CN102351725A - Process for synthesizing N-benzyl-3-(benzylamino)aspartic acid - Google Patents
Process for synthesizing N-benzyl-3-(benzylamino)aspartic acid Download PDFInfo
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- CN102351725A CN102351725A CN2011102124096A CN201110212409A CN102351725A CN 102351725 A CN102351725 A CN 102351725A CN 2011102124096 A CN2011102124096 A CN 2011102124096A CN 201110212409 A CN201110212409 A CN 201110212409A CN 102351725 A CN102351725 A CN 102351725A
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- dibromo
- succinic acid
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- ethanol
- benzylamine
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Abstract
The invention provides a novel process for synthesizing N-benzyl-3-(benzylamino)aspartic acid. In the method, a 2,3-dibromosuccinic acid ethanol solution is quantificationally dripped into benzylamine in a reverse dripping mode; the reaction is immediately performed in a high-concentration benzylamine system, so the released heat exactly boils ethanol by controlling the dripping speed of the 2,3-dibromosuccinic acid ethanol solution; and the total reflux of the ethanol is maintained, the reaction is complete after the dripping is finished, and the recovered ethanol is centrifuged so as to obtain a product which is high in yield and is white. The process is easy to operate, the reaction time is shortened, energy sources are saved, and the efficiency is improved.
Description
Technical field
The present invention relates to the synthetic field of organism, be specifically related to the compound method of N-benzyl-3-benzamido group aspartic acid.
Technical background
(have another name called dibenzyl amido Succinic Acid, on U.S. chemical abstract, can find, CAS:53079-45-1) be a kind of necessary midbody of synthesise vitamins H to N-benzyl-3-benzamido group aspartic acid, in chemical organic synthesis, also is widely used.The method of existing preparation N-benzyl-3-benzamido group aspartic acid is: benzylamine is splashed into 2; In the 3-dibromo-succinic acid ethanolic soln; When reaching suitable concentration afterreaction, benzylamine begins to be initiated; In ethanol, separate out the centrifugal product that obtains behind the recovery ethanol gradually through product after 12 hours the insulation reaction.But the very bad control of this method itself is reacting by heating, heat release again when reaction causes, in case control bad will causing danger, soaking time is very long simultaneously, and yield is on the low side, and resulting product appearance has a little faint yellowly, and purity is not high.
Summary of the invention
In order to solve the deficiency of prior art, the present invention provides the new synthetic process of a kind of N-benzyl-3-benzamido group aspartic acid, and technological reaction process of the present invention is controlled easily, and yield is high, and product appearance is a white, and purity is high.
The objective of the invention is to realize like this:
The synthesis technique of N-benzyl-3-benzamido group aspartic acid is characterized in that, adopts the reaction that feeds intake of anti-dropping mode, and the concrete operations step is following:
(1) benzylamine is added stops heating after being heated to 65-75 ℃ in the reaction kettle;
(2) absolute ethyl alcohol is joined 2, in the 3-dibromo-succinic acid, and stir, obtain 2,3-dibromo-succinic acid ethanolic soln, wherein 2, the mass/volume of 3-dibromo-succinic acid and absolute ethyl alcohol (g/ml) is 7: (25-35);
(3) step (2) is obtained 2,3-dibromo-succinic acid ethanolic soln is added drop-wise in the reaction kettle of step (1), through controlling 2; The rate of addition of 3-dibromo-succinic acid ethanolic soln makes institute's liberated heat just make the ethanol boiling, keeps the ethanol total reflux; After dropwising, reaction finishes, wherein; 2, the mass volume ratio g/ml of 3-dibromo-succinic acid and benzylamine is 1: (1.5-2.5);
(4) reaction finishes the back and reclaims etoh solvent, when the ethanol yield gets 80%, the temperature of system is reduced to below 30-35 ℃, and product is carried out suction filtration, the solid matter of suction filtration gained is dried obtain the final white product again.
Embodiment
The synthesis technique of experimental program one N-benzyl-3-benzamido group aspartic acid
Adopt method of the present invention with 2, the mode that 3-dibromo-succinic acid ethanolic soln is added drop-wise in the benzylamine is carried out building-up reactions, and concrete operations are following:
Get 2,3-dibromo-succinic acid 70g adds absolute ethyl alcohol 300ml stirring and dissolving; Put into constant pressure funnel, benzylamine 140ml is added in the flask, begin to drip 2 after being heated to 70 degree; 3-dibromo-succinic acid ethanolic soln; Occur white solid in the still immediately, with 25 degree water-bath coolings, control reaction temperature is no more than 75 degree.Dropwise heating in water bath insulation 75 degree reactions 2-12 hour.Reclaim amount of alcohol 80%, the temperature of flask is dropped to suction filtration below 35 ℃, obtain product after the oven dry.
Adopt above-mentioned identical dropping method to synthesize N-benzyl-3-benzamido group aspartic acid, measure under the different soaking times output of product and outward appearance comparing result such as table 1:
Table 1
| Sequence number | Soaking time | Output (g) | Color |
| 1 | 12 | 63.5 | Pearl |
| 2 | 6 | 63.4 | Off-white color |
| 3 | 4 | 63.5 | Off-white color |
| 4 | 2 | 63.4 | White |
| 5 | 0 | 63.5 | White |
Can find out from table 1, this synthesis technique, when 2,3-dibromo-succinic acid ethanolic soln drips, and reaction also finishes immediately, need not insulation, has shortened the reaction times, has improved production efficiency.
The synthesis technique of contrast experiment's scheme two N-benzyl-3-benzamido group aspartic acid
Be added drop-wise to 2 with benzylamine, the mode in the 3-dibromo-succinic acid ethanolic soln is carried out building-up reactions, and concrete operations are following:
Get 2,3-dibromo-succinic acid 70g adds absolute ethyl alcohol 300ml stirring and dissolving; Stop heating after being heated to 65 degree, begin to drip benzylamine, note observing beaker internal reaction situation;, micro-solid reduces dripping quantity when occurring immediately; Use 25 degree water-bath coolings simultaneously instead, control reaction temperature is no more than 75 degree, and it is 140ml that benzylamine drips total amount.Dropwise heating in water bath insulation 75 degree reactions 4-24 hour.Reclaim amount of alcohol 80%, filter below cooling to 35 degree, obtain product after the oven dry.
Adopt above-mentioned identical dropping method, measure under the different soaking times output of product and outward appearance comparing result such as table 2:
Table 2
| Sequence number | Soaking time | Output (g) | Color |
| 1 | 24 | 60.6 | Lead |
| 2 | 12 | 60.5 | Pearl |
| 3 | 6 | 56.3 | Pearl |
| 4 | 8 | 58.6 | Pearl |
| 5 | 10 | 59.8 | Pearl |
Can find out from table 2, adopt existing dropping method, drip benzylamine after, reaction does not finish, must be incubated 12 hours after, reaction could be accomplished, this traditional technology long reaction time, energy expenditure is big.
The data of above table 1 and table 2 have been passed through test of many times in the laboratory; Result's demonstration selects 2 for use, and 3-dibromo-succinic acid ethanolic soln drips very good like effect in the benzylamine, and N-benzyl-3-benzamido group aspartic acid yield improves 5%; Time shortens 8 hours, and the product appearance color is a white.
Claims (1)
1.N-the synthesis technique of benzyl-3-benzamido group aspartic acid is characterized in that, adopts the reaction that feeds intake of anti-dropping mode, the concrete operations step is following:
(1) benzylamine is added stops heating after being heated to 65-75 ℃ in the reaction kettle;
(2) absolute ethyl alcohol is joined 2, in the 3-dibromo-succinic acid, and stir, obtain 2,3-dibromo-succinic acid ethanolic soln, wherein 2, the mass/volume of 3-dibromo-succinic acid and absolute ethyl alcohol (g/ml) is 7: (25-35);
(3) step (2) is obtained 2,3-dibromo-succinic acid ethanolic soln is added drop-wise in the reaction kettle of step (1), through controlling 2; The rate of addition of 3-dibromo-succinic acid ethanolic soln makes institute's liberated heat just make the ethanol boiling, keeps the ethanol total reflux; After dropwising, reaction finishes, wherein; 2, the mass volume ratio g/ml of 3-dibromo-succinic acid and benzylamine is 1: (1.5-2.5);
(4) reaction finishes the back and reclaims etoh solvent, when the ethanol yield obtains 80%, the temperature of system is reduced to below 30-35 ℃, and product is carried out suction filtration, the solid matter of suction filtration gained is dried obtain the final white product again.
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| CN2011102124096A CN102351725A (en) | 2011-07-27 | 2011-07-27 | Process for synthesizing N-benzyl-3-(benzylamino)aspartic acid |
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| CN2011102124096A CN102351725A (en) | 2011-07-27 | 2011-07-27 | Process for synthesizing N-benzyl-3-(benzylamino)aspartic acid |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2489232A (en) * | 1949-11-22 | Synthesis of biotin | ||
| CN1310177A (en) * | 2000-02-24 | 2001-08-29 | 浙江大学 | Preparation of 1,3-dibenzyl-4,5-cis-dicarboxy-2-imidazolidone as D-biotin intermediate |
| JP2006232743A (en) * | 2005-02-25 | 2006-09-07 | Sumitomo Chemical Co Ltd | Method for producing dimethyl-1, 3-dibenzyl-2-oxo- imidazolidine-4, 5-dicarboxylate |
| JP2006232742A (en) * | 2005-02-25 | 2006-09-07 | Sumitomo Chemical Co Ltd | Method for producing 2, 3-bis-(benzylamino)succinic acid |
| JP2006265196A (en) * | 2005-03-25 | 2006-10-05 | Sumitomo Chemical Co Ltd | Method for separating methyl isobutyl ketone and benzylamine |
-
2011
- 2011-07-27 CN CN2011102124096A patent/CN102351725A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2489232A (en) * | 1949-11-22 | Synthesis of biotin | ||
| CN1310177A (en) * | 2000-02-24 | 2001-08-29 | 浙江大学 | Preparation of 1,3-dibenzyl-4,5-cis-dicarboxy-2-imidazolidone as D-biotin intermediate |
| JP2006232743A (en) * | 2005-02-25 | 2006-09-07 | Sumitomo Chemical Co Ltd | Method for producing dimethyl-1, 3-dibenzyl-2-oxo- imidazolidine-4, 5-dicarboxylate |
| JP2006232742A (en) * | 2005-02-25 | 2006-09-07 | Sumitomo Chemical Co Ltd | Method for producing 2, 3-bis-(benzylamino)succinic acid |
| JP2006265196A (en) * | 2005-03-25 | 2006-10-05 | Sumitomo Chemical Co Ltd | Method for separating methyl isobutyl ketone and benzylamine |
Non-Patent Citations (2)
| Title |
|---|
| SOLANGE LAVIELLE等: "A TOTAL SYNTHESIS OF BIOTIN BASED ON THE STEREOSELECTIVE ALKYLATION OF SULFOXIDES", 《JOURNAL OF AMERICAN CHEMICAL SOCIETY》 * |
| VENKATRAJ V.NARAYANAN,ERIK C.WIENER: "Metal-Directed Self-Assembly of Ethylenediamine-Based Dendrons", 《MACROMOLECULES》 * |
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Application publication date: 20120215 |