Synthesis method of (R, S-) nicotine

A synthesis method and nicotine technology, applied in the direction of organic chemistry, etc., can solve the problems of complicated separation and purification operation, difficult industrial production, expensive reagents, etc., and achieve the effect of simple operation method, easy large-scale production, and universality.

Active Publication Date: 2019-10-22
JINAN ENLIGHTEN BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Generally speaking, the existing methods for preparing racemic nicotine not only use expensive reagents, but also often adopt low-temperature reaction (or ultra-low temperature), with ma...

Method used

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  • Synthesis method of (R, S-) nicotine
  • Synthesis method of (R, S-) nicotine
  • Synthesis method of (R, S-) nicotine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050]Add 2.85g of magnesium chips and 30ml of anhydrous THF to a clean three-necked flask, install the magnet, replace the condenser with a nitrogen balloon; add 2.2g of ethyl bromide initiator at one time, stir at about 25°C at room temperature, and wait for initiation (heating, Mixed); after triggering, start to drop the mixture of THF and 3-bromopyridine (the mass ratio of THF to 3-bromopyridine is 2:1, 16g 3-bromopyridine and 32g THF), keep the temperature at about 30°C Reaction; after dripping, continue to keep warm for 3 hours, and then cool to about 20°C; start to add the mixture of N-methylpyrrolidone and THF (7g N-methylpyrrolidine and 20gTHF) dropwise, and keep the temperature below 25°C After the dropwise addition, transfer to room temperature to react overnight; the next day, start to drop 6N (ie: 6mol / L) hydrochloric acid at about 25°C to quench the reaction, and adjust the pH value to between 3 and 4; then add 6N alkali The pH value of the solution was adjusted ...

Embodiment 2

[0052] Disperse the obtained 9.15g enamine intermediate in 100ml of methanol, add 1g of 5% Pd / C catalyst, place it in an autoclave, after nitrogen replacement, fill it with 1.0MPa hydrogen, and stir at room temperature overnight; after the reaction, the system The pressure was released, the reaction solution was filtered, and the filtrate was concentrated to obtain crude R,S-nicotine. After distillation, 8.3 g of a colorless and transparent pure product (68-70°C, 0.2 mmHg) was obtained. The GC purity was 99.6%, and the yield was 90%.

[0053] ESI-MS 163.3(M+H), l H NMR (400MHz, CDCl 3 )δ8.54(m,1H),8.50-8.49(m,1H),7.68~7.70(dt,1H),7.24~7.27(dd,1H),3.27-3.23(m,1H),3.08(t, 1H),2.28~2.34(dd,1H),2.25-2.19(m,1H),2.17(s,3H),2.03-1.91(m,1H),1.87-1.80(m,1H),1.76-1.68( m,1H). Such as figure 1 shown by figure 1 It can be seen that the R,S-nicotine prepared by the two-step method of the present application has fewer steps, simple operation, high yield, low cost, and is suitable for in...

Embodiment 3

[0055] Add 2.85g of magnesium chips and 30ml of anhydrous THF to a clean three-necked flask, install the magnet, replace the condenser with a nitrogen balloon; add 2.2g of ethyl bromide initiator at one time, stir at about 25°C at room temperature, and wait for initiation (heating, Mixed); after triggering, start to drop the mixture of THF and 3-bromopyridine (the mass ratio of THF to 3-bromopyridine is 2:1, 16g 3-bromopyridine and 32g THF), keep the temperature at about 35°C Reaction; after dripping, continue to keep warm for 3 hours, and then cool to about 20°C; start to add the mixture of N-methylpyrrolidone and THF (7g N-methylpyrrolidine and 20gTHF) dropwise, and keep the temperature below 20°C After the dropwise addition, transfer to room temperature to react overnight; the next day, start to drop 6N (ie: 6mol / L) hydrochloric acid at about 25°C to quench the reaction, and adjust the pH value to between 3 and 4; then add 6N alkali Adjust the pH value of the solution to ab...

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Abstract

The invention relates to a synthesis method of (R, S-) nicotine. The synthesis method comprises the following steps: with 3-bromopyridine and magnesium chips as raw materials, preparing a 3-bromopyridine Grignard reagent; then adding N-methylpyrrolidone into an above system, performing a condensation reaction, performing a hydrolysis reaction after completion of the reaction, cooling, adjusting the pH to be alkaline, extracting, separating out an organic phase, concentrating, and distilling to obtain an enamine intermediate I; performing a reduction reaction on the enamine intermediate I in the presence of a metal reduction catalyst to obtain a target product R, S-nicotine. By the synthesis method, a two-step method is innovatively provided for preparing the R, S-nicotine, the steps are few, the operation is simple and convenient, the yield is high and the cost is low; in addition, the synthesis method is suitable for industrial scale-up production.

Description

technical field [0001] The invention belongs to the field of (R, S-) nicotine synthesis, and in particular relates to a synthesis method of (R, S-) nicotine. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Nicotine, commonly known as nicotine, is an alkaloid present in Solanaceae plants (Solanum genus) and is also an important component of tobacco. In addition to tobacco, nicotine is also present in the fruits of various Solanaceae plants, such as tomatoes, wolfberries and other plants that contain nicotine, and these vegetables and medicinal materials are recognized as healthy foods that are beneficial to the human body. Because of this, the World Health Organization vi...

Claims

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Application Information

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IPC IPC(8): C07D401/04
CPCC07D401/04
Inventor 高明李新王迦南汪运光李善科
Owner JINAN ENLIGHTEN BIOTECH CO LTD
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