CN101270092B - Method for synthesizing neotame - Google Patents
Method for synthesizing neotame Download PDFInfo
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- CN101270092B CN101270092B CN2008100709900A CN200810070990A CN101270092B CN 101270092 B CN101270092 B CN 101270092B CN 2008100709900 A CN2008100709900 A CN 2008100709900A CN 200810070990 A CN200810070990 A CN 200810070990A CN 101270092 B CN101270092 B CN 101270092B
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- dimethyl butyraldehyde
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Abstract
The present invention provides a synthetic method of Neotame, and relates to a sweetener, in particular to a method used for synthesizing the sweetener, Neotame, through the reaction of aspartame, 3, 3-dimethyl butyraldehyde and formic acid. And the present invention provides a synthetic method of Neotame, which has the advantages of simple process and cheap raw materials. The aspartame and the formic acid are added into methanol to prepare mixture A; the weight ratio of the methanol and the aspartame is equal to from 3 to 9 :1; the molar ratio of the formic acid and the aspartame is equal to from 1.2 to 3.0 :1; the 3, 3-dimethyl butyraldehyde is added in the mixture A; the molar ratio of the 3, 3-dimethyl butyraldehyde and the aspartame is equal to from 1.1 to 2.0 :1; after the reaction, the product is concentrated under the condition of reduced pressure to form pulp; and ethanol solution is used for recrystallization to prepare the Neotame.
Description
Technical field
The present invention relates to a kind of sweeting agent, especially relate to a kind ofly by L-aspartyl-L-phenylalanine methylester (being commonly called as aspartame) and 3,3-dimethyl butyraldehyde and formic acid react the sweet method of synthetic sweetener knob.
Background technology
Knob is sweet to be a kind of novel non-nutritive intense sweetener, its chemistry N-[N-(3, the 3-dimethylbutyl) by name-L-α-aspartoyl]-L-phenylalanine-1-methyl esters, its structural formula is as follows:
Knob is sweet
The sugariness that knob is sweet is 8000 times of sucrose, and has the pure sweet taste that is similar to sucrose, be widely used in the processed foods such as beverage, chewing gum, milk-product, jelly pudding, syrup, bread, biscuit cake, ice-creams, jam and pickles, to substitute sucrose and other sweeting agents.Knob is sweet also to have local flavor and strengthens characteristic, can reduce the usage quantity of essence and citric acid in the food effectively.As the non-nutritive sweeting agent, the sweet all groups that are not only applicable to comprise obesity, cardiovascular diseases and diabetic subject of knob also are applicable to the phenylketonuria patient of anorexia with aspartame.
Knob is sweet can be by to be reductive agent with the sodium cyanoborohydride, and with 3, the 3-dimethyl butyraldehyde carries out the N-alkylated reaction and synthesizes (referring to U.S. Pat 5,480,668) aspartame.Because sodium cyanoborohydride costs an arm and a leg, the synthesizing neotame cost is too high in this way, is unsuitable for suitability for industrialized production.Knob is sweet also can be by under the palladium or platinum catalysis that are carried on gac, and with 3, the 3-dimethyl butyraldehyde carries out the hydrogenation alkanisation to aspartame and synthesizes (referring to U.S. Pat 5,510,508; US5,728,862; US6,720,446), but adopt the noble metal catalyst cost higher, the technological operation complexity, and must possess sources of hydrogen.
Summary of the invention
The object of the present invention is to provide the method for the synthesizing neotame that a kind of technology is simple, the prices of raw and semifnished materials are cheap.
The present invention is with L-aspartyl-L-phenylalanine methylester and 3, and 3-dimethyl butyraldehyde and formic acid react synthesizing neotame, and reaction formula is as follows:
The present invention includes following steps:
1) in methyl alcohol, adds L-aspartyl-L-phenylalanine methylester and formic acid, get mixture A, press mass ratio, the proportioning of methyl alcohol and L-aspartyl-L-phenylalanine methylester is (3～9): 1, in molar ratio, the proportioning of formic acid and L-aspartyl-L-phenylalanine methylester is (1.2～3.0): 1;
2) add 3 in mixture A, the 3-dimethyl butyraldehyde reacts, in molar ratio, 3, the proportioning of 3-dimethyl butyraldehyde and L-aspartyl-L-phenylalanine methylester is (1.1～2.0): 1;
3) reaction after product concentrating under reduced pressure pulp;
4) use the aqueous ethanolic solution recrystallization, it is sweet to get knob.
Add 3 in mixture A, the temperature that the 3-dimethyl butyraldehyde reacts is preferably 35～65 ℃, and the time of reaction is preferably 8～24h, and the alcoholic acid mass percent concentration is preferably 15～50% in the aqueous ethanolic solution.
The present invention uses organic reducing agent formic acid cheap and easy to get, need not catalyzer in the reaction process, the reaction conditions gentleness, and conversion unit usefulness intermittently stirring tank gets final product, and greatly reduces production cost.
Embodiment
Following examples will the present invention is further illustrated:
Embodiment 1: place the four-hole boiling flask that has electric mixer, thermometer and reflux exchanger of the 500ml of water bath with thermostatic control to add 120g methyl alcohol to one, start and stir, add L-aspartyl-L-phenylalanine methylester 29.43g (0.1mol), add formic acid 5.52g (0.12mol), be warming up to 35 ℃, add 3,3-dimethyl butyraldehyde 11g (0.11mol).Keep 35 ℃ of reactions of temperature 24h.Be evaporated to pulpous state with Rotary Evaporators then, the adding mass percent concentration is 40% aqueous ethanolic solution 25ml, and heating for dissolving slowly cools to 0 ℃ and spends the night suction filtration.Filter cake is done with the cold deionized water wash of 15ml, filter, at 40 ℃ of following vacuum-drying 12h, obtains the sweet product 23.08g of knob, yield 61%, and purity is higher than 98%.
Embodiment 2: reaction unit and working method are with embodiment 1.Its difference is that temperature of reaction is 45 ℃, reaction times 12h.The result obtains the sweet product 24.33g of knob, yield 64.3%, and purity is higher than 98%.
Embodiment 3: reaction unit and working method are with embodiment 1.Its difference is that temperature of reaction is 65 ℃, reaction times 8h.The result obtains the sweet product 22.86g of knob, yield 60.4%, and purity is higher than 97%.
Embodiment 4: reaction unit and working method are with embodiment 1.Its difference is 3, and 3-dimethyl butyraldehyde add-on is 15g (0.15mol).The result obtains the sweet product 23.65g of knob, yield 62.5%, and purity is higher than 98%.
Embodiment 5: reaction unit and working method are with embodiment 1.Its difference is 3, and 3-dimethyl butyraldehyde add-on is 20g (0.2mol).The result obtains the sweet product 23.77g of knob, yield 62.8%, and purity is higher than 97%.
Embodiment 6: experimental installation and working method are with embodiment 1.Its difference is that the formic acid add-on is 9.2g (0.2mol).The result obtains the sweet product 23.50g of knob, yield 62.1%, and purity is higher than 98%.
Embodiment 7: experimental installation and working method are with embodiment 1.Its difference is that the formic acid add-on is 13.8g (0.3mol).The result obtains the sweet product 23.2g of knob, yield 61.3%, and purity is higher than 98%.
Embodiment 8: experimental installation and working method are with embodiment 1.Its difference is that the add-on of methyl alcohol is 264.87 grams.The result obtains the sweet product 23.46g of knob, yield 62%, and purity is higher than 98%.
Embodiment 9: experimental installation and working method are with embodiment 1.Its difference is that the add-on of methyl alcohol is 88.29 grams.The result obtains the sweet product 22.15g of knob, yield 58.5%, and purity is higher than 97%.
Embodiment 10: experimental installation and working method are with embodiment 1.The mass percent concentration that its difference is to add aqueous ethanolic solution is 15%.The result obtains the sweet product 24.65g of knob, yield 65.1%, and purity is higher than 97%.
Embodiment 11: experimental installation and working method are with embodiment 1.The mass percent concentration that its difference is to add aqueous ethanolic solution is 50%.The result obtains the sweet product 22.95g of knob, yield 60.6%, and purity is higher than 98%.
Claims (5)
1. the method for a synthesizing neotame is characterized in that L-aspartyl-L-phenylalanine methylester and 3,3-dimethyl butyraldehyde and formic acid reaction synthesizing neotame, and reaction formula is as follows:
2. the method for a kind of synthesizing neotame as claimed in claim 1 is characterized in that may further comprise the steps:
1) add L-aspartyl-L-phenylalanine methylester and formic acid in methyl alcohol, get mixture A, press mass ratio, the proportioning of methyl alcohol and L-aspartyl-L-phenylalanine methylester is 3～9: 1, and in molar ratio, the proportioning of formic acid and L-aspartyl-L-phenylalanine methylester is 1.2～3.0: 1;
2) add 3 in mixture A, the 3-dimethyl butyraldehyde reacts, in molar ratio, 3, the proportioning of 3-dimethyl butyraldehyde and L-aspartyl-L-phenylalanine methylester is 1.1～2.0: 1;
3) reaction after product concentrating under reduced pressure pulp;
4) use the aqueous ethanolic solution recrystallization, it is sweet to get knob.
3. the method for a kind of synthesizing neotame as claimed in claim 2 is characterized in that adding 3 in mixture A, and the temperature that the 3-dimethyl butyraldehyde reacts is 35～65 ℃.
4. as the method for claim 2 or 3 described a kind of synthesizing neotames, it is characterized in that adding 3 in mixture A, the time that the 3-dimethyl butyraldehyde reacts is 8～24h.
5. the method for a kind of synthesizing neotame as claimed in claim 2 is characterized in that the alcoholic acid mass percent concentration is 15～50% in the described aqueous ethanolic solution.
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| CN2008100709900A CN101270092B (en) | 2008-04-30 | 2008-04-30 | Method for synthesizing neotame |
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| CN2008100709900A CN101270092B (en) | 2008-04-30 | 2008-04-30 | Method for synthesizing neotame |
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| CN101270092A CN101270092A (en) | 2008-09-24 |
| CN101270092B true CN101270092B (en) | 2010-12-08 |
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| CN103145796B (en) * | 2013-03-25 | 2015-02-04 | 重庆民泰香料化工有限责任公司 | Synthesis process of neotame |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3933781A (en) * | 1973-11-05 | 1976-01-20 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine alkyl esters |
| US4730076A (en) * | 1985-12-18 | 1988-03-08 | Nippon Kayaku Kabushiki Kaisha | Process for producing α-aspartyl-phenylalanine ester |
| US5480668A (en) * | 1992-11-12 | 1996-01-02 | Nofre; Claude | N-substituted derivatives of aspartame useful as sweetening agents |
| US5510508A (en) * | 1994-05-09 | 1996-04-23 | Claude; Nofre | Method of preparing a compound derived from aspartame, useful as a sweetening agent |
| US5728862A (en) * | 1997-01-29 | 1998-03-17 | The Nutrasweet Company | Method for preparing and purifying an N-alkylated aspartame derivative |
| US6720446B2 (en) * | 2001-11-05 | 2004-04-13 | The Nutrasweet Company | Catalyst modification to enhance neotame production |
-
2008
- 2008-04-30 CN CN2008100709900A patent/CN101270092B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3933781A (en) * | 1973-11-05 | 1976-01-20 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine alkyl esters |
| US4730076A (en) * | 1985-12-18 | 1988-03-08 | Nippon Kayaku Kabushiki Kaisha | Process for producing α-aspartyl-phenylalanine ester |
| US5480668A (en) * | 1992-11-12 | 1996-01-02 | Nofre; Claude | N-substituted derivatives of aspartame useful as sweetening agents |
| US5510508A (en) * | 1994-05-09 | 1996-04-23 | Claude; Nofre | Method of preparing a compound derived from aspartame, useful as a sweetening agent |
| US5728862A (en) * | 1997-01-29 | 1998-03-17 | The Nutrasweet Company | Method for preparing and purifying an N-alkylated aspartame derivative |
| US6720446B2 (en) * | 2001-11-05 | 2004-04-13 | The Nutrasweet Company | Catalyst modification to enhance neotame production |
Non-Patent Citations (3)
| Title |
|---|
| 吐松等.新型强力甜味剂纽甜的合成研究进展.《化工进展》.2008,第27卷(第1期),6-8，4-6. * |
| 陈国钦等.新型强力甜味剂纽甜的合成研究进展.《化工时刊》.2008,第22卷(第2期),53-55. * |
| 马明华等.甲磺酸培氟沙星合成工艺改进.《中国医药工业杂志》.1996,第27卷(第3期),100-101. * |
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