CN112125883A - Synthesis method of racemic nicotine - Google Patents
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- CN112125883A CN112125883A CN202011140409.5A CN202011140409A CN112125883A CN 112125883 A CN112125883 A CN 112125883A CN 202011140409 A CN202011140409 A CN 202011140409A CN 112125883 A CN112125883 A CN 112125883A
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses a method for synthesizing racemic nicotine, which comprises the following steps: s1: 3- (1-pyrroline-2-yl) pyridine, a solvent and hydrogen are introduced into a first fixed bed reactor filled with a metal catalyst, and a crude product of 3- (1-pyrroline-2-yl) pyridine mixed solution is obtained after an outlet is cooled; s2: and (3) taking the crude product of the 3- (1-pyrrolidine-2-yl) pyridine and the methylating agent to pass through a solid second fixed bed reactor filled with a solid base catalyst, and cooling an outlet to obtain the racemic nicotine. The continuous flow fixed bed method for preparing racemic nicotine realizes the continuity of production, shortens the reaction time, simplifies the reaction operation, reduces the use of solvents, reduces the discharge of waste water and waste liquid, and is convenient for the recovery of catalysts.
Description
Technical Field
The invention relates to the technical field of organic synthesis, and in particular relates to a method for synthesizing racemic nicotine.
Background
Nicotine, also known as nicontine, is an alkaloid present in plants of the solanaceae family (solanum genus), an important component of tobacco, and is also a typical nicotinic acetylcholine receptor agonist, having a modulatory effect on both nicotinic acetylcholine receptors and the central nervous system. Their success has been reported in the treatment of Tourette's syndrome (Tourette's), Alzheimer's disease, schizophrenia and other diseases associated with neurological disorders. Common modes of administration are chewable tablets, creams, transdermal patches, tablets, nasal sprays and electronic cigarettes.
In recent years, the market for new tobacco products has grown faster and faster worldwide, and the demand for nicotine has also increased. Most of nicotine used at present is natural nicotine extracted from plants, and hazardous substances contained in tobacco can be extracted together in the extraction process, particularly, the special nitrosamine in the tobacco is difficult to treat the hazardous substances cleanly even in purity meeting the requirements of pharmacopoeia. The synthesized nicotine has no hazardous substances, and is more beneficial to application and popularization.
Natural nicotine is essentially levorotatory and its toxicity is by itself much greater than that of racemic nicotine. The two have substantial similarity in pharmacological activity. The synthesized racemic nicotine is therefore increasingly appreciated.
The journal of Organic Chemistry, 1990, 55(6), 1736-44; the synthesis of racemic nicotine via a four-step reaction starting from pyrrolidine is reported, the tert-butyllithium involved in the document and the low temperature of-120 ℃ in the reaction increase the difficulty of industrial production, and the yield of the method is low.
Document Synlett, 2009(15), 2497-; a method for preparing racemic nicotine by using 3-pyridylaldehyde as a starting material is reported, and a Grignard reagent is involved in the reaction, so that the application of the racemic nicotine in industrialization is limited.
Patent US2010209006Al describes a four-step process for the preparation of racemic nicotine starting from methyl nicotinate by condensation with explosive sodium hydride and methylation with formol formic acid, using a synthetic route using methyl nicotinate as starting material, which generates a large amount of waste water during the purification process.
Patent US20160115150 carries out the synthesis of racemic nicotine starting from ethyl nicotinate and N-vinylpyrrolidone, which method also involves the problems of the previous patent.
In a word, in the existing method for preparing racemic nicotine, the used reagents are expensive, the reaction conditions are harsh, and more waste water and waste liquid are generated, which is not beneficial to the industrialized production.
Disclosure of Invention
The present invention aims to overcome the above-mentioned shortcomings and provide a technical solution to solve the above-mentioned problems.
A method of synthesizing racemic nicotine comprising the steps of:
s1: 3- (1-pyrroline-2-yl) pyridine, a solvent and hydrogen are introduced into a first fixed bed reactor filled with a metal catalyst, and a crude product of 3- (1-pyrroline-2-yl) pyridine mixed solution is obtained after an outlet is cooled;
s2: and (3) taking the crude product of the 3- (1-pyrrolidine-2-yl) pyridine and the methylating agent to pass through a solid second fixed bed reactor filled with a solid base catalyst, and cooling an outlet to obtain the racemic nicotine.
Further, the step of preparing the crude 3- (1-pyrrolidin-2-yl) pyridine mixed solution in the step S1 specifically includes the steps of:
(1) charging a metal catalyst into a first fixed bed reactor;
(2) mixing and heating 3- (1-pyrroline-2-yl) pyridine and a solvent, atomizing through an atomizing nozzle, introducing into a mixer, and introducing hydrogen into the mixer to obtain mixed gas;
(3) and (3) pumping the mixed gas into a first fixed bed reactor, arranging a gas-liquid separator at the outlet of the fixed window fixed bed reactor for separation, cooling, and collecting liquid to obtain the 3- (1-pyrrolidine-2-yl) pyridine mixed solution.
Further, the step of preparing racemic nicotine in step S2 specifically comprises the following steps:
(1) charging a solid base catalyst into the second fixed bed reactor;
(2) respectively heating the 3- (1-pyrrolidine-2-yl) pyridine mixed solution and a methylating agent, and then filling the heated mixed solution and the methylating agent into a second fixed bed reactor;
(3) and carrying out gas-liquid separation at an outlet of the second fixed bed reactor, and collecting liquid to obtain the high-purity racemic nicotine.
Further, the temperature of mixing and heating in the step (2) is 40-80 ℃, the temperature of the first fixed bed reactor is 80-150 ℃, the pressure is 0.2-1.8Mpa, and the space velocity is 50-200 mL/min.
Further, the temperature of the second fixed bed reactor is 100-300 ℃, the pressure is 0.5-2Mpa, and the space velocity is 50-200 mL/min.
Further, the outlet cooling temperature of the second fixed bed reactor in the step (3) is 80-150 ℃.
Further, the solvent at least comprises one of methanol, ethanol, dimethyl carbonate and toluene.
Furthermore, the metal catalyst at least comprises one of palladium carbon, Raney nickel, platinum carbon, palladium alumina and palladium molecular sieve, and the particle size of the metal catalyst is 0.1 mm-5 mm.
Further, the solid base catalyst at least comprises one of sodium hydroxide, potassium fluoride, sodium fluoride, potassium carbonate, sodium carbonate, alumina-supported potassium hydroxide, alumina-supported sodium carbonate, alumina-supported potassium carbonate, molecular sieve-supported sodium carbonate, molecular sieve-supported potassium hydroxide and molecular sieve-supported sodium hydroxide, and the particle size of the solid base catalyst is 0.5 mm-3 mm.
Further, the methylating agent is dimethyl carbonate.
Compared with the prior art, the invention has the following beneficial effects: the continuous flow fixed bed method for preparing racemic nicotine realizes the continuity of production, shortens the reaction time, simplifies the reaction operation, reduces the use of solvents, reduces the discharge of waste water and waste liquid, and is convenient for the recovery of catalysts.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be 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.
A method of synthesizing racemic nicotine comprising the steps of:
s1: 3- (1-pyrroline-2-yl) pyridine, a solvent and hydrogen are introduced into a first fixed bed reactor filled with a metal catalyst, and a crude product of 3- (1-pyrroline-2-yl) pyridine mixed solution is obtained after an outlet is cooled;
s2: and (3) taking the crude product of the 3- (1-pyrrolidine-2-yl) pyridine and the methylating agent to pass through a solid second fixed bed reactor filled with a solid base catalyst, and cooling an outlet to obtain the racemic nicotine.
Further, the step of preparing the crude 3- (1-pyrrolidin-2-yl) pyridine mixed solution in the step S1 specifically includes the steps of:
(1) charging a metal catalyst into a first fixed bed reactor;
(2) mixing and heating 3- (1-pyrroline-2-yl) pyridine and a solvent, atomizing through an atomizing nozzle, introducing into a mixer, and introducing hydrogen into the mixer to obtain mixed gas;
(3) and (3) pumping the mixed gas into a first fixed bed reactor, arranging a gas-liquid separator at the outlet of the fixed window fixed bed reactor for separation, cooling, and collecting liquid to obtain the 3- (1-pyrrolidine-2-yl) pyridine mixed solution.
Further, the step of preparing racemic nicotine in step S2 specifically comprises the following steps:
(1) charging a solid base catalyst into the second fixed bed reactor;
(2) respectively heating the 3- (1-pyrrolidine-2-yl) pyridine mixed solution and a methylating agent, and then filling the heated mixed solution and the methylating agent into a second fixed bed reactor;
(3) and carrying out gas-liquid separation at an outlet of the second fixed bed reactor, and collecting liquid to obtain the high-purity racemic nicotine.
Further, the temperature of mixing and heating in the step (2) is 40-80 ℃, the temperature of the first fixed bed reactor is 80-150 ℃, the pressure is 0.2-1.8Mpa, and the space velocity is 50-200 mL/min.
Further, the temperature of the second fixed bed reactor is 100-300 ℃, the pressure is 0.5-2Mpa, and the space velocity is 50-200 mL/min.
Further, the outlet cooling temperature of the second fixed bed reactor in the step (3) is 80-150 ℃.
Aiming at the problems of complex steps, complex operation, large waste water and waste liquid amount and the like of the existing method for preparing the racemic nicotine, the invention provides a synthetic route for preparing the racemic nicotine by a fixed bed, which is as follows:
to specifically illustrate the technical solution of the present invention, the present invention also discloses the following specific examples.
[ EXAMPLE one ] Synthesis of 3- (1-pyrrolin-2-yl) pyridine
151 g of ethyl nicotinate, 600 g of toluene, 5 g of ethanol and 90 g of sodium ethoxide are added into a reaction bottle under stirring, the reaction is heated to 80-85 ℃, the reaction is carried out under anhydrous condition, and nitrogen is introduced. Adding 133 g of 1-vinyl-2 pyrrolidone dropwise into a reaction bottle at 80-85 ℃, heating to 95-100 ℃ for reaction for 6 hours, cooling to 40 ℃, concentrating, evaporating the solvent, adding 2 times of 10% HCl solution in volume into the residual mixed solution for quenching reaction, keeping the temperature at 40-50 ℃, then pouring the mixed solution into 1 time of 30% HCl solution in volume, heating to 95-100 ℃ for reflux reaction, and reacting for 12 hours. After the reaction is finished, the temperature is reduced to 30 ℃, the pH value is adjusted to be more than 10 by using sodium hydroxide aqueous solution, dichloromethane is used for extraction for 3 times, organic phases are combined, and crude products of 3- (1-pyrroline-2-yl) pyridine are obtained by concentration, wherein the conversion rate is about 50%.
[ EXAMPLE II ] Synthesis of 3- (1-pyrrolin-2-yl) pyridine
133 g of 1-vinyl-2 pyrrolidone and 800 g of N, N-dimethylformamide are added into a reaction bottle under stirring, 75 g of sodium hydrogen is slowly added under the condition of ensuring that the reaction bottle is anhydrous, the reaction temperature is controlled to be not higher than 60 ℃, then 151 g of ethyl nicotinate is dropwise added into the reaction bottle at the temperature of 80-85 ℃, and the temperature is increased to 95-100 ℃ for reaction for 6 hours. Cooling to 60 deg.c, concentrating and evaporating solvent. To the remaining mixture was added 2 volumes of 10% HCl solution to quench the reaction, maintaining the temperature at 40-50 ℃. The mixture was then poured into 1 volume of 30% HCl solution and the reaction was started by heating to 95-100 deg.C under reflux. The reaction time was 12 hours. After the reaction is finished, the temperature is reduced to 30 ℃, the pH value is adjusted to be more than 10 by using sodium hydroxide aqueous solution, dichloromethane is used for extraction for 3 times, organic phases are combined, and the crude product of the 3- (1-pyrroline-2-yl) pyridine is obtained by concentration.
[ EXAMPLE III ] Synthesis of racemic Nicotine
First 5 grams of the metal catalyst was charged to a first fixed bed reactor, then 100 grams of 3- (1-pyrrolin-2-yl) pyridine and ethanol were mixed in a 1: 1.5, putting the mixture into a feeding tank for mixing, heating the mixture to 50 ℃, atomizing the mixture through an atomizing nozzle, mixing the mixture with hydrogen in a mixer, then pumping the mixture into a fixed bed reactor, wherein the temperature of the reactor is 100 ℃, the reaction pressure is 0.6MPa, and the weight space velocity is 50ml/min, separating the mixture at an outlet gas-liquid separator, cooling the mixture to obtain a 3- (1-pyrrolidine-2-yl) pyridine mixed solution, concentrating the mixture to obtain 3- (1-pyrrolidine-2-yl) pyridine as a raw material for the next stage, then putting 10 g of a solid base catalyst with the solid loading of 10 percent into a second fixed bed reactor, respectively putting the raw material and a methylation reagent into the feeding tank, heating the raw material and the methylation reagent to 80 ℃, and mixing the raw material with the solid base catalyst with the solid loading of: feeding is carried out at a space velocity ratio of 1.5, the feeding space velocity is 50ml/min, the space velocity of a methylating agent is 75ml/min, the reaction temperature of the second fixed bed reactor is 280 ℃, the reaction pressure is 1.0MPa, the separation temperature of an outlet gas-liquid separator is 110 ℃, unreacted methylating agents, by-product ethanol, carbon dioxide and the like are gases at the temperature, the product racemized nicotine is changed into liquid, the gas part is condensed by cold to be returned into liquid, the liquid can be refined and then used again, and the product conversion rate can reach 80.0%.
[ EXAMPLE IV ] Synthesis of racemic Nicotine
First 5 grams of the metal catalyst was charged to a first fixed bed reactor, then 100 grams of 3- (1-pyrrolin-2-yl) pyridine and ethanol were mixed in a 1: 1.5, putting the mixture into a feeding tank for mixing, heating the mixture to 50 ℃, atomizing the mixture through an atomizing nozzle, mixing the mixture with hydrogen in a mixer, then pumping the mixture into a fixed bed reactor, wherein the temperature of the reactor is 100 ℃, the reaction pressure is 0.6MPa, and the weight space velocity is 50ml/min, separating the mixture at an outlet gas-liquid separator, cooling the mixture to obtain a 3- (1-pyrrolidine-2-yl) pyridine mixed solution, concentrating the mixture to obtain 3- (1-pyrrolidine-2-yl) pyridine as a raw material for the next stage, then putting 10 g of a solid base catalyst with the solid loading of 10 percent into a second fixed bed reactor, respectively putting the raw material and a methylation reagent into the feeding tank, heating the raw material and the methylation reagent to 80 ℃, and mixing the raw material with the solid base catalyst with the solid loading of: feeding is carried out at a space velocity ratio of 1.5, the feeding space velocity is 50ml/min, the space velocity of a methylating agent is 75ml/min, the reaction temperature of the second fixed bed reactor is 280 ℃, the reaction pressure is 0.8MPa, the separation temperature of an outlet gas-liquid separator is 110 ℃, unreacted methylating agents, by-products ethanol, carbon dioxide and the like are gases at the temperature, the products racemized nicotine are changed into liquid, the gas part is condensed back to the liquid through cooling and can be refined and reused, and the product conversion rate can reach 74.0%.
[ EXAMPLE V ] Synthesis of racemic Nicotine
First 5 grams of the metal catalyst was charged to a first fixed bed reactor, then 100 grams of 3- (1-pyrrolin-2-yl) pyridine and ethanol were mixed in a 1: 1.5, putting the mixture into a feeding tank for mixing, heating the mixture to 60 ℃, atomizing the mixture through an atomizing nozzle, mixing the mixture with hydrogen in a mixer, then pumping the mixture into a fixed bed reactor, wherein the temperature of the reactor is 80 ℃, the reaction pressure is 0.5MPa, and the weight space velocity is 50ml/min, separating the mixture at an outlet gas-liquid separator, cooling the mixture to obtain a 3- (1-pyrrolidine-2-yl) pyridine mixed solution, concentrating the mixture to obtain 3- (1-pyrrolidine-2-yl) pyridine as a raw material for the next stage, then putting 10 g of a solid base catalyst with the solid loading of 10 percent into a second fixed bed reactor, respectively putting the raw material and a methylation reagent into the feeding tank, heating the raw material and the methylation reagent to 80 ℃, and mixing the raw material with the solid base catalyst with the solid loading of: feeding is carried out at a space velocity ratio of 1.5, the feeding space velocity is 60ml/min, the space velocity of a methylating agent is 75ml/min, the reaction temperature of the second fixed bed reactor is 290 ℃, the reaction pressure is 1.0MPa, the separation temperature of an outlet gas-liquid separator is 110 ℃, unreacted methylating agents, by-product ethanol, carbon dioxide and the like are gases at the temperature, the racemized nicotine of the product is changed into liquid, the gas part is condensed back to the liquid through cooling and can be refined and reused, and the product conversion rate can reach 72.0%.
[ EXAMPLE six ] Synthesis of racemic Nicotine
First 5 grams of the metal catalyst was charged to a first fixed bed reactor, then 100 grams of 3- (1-pyrrolin-2-yl) pyridine and ethanol were mixed in a 1: 1.5, putting the mixture into a feeding tank for mixing, heating the mixture to 60 ℃, atomizing the mixture through an atomizing nozzle, mixing the mixture with hydrogen in a mixer, then pumping the mixture into a fixed bed reactor, wherein the temperature of the reactor is 100 ℃, the reaction pressure is 0.8MPa, and the weight space velocity is 50ml/min, separating the mixture at an outlet gas-liquid separator, cooling the mixture to obtain a 3- (1-pyrrolidine-2-yl) pyridine mixed solution, concentrating the mixture to obtain 3- (1-pyrrolidine-2-yl) pyridine as a raw material for the next stage, then putting 10 g of a solid base catalyst with the solid loading of 10 percent into a second fixed bed reactor, respectively putting the raw material and a methylation reagent into the feeding tank, heating the raw material and the methylation reagent to 80 ℃, and mixing the raw material with the solid base catalyst with the solid loading of: feeding is carried out at a space velocity ratio of 1.5, the feeding space velocity is 100ml/min, the space velocity of a methylating agent is 75ml/min, the reaction temperature of the second fixed bed reactor is 290 ℃, the reaction pressure is 1.2MPa, the separation temperature of an outlet gas-liquid separator is 110 ℃, unreacted methylating agents, by-product ethanol, carbon dioxide and the like are gases at the temperature, the product racemized nicotine is changed into liquid, the gas part is condensed by cold to be returned into liquid, the liquid can be refined and then used again, and the product conversion rate can reach 72.0%.
[ EXAMPLE seventy ] Synthesis of racemic Nicotine
First 5 grams of 1 metal catalyst was charged to a first fixed bed reactor, then 100 grams of 3- (1-pyrrolin-2-yl) pyridine and ethanol were mixed in a 1: 2.0, putting the mixture into a feeding tank for mixing, heating the mixture to 60 ℃, atomizing the mixture through an atomizing nozzle, mixing the mixture with hydrogen in a mixer, then pumping the mixture into a fixed bed reactor, wherein the temperature of the reactor is 110 ℃, the reaction pressure is 0.8MPa, and the weight space velocity is 60ml/min, separating the mixture at an outlet gas-liquid separator, cooling the mixture to obtain a 3- (1-pyrrolidine-2-yl) pyridine mixed solution, concentrating the mixture to obtain 3- (1-pyrrolidine-2-yl) pyridine as a raw material for the next stage, then putting 10 g of a solid base catalyst with the solid loading of 10 percent into a second fixed bed reactor, respectively putting the raw material and a methylation reagent into the feeding tanks, heating the raw material and the methylation reagent to 80 ℃, and mixing the raw material with the solid base catalyst with the solid loading of: feeding is carried out at a space velocity ratio of 1.5, the feeding space velocity is 100ml/min, the space velocity of a methylating agent is 75ml/min, the reaction temperature of the second fixed bed reactor is 290 ℃, the reaction pressure is 1.4MPa, the separation temperature of an outlet gas-liquid separator is 110 ℃, unreacted methylating agents, by-product ethanol, carbon dioxide and the like are gases at the temperature, the product racemized nicotine is changed into liquid, the gas part is condensed by cold to be returned into liquid, the liquid can be refined and then used again, and the product conversion rate can reach 80.0%.
In the embodiment in which the above-described embodiments are used,
the solvent at least comprises one of methanol, ethanol, a methylating agent and toluene;
the metal catalyst at least comprises one of palladium carbon, Raney nickel, platinum carbon, palladium alumina and palladium molecular sieve, and the particle size of the metal catalyst is 0.1-5 mm;
further, the solid base catalyst at least comprises one of sodium hydroxide, potassium fluoride, sodium fluoride, potassium carbonate, sodium carbonate, alumina-supported potassium hydroxide, alumina-supported sodium carbonate, alumina-supported potassium carbonate, molecular sieve-supported sodium carbonate, molecular sieve-supported potassium hydroxide and molecular sieve-supported sodium hydroxide, and the particle size of the solid base catalyst is 0.5 mm-3 mm;
the methylating agent is dimethyl carbonate.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Claims (10)
1. A method of synthesizing racemic nicotine comprising the steps of:
s1: 3- (1-pyrroline-2-yl) pyridine, a solvent and hydrogen are introduced into a first fixed bed reactor filled with a metal catalyst, and a crude product of 3- (1-pyrroline-2-yl) pyridine mixed solution is obtained after an outlet is cooled;
s2: and (3) taking the crude product of the 3- (1-pyrrolidine-2-yl) pyridine and the methylating agent to pass through a solid second fixed bed reactor filled with a solid base catalyst, and cooling an outlet to obtain the racemic nicotine.
2. The method of claim 1, wherein the step of preparing the crude 3- (1-pyrrolidin-2-yl) pyridine mixed solution in the step S1 comprises the following steps:
(1) charging a metal catalyst into a first fixed bed reactor;
(2) mixing and heating 3- (1-pyrroline-2-yl) pyridine and a solvent, atomizing through an atomizing nozzle, introducing into a mixer, and introducing hydrogen into the mixer to obtain mixed gas;
(3) and (3) pumping the mixed gas into a first fixed bed reactor, arranging a gas-liquid separator at the outlet of the fixed window fixed bed reactor for separation, cooling, and collecting liquid to obtain the 3- (1-pyrrolidine-2-yl) pyridine mixed solution.
3. The method of claim 1, wherein the step of S2 to obtain racemic nicotine specifically comprises the following steps:
(1) charging a solid base catalyst into the second fixed bed reactor;
(2) respectively heating the 3- (1-pyrrolidine-2-yl) pyridine mixed solution and a methylating agent, and then filling the heated mixed solution and the methylating agent into a second fixed bed reactor;
(3) and carrying out gas-liquid separation at an outlet of the second fixed bed reactor, and collecting liquid to obtain the high-purity racemic nicotine.
4. The method of claim 2, wherein the mixing and heating in step (2) is carried out at a temperature of 40-80 ℃, a temperature of 80-150 ℃, a pressure of 0.2-1.8Mpa, and a space velocity of 50-200 mL/min.
5. The method as claimed in claim 3, wherein the temperature of the second fixed bed reactor is 100-300 ℃, the pressure is 0.5-2Mpa, and the space velocity is 50-200 mL/min.
6. The method for synthesizing racemic nicotine according to claim 3, wherein the outlet cooling temperature of the second fixed bed reactor in step (3) is 80-150 ℃.
7. A method of synthesising a racemic nicotine as claimed in claim 1, 2 or 3 wherein the solvent comprises at least one of methanol, ethanol, dimethyl carbonate, toluene.
8. The method for synthesizing racemic nicotine according to claim 1, 2 or 3, wherein the metal catalyst comprises at least one of palladium carbon, Raney nickel, platinum carbon, palladium alumina and palladium molecular sieve, and the particle size of the metal catalyst is 0.1 mm-5 mm.
9. The method of claim 1, 2 or 3, wherein the solid base catalyst comprises at least one of sodium hydroxide, potassium fluoride, sodium fluoride, potassium carbonate, sodium carbonate, alumina-supported potassium hydroxide, alumina-supported sodium carbonate, alumina-supported potassium carbonate, molecular sieve-supported sodium carbonate, molecular sieve-supported potassium hydroxide, and molecular sieve-supported sodium hydroxide, and the particle size of the solid base catalyst is 0.5mm to 3 mm.
10. A process for the synthesis of racemic nicotine according to claim 1, 2 or 3, wherein the methylating agent is dimethyl carbonate.
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