CH310363A - Process for the preparation of an acyl mercaptoalkylamine. - Google Patents
Process for the preparation of an acyl mercaptoalkylamine.Info
- Publication number
- CH310363A CH310363A CH310363DA CH310363A CH 310363 A CH310363 A CH 310363A CH 310363D A CH310363D A CH 310363DA CH 310363 A CH310363 A CH 310363A
- Authority
- CH
- Switzerland
- Prior art keywords
- parts
- preparation
- mercaptoalkylamine
- acyl
- volume
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 5
- 125000002252 acyl group Chemical group 0.000 title description 2
- UIJGNTRUPZPVNG-UHFFFAOYSA-N benzenecarbothioic s-acid Chemical compound SC(=O)C1=CC=CC=C1 UIJGNTRUPZPVNG-UHFFFAOYSA-N 0.000 claims description 4
- 229960000903 pantethine Drugs 0.000 claims description 3
- 239000011581 pantethine Substances 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- ZNXZGRMVNNHPCA-UHFFFAOYSA-N pantetheine Chemical compound OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS ZNXZGRMVNNHPCA-UHFFFAOYSA-N 0.000 description 2
- 235000019161 pantothenic acid Nutrition 0.000 description 2
- 239000011713 pantothenic acid Substances 0.000 description 2
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 1
- 240000002605 Lactobacillus helveticus Species 0.000 description 1
- -1 N- (+) - pantothenyl-ethylenimine Chemical compound 0.000 description 1
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 description 1
- 235000008975 pantethine Nutrition 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines Acylmercaptoalkylamins.
Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstellung von N-(+)- Pantothenyl-S-benzoyl-, B-mereapto-äthylamin 3S [ (+)-S-Benzoyl-pantethein] der Formel
EMI1.1
Dieses neue Derivat des Pantetheins ist ein Baustein der unmittelbar aktiven, acylüber- tragenden Formen des Coenzyms A und hat im Stoffwechselgeschehen der tierischen Zellen eine grosse Bedeutung. Es besitzt eine ebenso gute wachstumsfördernde Wirkung, z. B. auf die Milchsäurebakterien L. helveticus und L. bulgaricus, wie das Pantethein selbst. Im.
Gegensatz zu Pantethein stellt es eine gut kristallisierende Verbindung vom F. = 116 dar.
Eine wesentliche Bedeutung der nach dem vorliegenden Verfahren erhaltenen Verbindung besteht aueh darin, dass sich der mit dem Schwefelatom verbundene Benzoylrest selektiv leieht abspalten lässt, so dass sich diese Verbindung zur Einführung des Ben zoylrestes in aktiven Wasserstoff enthaltende Verbindungen sehr gut eignet. Wenn man z. B. auf die Verbindung Ammoniak oder Aminogruppen enthaltende Verbindungen, wie Amine, Aminocarbonsäuren oder Hydroxylamine, einwirken lässt, so entstehen dabei ausser dem Pantethein die entsprechenden Säureamide. In analoger Weise kann man die Verbindung auch mit Hydroxylgruppen enthaltenden Verbindungen, wie mit Wasser oder Alkoholen, umsetzen.
Die neue Verbindung soll als Heilmittel oder als Zwischenprodukt dienen.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man das N- (+)- Pantothenyl-äthylenimin der Formel
EMI1.2
mit Thiobenzoesäure umsetzt.
Die Reaktion kann in Gegenwart von organischen Verdünnungsmitteln, wie Ather, Benzol, Toluol, Dimethylformamid, oder auch in Anwesenheit von Wasser durchgeführt werden. Sie verläuft bereits bei tiefer Tem peratur ; vorzugsweise arbeitet man bei Zim mertemperatur.
Fiir die Herstellung des N- (+)-Panto thenyl-äthylenimins wird vorteilhaft ein neues, eigenartiges Verfahren verwendet, welches darin besteht, dass man auf ein Anhydrid einer Halbesterkohlensäure und der Pantothensäure Äthylenimin in Gegenwart eines säurebindenden Mittels, wie z. B. eines tertiären Amins, einwirken lässt.
Beispiel :
10 Gewichtsteile (+)-Calcium-panto- thenat werden in 10 Volumteilen Wasser gelöst und mit 10 Volumteilen Triäthyl- amin versetzt. Das Calcium wird mit einer genau äquivalentenMenge einer wässrigen Oxal säurelosung gefällt. Nach Filtration und Verdampfen des Losungsmittels hinterbleiben 12,5 Gewichtsteile sirupöses Triäthyl- ammonium-pantothenat. Die Verbindung wird in 25 Volumteilen trockenem Dimethyl- formamid gelost und auf-5 abgekühlt. Bei dieser Temperatur werden nun 4,1 Gewichtsteile Chlorkohlensäure-äthylester, in 20 Volumteilen Essigester gelost, tropfenweise eingerührt.
Nach 10 Minuten wird die entstandene Mischung, ungeachtet des auskristallisier- ten Triäthylammoniumchlorids, unter Rühren in eine auf-5 gekühlte Lösung von 2 Ge wichtsteilen Äthylenimin und 5 Gewichtsteilen Triäthylamin in 50 Volumteilen Essigester schnell portionenweise zugegeben. Nach 20 Minuten wird dieses entstandene Gemisch in kalte Thiobenzoesäurelosung (7 Gewichtsteile Thiobenzoesäure in 100 Volumteilen Essigester) eingegossen. Nachdem die (gelbe) Mischung 30 Minuten bei 0 gestanden hat, wird sie filtriert und bei tiefer Temperatur, zuerst im Wasserstrahlvakuum, dann im Feinvakuum (0,05 mm Hg), von Lösungsmitteln befreit.
Der Rückstand wird in 1000 Volumteilen Wasser gelöst und zuerst mit Äther (3mal 500 Volumteilen) extrahiert. Das N-Pantothenyl-S benzoyl-XB-mercapto-äthylamin [ (+)-S-Benzoyl-pantethein] wird durch Extraktion der wässrigen Phase mit Essigester (5mal 500 Volumteile) isdliert und durch Kristallisation aus trockenem Essigester gereinigt. Ausbeute : 8 Gewichtsteile ; F. = 116 . DieÄtherextrakte deponieren nach dem Trocknen mit Natriumsulfat beim Aufbewahren im Kühlschrank (-10 ) eine weitere Menge der kristallisier- ¯ten Verbindung. Zur Analyse wird dreimal l aus Essigester umkristallisiert und bei 0,05 mm Hg während 5 Stunden bei 60 getrocknet.
Farblose, flache Nadeln, F. = 116 ; [a] D6 = + 31 (+ 4 , c = 1, Äthanol).
Process for the preparation of an acyl mercaptoalkylamine.
The present patent relates to a process for the preparation of N - (+) - pantothenyl-S-benzoyl-, B-mereapto-ethylamine 3S [(+) - S-benzoyl-pantethein] of the formula
EMI1.1
This new derivative of pantethin is a component of the directly active, acyl-transferring forms of coenzyme A and is of great importance in the metabolic processes of animal cells. It has an equally good growth-promoting effect, e.g. B. on the lactic acid bacteria L. helveticus and L. bulgaricus, such as the Pantethein itself. Im.
In contrast to Pantethein, it is a well-crystallizing compound of F. = 116.
Another important aspect of the compound obtained by the present process is that the benzoyl radical linked to the sulfur atom can be selectively split off, so that this compound is very suitable for introducing the benzoyl radical into compounds containing active hydrogen. If you z. B. on the compound ammonia or compounds containing amino groups, such as amines, aminocarboxylic acids or hydroxylamines, to act, the corresponding acid amides are formed in addition to the pantethine. In an analogous manner, the compound can also be reacted with compounds containing hydroxyl groups, such as with water or alcohols.
The new compound is intended to serve as a remedy or as an intermediate.
The process according to the invention is characterized in that the N- (+) - pantothenyl-ethyleneimine of the formula
EMI1.2
with thiobenzoic acid.
The reaction can be carried out in the presence of organic diluents, such as ether, benzene, toluene, dimethylformamide, or else in the presence of water. It already runs at low temperatures; it is preferable to work at room temperature.
For the preparation of the N- (+) - pantothenyl-ethylenimine, a new, peculiar process is advantageously used, which consists in that on an anhydride of a half-carbonic acid and the pantothenic acid ethylenimine in the presence of an acid-binding agent such as. B. a tertiary amine, can act.
Example:
10 parts by weight of (+) calcium pantothenate are dissolved in 10 parts by volume of water and 10 parts by volume of triethylamine are added. The calcium is precipitated with an exactly equivalent amount of an aqueous oxalic acid solution. After filtration and evaporation of the solvent, 12.5 parts by weight of syrupy triethylammonium pantothenate remain. The compound is dissolved in 25 parts by volume of dry dimethylformamide and cooled to -5. At this temperature 4.1 parts by weight of ethyl chlorocarbonate, dissolved in 20 parts by volume of ethyl acetate, are stirred in dropwise.
After 10 minutes, the resulting mixture, regardless of the triethylammonium chloride that crystallizes out, is added rapidly in portions with stirring to a cooled solution of 2 parts by weight of ethyleneimine and 5 parts by weight of triethylamine in 50 parts by volume of ethyl acetate. After 20 minutes, this resulting mixture is poured into cold thiobenzoic acid solution (7 parts by weight of thiobenzoic acid in 100 parts by volume of ethyl acetate). After the (yellow) mixture has stood at 0 for 30 minutes, it is filtered and freed from solvents at low temperature, first in a water-jet vacuum, then in a fine vacuum (0.05 mm Hg).
The residue is dissolved in 1000 parts by volume of water and first extracted with ether (3 times 500 parts by volume). The N-pantothenyl-S benzoyl-XB-mercapto-ethylamine [(+) - S-benzoyl-pantethine] is isolated by extracting the aqueous phase with ethyl acetate (5 times 500 parts by volume) and purified by crystallization from dry ethyl acetate. Yield: 8 parts by weight; F. = 116. After drying with sodium sulfate, the ether extracts deposit a further amount of the crystallized compound when stored in the refrigerator (-10). For analysis, l is recrystallized three times from ethyl acetate and dried at 0.05 mm Hg at 60 for 5 hours.
Colorless, flat needles, F. = 116; [a] D6 = + 31 (+ 4, c = 1, ethanol).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH310363T | 1952-07-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH310363A true CH310363A (en) | 1955-10-15 |
Family
ID=4494156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH310363D CH310363A (en) | 1952-07-03 | 1952-07-03 | Process for the preparation of an acyl mercaptoalkylamine. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH310363A (en) |
-
1952
- 1952-07-03 CH CH310363D patent/CH310363A/en unknown
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