CN106083633B

CN106083633B - A kind of synthetic method of isocampanyl carboxamide compound

Info

Publication number: CN106083633B
Application number: CN201610404010.0A
Authority: CN
Inventors: 范国荣; 翁玉辉; 肖转泉; 陈金珠; 王宗德; 王鹏; 陈尚钘
Original assignee: Jiangxi Agricultural University
Current assignee: Jiangxi Agricultural University
Priority date: 2016-06-12
Filing date: 2016-06-12
Publication date: 2021-08-24
Anticipated expiration: 2036-06-12
Also published as: CN106083633A

Abstract

本发明公开了一种异莰烷基甲酰胺类化合物的合成方法，具体步骤如下：以异莰烷基甲酸为原料，在第一有机溶剂的反应器中加入酰卤化试剂，加热搅拌，冷凝回流，反应结束后蒸出溶剂及酰卤化试剂，再减压蒸出目标产物；在第二有机溶剂的反应器中依次加入芳香胺和异莰烷基甲酰卤，搅拌回流4‑5h；反应结束后，冷却析出粗产品，再用第三溶剂进行纯化，干燥，得到异莰烷基甲酰胺类化合物。本发明中异莰烷基甲酸与酰卤化试剂反应生成异莰烷基甲酰卤，再与芳香胺类化合物反应得到异莰烷基甲酰胺类化合物，在酰胺中引入异莰烷基团，最终得到产物，其实验条件温和，步骤简便，时间短，产率高，安全环保，后处理方便。The invention discloses a method for synthesizing isobornylformamide compounds. The specific steps are as follows: using isobornylformic acid as a raw material, adding an acid halide reagent to a reactor of a first organic solvent, heating and stirring, condensing and refluxing , steam the solvent and the acid halide reagent after the reaction, and then steam the target product under reduced pressure; add aromatic amine and isobornyl formyl halide successively in the reactor of the second organic solvent, and stir and reflux for 4-5h; the reaction ends After that, the crude product is cooled and precipitated, purified with a third solvent, and dried to obtain isobornyl carboxamide compounds. In the present invention, isobornylformic acid reacts with an acyl halide reagent to generate isobornylformyl halide, and then reacts with an aromatic amine compound to obtain an isobornylformamide compound, and an isobornane group is introduced into the amide, and finally The obtained product has mild experimental conditions, simple steps, short time, high yield, safety and environmental protection, and convenient post-processing.

Description

Synthetic method of isoborneol formamide compound

Technical Field

The invention relates to the technical field of fine organic synthesis, in particular to a synthesis method of an isoborneol formamide compound.

Background

Many organic amine compounds have certain biological activity and can be used as intermediates for synthesizing amides, Schiff bases, quaternary ammonium salts and the like. Amides are a class of compounds with a special structure of O ═ C — N, and possess a number of biological activities. The compound has wide application in the aspects of tumor resistance, insect repelling, bacteriostasis, insect pest control and the like, particularly, a series of amide compounds are synthesized by taking a plant source compound as a precursor and performing molecular modification through a chemical means, and the compound has good biological activity. Therefore, it has been regarded as one of the popular research fields by long-term attention.

On the other hand, turpentine is a natural renewable resource, and the processed product is widely applied to the fields of chemical industry, pesticides, medicines, fine chemicals and the like, so that better economic benefit is realized. Camphene isomerized from pinene, which is the main component of turpentine, has research reports in the aspects of medicines, spices, antibacterial agents, materials and the like, and also exists in various natural volatile oils such as camphor oil, citronella oil, cedar oil and the like, so that products synthesized by taking camphene as a raw material have potential application values in the industries such as medicines, cosmetics, essence and spices and the like. In recent years, chemical modification of the structure of natural chemicals to synthesize bioactive compounds has become one of the hot research focuses in forestry chemistry and organic synthetic chemistry.

The derivatives synthesized by camphene have better application in the flavor and fragrance industry, but the application reports in other industries are few, and in order to carry out deep activity screening on the camphene derivatives and related application research thereof, the variety and the amount of the compounds need to be increased. Therefore, the isoborneol formamide is obtained through two-step reaction on the basis that isoborneol formic acid is obtained through a series of steps and reaction of camphene. At present, no synthesis method of the isoborneol formamide compound exists.

Disclosure of Invention

The invention aims to provide a method for synthesizing isoborneol formamide compounds with high yield, safety and environmental protection, so as to solve the problems in the background technology.

In order to achieve the purpose, the invention provides the following technical scheme:

a method for synthesizing isoborneol formamide compounds comprises the following specific steps:

(1) adding an acyl halogenation reagent into a reactor of a first organic solvent by taking isoborneol formic acid as a raw material, heating and stirring, condensing and refluxing, evaporating out the solvent and the acyl halogenation reagent after the reaction is finished, and then decompressing and evaporating out a target product isoborneol formyl halide;

(2) sequentially adding aromatic amine and the isoborneol formyl halide obtained in the step (1) into a reactor of a second organic solvent, wherein the molar ratio of the aromatic amine to the isoborneol formyl is 1-1.1: 1, stirring and refluxing for 4-5h, and tracking the reaction progress by a gas phase; after the reaction is finished, cooling to separate out a crude product, purifying by using a third solvent, and drying to obtain the isoborneol formamide compound, wherein the reaction formula is as follows:

wherein, R is substituent groups at different positions on a benzene ring.

As a further scheme of the invention: the acyl halide reagent in the step (1) is thionyl chloride.

As a further scheme of the invention: and (3) in the step (2), the aromatic amine is substituted aniline.

As a further scheme of the invention: the substituted aniline is o-toluidine, p-toluidine, o-chloroaniline, m-chloroaniline, p-chlorobenzyl, o-nitroaniline, m-nitroaniline, o-methoxyaniline, p-bromoaniline or p-methoxyaniline.

As a further scheme of the invention: the reactors in the step (1) and the step (2) are both reactors with hydrogen chloride gas absorption devices.

As a further scheme of the invention: the first organic solvent in the step (1) is 1, 2-dichloroethane; the second organic solvent in step (1) is benzene.

As a further scheme of the invention: the third solvent used in the purification in the step (2) is methanol or ethanol.

Compared with the prior art, the invention has the beneficial effects that:

the invention uses isoborneol formic acid as raw material, firstly reacts with acyl halide reagent to generate isoborneol formyl halide, then reacts with aromatic amine compound to obtain isoborneol formyl amine compound, introduces isoborneol group into amide, and finally obtains aromatic amine amide containing isoborneol. The method has the advantages of mild experimental conditions, simple and convenient steps, short time, high yield, safety, environmental protection and convenient post-treatment.

Detailed Description

The technical solution of the present patent will be described in further detail with reference to the following embodiments.

Example 1

wherein, R is substituent groups at different positions on a benzene ring.

Example 1

(1) adding 91.1g of dry isobornene formic acid and 50g of 1, 2-dichloroethane into a 250mL three-neck flask, slightly heating to dissolve the isobornene formic acid and the 1mL of DMF; a reflux condensing pipe is arranged, and a hydrogen chloride tail gas absorption device is arranged above the reflux condensing pipe; at room temperature, a mixed solution of 89.2g of thionyl chloride and 30g of 1, 2-dichloroethane is dropwise added with a constant pressure dropping funnel while stirring, and the dropping speed is controlled to prevent overheating of the reaction; after the dropwise addition is finished, heating and refluxing are carried out, and heating and stirring are stopped when no hydrogen chloride gas escapes from the tail gas; a distillation device is changed to evaporate the solvent and the thionyl chloride which is not reacted completely, and the target product isoborneol formyl chloride is evaporated under reduced pressure; the molecular formula of the isobornene formyl chloride is C₁₁H₁₇ClO, molecular weight 200.1, colorless transparent liquid, yield 78.5%, boiling point: 117-;

(2) adding 0.05mol of aromatic amine and 60g of benzene into a 150mL dry three-neck flask provided with a reflux condenser pipe and a hydrogen chloride gas absorption device, dropwise adding a mixed solution of 10g of isoborneol formyl chloride and 10g of benzene at room temperature while stirring, heating to about 90 ℃ after dropwise adding, stirring and refluxing, and stopping or tracking the reaction process by gas phase until no hydrogen chloride gas escapes; and after the reaction is finished, standing, cooling to separate out a solid, filtering, leaching with cold benzene, recrystallizing with solid methanol, and drying in vacuum to obtain a solid powdery product of the aromatic amide containing the isobornene.

The product obtained in the step (2) is as follows:

1) n-o-chlorophenyl isobornene formamide with molecular formula of C₁₇H₂₂ClNO, molecular weight 291.14, white solid, yield 79.1%, melting point 126.1-127.1 deg.C;

2) n-m-chlorophenyl isobornene formamide with molecular formula of C₁₇H₂₂ClNO, molecular weight 291.14, white solid, yield 81.8%, melting point 122.2-123.7 ℃;

3) n-p-chlorophenyl isobornene formamide with molecular formula of C₁₇H₂₂ClNO, molecular weight 291.14, white solid, yield 85.5%, melting point 173.1-174.5 deg.C;

4) n- (o-nitrophenyl) isobornene formamide with molecular formula C₁₇H₂₂N₂O₃Molecular weight of 302.16, light yellow solid, yield of 86.8%, melting point of 100.2-101.9 ℃;

5) n- (m-nitrophenyl) isobornene formamide with molecular formula C₁₇H₂₂N₂O₃Molecular weight 302.16, white solid, yield 80.7%, melting point 134.4-135.4 ℃;

6) n-o-tolyl isobornene formamide with molecular formula of C₁₈H₂₅NO, molecular weight 271.19, white solid, yield 84.4%, melting point 149.1-150.5 ℃;

7) n-p-tolyl isobornene formamide with molecular formula of C₁₈H₂₅NO, molecular weight 271.19, white solid, yield 76.4%, melting point 150.0-151.9 ℃;

8) n- (o-methoxyphenyl) isoA bornylformamide; molecular formula C₁₈H₂₅NO₂Molecular weight of

287.19, white solid, 74.6% yield, melting point 104.7-106.4 ℃;

9) n- (p-methoxyphenyl) isobornene formamide with molecular formula of C₁₈H₂₅NO₂Molecular weight of

287.19, white solid, yield 67.3%, melting point 120.7-122.2 ℃;

10) n-p-bromophenylisobornene formamide with molecular formula C₁₇H₂₂BrNO, molecular weight 335.09, white solid, 75.4% yield, 181.5-182.4 ℃ melting point.

Although the preferred embodiments of the present patent have been described in detail, the present patent is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present patent within the knowledge of those skilled in the art.

Claims

1. a synthetic method of isobornyl formamide compound, is characterized in that, concrete steps are as follows:

(1) take isobornyl formic acid as raw material, add thionyl chloride in the reactor of 1,2-dichloroethane solvent, heat and stir, condensate reflux, steam solvent and thionyl chloride after reaction finishes, then reduce Autoclave the target product isobornyl formyl chloride;

(2) in the reactor of benzene solvent, add substituted aniline and the isobornyl formyl chloride obtained in step (1) successively, the mol ratio of substituted aniline and isobornyl formyl is 1-1.1: 1, stirring and refluxing 4 -5h, the progress of the gas phase tracking reaction; after the reaction, cooling and separating out the crude product, then purifying with methanol or ethanol solvent, and drying to obtain isobornyl carboxamide compounds, the reaction formula is:

Wherein, R is a substituent at different positions on the benzene ring;

Described substituted aniline is o-toluidine, p-toluidine, o-chloroaniline, m-chloroaniline, p-chlorobenzene, o-nitroaniline, m-nitroaniline, o-methoxyaniline, p-bromoaniline or p-methoxyaniline aniline.

2. the synthetic method of isobornyl carboxamide compound according to claim 1, is characterized in that, the reactor in described step (1) and step (2) is the reaction with hydrogen chloride gas absorption device device.