Process for synthesizing ketimine by solvent method

Abstract

The invention discloses a process for synthesizing ketimine by a solvent method. The process comprises the following steps: putting a raw material ketone, a solvent and an acidic material catalyst into a reactor, introducing ammonia to carry out amination reaction at the temperature of 50-110 DEG C for 2-5 hours, ending the experiment, and detecting the product by HPLC (High Performance Liquid Chromatography), so that the yield can reach more than 90%. The method has the advantages that the reaction pressure is normal pressure, and the equipment investment is small; the organic solvent added in the reaction can greatly improve the yield of the reaction.

Description

Technical Field

[0001] 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 Art

[0002] Ketimine is a good organic synthesis intermediate, used in the fields of biomedicine, chemical industry, pesticide, etc. At present, the industry generally adopts the direct reaction of ketone and ammonia under the catalysis of ammonium chloride to synthesize ketimine. This method has cheap raw materials, few by-products, and the yield can reach 85%-95%, but it has high requirements on the reaction device and conditions. In the public technology, it can also be prepared by the composite reaction of Grignard reagent-nitrile and then decomposed by pure ammonia, but the by-product of this method is a viscous substance, which makes separation more difficult, and the imine is easily hydrolyzed, and the yield is between 53%-64%; there is also anhydrous methanol instead of ammonia to decompose the reaction product of Grignard reagent-nitrile, the reaction time is shortened, and the yield is increased to 61%-81%; there is also a method of using ketoxime as a raw material to heat and decompose it into ketimine and ketone under the catalysis of carbon dioxide, and the yield is 59%-66%.

[0003] BASF disclosed a method for preparing benzophenone imine in patent 200780008620.8, which uses benzophenone to react in ammonia and in the presence of titanium dioxide, and the reaction yield can reach 95%. However, this method is a high-pressure reaction, and the equipment investment and operation costs are high. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a process for synthesizing ketimine by a solvent method.

[0005] The object of the present invention is achieved by the following technical scheme. A process for synthesizing ketimine by solvent method comprises the following steps:

[0006] Step 1: Put the raw material ketone, solvent and acidic catalyst into a three-necked flask;

[0007] Step 2: seal the left opening of the three-necked flask with a thermometer sleeve, and connect the middle opening of the three-necked flask to the water removal device;

[0008] Step 3: Ammonia gas is continuously introduced into the right opening of the three-necked flask to carry out amination reaction. The reaction pressure is normal pressure, and water is continuously removed through a water removal device during the reaction;

[0009] Step 4: After stirring and reacting for 2-5 hours, the liquid phase is collected to obtain a ketimine product.

[0010] Preferably, the molar ratio of the raw materials ketone and ammonia is 1:1-2, the amount of solvent used is 2-4 times the mass of ketone, preferably 3 times, and the amount of catalyst used is 5%-50% of the mass of ketone, preferably 30% to 45%.

[0011] Furthermore, the process temperature is 50-110°C, preferably 80-100°C.

[0012] Furthermore, the raw material ketone is one or a mixture of acetone, butanone, benzophenone, and acetobenzoate, preferably benzophenone.

[0013] Furthermore, the solvent is one or a mixture of anhydrous ethanol, n-butanol, cyclohexanol, and dimethyl sulfoxide.

[0014] Furthermore, the catalyst is one or a mixture of glacial acetic acid, p-toluenesulfonic acid, oxalic acid, ammonium chloride aqueous solution and strong acid ion resin.

[0015] Furthermore, the water removal device adopts a water separator with a molecular sieve, and water is continuously removed through the water separator during the reaction process; or external circulation distillation is used to remove water while reacting.

[0016] The beneficial effects of the present invention are: the reaction temperature is low, the reaction pressure is normal pressure, and the equipment investment is small; the organic solvent added in the reaction can greatly improve the reaction yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art or ordinary technicians, other drawings can be obtained based on these drawings without paying creative work. Figure 1 It is the chromatogram of benzophenone imine of the embodiment of the present invention. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0019] The invention provides a process for synthesizing ketimine by a solvent method. The process adopts a reaction in an organic solvent without pressurization, and an acidic substance catalyst is added. The catalyst and the solvent can improve the utilization rate of ammonia, so that an imine product with a higher yield can be obtained.

[0020] Example 1

[0021] 40 g of raw material benzophenone, 150 mL of cyclohexanol solvent and 3 g of glacial acetic acid catalyst were placed in a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 80° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 85.3% calculated based on the benzophenone feed.

[0022] Example 2

[0023] 40 g of raw material benzophenone, 150 mL of cyclohexanol solvent and 10 g of glacial acetic acid catalyst were placed in a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 80° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 86.5% calculated based on the benzophenone feed.

[0024] Example 2

[0025] 40 g of raw material benzophenone, 150 mL of n-butanol solvent and 10 g of p-toluenesulfonic acid were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 80° C., magnetic stirring was applied, and after reacting for 3 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 88.3% calculated based on the benzophenone feed.

[0026] Example 3

[0027] 40 g of raw material benzophenone, 150 mL of cyclohexanol solvent and 17 g of ammonium chloride aqueous solution were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 100° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 95.8% calculated based on the benzophenone feed.

[0028] Example 4

[0029] 40 g of raw material benzophenone, 150 mL of cyclohexanol solvent and 17 g of strong acid ion resin were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 100° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 92.2% calculated based on the benzophenone feed.

[0030] Example 5

[0031] 40 g of raw material benzophenone, 150 mL of dimethyl sulfoxide solvent and 17 g of strong acid ion resin were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 100° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 93.2% calculated based on the benzophenone feed.

[0032] Example 6

[0033] 40 g of raw material benzophenone, 150 mL of dimethyl sulfoxide solvent and 17 g of strong acid ion resin were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 110° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 92.8% calculated based on the benzophenone feed.

[0034] Example 7

[0035] 40 g of raw material benzophenone, 150 mL of n-butanol solvent and 17 g of glacial acetic acid were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 110° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 94.2% calculated based on the benzophenone feed.

[0036] Example 8

[0037] 40 g of raw material benzophenone, 150 mL of cyclohexanol solvent and 17 g of glacial acetic acid were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 110° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 95.3% calculated based on the benzophenone feed.

[0038] Example 9

[0039] 40 g of raw material benzophenone, 150 mL of dimethyl sulfoxide solvent and 17 g of strong acid ion resin were put into a 500 mL three-necked flask, the middle opening of the three-necked flask was connected with a water separator containing dried (500° C.) molecular sieves, ammonia was introduced into the right opening for amination reaction, the left opening was sealed with a thermometer sleeve, a mercury thermometer was inserted to measure the reaction temperature, the reaction temperature was controlled at 110° C., magnetic stirring was applied, and after reacting for 2 h, the mixture was taken out and placed in a 50 mL centrifuge tube, and the liquid phase was taken for HPLC detection. The yield of benzophenone imine was 95.2% calculated based on the benzophenone feed.

[0040] The calculation method of the yield of benzophenone imine is as follows: Figure 1 As shown, the chromatogram of benzophenone imine, the yield of imine was calculated by peak area.

[0041] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. A process for synthesizing ketimine by a solvent method, characterized in that: The steps include: Step 1: Put the raw material ketone, solvent and acidic catalyst into a three-necked flask; Step 2: seal the left opening of the three-necked flask with a thermometer sleeve, and connect the middle opening of the three-necked flask to the water removal device; Step 3: Ammonia gas is continuously introduced into the right opening of the three-necked flask to carry out amination reaction. The reaction pressure is normal pressure, and water is continuously removed through a water removal device during the reaction; Step 4: After stirring and reacting for 2-5 hours, the liquid phase is collected to obtain a ketimine product.

2. The process for synthesizing ketimine by solvent method according to claim 1, characterized in that: The molar ratio of the raw material ketone to ammonia is 1:1-2, the amount of the solvent is 2-4 times the mass of the ketone, and the amount of the catalyst is 5%-50% of the mass of the ketone.

3. The process for synthesizing ketimine by solvent method according to claim 2, characterized in that: The process temperature is 50-110°C.

4. The process for synthesizing ketimine by solvent method according to claim 3, characterized in that: The raw material ketone is one or a mixture of acetone, butanone, benzophenone and acetobenzoate.

5. The process for synthesizing ketimine by solvent method according to claim 4, characterized in that: The solvent is one or a mixture of anhydrous ethanol, n-butanol, cyclohexanol and dimethyl sulfoxide.

6. The process for synthesizing ketimine by solvent method according to claim 5, characterized in that: The catalyst is one or a mixture of glacial acetic acid, p-toluenesulfonic acid, oxalic acid, ammonium chloride aqueous solution and strong acid ion resin.

7. The process for synthesizing ketimine by solvent method according to claim 6, characterized in that: The dehydration device adopts a water separator with a molecular sieve, and water is continuously removed through the water separator during the reaction process; or external circulation distillation is adopted to remove water while reacting.

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