CN106083633B - Synthetic method of isoborneol formamide compound - Google Patents
Synthetic method of isoborneol formamide compound Download PDFInfo
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- CN106083633B CN106083633B CN201610404010.0A CN201610404010A CN106083633B CN 106083633 B CN106083633 B CN 106083633B CN 201610404010 A CN201610404010 A CN 201610404010A CN 106083633 B CN106083633 B CN 106083633B
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- isoborneol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
Abstract
The invention discloses a method for synthesizing isoborneol formamide compounds, which comprises the following steps: 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; sequentially adding aromatic amine and isoborneol formyl halide into a reactor of a second organic solvent, and stirring and refluxing for 4-5 h; and 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. The isoborneol formic acid reacts with the acyl halide to generate isoborneol formyl halide, then the isoborneol formyl halide reacts with the aromatic amine compound to obtain an isoborneol formamide compound, an isoborneol group is introduced into amide, and a product is finally obtained.
Description
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
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.
Example 1
A method for synthesizing isoborneol formamide compounds comprises the following specific steps:
(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.
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.
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 (2)
1. A synthetic method of isoborneol formamide compounds is characterized by comprising the following specific steps:
(1) adding thionyl chloride into a reactor of a 1, 2-dichloroethane solvent by taking isoborneol formic acid as a raw material, heating and stirring, condensing and refluxing, evaporating the solvent and thionyl chloride after the reaction is finished, and then decompressing and evaporating a target product isoborneol formyl chloride;
(2) sequentially adding substituted aniline and the isoborneol formyl chloride obtained in the step (1) into a benzene solvent reactor, wherein the molar ratio of the substituted aniline to the isoborneol formyl is 1-1.1: 1, stirring and refluxing for 4-5h, and tracking the reaction progress by gas phase; after the reaction is finished, cooling to separate out a crude product, purifying by using a methanol or ethanol 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;
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.
2. The method of synthesizing isoborneol carboxamides according to claim 1, wherein the reactors in step (1) and step (2) are both reactors having a hydrogen chloride gas absorption device.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101253155A (en) * | 2005-08-31 | 2008-08-27 | 霍夫曼-拉罗奇有限公司 | 11-beta-hydroxysteroid dehydrogenase-1-inhibitor-diabetes-type 2-1 |
| WO2015138969A1 (en) * | 2014-03-13 | 2015-09-17 | Salk Institute For Biological Studies | Analogs of fexaramine and methods of making and using |
| CN105254530A (en) * | 2015-10-14 | 2016-01-20 | 江西农业大学 | Method for synthesizing Schiff base compound containing camphenyl |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101253155A (en) * | 2005-08-31 | 2008-08-27 | 霍夫曼-拉罗奇有限公司 | 11-beta-hydroxysteroid dehydrogenase-1-inhibitor-diabetes-type 2-1 |
| WO2015138969A1 (en) * | 2014-03-13 | 2015-09-17 | Salk Institute For Biological Studies | Analogs of fexaramine and methods of making and using |
| CN105254530A (en) * | 2015-10-14 | 2016-01-20 | 江西农业大学 | Method for synthesizing Schiff base compound containing camphenyl |
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