CN116554143B - Preparation process of (S) -nicotine - Google Patents
Preparation process of (S) -nicotine Download PDFInfo
- Publication number
- CN116554143B CN116554143B CN202310401027.0A CN202310401027A CN116554143B CN 116554143 B CN116554143 B CN 116554143B CN 202310401027 A CN202310401027 A CN 202310401027A CN 116554143 B CN116554143 B CN 116554143B
- Authority
- CN
- China
- Prior art keywords
- nicotine
- reaction
- added
- catalyst
- compound
- 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.)
- Active
Links
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims abstract description 52
- 229960002715 nicotine Drugs 0.000 title claims abstract description 38
- 229930182840 (S)-nicotine Natural products 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 66
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- CFONOJVUTZAMCB-UHFFFAOYSA-N 4-oxo-4-(pyridin-3-yl)butanal Chemical compound O=CCCC(=O)C1=CC=CN=C1 CFONOJVUTZAMCB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 8
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- 229960005190 phenylalanine Drugs 0.000 claims description 10
- 238000000746 purification Methods 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 239000011259 mixed solution Substances 0.000 claims 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 abstract description 3
- 125000003963 dichloro group Chemical group Cl* 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000005586 smoking cessation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 241000208125 Nicotiana Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229910002554 Fe(NO3)3·9H2O Inorganic materials 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000208292 Solanaceae Species 0.000 description 1
- 235000002634 Solanum Nutrition 0.000 description 1
- 241000207763 Solanum Species 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003958 fumigation Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960001238 methylnicotinate Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- -1 sodium triacetoxyborohydride Chemical compound 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a preparation process for synthesizing (S) -nicotine, and belongs to the field of chemical synthesis. The synthesis method of the novel (S) -nicotine provided by the invention comprises the steps of reacting 4- (3-pyridyl) -4-oxo butyraldehyde serving as an initial raw material with dichloro serving as a solvent under the catalysis of acetic acid to generate a compound I; under the action of a Cu/ZnFe catalyst, the compound I takes methylene dichloride as a solvent, hydrogen is introduced, and nicotine derivatives are generated through hydrogenation; palladium carbon is used as a catalyst, dichloromethane is used as a solvent, after hydrogenation reaction of nicotine derivatives, palladium carbon is filtered, formaldehyde is added, sodium borohydride is used as a reducing agent, nicotine is generated through reaction, and the (S) -nicotine is purified, wherein the yield is 85.9%, and the purity is 99.2%.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation process of (S) -nicotine.
Background
Nicotine, a chemical name of Nicotine, is an organic compound of formula C 10 H 14 N 2 Molecular weight 162.28, density 1.0071g/cm3, boiling point 247 ℃, melting point-79 ℃, flash point 95 ℃, are extremely toxic, are alkaloids existing in Solanaceae plants (Solanum), are usually mainly existing in natural tobacco, and account for more than 95% of total alkaloids in tobacco.
The application of nicotine is very wide. In agriculture, the nicotine pesticide belongs to plant pesticide, and can be widely used as pesticide for crops such as grain, oil, vegetables, fruit, pasture, etc. due to its features of fumigation, stomach toxicity, rapid degradation, no residue, etc. Is a special raw material for developing medicaments for treating diseases such as cardiovascular diseases, skin diseases, snake venom and the like in medicine; the nicotine can also be used as a clinical first-line smoking cessation drug, and the developed nicotine smoking cessation candy has remarkable clinical smoking cessation effect and becomes one of the safe and effective smoking cessation methods nowadays; nicotinic acid synthesized by nicotine belongs to vitamin B, and can effectively treat Alzheimer's disease, parkinson's disease and other diseases. In the cosmetic industry, nicotinic acid can synthesize nicotinamide, and is a good raw material for daily chemical production of cosmetics and skin care products.
Documents Journal of the Chemical Society, perkin Transactions I,2002 (2), 143-154 report the reaction of 4- (3-pyridyl) -4-oxobutanal and aminoalcohol at-78 ℃ to give nicotinic derivatives using sodium triacetoxyborohydride as a reducing agent.
The method has harsh reaction conditions, and the purity of the obtained product is not high, which is not beneficial to industrial production.
Document Organic Syntheses, [ J ],1998,215-218 reports a process for producing racemic nicotine by a four-step reaction using methyl nicotinate as a raw material.
The method has the advantages of simple reaction, mild condition, low reaction yield, large amount of coal tar and difficult removal.
Document Journal of the American Chemical Society,2015,90-93 reports the synthesis of nicotine from 2-bromo-5-4, 5-dihydropyrrole-2-pyridine under catalytic hydrogenation with chiral catalysts.
The reaction uses an expensive chiral catalyst, has high cost, is unfavorable for industrial production, and has potential safety hazard because the reaction needs to be carried out under high pressure.
In view of the above, the prior art methods for synthesizing nicotine have disadvantages, and there is a need to develop more economical, more efficient and safer synthesis techniques.
Disclosure of Invention
The synthesis method of the novel nicotine provided by the invention is that 4- (3-pyridyl) -4-oxo butyraldehyde is adopted as an initial raw material, and is reacted with L-phenylalanine under the catalysis of acetic acid to generate a compound I; under the action of a Cu/ZnFe catalyst, the compound I takes methylene dichloride as a catalyst, hydrogen is introduced, and nicotine is generated by hydrogenation; palladium carbon is used as a catalyst, dichloromethane is used as a solvent, nicotine derivatives are subjected to hydrogenation reaction, palladium carbon is filtered, formaldehyde is added, sodium borohydride is used as a reducing agent, and the reaction is carried out to generate (S) -nicotine.
The invention provides a preparation process of (S) -nicotine, which is realized by the following technical scheme:
a synthetic method of (S) -nicotine comprises the following reaction routes:
(1) Reacting 4- (3-pyridyl) -4-oxo butyraldehyde with L-phenylalanine to generate a compound I by taking dichloro as a solvent under the catalysis of acetic acid;
(2) Under the action of a Cu/ZnFe catalyst, the compound I takes methylene dichloride as a solvent, hydrogen is introduced, and nicotine is generated by catalytic hydrogenation;
(3) Palladium carbon is used as a catalyst, dichloromethane is used as a solvent, after hydrogenation reaction of the nicotine derivative, the palladium carbon is filtered, formaldehyde and sodium borohydride are added for reaction, and the (S) -nicotine is generated by purification.
Further preferably, the reaction temperature is preferably from-15℃to-25 ℃.
Further preferably, the molar ratio of the 4- (3-pyridyl) -4-oxo-butyraldehyde to the L-phenylalanine is 1:1.5-2.
Further preferably, in the catalytic hydrogenation reaction using methylene dichloride as a solvent, the addition amount of the catalyst Cu/ZnFe is 3% of the mass of the compound I.
Further preferably, the molar amount of the added nicotine derivative and formaldehyde is 1:1.5.
Further preferably, the resulting product is purified with a purification liquid, wherein the purification liquid is a mixture of n-hexane and isopropanol, wherein the volume ratio of n-hexane to isopropanol is 85:15.
The traditional method for preparing and generating (S) -nicotine has harsh reaction conditions, uses expensive chiral catalysts, and has low purity of the obtained product, thus being not beneficial to industrial production. The method has the advantages of safe and reliable reaction, low cost, simple and easily obtained raw materials and catalysts, excellent reaction activity and selectivity, high purity of the obtained product and good industrial amplification prospect.
Detailed Description
Preparation of Cu/ZnFe catalyst
4.86g Zn (NO) 3 ) 2 ·6H 2 O，1.87g Fe(NO 3 ) 3 ·9H2O，1.75g Al(NO 3 ) 3 ·9H 2 O was dissolved in 50mL of distilled water. 30mL (NH) at a concentration of 0.1M was used 4 ) 2 CO 3 The aqueous solution was added dropwise to the above solution at a rate of 2mL/min at 80℃and the mixture was aged at the same temperature for 2 hours. The precipitate was filtered and washed with distilled water, and the solid powder was dried overnight at 100 ℃ and then calcined in air at 400 ℃ for 1 hour. Then 0.18g of Cu (NO) 3 ) 2 ·3H 2 O was dissolved in 1mL of deionized water, and then Cu (NO 3 ) 2 Is added to 1g of ZnFe carrier. The product was dried overnight at 100 ℃ and calcined in air at 300 ℃ for 4 hours to give a Cu/ZnFe catalyst.
All compounds I of this detailed description have the formula: c (C) 18 H 18 N 2 O 3 ，
The specific structural formula is as follows:
the chemical formula of the nicotine derivative is as follows: c (C) 18 H 20 N 2 O 2 ，
The specific structural formula is as follows:
example 1:
to a 100mL three-necked flask, 4- (3-pyridyl) -4-oxobutanal (10 g,1 eq) and L-phenylalanine (21.97 g,2 eq), acetic acid (5 mL), methylene chloride (50 mL) were added, and after completion of the reaction, the acetic acid and methylene chloride were distilled off under reduced pressure and the obtained crude product was recrystallized from ethanol (50 mL) to give compound I in a yield of 88.2% and a liquid phase purity of 99.1%.
Example 2:
to a 100mL three-necked flask, 4- (3-pyridyl) -4-oxobutanal (10 g,1 eq) and L-phenylalanine (21.97 g,2 eq), acetic acid (5 mL), methylene chloride (50 mL) were added, and after completion of the reaction, the acetic acid and methylene chloride were distilled off under reduced pressure and the obtained crude product was recrystallized from ethanol (50 mL) to give compound I in a yield of 90.4% and a liquid phase purity of 99.2%.
Example 3:
to a 100mL three-necked flask, 4- (3-pyridyl) -4-oxobutanal (10 g,1 eq) and L-phenylalanine (16.48 g,1.5 eq), acetic acid (5 mL) and methylene chloride (50 mL) were added, the reaction was carried out at-25℃for 8 hours, and after completion of the reaction, the acetic acid and methylene chloride were distilled off under reduced pressure, and the obtained crude product was recrystallized from ethanol (50 mL) and filtered to give compound I in a yield of 89.5% and a purity of 99% in a liquid phase.
Example 4:
to a 100mL three-necked flask was added compound I (20 g,1 eq), cu/ZnFe catalyst (60 mg), methylene chloride (50 mL), and the mixture was continuously subjected to hydrogenation at 50℃for 10 hours. After the reaction is finished, the temperature is reduced to room temperature, and the Cu/ZnFe catalyst is filtered. The filtrate is concentrated in vacuum to obtain the nicotine derivative with the yield of 88.2% and the purity of 98.5%.
Example 5:
to a 100mL three-necked flask, a nicotine derivative (10 g,1 eq) was added, methylene chloride (50 mL) was added, palladium on carbon was added, and hydrogen gas was introduced to conduct hydrogenation reaction at 60℃for 6 hours. After the reaction, palladium on carbon was filtered, and formaldehyde (1 eq) and sodium borohydride (0.4 eq) were added and heated to 70℃for reaction for 4 hours. Water (20 mL) was slowly added, the solution was extracted and the organic phase was distilled off. The obtained product was purified with a purification solution (n-hexane: isopropanol=85:15), heated, cooled, crystallized, and filtered to obtain purified (S) -nicotine with a product yield of 83.7% and a purity of 99.1%.
Example 6:
to a 100mL three-necked flask, a nicotine derivative (10 g,1 eq) was added, methylene chloride (50 mL) was added, palladium on carbon was added, and hydrogen gas was introduced to conduct hydrogenation reaction at 60℃for 6 hours. After the reaction was completed, palladium on carbon was filtered, and formaldehyde (1.5 eq) and sodium borohydride (0.4 eq) were added and heated to 70℃for reaction for 4 hours. Slowly adding water (20 mL), extracting, separating liquid, steaming the organic phase, purifying the obtained product with purified liquid (n-hexane: isopropanol=85:15), specifically heating, cooling, crystallizing, and filtering to obtain purified (S) -nicotine, wherein the yield of (S) -nicotine is 85.9%, and the purity is 99.2%.
Comparative example 1:
to a 100mL three-necked flask, 4- (3-pyridyl) -4-oxobutanal (10 g,1 eq) and L-phenylalanine (21.97 g,2 eq), acetic acid (5 mL), methylene chloride (50 mL) were added, and after completion of the reaction, the acetic acid and methylene chloride were distilled off under reduced pressure and the crude product obtained was recrystallized from ethanol (50 mL) to give 5.43g of Compound I in a yield of 45.2% and a liquid phase purity of 91.2%.
Comparative example 2:
to a 100mL three-necked flask, 4- (3-pyridyl) -4-oxobutanal (10 g,1 eq) and L-phenylalanine (1.2 eq), acetic acid (5 mL), methylene chloride (50 mL) were added, and after the reaction was completed, the acetic acid and methylene chloride were distilled off under reduced pressure, and the obtained crude product was recrystallized from ethanol (50 mL) to obtain compound I in a yield of 78.2% and a liquid phase purity of 95.5%.
Comparative example 3:
to a 100mL three-necked flask, a nicotine derivative (10 g,1 eq) was added, methylene chloride (50 mL) was added, palladium on carbon was added, and hydrogen gas was introduced to conduct hydrogenation reaction at 60℃for 6 hours. After the reaction was completed, palladium on carbon was filtered, and formaldehyde (1.5 eq) and sodium borohydride (0.4 eq) were added and heated to 70℃for reaction for 4 hours. Water (20 mL) was slowly added, the solution was extracted and the organic phase was distilled off. The product obtained was purified with a purification solution (water: acetonitrile=85:15), heated, cooled, crystallized, filtered to obtain purified (S) -nicotine with a yield of 56.2% and a purity of 91.2%.
Comparative example 4:
to a 100mL three-necked flask, a nicotine derivative (10 g,1 eq) was added, methylene chloride (50 mL) was added, palladium on carbon was added, and hydrogen gas was introduced to conduct hydrogenation reaction at 60℃for 6 hours. After the reaction was completed, palladium on carbon was filtered, and formaldehyde (1.5 eq) and sodium borohydride (0.4 eq) were added and heated to 70℃for reaction for 4 hours. Water (20 mL) was slowly added, the solution was extracted and the organic phase was distilled off. The obtained product was purified with a purification solution (n-hexane: isopropanol=50:50), heated, cooled, crystallized, and filtered to obtain purified (S) -nicotine with a yield of 72.9% and a purity of 93.4%.
While the foregoing describes the embodiments of the present invention, it should be understood that the present invention is not limited to the embodiments, and that various modifications and changes can be made by those skilled in the art without any inventive effort.
Claims (6)
1. A method of preparing (S) -nicotine, the method comprising:
(1) Under the catalysis of acetic acid, using methylene dichloride as a solvent, and reacting 4- (3-pyridyl) -4-oxo butyraldehyde with L-phenylalanine to obtain a compound I;
(2) Under the action of a Cu/ZnFe catalyst, the solvent is methylene dichloride, hydrogen is introduced, and nicotine derivatives are generated through hydrogenation;
(3) Palladium carbon is used as a catalyst, nicotine derivatives are subjected to hydrogenation reaction, the palladium carbon is filtered, formaldehyde and sodium borohydride are added, and the (S) -nicotine is generated by purification.
2. The method for producing (S) -nicotine according to claim 1, wherein the reaction temperature in the step (1) is-15 ℃ to-25 ℃.
3. The method for producing (S) -nicotine according to claim 1, wherein the molar ratio of 4- (3-pyridyl) -4-oxobutanal to L-phenylalanine in step (1) is 1:1.5-2.
4. The method for producing (S) -nicotine according to claim 1, wherein the catalyst Cu/ZnFe of step (2) is added in an amount of 3% by mass of the compound I.
5. The method for producing (S) -nicotine according to claim 1, wherein the molar amount of the nicotine derivative and formaldehyde in step (3) is 1:1.5.
6. The method for preparing (S) -nicotine according to claim 1, wherein the purification method comprises dissolving (S) -nicotine in a mixed solution of n-hexane and isopropanol, heating, cooling, crystallizing, and filtering to obtain purified (S) -nicotine, wherein the mass ratio of n-hexane to isopropanol is 85:15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310401027.0A CN116554143B (en) | 2023-04-14 | 2023-04-14 | Preparation process of (S) -nicotine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310401027.0A CN116554143B (en) | 2023-04-14 | 2023-04-14 | Preparation process of (S) -nicotine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116554143A CN116554143A (en) | 2023-08-08 |
| CN116554143B true CN116554143B (en) | 2024-03-26 |
Family
ID=87488879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310401027.0A Active CN116554143B (en) | 2023-04-14 | 2023-04-14 | Preparation process of (S) -nicotine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116554143B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022105482A1 (en) * | 2020-11-18 | 2022-05-27 | 山东金城医药化工有限公司 | Method for preparing nicotine of high optical purity |
-
2023
- 2023-04-14 CN CN202310401027.0A patent/CN116554143B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022105482A1 (en) * | 2020-11-18 | 2022-05-27 | 山东金城医药化工有限公司 | Method for preparing nicotine of high optical purity |
Non-Patent Citations (1)
| Title |
|---|
| Synthesis of 15N-labelled nornicotine and 15N-labelled nicotine;Giang Vo-Thanh 等;JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS;20011231(第44期);881-888 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116554143A (en) | 2023-08-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110357853B (en) | Synthesis method of (R, S-) nicotine | |
| CN112409327A (en) | Preparation method of high-optical-purity nicotine | |
| CN112745294B (en) | Synthesis method of (R, S-) nicotine | |
| CN1434800A (en) | Pyridine-1-oxide derivative, and process for its transformation into pharmaceutically effective compunds | |
| CN116554143B (en) | Preparation process of (S) -nicotine | |
| US4191828A (en) | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine | |
| JPH01193246A (en) | Production of 2,3-dichloropyridine | |
| JPH0136462B2 (en) | ||
| CN110713471B (en) | Synthetic method of trimetazidine hydrochloride | |
| CN108602758B (en) | Process for preparing trans-4-amino-1-cyclohexanecarboxylic acids and derivatives thereof | |
| CN111233827A (en) | 2, 5-disubstituted selenophene compound and synthetic method thereof | |
| CN111100062A (en) | Synthesis method of donepezil hydrochloride | |
| JP4197763B2 (en) | Method for producing anhydrous 2-amino-1-methoxypropane | |
| CN112625015B (en) | Preparation method of 2- (1, 3-dihydro-2-isobenzofuran) -1-acetophenone compound | |
| CN116178210B (en) | Preparation method of citronellyl nitrile derivative | |
| CN104140376B (en) | A kind of method of synthesizing 5-ALA | |
| JP4397990B2 (en) | Purification method of 3-alkylflavanonol derivatives | |
| CN114933558B (en) | Method for preparing chiral amino compound by catalytic reduction of chiral nitro compound | |
| CN114436803B (en) | Preparation method of 3- (4-chlorophenyl) -1, 5-diphenylpentane-1, 5-dione compound | |
| JPS63295528A (en) | Production of glyoxylic acids | |
| JPH06749B2 (en) | Method for producing aminomethylpyridine | |
| JPS60172964A (en) | Cinnamic acid derivative and its preparation | |
| CN115141140A (en) | Synthetic method of 3, 5-dichloropyridine | |
| CN117105909A (en) | Preparation method of intermediate of lasmidbody | |
| JPS59130832A (en) | 4-halogeno-2-chloro-3-phenylcrotonaldehyde |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |