CN100432097C - Synthetic methods for nutame - Google Patents
Synthetic methods for nutame Download PDFInfo
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- CN100432097C CN100432097C CNB2006101235921A CN200610123592A CN100432097C CN 100432097 C CN100432097 C CN 100432097C CN B2006101235921 A CNB2006101235921 A CN B2006101235921A CN 200610123592 A CN200610123592 A CN 200610123592A CN 100432097 C CN100432097 C CN 100432097C
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Abstract
This invention discloses a synthesis method for Neotame. The said method includes the following steps: (1) carrying out a reaction of tert-butanol with hydrochloric acid to obtain tert-butyl chloride; (2) adding catalyst in tert-butyl chloride, and charging ethylene gas and reacting to obtain 3, 3-dimethyl-1-chlorobutane; (3) oxidating 3, 3-dimethyl-1-chlorobutane to obtain 3, 3-dimethyl butyraldehyde, and purifying; and (4) carrying out a reaction of 3, 3-dimethyl butyraldehyde with aspartame to form imine, and catalytic-hydrogenating to obtain Neotame. The invention has the advantages of simple process, easy operation, low cost, and high purity of the product.
Description
Technical field
The present invention relates to the sweet synthetic method of a kind of foodstuff additive knob.
Background technology
Knob sweet (NTM) is a kind of novel powerful sweeting agent, is the s-generation product of aspartame (APM), its chemistry N-(N-(3, the 3-dimethylbutyl)) by name-L-a-l-asparagine-L-phenylalanine-1-methyl esters.
Structural formula is:
The sugariness that knob is sweet is 8000 times of sucrose, and sweet taste is pure, and sweet taste characteristic and sucrose are about the same; Good stability has overcome the shortcoming of aspartame stability difference; No carious tooth is to the positive effect that takes care of one's teeth; In food, add excellent flavors such as sweet taste, saline taste, tart flavour are maintained even improve, undesirable taste such as bitter taste, astringent taste and some irritating smell then can be alleviated or cover; Energy value is almost nil, can not cause the fluctuation of blood sugar in the health.Used as foodstuff additive by a plurality of countries and regions approval such as the U.S., European Union, Japan.2003, China Ministry of Health also ratifies sweet can the measuring on demand as sweeting agent of knob and makes an addition in the varieties of food items, for example: beverage, cake, can or the like, its range of application was very extensive.
The sweet synthetic method of knob is existing multiple, and these methods respectively have advantage, but also exists not enoughly, and, severe reaction conditions, complex process not high as product purity, productive rate is low, production cost is high.US 5,480, and 668 (1996) earlier with aspartame and 3,3-dimethyl butyraldehyde formation imines, and next reducing imines with a reductive agent sodium cyanoborohydride again, to obtain knob sweet.Because the price of sodium cyanoborohydride is more expensive, consume too big, too high with the sweet cost of this explained hereafter knob.Knob is sweet also can to prepare [US 6,077,962 (2000)] by the amino acid whose peptideization in unit, this mode reaction conditions gentleness, but long reaction time, and productive rate is undesirable.Knob is sweet can also to prepare (WO0190,138) by the oxazolidone intermediate, and in this method, the azanyl derivative of aspartic acid earlier forms the oxazolidone intermediate with Perfluoroacetone, and to obtain knob sweet with phenylalanine methyl ester reaction open loop again for the latter.It is too complicated to produce the sweet technology of knob in this way, is unfavorable for industrialization.
Summary of the invention
The present invention is directed to the deficiency that above-mentioned prior art exists, provide a kind of knob sweet synthetic method.
For reaching above-mentioned purpose, the synthetic method that knob of the present invention is sweet in turn includes the following steps:
A, the trimethyl carbinol and hydrochloric acid are reacted, make tertiary butyl chloride;
B, the tertiary butyl chloride of gained is added the catalyzer iron bromide, feeds ethylene gas and react, make 3,3-dimethyl-1-chlorobutane;
C, with 3,3-dimethyl-1-chlorobutane oxidation makes 3,3-dimethyl butyraldehyde, purifying 3,3-dimethyl butyraldehyde;
D, with 3, it is sweet that imines hydrogenation under catalyst action that the reaction of 3-dimethyl butyraldehyde and aspartame generates makes knob.
As preferred version, used oxygenant is a methyl-sulphoxide in the described C step.As preferred version, in the described C step, in oxidizing reaction, add magnesium chloride as catalyzer.As preferred version, separate purification 3,3-dimethyl butyraldehyde with sodium bisulfite method in the described C step.As preferred version, used catalyzer is a Raney's nickel in the described D step, platinum and carbon, or palladium and carbon.
In order further to improve productive rate, as preferred version, in the described A step, in the there-necked flask of being furnished with agitator, water-bath, condenser west tube, drop into the trimethyl carbinol, drip concentrated hydrochloric acid under the stirring at room, under 55～60 ℃ of temperature, react and do not distillate to there being product, tertiary butyl chloride.
The present invention has following advantage and effect with respect to prior art: have that technology is simple, easy and simple to handle, production cost is low, the characteristics that product purity is high are fit to industrialization very much.
Embodiment
The present invention is described in further detail below in conjunction with embodiment.
Embodiment one:
The synthetic method that a kind of knob provided by the invention is sweet follows these steps to make successively:
1. the preparation of tertiary butyl chloride
Drop into trimethyl carbinol 7.4g in the there-necked flask of being furnished with agitator, water-bath, condenser west tube, drip concentrated hydrochloric acid 7.3g under the stirring at room, 30min dropwises, and reacts not distillate to there being product under 55～60 ℃ of temperature, gets tertiary butyl chloride 8.3g, productive rate 90%.
2. 3, the preparation of 3-dimethyl-1-chlorobutane (DMCB)
Gained tertiary butyl chloride 8.3g is changed in the three-necked bottle of band thermometer and logical, vapor pipe and be cooled to below-10 ℃, add iron bromide powder 0.1g, feed ethylene gas, jolt three-necked bottle and begin reaction.Maintain the temperature in the reaction process between-7 ℃～0 ℃ always, note adjustments of gas speed at any time, control speed of reaction well, in case temperature is too high, question response stops after no longer absorbing ethylene gas, about one hour of time; Reaction solution is changed in the separating funnel, add an amount of distilled water wash reaction solution, repetitive scrubbing for several times till the oil reservoir water white transparency of upper strata, is removed lower aqueous layer with separating funnel; The upper strata anhydrous sodium sulfate drying is used the B suction filtration, through distillation, collects 111 ℃～125 ℃ fractions again, gets DMCB 9.5g, productive rate 88%.
3. 3, the preparation of 3-dimethyl butyraldehyde (DMBA)
30mL puts into three-necked bottle with dimethyl sulfoxide (DMSO), adds salt of wormwood 11.0g with the organic acid that neutralization generates, and adds magnesium chloride 0.5g again as catalyzer.With the nitrogen flooding deacration repeatedly, heat temperature raising to 120 ℃ slowly drips 3 under violent stirring, and 3-dimethyl-1-chlorobutane 9.5g is to reaction system, and beginning has gas evolution after the reaction, keeps isothermal reaction 10 hours, filter, oily liquids.Add water 20mL, supernatant liquid is collected in the solution layering.Be cooled to below 5 ℃, under violent stirring, drip the saturated solution that contains the 7g sodium bisulfite.Collect the gained solid, solid is joined in the flask with the 6g sodium bicarbonate, add suitable quantity of water, 100～106 ℃ cut is collected in distillation, gets DMBA2.8g, productive rate 35%.
4. the sweet preparation of knob
Add APM 20.0g in autoclave, water 37.0g and methyl alcohol 75.0g add 5%Pa/C catalyzer 2.0g and DMBA 6.7g again, stir with 450rps speed.With nitrogen flooding air 4 times, drive nitrogen 4 times with hydrogen again, and keep 0.5Mpa pressure, be warming up to 80 ℃, stir with 1000rps speed, reacted 2 hours, after reaction stops, use nitrogen flooding hydrogen, question response liquid is cooled to suction filtration after the room temperature, with 50g distilled water wash catalyzer.In refrigerator overnight, suction filtration gets white solid with suction filtration liquid.Do recrystallization with the first alcohol and water and get crystal 12g, 78 ℃～84 ℃ of fusing points, productive rate is 44%.
The foregoing description is a preferred implementation of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (6)
1, the sweet synthetic method of a kind of knob is characterized in that in turn including the following steps:
A, the trimethyl carbinol and hydrochloric acid are reacted, make tertiary butyl chloride;
B, the tertiary butyl chloride of gained is added the catalyzer iron bromide, feeds ethylene gas and react, make 3,3-dimethyl-1-chlorobutane;
C, with 3,3-dimethyl-1-chlorobutane oxidation makes 3,3-dimethyl butyraldehyde, purifying 3,3-dimethyl butyraldehyde;
D, with 3, it is sweet that imines hydrogenation under catalyst action that the reaction of 3-dimethyl butyraldehyde and aspartame generates makes knob.
2, the sweet synthetic method of a kind of knob according to claim 1 is characterized in that used oxygenant is a methyl-sulphoxide in the described C step.
3, the sweet synthetic method of a kind of knob according to claim 1 is characterized in that in the described C step, adds magnesium chloride as catalyzer in oxidizing reaction.
4, synthetic method according to claim 1 is characterized in that separating purification 3,3-dimethyl butyraldehyde with sodium bisulfite method in the described C step.
5, the sweet synthetic method of a kind of knob according to claim 1 is characterized in that catalyzer used in the described D step is a Raney's nickel, platinum and carbon, or palladium and carbon.
6, synthetic method according to claim 1, it is characterized in that: in the described A step, in the there-necked flask of being furnished with agitator, water-bath, condenser west tube, drop into the trimethyl carbinol, drip concentrated hydrochloric acid under the stirring at room, under 55～60 ℃ of temperature, react and do not distillate to there being product, tertiary butyl chloride.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101235921A CN100432097C (en) | 2006-11-16 | 2006-11-16 | Synthetic methods for nutame |
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| CNB2006101235921A CN100432097C (en) | 2006-11-16 | 2006-11-16 | Synthetic methods for nutame |
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| CN1966518A CN1966518A (en) | 2007-05-23 |
| CN100432097C true CN100432097C (en) | 2008-11-12 |
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| CNB2006101235921A Expired - Fee Related CN100432097C (en) | 2006-11-16 | 2006-11-16 | Synthetic methods for nutame |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101124980B (en) * | 2007-09-25 | 2011-05-25 | 上海师范大学 | Composite sweetener containing neotame |
| CN101920196B (en) * | 2010-07-26 | 2012-10-03 | 暨南大学 | Hydrogenation catalyst for synthesizing neotame and preparation method thereof |
| CN102167722A (en) * | 2010-12-29 | 2011-08-31 | 宁宗超 | Method for preparing neotame |
| CN102295541B (en) * | 2011-08-16 | 2013-04-17 | 济南诚汇双达化工有限公司 | Preparation method of 3,3-dimethyl butyraldehyde |
| CN104177473B (en) * | 2014-08-20 | 2017-08-11 | 山东奔月生物科技有限公司 | The synthetic method of neotame |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1833542A (en) * | 2004-03-16 | 2006-09-20 | 卡夫食品集团公司 | Improved method for drying neotame with co-agents |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1833542A (en) * | 2004-03-16 | 2006-09-20 | 卡夫食品集团公司 | Improved method for drying neotame with co-agents |
Non-Patent Citations (2)
| Title |
|---|
| 新一代强力甜味剂---纽甜. 林洪，林杰.精细与专用化学品，第13卷第15期. 2005 |
| 新一代强力甜味剂———纽甜. 林洪，林杰.精细与专用化学品，第13卷第15期. 2005 * |
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| CN1966518A (en) | 2007-05-23 |
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