CN112724086B - Preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole - Google Patents
Preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole Download PDFInfo
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- CN112724086B CN112724086B CN202110111437.2A CN202110111437A CN112724086B CN 112724086 B CN112724086 B CN 112724086B CN 202110111437 A CN202110111437 A CN 202110111437A CN 112724086 B CN112724086 B CN 112724086B
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention discloses a preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole, which comprises the steps of placing malononitrile, benzaldehyde, phenylhydrazine and a magnetic silica gel supported ionic liquid catalyst in a reaction bottle, taking ethanol as a solvent, stirring and reacting for 0.5-10 h at 20-60 ℃, and obtaining a target product, namely 5-amino-4-nitrile-1, 3-diphenylpyrazole by a one-pot method. The catalyst of the invention has high efficiency and high selectivity, is easy to recycle and can be recycled for a plurality of times. The reaction process is simple to operate, mild in condition and environment-friendly, and is beneficial to large-scale industrial production.
Description
Technical Field
The invention relates to a novel method for preparing 5-amino-4-nitrile-1, 3-diphenylpyrazole by catalysis of a magnetic supported ionic liquid, belonging to the technical field of fine chemical engineering.
Background
5-amino-4-nitrile-1, 3-diphenylpyrazole is an important structural unit of many drug molecules, and is widely applied to the production of medicines, pesticides, functional active molecules and other compounds.
At present, the main method for preparing 5-amino-4-nitrile-1, 3-diphenylpyrazole at home and abroad is carried out by using malononitrile, benzaldehyde and phenylhydrazine through one-pot reaction. At present, various catalytic preparation methods such as a magnetic nano metal catalyst, a palladium catalytic system, bromo-acid, a nitric acid-acetic anhydride catalytic system and other catalytic systems have been reported, but the methods have the problems of low atom utilization rate, low yield, troublesome operation, high production cost, serious environmental pollution caused by byproducts and the like. Therefore, the important problem to be solved urgently is to find a more efficient, simple to operate, good in selectivity and environment-friendly green synthesis method.
The ionic liquid can be used as a green solvent and a catalyst, and the supported ionic liquid catalyst combines the advantages of a homogeneous catalyst and a heterogeneous catalyst, can play a unique role in the catalytic and organic reaction processes, and is the most promising reaction medium and a very ideal catalytic system in green chemistry. The traditional ionic liquid has unique catalytic activity in catalytic synthesis of pyrazole compounds, but has the defects of large dosage of the ionic liquid, difficult separation and purification of a catalytic system and a product and the like, and the practical application of the ionic liquid is greatly limited. In view of the important application value and the defects of large usage amount, difficult recovery and the like of the traditional ionic liquid in the field of organic catalysis. Therefore, the development of a catalytic reaction system which is constructed based on the novel supported ionic liquid and has the advantages of simple operation, high catalytic activity, high selectivity and convenient recycling has very important significance.
Disclosure of Invention
The invention provides a preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole, which has the characteristics of simple operation, mild condition, good selectivity, high yield and purity and the like, and is a novel green and environment-friendly method.
The technical scheme of the invention is that the preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole is characterized in that malononitrile, benzaldehyde and phenylhydrazine are used as raw materials, magnetic silica gel supported ionic liquid is used as a catalyst, ethanol is used as a solvent, heating and stirring are carried out, after the reaction is finished, a catalyst phase is separated and recovered through an external magnetic field, crystals are separated out from an organic phase of a product, and the organic phase of the product is filtered and dried to obtain a target product.
Further, the preparation of the catalysts used according to the invention is carried out with reference to the literature (R.Fehrmann, A.Riisager, M.Haumann, Supported ionic liquids: Fundamentals and applications, Wiley-VCH Verlag, Weinheim, 2014; Deng Yong, Ionic liquids properties, preparation and application, Chinese petrochemical Press, 2010; M.Shao, F.Ning, J.ZHao, M.Wei, D.G.Evans, X.Duan, J.Am.Chem.Soc.2012,134, 1071-1077), the catalysts having the following structure:
wherein the anion is BF 4 、OH、LaCl 4 、ZnCl 3 Any one of them. Namely, the catalyst is one of magnetic load type fluoborate ionic liquid, magnetic load type hydroxide ion liquid, magnetic load type lanthanum chloride ion liquid and magnetic load type zinc chloride ion liquid. The magnetic load type hydroxide ion liquid or the magnetic load type lanthanum chloride ion liquid is preferred.
Further, the molar ratio of the raw materials of malononitrile, benzaldehyde and phenylhydrazine is 1: 1: 1-2, preferably 1: 1: 1.
further, the reaction temperature is 20-60 ℃, preferably 20-30 ℃.
Furthermore, the reaction time is 0.5-10 h, preferably 1-4 h.
Furthermore, the dosage of the catalyst is 0.5-50% of the mass of the benzaldehyde material.
Furthermore, the dosage of the catalyst is 5-30% of the mass of the benzaldehyde material.
And further, filtering the obtained crystals, and drying without recrystallization to obtain the pure product 5-amino-4-nitrile-1, 3-diphenylpyrazole.
The catalytic reaction principle of the invention is as follows:
when the magnetic supported ionic liquid is used for catalyzing and preparing 5-amino-4-nitrile-1, 3-diphenylpyrazole, after the reaction is finished, a heterogeneous catalyst is deposited at the bottom of a container, the catalyst can be separated and recovered through an external magnetic field, the recovered magnetic supported ionic liquid catalyst can be recycled without being treated, and the magnetic supported ionic liquid catalyst is fed in proportion for the next batch of catalytic reaction.
According to the method for preparing 5-amino-4-nitrile-1, 3-diphenylpyrazole, the key technology is that a magnetic load type ionic liquid is adopted to catalyze malononitrile, benzaldehyde and phenylhydrazine to perform condensation reaction to obtain a target pure product.
Compared with the prior art, the invention has the advantages that: (1) the magnetic load type ionic liquid catalyst has high activity and good stability and is easy to recycle. (2) The reaction process is heterogeneous catalysis, the product phase and the magnetic catalyst phase are easy to separate, and the catalyst can be separated and recovered through an external magnetic field. (3) The whole reaction system has high efficiency and high selectivity, mild reaction conditions, no need of purification process to obtain pure product, and environment-friendly catalysis process, which is beneficial to industrial production.
Drawings
FIG. 1 is a liquid chromatogram of the product obtained in example 3.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention.
Example 1
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol), magnetic supported hydroxide ion liquid (0.3g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 3 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 90%, and the purity is 98.7%.
Example 2
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol), magnetic supported fluoborate ionic liquid (0.3g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 3 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 85 percent, and the purity is 97.2 percent.
Example 3
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol), magnetic supported lanthanum chloride salt ionic liquid (0.3g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 1.5 h. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 93 percent, and the purity is 99.0 percent.
Example 4
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol), magnetic supported zinc chloride salt ionic liquid (0.3g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 1.5 h. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 84%, and the purity is 97.8%.
Example 5
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (15mmol), magnetic supported hydroxide ion liquid (0.15g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 20 ℃, and the reaction is stirred for 3 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 74 percent, and the purity is 97.1 percent.
Example 6
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (20mmol), magnetic supported hydroxide ion liquid (0.1g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 20 ℃, and the reaction is stirred for 6 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 63 percent, and the purity is 95.2 percent.
Example 7
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol), magnetic supported lanthanum chloride salt ionic liquid (0.3g) and ethanol (20mL) are added into a reaction flask, the temperature is controlled at 40 ℃, and the reaction is stirred for 1 h. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 89%, and the purity is 97.4%.
Example 8
Benzaldehyde (10mmol), malononitrile (12mmol), phenylhydrazine (20mmol) and a magnetic carrier Fe are added into a reaction flask 3 O 4 @SiO 2 (0.45g) and ethanol (20mL) at 50 ℃ for 10h with stirring. After the reaction is finished, the catalyst is separated out through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 56.5 percent, and the purity is 96.2 percent.
Example 9
Benzaldehyde (10mmol), malononitrile (10mmol), phenylhydrazine (10mmol) and lanthanum chloride salt ionic liquid IL-LaCl are added into a reaction flask 4 (0.35g) and ethanol (20mL) at 30 ℃ for 2.5h with stirring. After the reaction is finished, the ionic liquid catalyst is separated out through liquid-liquid separation, and the organic phase of the product slowly meetsSeparating out crystals, filtering the crystals and drying to obtain the target pure product with the yield of 83 percent and the purity of 97.8 percent.
Example 10
Benzaldehyde (1mol), malononitrile (1mol), phenylhydrazine (1mol), magnetic supported hydroxide ionic liquid (30g) and ethanol (1000mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 1.5 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 92%, and the purity is 98.5%.
Example 11
Benzaldehyde (1mol), malononitrile (1mol), phenylhydrazine (1mol), magnetic supported lanthanum chloride salt ionic liquid (30g) and ethanol (1000mL) are added into a reaction flask, the temperature is controlled at 25 ℃, and the reaction is stirred for 1.5 hours. After the reaction is finished, the catalyst is recovered through an external magnetic field, crystals are slowly separated out from the product organic phase, the crystals are filtered and dried, and the target pure product can be obtained, wherein the yield is 95 percent, and the purity is 98.8 percent.
Example 12
The catalyst in the embodiment 1 is recycled, the reaction is carried out according to the conditions in the embodiment 1, the recycled catalyst is reused for 10 times, the catalytic activity of the reaction is not reduced, the yield of the biphenyl is 82-90%, and the purity is more than 98%.
Example 13
The catalyst in the embodiment 3 is recycled, the reaction is carried out according to the conditions in the embodiment 3, the recycled catalyst is reused for 10 times, the catalytic activity of the reaction is not reduced, the yield of the biphenyl is 85-92%, and the purity is more than 98%.
Claims (10)
1. A preparation method of 5-amino-4-nitrile-1, 3-diphenylpyrazole is characterized in that malononitrile, benzaldehyde and phenylhydrazine are used as raw materials, magnetic silica gel supported ionic liquid is used as a catalyst, ethanol is used as a solvent, heating and stirring are carried out, after the reaction is finished, a catalyst phase is separated and recovered through an external magnetic field, organic crystals of a product are separated out, and the organic crystals are filtered and dried to obtain a target product;
the catalyst has the following structure:
wherein the anion is LaCl 4 。
2. The method of claim 1, wherein: the molar ratio of the raw materials of malononitrile, benzaldehyde and phenylhydrazine is 1: 1.
3. The method of claim 1, wherein: the reaction temperature is 20-60 ℃.
4. The method of claim 1, wherein: the reaction temperature is 20-30 ℃.
5. The method of claim 1, wherein: the reaction time is 0.5-10 h.
6. The method of claim 1, wherein: the reaction time is preferably 1-4 h.
7. The method of claim 1, wherein: the dosage of the catalyst is 0.5-50% of the mass of the benzaldehyde material.
8. The method of claim 7, wherein: the dosage of the catalyst is 5-30% of the mass of the benzaldehyde material.
9. The method of claim 1, wherein: and filtering the obtained crystals, and drying without recrystallization to obtain the pure product 5-amino-4-nitrile-1, 3-diphenylpyrazole.
10. The method of claim 1, wherein: the recovered catalyst is used in catalytic circulation.
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