CN1500795A - Method for synthesizing high purity dextrose octylame - Google Patents
Method for synthesizing high purity dextrose octylame Download PDFInfo
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- CN1500795A CN1500795A CNA02134079XA CN02134079A CN1500795A CN 1500795 A CN1500795 A CN 1500795A CN A02134079X A CNA02134079X A CN A02134079XA CN 02134079 A CN02134079 A CN 02134079A CN 1500795 A CN1500795 A CN 1500795A
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- octyl amine
- octylglucamine
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Abstract
The present invention provides the preparation process of gluco-octyl amine. Glucose and n-octyl amine in the molar ratio o 1.05 are reacted to produce Schiff base; co-catalyst/RaneyNi system is added to catalytically hydrogenate Schiff base to produce gluco-octyl amine; and through cooling crystallization, centrifugal separation, washing with mixed solvent containing no methanol and drying, refined gluco-octyl amine with purity up to 99.5 % is obtained with product yield up to 76 %, low cost and no environmental pollution.
Description
Technical field
The present invention relates to the synthetic method of a kind of chiral drug and agricultural chemicals alkalescence resolving agent, specifically, the present invention relates to a kind of synthetic method of high purity dextrose octylame.
Background technology
N-Octylglucamine is the resolving agent that is used for non-steroidal anti-inflammatory analgesics Naproxen Base (Naproxen), Ibuprofen BP/EP (Ibuprofen) and metaxanin chiral drugs such as (Metalaxyl) and agricultural chemicals fractionation.For the fractionation of above-mentioned chiral drug and agricultural chemicals, explored several different methods, comprising: biological enzyme, chromatography, induced crystallization method and adopt the common crystallization process of alkaline resolving agent.Biological enzyme and chromatography all are subject to the condition limitation, and industrial application is limited; The induced crystallization method is still needed and is done a large amount of processing condition research; Be preferably the common crystallization process that adopts alkaline resolving agent, good resolving agent is first elected N-Octylglucamine.
Number of research projects has been carried out in the preparation of N-Octylglucamine both at home and abroad over nearly 20 years, first-selected preparation method is by metal catalyst catalytic hydrogenation Schiff alkali.1972, it was that catalyzer carries out the technology that shortening prepares N-Octylglucamine to Schiff alkali that Perey G.Holton has proposed with Raney nickel, but productive rate is very low, and 20-40% is only arranged, and does not have industrial value.Holton technology that people such as China Zhang Linze in 1985 have adopted the increasing catalyst levels and the method improvement in increase reaction times, the report productive rate reaches 60%, but cost is than higher.People such as the Li Xue soldier of Tsing-Hua University made catalyzer with Raney nickel in 1988, form the synthetic N-Octylglucamine of catalytic hydrogenation behind the Schiff alkali by n-octyl amine, reported, improve activity of such catalysts by in reaction system, adding triethylamine, make reaction yield reach 71.4%, but do not have the report of product purity.In addition, existing technology is used methyl alcohol conduct-washing composition, and strong toxicity and washing effect are bad.
Summary of the invention
By the purity that above-mentioned prior art is existed and the research of yield issues, we think that it is its committed step that Schiff base catalysis hydrogenation generates N-Octylglucamine, and the factor that influences this step has: 1. the absorption of catalyst surface and desorption rate.Adsorption rate is too high, and reaction substrate increases the side reaction odds at the overstand of catalyst surface; Desorption rate is too high, and reaction substrate is too short in the residence time of catalyst surface, and reaction is incomplete, and yield is low; 2. solvent system is to the solubility property of reaction substrate.Regulate the solvability of solvent, can change absorption and the desorption rate of reaction substrate, and then influence the generation and the reaction yield of side reaction at catalyst surface to reaction substrate; 3. Fan Ying temperature, pressure and material proportion also are the factors that influences this reaction.
The technical solution adopted for the present invention to solve the technical problems is: by metal catalyst catalytic hydrogenation Schiff alkali, it is characterized in that carrying out according to the following steps:
A. glucose and n-octyl amine generate Schiff alkali;
B. adding promotor/RaneyNi system makes Schiff base catalysis hydrogenation generate N-Octylglucamine;
C. with N-Octylglucamine crystallisation by cooling, centrifugation;
D. obtain the purified N-Octylglucamine with the mixed solvent washed twice that does not contain methyl alcohol, dry getting final product.
The present invention is achieved by the following technical solutions:
1. Preparation of catalysts
30gNaOH is dissolved in the 120ml water, ice-water bath is chilled to zero degree, electronic stirring slowly adds the 30g aluminum-nickel alloy down, reaction below 25 degrees centigrade 2-3 hour, continue to stir 0.5 hour, room temperature was placed 2-3 hour, was warming up to 95-100 degree centigrade and continued reaction 2-3 hour, wash with water to neutrality, wash 3 times with ethanol again.With the RaneyNi that makes place under the ethanol liquid level preserve standby.
2. the preparation of promotor ZCMT
3. the preparation of N-Octylglucamine
N-octyl amine, glucose, solvent and catalyzer are measured in the input autoclave according to a certain ratio, and sealing feeds hydrogen to 1.2～1.4Mpa, be warming up to 55～65 degrees centigrade, react after 2 hours, white crystals is separated out in cooling, filter, dried 2 hours down, get product for 70 degrees centigrade.After reaction is finished, allow the reaction solution naturally cooling, the product crystallization is separated out, through centrifugation, and product mixed solvent washed twice, drying gets product.
Operational path is as follows:
Glucose+n-octyl amine → Schiff alkali → shortening → crystallisation by cooling → washing → centrifugal
Separation → drying → product
The invention has the beneficial effects as follows: can obtain purity 99.2% by above scheme, the high purity dextrose octylame of yield 76%.Unreacted raw material, catalyzer quantitatively add in the new reaction system in batches and use after Separation and Recovery in this technology; Reuse after the solvent recuperation; This technology only has a small amount of discharge of wastewater, and about 100 kilograms of the about waste discharges of one ton of product of average every production are handled the back qualified discharge according to the pertinent regulations of state.Reach and save cost and free of contamination purpose.
Embodiment
The present invention is achieved by the following technical solutions:
1, Preparation of catalysts
30gNaOH is dissolved in the 120ml water, ice-water bath is chilled to zero degree, electronic stirring slowly adds the 30g aluminum-nickel alloy down, reaction below 25 degrees centigrade 2-3 hour, continue to stir 0.5 hour, room temperature was placed 2-3 hour, was warming up to 95-100 degree centigrade and continued reaction 2-3 hour, wash with water to neutrality, wash 3 times with ethanol again.With the RaneyNi that makes place under the ethanol liquid level preserve standby.
2, the preparation of catalyzer ZCMT
3, the preparation of N-Octylglucamine
N-octyl amine, glucose, solvent and catalyzer are measured in the input autoclave according to a certain ratio, and sealing feeds hydrogen to 1.2～1.4Mpa, be warming up to 55～65 degrees centigrade, react after 2 hours, white crystals is separated out in cooling, filter, dried 2 hours down, get product for 70 degrees centigrade.After reaction is finished, allow the reaction solution naturally cooling, the product crystallization is separated out, through centrifugation, and product mixed solvent washed twice, drying gets product.
Operational path is as follows:
Glucose+n-octyl amine → Schiff alkali → shortening → crystallisation by cooling → washing → centrifugation → drying → product
Below by embodiment the present invention is further specified.
Embodiment 1: reactor: 200 liters
Charging capacity: n-octyl amine 15.0KG
Glucose 22.0KG
Catalyst/co-catalyst 1.88KG
135.0 liters of solvent SOW-4
Reaction conditions: 55 ℃ of temperature of reaction
Pressure 1.20Mpa
Reaction times 3h
Product yield 76%, product purity 99.5%.
Embodiment 2:
Reactor: 1000 liters
Charging capacity: n-octyl amine 70.0KG (imported raw material)
Glucose 97.7KG (homemade)
Catalyst/co-catalyst 8.4KG
650.0 liters of solvent SOW-4 (homemade)
Reaction conditions: 55 ℃ of temperature of reaction
Pressure 1.20Mpa
Reaction times 3h
Product yield reaches 76.3 %, product purity 99.2%.
Embodiment 3: promotor is to the influence of reaction
The promoter products fusing point (℃) heavy (g) productive rate (%) of product
No 122-122.5 9.1 16.7
ZCMT-1 122-122.5 34.4 16.7
ZCMT-2 121.5-123 35.3 64.8
ZCMT-3 122-122.5 37.3 68.6
ZCMT-4 122-123.5 37.6 68.9
ZCMT-5 122-123.5 39.8 73.1
ZCMT-6 122-123.5 41.7 76.5
Reaction conditions: 55 ℃ of temperature of reaction, pressure 1.20Mpa.Reaction times 2h
Charging capacity: 35.0g glucose, the 24.0g n-octyl amine, the 0.86g promotor, 2.14gRaneyNi,
220ml solvent (SOW-4)
Embodiment 4: promotor/RaneyNi proportioning is to the influence of reaction
ZCMT-6/RaneyNi product fusing point (℃) heavy (g) productive rate (%) of product
1∶3.5 122-123.5 31.8 58.4
1∶2.5 122-123.5 41.7 76.5
1∶1.5 122-123.5 35.5 65.0
1∶1 121-123 34.4 63.0
Reaction conditions: 55 ℃ of temperature of reaction, pressure 1.20Mpa.Reaction times 2h
Charging capacity: 35.0g glucose, 24.0g n-octyl amine, 220ml solvent (SOW-4)
When promotor and catalyst ratio were 1: 2.5, productive rate was the highest.
Embodiment 5: solvent system is to the influence of reaction
The solvent product fusing point (℃) heavy (g) productive rate (%) of product
SOW-1 122-123.5 36.2 66.4
SOW-2 122-123 40.2 73.8
SOW-3 121.5-123 41.1 75.5
SOW-4 122-123.5 41.7 76.5
Reaction conditions: 55 ℃ of temperature of reaction, pressure 1.20Mpa.
Charging capacity: 35.0g glucose, 24.0g n-octyl amine, 220ml solvent (SOW-4)
The productive rate best result can reach 76.5%.
Embodiment 6: temperature is to the influence of reaction
Temperature of reaction product fusing point (℃) heavy (g) productive rate (%) of product
40 121.5-122.5 34.5 63.4
50 122.5-123.5 41 75.2
60 122-123.5 41.4 76.0
70 122-123.5 40.9 75.1
80 121-123 36.2 66.5
Reaction conditions: pressure 1.20Mpa.Reaction times 2h
-charging capacity: 35.0g glucose, 24.0g n-octyl amine, 3.0gRaneyNi, 220ml solvent (SOW-4)
Embodiment 7: pressure is to the influence of reaction
Pressure (Mpa) product fusing point (℃) heavy (g) productive rate (%) of product
0.8 122-123.5 29.1 53.4
1.0 121.5-123.5 36.9 67.8
1.2 122-123.5 41.7 76.5
1.4 122-123 40.0 73.3
Reaction conditions: 55 ℃ of temperature of reaction, reaction times 2h.
Charging capacity: 35.0g glucose, 24.0g n-octyl amine, 220ml solvent (SOW-4)
Embodiment 8: the proportioning of glucose and n-octyl amine is to the influence of reaction
Glucose and n-octyl amine (mol/mol0 product fusing point (℃) heavy (g) productive rate (%) of product
1.25∶1 122-123.5 41.8 76.7
1.15∶1 121.5-123 41.8 76.7
1.05∶1 122-123.5 41.7 76.5
1∶1 122.5-123.5 39.8 73.0
0.9∶1 122-123.5 37.3 68.5
0.8∶1 122-123.5 33.4 61.3
Reaction conditions: 55 ℃ of temperature of reaction, pressure 1.20Mpa.Reaction times 2h
Charging capacity: 3.0g catalyzer, 220ml solvent (SOW-4)
Claims (7)
1. the synthetic method of a high purity dextrose octylame by metal catalyst catalytic hydrogenation Schiff alkali, is characterized in that carrying out according to the following steps:
A. glucose and n-octyl amine generate Schiff alkali;
B. adding promotor/RaneyNi system makes Schiff base catalysis hydrogenation generate N-Octylglucamine;
C. with N-Octylglucamine crystallisation by cooling, centrifugation;
D. obtain the purified N-Octylglucamine with the mixed solvent washed twice that does not contain methyl alcohol, dry getting final product.
2. method according to claim 1 is characterized in that the mol ratio of glucose and n-octyl amine is 1.05～1.25: 1 among the step a.
3. method according to claim 1 is characterized in that using among the step b ZCMT-6 promotor.
4. method according to claim 1 is characterized in that the weight proportion of promotor and RaneyNi is 1: 2.5 among the step b.
5. method according to claim 1 is characterized in that steps d adopts SOW series solvent system.
6. method according to claim 1, the temperature of reaction that it is characterized in that step a～b is 55～65 ℃.
7. method according to claim 1 is characterized in that pressure is 1.2～1.4Mpa in the reaction of step a～b.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA02134079XA CN1500795A (en) | 2002-11-15 | 2002-11-15 | Method for synthesizing high purity dextrose octylame |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA02134079XA CN1500795A (en) | 2002-11-15 | 2002-11-15 | Method for synthesizing high purity dextrose octylame |
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| CN1500795A true CN1500795A (en) | 2004-06-02 |
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| CNA02134079XA Pending CN1500795A (en) | 2002-11-15 | 2002-11-15 | Method for synthesizing high purity dextrose octylame |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105749289A (en) * | 2016-03-02 | 2016-07-13 | 中国医学科学院医学生物学研究所 | Lyophilization protectant and application thereof in lyophilized live attenuated hepatitis A vaccine |
| CN112457206A (en) * | 2020-12-12 | 2021-03-09 | 弘健制药(上海)有限公司 | Refining process of meglumine |
-
2002
- 2002-11-15 CN CNA02134079XA patent/CN1500795A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105749289A (en) * | 2016-03-02 | 2016-07-13 | 中国医学科学院医学生物学研究所 | Lyophilization protectant and application thereof in lyophilized live attenuated hepatitis A vaccine |
| CN105749289B (en) * | 2016-03-02 | 2019-01-08 | 中国医学科学院医学生物学研究所 | A kind of freeze drying protectant and its application in freeze-dried type attenuated live vaccine for hepatitis A |
| CN112457206A (en) * | 2020-12-12 | 2021-03-09 | 弘健制药(上海)有限公司 | Refining process of meglumine |
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