DE1207390B - Process for the production of purine - Google Patents
Process for the production of purineInfo
- Publication number
- DE1207390B DE1207390B DEF34484A DEF0034484A DE1207390B DE 1207390 B DE1207390 B DE 1207390B DE F34484 A DEF34484 A DE F34484A DE F0034484 A DEF0034484 A DE F0034484A DE 1207390 B DE1207390 B DE 1207390B
- Authority
- DE
- Germany
- Prior art keywords
- purine
- aminoacetonitrile
- formamide
- production
- methyleniminoacetonitrile
- 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.)
- Pending
Links
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 16
- GFZMFCVDDFHSJK-UHFFFAOYSA-N 2-(methylideneamino)acetonitrile Chemical group C=NCC#N GFZMFCVDDFHSJK-UHFFFAOYSA-N 0.000 claims description 7
- 150000008361 aminoacetonitriles Chemical class 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000003377 acid catalyst Substances 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-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
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 3
- -1 amyl alcohols Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000006825 purine synthesis Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003918 triazines Chemical class 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
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Verfahren zur Herstellung von Purin Gegenstand des Patents 1150 988 ist ein Verfahren zur Herstellung von Purin, das dadurch gekennzeichnet ist, daß Salze oder Acylderivate des a-Aminoacetonitrils mit Trisformaminomethan, Formamidinacetat oder Formamid bei erhöhter Temperatur umgesetzt werden.Process for the production of purine The subject of patent 1150 988 is a process for the production of purine, which is characterized in that salts or acyl derivatives of α-aminoacetonitrile are reacted with trisformaminomethane, formamidine acetate or formamide at elevated temperature.
In Abänderung dieses Verfahrens wurde nun gefunden, daß man in einfacher Weise Purin erhält, wenn man an Stelle des dort eingesetzten Derivates von oc-Aminoacetonitril Methyleniminoacetonitril mit Trisformaminomethan, Formamidinacetat oder Formamid unter Verwendung eines organischen Lösungsmittels in Gegenwart eines sauren Katalysators bei einer Temperatur zwischen 80 und 200°C, vorzugsweise bei 120 bis 180°C, umsetzt.Modifying this procedure has now been found to be easier Wise purine is obtained if instead of the derivative of oc-aminoacetonitrile used there Methyleniminoacetonitrile with trisformaminomethane, formamidine acetate or formamide using an organic solvent in the presence of an acidic catalyst at a temperature between 80 and 200 ° C, preferably at 120 to 180 ° C, is reacted.
Als Lösungsmittel eignen sich Säureamide, z. B. Formamid und Dimethylformamid, Carbonsäuren, insbesondere Eisessig, und Alkohole, wie Propanol, Butanol, Amylalkohole und Glykolmonoalkyläther, z. B. Glykolmonomethyläther. Das Verfahren gemäß der Erfindung wird zweckmäßig in der Weise durchgeführt, daß man im Rahmen der oben gegebenen Definition des Verfahrens die Schiffsche Base zusammen mit der Formylierungskomponente in Gegenwart eines Lösungsmittels, gegebenenfalls eines Lösungsmittelgemisches, wie Säureamid und Alkohol, unter Zugabe eines sauren Katalysators, wie Schwefelsäure, umsetzt.Acid amides are suitable as solvents, e.g. B. formamide and dimethylformamide, Carboxylic acids, especially glacial acetic acid, and alcohols such as propanol, butanol, amyl alcohols and glycol monoalkyl ethers, e.g. B. glycol monomethyl ether. The method according to the invention is expediently carried out in such a way that one within the scope of the above Definition of the process the Schiff base together with the formylation component in the presence of a solvent, optionally a solvent mixture, such as acid amide and alcohol, with the addition of an acidic catalyst such as sulfuric acid, implements.
Das erfindungsgemäße Verfahren stellt eine erhebliche Verbesserung der in »Angewandte Chemie«, Bd. 73, 21. Januar 1961, S. 63, referierten Arbeitsweise des Hauptpatents dar. Es ist nämlich möglich, das als Ausgangsstoff benötigte Methyleniminoacetonitril in nicht beanspruchter Weise durch einfaches Zusammengeben von Formamid, Ammonchlorid und Natriumcyanid in Ausbeuten von etwa 70 °/o herzustellen, während die Darstellung der acylierten Aminoacetonitrile zusätzlich noch zwei weitere Reaktionsstufen erfordert. Zu ihrer Darstellung muß das Methyleniminoacetonitril in alkoholischer Lösung in Gegenwart von Säure, z. B. Schwefelsäure, gespalten und das auf diese Weise in etwa 65°/oiger Ausbeute entstandene Salz, z. B. das Sulfat des Aminoacetonitrils, nach bekannten Methoden in alkalischer Lösung mit Säurechlorid acetyliert werden. Die auf das Methyleniminoacetonitrit bezogene Ausbeute an Purin liegt also für das erfindungsgemäße Verfahren wesentlich höher als bei der Verwendung von acyliertem Aminoacetonitril.The method according to the invention represents a considerable improvement the working method reported in "Angewandte Chemie", Vol. 73, January 21, 1961, p. 63 of the main patent. It is possible to use the methyleniminoacetonitrile required as a starting material in a manner not claimed by simply adding formamide and ammonium chloride together and to produce sodium cyanide in yields of about 70% during the preparation the acylated aminoacetonitrile also requires two further reaction stages. For their representation, the methyleniminoacetonitrile must be in alcoholic solution in Presence of acid, e.g. B. sulfuric acid, split and in this way roughly 65% yield resulting salt, e.g. B. the sulfate of aminoacetonitrile, after known methods are acetylated in alkaline solution with acid chloride. the based on the methyleniminoacetonitrite yield of purine is therefore for that according to the invention Process significantly higher than when using acylated aminoacetonitrile.
Weiterhin ist es überraschend, daß Methyleniminoacetonitril an Stelle von acyliertem Aminoacetonitril zur Purinsynthese verwendet werden kann. Das Methyleniminoacetonitril liegt als trimere Verbindung, d. h. als hydriertes Triazinderivat vor. Entsprechende tertiäre Amine, wie N,N-dialkylierte Aminoacetonitrile, reagieren jedoch nicht mit Trisformaminomethan und Formamid. Unter der Annahme, daß bei dem Verfahren gemäß der Erfindung durch die Gegenwart von Säure primär eine Spaltung zum Aminoacetonitril erfolgt, müßten in dem Reaktionsgemisch neben der angewandten Säure noch Formaldehyd, Formamid, Trisformaminomethan und Aminoacetonitril vorliegen. Auf Grund der in diesem Reaktionsgemisch sich ergebenden vielfältigen Reaktionsmöglichkeiten, z. B. in Richtung auf die Entstehung von Methylolverbindungen oder eine durch den Säureeinfluß bewirkte Zersetzung der Reaktionskomponenten, war es in keiner Weise vorauszusehen, daß nach dem erfindungsgemäßen Verfahren Purin in ausgezeichneter Reinheit und guter Ausbeute entstehen würde.Furthermore, it is surprising that methyleniminoacetonitrile in place of acylated aminoacetonitrile can be used for purine synthesis. The methyleniminoacetonitrile lies as a trimeric compound, d. H. as a hydrogenated triazine derivative. Appropriate tertiary amines such as N, N-dialkylated aminoacetonitriles, however, do not react Trisformaminomethane and formamide. Assuming that the procedure according to of the invention primarily a cleavage to aminoacetonitrile due to the presence of acid takes place, formaldehyde would have to be in the reaction mixture in addition to the acid used, Formamide, trisformaminomethane and aminoacetonitrile are present. Because of the in this Reaction mixture resulting diverse reaction possibilities, z. B. in the direction on the formation of methylol compounds or one caused by the influence of acids Decomposition of the reaction components, it was in no way to be foreseen that after the purine process according to the invention in excellent purity and good yield would arise.
Beispiel 3,4 g Methyleniminöacetonitril werden mit 36 g Trisformaminomethan, 25 ccm Formamid und 2,5 g konzentrierter Schwefelsäure 4 Stunden auf 160'C erhitzt. Anschließend wird das Reaktionsgemisch mit Soda neutralisiert, zur Trockne eingeengt, durch Behandeln mit absolutem Äthanol von den Salzen getrennt, nochmals eingeengt, mit Wasser aufgenommen und mit Chloroform extrahiert. Nach Abziehen des Lösungsmittels beträgt die Ausbeute an Purin vom Schmelzpunkt 215'C 300/, der Theorie.Example 3.4 g of methyleniminoacetonitrile are heated to 160.degree. C. for 4 hours with 36 g of trisformaminomethane, 25 cc of formamide and 2.5 g of concentrated sulfuric acid. The reaction mixture is then neutralized with soda, concentrated to dryness, separated from the salts by treatment with absolute ethanol, concentrated again, taken up in water and extracted with chloroform. After the solvent has been stripped off, the purine yield with a melting point of 215 ° C. is 300% of theory.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF34484A DE1207390B (en) | 1961-07-21 | 1961-07-21 | Process for the production of purine |
| GB161562A GB983114A (en) | 1961-01-16 | 1962-01-16 | Process for the manufacture of purines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF34484A DE1207390B (en) | 1961-07-21 | 1961-07-21 | Process for the production of purine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1207390B true DE1207390B (en) | 1965-12-23 |
Family
ID=7095571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF34484A Pending DE1207390B (en) | 1961-01-16 | 1961-07-21 | Process for the production of purine |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1207390B (en) |
-
1961
- 1961-07-21 DE DEF34484A patent/DE1207390B/en active Pending
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