阅读说明：本技术 一种利用桐油制备桐油酸酰胺的方法 (Method for preparing elaeostearic acid amide by using tung oil ) 是由 黄立新 成江 张彩虹 谢普军 于 2019-07-01 设计创作，主要内容包括：本发明公开一种利用桐油制备桐油酸酰胺的方法。该方法利用桐油在催化剂作用下反应合成桐油酸酯,将其与胺基化合物反应制备桐油基酰胺,进一步经重结晶纯化得到具有抗菌活性的桐油酸酰胺衍生物。本发明与现有技术相比,本产品原料简单易得,方法操作简单。随着酰胺基团的引入,衍生物对金黄葡萄球菌、大肠杆菌均具有较好的抗菌活性,赋予了桐油分子新的生物活性。显示出在医药领域的广阔前景,同时为桐油的深加工利用提供途径。(The invention discloses a method for preparing elaeostearic acid amide by using tung oil. The method utilizes tung oil to react and synthesize tung oil ester under the action of a catalyst, the tung oil ester reacts with an amino compound to prepare tung oil based amide, and the tung oil based amide derivative with antibacterial activity is further obtained by recrystallization and purification. Compared with the prior art, the invention has the advantages of simple and easily obtained raw materials and simple method operation. With the introduction of amide groups, the derivatives have better antibacterial activity on staphylococcus aureus and escherichia coli, and endow new biological activity to tung oil molecules. Shows wide prospect in the field of medicine and provides a way for deep processing and utilization of tung oil.)

1. A method for preparing elaeostearic acid amide by using tung oil is characterized by comprising the following steps:

the first step is as follows: preparing eleostearic acid ester: weighing tung oil and primary alcohol according to a certain molar ratio, adding into a methanol solution of a proper amount of potassium hydroxide, heating and refluxing at a certain temperature, and carrying out an ester exchange reaction. After the reaction is finished, adding a proper amount of distilled water to wash for three times, and extracting with a proper amount of n-hexane. And distilling the upper layer liquid under reduced pressure to obtain eleostearate.

The second step is that: amidating eleostearic acid: weighing eleostearic acid ester and an amino compound according to a molar ratio of 1: 1-1.2, adding a proper amount of sodium methoxide in methanol solution into methyl eleostearate, slowly adding primary amine, then starting heating reflux reaction, carrying out thin-layer chromatography tracking detection, and adding a proper amount of water for washing after the reaction is completed. Adding petroleum ether, shaking for extraction, collecting the upper layer liquid, removing solvent under reduced pressure, and drying with anhydrous sodium sulfate. And adding absolute ethyl alcohol with the volume ratio of 1: 0.5-3 into the crude product, recrystallizing at low temperature, filtering, and evaporating the solvent to dryness to obtain the corresponding elaeostearic acid amide derivative.

2. The method of claim 1, wherein the tung oil is extracted from unprocessed seeds of tung oil tree of the genus erythrina of the family Euphorbiaceae.

3. As claimed in claim 1, eleostearic acid is the major fatty acid in tung oil, 9,11, 13-octadecenoic acid.

4. The first step of claim 1, wherein the molar ratio of the primary alcohol to the tung oil is 1: 1-5, the reaction temperature is 50-70 ℃, and the reaction time is 1-5 h.

5. The first step of claim 1, wherein the concentration of the methanolic solution of potassium hydroxide is 1 to 2mol/L and the amount of n-hexane added is 20 to 30 mL.

6. As in the second step of claim 1, the eleostearic acid ester compound is preferably a lower fatty acid ester selected from methyl eleostearate, ethyl eleostearate or isopropyl eleostearate.

7. The second step of claim 1, wherein the amine-based compound in the second step is preferably an aliphatic amine, an aromatic amine, a monoamine, a diamine or a polyamine, and specifically, aniline, p-chloroaniline, 4-methoxyaniline, 4-trifluoromethoxyaniline, o-methylcyclohexylamine, or the like.

8. The second step of claim 1, wherein the molar ratio of the amine reacted with eleostearate is 1:1 to 1.3, the reaction temperature is 50 to 80 ℃, and the reaction time is 1 to 5 hours.

9. The second step of claim 1 wherein the tung oil acid amide derivative has the general structural formula:

wherein: r represents phenyl, p-chlorophenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, or o-methylcyclohexyl. Among the preferred compounds of formula (I) are: (a) tung benzamide; (b) p-chlorotung benzamide; (c) 4-methoxy tung benzamide; (d) 4-trifluoromethoxytung benzamide; (e) o-methylcyclohexylamine.

10. The second step of claim 1, wherein the volume ratio of the amide derivative to methanol is 1:1 to 10, the recrystallization temperature is-5 to-25 ℃, and the recrystallization time is 3 to 12 hours.

Technical Field

The invention relates to a preparation method of a tung oil-based amide derivative with antibacterial activity, in particular to a method for preparing a tung oil-based amide derivative with antibacterial activity by using tung oil as a raw material.

Background

The tung oil is a natural vegetable oil extracted from tung oil seeds. China has the most abundant tung oil resources and is the largest tung oil producing country. The annual output reaches more than 10 ten thousand tons and accounts for 80 percent of the world tung oil. The main component of the tung oil is triglyceride of eleostearic acid, which is the main fatty acid in the tung oil. At present, China has low utilization technology level of tung oil, and the tung oil is mainly directly used as an anticorrosive coating or indirectly used as biodiesel conversion and modified resin. The Chinese patent with the publication number of CN103601703A discloses a method for preparing epoxidized methyl eleostearate from tung oil, which takes tung oil as a raw material, obtains the methyl eleostearate through ester exchange reaction, and synthesizes the epoxidized methyl eleostearate through epoxidation reaction under the action of a solid acid catalyst; the Chinese patent with the publication number of CN103881341A discloses a tung oil derivative modified unsaturated polyester resin composition, which is heated, reacted and cured after an initiator and an accelerator are added to form a tung oil derivative monomer and unsaturated polyester macromolecule blended structure compound; the Chinese invention patent with the publication number of CN102604015A discloses a methyl-esterified tung oil modified aqueous polyurethane emulsion to prepare a modified aqueous polyurethane emulsion; the above inventions all use tung oil as raw material, but do not relate to biological application using tung oil as raw material. The amide and the derivative thereof have broad-spectrum biological activity and are widely applied to the fields of industry, agriculture, medicine, molecular biology, analytical chemistry, daily life and the like. As plant regulators and herbicides in agriculture; in the aspect of medicine, the medicine is used as anti-AIDS medicine, anti-cancer medicine and anti-tuberculosis medicine; the prior research shows that the introduction of amide groups can enable the compound to have stronger biological activity, thereby improving the potential application prospect of the compound.

Disclosure of Invention

The invention provides a preparation method of a tung oil-based amide derivative with antibacterial activity by using tung oil as a raw material aiming at a special group of tung oil acid based on the problems of less development and low utilization rate in the aspect of the bioactivity of tung oil, and provides a new way for deep processing and utilization of tung oil.

In order to achieve the purpose, the invention provides a method for preparing elaeostearic acid amide by using tung oil, which comprises the following steps:

the first step is as follows: preparing eleostearic acid ester: weighing tung oil and primary alcohol according to a certain molar ratio, adding into a methanol solution of a proper amount of potassium hydroxide, heating and refluxing at a certain temperature, and carrying out an ester exchange reaction. After the reaction is finished, adding a proper amount of distilled water to wash for three times, and extracting with a proper amount of n-hexane. And distilling the upper layer liquid under reduced pressure to obtain eleostearate.

The second step is that: amidating eleostearic acid: weighing eleostearic acid ester and an amino compound according to a molar ratio of 1: 1-1.2, adding a proper amount of sodium methoxide in methanol solution into methyl eleostearate, slowly adding primary amine, then starting heating reflux reaction, carrying out thin-layer chromatography tracking detection, and adding a proper amount of water for washing after the reaction is completed. Adding petroleum ether, shaking for extraction, collecting the upper layer liquid, removing solvent under reduced pressure, and drying with anhydrous sodium sulfate. And adding absolute ethyl alcohol with the volume ratio of 1: 0.5-3 into the crude product, recrystallizing at low temperature, filtering, and evaporating the solvent to dryness to obtain the corresponding elaeostearic acid amide derivative.

The tung oil is squeezed from unprocessed seeds of tung oil tree of the genus erythrina of the family Euphorbiaceae.

The eleostearic acid is the main fatty acid in the eleostearic oil, and is 9,11, 13-octadecenoic acid.

The mole ratio of the primary alcohol reacted with the tung oil in the first step is 1: 1-5, the reaction temperature is 50-70 ℃, and the reaction time is 1-5 hours. The concentration of the methanol solution of potassium hydroxide is 1-2 mol/L, and the addition amount of n-hexane is 20-30 mL.

The eleostearic acid ester compound in the second step is preferably a lower fatty acid ester, and is one of methyl eleostearate, ethyl eleostearate or isopropyl eleostearate.

The amine-based compound in the second step is preferably an aliphatic amine, an aromatic amine, a monoamine, a diamine, or a polyamine. Specifically, aniline, p-chloroaniline, 4-methoxyaniline, 4-trifluoromethoxyaniline, o-methylcyclohexylamine and the like can be mentioned.

In the second step, the tung oil acid amide derivative has the following structural general formula:

wherein: r represents phenyl, p-chlorophenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, or o-methylcyclohexyl. Among the preferred compounds of formula (I) are: (a) tung benzamide; (b) p-chlorotung benzamide; (c) 4-methoxy tung benzamide; (d) 4-trifluoromethoxytung benzamide; (e) o-methyl cyclohexylamine;

the molar ratio of the amine reacted with the eleostearate in the second step is 1: 1-1.3, the reaction temperature is 50-80 ℃, and the reaction time is 1-5 hours. The volume ratio of the amide derivative to the ethanol is 1: 1-10, the recrystallization temperature is-5 to-25 ℃, and the recrystallization time is 3-12 h.

Advantageous effects

Compared with the prior art, the invention provides a preparation method of tung oil-based amide derivatives, the raw materials of the product are simple and easy to obtain, the method is simple to operate, and a way is provided for deep processing and utilization of tung oil, which is specifically shown in the following steps: (1) the wood oil which is a unique forest product in China is used as a raw material, and the yield is high, simple and easy to obtain. (2) The introduction of the amide group endows eleostearic acid molecules with new biological activity, and has wide prospect in the field of medicine.

Drawings

FIG. 1 is an infrared spectrum of an ethanol solution of tung benzamide.

FIG. 2 is an infrared spectrum of an ethanol solution of p-chlorotung benzamide.

Detailed Description