阅读说明：本技术 一种氨基酸酯盐酸盐溶液的制备方法 (Preparation method of amino acid ester hydrochloride solution ) 是由 李阳 洪永德 姜书华 吴文忠 于 2019-12-12 设计创作，主要内容包括：本发明涉及化合物合成,具体的说是一种氨基酸酯盐酸盐溶液的制备方法。将浓盐酸通过正庚烷搅拌下回流分水,得脱水盐酸；将脱水盐酸与醇于80-150℃下搅拌回流进行酯化反应,即得氨基酸酯盐酸盐。本发明酯化反应直接利用浓盐酸进行反应,避免了使用气体氯化氢的不便利之处和安全隐患；并且在酯化反应过程中使用正庚烷对浓盐酸进行脱水,和分子筛的除水联用,解决了浓盐酸中含水量过大抑制酯化反应的问题。(The invention relates to compound synthesis, in particular to a preparation method of an amino acid ester hydrochloride solution. Refluxing and dividing water of concentrated hydrochloric acid by stirring with n-heptane to obtain dehydrated hydrochloric acid; stirring and refluxing the dehydrated hydrochloric acid and alcohol at 80-150 ℃ for esterification reaction to obtain the amino acid ester hydrochloride. The esterification reaction directly utilizes concentrated hydrochloric acid to carry out reaction, thereby avoiding inconvenience and potential safety hazard caused by using gaseous hydrogen chloride; in addition, n-heptane is used for dehydrating concentrated hydrochloric acid in the esterification reaction process, and the dehydration of the molecular sieve is combined, so that the problem that the esterification reaction is inhibited due to the overlarge water content in the concentrated hydrochloric acid is solved.)

1. A preparation method of an amino acid ester hydrochloride solution is characterized by comprising the following steps: refluxing and dividing water of concentrated hydrochloric acid by stirring with n-heptane to obtain dehydrated hydrochloric acid; stirring and refluxing the dehydrated hydrochloric acid and alcohol at 80-150 ℃ for esterification reaction to obtain the amino acid ester hydrochloride.

2. A process for the preparation of the amino acid ester hydrochloride solution according to claim 1, characterized in that: the weight volume (g/ml) ratio of the n-heptane, the concentrated hydrochloric acid and the alcohol is 1:1-3: 8-10.

3. A process for the preparation of the amino acid ester hydrochloride solution according to claim 1 or 2, characterized in that: the concentrated hydrochloric acid is dehydrated into: dropping concentrated hydrochloric acid into amino acid, stirring at 30-80 deg.C for dissolving, adding n-heptane after dissolving, mixing with water separator at 80-100 deg.C, stirring with n-heptane and water, azeotropy condensing, refluxing, and separating water for 2 hr to obtain dehydrated hydrochloric acid.

4. A process for the preparation of the amino acid ester hydrochloride solution according to claim 3, characterized in that: and (3) stirring and refluxing the dehydrated hydrochloric acid and alcohol at the temperature of 60-130 ℃ for esterification reaction for 10-20h to obtain the amino acid ester hydrochloride.

5. A process for the preparation of the amino acid ester hydrochloride solution according to claim 4, characterized in that: and adding a molecular sieve in the esterification reaction process, wherein the addition amount of the molecular sieve is 2-4 times of the mass of the amino acid.

6. The process for the preparation of the amino acid ester hydrochloride solution according to claim 4, characterized in that: the adding amount of the n-heptane is 0.5-4 times of the mass of the amino acid; wherein the amino acid is aliphatic, aromatic or heterocyclic amino acid; the mass ratio of the amino acid to the concentrated hydrochloric acid is 1: 1-2.

7. The process for the preparation of the amino acid ester hydrochloride solution according to claim 6, characterized in that: the amino acid is alanine, glycine, valine, isoleucine, leucine, phenylalanine or tyrosine.

8. The process for the preparation of the amino acid ester hydrochloride solution according to claim 4, characterized in that: after refluxing and water separation, the mixture is further concentrated and distilled at the temperature of 60-80 ℃ to obtain n-heptane for reuse.

9. A process for the preparation of the amino acid ester hydrochloride solution according to claim 4, characterized in that: the concentration of the concentrated hydrochloric acid is 36-38%.

10. A process for the preparation of the amino acid ester hydrochloride solution according to claim 4, characterized in that: the alcohol is methanol, ethanol or isopropanol; the molecular sieve is a 3A type molecular sieve or a 4A type molecular sieve.

Technical Field

The invention relates to compound synthesis, in particular to a preparation method of an amino acid ester hydrochloride solution.

Background

At present, the proton acid method is most widely applied in the preparation method of synthetic amino acid ester salt. Most of them are used for synthesizing amino acid ester sulfate, but the disadvantages of difficult separation of product mixture, low yield and the like exist. In the synthesis of the amino acid ester hydrochloride, the existence of water can inhibit the esterification reaction due to the problem of large water content of concentrated hydrochloric acid, so the conversion rate is low; furthermore, most of the methods mainly adopt direct introduction of hydrogen chloride gas, but hydrogen chloride is volatile and has strong corrosivity, so that a preparation method which is simple in process and beneficial to industrial production is needed.

The resin catalysis method and the zeolite catalysis method which are started in recent years respectively use strong acid type cation resin and ultrastable zeolite to realize normal temperature esterification and can be repeatedly used, but have the defects of low yield and long processing time of processes such as reaction, elution and the like.

Disclosure of Invention

The invention aims to provide a preparation method of an amino acid ester hydrochloride solution.

In order to achieve the purpose, the invention adopts the technical scheme that:

a preparation method of amino acid ester hydrochloride solution comprises refluxing concentrated hydrochloric acid with n-heptane under stirring for water separation to obtain dehydrated hydrochloric acid; stirring and refluxing the dehydrated hydrochloric acid and alcohol at 80-150 ℃ for esterification reaction to obtain the amino acid ester hydrochloride.

The weight volume (g/ml) ratio of the n-heptane, the concentrated hydrochloric acid and the alcohol is 1:1-3: 8-10.

The concentrated hydrochloric acid is dehydrated into: dropping concentrated hydrochloric acid into amino acid, stirring and dissolving at 30-80 deg.C, adding n-heptane after dissolving, mixing, placing in a water separator, heating to 80-100 deg.C, stirring n-heptane and water, azeotropy, condensing, refluxing, and separating water for 2 hr to obtain dehydrated hydrochloric acid.

The dehydrated hydrochloric acid and alcohol are stirred and refluxed at the temperature of 60-130 ℃ for esterification reaction for 10-20h to obtain amino acid ester hydrochloride; wherein, molecular sieve is added in the esterification reaction to remove water so as to ensure that the esterification reaction is complete.

And adding a molecular sieve in the esterification reaction process, wherein the addition amount of the molecular sieve is 2-4 times of the mass of the amino acid.

The adding amount of the n-heptane is 0.5-4 times of the mass of the amino acid; wherein the amino acid is aliphatic, aromatic or heterocyclic amino acid; the mass ratio of the amino acid to the concentrated hydrochloric acid is 1: 1-2.

The amino acid is alanine, glycine, valine, isoleucine, leucine, phenylalanine or tyrosine.

After refluxing and water separation, the mixture is further concentrated and distilled at the temperature of 60-80 ℃ to obtain n-heptane for reuse.

The concentration of the concentrated hydrochloric acid is 36-38%.

The alcohol is methanol, ethanol or isopropanol; the molecular sieve is a 3A type molecular sieve or a 4A type molecular sieve.

The invention has the advantages that:

1. the esterification reaction directly utilizes concentrated hydrochloric acid to carry out reaction, thereby avoiding inconvenience and potential safety hazard caused by using gaseous hydrogen chloride; the concentrated hydrochloric acid is dehydrated by using n-heptane, so that the problem that the esterification reaction is inhibited due to the overlarge water content in the concentrated hydrochloric acid is solved.

2. In the esterification reaction process, the dehydrated HCl is introduced into the mixture of amino acid and alcohol, the reflux reaction has good reproducibility, the reaction period is short, the product is easy to separate, and meanwhile, the operability of industrial production is improved by further directly using concentrated hydrochloric acid.

3. In the reaction process, n-heptane and water are subjected to azeotropy, and water is separated by using a water separator, so that the aim of reducing the water content in a system can be fulfilled, and the requirement of an esterification reaction can be met; in the reaction process, water is removed once through the water carried by the n-heptane, repeated concentration and water removal are not needed in the esterification step, and only heating, stirring and refluxing are needed.

4. In the reaction process, the reaction mixture after water removal is directly subjected to n-heptane removal and then stirred and refluxed, so that the process of concentrating, removing alcohol and replenishing for many times is omitted, the operation steps are reduced, and the reaction efficiency is improved.

5. And a molecular sieve is used for removing water in the esterification reaction process, so that the esterification reaction is more nearly complete, and higher yield is obtained.

Detailed Description

The following examples are presented to further illustrate embodiments of the present invention, and it should be understood that the embodiments described herein are for purposes of illustration and explanation only and are not intended to limit the invention.