in over 30 minutes while cooling with ice. After one hour, 380 g of thioacetic acid are inerted with stirring and moderate cooling; 21/2 to 3 hours are added dropwise so that the reaction temperature does not rise above 35. The mixture is stirred for a further 15 hours at room temperature. The reaction mixture is then distributed between water and ethyl acetate. By concentrating the ethyl acetate solution to about 1 liter, 260 g of a crystallized substance initially precipitate, which is then filtered off.
It mainly consists of meso-2,3-diacetylthio-succinic acid, which can be purified by dissolving it from ethyl acetate. The dl-2,3-diacetylthiosuccinic acid is obtained by concentrating the filtrate and adding petroleum ether. To clean it, it is boiled with dibutyl ether and then redissolved from ethyl acetate petroleum ether. 75 g of pure compound with a melting point of 150-152 are obtained.
19 g of dl-2,3-diacetylthio-succinic acid are dissolved in 190 ml of 3N sodium hydroxide solution and left at room temperature for 2 minutes. Then it is cooled to 0, saturated with common salt, made Congo acidic with hydrochloric acid and extracted with ether. The residue obtained after concentrating the ethereal solution is redissolved from isopropyl ether. 10.5 g of dl-2,3-dimercapto-succinic acid with a melting point of 126-127 are obtained.
Example 2
2.6 g of dl-2, 3-dimercapto-succinic acid obtained according to Example 1 are dissolved in 150 ml of ether and the amount of an ethereal diazomethane solution calculated for the methylation of 2 carboxyl groups is added. It is then washed with bicarbonate solution and water, the ethereal solution is dried over sodium sulfate, concentrated and the resulting dl-2,3-dimercapto-succinic acid dimethyl ester is purified by distillation under high vacuum, a colorless oil passing over. Boiling point 80/0.01 mm Hg.
The dimethyl ester can also be made as follows:
40 g of dl-2, 3-dimercapto-succinic acid are concentrated in a solution of 20 ml. Sulfuric acid refluxed in 300 ml of methanol for 5 hours.
After cooling, the solution is concentrated in vacuo to about 100 ml, diluted with 400 ml of ether and washed neutral. After drying over sodium sulfate, the ethereal solution is concentrated and the resulting dl-2,3-dimercapto-succinic acid dimethyl ester is distilled in a high vacuum. 35 g of colorless oil with a boiling point of 80¯ / 0.01 mm Hg are obtained.
Example 3
4.5 g of dl-2, 3-dimercapto-succinic acid obtained according to Example 1 are dissolved in 250 ml of methanol, and a solution of 20 g of brucine in 250 ml of methanol is added. The brucine salt of dl-2,3 dimercapto-succinic acid crystallizes out spontaneously (23 g, melting point 156-158). For optical splitting, 240 ml of hydrochloric acid are poured over it and shaken well for 2 hours. This gives 9.4 g of insoluble fractions, which are processed further below into (+) - 2,3-dimercapto-succinic acid.
To obtain the (-) - rotating acid, the hydrochloric acid solution is saturated with common salt and extracted three times with ether. The residue obtained after drying and concentrating the ether extracts, after redissolving from benzene, gives 600 mg of crystals with a melting point of 110-115; [a] 22D = -50¯ (c = 1 in ether). A (-) - 2,3-Dimercaptosuccinic acid with a melting point of 125-126 can be obtained by repeated dissolving from ethyl acetate-petroleum ether, [a] 2D = -130 (c = 1 in ¯ther).
To obtain the (+) - rotating antipode, the 9.4 g of the brucine salt, which is insoluble in hydrochloric acid, are recrystallized once from methanol, giving a brucine salt with a melting point of 275-280, which after dissolving in a little water, acidifying with hydrochloric acid, saturating with Table salt and extraction with ether gives 300 mg of a (+) - 2, 3-dimercapto-succinic acid with a melting point of 125; [a] D = + 116 (c = 1 in ether). After redissolving twice from ethyl acetate-petroleum ether, 100 mg of pure (+) - 2,3-dimercapto-succinic acid with a melting point of 125-126 are obtained; [a] 2D = + 128 (c = 1 in ether).
The analogous treatment of dl-2,3-diacetylthiosuccinic acid with brucine in methanol gives a brucine salt of melting point 130-131; [α] 21D = -67 (c = 0.7 in dimethylformamide). To obtain the optically active 2,3-dimercapto-succinic acid, the brucine salt of the diacetylthio compound is suspended in dilute sodium hydroxide solution and shaken for 5 minutes. After filtration of the brucine which has separated out, it is acidified to Congo with hydrochloric acid and extracted with ether. The residue obtained after drying the ethereal solution over sodium sulfate and concentration consists of (-) - 2,3-dimercapto-succinic acid.
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH215160A CH395967A (en) | 1960-02-26 | 1960-02-26 | Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acid |
| BE600511A BE600511A (en) | 1960-02-26 | 1961-02-23 | Process for the preparation of dicarboxylic acid derivatives containing sulfur |
| GB691161A GB908986A (en) | 1960-02-26 | 1961-02-24 | Sulphur-containing dicarboxylic acids and derivatives thereof and a process for the manufacture of same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH215160A CH395967A (en) | 1960-02-26 | 1960-02-26 | Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH395967A true CH395967A (en) | 1965-07-31 |
Family
ID=4227064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH215160A CH395967A (en) | 1960-02-26 | 1960-02-26 | Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acid |
Country Status (3)
| Country | Link |
|---|---|
| BE (1) | BE600511A (en) |
| CH (1) | CH395967A (en) |
| GB (1) | GB908986A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4550193A (en) * | 1982-06-07 | 1985-10-29 | Johnson & Johnson Baby Products Company | Process for the preparation of 2,3-dimercaptosuccinic acid and its lower alkyl esters |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2214507A (en) * | 1988-01-19 | 1989-09-06 | Erling Sundrehagen | 2,3-dithiosuccinic acid derivative and their use |
| DK1622569T3 (en) | 2003-04-24 | 2015-12-14 | Incyte Holdings Corp | AZA-SPIRO-alkane derivatives as inhibitors of metalloproteases |
| US8003748B2 (en) | 2004-02-17 | 2011-08-23 | Chevron Phillips Chemical Company, Lp | Polythiourethane compositions and processes for making and using same |
| BRPI0507783A (en) | 2004-02-17 | 2007-07-17 | Chevron Phillips Chemical Co | thiol ester composition process for producing a thiol ester composition, hydroxy thiol ester composition, process for producing a hydroxy thiol ester composition, cross-linked thiol ester composition, process for producing a cross-linked thiol ester composition, controlled release fertilizer material and process for production of controlled release fertilizer material |
| US7585932B2 (en) | 2005-08-16 | 2009-09-08 | Chevron Phillips Chemical Company Lp | Polymer compositions and processes for making and using same |
| US7910666B2 (en) | 2005-08-16 | 2011-03-22 | Chevron Phillips Chemical Company Lp | Mercaptan-hardened epoxy polymer compositions and processes for making and using same |
| GB2485824B (en) * | 2010-11-25 | 2017-12-20 | The Queen's Univ Of Belfast | Process for removing organic acids from crude oil and crude oil distillates |
| CN104211679B (en) * | 2013-06-05 | 2017-05-24 | 首都医科大学 | 1,3-dithiolane derivatives, synthesis, nano structure, activity, and application thereof as lead dispelling agent |
-
1960
- 1960-02-26 CH CH215160A patent/CH395967A/en unknown
-
1961
- 1961-02-23 BE BE600511A patent/BE600511A/en unknown
- 1961-02-24 GB GB691161A patent/GB908986A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4550193A (en) * | 1982-06-07 | 1985-10-29 | Johnson & Johnson Baby Products Company | Process for the preparation of 2,3-dimercaptosuccinic acid and its lower alkyl esters |
Also Published As
| Publication number | Publication date |
|---|---|
| BE600511A (en) | 1961-08-23 |
| GB908986A (en) | 1962-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH395967A (en) | Process for the preparation of racemic and optically active 2,3-dimercaptosuccinic acid | |
| DE2449492A1 (en) | METHOD FOR PRODUCING OPTICALLY ACTIVE P-HYDROXYPHENYLGLYCINE | |
| DE668489C (en) | Process for the preparation of 2,4-dioxo-3, 3-dialkyltetrahydropyridine-6-carboxylic acid esters or the corresponding free acids | |
| DE1227914B (en) | Process for the preparation of 3- (1, 2-dithia-cyclopentyl) -5-pentanoic acid | |
| DE2627985C3 (en) | 4-homoisotwistane-3-carboxylic acid ester and process for their preparation | |
| DE1963991B2 (en) | Process for the preparation of a derivative of L-3,4-dihydroxyphenylalanine | |
| DE921870C (en) | Process for the preparation of 0, 0-dimethyl-0-4-nitro-3-chlorophenyl thiophosphate | |
| DE1294953B (en) | The monocarbamate of 2,3-dimethyl-2-n-propyl-3-p-chlorophenyl-1,3-propanediol and process for its preparation | |
| DE1125922B (en) | Process for the production of new phosphorane compounds | |
| DE924450C (en) | Process for the preparation of coumarin derivatives | |
| DE917424C (en) | Process for the preparation of N-acetyl-propargyl-arylamines and their p-position substitution products | |
| DE2032097C (en) | Process for the separation of (+) trans-chrysanthemum monocarboxylic acid from (+) - trans-chrysanthemum monocarboxylic acid | |
| DE825684C (en) | Process for the production of carboxylic acid esters | |
| DE951997C (en) | Process for the preparation of ª ‡ -amino-benzoyl acetic acids | |
| AT228804B (en) | Process for the preparation of thionothiol phosphoric acid esters | |
| AT224119B (en) | Process for the isomerization of basic substituted tricyclic compounds | |
| AT222815B (en) | Process for the production of new tropic acid esters | |
| DE1074585B (en) | Process for the preparation of 5 phenyl 5-ethyltetrahydro-1,3-oxazm -24 diones | |
| CH411901A (en) | Process for the preparation of heterocyclic compounds | |
| CH437354A (en) | Process for the preparation of 1- (acylphenyl) -2-amino-1,3-propanediols | |
| AT33110B (en) | Process for the preparation of alkyloxyacetyl compounds of alcohols of the hydroaromatic series. | |
| DE2163032C2 (en) | Process for the preparation of the optically active forms of α-azidophenylacetic acid | |
| AT261592B (en) | Process for the preparation of L - (-) - α-methyl-β- (3,4-dihydroxyphenyl) alanine | |
| CH427770A (en) | Process for the preparation of a-keto-y-lactones | |
| DE1033652B (en) | Process for the resolution of racemic ª ‡ -oxy-ª ‰, ª ‰ -dimethyl-ª † -butyrolactone into its d (-) - and 1 (+) - stereomers |