CH240352A - Process for the preparation of a derivative of a thiophan-3-one-4-carboxylic acid ester. - Google Patents
Process for the preparation of a derivative of a thiophan-3-one-4-carboxylic acid ester.Info
- Publication number
- CH240352A CH240352A CH240352DA CH240352A CH 240352 A CH240352 A CH 240352A CH 240352D A CH240352D A CH 240352DA CH 240352 A CH240352 A CH 240352A
- Authority
- CH
- Switzerland
- Prior art keywords
- carboxylic acid
- thiophan
- preparation
- derivative
- ethyl ester
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- LXXNWCFBZHKFPT-UHFFFAOYSA-N Ethyl 2-mercaptopropionate Chemical compound CCOC(=O)C(C)S LXXNWCFBZHKFPT-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
Verfahren zur Darstellung eines Abkömmlings eines Thiophan-3-on-4-carbonsäur eesters. Thiophan-3-on-4-carbonsäureester, die in Stellung 2 aliphatische Substituenten (X) tragen und somit der Formel I
EMI0001.0008
(R = niederes Alkyl) entsprechen,
sind wich tige Ausgangsmaterialien für die Herstellung pharmazeutisch brauchbarer Präparate von der Art des Biotins. Der in 2-Stellung be findliche Substituent X besitzt aliphatischen Charakter und kann z. B. die Gruppe -CH2CH?COOC2H5, -CH2CH2CH20CHg, -(CH2)40CHe, -(CH2)4CN usw.
. bedeuten.
Es wurde gefunden, dass sich Verbindun gen dieser Konstitution aus Sulfid-a-propion- säure-(X-essigsäure)-estern der allgemeinen Formel II
EMI0001.0021
worin R eine niedere Alkylgruppe und X einen aliphatischen Rest bedeuten, herstellen lassen, indem man diese der Einwirkung von Kondensationsmitteln, wie Natriumalkoholat. Natriumamid usw., unterwirft. Dabei erfolgt Ringschluss unter Bildung der Verbindungen I.
Gegenstand des vorliegenden Patentes ist ein Verfahren zur Darstellung eines Abkömm lings eines Thiophan-3-on-4-carbonsäureesters, welches dadurch gekennzeichnet ist, dass ss Mercaptopropionsäureäthylestermita-Halogen glutarsäureäthylester umgesetzt und die ent standene Verbindung mit einem Kondensa tionsmittel behandelt wird.
Der bisher unbekannte 2-(Carbäthogyäthyl)- thiophan-3-on-4-carbonsäure-äthylester destil liert unter 0,02 mm Druck bei 123<B>0</B> als farb- lose Flüssigkeit und gibt mit Eisenchlorid eine intensiv rotviolette Farbreaktion.
Die neue Verbindung soll zur Herstellung pharmazeutisch verwendbarer Stoffe dienen. <I>Beispiel:</I> Zu einer Lösung von 1,0 Gewichtsteilen Natrium in 20 Raumteilen'#Äthariol werden bei 0 in Stickstoff-Atmosphäre 6,6 Gewichts teile @j-Mercapto-propionsäureäthylester zu tropfen gelassen, hierauf unter starker Kühlung 12 Gewichtsteile a-Brom-glutarsäureäthy lester, die in wenig Alkohol gelöst sind. Die Reak tionsmasse bleibt 2 Stunden in der Kälte mischung stehen, wird hierauf eine halbe Stunde auf 15 und zum Schluss noch eine halbe Stunde zum Sieden erhitzt.
Nach der Entfernung des Alkohols im Vakuum versetzt man den Rückstand mit wenig Wasser, zieht mit Äther aus und erhält nach dem Ver dunsten des Lösungsmittels den Sulfid-ss-pro- pionsäure-a-glutarsäureester der Formel III
EMI0002.0012
als farblose Flüssigkeit, die bei 0,02 mm Druck bei 150-153 destilliert.
Zwecks Überführung der vorbesehriebenen Verbindung in das Thiophanon-Derivat IV
EMI0002.0016
lif, t man zu einer Suspension von 0,8 Ge wichtsteilen amorphem Natriumäthylat in<B>50</B> Raumteilen Toluol unter Rühren 1,9 Gewichts teile der Verbindung HI zutropfen und erhitzt das Reaktionsgemisch unter ständigem Rühren 9 Stunden auf<B>110'.</B> Hierauf giesst man das Reaktionsprodukt auf Eis, dem 1,5 Raumteile Eisessig zugesetzt sind, extrahiert mit peroxyd- freiem Äther und verdampft die Ätherlösung.
Das zurückbleibende Öldestilliert unter 0,02 mm Druck bei 123 als farblose Flüssigkeit. Die Verbindung, die mit Eisenchlorid eine intensiv rotviolette Farbreaktion gibt, ist das Thiophanon-Derivat IV (2-[Carbäthoxyäthyl]- thiophan-3-on-4-carbonsäure-äthylester).
Process for the preparation of a derivative of a thiophan-3-one-4-carboxylic acid ester. Thiophan-3-one-4-carboxylic acid esters which have aliphatic substituents (X) in position 2 and are thus of the formula I.
EMI0001.0008
(R = lower alkyl) correspond to
are important starting materials for the production of pharmaceutically usable preparations of the biotin type. The 2-position sensitive substituent X has an aliphatic character and can, for. B. the group -CH2CH? COOC2H5, -CH2CH2CH20CHg, - (CH2) 40CHe, - (CH2) 4CN etc.
. mean.
It has been found that compounds of this constitution of sulfide-a-propionic acid (X-acetic acid) esters of the general formula II
EMI0001.0021
where R is a lower alkyl group and X is an aliphatic radical, can be prepared by exposing them to the action of condensing agents such as sodium alcoholate. Sodium amide, etc., subject. Ring closure takes place with the formation of compounds I.
The subject of the present patent is a process for the preparation of a descendant of a thiophan-3-one-4-carboxylic acid ester, which is characterized in that ss mercaptopropionic acid ethyl ester, halogen-glutaric acid ethyl ester and the resulting compound is treated with a condensation agent.
The previously unknown 2- (carbethogyethyl) thiophan-3-one-4-carboxylic acid ethyl ester distills under 0.02 mm pressure at 123 <B> 0 </B> as a colorless liquid and gives an intensely red-violet color with ferric chloride Color reaction.
The new compound is intended to be used for the production of pharmaceutically acceptable substances. <I> Example: </I> To a solution of 1.0 part by weight of sodium in 20 parts by volume of ethariol, 6.6 parts by weight of ethyl mercapto-propionate are allowed to drop at 0 in a nitrogen atmosphere, then with strong cooling 12 parts by weight of a-bromo-glutaric acid ethyl ester, which are dissolved in a little alcohol. The reaction mass remains in the cold mixture for 2 hours, is then heated to the boil for half an hour to 15 and finally another half hour.
After the alcohol has been removed in vacuo, the residue is treated with a little water, extracted with ether and, after the solvent has evaporated, the sulfide-β-propionic acid-α-glutaric acid ester of the formula III is obtained
EMI0002.0012
as a colorless liquid that distills at 150-153 at 0.02 mm pressure.
For the purpose of converting the prescribed compound into the thiophanone derivative IV
EMI0002.0016
1.9 parts by weight of the compound HI are added dropwise with stirring to a suspension of 0.8 parts by weight of amorphous sodium ethylate in 50 parts by volume of toluene, and the reaction mixture is heated for 9 hours with constant stirring 110 '. </B> The reaction product is then poured onto ice to which 1.5 parts by volume of glacial acetic acid are added, extracted with peroxide-free ether and the ether solution evaporated.
The remaining oil distilled under 0.02 mm pressure at 123 as a colorless liquid. The compound which gives an intense red-violet color reaction with iron chloride is the thiophanone derivative IV (2- [carbethoxyethyl] thiophan-3-one-4-carboxylic acid ethyl ester).
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH234105T | 1943-02-17 | ||
| CH240352T | 1943-02-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH240352A true CH240352A (en) | 1945-12-15 |
Family
ID=25727827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH240352D CH240352A (en) | 1943-02-17 | 1943-02-17 | Process for the preparation of a derivative of a thiophan-3-one-4-carboxylic acid ester. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH240352A (en) |
-
1943
- 1943-02-17 CH CH240352D patent/CH240352A/en unknown
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