CN113698320A - Preparation method of L-Carlactonitrile - Google Patents
Preparation method of L-Carlactonitrile Download PDFInfo
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- CN113698320A CN113698320A CN202111116536.6A CN202111116536A CN113698320A CN 113698320 A CN113698320 A CN 113698320A CN 202111116536 A CN202111116536 A CN 202111116536A CN 113698320 A CN113698320 A CN 113698320A
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- hydroxybutyronitrile
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/16—Preparation of carboxylic acid nitriles by reaction of cyanides with lactones or compounds containing hydroxy groups or etherified or esterified hydroxy groups
Abstract
The invention discloses a preparation method of L-Carlactonitrile, which specifically comprises the following steps: (1) taking (R) - (-) -epichlorohydrin as an initial raw material, mixing the (R) - (-) -epichlorohydrin with a solvent and a catalyst, then dropwise adding hydrocyanic acid to react, and obtaining an intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile through desolventizing and rectifying treatment after the reaction is finished; (2) mixing (R) - (+) -4-chloro-3-hydroxybutyronitrile, trimethylamine hydrochloride and a solvent, then dropwise adding ammonia water for reaction, controlling the reaction temperature and the pH value, and obtaining the product L-Carlactonitrile and a byproduct ammonium chloride through desolventizing and recrystallization after the reaction is finished. The preparation method is simple and feasible, the whole process does not generate cyanogen-containing wastewater and waste salt, the yield and the chemical purity of the product are high, the whole process is green and environment-friendly, the atom economy is high, a byproduct ammonium chloride salt can create certain economic value, and the method is suitable for large-scale industrial amplification production.
Description
Technical Field
The invention belongs to the field of medicinal chemistry, and particularly relates to a preparation method of L-carnitine important intermediate L-Carlactonitrile.
Background
L-carnitine, known as beta-hydroxy-gamma-trimethylammonium butyrate and vitamin BT, is a vitamin compound essential to human bodies. L-carnitine is an important food nutrition enhancer and is widely applied to infant food, weight-losing food, sportsman food and middle-aged and elderly people nutrition supplements. At present, the production method of L-carnitine mainly comprises three methods: the extraction method, the chemical synthesis method and the biological synthesis method, wherein the chemical synthesis method mainly comprises the following steps: chemical resolution method, asymmetric synthesis and asymmetric catalysis. In a plurality of process routes for synthesizing the L-carnitine by asymmetric chemistry, L-Carlactonitrile is an important chiral intermediate, so the quality of the L-carnitine is directly influenced by the chemical purity and the optical purity of the L-Carlactonitrile.
Patents CN101838212A and CN101823974A propose methods for preparing L-carnitine by using (R) - (-) -3-chloro-1, 2-propanediol as chiral starting material, first preparing L-carbanitrile, and then hydrolyzing and desalting by ion exchange. In patent CN101838212A, (R) - (-) -3-chloro-1, 2-propanediol is first reacted with triethyl orthoacetate to obtain a cyclic condensate, which is then reacted with trimethylbromosilane to obtain a bromide, which is then reacted with sodium cyanide to obtain cyanide, which is finally reacted with trimethylamine to obtain L-Carlactonitrile. In patent CN101823974A, (R) - (-) -3-chloro-1, 2-propanediol is reacted with thionyl chloride to produce a cyclic sulfinate intermediate, which is then reacted with KCN or NaCN to obtain chlorobutyl nitrile, and finally the chlorobutyl nitrile is reacted in trimethylamine solution to prepare L-Carlactonitrile. Although the two preparation methods use the byproduct (R) - (-) -3-chloro-1, 2-propanediol obtained by chiral resolution of racemic epichlorohydrin as a raw material to realize the reutilization of the byproduct, the two process routes have the problems of longer route, complex operation, low overall yield and the like, so the difficulty of realizing industrial application is higher.
Patent CN102516105A discloses a preparation method of L-carnitine hydrochloride by using (R) - (-) -epichlorohydrin, hydrocyanic acid and trimethylamine as raw materials to synthesize L-canacyanol by one-step method, and then hydrolyzing L-canacyanol. The preparation method is simple, but considering the particularity of the raw material hydrocyanic acid, the boiling point is low (26 ℃) and extremely toxic, the reaction temperature and the reaction pressure are high, the reaction temperature of (R) - (-) -epichlorohydrin, hydrocyanic acid and trimethylamine is 20-100 ℃ under the action of an alkali catalyst, the reaction pressure is 0.05MPa-2.0MPa, the requirements on the equipment conditions and the safety of the process operation are high, and the practical application value of the process is not high.
The mature process route for industrially preparing the L-Carlactonitrile at present comprises the following steps: taking (S) - (+) -epichlorohydrin as an initial raw material, firstly carrying out quaternization reaction with trimethylammonium hydrochloride to obtain L-quaternary ammonium salt, and then carrying out cyanidation reaction with sodium cyanide to prepare the L-capronitrile. Although the process route is simple and feasible, in the actual industrial production process, a large amount of sodium chloride is generated in the second-step cyanidation reaction, sodium cyanide which is not completely reacted is mixed in the second-step cyanidation reaction, the treatment of part of solid wastes increases the production cost, and the complete separation of the sodium chloride and the L-Carlactonitrile is difficult to realize due to the similar properties of the sodium chloride and the L-Carlactonitrile, and the process steps are complicated.
Therefore, in view of these practical problems, a technical problem to be solved is urgently needed by those skilled in the art how to provide a simpler and more feasible method for preparing L-carnononitrile, which is both environmentally friendly and economical.
Disclosure of Invention
In view of the above, the invention provides a simple and feasible preparation method of L-Carlactonitrile with high yield, environmental protection and suitability for industrial production, so as to solve the defects in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of L-Carlactonitrile comprises the following steps:
the method specifically comprises the following steps:
(1) cyanidation reaction: mixing (R) -epichlorohydrin with a solvent and a catalyst, dripping hydrocyanic acid, reacting for 4 hours at 15-20 ℃, and finally performing desolventizing and rectifying treatment to obtain an intermediate (R) -4-chloro-3-hydroxybutyronitrile;
(2) and (3) carrying out an amination reaction: mixing (R) -4-chloro-3-hydroxybutyronitrile, trimethylamine hydrochloride and a solvent, adjusting the pH value, reacting for 16 hours at the temperature of 30-60 ℃, and then carrying out desolventizing and recrystallization treatment to obtain L-Carlactonitrile and a byproduct ammonium chloride.
Preferably, the weight ratio of the (R) -epichlorohydrin to the solvent in step (1) is 1.0: (1.0-3.0);
preferably, the solvent in step (1) is an organic solvent;
further, the organic solvent is any one of methanol, ethanol and isopropanol.
Adopt above-mentioned further beneficial effect to lie in: because of the particularity of the raw material hydrocyanic acid, the self-polymerization reaction is easy to occur under the conditions of water and alkali. Compared with the method using water as a solvent, the method using an organic solvent in the cyanidation reaction process can remarkably reduce the self-polymerization reaction of hydrocyanic acid in the reaction process. In addition, since this step is a ring-opening reaction of an epoxy compound under basic conditions, the nucleophile CN-is selected to attack a ring carbon atom having less substituents, cleavage of the C-O bond proceeds almost simultaneously with the formation of a bond between the nucleophile and the ring carbon atom, and a product is produced. The solvent provided by the invention is a protonic alcohol solvent, and the use of the solvent can not only reduce the concentration of raw materials, effectively take away reaction heat, avoid explosive reaction, maintain stable reaction, but also weaken the nucleophilicity of polar solute molecules HCN to a certain extent, reduce the reaction rate, reduce the occurrence of side reactions and improve the reaction selectivity.
Preferably, the catalyst used in step (1) is in an amount of 1% to 5% by weight of (R) -epichlorohydrin.
Preferably, the catalyst is an organic base;
further, the organic base is any one of diethylamine, triethylamine and ethylenediamine.
The beneficial effects brought by adopting the method are as follows: compared with inorganic alkali, the organic alkali used as the catalyst can be better dissolved and dispersed in an organic solvent system to provide alkaline conditions, and inorganic waste salt containing cyanogen can not be generated after the reaction is finished, so that the post-treatment difficulty and the environmental protection pressure are reduced. The dosage of the catalyst is based on the pH value condition that the reaction system can efficiently carry out.
Preferably, the molar ratio of the (R) -epichlorohydrin to the hydrocyanic acid in step (1) is 1.0: (1.05-1.2).
The beneficial effect that above-mentioned preferred scheme brought does: in the cyaniding reaction process, the main raw material (R) - (-) -epichlorohydrin can be well and completely reacted by properly excessive raw material hydrocyanic acid, and the reaction system reduces the self-polymerization reaction of hydrocyanic acid from the result of the cooperation of the protonic alcohol organic solvent and the organic base catalyst, which can also reduce the dosage of hydrocyanic acid to a certain extent. Therefore, the optimal molar ratio of the two components can not only save the use of raw materials, but also ensure the complete reaction.
Preferably, the molar ratio of the (R) -4-chloro-3-hydroxybutyronitrile to trimethylamine hydrochloride in step (2) is 1.0: (1.0-2.0).
The beneficial effects of the above preferred scheme are: : in the process of the amination, in order to ensure that the main raw material (R) - (+) -4-chloro-3-hydroxybutyronitrile is completely reacted, the trimethylamine hydrochloride needs to be properly excessive, and the optimal molar ratio of the two materials can not only save the use of raw materials, but also ensure the complete reaction.
Preferably, the weight ratio of the (R) -4-chloro-3-hydroxybutyronitrile to the solvent in step (2) is 1.0: 1.0 to 5.0.
Preferably, the solvent in the step (2) is an organic solvent;
further, the organic solvent is any one of methanol, ethanol and isopropanol.
Adopt above-mentioned further beneficial effect to lie in: the elimination of the chiral-OH group on the carbon atom of the starting (R) - (+) -4-chloro-3-hydroxybutyronitrile and the-H groups on the adjacent carbon atoms may take place
The addition reaction leads to the reduction of the optical purity of the product, and the use of the organic alcohol solvent can play a role in protecting the-OH group to a certain extent through the formation of a hydrogen bond. And at the beginning of the reaction, all raw materials can be dissolved in a solvent to form a homogeneous system, along with the reaction, the L-Carlactonitrile and the byproduct ammonium chloride have poor solubility in an alcohol solvent and are gradually separated out, so that the raw materials and the products can be effectively separated, after simple filtration, mother liquor containing a small amount of raw materials can be recycled, and the mixed L-Carlactonitrile and byproduct ammonium chloride can be communicatedAnd separating by recrystallization. When the single-batch yield is obtained, part of the L-Carlactonitrile product and the by-product ammonium chloride dissolved by the water brought by the ammonia water can be recrystallized after the solvent and water are removed by reduced pressure distillation.
Preferably, in the step (2), the pH is adjusted by dropwise adding ammonia water so that the pH value in the system is always maintained at 8.5-9.0.
The beneficial effects of the above preferred scheme are: the amination reaction is a nucleophilic substitution reaction on saturated carbon atoms, wherein trimethylamine hydrochloride is a nucleophilic reagent, and-Cl connected with C in (R) - (+) -4-chloro-3-hydroxybutyronitrile is a leaving group. The addition of ammonia water can neutralize HCl generated in the reaction in time, maintain the pH value of the reaction system and generate a byproduct ammonium chloride.
Preferably, the optimum reaction temperature in step (2) is 40-55 ℃.
The beneficial effects of the above preferred scheme are: the amination reaction needs to be carried out efficiently under suitable temperature conditions. From the reaction kinetics and thermodynamics point of view: the temperature is too low, the reaction is difficult to occur or the reaction speed is too slow; when the temperature is too high, the main reaction speed is increased, and the side reaction speed is also increased, which is not favorable for the reaction.
Preferably, the solvent used in the recrystallization in the step (2) is a mixed solvent of acetonitrile and methanol, wherein the weight ratio of methanol to acetonitrile is 1.0: (1.0-5.0).
The beneficial effects of the above preferred scheme are: since the product L-canavanine nitrile and the by-product ammonium chloride are somewhat similar in nature, for example: both are readily soluble in water and insoluble in alcoholic organic solvents. By utilizing the principle of similar phase solubility and a large number of verification experiments, the invention provides a method for separating L-Carlactonitrile and ammonium chloride by using a mixed solvent of acetonitrile and methanol as a recrystallization solvent. This is due to the fact that L-Carlactonitrile is soluble in acetonitrile, whereas ammonium chloride is insoluble in both methanol and acetonitrile. The method comprises the following specific steps: adding the mixture into a mixed solvent of acetonitrile and methanol in a certain ratio, heating and refluxing for reaction for 0.5-1 hour, filtering while the mixture is hot to obtain a filter cake, namely ammonium chloride, and distilling the filtrate under reduced pressure to remove the solvent to obtain the product L-Carlactonitrile.
According to the technical scheme, compared with the prior art, the invention has the following beneficial effects:
the invention adopts a two-step method to prepare the L-Carlactonitrile by cyanidation and ammonification. The preparation method is simple and feasible, the whole process does not generate cyanogen-containing wastewater and waste salt, the yield and the chemical purity of the product are high, the whole process is green and environment-friendly, the atom economy is high, a byproduct ammonium chloride salt can create certain economic value, and the method is suitable for large-scale industrial amplification production.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
(1) Preparation of (R) - (+) -4-chloro-3-hydroxybutyronitrile
100g of (R) - (-) -epichlorohydrin, 200g of methanol and 3g of triethylamine were added to a 500mL three-necked flask, and the temperature was reduced to 15 to 20 ℃ with stirring. Then slowly dripping 35.04g of hydrocyanic acid into the flask, controlling the temperature to be 15-20 ℃ in the process, and stirring for reacting for 4 hours after dripping. After the reaction is finished, the methanol is removed by reduced pressure distillation at 50-60 ℃, the recovered methanol can be recycled, and then the mixture is heated to 80-90 ℃ for high vacuum rectification to obtain 120.05g of an intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, wherein the gas phase content is 99.16%, the specific rotation [ alpha ] D25 is 16.9 degrees, and the molar yield is 92.91%.
(2) Preparation of L-Carlactonitrile
100g of the previously prepared intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, 300g of methanol and 103.90g of trimethylamine hydrochloride were put into a 1000mL three-necked flask, equipped with a thermometer and a pH meter, and stirred to raise the temperature to 40 ℃. Then, 25% ammonia water solution is slowly dripped into the flask to maintain the pH value between 8.5 and 9.0, the temperature is controlled to be between 40 and 45 ℃ in the process, and the reaction is carried out for 16 hours under the condition of heat preservation. After the reaction is finished, the solvent and water are removed by reduced pressure distillation, the obtained viscous liquid is pulped by 100g of methanol and then filtered, and a filter cake is washed by a small amount of methanol. Adding the filter cake into a mixed solvent of 200g of methanol and 300g of acetonitrile, stirring and heating until reflux reaction is carried out for 0.5h, and filtering while the solution is hot to obtain a byproduct ammonium chloride. The filtrate was distilled under reduced pressure to remove the solvent, and dried to obtain 119.50g of L-Carlactonitrile as a white crystalline solid product having a melting point: 248.9-249.3 ℃, specific rotation [ alpha ] D25 ═ 27.27 ℃, and molar yield 79.97%.
Remarking: in the process of removing the solvent methanol by distillation under reduced pressure, the water introduced into the ammonia water can be carried out together due to the azeotropic boiling of methanol and water.
Example 2
(1) Preparation of (R) - (+) -4-chloro-3-hydroxybutyronitrile
100g of (R) - (-) -epichlorohydrin, 200g of ethanol and 3g of triethylamine are added into a 500mL three-neck flask, and the temperature is reduced to 15-20 ℃ by stirring. Then 33.58g of hydrocyanic acid is slowly dripped into the flask, the process is controlled at 15-20 ℃, and the mixture is stirred and reacts for 4 hours after dripping. After the reaction is finished, the methanol is removed by reduced pressure distillation at 50-60 ℃, the recovered methanol can be recycled, and then the intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile 121.10g is obtained by high vacuum rectification when the temperature is raised to 80-90 ℃, the gas phase content is 99.28%, the specific rotation [ alpha ] D25 is 16.8 degrees, and the molar yield is 93.72 percent.
(2) Preparation of L-Carlactonitrile
100g of the previously prepared intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, 400g of methanol and 119.88g of trimethylamine hydrochloride were put into a 1000mL three-necked flask, equipped with a thermometer and a pH meter, and stirred to raise the temperature to 45 ℃. Then, 25% ammonia water solution is slowly dripped into the flask to maintain the pH value between 8.5 and 9.0, the temperature is controlled between 45 and 50 ℃ in the process, and the reaction is carried out for 16 hours under the condition of heat preservation. After the reaction is finished, the solvent and water are removed by reduced pressure distillation, the obtained viscous liquid is pulped by 100g of methanol and then filtered, and a filter cake is washed by a small amount of methanol. Adding the filter cake into a mixed solvent of 100g of methanol and 400g of acetonitrile, stirring and heating until reflux reaction is carried out for 0.5h, and filtering while the solution is hot to obtain a byproduct ammonium chloride. The filtrate was distilled under reduced pressure to remove the solvent, and dried to obtain 120.90g of L-Carlactonitrile as a white crystalline solid product having a melting point: 248.9-249.2 ℃, specific rotation [ alpha ] D25 ═ 27.25 ℃, and molar yield 80.90%.
Example 3
(1) Preparation of (R) - (+) -4-chloro-3-hydroxybutyronitrile
100g of (R) - (-) -epichlorohydrin, 150g of methanol and 3g of triethylamine were added to a 500mL three-necked flask, and the temperature was reduced to 15 to 20 ℃ with stirring. Then slowly dripping 30.66g of hydrocyanic acid into the flask, controlling the temperature to be 15-20 ℃ in the process, and stirring for reacting for 4 hours after dripping. After the reaction is finished, the methanol is removed by reduced pressure distillation at 50-60 ℃, the recovered methanol can be recycled, and then the intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile 118.05g is obtained by high vacuum rectification after the temperature is raised to 80-90 ℃, the gas phase content is 99.05%, the specific rotation [ alpha ] D25 is 16.6 degrees, and the molar yield is 91.36%.
(2) Preparation of L-Carlactonitrile
100g of the previously prepared intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, 400g of ethanol and 119.88g of trimethylamine hydrochloride were put into a 1000mL three-necked flask, equipped with a thermometer and a pH meter, and stirred to raise the temperature to 50 ℃. Then, 25% ammonia water solution is slowly dripped into the flask to maintain the pH value between 8.5 and 9.0, the temperature is controlled between 50 and 55 ℃ in the process, and the reaction is carried out for 16 hours under the condition of heat preservation. After the reaction is finished, the solvent and water are removed by reduced pressure distillation, the obtained viscous liquid is pulped by 100g of ethanol and then filtered, and a filter cake is washed by a small amount of methanol. Adding the filter cake into a mixed solvent of 100g of methanol and 400g of acetonitrile, stirring and heating until reflux reaction is carried out for 0.5h, and filtering while the solution is hot to obtain a byproduct ammonium chloride. The filtrate was distilled under reduced pressure to remove the solvent, and dried to obtain 116.80g of L-Carlactonitrile as a white crystalline solid product having a melting point: 248.7-249.1 ℃, specific rotation [ alpha ] D25 ═ 27.20 ℃, and molar yield 78.16%.
Comparative example 1
(1) Preparation of (R) - (+) -4-chloro-3-hydroxybutyronitrile
100g of (R) - (-) -epichlorohydrin, 100g of ethanol and 3g of triethylamine were added to a 500mL three-necked flask, and the temperature was reduced to 15 to 20 ℃ with stirring. Then slowly dripping 30.66g of hydrocyanic acid into the flask, controlling the temperature to be 15-20 ℃ in the process, and stirring for reacting for 4 hours after dripping. After the reaction is finished, the methanol is removed by reduced pressure distillation at 50-60 ℃, the recovered methanol can be recycled, and then the intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile is obtained by high vacuum rectification at 80-90 ℃ with the gas phase content of 99.01 percent, the specific rotation [ alpha ] D25 being 16.7 degrees and the molar yield being 85.21 percent.
Remarking: when the amount of the solvent used is small, impurities in the reaction process increase; when the amount of hydrocyanic acid used is small, the reaction of the raw material (R) - (-) -epichlorohydrin is incomplete, thereby resulting in a significant decrease in the final molar yield.
(2) Preparation of L-Carlactonitrile
100g of the previously prepared intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, 400g of methanol and 87.91g of trimethylamine hydrochloride were put into a 1000mL three-necked flask, equipped with a thermometer and a pH meter, and stirred to raise the temperature to 55 ℃. Then, 25% ammonia water solution is slowly dripped into the flask to maintain the pH value between 8.5 and 9.0, the temperature is controlled to be between 55 and 60 ℃ in the process, and the reaction is carried out for 16 hours under the condition of heat preservation. After the reaction is finished, the solvent and water are removed by reduced pressure distillation, the obtained viscous liquid is pulped by 100g of methanol and then filtered, and a filter cake is washed by a small amount of methanol. Adding the filter cake into a mixed solvent of 100g of methanol and 400g of acetonitrile, stirring and heating until reflux reaction is carried out for 0.5h, and filtering while the solution is hot to obtain a byproduct ammonium chloride. The filtrate was distilled under reduced pressure to remove the solvent, and dried to obtain 110.55g of L-Carlactonitrile as a white crystalline solid product having a melting point: 248.5-249.3 ℃, specific rotation [ alpha ] D25 ═ 27.22 ℃ and molar yield 73.98%.
When trimethylamine hydrochloride is used in a small amount and the reaction temperature is high, the intermediate (R) - (+) -4-chloro-3-hydroxybutyronitrile, although the dot plate showed complete reaction, is not completely converted into the product L-carbanitrile, resulting in a decrease in the final yield, and we hypothesize that some side reaction occurred or some reaction intermediate was present.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. The preparation method of L-Carlactonitrile is characterized in that the synthetic route is as follows:
the method specifically comprises the following steps:
(1) cyanidation reaction: mixing (R) -epichlorohydrin with a solvent and a catalyst, dripping hydrocyanic acid, reacting for 4 hours at 15-20 ℃, and finally performing desolventizing and rectifying treatment to obtain an intermediate (R) -4-chloro-3-hydroxybutyronitrile;
(2) and (3) carrying out an amination reaction: mixing (R) -4-chloro-3-hydroxybutyronitrile, trimethylamine hydrochloride and a solvent, adjusting the pH value, reacting for 16 hours at the temperature of 30-60 ℃, and then carrying out desolventizing and recrystallization treatment to obtain L-Carlactonitrile and a byproduct ammonium chloride.
2. The process according to claim 1, wherein the weight ratio of (R) -epichlorohydrin to solvent in step (1) is 1.0: (1.0-3.0).
3. The process according to claim 1, wherein the catalyst is used in an amount of 1-5% by weight based on the weight of (R) -epichlorohydrin in step (1).
4. The process according to claim 1, wherein the molar ratio of (R) -epichlorohydrin to hydrocyanic acid in step (1) is 1.0: (1.05-1.2).
5. The process according to claim 1, wherein the catalyst in the step (1) is an organic base; and (3) the solvent in the step (1) and the solvent in the step (2) are both organic solvents.
6. The method according to claim 5, wherein the organic base is any one of diethylamine, triethylamine and ethylenediamine; the organic solvent is any one of methanol, ethanol and isopropanol.
7. The process according to claim 1, wherein the molar ratio of the (R) -4-chloro-3-hydroxybutyronitrile to trimethylamine hydrochloride in step (2) is 1.0: (1.0-2.0).
8. The process according to claim 1, wherein the weight ratio of the (R) -4-chloro-3-hydroxybutyronitrile to the solvent in step (2) is 1.0: 1.0 to 5.0.
9. The process according to claim 1, wherein the pH in the step (2) is adjusted so that the pH in the system is maintained at 8.5 to 9.0 by dropwise addition of aqueous ammonia.
10. The method for preparing L-canavanine nitrile according to claim 1, wherein the solvent used in the recrystallization in the step (2) is a mixed solvent of acetonitrile and methanol, wherein the weight ratio of methanol to acetonitrile is 1.0: (1.0-5.0).
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114436872A (en) * | 2022-02-22 | 2022-05-06 | 华今(山东)新材料科技有限公司 | Low-cost L-carnitine preparation method |
| CN115367773A (en) * | 2022-08-29 | 2022-11-22 | 辽宁科硕营养科技股份有限公司 | Environment-friendly L-carnitine production process |
| CN115894292A (en) * | 2022-12-16 | 2023-04-04 | 山东阳谷华泰化工股份有限公司 | Preparation method of L-Carlactonitrile |
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| CN114436872A (en) * | 2022-02-22 | 2022-05-06 | 华今(山东)新材料科技有限公司 | Low-cost L-carnitine preparation method |
| CN114436872B (en) * | 2022-02-22 | 2023-08-18 | 华今(山东)新材料科技有限公司 | Low-cost preparation method of L-carnitine |
| CN115367773A (en) * | 2022-08-29 | 2022-11-22 | 辽宁科硕营养科技股份有限公司 | Environment-friendly L-carnitine production process |
| CN115894292A (en) * | 2022-12-16 | 2023-04-04 | 山东阳谷华泰化工股份有限公司 | Preparation method of L-Carlactonitrile |
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