阅读说明：本技术 一种盐酸甜菜碱的制备方法 (Preparation method of betaine hydrochloride ) 是由 严选军 佀青峰 邵洪宝 楼航波 徐海宝 于 2021-11-15 设计创作，主要内容包括：本发明提供一种盐酸甜菜碱的制备方法,该方法包括如下步骤：首先在三甲胺水溶液中滴加加入氯乙腈,形成季铵盐中间体,然后再在酸性条件下水解,中间体无需分离一锅烩,最后得到含量高,不含盐的盐酸甜菜碱精品。(The invention provides a preparation method of betaine hydrochloride, which comprises the following steps: firstly, adding chloroacetonitrile dropwise into a trimethylamine aqueous solution to form a quaternary ammonium salt intermediate, then hydrolyzing under an acidic condition, wherein the intermediate does not need to be separated and stewed in one pot, and finally obtaining a high-content and salt-free refined betaine hydrochloride product.)

1. A preparation method of betaine hydrochloride is characterized by comprising the following steps:

step 1: adding 1.95-2.17 parts by weight of 40% trimethylamine aqueous solution into a reactor, stirring and dropwise adding 1 part of chloroacetonitrile at room temperature, and keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process;

step 2: after the dropwise addition is finished, heating to 50-55 ℃, and continuously stirring for reaction for 2-3 hours;

and step 3: after the reaction is finished, adding 4-10 parts by weight of 20% hydrochloric acid, heating to a reflux state, and continuously stirring for reaction for 4-6 hours;

and 4, step 4: after the reaction is finished, evaporating and crystallizing the obtained betaine hydrochloride solution, filtering and collecting separated solid, and performing vacuum drying to obtain a refined betaine hydrochloride product;

the reaction formula is as follows:

Technical Field

The invention belongs to the technical field of feed additives, and particularly relates to a preparation method of betaine hydrochloride.

Background

Due to the structure of betaine, it can provide active methyl group, which can form methyl transferase with cysteine, participate in methyl reaction in organism metabolism, play important role in life activity, and is called as "life methylating agent".

However, because the quaternary ammonium salt and the intramolecular salt of the betaine have strong hygroscopicity, and are easy to absorb moisture in the transportation and storage processes, the use quality is influenced, so that the betaine can be generally prepared into a compound salt form, which is beneficial to transportation and storage, and can develop other effects. Among them, betaine hydrochloride is one of the most important double salt forms, and the betaine hydrochloride can better exert the efficacy of betaine due to high water solubility. Meanwhile, researches show that the betaine hydrochloride also has various pharmacological effects of promoting the regeneration of liver cells, protecting liver function, regulating gastrointestinal dysfunction, treating hangover and the like.

At present, the main preparation methods of betaine include the following methods:

one is prepared by the reaction of trimethylamine gas, chloroacetic acid and caustic soda, the method is a production method commonly applied in China at present, but a small amount of sodium chloride impurities can be introduced into the betaine prepared by the method in the purification process, and the betaine can not meet the requirements of some fields with special requirements on salt content;

the second method is to adopt trimethylamine gas and methyl chloroacetate to react in the presence of an organic solvent to obtain corresponding intermediate ammonium salt, and crack the intermediate ammonium salt at high temperature (150-250 ℃) after separation to obtain a product, wherein the reaction conditions are harsh and difficult to industrialize. Or the obtained intermediate ammonium salt is hydrolyzed to obtain a product, the method can avoid the generation of inorganic salt impurities, but the hydrolysis reaction of the ester belongs to a balanced reaction, the utilization rate of raw materials is unsatisfactory, and the use of trimethylamine gas requires pressure equipment, thereby increasing the operation difficulty;

the third method is prepared by reacting glycine and diazomethane, but since diazomethane is a gas at normal temperature and is explosive, flammable, highly toxic and highly irritant, special conditions are required for transportation, storage and use, so that the cost is high, and the method is not basically adopted at present.

On the basis of summarizing relevant experiences at home and abroad, a new route is provided, new raw materials are adopted, the conversion rate of the reaction is improved, the equipment is simple, the operation is simple and convenient, a solvent and a pressure device are not needed, the raw materials are sold in the market, the price is proper, the supply is sufficient, and the method is provided for further reducing the cost of industrial mass production of products.

Disclosure of Invention

In order to overcome the technical problems, the invention provides a preparation method of betaine hydrochloride, which comprises the following specific scheme:

a preparation method of betaine hydrochloride is characterized by comprising the following steps:

step 1: adding 1.95-2.17 parts by weight of 40% trimethylamine aqueous solution into a reactor, stirring and dropwise adding 1 part of chloroacetonitrile at room temperature, and keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process;

step 2: after the dropwise addition is finished, heating to 50-55 ℃, and continuously stirring for reaction for 2-3 hours;

and step 3: after the reaction is finished, adding 4-10 parts by weight of 20% hydrochloric acid, heating to a reflux state, and continuously stirring for reaction for 4-6 hours;

and 4, step 4: after the reaction is finished, evaporating and crystallizing the obtained betaine hydrochloride solution, filtering and collecting separated solid, and performing vacuum drying to obtain a refined betaine hydrochloride product;

the reaction formula is as follows:

compared with the prior art, the invention has outstanding substantive characteristics and remarkable progress, and particularly has the following advantages:

1. the new process method adopted by the invention has simple steps, and the generated quaternary ammonium salt intermediate can be well dissolved in water, so that the whole production process does not need to use an organic solvent, thereby reducing pollution and simultaneously reducing cost;

2. inorganic salt is not generated in the production process of the new process, the conversion efficiency of raw materials can be effectively improved by utilizing the difference of solubility, and the obtained product has better purity and yield;

3. the raw materials in each step of the method are commercially available, the source is wide, the supply is sufficient, the reaction conditions are relatively mild, the process is simple, the reactions in each step are conventional operations and are easy to control, only trace waste water is generated, the waste water can be further recycled after treatment, and the whole process is relatively compounded with the concept of green chemistry.

Detailed Description

The technical solution of the present invention will be described in detail by the following embodiments.

Example 1

Adding a 40 wt% trimethylamine aqueous solution (162.5g, about 1.1mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (750g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 6 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and performing vacuum drying to obtain 152.1g of refined betaine hydrochloride, wherein the yield is about 99.1%.

The obtained refined betaine hydrochloride product has melting point of 227.2-228.3 deg.C (in different parts)

The solution(s),¹H-NMR(d-DMSO):

δ3.29(9H,s),4.43(2H,s).MS(EI),m/z 119(M-Cl),155(M+H)。

example 2

Adding 40% by weight of trimethylamine aqueous solution (147.5g, 1.0mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20% by weight of hydrochloric acid (230g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 4 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining refined betaine hydrochloride 141.8g after vacuum drying, wherein the yield is about 92.4%.

Example 3

Adding a 40 wt% trimethylamine aqueous solution (155g, about 1.05mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (500g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 148.2g of refined betaine hydrochloride solution after vacuum drying, wherein the yield is about 96.5%.

Example 4

Adding 40% by weight of trimethylamine aqueous solution (147.5g, 1.0mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under the condition of room temperature and stirring, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20% by weight of hydrochloric acid (240g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 4 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 145.3g of refined betaine hydrochloride product after vacuum drying, wherein the yield is about 94.7%.

Example 5

Adding 40% by weight of trimethylamine aqueous solution (157.5g, about 1.07mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 2 hours, adding 20% by weight of hydrochloric acid (550g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 146.6g of refined betaine hydrochloride product after vacuum drying, wherein the yield is about 95.5%.

Example 6

Adding a 40 wt% trimethylamine aqueous solution (162.5g, about 1.1mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (700g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and performing vacuum drying to obtain 150.7g of refined betaine hydrochloride, wherein the yield is about 98.2%.

Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention and not to limit it; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art will understand that: modifications to the specific embodiments of the invention or equivalent substitutions for parts of the technical features may be made; without departing from the spirit of the present invention, it is intended to cover all aspects of the invention as defined by the appended claims.