DE2137044C3 - Process for the preparation of guanldinomercaptocarboxylic acids and their use - Google Patents
Process for the preparation of guanldinomercaptocarboxylic acids and their useInfo
- Publication number
- DE2137044C3 DE2137044C3 DE19712137044 DE2137044A DE2137044C3 DE 2137044 C3 DE2137044 C3 DE 2137044C3 DE 19712137044 DE19712137044 DE 19712137044 DE 2137044 A DE2137044 A DE 2137044A DE 2137044 C3 DE2137044 C3 DE 2137044C3
- Authority
- DE
- Germany
- Prior art keywords
- acids
- solution
- cooh
- guanidinomercaptocarboxylic
- preparation
- 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.)
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Links
- 238000000034 method Methods 0.000 title claims description 5
- 239000002253 acid Substances 0.000 title description 3
- 150000007513 acids Chemical class 0.000 title 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- ANQQHTQWYIYMOW-UHFFFAOYSA-N N(C(=N)N)SC(=O)O Chemical class N(C(=N)N)SC(=O)O ANQQHTQWYIYMOW-UHFFFAOYSA-N 0.000 claims description 6
- 230000000875 corresponding Effects 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000005755 formation reaction Methods 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims 1
- MDBRABWLQUVUBW-UHFFFAOYSA-N aminosulfanylformic acid Chemical class NSC(O)=O MDBRABWLQUVUBW-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atoms Chemical group C* 0.000 claims 1
- 150000001912 cyanamides Chemical class 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- XZMCDFZZKTWFGF-UHFFFAOYSA-N carbodiimide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 150000002019 disulfides Chemical class 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- SJDFZAUTVZNQJD-UHFFFAOYSA-N 3-[[2-carboxy-2-(diaminomethylideneamino)ethyl]disulfanyl]-2-(diaminomethylideneamino)propanoic acid Chemical compound NC(N)=NC(C(O)=O)CSSCC(C(O)=O)N=C(N)N SJDFZAUTVZNQJD-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000510 mucolytic Effects 0.000 description 3
- 229960000583 Acetic Acid Drugs 0.000 description 2
- 229960002433 Cysteine Drugs 0.000 description 2
- 229960001305 Cysteine Hydrochloride Drugs 0.000 description 2
- 229960003067 Cystine Drugs 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine zwitterion Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- -1 Mercapto compound Chemical class 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N Potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L Sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- QIJRTFXNRTXDIP-JIZZDEOASA-N [(1R)-1-carboxy-2-sulfanylethyl]azanium;chloride;hydrate Chemical compound O.Cl.SC[C@H](N)C(O)=O QIJRTFXNRTXDIP-JIZZDEOASA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 239000003638 reducing agent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- COVQXPJCMCBBPX-UHFFFAOYSA-N sulfanylcarbamic acid Chemical class OC(=O)NS COVQXPJCMCBBPX-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XWRZKLKALVJDDS-UHFFFAOYSA-N 2-(diaminomethylideneazaniumyl)-3-sulfanylpropanoate Chemical compound NC(N)=NC(CS)C(O)=O XWRZKLKALVJDDS-UHFFFAOYSA-N 0.000 description 1
- PJQKUNRRFVDXDY-UHFFFAOYSA-N 3-(2-chloro-4-methylphenyl)-2-methylquinazolin-4-one;hydrochloride Chemical compound Cl.ClC1=CC(C)=CC=C1N1C(=O)C2=CC=CC=C2N=C1C PJQKUNRRFVDXDY-UHFFFAOYSA-N 0.000 description 1
- 229960004308 ACETYLCYSTEINE Drugs 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- KBUPNZFOBJQLAL-DKWTVANSSA-N C(N)(=N)N[C@@H](CS)C(=O)O.N(C(=N)N)C(C(=O)O)CS Chemical compound C(N)(=N)N[C@@H](CS)C(=O)O.N(C(=N)N)C(C(=O)O)CS KBUPNZFOBJQLAL-DKWTVANSSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- OBVUKYHBTABSAY-UHFFFAOYSA-N N(C(=N)N)C(C(=O)O)CCSSCCC(C(=O)O)NC(=N)N Chemical compound N(C(=N)N)C(C(=O)O)CCSSCCC(C(=O)O)NC(=N)N OBVUKYHBTABSAY-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic Effects 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229910052570 clay Inorganic materials 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- ZZTSQZQUWBFTAT-UHFFFAOYSA-N diethylcyanamide Chemical compound CCN(CC)C#N ZZTSQZQUWBFTAT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- ZTVZLYBCZNMWCF-UHFFFAOYSA-N homocystine zwitterion Chemical compound [O-]C(=O)C([NH3+])CCSSCCC([NH3+])C([O-])=O ZTVZLYBCZNMWCF-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 1
- 230000001530 keratinolytic Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000001264 neutralization Effects 0.000 description 1
- VVNCNSJFMMFHPL-UHFFFAOYSA-N penicillamine Chemical compound CC(C)(S)C(N)C(O)=O VVNCNSJFMMFHPL-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002965 rope Substances 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N tin hydride Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Description
säure. . . . . . ,acid. . . . . . ,
Dieses vermutete Reaktionsschema ist wie folgt:This presumed reaction scheme is as follows:
N(R)2 N (R) 2
(D(D
und der entsprechenden Disulfide, wobei R Wasserstoff oder ein C1- bis C3-Alkylrest und η Null ode; I bedeutet, dadurch gekennzeichnet, daß man Mercaptoaminocarbonsäuren der Formelnand the corresponding disulfides, where R is hydrogen or a C 1 - to C 3 -alkyl radical and η zero ode; I means, characterized in that one mercaptoaminocarboxylic acids of the formulas
HS-C(R)2-(CH2Jn-CR-COOHHS-C (R) 2 - (CH 2 J n -CR-COOH
II.
NHRNHR
undand
C(R)2- (CH2)„—CR- COOHC (R) 2 - (CH 2 ) "- CR-COOH
NHRNHR
SHSH
(II)(II)
ii-Guanidinocarbonsäur:n konnte man aus «-Aminocarbonsäuren bislang nur durch Umsetzung mit S-Alkylisothioharnstolfen oder O-Alkylisoharnstoffen darstellen, siehe Hoppe — Seylers. Z. Physiol. Chemie, 335 (1961,. S. 272-274. Die hierin beschriebene Reaktion von S c h i 11 e ist ebenfalls in Soc. Chim. France (1948). S. 181 185. zur Her-N=C-N(R)2 + HS-C(R)2-(CH2In-CR-COOHii-guanidinocarboxylic acid: n could hitherto only be prepared from α-amino carboxylic acids by reaction with S-alkylisothioureas or O-alkylisoureas, see Hoppe - Seylers. Z. Physiol. Chemie, 335 (1961, p. 272-274. The reaction of S chi 11 e described herein is also in Soc. Chim. France (1948), p. 181 185. for Her-N = CN (R) 2 + HS-C (R) 2 - (CH 2 I n -CR-COOH
NHRNHR
HNHN
(R2)N(R 2 ) N
C-S-C(R)2-(CH2In-CR-COOHCSC (R) 2 - (CH 2 I n -CR-COOH
NHRNHR
/C(R)2-(CH2)„-CR-COOH\/ C (R) 2 - (CH 2 ) "- CR-COOH \
bzw. deren Disulfide in neutraler oder schwach alkalischer Lösung mit einem Cyanamid der Formel 4uor their disulfides in neutral or weakly alkaline solution with a cyanamide of Formula 4u
N = C- N(R)2 N = C-N (R) 2
zur Reaktion bringt, wobei im zuletzt genannten Fall eine katalytische Menge der entsprechenden Merkaptoverbindung zugesetzt wird, und gegebenenfalls die Disulfide der Guanidinomercaptocarbonsäuren mit üblichen Reduktionsmitteln behandelt. brings to reaction, in the latter case a catalytic amount of the corresponding Mercapto compound is added, and optionally the disulfides of guanidinomercaptocarboxylic acids treated with common reducing agents.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man das Disulfid einer Mercaptoaminocarbonsäure der Formel 11 in Gegenwart einer reduzierend wirkenden Substanz mit dem Cyanamid umsetzt.2. The method according to claim 1, characterized in that the disulfide of a mercaptoaminocarboxylic acid of formula 11 reacts with the cyanamide in the presence of a reducing substance.
3. Verwendung der Guanidinomercaptocarbonsäuren der Formeln I als keratolytisch wirkende Substanzen.3. Use of the guanidinomercaptocarboxylic acids of the formula I as keratolytic Substances.
HS—C(R)2—(CH2)n—CRCOOHHS-C (R) 2 - (CH 2 ) n -CRCOOH
NR
HN=CNO
HN = C
N(R)2 N (R) 2
Die nach dem erfindungsgemäßen Verfahren hergestellten Guanidinomercaptocarbonsäuren der zuvorThe guanidinomercaptocarboxylic acids prepared by the process according to the invention of the above
angegebenen Formel stellen z. B. potente keratolvtisch oder mucolytisch wirkende Substanzen dar. die als haarverformende oder schleimlösende Mittel eingesetzt werden können. So ergaben Vergleichsversuche, daß die gemäß der Erfindung verwendete Verbindunggiven formula represent z. B. potent keratolvic or mucolytic substances are used as hair-shaping or expectorant agents can be. Thus, comparative tests showed that the compound used according to the invention
Guanylcystein eine etwa dreifach bessere mucclytische Wirksamkeit als das bekannte Mucolytikum Acetylcystein besitzt.Guanylcysteine has about three times better muclytic effectiveness than the well-known mucolytic acetylcysteine owns.
Bessere mucolytische Wirksamkeit zeigt ebenfallsAlso shows better mucolytic effectiveness
N - Guanyl - DL - penicillamin und N - Guanyl-DL-isocystein. N - guanyl - DL - penicillamine and N - guanyl-DL-isocysteine.
Die erhöhte Reaktionsfähigkeit der Thiolgruppe läßt generell überall dort die Anwendung der nach dem erhndungsgemäßen Verfahren hergestellten Verbindungen als vorteilhaft erscheinen, wo z. B. Cystein oder ähnliche Verbindungen aufgrund ihrer Thiolgruppe eingesetzt werden.The increased reactivity of the thiol group generally decreases the application of the everywhere there Compounds produced by the process according to the invention appear to be advantageous where, for. B. cysteine or similar compounds are used because of their thiol group.
Das erfindungsgemäße Verfahren wird anhand der folgenden Beispiele näher erläutert.The process according to the invention is explained in more detail with the aid of the following examples.
175,5 g Cysteinhydrochlorid-monohydral (1 Mol) und 84 g Cyanamidlösung, 50%ig (1 Mol), werden mit 100 ml Wasser und 150 g Eis versetzt. Unter Eiskühlung stellt man den pH-Wert mit konz. Natronlauge auf 8. Die Temperatur steigt trotz Kühlung auf 40GC an. Man hält das pH etwa 30 Minuten bei 8. Es scheiden sich grobe Kristalle, meist in Form viereckiger Doppelpyramiden, ab, die alsbald abgesaugt werden. Man wäscht nacheinander mit Wasser, Alkohol und Aceton. Nach Trocknen erhält man 121 g 2-Guanidino-3-mercaptopropionsäure (= 74% d.Th.).175.5 g of cysteine hydrochloride monohydral (1 mol) and 84 g of 50% cyanamide solution (1 mol) are mixed with 100 ml of water and 150 g of ice. While cooling with ice, adjust the pH with conc. Sodium hydroxide solution to 8. The temperature rises to 40 ° C. in spite of cooling. The pH is kept at 8 for about 30 minutes. Coarse crystals separate out, mostly in the form of square double pyramids, which are then suctioned off. Wash successively with water, alcohol and acetone. After drying, 121 g of 2-guanidino-3-mercaptopropionic acid (= 74% of theory) are obtained.
QH9N3O2S (163,19):QH 9 N 3 O 2 S (163.19):
Berechnet ... C 29,43, H 5,56, N 25,75, S 19,65;
gefunden .... C 29,61, H 5,48, N 25,70. S 19,21.Calculated ... C 29.43, H 5.56, N 25.75, S 19.65;
found .... C 29.61, H 5.48, N 25.70. S 19.21.
24 g Cystein (0,1 Mol) werden in 100 ml Wasser suspendiert und mit 20 m! konz. Ammoniaklösung versetzt. Unter Rühren gibt man dazu 20 ml einer 50%igen Cyanamidlösung und 1,5 g Cysteinhydrochlorid. Nach kurzer Zeit steigt die Temperatur auf 40—45'C an, ohne daß Lösung eintritt. In der Suspension finden sich jedoch jetzt ausschließlich rechteckige Blättchen, die man absaugt und trocknet. Man erhält 32,6 g 3,3'-Dithio-bis-(2-guanidinopropionsäure) = Ν,Ν'-Diguanylcystin.24 g of cysteine (0.1 mol) are suspended in 100 ml of water and 20 ml! conc. Ammonia solution offset. 20 ml of a 50% strength cyanamide solution and 1.5 g of cysteine hydrochloride are added with stirring. After a short time the temperature rises to 40-45 ° C without the occurrence of solution. In the In the suspension, however, there are now only rectangular leaves that are sucked off and dried. 32.6 g of 3,3'-dithio-bis (2-guanidinopropionic acid) = Ν, Ν'-diguanylcystine are obtained.
C8H16NnO4S2 (324,32):C 8 H 16 N n O 4 S 2 (324.32):
Berechnet ... C 29,60, H 4,98, N 25,92:
gefunden .... C 29,68, H 4,91, N 25,77.Calculated ... C 29.60, H 4.98, N 25.92:
found .... C 29.68, H 4.91, N 25.77.
Zu einer Suspension von 24 g Cystin (0.1 Mci) in 100 ml Wasser und 20 ml konz. Ammoniak werden 20 ml einer 50%igen Cyanamidlösung und 0,5 g Kaliumcyanid gegeben. Nach kurzer Zeit steigt die Temperatur an, ohne daß Lösung eintritt. Die Kristalle haben sich in rechteckige Blättchen umgewandelt, von denen abgesaugt wird.To a suspension of 24 g of cystine (0.1 Mci) in 100 ml of water and 20 ml of conc. Become ammonia 20 ml of a 50% cyanamide solution and 0.5 g of potassium cyanide are added. After a short time, the Temperature without any solution entering. The crystals have turned into rectangular leaves, from which is sucked off.
Ausbeute: 29,9 g 3,3' - Dithio - bis - (2 - guanidinopropionsäure) = Ν,Ν'-Diguanylcystin.Yield: 29.9 g of 3,3 '- dithio - bis - (2 - guanidinopropionic acid) = Ν, Ν'-diguanylcystine.
C8H16N6O4S2 (324,32):
Berechnet ... C 29,60, H 4,98, N 25.92:
gefunden .... C 29,74, H 5.05, N 25,86.C 8 H 16 N 6 O 4 S 2 (324.32):
Calculated ... C 29.60, H 4.98, N 25.92:
found .... C 29.74, H 5.05, N 25.86.
Zu einer Suspension von 24 g Cystin (0,1 Mol) in 100 ml Wasser und 20 ml konz. Ammoniak gibt man 20 ml 5()%ige Cyanamidlösung und 1 g Natriumsulfit. Die Temperatur steigt allmählich auf 50 C an, und die in der Suspension vorhandenen Kristalle wandeln sich, ohne daß Lösung eintritt, in rechteckige Blättchen um, von denen abgesaugt wird.To a suspension of 24 g of cystine (0.1 mol) in 100 ml of water and 20 ml of conc. Ammonia is given 20 ml 5 ()% cyanamide solution and 1 g sodium sulfite. The temperature gradually rises to 50 C, and the crystals present in the suspension change into rectangular ones without the entry of solution Leaflets around which are suctioned off.
Ausbeute: 30,15 g 3,3'- Dithiobis-(2-guanidinopropionsäure). Yield: 30.15 g of 3,3'-dithiobis (2-guanidinopropionic acid).
S Zu einer Suspension von 26,8 g Homocystin (0,1 Mol) in 200 ml Wasser und 20 ml konz. Ammoniak werden 20 ml einer 50%igen Cyanamidlösung und 1 g Kaliumcyanid gegeben. Allmählich tritt Erwärmung ein, und der Kristallbrei verwandelt ίο sich in einen solchen aus rautenförmigen Blättchen.S To a suspension of 26.8 g homocystine (0.1 mol) in 200 ml water and 20 ml conc. ammonia 20 ml of a 50% strength cyanamide solution and 1 g of potassium cyanide are added. Gradually occurs Warming up, and the crystal pulp transforms ίο into one made of diamond-shaped leaves.
Ausbeute: 29,4 g 4,4'- Dithiobis - (2 - guanidinobuttersäure). Das Produkt ist dünnschichtchromatographisch einheitlich.Yield: 29.4 g of 4,4'-dithiobis (2-guanidinobutyric acid). The product is thin-layer chromatography uniformly.
C10H20N6O4S2 (352,37):C 10 H 20 N 6 O 4 S 2 (352.37):
Berechnet ... C 34,09, H 5,72, N 23,85; gefunden .... C 34,03, H 5,76, N 23,79.Calculated ... C 34.09, H 5.72, N 23.85; found .... C 34.03, H 5.76, N 23.79.
Man löst 40,5 g 3,3'-Dithiobis-(2-guanidinopropionsäure) = Ν,Ν'-Diguanykystin (0,125 Mol) in 200 ml Wasser durch Zusatz von 40 ml konz. Salzsäure auf und gibt zu dieser Lösung, die sich in einem als Elektrolysiergefäß dienenden Becherglas befindet,40.5 g of 3,3'-dithiobis (2-guanidinopropionic acid) = Ν, Ν'-diguanykystin (0.125 mol) are dissolved in 200 ml Water by adding 40 ml of conc. Hydrochloric acid and is added to this solution, which is in an as Beaker serving the electrolysis vessel,
200—300 mg Zinn hinzu. Als Kathode befindet sich ein Kupferblech am Boden des Becherglases, in die Kathodenlösung taucht ein mit halbkonzentrierter Salzsäure gefüllter Tonzylinder ein, der als Diaphragma dient. In die Salzsäure taucht als Anode ein Kohlestab ein. Man legt eine Gleichspannung aus einer Niederstromquelle an und reduziert bei einer Stromstärke von 2 A innerhalb von 5—6 Stunden das Disulfid zur entsprechenden Mercaptoverbindung. Den Verlauf der Reaktion kontrolliert man durch Titration der gebildeten SH-Gruppen.Add 200-300 mg of tin. As a cathode, there is a copper sheet at the bottom of the beaker, into which Cathode solution is immersed in a clay cylinder filled with half-concentrated hydrochloric acid, which acts as a diaphragm serves. A carbon rod dips into the hydrochloric acid as an anode. A direct voltage is laid out a low-current source and, at a current strength of 2 A, reduces this within 5–6 hours Disulfide to the corresponding mercapto compound. The course of the reaction is checked Titration of the formed SH groups.
Die reduzierte Lösung wird filtriert und zu einem dicVen Sirup eingeengt, den man in 70 ml Äthanol aufnimmt und bei 40 C neutralisiert. Man rührt 30 Minuten unter Kühlen nach, saugt ab, wäscht mit Äthanol und trocknet an der Luft. Man erhält 29,3 g 2-Guanidino-3-mercaptopropionsäure (— N-Guanylcystein) = 72% d.Th.The reduced solution is filtered and concentrated to a thick syrup, which is dissolved in 70 ml of ethanol absorbs and neutralizes at 40 C. The mixture is stirred for 30 minutes while cooling, filtered off with suction, washed with Ethanol and air dry. 29.3 g of 2-guanidino-3-mercaptopropionic acid (- N-guanylcysteine) are obtained = 72% of the total
C4H9N3O2S (163,19):C 4 H 9 N 3 O 2 S (163.19):
Berechnet ... C 29,43, H 5,56, N 25,75, S 19,65: gefunden .... C 29,55, H 5,49, N 25,81, S 19,18.Calculated ... C 29.43, H 5.56, N 25.75, S 19.65: found .... C 29.55, H 5.49, N 25.81, S 19.18.
35 g Isocystein-hydrochlorid (0,2 Mol) werden in
50 ml Wasser gelöst und mit 16,8 g Cyanamidlösung. 50%ig (0,2 Mol) versetzt. Unter Eiükühlung wird das
pH mit konz. Natronlauge auf 7,5—8,0 gestellt. Trotz
der Kühlung erfolgt starke Erwärm»ng. Während der schnell einsetzenden Kristallbildung steigt der
pH-Wert über 8 an und wird mit Eisessig auf 7,8— 0,8
zurückgestellt. Man isoliert kräftige sechsseitige Kristalle des N-Guanylisocysteins in einer Ausbeute von
31g.
C4H9N3O2S (163,19):35 g of isocysteine hydrochloride (0.2 mol) are dissolved in 50 ml of water and mixed with 16.8 g of cyanamide solution. 50% (0.2 mol) added. The pH is adjusted with conc. Sodium hydroxide solution set to 7.5-8.0. Despite the cooling, there is strong warming. During the rapid onset of crystal formation, the pH rises above 8, and 8 is 0.8 to 7 with glacial acetic acid, reset. Strong six-sided crystals of N-guanyl isocysteine are isolated in a yield of 31 g.
C 4 H 9 N 3 O 2 S (163.19):
Berechnet ... C 29,43, H 5,56. N 25,75. S 19.65: gefunden .... C 29.33. H 5.63. N 25,67, S 19.38.Calculated ... C 29.43, H 5.56. N 25.75. S 19.65: found .... C 29.33. H 5.63. N 25.67, S 19.38.
15 g Isocystein-hydrochlorid werden in 50 ml Wasser und 60 ml Dioxan suspendiert und mit 9.8 g N,N-Diäthylcyanamid versetzt. Mit insgesamt 12 ml konzentrierter Natronlauge wird der pH-Wert bei 815 g of isocysteine hydrochloride are dissolved in 50 ml of water and 60 ml of dioxane are suspended and 9.8 g of N, N-diethylcyanamide are added. With a total of 12 ml concentrated sodium hydroxide solution, the pH value is 8
gehalten. Nach etwa 15 Minuten fällt ein Niederschlag in Form eines dicken Kristallbreis aus. Man erhält 16,3 g rohes N-(N',N'-Diäthylguanyl)-isocystein. das man aus Wasser umkristallisiert. Die sechsseiligen. quaderförmigen Kristalle sind schwer löslich in heißem und unlöslich kaltem Methanol.held. After about 15 minutes a precipitate falls in the form of a thick crystal pulp. 16.3 g of crude N- (N ', N'-diethylguanyl) isocysteine are obtained. that is recrystallized from water. The six-rope. cuboid crystals are sparingly soluble in hot and insoluble cold methanol.
1,5 g DL-Penicillamin werden in 20 ml Wasser gelöst und mit 2,4 ml Cyanamidlösung (50%ig) versetzt. Mit einigen Tropfen kenz. Natronlauge wird die Lösung auf pH 8 gebracht und dieser pH-Wert durch Zusatz geringer Mengen Eisessig gehalten. Nach wenigen Minuten tritt Kristallisation ein. Man erhält 6eckige längliche Blättchen. Nach 2stündigem Nachrühren wird auf pH 7 gestellt und nach Stehen über Nacht im Eisschrank abgesaugt und mit Wasser. Alkohol und Aceton gewaschen.1.5 g of DL-penicillamine are in 20 ml of water dissolved and mixed with 2.4 ml of cyanamide solution (50%). With a few drops of kenz. Caustic soda is used the solution was brought to pH 8 and this pH was maintained by adding small amounts of glacial acetic acid. Crystallization occurs after a few minutes. Hexagonal elongated leaflets are obtained. After 2 hours Stirring is then adjusted to pH 7 and, after standing overnight in the refrigerator, filtered off with suction and washed with water. Alcohol and acetone washed.
Ausbeute: 1,8 g N-Guanyl-DL-penicillamin.Yield: 1.8 g of N-guanyl-DL-penicillamine.
C.H.,N,O2S (191,25):CH, N, O 2 S (191.25):
Berechnet ... C 37.75, H 6,87, N 21,98. S 16.76:
»efunden .... C 37,63, H 6,92. N 21,78. S 16.61.Calculated ... C 37.75, H 6.87, N 21.98. S 16.76:
Found .... C 37.63, H 6.92. N 21.78. S 16.61.
Claims (1)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712137044 DE2137044C3 (en) | 1971-07-23 | Process for the preparation of guanldinomercaptocarboxylic acids and their use | |
| CH684872A CH583189A5 (en) | 1971-07-23 | 1972-05-09 | |
| AT550173A AT323899B (en) | 1971-07-23 | 1972-05-17 | KERATOLYTIC COSMETIC AGENTS |
| AT429072A AT313915B (en) | 1971-07-23 | 1972-05-17 | Process for the production of new guanidinomercaptocarboxylic acids |
| FR7226402A FR2150709B1 (en) | 1971-07-23 | 1972-07-21 | |
| CA147,646A CA983954A (en) | 1971-07-23 | 1972-07-21 | Guanidinomercaptocarboxylic acids |
| GB3446072A GB1385092A (en) | 1971-07-23 | 1972-07-24 | Guanidino-mercaptocarboxylic acids and their disulphides processes for their preparation and compositions coantaining them elevator motor control system employing power aplifier with output current limitting arrangement |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712137044 DE2137044C3 (en) | 1971-07-23 | Process for the preparation of guanldinomercaptocarboxylic acids and their use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2137044A1 DE2137044A1 (en) | 1973-02-01 |
| DE2137044B2 DE2137044B2 (en) | 1976-09-09 |
| DE2137044C3 true DE2137044C3 (en) | 1977-04-28 |
Family
ID=
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