CN111747925B - A kind of nicotine purification method - Google Patents

Abstract

The present invention provides a method for purifying nicotine, which comprises the following steps: putting the nicotine to be treated into a short-path molecular distiller, rectifying under the conditions of a temperature of 20-60° C. and a pressure of 10-20 mbar, taking heavy components, The heavy components are put into the short-path molecular distiller again, rectified at a temperature of 40-80 °C and a pressure of 0.01-1 mbar, and the light components are taken, and the light components are dissolved in the mobile phase. In the high-speed countercurrent chromatograph for establishing the stationary phase-mobile phase dynamic equilibrium, the nicotine solution is collected by using the ultraviolet detector spectrum or high performance liquid chromatography, and the nicotine solution is concentrated to obtain high-purity nicotine, and the nicotine purification method of the present invention is simple, And the purification method can greatly reduce the production input and improve the purity and yield of nicotine.

Description

A kind of nicotine purification method

technical field

The invention relates to the technical field of purification of natural products, in particular to a method for purifying nicotine.

Background technique

Nicotine, also known as nicotine, is an important pharmaceutical and chemical raw material. It is mainly extracted from tobacco leaves or tobacco stems. At present, lye is used in industrial production to extract free nicotine from tobacco raw materials, and then extracted with organic solvents. After acid extraction and organic solvent extraction, nicotine with relatively high purity is obtained. Since the boiling point of nicotine is quite different from that of conventional organic solvents, there will be some boiling points in the nicotine obtained after rectification and extraction of organic solvents. Higher impurities, such as dehydroaneonicotine, mesmin, cotinine, L(-)-star aniseline, etc. Some of the impurities, such as mesmin and cotinine, are quite close to the boiling point of nicotine. It is difficult to separate these impurities by means of boiling point difference separation. Although the method of adsorption separation using resin can effectively separate different products, it still consumes a lot of solvent and time to clean and restore the resin after separation, so that the overall nicotine The efficiency of purification is reduced, and waste solvents are easily produced.

Therefore, how to provide a nicotine purification method that has industrial application prospects, can effectively purify nicotine, and is not easy to produce three wastes is a technical problem that needs to be solved urgently in this field.

Contents of the invention

In view of this, the present invention proposes a purification method capable of effectively separating nicotine with similar boiling points and producing less waste solvent.

The technical scheme of the present invention is achieved in this way: the present invention provides a kind of nicotine purification method, comprises the following steps:

Step 1. Put the nicotine to be treated into a short-range molecular still, rectify at a temperature of 20-60°C and a pressure of 10-20mbar, and obtain heavy components;

Step 2. Put the heavy component obtained in step 1 into the short-range molecular still, rectify at a temperature of 40-80°C and a pressure of 0.01-1mbar, and take the light component;

Step 3. Dissolve the light components obtained in step 2 in the mobile phase, enter the high-speed countercurrent chromatograph with established stationary phase-mobile phase dynamic equilibrium through the injection valve, and collect nicotine by using ultraviolet detector spectrum or high performance liquid chromatography solution;

Step 4, concentrating the nicotine solution obtained in Step 3 to obtain high-purity nicotine.

On the basis of the above technical solutions, preferably, in step 1, the temperature is 40-60° C., and the pressure is 10-15 mbar.

On the basis of the above technical solution, preferably, in step 2, the temperature is 60-80° C., and the pressure is 0.01-0.05 mbar.

On the basis of the above technical scheme, preferably, in step 3, the method for establishing the stationary phase-mobile phase dynamic equilibrium of the high-speed countercurrent chromatograph includes:

Step 1, prepare stationary phase solvent system and mobile phase solvent system respectively;

Step 2: Fill the high-speed countercurrent chromatograph with the stationary phase, set the temperature of the constant temperature circulator, adjust the speed of the main engine of the high-speed countercurrent chromatograph, and finally pump in the mobile phase and detect it with an ultraviolet detector. When the mobile phase obviously flows out, then High-speed countercurrent chromatography has established stationary phase-mobile phase dynamic equilibrium.

More preferably, the preparation method of the stationary phase solvent system and the mobile phase solvent system comprises mixing and stirring petroleum ether, ethyl acetate, methanol and water, and then standing for stratification, taking the upper layer as the stationary phase, and the lower layer as the mobile phase .

On the basis of the above technical scheme, preferably, the volume ratio of petroleum ether: ethyl acetate: methanol: water is (3-5): (3-5): (4-7): (3-6) .

On the basis of the above technical scheme, preferably, the volume ratio of petroleum ether: ethyl acetate: methanol: water is (3-4): (3-4): (5-6): (5-6) .

On the basis of the above technical solution, preferably, in step 3, the temperature of the constant temperature circulator is 20-30°C.

On the basis of the above technical solutions, preferably, in step 3, the speed of the main engine of the high-speed countercurrent chromatograph is 800-1200r/min.

On the basis of the above technical solutions, preferably, the pumping speed of the mobile phase is 0.5-5ml/min.

Compared with the prior art, the nicotine purification method of the present invention has the following beneficial effects:

(1) The present invention uses a short-range molecular still to perform two rectifications on the crude nicotine product to remove low-boiling impurities and high-boiling impurities respectively, reduce the types of impurities in the crude nicotine product, and then use a high-speed countercurrent chromatograph to separate the impurities. It requires a high-temperature process of conventional rectification, and does not require a large amount of cost caused by resin tower adsorption and resin tower cleaning process. The production efficiency is high, and it can also produce as much pure nicotine as possible, which has a good application prospect;

(2) The entire purification method has simple steps, and the distillation efficiency of the short-range molecular still is high. At the same time, it can prevent the nicotine from being at a higher temperature and avoid the generation of more impurities. Purification of nicotine by countercurrent chromatography can reduce the input of raw materials and increase the yield, and at the same time, the operation method is simple and has good application prospects.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only These are some embodiments of the present invention. Those skilled in the art can also obtain other drawings based on these drawings without creative work.

Fig. 1 is the nicotine solution gas chromatography-mass spectrogram of the heavy component obtained in Example 1;

Fig. 2 is the nicotine solution gas chromatography-mass spectrogram of light component obtained in embodiment 1;

Fig. 3 is the gas chromatography-mass spectrogram of the high-purity nicotine solution obtained in Example 1.

Detailed ways

The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the implementation manners in the present invention, all other implementation manners obtained by persons of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

Example 1

The nicotine purification method of the present embodiment is as follows:

Put the conventionally prepared nicotine with lower purity into the short-range molecular still, keep the temperature in the short-range molecular still at 60°C, and the pressure at 20mbar, rectify the nicotine, and take the heavy components;

Put the heavy component into another short-range molecular still, keep the temperature in the short-range molecular still at 80°C, and the pressure at 1mbar, rectify the heavy component, and take the light component;

Prepare petroleum ether, ethyl acetate, methanol, and water at a volume ratio of 3:3:4:3, mix and stir, stand and separate layers, take the lower layer as the mobile phase, and the upper layer as the stationary phase, and pour it into the high-speed countercurrent chromatograph Inject the stationary phase until the stationary phase is full of the high-speed countercurrent chromatograph, then turn on the main engine of the high-speed countercurrent chromatograph, and adjust the rotation speed to 800r/min, keep the temperature of the constant temperature circulator at 20°C, and inject the sample at a speed of 0.5ml/min Phase, continue to inject samples until there is obvious flow of mobile phase, dissolve the light component in the mobile phase and continue to inject, and use a UV detector to detect the mobile phase, the wavelength of the UV detector is 240nm-280nm, when the UV detector When it is detected that the effluent mobile phase contains the peak shape of nicotine, the mobile phase starts to be collected, and after collection, it is concentrated to obtain high-purity nicotine.

Example 2

The nicotine purification method of the present embodiment is as follows:

Put the conventionally prepared nicotine with lower purity into the short-range molecular still, keep the temperature in the short-range molecular still at 20°C, and the pressure at 10mbar, rectify the nicotine, and take the heavy components;

Put the heavy component into another short-range molecular still, keep the temperature in the short-range molecular still at 40°C, and the pressure at 0.01mbar, rectify the heavy component, and take the light component;

Prepare petroleum ether, ethyl acetate, methanol, and water at a volume ratio of 5:5:7:6, mix and stir, stand and separate layers, take the lower layer as the mobile phase, and the upper layer as the stationary phase, and pour it into the high-speed countercurrent chromatograph Inject the stationary phase until the stationary phase is full of the high-speed countercurrent chromatograph, then turn on the main engine of the high-speed countercurrent chromatograph, and adjust the rotation speed to 1200r/min, keep the temperature of the constant temperature circulator at 30°C, and inject the mobile phase at a speed of 5ml/min , continue to inject samples until there is obvious flow of mobile phase, dissolve the light components in the mobile phase and continue to inject samples, and use a UV detector to detect the mobile phase, the wavelength of the UV detector is 240nm-280nm, when the UV detector detects When the mobile phase flowing out contains the peak shape of nicotine, start to collect the mobile phase, and concentrate after collection to obtain high-purity nicotine.

Example 3

The nicotine purification method of the present embodiment is as follows:

Put the conventionally prepared nicotine with lower purity into the short-range molecular still, keep the temperature in the short-range molecular still at 40°C, and the pressure at 15mbar, rectify the nicotine, and take the heavy components;

Put the heavy component into another short-range molecular still, keep the temperature in the short-range molecular still at 60°C, and the pressure at 0.05mbar, rectify the heavy component, and take the light component;

Prepare petroleum ether, ethyl acetate, methanol, and water at a volume ratio of 4:4:6:6, mix and stir, stand and separate layers, take the lower layer as the mobile phase, and the upper layer as the stationary phase, and pour it into the high-speed countercurrent chromatograph Inject the stationary phase until the stationary phase is full of the high-speed countercurrent chromatograph, then turn on the host of the high-speed countercurrent chromatograph, and adjust the rotation speed to 1000r/min, keep the temperature of the constant temperature circulator at 25°C, and inject the mobile phase at a speed of 3ml/min , continue to inject samples until there is obvious flow of mobile phase, dissolve the light components in the mobile phase and continue to inject samples, and use a UV detector to detect the mobile phase, the wavelength of the UV detector is 240nm-280nm, when the UV detector detects When the mobile phase flowing out contains the peak shape of nicotine, start to collect the mobile phase, and concentrate after collection to obtain high-purity nicotine.

Example 4

The nicotine purification method of the present embodiment is as follows:

Put the conventionally prepared nicotine with lower purity into the short-range molecular still, keep the temperature in the short-range molecular still at 40°C, and the pressure at 12mbar, rectify the nicotine, and take the heavy components;

Put the heavy component into another short-range molecular still, keep the temperature in the short-range molecular still at 60°C, and the pressure at 0.02mbar, rectify the heavy component, and take the light component;

Prepare petroleum ether, ethyl acetate, methanol and water at a volume ratio of 4:4:5:5, mix and stir, let stand to separate layers, take the lower layer as the mobile phase, and the upper layer as the stationary phase, and pour it into the high-speed countercurrent chromatograph Inject the stationary phase until the stationary phase is full of the high-speed countercurrent chromatograph, then turn on the main engine of the high-speed countercurrent chromatograph, and adjust the rotation speed to 1000r/min, keep the temperature of the constant temperature circulator at 25°C, and inject the sample flow at a speed of 2.6ml/min Phase, continue to inject samples until there is obvious flow of mobile phase, dissolve the light component in the mobile phase and continue to inject, and use a UV detector to detect the mobile phase, the wavelength of the UV detector is 240nm-280nm, when the UV detector When it is detected that the effluent mobile phase contains the peak shape of nicotine, the mobile phase starts to be collected, and after collection, it is concentrated to obtain high-purity nicotine.

Perform gas chromatography-mass spectrometry detection on the high-purity nicotine prepared in the above-mentioned Examples 1-4 and the heavy and light components obtained in the middle, and calculate the yield of the high-purity nicotine prepared in Examples 1-4 at the same time , the detection and calculation results are as follows:

The detection result of gained high-purity nicotine is as follows:

The detection result of gained light component is as follows:

The detection results of the obtained heavy components are as follows:

The yield of embodiment 1-4 is as follows

In the nicotine purification method of the present invention, a short-range molecular still is used for preliminary purification, and impurities with large differences in boiling points and other alkaloids are separated. Additional impurities are produced during the distillation process, which affects the quality and yield of nicotine, and the pretreatment of the short-range molecular still can improve the efficiency of purification production, and then use the high-speed countercurrent chromatography to process the nicotine purified by two distillations. For further separation, since some impurities in nicotine are close to the boiling point of nicotine, it is difficult to separate them by conventional rectification, and the temperature of nicotine is relatively high, rectification requires high temperature treatment, and it is easy to generate foreign impurities again. The stationary phase and mobile phase system to separate nicotine, using high-speed countercurrent chromatography for separation can reduce the loss of materials, and does not require a large amount of solvents and solid-phase adsorption materials, which greatly reduces costs, and prevents waste solvents from polluting the environment, avoiding Eliminate the elution step and shorten the production process.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of the present invention. within the scope of protection.

Claims (6)

1. a nicotine purification method, is characterized in that, comprises the steps: Step 1. Put the nicotine to be treated into a short-range molecular still, rectify at a temperature of 20-60°C and a pressure of 10-20mbar, and obtain heavy components; Step 2. Put the heavy component obtained in step 1 into the short-range molecular still, rectify at a temperature of 40-80°C and a pressure of 0.01-1mbar, and take the light component; Step 3. Dissolve the light components obtained in step 2 in the mobile phase, enter the high-speed countercurrent chromatograph with established stationary phase-mobile phase dynamic equilibrium through the injection valve, and collect nicotine by using ultraviolet detector spectrum or high performance liquid chromatography solution; Step 4, concentrating the nicotine solution obtained in Step 3 to obtain nicotine; In step 3, the method for establishing the stationary phase-mobile phase dynamic equilibrium of the high-speed countercurrent chromatograph includes: S1, prepare stationary phase solvent system and mobile phase solvent system respectively; S2. Fill the high-speed countercurrent chromatograph with the stationary phase, set the temperature of the constant temperature circulator, adjust the speed of the main engine of the high-speed countercurrent chromatograph, and finally pump the mobile phase into it and detect it with an ultraviolet detector. Countercurrent chromatography has established stationary phase-mobile phase dynamic equilibrium; The preparation method of the stationary phase solvent system and the mobile phase solvent system comprises mixing and stirring petroleum ether, ethyl acetate, methanol and water, and then standing and layering, taking the upper layer as the stationary phase, and the lower layer as the mobile phase; The volume ratio of petroleum ether: ethyl acetate: methanol: water is (3-5): (3-5): (4-7): (5-6). 2 . The method for purifying nicotine according to claim 1 , wherein in step 1, the temperature is 40-60° C. and the pressure is 10-15 mbar. 3. The method for purifying nicotine according to claim 1, characterized in that, in step 2, the temperature is 60-80°C and the pressure is 0.01-0.05mbar. 4. The method for purifying nicotine according to claim 1, characterized in that, in step 3, the temperature of the constant temperature circulator is 20-30°C. 5. The method for purifying nicotine according to claim 1, characterized in that, in step 3, the speed of the host of the high-speed countercurrent chromatograph is 800-1200r/min. 6. The method for purifying nicotine according to claim 1, characterized in that the pumping speed of the mobile phase is 0.5-5ml/min.

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