DE1201841B - Process for the preparation of beta [2-carboxy-indolyl- (3)] - alpha-aminopropionic acid - Google Patents
Process for the preparation of beta [2-carboxy-indolyl- (3)] - alpha-aminopropionic acidInfo
- Publication number
- DE1201841B DE1201841B DEA33365A DEA0033365A DE1201841B DE 1201841 B DE1201841 B DE 1201841B DE A33365 A DEA33365 A DE A33365A DE A0033365 A DEA0033365 A DE A0033365A DE 1201841 B DE1201841 B DE 1201841B
- Authority
- DE
- Germany
- Prior art keywords
- carboxy
- indolyl
- preparation
- aminopropionic acid
- beta
- 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
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 5
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 title 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- LCTONWCANYUPML-UHFFFAOYSA-N PYRUVIC-ACID Natural products CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims description 6
- 229940107700 pyruvic acid Drugs 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 5
- RERZNCLIYCABFS-UHFFFAOYSA-N harmaline Chemical compound C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 claims description 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- PPSIMJYXLLXZSK-QMMMGPOBSA-N 3-[(2S)-2-amino-2-carboxyethyl]-1H-indole-2-carboxylic acid Chemical compound C(=O)(O)C1=C(C[C@H](N)C(=O)O)C2=CC=CC=C2N1 PPSIMJYXLLXZSK-QMMMGPOBSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—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)
- Indole Compounds (AREA)
Description
Verfahren zur Herstellung von ß-[2-Carboxy-indolyl-(3)]-a-aminopropionsäure Gegenstand der Erfindung ist ein Verfahren zur Herstellung von j3-[2-Carboxyindolyl-(3)]-a-aminopropionsäure (2-Carboxy-tryptophan) der Formel bei dem man 6-Carboxy-2-pyrono[3,4-b]indol der Formel mit einem Alkalihydroxyd behandelt und die erhaltene ß-[2-Carboxy-indolyl-(3)]-brenztraubensäure mit Wasserstoff in Gegenwart von Ammoniak und einem Nickelkatalysator bei erhöhter Temperatur und unter erhöhtem Druck reduziert. Die Herstellung des als Ausgangsmaterial verwendeten 6-Carboxy-2-pyrono[3.4-b]indols ist von Setsuji S a k u r a i und Tamio I t o in Nippon Kagaku, Zasshi, Bd. 78 (1957), S. 1665 bis 1668, beschrieben.Process for the preparation of ß- [2-carboxy-indolyl- (3)] - a-aminopropionic acid The invention relates to a process for the preparation of j3- [2-carboxyindolyl- (3)] - a-aminopropionic acid (2-carboxy- tryptophan) of the formula in which one has 6-carboxy-2-pyrono [3,4-b] indole of the formula treated with an alkali hydroxide and reduced the β- [2-carboxy-indolyl- (3)] - pyruvic acid obtained with hydrogen in the presence of ammonia and a nickel catalyst at elevated temperature and under elevated pressure. The preparation of the 6-carboxy-2-pyrono [3.4-b] indole used as starting material is described by Setsuji S akurai and Tamio I to in Nippon Kagaku, Zasshi, Vol. 78 (1957), pp. 1665 to 1668.
Die@-[2-Carboxy-indolyl-(3)]-a-aminopropionsäure dient als Zwischenprodukt zur Herstellung von Tryptophan.The @ - [2-carboxy-indolyl- (3)] - a-aminopropionic acid serves as an intermediate product for the production of tryptophan.
Nachstehend wird der Reaktionsverlauf des erfindungsgemäßen Verfahrens formelmäßig wiedergegeben: Das 6-Carboxy-2-pyrono[3,4-b]indol wird unter Rühren z. B. in einer 20o/oigen wäßrigen Alkalihydroxydlösung suspendiert. Die Reaktion verläuft vollständig in 60 bis 90 Minuten bei gewöhnlicher Temperatur und in 5 bis 6 Minuten bei 80°C. Die Isolierung der so gebildeten f-[2-Carboxy indolyl-(3)]-brenztraubensäure kann aus dem Reaktionsgemisch durch Kühlen und Ansäuern, z. B. mit 20o/oiger Schwefelsäure auf pH 1,5, und Extrahieren der Verbindung mit einem Lösungsmittel, wie Äthyläther oder Äthylacetat, durchgeführt werden. Man erhält dann reine f-[2-Carboxy-indolyl-(3)]-brenztraubensäure. Diese Verbindung geht bei erhöhter Temperatur in das 6-Carboxy-2-pyrono[3,4-b]indol über. F. des 2,4-Dinitrophenylhydrazons (aus Wasser-Äthanol) 227 bis 228'C. Es ist jedoch nicht notwendig, die f-[2-Carboxy-indolyl-(3)]-brenztraubensäure vor dem Hydrieren aus dem Reaktionsgemisch zu isolieren.The course of the reaction of the process according to the invention is shown in a formula below: The 6-carboxy-2-pyrono [3,4-b] indole is stirred, for. B. suspended in a 20% aqueous alkali metal hydroxide solution. The reaction proceeds to completion in 60 to 90 minutes at ordinary temperature and in 5 to 6 minutes at 80 ° C. The isolation of the f- [2-carboxy indolyl- (3)] - pyruvic acid thus formed can be carried out from the reaction mixture by cooling and acidification, for. B. with 20% sulfuric acid to pH 1.5, and extracting the compound with a solvent such as ethyl ether or ethyl acetate, can be carried out. Pure f- [2-carboxy-indolyl- (3)] - pyruvic acid is then obtained. This compound changes into 6-carboxy-2-pyrono [3,4-b] indole at an elevated temperature. F. of 2,4-dinitrophenylhydrazone (from water-ethanol) 227 to 228 ° C. However, it is not necessary to isolate the f- [2-carboxy-indolyl- (3)] - pyruvic acid from the reaction mixture before hydrogenation.
Beispiel 19,5 g 6-Carboxy-2-pyrono[3,4-b]indol werden einer Lösung von 29 g Kaliumhydroxyd in 100 ccm Wasser zugefügt und 1 Stunde bei 25°C gerührt. Dem ß-[2-Carboxy-indolyl-(3)]-brenztraubensäure enthaltenden Gemisch werden 200 ccm 28o/oiges Ammoniakwasser, 100 ccm Wasser und 5 g Raney-Nickel als Katalysator zugefügt. Das Gemisch wird bei einem Druck von 50 atm. und einer Temperatur von 50'C hydriert. Die Reaktion ist in 90 Minuten beendet. Das Nickel wird abfiltriert und das Ammoniak aus dem Reaktionsgemisch ausgetrieben. Nach dem Konzentrieren auf 100 ccm wird die Lösung durch Zusatz von 200%iger Schwefelsäure auf einen pH-Wert von 2,5 eingestellt. Die ausgeschiedenen Kristalle werden zur Entfernung des Kaliumsulfats mit heißem Wasser gewaschen und anschließend mit 100 ccm Äthanol gewaschen.Example 19.5 g of 6-carboxy-2-pyrono [3,4-b] indole become a solution of 29 g of potassium hydroxide in 100 ccm of water were added and the mixture was stirred at 25 ° C. for 1 hour. The ß- [2-carboxy-indolyl- (3)] - pyruvic acid-containing mixture are 200 ccm 28% ammonia water, 100 ccm water and 5 g Raney nickel as a catalyst added. The mixture is at a pressure of 50 atm. and a temperature of 50'C hydrogenated. The reaction is complete in 90 minutes. The nickel is filtered off and expelling the ammonia from the reaction mixture. After focusing on The solution is 100 ccm by adding 200% sulfuric acid to a pH value set from 2.5. The precipitated crystals are used to remove the potassium sulfate washed with hot water and then washed with 100 cc of ethanol.
Es werden 21 g (95%)-(p-[2-Carboxy-indolyl-(3)]-a-aminopropionsäure erhalten. F.220 bis 222°C (Zersetzung). Nach Umkristallisieren aus Wasser enthält die Verbindung 1 Mol Kristallwasser. F. 226 bis 228°C (Zersetzung).There are 21 g (95%) - (p- [2-carboxy-indolyl- (3)] - a-aminopropionic acid obtain. F. 220 to 222 ° C (decomposition). Contains after recrystallization from water the compound 1 mole of water of crystallization. M.p. 226 to 228 ° C (decomposition).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1201841X | 1958-12-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1201841B true DE1201841B (en) | 1965-09-30 |
Family
ID=14779978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEA33365A Pending DE1201841B (en) | 1958-12-18 | 1959-11-25 | Process for the preparation of beta [2-carboxy-indolyl- (3)] - alpha-aminopropionic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1201841B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2527366A (en) * | 1946-11-07 | 1950-10-24 | Dow Chemical Co | Production of amino acids |
| US2829145A (en) * | 1956-07-27 | 1958-04-01 | Du Pont | Production of tryptophan |
-
1959
- 1959-11-25 DE DEA33365A patent/DE1201841B/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2527366A (en) * | 1946-11-07 | 1950-10-24 | Dow Chemical Co | Production of amino acids |
| US2829145A (en) * | 1956-07-27 | 1958-04-01 | Du Pont | Production of tryptophan |
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