CN119899128A - A process for synthesizing ketimine by solvent method - Google Patents
A process for synthesizing ketimine by solvent method Download PDFInfo
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- CN119899128A CN119899128A CN202510085775.1A CN202510085775A CN119899128A CN 119899128 A CN119899128 A CN 119899128A CN 202510085775 A CN202510085775 A CN 202510085775A CN 119899128 A CN119899128 A CN 119899128A
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- ketimine
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
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Abstract
The invention discloses a process for synthesizing ketimine by a solvent method. The process is that raw material ketone, solvent and acid catalyst are put into a reactor, ammonia is introduced to carry out amination reaction, the temperature is 50-110 ℃, after 2-5 hours of reaction, the experiment is finished, and the yield of the product can reach more than 90% through HPLC detection. The invention has the advantages that the reaction pressure is normal pressure, the equipment investment is small, and the yield of the reaction can be greatly improved by adding the organic solvent in the reaction.
Description
Technical Field
The invention belongs to the technical field of fine organic chemical synthesis, and mainly relates to a process for synthesizing ketimine by a solvent method.
Background
Ketimine is a good organic synthesis intermediate and is used in the fields of biological medicine, chemical industry, pesticides and the like. At present, ketone and ammonia are generally used for directly reacting and synthesizing ketimine under the catalysis of ammonium chloride in industry, and the method has the advantages of cheap raw materials, few byproducts, high yield of 85% -95%, and high requirements on reaction devices and conditions. The method can also be prepared by utilizing the composite reaction of the Grignard reagent and the nitrile and then decomposing pure ammonia, but the separation difficulty is increased because the byproducts are sticky substances, the imine is easy to hydrolyze, the yield is between 53 and 64 percent, the reaction time is shortened, the yield is improved to 61 to 81 percent by replacing ammonia with anhydrous methanol to decompose the reaction product of the Grignard reagent and the nitrile, and the ketoxime is adopted as a raw material to be heated and decomposed into ketimine and ketone under the catalysis of carbon dioxide, so that the yield is between 59 and 66 percent.
The basf in patent 200780008620.8 discloses a preparation method of benzophenone imine, which adopts benzophenone to react in ammonia and titanium dioxide to obtain the reaction yield reaching 95 percent. However, the method is a high-pressure reaction, and the equipment investment and the operation cost are high.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a process for synthesizing ketimine by a solvent method.
The aim of the invention is achieved by the following technical scheme. A process for synthesizing ketimine by solvent method comprises the following steps:
step one, putting raw material ketone, a solvent and an acidic substance catalyst into a three-neck flask;
Step two, the left side opening of the three-mouth flask is sealed by a thermometer sleeve, and the middle opening of the three-mouth flask is connected with a water removing device;
Step three, ammonia is continuously introduced into the right side opening of the three-opening flask to carry out amination reaction, the reaction pressure is normal pressure, and water is continuously removed through a water removing device in the reaction process;
and step four, stirring and reacting for 2 to 5 hours, and taking a liquid phase to obtain a ketimine product.
Preferably, the molar ratio of the raw material ketone to the ammonia is 1:1-2, the dosage of the solvent is 2-4 times, preferably 3 times, of the mass of the ketone, and the dosage of the catalyst is 5% -50%, preferably 30% -45%, of the mass of the ketone.
Still further, the process temperature is 50-110 ℃, preferably 80-100 ℃.
Further, the raw ketone is one or a mixture of more of acetone, butanone, benzophenone and diacetone, preferably benzophenone.
Further, the solvent is one or a mixture of more than one of absolute ethyl alcohol, n-butanol, cyclohexanol and dimethyl sulfoxide.
Further, the catalyst is one or a mixture of a plurality of glacial acetic acid, p-toluenesulfonic acid, oxalic acid, an ammonium chloride aqueous solution and a strong acid ion resin.
Furthermore, the water removing device adopts a water separator with a molecular sieve, and continuously removes water through the water separator in the reaction process, or adopts the external circulation distillation to remove water while reacting.
The invention has the advantages that the reaction temperature is lower, the reaction pressure is normal pressure, the equipment investment is smaller, and the organic solvent added in the reaction can greatly improve the yield of the reaction.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art or ordinary skill. FIG. 1 is a chromatogram of a benzophenone imine according to an embodiment of the invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by a person skilled in the art without any inventive effort, are intended to be within the scope of the present invention, based on the embodiments of the present invention.
The invention provides a process for synthesizing ketimine by a solvent method, which adopts the reaction in an organic solvent without pressurization, and an acidic substance catalyst is added, so that the utilization rate of ammonia can be improved by the catalyst and the solvent, and an imine product with higher yield can be obtained.
Example 1
40G of raw material benzophenone, 150mL of cyclohexanol solvent and 3g of glacial acetic acid catalyst are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a dried (500 ℃) molecular sieve, ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermometer sleeve, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 80 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out for HPLC detection, and the benzophenone imine yield is calculated to be 85.3%.
Example 2
40G of raw material benzophenone, 150mL of cyclohexanol solvent and 10g of glacial acetic acid catalyst are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a dried (500 ℃) molecular sieve, ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermometer sleeve, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 80 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out for HPLC detection, and the benzophenone imine yield is calculated to be 86.5%.
Example 2
40G of raw material benzophenone, 150mL of n-butanol solvent and 10g of p-toluenesulfonic acid are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after drying (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is closed by a thermo-well tube, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 80 ℃, magnetic stirring is carried out, after the reaction is carried out for 3 hours, the raw material benzophenone is taken out, placed in a 50mL centrifuge tube, liquid phase is taken out for HPLC detection, and the benzophenone imine yield is calculated to be 88.3%.
Example 3
40G of raw material benzophenone, 150mL of cyclohexanol solvent and 17g of ammonium chloride aqueous solution are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a dried (500 ℃) molecular sieve, ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermometer sleeve, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 100 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out for HPLC detection, and the benzophenone imine yield is calculated to be 95.8%.
Example 4
40G of raw material benzophenone, 150mL of cyclohexanol solvent and 17g of strong acid ion resin are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after drying (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is closed by a thermometer sleeve, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 100 ℃, magnetic stirring is carried out, after 2 hours of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out for HPLC detection, and the benzophenone imine yield is calculated to be 92.2%.
Example 5
40G of raw material benzophenone, 150mL of dimethyl sulfoxide solvent and 17g of strong acid ion resin are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after being dried (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermo-well tube, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 100 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out to carry out HPLC detection, and the benzophenone imine yield is calculated to be 93.2%.
Example 6
40G of raw material benzophenone, 150mL of dimethyl sulfoxide solvent and 17g of strong acid ion resin are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after being dried (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermo-well tube, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 110 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out to carry out HPLC detection, and the yield of benzophenone imine is calculated to be 92.8%.
Example 7
40G of raw material benzophenone, 150mL of n-butanol solvent and 17g of glacial acetic acid are put into a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after drying (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is closed by a thermowell tube, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 110 ℃, magnetic stirring is carried out, after 2 hours of reaction, the raw material benzophenone is taken out, placed into a 50mL centrifuge tube, liquid phase is taken into an HPLC (high performance liquid chromatography) for detection, and the yield of benzophenone imine is calculated to be 94.2%.
Example 8
40G of raw material benzophenone, 150mL of cyclohexanol solvent and 17g of glacial acetic acid are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a dried (500 ℃) molecular sieve, ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is closed by a thermometer sleeve, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 110 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out, HPLC detection is carried out, and the benzophenone imine yield is calculated to be 95.3%.
Example 9
40G of raw material benzophenone, 150mL of dimethyl sulfoxide solvent and 17g of strong acid ion resin are placed in a 500mL three-neck flask, the middle opening of the three-neck flask is connected by a water separator provided with a molecular sieve after being dried (500 ℃), ammonia gas is introduced into the right opening to carry out amination reaction, the left opening is sealed by a thermo-well tube, a mercury thermometer is inserted to measure the reaction temperature, the reaction temperature is controlled at 110 ℃, magnetic stirring is carried out, after 2h of reaction, the raw material benzophenone is taken out and placed in a 50mL centrifuge tube, liquid phase is taken out to carry out HPLC detection, and the benzophenone imine yield is calculated to be 95.2%.
The method for calculating the yield of the benzophenone imine is as shown in figure 1, wherein the yield of the benzophenone imine is calculated through peak area by a chromatogram of the benzophenone imine.
The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any changes or substitutions easily contemplated by those skilled in the art within the scope of the present invention should be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (7)
1. A process for synthesizing ketimine by solvent method is characterized by comprising the following steps:
step one, putting raw material ketone, a solvent and an acidic substance catalyst into a three-neck flask;
Step two, the left side opening of the three-mouth flask is sealed by a thermometer sleeve, and the middle opening of the three-mouth flask is connected with a water removing device;
Step three, ammonia is continuously introduced into the right side opening of the three-opening flask to carry out amination reaction, the reaction pressure is normal pressure, and water is continuously removed through a water removing device in the reaction process;
and step four, stirring and reacting for 2 to 5 hours, and taking a liquid phase to obtain a ketimine product.
2. The process for synthesizing ketimine by solvent method according to claim 1, wherein the molar ratio of raw material ketone and ammonia is 1:1-2, the solvent is 2-4 times of the ketone mass, and the catalyst is 5% -50% of the ketone mass.
3. The process for synthesizing ketimine by solvent process according to claim 2, wherein the process temperature is 50-110 ℃.
4. The process for synthesizing ketimine by using a solvent method according to claim 3, wherein the raw material ketone is one or a mixture of more of acetone, butanone, benzophenone and diacetone.
5. The process for synthesizing ketimine by using a solvent as set forth in claim 4, wherein the solvent is one or a mixture of several of absolute ethyl alcohol, n-butanol, cyclohexanol and dimethyl sulfoxide.
6. The process for synthesizing ketimine by solvent method according to claim 5, wherein the catalyst is one or a mixture of more of glacial acetic acid, p-toluenesulfonic acid, oxalic acid, aqueous solution of ammonium chloride and strongly acidic ionic resin.
7. The process for synthesizing ketimine by using a solvent method according to claim 6, wherein the water removing device adopts a water separator with a molecular sieve, and continuously removes water through the water separator in the reaction process, or adopts external circulation distillation to remove water while reacting.
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| CN202510085775.1A CN119899128A (en) | 2025-01-20 | 2025-01-20 | A process for synthesizing ketimine by solvent method |
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| CN202510085775.1A CN119899128A (en) | 2025-01-20 | 2025-01-20 | A process for synthesizing ketimine by solvent method |
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