CN113185460A - Preparation method of triarylpyrazole compound and product thereof - Google Patents
Preparation method of triarylpyrazole compound and product thereof Download PDFInfo
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- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
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Abstract
The invention discloses a preparation method of triaryl pyrazole compound and a product thereof, which comprises the steps of simultaneously adding arylformyl ethylene oxide, aryl hydrazine, triethylamine and ethanol into a microwave synthesizer, and fully and uniformly mixing a solid-liquid system; pre-stirring for 20-60 seconds, performing microwave radiation treatment for 15-20 min at 80-100 ℃, tracking the reaction process by TLC (thin layer chromatography) until the arylformyl ethylene oxide is completely reacted, and taking out the reactor and cooling to room temperature; and then washing with water, fully stirring, extracting with ethyl acetate, removing the solvent by rotary evaporation, and performing column chromatography by using a mixture of 200-300-mesh crude silica gel and ethyl acetate and petroleum ether as an eluent to obtain the target product. The pyrazole compound has the advantages of mild reaction conditions, short reaction time, excellent yield, simple operation, convenient post-treatment and the like, provides a new and effective synthetic method and strategy for constructing a heterocyclic skeleton, and meets the environment-friendly requirement of green chemistry.
Description
Technical Field
The invention belongs to the field of organic compound synthesis, and particularly relates to a preparation method of a triarylpyrazole compound and a product thereof.
Background
Nitrogen-containing heterocyclic compounds are an important class of organic compounds. In view of molecular structure, nitrogen-containing compounds have been attracting much attention as drugs because of their numerous physiological activities. Among the nitrogen-containing five-membered heterocyclic compounds, compounds containing pyrazole ring structural units have wide biological activity, and thus have wide application in medicines and pesticides.
In recent years, studies on the pharmaceutical activity of pyrazole derivatives have been receiving attention. According to the reports of documents, the pyrazole derivatives also have the effects of reducing fever, relieving pain, tranquilizing and hypnotizing, resisting convulsion, resisting histamine, resisting depression and filtering pathogens, resisting tumors and the like, and certain medicines containing the pyrazole structural skeleton have good curative effect in medicine. The most important representative of the application of the pyrazole compounds as medicaments is 1- (3-trifluoromethylphenyl) -3-amino pyrazoline (BW755C), is a dual inhibitor of cyclooxygenase and lipoxygenase, and has good anti-inflammatory efficacy.
The arylpyrazoles are structural units with important biological activity and pharmacological property, have the effects of resisting microorganisms, resisting inflammation, reducing blood sugar, resisting hypertension, relieving pain and the like, and are currently used as one of important components of a drug development project.
The existing methods for synthesizing pyrazole derivatives mostly use expensive transition metal oxidants, use toxic organic solvents and have complex operation. Therefore, there is a need in the art to develop a simple, efficient and green synthetic method for synthesizing 1,3, 5-triarylpyrazoles.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made keeping in mind the above and/or other problems occurring in the prior art.
Therefore, the present invention aims to overcome the defects in the prior art and provide a preparation method of triaryl pyrazole compounds.
In order to solve the technical problems, the invention provides the following technical scheme: a process for preparing a triarylpyrazole compound, which comprises,
adding arylformyl ethylene oxide, aryl hydrazine, triethylamine and ethanol into a microwave synthesizer at the same time, and fully and uniformly mixing a solid-liquid system;
pre-stirring for 20-60 seconds, performing microwave radiation treatment for 15-20 min at 80-100 ℃, tracking the reaction process by TLC (thin layer chromatography) until the arylformyl ethylene oxide is completely reacted, and taking out the reactor and cooling to room temperature;
and then washing with water, fully stirring, extracting with ethyl acetate, removing the solvent by rotary evaporation, and performing column chromatography by using a mixture of 200-300-mesh crude silica gel and ethyl acetate and petroleum ether as an eluent to obtain the target product.
As a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the arylformyl ethylene oxide comprises one of 3-phenyl-2, 3-epoxy-1-phenyl acetone, (3- (4-chlorphenyl) ethylene oxide-2-yl) (phenyl) ketone, (3- (2, 4-dichlorophenyl) ethylene oxide-2-yl) (phenyl) ketone, phenyl (3-phenyl ethylene oxide-2-yl) ketone, 1, 3-diphenyl-2, 3-epoxy-1-acetone and (3- (4-bromophenyl) oxaproyl ring-2-yl) (phenyl) ketone.
As a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the aryl hydrazine comprises one of p-bromophenylhydrazine, phenylhydrazine, 3-methylphenylhydrazine, p-fluorophenylhydrazine and 3-bromophenylhydrazine.
As a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the molar ratio of the arylformyl ethylene oxide to the arylhydrazine to the triethylamine is 1: 1: 1.
as a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the arylformyl oxirane and ethanol were present in mmol: the mL is 1: 2.
As a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the mixture of ethyl acetate and petroleum ether is used as an eluent, wherein the volume ratio of the mixture of ethyl acetate and petroleum ether is 1: 5.
As a preferable embodiment of the process for producing the triarylpyrazole compound according to the invention, wherein: the microwave radiation treatment temperature is 100 ℃.
It is a further object of the present invention to overcome the deficiencies of the prior art by providing a product prepared by a process for the preparation of triarylpyrazole compounds.
(1) The method successfully develops an efficient synthesis method of the pyrazole compounds with the participation of the arylformyl ethylene oxide derivatives, under the promotion of microwaves, in an ethanol solvent, triethylamine is used as an alkali catalyst, and 3-phenyl-2, 3-epoxy-1-phenyl acetone and phenylhydrazine with a 1, 2-double nucleophilic center are used as raw materials to rapidly synthesize a series of pyrazole derivatives.
(2) The pyrazole compound has the advantages of mild reaction conditions, short reaction time, excellent yield, simple operation, convenient post-treatment and the like, provides a new and effective synthetic method and strategy for constructing a heterocyclic skeleton, and meets the requirement of green chemical environment friendliness.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
FIG. 1 is a perspective view of the molecular structure of Compound 3i in an example of the present invention.
FIG. 2 is a diagram of a possible reaction mechanism in an example of the present invention.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
The synthesis method comprises the following steps:
aroyloxirane (1.0mmol), arylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a 10mL reaction vessel special for Emrys (TM) Creator microwave synthesizer (purchased from Biotage corporation, Sweden), after the solid-liquid system is fully and uniformly mixed, the mixture is automatically pre-stirred for 20-60s by the instrument, under the condition of 100 ℃, microwave radiation is carried out for 15-20 min (the maximum power is 200W), the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature.
Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Performing column chromatography by using 200-300 mesh crude silica gel (the aperture of the crude silica gel is 200-300 mesh, the H-type silica gel column chromatography is special for use and is supplied by Qingdao ocean silica gel plate company), and using a mixture of ethyl acetate and petroleum ether (1:5V/V) as an eluent to obtain a target product.
The raw materials of the arylformyl ethylene oxide and the arylhydrazine required by the reaction are simple and easy to obtain, the cost is low, the yield of the synthesized series of triaryl pyrazole compounds is over 80 percent, and the reaction process is simple, rapid, efficient and green.
The chemical reaction equation related to the invention is as follows:
wherein Ar is1，Ar2，Ar3All represent benzene rings or benzene rings containing different substituents and different positions.
Example 1
The method is characterized in that 3-phenyl-2, 3-epoxy-1-phenyl acetone and p-bromophenylhydrazine are used as raw materials, and the reaction is carried out under different catalysts such as sodium hydroxide, sodium ethoxide, potassium carbonate, cesium carbonate and triethylamine to investigate the influence of the catalysts on the reaction:
(1) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of sodium hydroxide was used as an alkaline accelerator, ethanol was used as a solvent, and the reaction was carried out at 80 ℃ for 15min, whereby the yield of the final target product 3 was 31% (entry 1).
(2) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of sodium ethoxide was used as an alkali accelerator, acetonitrile was used as a solvent, and the reaction was carried out at 80 ℃ for 15min, whereby the yield of the final target product 3 was 52% (entry 2).
(3) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of sodium ethoxide was used as an alkali accelerator, ethanol was used as a solvent, and the reaction was carried out at 80 ℃ for 15min, whereby the yield of the final target product 3 was 63% (entry 3).
(4) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of potassium carbonate as an alkaline accelerator, ethylene glycol as a solvent, and a reaction at 80 ℃ for 15min, and a trace amount of the objective product was detected (entry 4).
(5) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of cesium carbonate as an alkali promoter, and ethylene glycol as a solvent were reacted at 80 ℃ for 15min, and as a result, a trace amount of the objective product was detected (entry 5).
(6) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of cesium carbonate as an alkali promoter, and N, N-dimethylformamide as a solvent were reacted at 80 ℃ for 20min, whereby the formation of the objective product 3 was not monitored (entry 6).
(7) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of triethylamine was used as an alkaline accelerator, and N, N-dimethylformamide was used as a solvent, and the reaction was carried out at 80 ℃ for 15min, whereby the yield of the final target product 3 was 32% (entry 7).
(8) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of triethylamine was used as an alkaline accelerator, acetonitrile was used as a solvent, and the reaction was carried out at 80 ℃ for 15min, and as a result, a trace amount of the objective product was detected (entry 8).
(9) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of triethylamine was used as an alkaline accelerator, and the reaction was carried out at 80 ℃ for 20min with ethanol as a solvent, whereby the yield of the final target product 3 was 76% (entry 9).
(10) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of triethylamine was used as an alkaline accelerator, and the reaction was carried out at 100 ℃ for 15min with ethanol as a solvent, whereby the yield of the final target product 3 was 87% (entry 10).
(11) 3-phenyl-2, 3-epoxy-1-phenylacetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) were used as raw materials, 0.5equiv of triethylamine was used as an alkaline accelerator, and the reaction was carried out at 120 ℃ for 15min with ethanol as a solvent, whereby the yield of the final target product 3 was 80% (entry 11).
The optimized conditions and results of the reaction conditions for the synthesis of compound 3 under microwave irradiation are shown in table 1.
TABLE 1 optimization of reaction conditions for the synthesis of Compound 3 under microwave irradiation
The experimental results show that the reaction can obtain better results under the catalysis of triethylamine: the yield of 3 is high.
The solvent of the reaction was screened: the reaction is carried out in different solvents (MeCN, DMF, EtOH) under the condition that triethylamine is used as a catalyst, and the result shows that ethanol is the best reaction solvent. Ethanol is used as a benign solvent, can well dissolve solid reactants, increases the contact between the reactants and the promoter, is beneficial to the reaction, and has poor catalytic effect when other solvents are adopted.
And (3) screening the reaction temperature: 3-phenyl-2, 3-epoxy-1-phenyl acetone and p-bromophenylhydrazine are taken as substrates, ethanol is taken as a solvent, and the influence of temperature on the reaction is examined. As can be seen from table 1, the experimental temperature was varied from 80 ℃ to 120 ℃ (see table 1), and it was found that when the temperature was varied from 80 ℃ to 100 ℃, the reaction yield was increased, but when the reaction temperature was increased to 120 ℃, the reaction time was not changed, and the yield was lowered (80%). Therefore, 100 ℃ is preferred as the optimum reaction temperature in the present invention.
Example 2
Synthesis of compound 3 a:
mixing (3- (4-chlorophenyl) oxiran-2-yl) (phenyl) methanone (1.0mmol), p-bromophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation.
And (3) performing column chromatography by using 200-300-mesh crude silica gel and a mixture (1:5V/V) of ethyl acetate and petroleum ether as an eluent to obtain a target product 3 a.
3a Compound characterization:
1-(4-Bromophenyl)-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-4-ol(3a)
Yellow solid,mp:124℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.84(d,J＝7.6Hz,2H,ArH),7.55-7.52(m,3H,ArH),7.48(d,J＝7.2Hz,2H,ArH),7.38-7.32(m,4H,ArH),7.03(d,J＝7.2Hz,2H,ArH),6.73(d,J＝8.0Hz,2H,CH),5.40(s,1H,CH),4.80(s,1H,OH)；
IR(KBr,v,cm-1):3262,1608,1596,1495,1323,1136,1033；
HRMS(ESI)m/z:calc.for C21H15BrClN2O:425.0056[M-H]-；found:425.0062.
example 3
Synthesis of 3b compound:
mixing (3- (4-chlorophenyl) oxiran-2-yl) (phenyl) methanone (1.0mmol), phenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature.
Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation.
And (3) performing column chromatography by using 200-300-mesh crude silica gel and a mixture (1:5V/V) of ethyl acetate and petroleum ether as an eluent to obtain a target product 3 b.
3b Compound characterization:
5-(4-Chlorophenyl)-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-ol(3b)
Yellow solid,mp:135.0-136.2℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)8.20(s,1H,ArH),8.03(d,J＝7.2Hz,2H,ArH),7.73(d,J＝8.0Hz,2H,ArH),7.58(t,J＝7.6Hz,2H,ArH),7.50(d,J＝2.0Hz,3H,ArH),7.38-7.34(m,3H,ArH),7.28(d,J＝7.6Hz,1H,ArH),7.08(d,J＝7.6Hz,2H,ArH),6.92(d,J＝7.2Hz,1H,CH),4.86(s,1H,CH),4.19(s,1H,OH)；
IR(KBr,v,cm-1):3352,1688,1542,1402,1298,1113,1048；
HRMS(ESI)m/z:calc.for C21H16ClN2O:347.0951[M-H]-；found:347.0923.
example 4
Synthesis of 3c Compounds
Mixing (3- (4-chlorophenyl) oxiran-2-yl) (phenyl) methanone (1.0mmol), 3-methylphenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. The column chromatography was carried out using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to obtain the target product 3 c.
3c Compound characterization:
5-(4-Chlorophenyl)-3-phenyl-1-(m-tolyl)-4,5-dihydro-1H-pyrazol-4-ol(3c)
White solid,mp:139.1-139.9℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.75(d,J＝7.2Hz,2H,ArH),7.52-7.36(m,7H,ArH),7.30(s,1H,ArH),7.05(s,1H,ArH),6.94(t,J＝7.6Hz,1H,ArH),6.79(d,J＝8.0Hz,1H,ArH),6.54(d,J＝7.2Hz,1H,CH),3.63(s,1H,CH),3.52(s,1H,OH),2.17(s,3H,CH3)；
13C NMR(100MHz,DMSO)δ145.9,143.8,142.7,137.8,132.9,132.5,129.1,129.0,128.9,128.5,127.8,125.9,120.5,116.2,112.6,94.1,52.9,21.9；
IR(KBr,v,cm-1):3316,1654,1524,1388,1264,1108,1033；
HRMS(ESI)m/z:calc.for C22H18ClN2O:361.1108[M-H]-；found:361.1096.
example 5
Synthesis of 3d Compounds
The reaction mixture was washed with (3- (4-bromophenyl) oxido-2-yl) (phenyl) methanone (1.0mmol), p-bromophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. The column chromatography was carried out using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to obtain the target product 3 d.
3d Compound characterization:
1,5-Bis(4-bromophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-4-ol(3d)
Yellow solid,mp:128.2-130.3℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.94(d,J＝7.2Hz,2H,ArH),7.72(d,J＝7.2Hz,2H,ArH),7.52-7.34(m,7H,ArH),7.25(d,J＝8.0Hz,2H,ArH),6.43(s,1H,CH),5.32(s,1H,CH),4.98(s,1H,OH)；
IR(KBr,v,cm-1):3286,1624,1577,1354,1224,1195,1043；
HRMS(ESI)m/z:calc.for C21H15Br2N2O:468.9551[M-H]-；found:468.9543.
example 6
Synthesis of 3e Compounds
Reacting (3- (4-bromophenyl) ringOxoethan-2-yl) (phenyl) methanone (1.0mmol), phenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. The column chromatography was carried out using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to obtain the target product 3 e.
3e Compound characterization:
5-(4-Bromophenyl)-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-ol(3e)
Pale Yellow solid,mp:132.2-133.1℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.85(d,J＝7.2Hz,2H,ArH),7.64(t,J＝7.2Hz,2H,ArH),7.55-7.42(m,3H,ArH),7.28-7.20(m,3H,ArH),7.07-7.01(m,2H,ArH),6.98(d,J＝8.0Hz,2H,ArH),6.53(d,J＝7.6Hz,1H,CH),5.24(s,1H,CH),5.03(d,J＝7.2Hz,1H,OH)；
IR(KBr,v,cm-1):3304,1716,1522,1308,1256,1178,1044；
HRMS(ESI)m/z:calc.for C21H16BrN2O:391.0446[M-H]-；found:391.0455.
example 7
Synthesis of 3f Compounds
(3- (4-bromophenyl) oxido-2-yl) (phenyl) methanone (1.0mmol), 3-methylphenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer at the same time, after the solid-liquid system is fully and uniformly mixed, the mixture is automatically pre-stirred for 20 to 60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, and the mixture is usedTLC tracks the reaction progress until the arylformyl oxirane is completely reacted, and the reactor is taken out and cooled to room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. The column chromatography is carried out by using crude silica gel with 200-300 meshes and a mixture of ethyl acetate and petroleum ether (1:5V/V) as an eluent to obtain the target product 3 f.
3f Compound characterization:
5-(4-Bromophenyl)-3-phenyl-1-(m-tolyl)-4,5-dihydro-1H-pyrazol-4-ol(3f)
Pale Yellow solid,mp:141.2-142.9℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.92(d,J＝7.2Hz,2H,ArH),7.62-7.44(m,4H,ArH),7.36-7.32(m,3H,ArH),7.28-7.16(m,2H,ArH),7.06(d,J＝7.6Hz,2H,ArH),6.62(d,J＝7.2Hz,1H,CH),5.22(d,J＝4.0Hz,1H,CH),5.15(d,J＝4.8Hz,1H,OH),2.34(s,3H,CH3)；
IR(KBr,v,cm-1):3286,1664,1508,1299,1207,1143,1012；
HRMS(ESI)m/z:calc.for C22H18BrN2O:405.0603[M-H]-；found:405.0588.
example 8
Synthesis of 3g Compound
The reaction mixture was washed with (3- (2, 4-dichlorophenyl) oxido-2-yl) (phenyl) methanone (1.0mmol), p-bromophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Column chromatography was carried out using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to give 3g of the desired product.
3g characterization of the compound:
5-(2,4-Dichlorophenyl)-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-ol(3g)
Yellow solid,mp:118.5-120.3℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.85(d,J＝7.2Hz,2H,ArH),7.51(d,J＝2.0Hz,1H,ArH),7.39(t,J＝7.2Hz,2H,ArH),7.33(d,J＝7.2Hz,1H,ArH),7.25-7.21(m,2H,ArH),7.08(d,J＝6.4Hz,1H,ArH),7.03(d,J＝8.0Hz,2H,ArH),6.85(d,J＝8.0Hz,2H,CH),5.56(s,1H,CH),5.13(d,J＝6.0Hz,1H,OH).
IR(KBr,v,cm-1):3298,1674,1556,1324,1202,1194,1088；
HRMS(ESI)m/z:calc.for C21H15Cl2N2O:381.0561[M-H]-；found:381.0566.
example 9
Synthesis of 3h Compound
Phenyl (3-phenyloxiran-2-yl) methanone (1.0mmol), p-fluorophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. The column chromatography is carried out by using crude silica gel with 200-300 meshes and a mixture of ethyl acetate and petroleum ether (1:5V/V) as an eluent to obtain a target product for 3 h.
3h Compound characterization:
5-(2-Chlorophenyl)-1-(4-fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-4-ol(3h)
Yellow solid,mp:123.5-125.3℃
1H NMR(400MHz,DMSO-d6)(δ,ppm)8.32(s,1H,ArH),8.05(d,J＝7.6Hz,2H,ArH),7.82(d,J＝8.0Hz,2H,ArH),7.58-7.42(m,2H,ArH),7.32(d,J＝2.0Hz,3H,ArH),7.18(d,J＝7.6Hz,1H,ArH),7.03(d,J＝7.6Hz,2H,ArH),6.85(d,J＝7.2Hz,1H,CH),5.13(s,1H,CH),4.84(s,1H,OH)；
IR(KBr,v,cm-1):3352,1656,1596,1495,1323,1136,1033；
HRMS(ESI)m/z:calc.for C21H16FN2O:331.1247[M-H]-；found:331.1242.
example 10
Synthesis of 3i Compounds
Phenyl (3-phenyloxido-2-yl) methanone (1.0mmol), p-bromophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Column chromatography was performed using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to give the target product 3 i.
3i Compound characterization:
1-(4-Bromophenyl)-3,5-diphenyl-4,5-dihydro-1H-pyrazol-4-ol(3i)
Pale Yellow solid,mp:123.5-125.3℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.85(d,J＝7.2Hz,2H,ArH),7.52-7.26(m,8H,ArH),7.19(d,J＝7.2Hz,2H,ArH),7.01(d,J＝8.4Hz,2H,ArH),6.53(s,1H,CH),5.21(s,1H,CH),5.04(s,1H,OH)；
13C NMR(100MHz,DMSO)δ149.27,143.06,138.89,132.11,131.79,129.58,129.09,128.18,126.51,126.22,115.19,110.68,82.45,72.52；
IR(KBr,v,cm-1):3312,1706,1532,1424,1312,1150,1020；
HRMS(ESI)m/z:calc.for C21H16BrN2O:391.0446[M-H]-；found:391.0430.
example 11
Synthesis of 3j Compound
Phenyl (3-phenyloxiran-2-yl) methanone (1.0mmol), 3-bromophenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Column chromatography was performed using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to give the desired product 3 j.
3j Compound characterization:
1-(3-Bromophenyl)-3,5-diphenyl-4,5-dihydro-1H-pyrazol-4-ol(3j)
IR(KBr,v,cm-1):3386,1686,1608,1478,1312,1214,1054；
HRMS(ESI)m/z:calc.for C21H16BrN2O:391.0446[M-H]-；found:391.0445.
example 12
Synthesis of 3k Compounds
Phenyl (3-phenyloxiran-2-yl) methanone (1.0mmol), phenylhydrazine (1.0 m)mol), and 1.0mol of triethylamine (Et)3N) and 2mL of ethanol (EtOH) are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully mixed uniformly, the mixture is automatically pre-stirred for 20-60s by the instrument, microwave radiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction process is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Column chromatography was performed using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to give the desired product 3 k.
3k Compound characterization:
1,3,5-Triphenyl-4,5-dihydro-1H-pyrazol-4-ol(3k)
Yellow solid,mp:116.0-117.6℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.84(d,J＝7.2Hz,2H,ArH),7.41(t,J＝7.6Hz,2H,ArH),7.36-7.32(m,3H,ArH),7.28-7.16(m,5H,ArH),7.06(d,J＝7.6Hz,2H,ArH),6.75(s,1H,ArH),6.44(d,J＝7.6Hz,1H,CH),5.16(d,J＝2.8Hz,1H,CH),5.03(d,J＝4.8Hz,1H,OH)；
13C NMR(100MHz,DMSO)δ148.3,143.9,139.5,132.1,129.5,129.5,129.1,128.8,128.1,126.3,126.2,119.5,113.2,82.4,72.7；
IR(KBr,v,cm-1):3356,1734,1612,1408,1395,1122,1076；
HRMS(ESI)m/z:calc.for C21H17N2O:313.1341[M-H]-；found:313.1340.
example 13
Synthesis of 3l Compound
Phenyl (3-phenyloxido-2-yl) methanone (1.0mmol), 3-methylphenylhydrazine (1.0mmol), and 1.0mol triethylamine (Et)3N) and 2mL of ethanol (EtOH) solvent are added into a special reaction container for 10mL of Emrys (TM) Creator microwave synthesizer, after the solid-liquid system is fully and uniformly mixed, the mixture is automatically pre-stirred for 20-60s by the instrument,microwave irradiation is carried out for 16min (the maximum power is 200W) at the temperature of 100 ℃, the reaction progress is tracked by TLC until the arylformyl ethylene oxide is completely reacted, and the reactor is taken out and cooled to the room temperature. Then 30mL of water was added, stirred well, then extracted 3 times with 4mL of ethyl acetate and the solvent was removed by rotary evaporation. Column chromatography was performed using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:5V/V) as eluent to give 3l of the desired product.
3l Compound characterization:
3,5-Diphenyl-1-(m-tolyl)-4,5-dihydro-1H-pyrazol-4-ol(3l)
Pale Yellow solid,mp:106.5-108.2℃；
1H NMR(400MHz,DMSO-d6)(δ,ppm)7.84(d,J＝7.2Hz,2H,ArH),7.41(t,J＝7.6Hz,2H,ArH),7.34(t,J＝6.4Hz,3H,ArH),7.28-7.20(m,3H,ArH),7.07-7.01(m,2H,ArH),6.76(d,J＝8.0Hz,1H,ArH),6.58(d,J＝7.2Hz,1H,ArH),6.46(d,J＝7.6Hz,1H,CH),5.16(s,1H,CH),5.01(d,J＝7.6Hz,1H,OH),2.23(s,3H,CH3)；
13C NMR(100MHz,DMSO)δ148.1,143.9,139.6,138.6,132.1,129.5,129.3,129.0,128.8,128.0,126.3,126.2,120.4,113.9,110.4,82.3,72.7,21.8；
IR(KBr,v,cm-1):3268,1664,1526,1477,1335,1251,1098；
HRMS(ESI)m/z:calc.for C22H19N2O:327.1497[M-H]-；found:327.1521.
TABLE 2 Synthesis of Compound 3 under microwave irradiation
As can be seen from Table 2, no matter the substituent on the aromatic ring of the arylhydrazine 2 is an electron donating group (such as methyl and methoxy) or an electron withdrawing group (such as chlorine and bromine), the target product can be synthesized efficiently without being influenced by the position of the substituent; when different substituents (such as fluorine, chlorine and bromine) are connected to the aromatic ring of the arylformyl oxirane 1, the arylformyl oxirane can be well suitable for the reaction and is not influenced by the positions of the substituents, and the target compound can be obtained with high yield.
Example 14
To further confirm the structure of the product, single crystals of compound 3i were grown and subjected to single crystal X-ray diffraction analysis. The crystallographic parameters of compound 3i are shown in table 3.
TABLE 3 crystallographic parameters of Compound 3i
Example 15
1- (4-bromophenyl) -3, 5-diphenyl-4, 5-dihydro-1H-pyrazol-4-ol:
1, 3-diphenyl-2, 3-epoxy-1-acetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol), 1.0equiv Et3N and 2mL EtOH are added into a 10mL microwave special reaction tube, a mixed system is automatically pre-stirred for 20s by an instrument, then under the condition of 100 ℃, microwave radiation is carried out for 15min, TLC tracking reaction is carried out until 1, 3-diphenyl-2, 3-epoxy-1-acetone completely reacts, the solvent is removed by washing with water, then ethyl acetate is used for extracting for 3 times of 4mL, and the solvent is removed by rotary evaporation. Then, column chromatography is carried out by using crude silica gel with 200-mesh and 300-mesh, ethyl acetate and petroleum ether mixture (1:4V/V) as eluent to obtain a light yellow target product, and the melting point: 123 ℃ and 125 ℃.
Example 16
5- (4-bromophenyl) -3-phenyl-1- (m-tolyl) -4, 5-dihydro-1H-pyrazol-4-ol:
adding (3- (4-bromophenyl) oxaprozin-2-yl) (phenyl) methanone (1.0mmol), 3-methylphenylhydrazine (1.0mmol), 1.0equiv Et3N and 2mL EtOH into a 10mL microwave special reaction tube, automatically pre-stirring a mixed system by an instrument for 20s, then irradiating the mixed system for 20min by microwave at 100 ℃, tracking the reaction by TLC until (3- (4-bromophenyl) oxaprozin-2-yl) (phenyl) methanone completely reacts, washing the obtained product with water to remove the solvent, extracting the product for 3 times by 4mL with ethyl acetate, and removing the solvent by rotary evaporation. Then column chromatography was carried out using 200-300 mesh crude silica gel, ethyl acetate and petroleum ether mixture (1:4V/V) as eluent to obtain a pale yellow target product (yield 76%), melting point: 141 ℃ and 143 ℃.
The possible reaction mechanism of the present invention is shown in FIG. 2: firstly, carrying out nucleophilic addition on a heterocyclic propane derivative 1 and an aryl hydrazine 2 to form an intermediate A, under an alkaline condition, attacking ethylene oxide by a secondary amine on the phenyl hydrazine and opening a ring to form an oxyanion, then carrying out intermolecular cyclization reaction to form an intermediate C, and finally carrying out deprotonation to obtain a target product 3.
Generally, the ring opening of the epoxide is easier to perform under the acidic condition, and the product after the ring opening is easier to react with other substrates under the acidic condition to construct a new compound skeleton. In the reaction process, the alkaline accelerator is added, so that one-step ring opening of the arylformyl ethylene oxide can be realized, further cyclization reaction is carried out, the polysubstituted pyrazole compound is constructed, the reaction byproduct is only water, and generation of other compounds is not involved.
Example 17
3-phenyl-2, 3-epoxy-1-phenyl acetone (1.0mmol) and p-bromophenylhydrazine (1.0mmol) are used as raw materials, 0.5equiv triethylamine is used as an alkaline promoter, ethanol (2ml) is used as a solvent, the reaction is carried out for 15min at the temperature of 100 ℃, and the yield of the final target product 3 is 87 percent
The results of the different raw material molar ratios are shown in Table 4.
TABLE 4
As can be seen from Table 4, the raw material ratio of the reaction is 1:1, and when p-bromophenylhydrazine is added in an excessively small amount, byproducts are generated, other side reactions are generated, and the product yield is reduced.
The method successfully develops a high-efficiency synthesis method of the pyrazole compound with the participation of the aryl formyl ethylene oxide derivative. Under the promotion of microwave, triethylamine is used as an alkali catalyst in an ethanol solvent, 3-phenyl-2, 3-epoxy-1-phenyl acetone and phenylhydrazine with a 1, 2-double nucleophilic center are used as raw materials, and a series of pyrazole derivatives are rapidly synthesized. The reaction has the advantages of mild condition, short reaction time, excellent yield, simple operation, convenient post-treatment and the like, provides a new and effective synthetic method and strategy for constructing the heterocyclic skeleton, and meets the requirement of green chemistry and environmental friendliness.
The method is rapid and efficient, and the reaction conditions are mild. The method is simple to operate, and solves the problems of complex post-treatment process, long reaction time, high energy consumption and the like.
The method can be used for efficiently constructing the pyrazole ring by one step, has wide substrate application range, can be used for preparing a series of compounds containing different substituent groups, and is not influenced by the position of the substituent group; the solvent required by the reaction is ethanol, so that the method is green and environment-friendly, has low toxicity and accords with the green chemical concept; mild reaction conditions, short reaction time, excellent yield, simple operation, convenient post-treatment and the like, provides a new and effective synthetic method and strategy for constructing the heterocyclic skeleton, and meets the requirement of green chemistry and environmental friendliness.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (8)
1. A process for preparing a triarylpyrazole compound, which comprises: comprises the steps of (a) preparing a mixture of a plurality of raw materials,
adding arylformyl ethylene oxide, aryl hydrazine, triethylamine and ethanol into a microwave synthesizer at the same time, and fully and uniformly mixing a solid-liquid system;
pre-stirring for 20-60 seconds, performing microwave radiation treatment for 15-20 min at 80-100 ℃, tracking the reaction process by TLC (thin layer chromatography) until the arylformyl ethylene oxide is completely reacted, and taking out the reactor and cooling to room temperature;
and then washing with water, fully stirring, extracting with ethyl acetate, removing the solvent by rotary evaporation, and performing column chromatography by using a mixture of 200-300-mesh crude silica gel and ethyl acetate and petroleum ether as an eluent to obtain the target product.
2. A process for preparing triarylpyrazole compounds as claimed in claim 1, wherein: the arylformyl ethylene oxide comprises one of 3-phenyl-2, 3-epoxy-1-phenyl acetone, (3- (4-chlorphenyl) ethylene oxide-2-yl) (phenyl) ketone, (3- (2, 4-dichlorophenyl) ethylene oxide-2-yl) (phenyl) ketone, phenyl (3-phenyl ethylene oxide-2-yl) ketone, 1, 3-diphenyl-2, 3-epoxy-1-acetone and (3- (4-bromophenyl) oxaproyl ring-2-yl) (phenyl) ketone.
3. A process for preparing triarylpyrazole compounds as claimed in claim 1, wherein: the aryl hydrazine comprises one of p-bromophenylhydrazine, phenylhydrazine, 3-methylphenylhydrazine, p-fluorophenylhydrazine and 3-bromophenylhydrazine.
4. A process for preparing triarylpyrazole compounds as claimed in claim 1, wherein: the molar ratio of the arylformyl ethylene oxide to the arylhydrazine to the triethylamine is 1: 1: 1.
5. a process for preparing a triarylpyrazole compound as claimed in any one of claims 1 to 4, wherein: the arylformyl oxirane and ethanol were present in mmol: the mL is 1: 2.
6. A process for preparing triarylpyrazole compounds as claimed in claim 1, wherein: the mixture of ethyl acetate and petroleum ether is used as an eluent, wherein the volume ratio of the mixture of ethyl acetate and petroleum ether is 1: 5.
7. A process for preparing triarylpyrazole compounds as claimed in claim 1, wherein: the microwave radiation treatment temperature is 100 ℃.
8. A product obtained by the process for producing a triarylpyrazole compound according to any one of claims 1 to 7.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111187256A (en) * | 2020-02-24 | 2020-05-22 | 北京工业大学 | Triazine trispyrazole compound and preparation method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| AFSAH, ELSAYED M.; KANDEEL, EZ-EL-DIN M.: "Mannich bases as synthetic intermediates: synthesis of 3- and 4-functionalized 2-pyrazolines", 《ZEITSCHRIFT FUER NATURFORSCHUNG, B: CHEMICAL SCIENCES》 * |
| GOUHAR, RASHA S.; RAAFAT, EMAN: "Synthesis of (3-(naphthalen-1-yl)oxiran-2-yl)(5,6,7,8-tetrahydronaphthalen-2-yl)methanone and reaction with some nucleophiles for anticancer evaluation", 《RESEARCH ON CHEMICAL INTERMEDIATES》 * |
| MARIE M. AHLSTRO¨M ET.AL.: "CYP2C9 Structure-Metabolism Relationships: Optimizing the Metabolic Stability of COX-2 Inhibitors", 《J. MED. CHEM.》 * |
| MOHAMED, SALWA F. ET AL.: "Anti-HSV-1 activity and mechanism of action of some new synthesized substituted pyrimidine, thiopyrimidine and thiazolopyrimidine derivatives", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| 王礼琛主编: "《有机化学》", 31 July 2006 * |
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