532-12-7Relevant academic research and scientific papers
Interconversion of nicotine enantiomers during heating and implications for smoke from combustible cigarettes, heated tobacco products, and electronic cigarettes
Moldoveanu, Serban C.
, p. 667 - 677 (2022/02/02)
Physiological properties of (R)-nicotine have differences compared with (S)-nicotine, and the subject of (S)- and (R)-nicotine ratio in smoking or vaping related items is of considerable interest. A Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method for the analysis of (S)- and (R)-nicotine has been developed and applied to samples of nicotine from different sources, nicotine pyrolyzates, several types of tobacco, smoke from combustible cigarettes, smoke from heated tobacco products, e-liquids, and particulate matter obtained from e-cigarettes aerosol. The separation was achieved on a Chiracel OJ-3 column, 250 × 4.6 mm with 3-μm particles using a nonaqueous mobile phase. The detection was performed using atmospheric pressure chemical ionization (APCI) in positive mode. The only transition measured for the analysis of nicotine was 163.1 → 84.0. The method has been summarily validated. For the analysis, the samples of tobacco and smoke from combustible cigarettes were subject to a cleanup procedure using solid phase extraction (SPE). It was demonstrated that nicotine upon heating above 450°C for several minutes starts decomposing, and some formation of (R)-enantiomer from a sample of 99% (S)-nicotine is observed. An analogous process takes place when a 99% (R)-nicotine is heated and forms low levels of (S)-nicotine. This interconversion has the effect of slightly increasing the content of (R)-nicotine in smoke compared with the level in tobacco for combustible cigarettes and for heated tobacco products. The (S)/(R) ratio of nicotine enantiomers in e-liquids was identical with the ratio for the particulate phase of aerosols generated by e-cigarette vaping.
Synthesis method of nicotine
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, (2021/07/10)
The invention belongs to the technical field of nicotine synthesis, and particularly relates to a synthesis method of nicotine. The invention discloses a synthesis method of nicotine. The synthesis method comprises the following steps: S1, synthesizing 1-(1-butenyl)-3-nicotyl-2-pyrrolidone, namely reacting 1-(1-butenyl)-pyrrolidone with nicotine ethyl ester under the condition of NaH catalysis by using an N,N-dimethyl formamide solution carrier to obtain the 1-(1-butenyl)-3-nicotyl-2-pyrrolidone; S2, synthesizing 3-cyclopentenyl amino-pyridine, namely concentrating the 1-(1-butenyl) 3-nicotinyl-2-pyrrolidone obtained in the step S1 under a certain condition, so as to obtain the 3-cyclopentenyl amino-pyridine, S3, synthesis of a nicotine precursor: introducing hydrogen into 3-cyclopentenyl amino-pyridine under the action of a Pd/C catalyst to obtain the nicotine precursor; and S4, synthesizing nicotine, namely obtaining nicotine from the nicotine precursor obtained in S3 under the action of formaldehyde and formic acid, wherein the chemical formulas are shown in specification.
Method for preparing nicotine
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Paragraph 0060-0065, (2020/04/22)
The invention relates to a method for preparing nicotine. The method comprises the following steps: (1) adding N-Cbz pyrrolidone, nicotinate, an alkaline catalyst and a reaction solvent into a reaction container, carrying out a reaction, quenching until the system is neutral, and removing the reaction solvent to obtain a first solid mixture; (2) adding the first solid mixture into an acidic solution, and carrying out a reflux reaction to obtain a second reaction mixture; and (3) adding formic acid or formate solid and a formaldehyde solution into the second reaction mixture, reacting, and purifying the product to obtain racemic nicotine. The preparation method disclosed by the invention has high yield, and the prepared racemic nicotine and the S-nicotine have high purity.
Synthesis method of racemic nicotine
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Paragraph 0049-0052, (2021/01/04)
The invention discloses a synthesis method of racemic nicotine. The method comprises the following steps: S1, introducing 3-(1-pyrrolin-2-yl) pyridine, a solvent and hydrogen into a first fixed bed reactor filled with a metal catalyst, and cooling at an outlet to obtain a crude product 3-(1-pyrrolidin-2-yl) pyridine mixed solution; and S2, taking the crude product 3-(1-pyrrolidine-2-yl) pyridine and a methylation reagent to pass through a solid second fixed bed reactor filled with a solid base catalyst, and cooling at an outlet to obtain racemic nicotine. The continuous flow fixed bed method is used for preparing racemic nicotine so that the continuity of production is realized, the reaction time is shortened, the reaction operation is simplified, the solvent consumption is reduced, the discharge of waste water and waste liquid is reduced, and the catalyst is convenient to recover.
ENANTIOMERIC SEPARATION OF RACEMIC NICOTINE BY ADDITION OF AN O,O'-DISUBSTITUTED TARTARIC ACID ENANTIOMER
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Page/Page column 8; 17, (2019/07/13)
The present invention relates to a method of separating racemic nicotine of Formula (l-a) as a mixture of the (R)- and (S)-enantiomers into the enantiomerically pure (S)- and (R)-nicotine represented by Formula (l-b) and (l-c), by adding a mixture of the L- and the D-enantiomer of a O,O'-disubstituted tartaric acid, wherein the molar ratio of the L- to the D-enantiomer is from 80:20 to 95:5, and obtaining the (S)-nicotine of formula (l-b), or by adding O,O'-dibenzoyl-D-tartaric acid and obtaining the (R)-nicotine of formula (l-c).
PREPARATION OF RACEMIC NICOTINE BY REACTION OF ETHYL NICOTINATE WITH N-VINYLPYRROLIDONE IN THE PRESENCE OF AN ALCOHOLATE BASE AND SUBSEQUENT PROCESS STEPS
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Page/Page column 14-16, (2019/07/13)
The present invention relates to a method of preparing racemic nicotine comprising: (i) reacting ethyl nicotinate and N-vinylpyrrolidone in the presence of an alcoholate base to 3-nicotinoyl-1-vinylpyrrolidin-2-one; (ii) reacting the 3-nicotinoyl-1-vinylpyrrolidin-2-one with an acid to myosmine; (iii) reducing the myosmine to nornicotine using a reducing agent; and (iv) methylating the nornicotine to obtain the racemic nicotine.
Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists
Wang, Junwei,Song, Qiao,Xu, Anhua,Bao, Yu,Xu, Yungen,Zhu, Qihua
, p. 15 - 25 (2017/03/02)
Opioid receptors play an important role in both behavioral and mood functions. Based on the structural modification of LY2456302, a series of aminobenzyloxyarylamide derivatives were designed and synthesized as κ opioid receptor antagonists. The κ opioid receptor binding ability of these compounds were evaluated with opioid receptors binding assays. Compounds 1a-d showed high affinity for κ opioid receptor. Especially for compound 1c, exhibited a significant Kivalue of 15.7?nM for κ opioid receptor binding and a higher selectivity over μ and δ opioid receptors compared to (±)LY2456302. In addition, compound 1c also showed potent κ antagonist activity with κ IC50?=?9.32?nM in [35S]GTP-γ-S functional assay. The potential use of the representative compounds as antidepressants was also investigated. The most potent compound 1c not only exhibited potent antidepressant activity in the mice forced swimming test, but also displayed the effect of anti-anxiety in the elevated plus-maze test.
NICOTINE COMPOSITION FOR VAPING DEVICES AND VAPING DEVICES EMPLOYING THE SAME
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Paragraph 0080; 0081, (2017/08/01)
A composition suitable for use in a vaping device includes a nicotine product that includes a synthetic nicotine that is substantially free of one or more contaminants and/or impurities normally associated with tobacco-derived nicotine. For example, the synthetic nicotine is substantially free of one or more of nicotine-1'- N-oxide, nicotyrine, nornicotyrine, 2',3-bipyridyl, cotinine, anabasine, and/or anatabine. The composition further comprises one or more pharmaceutically acceptable excipients, additives and/or solvents.
NICOTINE REPLACEMENT THERAPY PRODUCTS COMPRISING SYNTHETIC NICOTINE
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Paragraph 0095, (2017/08/01)
A composition suitable for use in nicotine replacement therapy products includes a nicotine product that includes a synthetic nicotine that is substantially free of one or more contaminants and/or impurities normally associated with tobacco-derived nicotine. For example, the synthetic nicotine is substantially free of one or more of nicotine-1′-N-oxide, nicotyrine, nornicotyrine, 2′,3-bipyridyl, cotinine, anabasine, and/or anatabine. The composition further comprises one or more pharmaceutically acceptable excipients, additives and/or carriers. The nicotine replacement therapy products may include any number of such products, including transdermal nicotine delivery patches, nicotine gums, synthetic chewing tobacco, synthetic snuff, and synthetic strips (e.g., dissolvable synthetic tobacco). Additionally, a method of treating nicotine addiction includes administering a nicotine replacement composition, e.g., via a nicotine replacement therapy product, to a user.
A Hofmann Rearrangement-Ring Expansion Cascade for the Synthesis of 1-Pyrrolines: Application to the Synthesis of 2,3-Dihydro-1H-pyrrolo[2,1-a]isoquinolinium Salts
Huang, He,Yang, Qinghua,Zhang, Qianqian,Wu, Jie,Liu, Yizhen,Song, Chuanjun,Chang, Junbiao
, p. 1130 - 1135 (2016/04/19)
Treatment of cyclobutanecarboxamide with bis(trifluoroacetoxy)iodobenzene, PhI(OCOCF3)2, resulted in the formation of 1-pyrroline via Hofmann rearrangement of the former followed by in situ ring expansion reaction of the cyclobutylamine intermediate. Further elaboration of this methodology to the synthesis of 2,3-dihydro-1H-pyrrolo[2,1-a]isoquinolinium salts has also been described.
