阅读说明：本技术 一种制备正壬酸香草酰胺的方法 (Method for preparing n-nonanoic vanilloylamine ) 是由 朱闻雷 于 2020-08-24 设计创作，主要内容包括：本发明涉及一种制备正壬酸香草酰胺的方法,该方法以3-甲氧基-4-羟基苄胺、正壬酸为原料,以二氯甲烷、甲苯、氟苯为溶剂,在芳基硼酸催化作用下脱水反应,制备合成正壬酸香草酰胺；3-甲氧基-4-羟基苄胺、正壬酸的物质的量的比为1.2:1,芳基硼酸的用量为3-甲氧基-4-羟基苄胺的物质的量的10％,脱水反应温度为25℃-85℃,反应时间为20min～5h；该方法还包括脱水缩合反应结束后降温至室温,加水搅拌后静置分层,取油状层,减压蒸馏回收有机溶剂,得到淡黄色透明液体后停止减压蒸馏,剩余液体冷却至室温,强力搅拌,得到正壬酸香草酰胺白色固体粉末。本发明的方法工艺简单、成本低、收率高、原子经济性高、反应条件低、产品纯度高、绿色环保。(The invention relates to a method for preparing vanillic amide n-nonanoate, which takes 3-methoxy-4-hydroxybenzylamine and n-nonanoic acid as raw materials, takes methylene chloride, toluene and fluorobenzene as solvents, and carries out dehydration reaction under the catalysis of aryl boric acid to prepare and synthesize vanillic amide n-nonanoate; the mass ratio of the 3-methoxy-4-hydroxybenzylamine to the n-nonanoic acid is 1.2:1, the dosage of the arylboronic acid is 10 percent of the mass of the 3-methoxy-4-hydroxybenzylamine, the dehydration reaction temperature is 25-85 ℃, and the reaction time is 20 min-5 h; the method also comprises the steps of cooling to room temperature after the dehydration condensation reaction is finished, adding water, stirring, standing for layering, taking an oily layer, carrying out reduced pressure distillation to recover the organic solvent, stopping reduced pressure distillation after obtaining a light yellow transparent liquid, cooling the residual liquid to room temperature, and carrying out strong stirring to obtain the n-nonanoic acid vanilloamide white solid powder. The method has the advantages of simple process, low cost, high yield, high atom economy, low reaction condition, high product purity and environmental protection.)

1. A method for preparing vanilloylamine n-nonanoate is characterized in that 3-methoxy-4-hydroxybenzylamine (1) and n-nonanoate (2) are used as raw materials, a molecular sieve is used as a water absorbent in an organic solvent at a certain temperature, stirring is carried out for a period of time under the catalysis of aryl boric acid, and after a crude product is crystallized and treated, vanillylamide n-nonanoate (3) is obtained, wherein the reaction formula is as follows:

wherein the content of the first and second substances,

the aryl boric acid has a structural formula shown in formula (I)

R₁Is selected from halogen, -CH₂NR₃R₄；

R₂Selected from hydrogen, -CX₃Nitro, cyano, -SO₃H；

R₃，R₄Independently selected from hydrogen, C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6Halogenoalkoxy, C_6-10Aryl radical, C_6-10A heteroaryl group;

x is halogen.

2. The method of claim 1, wherein R is₁Is halogen, R₂Is hydrogen.

3. The method of claim 1, wherein R is₁is-CH₂NR₃R₄，R₂is-CX₃Nitro, cyano, -SO₃H。

4. The method of claim 3, wherein R is₃，R₄Independently selected from C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6A haloalkoxy group.

5. The method of claim 4, wherein R is₃，R₄Independently selected from C_1-6Alkyl radical, C_1-6An alkoxy group.

6. The method of claim 1, wherein the halogen is F, Cl, Br, I.

7. The method of claim 6, wherein the halogen is I.

8. The method of claim 1, wherein the arylboronic acid is one or more of 2- ((N, N-diisopropyl) methyl) phenylboronic acid, 2- ((N, N-dimethyl) methyl) phenylboronic acid, 2- ((N, N-di-tert-butyl) methyl-4-trifluoromethyl) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-nitro) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-sulfonate) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-cyano) phenylboronic acid, o-iodophenylboronic acid, o-bromoboronic acid, o-chlorobenzoronic acid.

9. The method according to any one of claims 2 to 8, wherein the organic solvent is selected from one or more of dichloromethane, chloroform, ethyl acetate, cyclohexane, n-hexane, ethanol, fluorobenzene, tetrahydrofuran, methanol and acetone.

10. The method according to claim 9, wherein the organic solvent is one or more of dichloromethane, fluorobenzene, toluene, tetrahydrofuran and methanol.

11. The method of any one of claims 2 to 8, wherein the temperature is from room temperature to reflux.

12. The method according to claim 11, wherein the temperature is preferably in the range of 25 ℃ to 85 ℃.

13. The process according to any one of claims 2 to 8, wherein the reaction time is from 20min to 5 h.

14. The method according to claim 1, wherein the mass ratio of 3-methoxy-4-hydroxybenzylamine to n-nonanoic acid is 1:1 to 10: 1.

Technical Field

The invention relates to a novel method for preparing n-nonanoic vanilloylamine, in particular to a method for preparing n-nonanoic vanilloylamine by using aryl boric acid as a catalyst.

Background

N-nonanoic acid vanillylyamid (also called synthetic capsaicin) is a natural capsaicin analog, white or pale yellow solid with CAS registry number 404-86-4 and molecular formula C₁₇H₂₇NO₃The molecular weight is 293.4, the melting point is 56-58 ℃, the decomposition temperature is 340 ℃, and the water solubility is 27ppm at 25 ℃. The n-nonanoic acid vanillylamide has wide application in the fields of biological medicines, pesticides, functional coatings and the like. In medicine, n-nonanoic acidThe vanilloylamine can be used as a component of medicaments for treating rheumatic arthritis, neuralgia and the like, and can also be used for clinical dermatology due to the antibacterial and anti-inflammatory effects. In addition, the n-nonanoic acid vanillylamide can be used as a main component of a novel biological pesticide and a main raw material of a pollution-free marine antifouling paint, and can also be used in plastics such as polyethylene, polyvinyl chloride and the like to prevent eating damage of insects and rats. The pungency and irritation of the capsicine are three fifths of that of 8-methyl-N-vanillyl-6-nonenamide, the synthesis cost is not more than one tenth of that of the capsicine, and the capsicine has the potential of replacing natural capsaicin.

The structural formula of nona-orthoacid vanilloylamine is as follows:

Disclosure of Invention

The technical problem to be solved by the invention is to provide a novel method for preparing n-nonanoic vanilloylamine, which takes aryl boric acid as a dehydration condensation catalyst, has simple process, low cost, high yield, high atom economy, low reaction condition, high product purity and environmental protection, and solves the problems of low yield, no environmental protection, complex post-treatment and the like of the method for preparing n-nonanoic vanilloylamine in the prior art.

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

a method for preparing vanilloylamine n-nonanoate takes 3-methoxy-4-hydroxybenzylamine (1, vanillin amine) and n-nonanoic acid (2) as raw materials, takes a molecular sieve as a water absorbent in an organic solvent at a certain temperature, and after stirring and reacting for a period of time under the catalysis of aryl boric acid, a crude product is subjected to post-treatment to obtain vanillylamine n-nonanoate (3), wherein the reaction formula is as follows:

wherein the arylboronic acid has the structural formula shown in formula I

R₁Is selected from halogen, -CH₂NR₃R₄；

R₂Selected from hydrogen, -CX₃Nitro, cyano, -SO₃H；

R₃，R₄Independently selected from hydrogen, C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6Halogenoalkoxy, C_6-10Aryl radical, C_6-10A heteroaryl group;

x is halogen.

The method for preparing the n-nonanoic acid vanillylamide also comprises the steps of cooling to room temperature after the dehydration condensation reaction is finished, adding water, stirring, standing for layering, taking an oily layer, carrying out reduced pressure distillation to recover an organic solvent, stopping reduced pressure distillation after a light yellow transparent liquid is obtained, cooling the residual liquid to room temperature, and carrying out strong stirring to obtain n-nonanoic acid vanillylamide white solid powder.

Preferably, said R is₁When it is halogen, R₂Is hydrogen; or R₁is-CH₂NR₃R₄When R is₂is-CX₃Nitro, cyano, -SO₃H。

Preferably, R₃，R₄Independently selected from C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy radical, C_1-6A haloalkoxy group; further preferably, R₃，R₄Independently selectFrom C_1-6Alkyl radical, C_1-6An alkoxy group.

Preferably, the halogen is F, Cl, Br, I; further preferably I.

Preferably, the specific arylboronic acid is one or more of 2- ((N, N-diisopropyl) methyl) phenylboronic acid, 2- ((N, N-dimethyl) methyl) phenylboronic acid, 2- ((N, N-di-tert-butyl) methyl-4-trifluoromethyl) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-nitro) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-sulfo) phenylboronic acid, 2- ((N, N-diisopropyl) methyl-4-cyano) phenylboronic acid, o-iodophenylboronic acid, o-bromobenzeneboronic acid, o-chlorobenzeneboronic acid.

Preferably, the organic solvent is selected from one or more of dichloromethane, chloroform, ethyl acetate, cyclohexane, n-hexane, ethanol, fluorobenzene, toluene, tetrahydrofuran, methanol and acetone; further preferably, the organic solvent is one or more of dichloromethane, chloroform, n-hexane, toluene, fluorobenzene, tetrahydrofuran and methanol; further, the organic solvent is preferably one or more of dichloromethane, toluene and fluorobenzene.

Preferably, the reaction temperature is from room temperature to reflux, and further, the temperature is preferably from 25 ℃ to 85 ℃.

Preferably, the condensation reaction time is 20 min-5 h; further, the reaction time is preferably 30min to 3.5 hours.

Preferably, the mass ratio of the reaction raw material 3-methoxy-4-hydroxybenzylamine (1) to the n-nonanoic acid (2) is 1: 1-10: 1; the mass ratio of the further substances is 1.5: 1-3: 1; more preferably, the amount ratio of the substances is 1.2:1 to 2: 1.

Preferably, the molecular sieve isAnd (3) a molecular sieve.

Preferably, the reduced pressure distillation temperature is 40-70 ℃; further, the reduced pressure distillation temperature is 50-65 ℃; further, the reduced pressure distillation temperature was 60 ℃.

Preferably, the strong stirring crystallization time is 10 min-2 h; further, the stirring time is 20-75 min; further, the stirring time was 25 min.

The beneficial improvements obtained by the present invention are:

(1) the invention adopts aryl boric acid to catalyze n-nonanoic acid and vanillin amine to directly dehydrate to prepare the n-nonanoic acid vanillic amide, thereby avoiding a large amount of hydrogen chloride and sulfur dioxide generated by using thionyl chloride to generate acyl chloride to harm harmful gases of the environment. As no hydrogen chloride is generated in the reaction, alkali substances such as sodium hydroxide and the like are not required to be added for adjusting the pH value in the post-treatment, so that the pollution of a large amount of sodium salt is avoided, and the post-treatment is relatively simple.

(2) Under the catalysis of aryl boric acid, the yield of the target product is more than 95%, the purity is more than 99%, recrystallization is not needed for purification, and the use of a large amount of organic solvent is avoided.

Detailed Description

The following examples further illustrate the embodiments of the present invention in detail.