DE2944257A1 - METHOD FOR PRODUCING N-CYAN-N'-METHYL-N '' - (2-MERCAPTOAETHYL) GUANIDINE - Google Patents
METHOD FOR PRODUCING N-CYAN-N'-METHYL-N '' - (2-MERCAPTOAETHYL) GUANIDINEInfo
- Publication number
- DE2944257A1 DE2944257A1 DE19792944257 DE2944257A DE2944257A1 DE 2944257 A1 DE2944257 A1 DE 2944257A1 DE 19792944257 DE19792944257 DE 19792944257 DE 2944257 A DE2944257 A DE 2944257A DE 2944257 A1 DE2944257 A1 DE 2944257A1
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- guanidine
- cyano
- dithiobisethyl
- mol
- 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- Withdrawn
Links
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title description 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
- 229960003151 mercaptamine Drugs 0.000 claims description 4
- MHGGQXIPBPGZFB-UHFFFAOYSA-N methyl n-cyano-n'-methylcarbamimidothioate Chemical compound CSC(=NC)NC#N MHGGQXIPBPGZFB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Inorganic materials [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 2
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims 2
- 238000009833 condensation Methods 0.000 claims 2
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- ZORWZOOZJGMSTE-UHFFFAOYSA-N 1-cyano-2-methyl-3-(2-sulfanylethyl)guanidine Chemical compound N#CNC(=NC)NCCS ZORWZOOZJGMSTE-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000003969 polarography Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Classifications
-
- 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
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin durch Hydrogenolyse von 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)-guanidin. N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin ist eine Zwischenverbindung für die Herstellung von N-Cyan-N'-methyl-N"-[2-(5-methyl-imidazol-4-yl)-methyl-thio-äthylguanidin, das als Wirkstoff für Behandlung von Magen- und Zwölffingerdarmgeschwüren verwendet wird.The invention relates to a process for the preparation of N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine by hydrogenolysis of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) -guanidine -Cyan-N'-methyl-N "- (2-mercaptoethyl) guanidine is an intermediate compound for the production of N-Cyano-N'-methyl-N" - [2- (5-methyl-imidazol-4-yl) -methyl-thio-ethylguanidine, which is used as an active ingredient in the treatment of gastric and duodenal ulcers.
Es ist bereits bekannt, dass N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin durch Umsatz von Cysteamin mit N-Cyano-N',S-dimethyl-isothioharnstoff unter Verwendung von Natriumhydroxid hergestellt werden kann (NL-OS 75 10344).It is already known that N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine can be prepared by reacting cysteamine with N-cyano-N ', S-dimethyl-isothiourea using sodium hydroxide (NL -OS 75 10344).
Nun wurde gefunden, dass N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin leicht und in quantitativen Ausbeuten durch Hydrogenolyse von 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)-guanidin hergestellt werden kann.It has now been found that N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine easily and in quantitative yields by hydrogenolysis of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) -guanidine can be produced.
Das Verfahren ist dadurch gekennzeichnet, dass man das durch die Umsetzung von Cysteamin und N-Cyan-N',S-dimethyl-isothioharnstoff erhaltene 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)-guanidin der Formel I
(I)(I)
zum N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin unter solchen Bedingungen hydrogenolysiert, dass es am Cyanguanidinrest zu keiner Veränderung kommt.hydrogenolyzed to N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine under such conditions that there is no change in the cyanguanidine residue.
Gemäß vorliegender Erfindung wird das durch Kondensation von Cysteamin und N-Cyan-N',S-dimethyl-isothioharnstoff in einem niederen Alkohohl auf Siedepunkt während 2 bis 3 Stunden erhaltene 2,2'-Dithiobis-(N-Cyan-N'-methyl)guanidin in flüssigem Ammoniak suspendiert. Nach Versetzung mit 6 bis 9 Äquivalenten Natrium wird Ammoniak abgedampft, der Rückstand in Wasser gelöst, auf pH 4 angesäuert und N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)-guanidin wird auf übliche Weise isoliert.According to the present invention, the 2,2'-dithiobis- (N-cyano-N'-methyl ) guanidine suspended in liquid ammonia. After 6 to 9 equivalents of sodium have been added, ammonia is evaporated off, the residue is dissolved in water, acidified to pH 4 and N-cyano-N'-methyl-N "- (2-mercaptoethyl) -guanidine is isolated in the usual way.
Gemäß derselben Erfindung kann die Hydrogenolyse von 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)guanidin auch z.B. mit Lithiumaluminiumhydrid in einem organischen Lösungsmittel, mit Kalium- oder Natriumsulfid in einem wässerigen oder alkoholischen Medium sowie elektrolytisch durchgeführt werden.According to the same invention, the hydrogenolysis of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) guanidine can also be carried out, for example, with lithium aluminum hydride in an organic solvent, with potassium or sodium sulfide in an aqueous or alcoholic medium as well as electrolytically.
Die vorliegende Erfindung schließt auch andere Methoden nicht aus, die demselben Zweck wie oben angegeben dienen.The present invention also does not exclude other methods which serve the same purpose as stated above.
Ein Vorteil des vorliegenden Verfahrens liegt darin, dass dadurch die Möglichkeit einer erneuten Dimerisation im Laufe der Reaktion ausgeschlossen ist und ein reines Produkt in hohen Ausbeuten erhalten wird.One advantage of the present process is that it eliminates the possibility of renewed dimerization in the course of the reaction and a pure product is obtained in high yields.
Das Verfahren wird durch folgende Beispiele illustriert, die jedoch die Erfindung keineswegs einschränken sollen.The process is illustrated by the following examples, which, however, are in no way intended to restrict the invention.
Beispiel 1 In 100 ml Äthanol werden 4,8 g (0,062 Mol) Cysteamin und 8,0 g (0,062 Mol) N-Cyan-N',S-dimethyl-isothioharnstoff gegeben. Das Reaktionsgemisch wird 2,5 Stunden auf 75-78°C unter Rühren erhitzt. Äthanol wird eingedampft und der Rückstand, falls nötig, aus einem organischen Lösungsmittel umkristallisiert. Man erhält 7,87 g (82 %) 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)-guanidin, Smp. 158-160°C.Example 1 4.8 g (0.062 mol) of cysteamine and 8.0 g (0.062 mol) of N-cyano-N ', S-dimethyl-isothiourea are added to 100 ml of ethanol. The reaction mixture is heated to 75-78 ° C. with stirring for 2.5 hours. Ethanol is evaporated and the residue, if necessary, recrystallized from an organic solvent. 7.87 g (82%) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) -guanidine, melting point 158-160 ° C., are obtained.
Beispiel 2 In 30 ml flüssigem Ammoniak werden 1,57 g (0,005 Mol) 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)guanidin suspendiert und portionsweise mit 0,92 g (0,04 Mol) Natrium versetzt. Überschüssiges Natrium wird durch den Zusatz einer geringen Menge Ammoniumchlorid entfernt. Ammoniak wird abgedampft, der Rückstand in 8 ml Wasser gelöst und mit 10 %iger Salzsäure bis pH 4 angesäuert. Die wässerige Lösung wird dreimal mit je 25 ml Äthylacetat extrahiert. Der Äthylacetatextrakt wird auf Natriumsulfat getrocknet und nach der Eindampfung erhält man 1,57 g (99 %) N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)-guanidin in der Form eines zähen farblosen Öls, das dieselben physikalischen Konstanten wie die authentische Probe aufweist.Example 2 1.57 g (0.005 mol) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) guanidine are suspended in 30 ml of liquid ammonia and 0.92 g (0.04 mol) of sodium were added in portions. Excess sodium is removed by adding a small amount of ammonium chloride. Ammonia is evaporated, the residue is dissolved in 8 ml of water and acidified to pH 4 with 10% hydrochloric acid. The aqueous solution is extracted three times with 25 ml of ethyl acetate each time. The ethyl acetate extract is dried over sodium sulfate and, after evaporation, 1.57 g (99%) of N-cyano-N'-methyl-N "- (2-mercaptoethyl) -guanidine are obtained in the form of a viscous colorless oil which has the same physical properties Has constants like the authentic sample.
Beispiel 3 Zu einer Suspension von 0,14 g (0,0038 Mol) Lithiumaluminiumhydrid und 30 ml trocknem Äther gibt man 0,5 g (0,0016 Mol) 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)guanidin. Das Reaktionsgemisch wird 2 Stunden am Rückfluss erhitzt und anschließend wird vorsichtig 5 %ige Salzsäure bis zu pH 4 zugetropft. Die Ätherschicht wird abgetrennt und die saure Wasserschicht noch dreimal mit je 20 ml Äthylacetat extrahiert. Die vereinigten Äther- und Äthylacetatextrakte werden über Natriumsulfat getrocknet und nach der Einengung erhält man 0,376 g (75 %) N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin.Example 3 0.5 g (0.0016 mol) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) are added to a suspension of 0.14 g (0.0038 mol) of lithium aluminum hydride and 30 ml of dry ether ) guanidine. The reaction mixture is refluxed for 2 hours and then 5% hydrochloric acid is carefully added dropwise up to pH 4. The ether layer is separated and the acidic water layer is extracted three times with 20 ml of ethyl acetate each time. The combined ether and ethyl acetate extracts are dried over sodium sulfate and after concentration, 0.376 g (75%) of N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine is obtained.
Beispiel 4 Zu einer Suspension von 0,314 g (0,001 Mol) 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)guanidin in 10 ml Wasser wird eine Lösung von 0,5 g (0,002 Mol + 5 %iger Überschuss) Natief2S . 9Htief2O in 10 ml Wasser gegeben. Das Reaktionsgemisch wird 2 Stunden auf 80-90°C erhitzt, abgekühlt und dreimal mit je 10 ml Äthylacetat extrahiert. Der Wasserteil wird mit 1 N HCl bis zu pH 4 angesäuert und noch dreimal mit je 10 ml Äthylacetat extrahiert. Die vereinigten Äthylacetatextrakte werden über Natriumsulfat getrocknet und nach der Einengung erhält man 0,21 g (66 %) N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin.Example 4 A solution of 0.5 g (0.002 mol + 5% excess) is added to a suspension of 0.314 g (0.001 mol) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) guanidine in 10 ml of water ) Natief2S. 9Htief2O added to 10 ml of water. The reaction mixture is heated to 80-90 ° C. for 2 hours, cooled and extracted three times with 10 ml of ethyl acetate each time. The water part is acidified with 1 N HCl up to pH 4 and extracted three times with 10 ml of ethyl acetate each time. The combined ethyl acetate extracts are dried over sodium sulfate and, after concentration, 0.21 g (66%) of N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine are obtained.
Beispiel 5 Zu einer Lösung von 0,314 g (0,001 Mol) 2,2'-Dithiobisäthyl-(N-cyan-N'-methyl)guanidin in 20 ml Äthanol wird eine Lösung von 0,5 g (0,002 Mol + 5 %iger Überschuss) Natief2S . 9Htief2O in 3 ml Wasser gegeben. Das Reaktionsgemisch wird 2 Stunden am Rückfluss erhitzt, dann wird Äthanol eingeengt und der Wasserteil wird weiter wie im Beispiel 4 aufgearbeitet. Man erhält 0,18 g (57 %) N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)guanidin.Example 5 A solution of 0.5 g (0.002 mol + 5% excess) is added to a solution of 0.314 g (0.001 mol) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) guanidine in 20 ml of ethanol ) Natief2S. 9Htief2O in 3 ml of water. The reaction mixture is refluxed for 2 hours, then ethanol is concentrated and the water part is worked up further as in Example 4. 0.18 g (57%) of N-cyano-N'-methyl-N "- (2-mercaptoethyl) guanidine are obtained.
Beispiel 6 In 50 ml 0,1 N Kaliumchlorid werden 0,314 g (0,001 Mol) 2,2'-Dithiobisäthyl-(N-cyano-N'-methyl)guanidin gegeben und in einer Zelle von 100 ml unter Durchleiten von Stickstoff durch die Reaktionslösung bei konstantem Strom von 0,05 A mit einer Quecksilberkathode auf dem Boden der Zelle mit einer Oberfläche von 20 cmhoch2 und einer zentral angeordneten Bleianode (Anolyt ist 10 %ige Schwefelsäure) bei einer Temperatur von 20°C elektrolytisch reduziert. Der Katholyt und der Anolyt sind durch ein synthetisches Diaphragma getrennt und der Katholyt mit einem Magnetrührer gerührt. Der Reaktionsverlauf kann polarographisch oder dünnschichtchromatographisch (Chloroform:Äthanol = 9:3) verfolgt werden. Nach der beendeten Reaktion wird die wässerige Lösung dreimal mit je 25 ml Äthylacetat extrahiert. Der Äthylacetatextrakt wird auf Natriumsulfat getrocknet und dann bis zur Trockne eingeengt. Man erhält 0,186 g (59 %) N-Cyan-N'-methyl-N"-(2-mercaptoäthyl)-guanidin in der Form eines farblosen viskosen Öls.EXAMPLE 6 0.314 g (0.001 mol) of 2,2'-dithiobisethyl- (N-cyano-N'-methyl) guanidine are added to 50 ml of 0.1 N potassium chloride and the reaction solution is placed in a 100 ml cell while nitrogen is passed through Electrolytically reduced at a constant current of 0.05 A with a mercury cathode on the bottom of the cell with a surface area of 20 cm high and a centrally arranged lead anode (anolyte is 10% sulfuric acid) at a temperature of 20 ° C. The catholyte and the anolyte are separated by a synthetic diaphragm and the catholyte is stirred with a magnetic stirrer. The course of the reaction can be followed by polarography or thin-layer chromatography (chloroform: ethanol = 9: 3). After the reaction has ended, the aqueous solution is extracted three times with 25 ml of ethyl acetate each time. The ethyl acetate extract is dried over sodium sulfate and then concentrated to dryness. 0.186 g (59%) of N-cyano-N'-methyl-N "- (2-mercaptoethyl) -guanidine are obtained in the form of a colorless, viscous oil.
Beispiel 7 Es wird analog zum im Beispiel 6 beschriebenen Verfahren gearbeitet, mit dem Unterschied, dass man in einer methanolischen Lösung unter Zusatz von 0,3 g Natriumchlorid arbeitet und dass man das Produkt isoliert, indem man nach beendeter Reaktion Methanol bis zur Trockne einengt, den Rückstand inExample 7 The procedure described in Example 6 is repeated, with the difference that the reaction is carried out in a methanolic solution with the addition of 0.3 g of sodium chloride and that the product is isolated by concentrating methanol to dryness after the reaction has ended, the residue in
5 ml Wasser löst und mit Salzsäure zu pH 4 ansäuert. Nach Extrahieren mit Äthylacetat erhält man 0,236 g (75 %) des Produktes in der Form eines farblosen viskosen Öls.Dissolve 5 ml of water and acidify to pH 4 with hydrochloric acid. After extraction with ethyl acetate, 0.236 g (75%) of the product is obtained in the form of a colorless viscous oil.
Beispiel 8 In Analogie zum im Beispiel 6 beschriebenen Verfahren mit dem Unterschied, dass die Reaktion in Methanol unter Zusatz von 0,332 g (0,002 Mol) 5-Methyl-4-chlormethylimidasol-hydrochlorid als Elektrolyt durchgeführt wird und dass das Produkt wie im Beispiel 7 isoliert wird, erhält man 0,243 g (77 %) des Produktes in der Form eines farblosen viskosen Öls.Example 8 In analogy to the process described in Example 6, with the difference that the reaction is carried out in methanol with the addition of 0.332 g (0.002 mol) of 5-methyl-4-chloromethylimidaseole hydrochloride as the electrolyte and that the product is isolated as in Example 7 0.243 g (77%) of the product is obtained in the form of a colorless viscous oil.
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU255178A YU41127B (en) | 1978-11-02 | 1978-11-02 | Process for obtaining n-cyano-n-methyl-n-(2-mercaptoethyl)-guanidine |
| YU36579A YU41615B (en) | 1979-02-15 | 1979-02-15 | Process for obtaining n-cyano-n-methyl-n"-(2-mercaptoethyl)-quanidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2944257A1 true DE2944257A1 (en) | 1980-05-14 |
Family
ID=27130733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792944257 Withdrawn DE2944257A1 (en) | 1978-11-02 | 1979-11-02 | METHOD FOR PRODUCING N-CYAN-N'-METHYL-N '' - (2-MERCAPTOAETHYL) GUANIDINE |
Country Status (5)
| Country | Link |
|---|---|
| AT (1) | AT368991B (en) |
| CH (1) | CH645098A5 (en) |
| DE (1) | DE2944257A1 (en) |
| GB (1) | GB2035313B (en) |
| IT (1) | IT1192784B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2528833A1 (en) * | 1982-06-16 | 1983-12-23 | May & Baker Ltd | CYSTAMINE DERIVATIVES, PREPARATION THEREOF AND COMPOSITIONS AS GROWTH FACTOR CONTAINING THEM |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0623179B2 (en) * | 1986-09-01 | 1994-03-30 | 三井石油化学工業株式会社 | Cyanoguanidine derivative and method for producing the same |
| JPH0623180B2 (en) * | 1987-02-17 | 1994-03-30 | 三井石油化学工業株式会社 | Cyanoguanidine derivative and method for producing the same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7510344A (en) * | 1974-09-02 | 1976-03-04 | Smith Kline French Lab | PROCEDURE FOR PREPARING PHARMACOLOGICALLY ACTIVE COMPOUNDS. |
-
1979
- 1979-10-25 GB GB7937081A patent/GB2035313B/en not_active Expired
- 1979-10-25 CH CH960479A patent/CH645098A5/en not_active IP Right Cessation
- 1979-10-29 IT IT69110/79A patent/IT1192784B/en active
- 1979-10-31 AT AT0702779A patent/AT368991B/en not_active IP Right Cessation
- 1979-11-02 DE DE19792944257 patent/DE2944257A1/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7510344A (en) * | 1974-09-02 | 1976-03-04 | Smith Kline French Lab | PROCEDURE FOR PREPARING PHARMACOLOGICALLY ACTIVE COMPOUNDS. |
Non-Patent Citations (1)
| Title |
|---|
| C.A. 91, 175354 z * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2528833A1 (en) * | 1982-06-16 | 1983-12-23 | May & Baker Ltd | CYSTAMINE DERIVATIVES, PREPARATION THEREOF AND COMPOSITIONS AS GROWTH FACTOR CONTAINING THEM |
Also Published As
| Publication number | Publication date |
|---|---|
| IT7969110A0 (en) | 1979-10-29 |
| CH645098A5 (en) | 1984-09-14 |
| ATA702779A (en) | 1982-04-15 |
| AT368991B (en) | 1982-11-25 |
| GB2035313B (en) | 1983-01-06 |
| GB2035313A (en) | 1980-06-18 |
| IT1192784B (en) | 1988-05-04 |
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