CN101085745A - Modified synthesis method for L-theanine - Google Patents
Modified synthesis method for L-theanine Download PDFInfo
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- CN101085745A CN101085745A CNA2006100920837A CN200610092083A CN101085745A CN 101085745 A CN101085745 A CN 101085745A CN A2006100920837 A CNA2006100920837 A CN A2006100920837A CN 200610092083 A CN200610092083 A CN 200610092083A CN 101085745 A CN101085745 A CN 101085745A
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- Prior art keywords
- theanine
- reaction
- antioxidant
- ketone acid
- ethamine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/14—Preparation of carboxylic acid amides by formation of carboxamide groups together with reactions not involving the carboxamide groups
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Abstract
The invention relates to a method for synthesizing L- theanine. It takes L- pyrrolidone acid and waterless ethlamine as raw material, carrying out reaction under anti- oxidizing agent existence and with air discharged by dried ethlamine gas condition. The reaction temperature is 30- 59 Deg. C, the pressure is 0.4- 5.9 Mpa, and the productivity is apparently higher than that of under condition without anti- oxidizing agent and with air.
Description
Invention field
The present invention relates to organic chemistry and pharmaceutical chemistry field, particularly, the feature amino acid that the present invention relates to tealeaves is the improvement synthetic method of L-theanine.
Background technology
L-theanine (L-theanine) is for to be present in the feature amino acid of nature tealeaves and to be the L type, chemistry is by name: N-ethyl-L-glutaminate (N-ethyl-L-glutamine), U.S. chemical abstract registration number CAS:[3081-61-6], pure product are white, needle-shaped crystals, fusing point: 217-218 ℃ (decomposition), specific optical rotation: [α]
20 D:+7.7-+8.5 ° (5%, H
2O).
Its structural formula is as follows:
Because containing the L-theanine in the tealeaves is 2% only, wants to obtain from tealeaves and produce in batches the high L-theanine of purity, is very difficult.For satisfying market demand, prepare the L-theanine with chemical synthesis and have economic implications.
As far back as nineteen forty-two Israelis N.Lichtenstein (J.Am.Chem.Soc., 1942,64,1021-1022) first in the laboratory with tetramethyleneimine ketone acid and 33% ethylamine solution reaction (37 ℃, 20 days), obtain theanine, this method yield is very low.Nineteen fifty; the wine family of Japan is two youths (Japanese agriculture chemistry meeting will more; 1950; 23:269) proposing with L-L-glutamic acid-γ-ethyl ester is raw material; behind chloroformic acid benzyl ester protection amino,, be catalysed and reduced into the L-theanine with Pd/C again with the ethylamine solution reaction; use precious metal palladium to make catalyzer, the production cost height.
Nineteen fifty-one, the bridge pawl of Japan refined (Japanese agriculture chemistry meeting will, 1951,25:25-26) improved synthetic method, promptly use L-tetramethyleneimine ketone acid and pure ethamine rather than ethylamine solution,, make the yield of theanine bring up to 43.2% in 28-32 ℃ of placing response 14-28 days.
1964, T. Furuyama (Bull.Chem.Soc.Japan, 1964,37,1078) adopted dithiocarbonic anhydride protection amino and has synthesized theanine.
Nineteen sixty-five, it is raw material that N.Lichtenstein uses L-glutamic acid acetaldehyde instead, is reduced into theanine with Pd/C, and has applied for Israel's patent (Israeli, 23768,1965).
1966, and Y.Yamada etc. (Bull.Chem.Soc.Japan, 1966,39,1999-2000) once with L-tetramethyleneimine ketone acid XianCheng mantoquita, synthesize theanine with anhydrous ethylamine in 7 days method of 70 ℃ of reactions again, yield is improved, but the reaction times is oversize.
1997, (foodstuff additive handbook, Chemical Industry Press such as Ling Guanting, 1997,136-137) in book, point out, adopt L-L-glutamic acid thermal dehydration to generate the tetramethyleneimine ketone acid, and then under high pressure heat with anhydrous ethylamine and theanine, but do not see detailed process and data.
The amino synthetic method of protection that relates to the L-theanine also has patent documentation as JP570491A, JP9263573A, Jp11116542A, (fine chemistry industry, 2001,4, the articles of 223-224) delivering such as JP2000-36383A and Wang Sanyong.
We are in the experiment and pilot scale process of L-theanine, find that oxygen exists in the air, cause amination reaction generation side reaction or make the resultant oxidation, the color and luster variation, in order to make product reach repeatedly recrystallization of certain purity (〉=98.5%), but to reduce yield is cost, and therefore improving the anti-oxidation side reaction of reaction environment is crucial improvement synthetic method.
Goal of the invention
The object of the invention provides a kind of production synthetic method of L-theanine, with market raw material on sale, make the L-theanine have the characteristics of suitability for industrialized production, and keep the L-configuration, provide the edible and health care of people, medicinal use with lower, the colory product of price.
Summary of the invention
The invention provides improved L-theanine synthetic method, wherein react without protecting group, without rare gas elementes such as inflated with nitrogen; Under certain pressure and temperature, will shorten in the reaction times, improve yield, and through medium-scale production checking.
Technical scheme one of is improved:
After L-tetramethyleneimine ketone acid (commercially available, roc generationization limited liability company in Mianzhu City, Sichuan produce) fed intake, with dry ethamine gas the air in the closed reactor is drained back (and without rare gas element emptying) and carry out middle pressure with anhydrous ethylamine and react;
Reaction formula is as follows:
L-tetramethyleneimine ketone acid anhydrous ethylamine L-theanine
Be characterized in: under middle pressure and certain temperature, because the air in draining reactor, the friendly environment of an amination reaction of formation is avoided contingent oxidizing reaction, to ensureing product color, specific optical rotation, yield good effect is arranged all.
Two of technical scheme improvement:
With L-tetramethyleneimine ketone acid and anhydrous ethylamine (for example: quinoline, ethoxyquin, quinhydrones, vitamins C, Quercetin or butyl hydroxy anisol at antioxidant, perhaps their mixture) aminating reaction is carried out in the temperature pressurization in existing down, and wherein the consumption of antioxidant is 0.5-3 (weight) % of L-tetramethyleneimine ketone acid.The pressurized conditions of producing is 0.4-5.9MPa, and temperature of reaction is controlled between 30-59 ℃.
Three of technical scheme improvement:
With L-tetramethyleneimine ketone acid and anhydrous ethylamine in the presence of antioxidant (consumption be the technical scheme improvement two half), after with the anhydrous ethylamine of gasification the air that may exist in the reactor being drained, amination reaction is carried out in heating pressurization.Wherein the consumption of antioxidant is 0.25-1.5 (weight) % of L-tetramethyleneimine ketone acid.The pressurized conditions of producing is 0.45-5.9PMa, and temperature of reaction is controlled at 30-59 ℃.Product quality one of improve than technical scheme and two lack recrystallization one time, correspondingly yield also has raising.
Advantage of the present invention is: technological process is brief, easy to operate under pressurization, middle temperature reaction conditions, makes suitability for industrialized production feasible; Keep the L-configuration, consistent with the natural chemicals configuration, this point is very important, has produced beyond thought good result.Product quality, content and specific optical rotation are guaranteed, and L-theanine total recovery: 58.0-60.1% is better than the method for other operational paths.
The invention will be further described below by embodiment.It should be understood that the described preparation method of the embodiment of the invention is only used for illustrating the present invention, rather than limitation of the present invention, under design prerequisite of the present invention,, all belong to the scope of protection of present invention to preparation method's of the present invention simple modifications.Except as otherwise noted, the percentage ratio among the present invention is weight percentage.
Embodiment one
In 500L stainless steel pressure still, add 60Kg L-tetramethyleneimine ketone acid and 0.6Kg ethoxyquin, closed reactor adds 200Kg liquid anhydrous ethamine, slowly heat with hot water bath, interior temperature remains on 30-59 ℃, and middling speed stirs, and pressure remains on 0.4-5.9MPa, reacted 48 hours, reaction finishes, and reclaims excessive ethamine, and the ethamine of recovery can be reused and feed intake.The reaction product activated carbon decolorizing, 95% ethyl alcohol recrystallization gets elaboration 47.3Kg, yield: 58.5%, [α]
20 D+ 7.7～+ 8.5 ° (5%, H
2O), purity: (HPLC) 〉=98.5%.
Embodiment two
In 500L stainless steel pressure still, add 60Kg L-tetramethyleneimine ketone acid closed reactor, air in the still is drained, add liquid anhydrous ethamine 190Kg again with the dry ethamine gas in the steel cylinder, slowly heat with hot water bath, interior temperature remains on 30-59 ℃, and middling speed stirs, and pressure remains on 0.4-5.9MPa, reacted 60 hours, reaction finishes, and reclaims excessive ethamine, and the ethamine of recovery can be reused and feed intake.The reaction product activated carbon decolorizing, 95% ethyl alcohol recrystallization is used soaked in absolute ethyl alcohol, gets elaboration 38.9Kg, yield: 48.2%, [α]
20 D+ 7.7～+ 8.5 ° (5%, H
2O), purity: (HPLC) 〉=98.5%.
Embodiment three
In 1000L stainless steel pressure still, add 60Kg L-tetramethyleneimine ketone acid and antioxidant 0.6g quinoline, closed reactor, with the dry gas in the steel cylinder air in the still is drained, add liquid anhydrous ethamine 380Kg again, slowly heat with hot water bath, interior temperature remains on 30-59 ℃, middling speed stirs, pressure remains on 0.4-5.9MPa, reacts reactive crystallization 48 hours, reclaim excessive ethamine, the ethamine of recovery can repeat to feed intake to apply mechanically.The reaction product activated carbon decolorizing, 95% ethyl alcohol recrystallization gets elaboration 97.2Kg, yield: 60.1%, [α]
20 D+ 7.8～+ 8.5 ° (5%, H
2O), purity: (HPLC) 〉=98.5%.
Claims (6)
1. improvement synthetic method of producing the L-theanine, this method be with L-tetramethyleneimine ketone acid and anhydrous ethylamine antioxidant exist and oxygen free condition under react production L-theanine:
2. according to the process of claim 1 wherein that adding antioxidant is selected from quinoline, ethoxyquin, quinhydrones, vitamins C, Quercetin or butyl hydroxy anisol, perhaps their mixture.
3. according to the method for claim 1-2, wherein the consumption of antioxidant is 0.5-3 (weight) % of L-tetramethyleneimine ketone acid.
4. according to the method for claim 1-3, wherein temperature of reaction is to carry out between 30-59 ℃.
5. according to the method for claim 1-4, wherein reaction pressure is controlled between the 0.4-5.9MPa.
6. according to the method for claim 1-5, carry out amination reaction after draining air with exsiccant ethamine gas.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100920837A CN101085745A (en) | 2006-06-09 | 2006-06-09 | Modified synthesis method for L-theanine |
| PCT/CN2006/001658 WO2007143886A1 (en) | 2006-06-09 | 2006-07-13 | Improved synthesis method of l-theanine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100920837A CN101085745A (en) | 2006-06-09 | 2006-06-09 | Modified synthesis method for L-theanine |
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| Publication Number | Publication Date |
|---|---|
| CN101085745A true CN101085745A (en) | 2007-12-12 |
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ID=38831393
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100920837A Pending CN101085745A (en) | 2006-06-09 | 2006-06-09 | Modified synthesis method for L-theanine |
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| WO (1) | WO2007143886A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101717347B (en) * | 2009-12-01 | 2012-09-26 | 南京工业大学 | Method for preparing L-theanine by chemical method |
| CN103553959A (en) * | 2013-10-16 | 2014-02-05 | 浙江大学 | Method for synthesizing L-theanine by using L-pyroglutamic acid and anhydrous ethylamine |
| CN115043749A (en) * | 2022-06-08 | 2022-09-13 | 东华大学 | Preparation method of diamide diol |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1169782C (en) * | 2002-09-29 | 2004-10-06 | 暨南大学 | Method for synthesizing theanine |
| CN1244549C (en) * | 2003-12-24 | 2006-03-08 | 暨南大学 | Process for preparing theanine |
| CN1280261C (en) * | 2004-04-20 | 2006-10-18 | 南京莱尔生物化工有限公司 | Improved process for synthesizing L-theanine |
-
2006
- 2006-06-09 CN CNA2006100920837A patent/CN101085745A/en active Pending
- 2006-07-13 WO PCT/CN2006/001658 patent/WO2007143886A1/en active Application Filing
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101717347B (en) * | 2009-12-01 | 2012-09-26 | 南京工业大学 | Method for preparing L-theanine by chemical method |
| CN103553959A (en) * | 2013-10-16 | 2014-02-05 | 浙江大学 | Method for synthesizing L-theanine by using L-pyroglutamic acid and anhydrous ethylamine |
| CN103553959B (en) * | 2013-10-16 | 2015-04-29 | 浙江大学 | Method for synthesizing L-theanine by using L-pyroglutamic acid and anhydrous ethylamine |
| CN115043749A (en) * | 2022-06-08 | 2022-09-13 | 东华大学 | Preparation method of diamide diol |
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| Publication number | Publication date |
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| WO2007143886A1 (en) | 2007-12-21 |
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