CN110950838A - Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor - Google Patents
Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor Download PDFInfo
- Publication number
- CN110950838A CN110950838A CN201911089357.0A CN201911089357A CN110950838A CN 110950838 A CN110950838 A CN 110950838A CN 201911089357 A CN201911089357 A CN 201911089357A CN 110950838 A CN110950838 A CN 110950838A
- Authority
- CN
- China
- Prior art keywords
- nicotine
- nicotine salt
- microchannel reactor
- acetic acid
- seconds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for synthesizing nicotine salt by using a microchannel reactor under the condition of no solvent, which comprises the following steps: the molar ratio is 1: (1.1-6) respectively adding the liquid nicotine and acetic acid into an injector, pumping into a microchannel reactor, heating at 25-95 ℃ for reaction for 85-706 seconds, and discharging from a liquid receiving port after the system reaches a certain pressure to obtain the nicotine salt. The method has the advantages of mild reaction conditions, simple operation, low raw material cost, no solvent addition, environmental protection, no need of post-treatment purification, high yield, stable state and high purity of the prepared nicotine salt, effectively reduces the irritation of nicotine, and is suitable for industrial production.
Description
The technical field is as follows:
the invention relates to the field of tobacco products, in particular to a method for synthesizing nicotine salt by using a microchannel reactor under the condition of no solvent.
Background art:
nicotine (Nicotine), commonly known as Nicotine, has molecular weight of 162.23, is colorless or light yellow oily liquid at room temperature, is volatile, has pungent smell and optical activity, has two optical isomers, is alkaloid existing in solanaceae plants (solanum), is also an important component of tobacco, is a representative of N-choline receptor agonist, has effects on N1 and N2 receptors and central nervous system, and has no clinical application value.
Nicotine can cause addiction or dependence, and repeated use of nicotine also increases heart rate and increases blood pressure and decreases appetite. Large doses of nicotine can cause vomiting and nausea, and in severe cases, death. Tobacco typically contains nicotine. Electronic cigarettes also contain nicotine, a harmful substance of traditional tobacco.
The currently reported nicotine salt synthesis method uses an organic solvent, increases the production cost and is not environment-friendly, and the method for preparing the composite nicotine salt and the solution thereof invented by Shenzhen concentric investment Limited also uses propylene glycol and glycerol as diluents (CN 109619655A). A process for preparing nicotine salt by solvent-free method is disclosed, which is carried out by mixing organic acid with liquid nicotine, heating while stirring, cooling to room temperature, and taking out to obtain nicotine salt (CN 109288115A). The method has the disadvantages of no continuous production, low efficiency and different batches.
The invention content is as follows:
the invention aims to provide a method for synthesizing nicotine salt by utilizing a microchannel reactor under the solvent-free condition, which has the advantages of mild reaction condition, simple operation, low raw material cost, no solvent addition, environmental protection, no need of post-treatment purification, high yield, stable state and high purity of the prepared nicotine salt, effectively reduces the irritation of nicotine and is suitable for industrial production.
The invention is realized by the following technical scheme:
a method for synthesizing a nicotine salt using a microchannel reactor in the absence of a solvent, the method comprising the steps of: the molar ratio is 1: (1.1-6) respectively adding the liquid nicotine and acetic acid into an injector, pumping into a microchannel reactor, heating at 25-95 ℃ for reaction for 85-706 seconds, and discharging from a liquid receiving port after the system reaches a certain pressure to obtain the nicotine salt.
The microchannel reactor is a Labtrix Start model of Chemtrix company, and the model numbers of the reactor chips are 3223 and 3224.
The pumping rate is 0.5-2uL/min of nicotine and 0.3-5.2uL/min of acetic acid.
The molar ratio of the liquid nicotine to the formic acid or the acetic acid is preferably 1:1.5-6, the reaction temperature is preferably 55-85 ℃, and the reaction time is preferably 105-706 seconds.
The invention has the following beneficial effects: the method has the advantages of mild reaction conditions, simple operation, low raw material cost, no solvent addition, environmental protection, no need of post-treatment purification, high yield, stable state and high purity of the prepared nicotine salt, effectively reduces the irritation of nicotine, and is suitable for industrial production.
The specific implementation mode is as follows:
the following is a further description of the invention and is not intended to be limiting.
Example 1:
mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.1, add syringe into the microchannel reaction chip, dwell at 25 ℃ for about 85 seconds, collect at the interface to prepare nicotine salt with 56.25% LC-MS normalized yield.
MS(ESI+):m/z:163([M-H]+).
Example 2
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.2 Add Syringe into microchannel reaction chip, at 75 degrees C for about 129 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 32%.
MS(ESI+):m/z:163([M-H]+).
Example 3
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.3 Add Syringe into the microchannel reaction chip, at 75 degrees C for about 95 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 35%.
MS(ESI+):m/z:163([M-H]+).
Example 4
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.4 Add Syringe into the microchannel reaction chip, at 75 degrees C for about 100 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 46.67%.
MS(ESI+):m/z:163([M-H]+).
Example 5
Mixing liquid nicotine and acetic acid according to a molar ratio of 1:1.5 Add Syringe into the microchannel reaction chip, at 75 degrees C for about 105 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 77.78%.
MS(ESI+):m/z:163([M-H]+).
Example 6
Mixing liquid nicotine and acetic acid according to a molar ratio of 1:1.5 Add Syringe into the microchannel reaction chip, at 95 ℃ for about 105 seconds, collected at the interface as the nicotine salt prepared, with LC-MS normalized yield of 72.73%.
MS(ESI+):m/z:163([M-H]+).
Example 7
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.6 Add Syringe into the microchannel reaction chip, at 75 degrees C for about 109 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 50%.
MS(ESI+):m/z:163([M-H]+).
Example 8
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.7 Add Syringe into the microchannel reaction chip, dwell at 75 deg.C for about 114 seconds, collect at the interface to give the nicotine salt prepared, LC-MS normalized yield 53.33%.
MS(ESI+):m/z:163([M-H]+).
Example 9
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 1.8 Add Syringe into the microchannel reaction chip, at 75 degrees C for about 118 seconds, collected in the liquid connection for the preparation of nicotine salt, LC-MS normalized yield of 50%.
MS(ESI+):m/z:163([M-H]+).
Example 10
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 4 syringe into the microchannel reaction chip, and residence time at 75 ℃ for about 706 seconds, collected at the access port as the nicotine salt prepared, with an LC-MS normalized yield of 88.23%.
MS(ESI+):m/z:163([M-H]+).
Example 11
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 5 into a syringe, passed over the microchannel reaction chip, and left at 55 ℃ for about 385 seconds, collected at the access port as the nicotine salt prepared, with an LC-MS normalized yield of 89.67%.
MS(ESI+):m/z:163([M-H]+).
Example 12
Mixing liquid nicotine and acetic acid according to a molar ratio of 1: 6 Add syringe into the microchannel reaction chip, dwell at 85 deg.C for about 105 seconds, collect at the interface to prepare nicotine salt with LC-MS normalized yield of 91.33%.
MS(ESI+):m/z:163([M-H]+)。
Claims (4)
1. A method for synthesizing a nicotine salt using a microchannel reactor in the absence of a solvent, the method comprising the steps of: the molar ratio is 1: (1.1-6) respectively adding the liquid nicotine and acetic acid into an injector, pumping into a microchannel reactor, heating at 25-95 ℃ for reaction for 85-706 seconds, and discharging from a liquid receiving port after the system reaches a certain pressure to obtain the nicotine salt.
2. The method for synthesizing nicotine salt under solvent-free conditions by using the microchannel reactor as claimed in claim 1, wherein the microchannel reactor is Labtrix Start from Chemtrix, and the model of the reactor chip is 3223, 3224.
3. The method of claim 1, wherein the pumping rate is 0.5-2uL/min nicotine and 0.3-5.2uL/min acetic acid.
4. The method of claim 1, wherein the molar ratio of liquid nicotine to acetic acid is 1:1.5-6, the reaction temperature is 55-85 ℃, and the reaction time is 105-706 seconds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911089357.0A CN110950838A (en) | 2019-11-08 | 2019-11-08 | Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911089357.0A CN110950838A (en) | 2019-11-08 | 2019-11-08 | Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110950838A true CN110950838A (en) | 2020-04-03 |
Family
ID=69976651
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911089357.0A Pending CN110950838A (en) | 2019-11-08 | 2019-11-08 | Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110950838A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2611418A (en) * | 2021-09-02 | 2023-04-05 | Bae Systems Plc | Improved flow synthesis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107536099A (en) * | 2017-09-14 | 2018-01-05 | 昌宁德康生物科技（深圳）有限公司 | A kind of nicotine salt and preparation method thereof |
| CN109288115A (en) * | 2018-10-16 | 2019-02-01 | 云南拓宝科技有限公司 | A kind of nicotine salt and preparation method thereof of solventless method preparation |
-
2019
- 2019-11-08 CN CN201911089357.0A patent/CN110950838A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107536099A (en) * | 2017-09-14 | 2018-01-05 | 昌宁德康生物科技（深圳）有限公司 | A kind of nicotine salt and preparation method thereof |
| CN109288115A (en) * | 2018-10-16 | 2019-02-01 | 云南拓宝科技有限公司 | A kind of nicotine salt and preparation method thereof of solventless method preparation |
Non-Patent Citations (2)
| Title |
|---|
| 刘熠 等: "微通道反应器的研究进展", 《辽宁化工》 * |
| 赵述芳 等: "液滴流微反应器的基础研究及其应用", 《化工进展》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2611418A (en) * | 2021-09-02 | 2023-04-05 | Bae Systems Plc | Improved flow synthesis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110357853B (en) | Synthesis method of (R, S-) nicotine | |
| CN112745294B (en) | Synthesis method of (R, S-) nicotine | |
| JP2007269658A (en) | Method for producing dialkylimidazole and dialkyl imidazole obtained thereby | |
| CN105481726A (en) | Preparation method of metformin hydrochloride | |
| Keely Jr et al. | The 3-arylpyrrolidine alkaloid synthon. A new synthesis of dl-mesembrine | |
| CN114149324B (en) | Synthesis method of 6-hydroxy-8-chlorooctanoic acid ethyl ester, 6, 8-dichloro octanoic acid ethyl ester and lipoic acid | |
| CN110950838A (en) | Method for synthesizing nicotine salt under solvent-free condition by using microchannel reactor | |
| CN115232055A (en) | Synthesis method of arbidol hydrochloride | |
| CN110540546B (en) | Production process of tricyclazole | |
| CN112624923A (en) | Preparation method of 4-methoxy methyl acetoacetate | |
| CN107698471A (en) | It is a kind of to MSM benzaldehyde preparation method | |
| CN112457203B (en) | Preparation method of 2-amino-2-methyl-1-propanol | |
| CN101696157A (en) | Method for preparing 1,2,4-butanetriol | |
| CN105439837B (en) | Synthetic method of 6-bromoisovanillin | |
| Searles et al. | The Synthesis of 3-Alkyl-4-methylquinolines1 | |
| CN111116339B (en) | Method for artificially synthesizing curcumin and derivatives thereof | |
| CN106866663A (en) | A kind of process of praziquantel synthesis | |
| CN110003083B (en) | Process method for preparing S-indoline-2-carboxylic acid by using Ir catalyst | |
| CH626074A5 (en) | ||
| CN112552345A (en) | Preparation method of NK-1 receptor antagonist | |
| US3096244A (en) | Substituted butyric acid amide and analgesia | |
| CN105646617A (en) | Method for preparing tulathromycin | |
| CN116239529B (en) | Preparation method of N-methyltetrahydroquinoline alkaloid with participation of carbon dioxide | |
| CN110642770B (en) | Preparation method of 5-methoxyindole | |
| CN117510328B (en) | Preparation method of methyl 4-chlorobutyrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200403 |
|
| RJ01 | Rejection of invention patent application after publication |