CN114456117A - Iodine-promoted method for preparing N-arylpyrazole compound - Google Patents

Iodine-promoted method for preparing N-arylpyrazole compound Download PDF

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CN114456117A
CN114456117A CN202210202175.5A CN202210202175A CN114456117A CN 114456117 A CN114456117 A CN 114456117A CN 202210202175 A CN202210202175 A CN 202210202175A CN 114456117 A CN114456117 A CN 114456117A
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CN114456117B (en
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李登科
沈先福
彭天凤
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Qujing Normal University
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    • 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
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Abstract

The invention discloses an iodine-promoted method for preparing N-arylpyrazole compounds, which relates to the technical field of organic synthesis and comprises the following steps: the N-aryl-3-pyrazolidinone compound is used as an initial raw material, dimethyl sulfoxide is used as a reaction solvent, iodine is used as a catalyst, the N-aryl-3-pyrazolidinone compound is subjected to dehydroaromatization under the reaction condition of 120 ℃ of 100 ℃, a series of N-aryl pyrazolidinone compounds with novel structures are prepared, and the N-aryl pyrazolone compounds can be directly used and can be used as substrates for other reactions, the adopted reaction condition is mild, the operation steps and the post-treatment process are simple, the product yield is high and is 51% -88%.

Description

Iodine-promoted method for preparing N-arylpyrazole compound
Technical Field
Relates to the technical field of organic synthesis, in particular to an iodine-promoted method for preparing N-arylpyrazole compounds.
Background
Currently, more than half of the drug molecules belong to the nitrogen-containing heterocyclic compounds. The pyrazole compounds are used as an important nitrogen-containing heterocyclic structural unit, widely exist in various natural products and drug molecules, and are important building blocks for constructing bioactive compounds in the research and development of new drugs. N-aryl-substituted pyrazoles have received increasing attention as important components thereof and have been the focus of research. Celecoxib (Celebrex), for example, for relief of symptoms and signs of osteoarthritis, relief of symptoms and signs of rheumatoid arthritis in adults, treatment of acute pain in adults; rimonabant (Acomplia), the first type 1 cannabinoid receptor (CB1) inhibitor antiobesity drug in the world, and has the functions of insulin sensitization and lipid metabolism disorder improvement.
Many methods have been developed for synthesizing N-arylpyrazoles, of which the synthesis of N-arylpyrazoles by cyclocondensation of N-arylhydrazines with 1, 3-dicarbonyl compounds or their substitutes is the most common. However, this process is generally a mixture of two regioselective isomers for asymmetric 1, 3-diketones. An alternative method is to catalyze the N-arylation of 1-hydropyrazoles, but in the case of asymmetric pyrazoles as starting materials, the reaction also faces regioselectivity problems, since pyrazoles can act as tautomers, thereby giving rise to dual nucleophilic abilities. Moreover, the existing synthesis methods of the N-arylpyrazole compounds are mostly carried out at higher temperature under the protection of metal, long reaction time and inert gas, the reaction conditions are harsh, the operation steps and the post-treatment process are complex, and the yield is low.
Disclosure of Invention
The invention aims to provide an iodine-promoted method for preparing N-arylpyrazole compounds, which has mild reaction conditions and simple operation steps and post-treatment process, is used for solving the problems in the prior art, simultaneously improves the yield, and is suitable for preparing a large amount of N-arylpyrazole compounds.
In order to achieve the purpose, the invention provides the following scheme:
the invention provides an iodine-promoted method for preparing N-arylpyrazole compounds, which comprises the following steps: the N-aryl-3-pyrazolidinone compound is prepared by taking an N-aryl-3-pyrazolidinone compound as an initial raw material, dimethyl sulfoxide (DMSO) as a reaction solvent and iodine as a catalyst, and dehydroaromatizing the N-aryl-3-pyrazolidinone compound under the reaction condition of 100-120 ℃.
The invention provides a preparation method of an N-arylpyrazole compound, which takes an easily obtained N-aryl-3-pyrazolidone compound (32.4mg-48.0mg) as an initial raw material, dimethyl sulfoxide (DMSO) as a reaction solvent, iodine (2.5-5.0mg) as a catalyst, and the N-aryl-3-pyrazolidone compound is subjected to dehydrogenation and aromatization processes under the air condition at the temperature of 100-120 ℃ (thin-layer chromatography monitoring), so that a series of N-arylpyrazole compounds with novel structures are obtained in a green and high-efficiency manner. The product prepared by the method can be directly used and can also be used as a substrate for other reactions, the adopted reaction conditions are mild, the operation steps and the post-treatment process are simple, and the product yield is high and is 51-88%.
Further, the structural formula of the N-aryl-3-pyrazolidinone compound is shown as formula 1, wherein R in the formula 11H, 2-Me, 2, 4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF3；R2H or Ph; r3H or Me;
Figure BDA0003529819380000021
further, the structural formula of the N-arylpyrazole compound is shown in formula 2, wherein R in formula 21H, 2-Me, 2, 4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF3；R2H or Ph; r3H or Me;
Figure BDA0003529819380000022
further, the reaction time is 18-24h, and the thin layer chromatography is used for monitoring during the reaction process.
Further, the mass ratio of the N-aryl-3-pyrazolidinone compound to the iodine is (32.4-48.0): (2.5-5.0).
Further, the reaction was carried out under an air atmosphere.
Further, after the reaction at 100-120 ℃, the method also comprises the processes of extraction, drying and column chromatography separation.
Further, after the reaction is finished, the reaction product is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound (the yield is 51% -88%).
The N-arylpyrazole compound prepared by the invention can be used for synthesizing bactericides or drug intermediates.
The invention discloses the following technical effects:
1. the reaction condition is mild, a transition metal catalyst is not needed, the reaction is carried out at the temperature of 100-120 ℃, the energy consumption is low, the environment protection is facilitated, and the preparation of a large amount of N-aryl pyrazole compounds is facilitated.
2. The reaction has better atom economy and high product yield.
3. The reaction substrate has wide range and strong functional group compatibility.
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In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required in the embodiments will be briefly described below, 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 that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a reaction scheme of the preparation process of the present invention;
FIG. 2 is a synthesis scheme of N-arylpyrazole compound 2a according to example 1;
FIG. 3 is a synthesis scheme of N-arylpyrazole compound 2b according to example 2;
FIG. 4 is a scheme showing the synthesis scheme of N-arylpyrazole compound 2c according to example 3;
FIG. 5 is a synthesis scheme of N-arylpyrazole compound 2d in example 4;
FIG. 6 is a synthesis scheme of N-arylpyrazole compound 2e according to example 5;
FIG. 7 is a synthesis scheme of N-arylpyrazole compound 2f according to example 6;
FIG. 8 is a scheme for the synthesis of 2g of an N-arylpyrazole compound of example 7;
FIG. 9 is a scheme showing the synthesis scheme of 2h, an N-arylpyrazole compound obtained in example 8;
FIG. 10 is a synthesis scheme of N-arylpyrazole compound 2i in example 9;
FIG. 11 is a synthesis scheme of N-arylpyrazole compound 2j in example 10;
FIG. 12 is a synthesis scheme of N-arylpyrazole compound 2k according to example 11;
FIG. 13 is a synthesis scheme of 2l, an N-arylpyrazole compound of example 12;
FIG. 14 is a synthesis scheme of N-arylpyrazole compound 2m according to example 13;
FIG. 15 is a synthesis scheme of N-arylpyrazole compound 2N according to example 14;
FIG. 16 is a scheme showing the synthesis of 2o, an N-arylpyrazole compound of example 15;
FIG. 17 is a schematic diagram showing the synthesis of pyraclotrobin, a pyrazole bactericide, from Compound 2 d.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every intervening value, to the extent any stated value or intervening value in a stated range, and any other stated or intervening value in a stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The description and examples are intended to be illustrative only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
The reaction scheme of the preparation process of the present invention is shown in FIG. 1.
Example 1
Synthesis of N-arylpyrazoles 2a (FIG. 2 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), followed by weighing N-aryl-3-pyrazolidinone compound 1a (0.20mmol, 32.4mg) and dissolving in dimethyl sulfoxide solvent (2.0mL), covering the reaction tube with a lid, transferring the reaction tube to a 100 ℃ oil bath, and reacting for 18 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1a completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio), so as to obtain the N-arylpyrazole compound 2a (28.3mg, yield 88%).1H NMR(400MHz,DMSO-d6):δ10.26(s,1H),8.22(d,J＝2.6Hz,1H),7.69-7.66(m,2H),7.44-7.40(m,2H),7.19-7.15(m,1H),5.81(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.7,139.8,129.4,128.5,124.6,116.8,94.4.
Example 2
Synthesis of N-arylpyrazoles 2b (FIG. 3 for the scheme):
in a 25mL reaction tube, a magnetic stirrer and iodine were added(5.0 mol%, 2.5mg), N-aryl-3-pyrazolidinone compound 1b (0.20mmol, 35.2mg) is weighed and added, then dimethyl sulfoxide solvent (2.0mL) is added for dissolution, a reaction tube cover is covered, the mixture is transferred to a 100 ℃ oil bath kettle, and the reaction is carried out for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the raw material 1b completely reacts, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2b (30.0mg, yield 86%).1H NMR(400MHz,DMSO-d6):δ10.22(s,1H),8.14(d,J＝2.6Hz,1H),7.56-7.54(m,2H),7.22-7.20(m,2H),5.77(d,J＝2.6Hz,1H),2.29(s,3H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.5,137.7,133.8,129.8,128.2,116.8,94.0,20.4.
Example 3
Synthesis of N-arylpyrazole Compound 2c (FIG. 4 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone compound 1c (0.20mmol, 36.0mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 20 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1c completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio), so as to obtain an N-arylpyrazole compound 2c (22.0mg, yield 62%).1H NMR(400MHz,DMSO-d6):δ10.27(s,1H),8.20(d,J＝2.6Hz,1H),7.71-7.67(m,2H),7.30-7.25(m,2H),5.80(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.8,159.3(d,JC-F＝239.5Hz),136.5(d,JC-F＝2.6Hz),128.7,118.6(d,JC-F＝8.2Hz),116.1(d,JC-F＝22.7Hz),94.4；19F NMR(376MHz,DMSO-d6):δ-118.77to-118.84(m,1F).
Example 4
Synthesis of N-arylpyrazoles 2d (FIG. 5 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone compound 1d (0.20mmol, 39.2mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 18 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1d completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio), so as to obtain N-arylpyrazole compound 2d (33.8mg, yield 87%). .1H NMR(400MHz,DMSO-d6):δ10.36(s,1H),8.25(d,J＝2.6Hz,1H),7.72-7.68(m,2H),7.49-7.46(m,2H),5.83(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.9,138.7,129.3,128.8,128.5,118.3,95.0.
Example 5
Synthesis of N-arylpyrazoles 2e (FIG. 6 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone compound 1e (0.20mmol, 48.0mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 22 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1e is completely reacted, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2e (27.2mg, yield rate)57%). The reason for the lower yield of compound 2 e: part of the starting materials decompose during the reaction.1H NMR(400MHz,DMSO-d6):δ10.37(s,1H),8.25(d,J＝2.6Hz,1H),7.66-7.63(m,2H),7.61-7.59(m,2H),5.83(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.9,139.1,132.2,128.8,118.7,116.6,95.0.
Example 6
Synthesis of N-arylpyrazoles 2f (FIG. 7 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone compound 1f (0.20mmol, 46.0mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 24 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1f completely reacts, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2f (34.0mg, yield 75%).1H NMR(400MHz,DMSO-d6):δ10.53(s,1H),8.39(d,J＝2.6Hz,1H),7.89-7.87(m,2H),7.79-7.77(m,2H),5.91(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ163.4,142.6,129.4,126.8(q,JC-F＝3.8Hz),124.5(q,JC-F＝32.0Hz),124.4(q,JC-F＝269.8Hz),116.8,96.0；19F NMR(376MHz,DMSO-d6):δ-60.39(s,3F).
Example 7
Synthesis of 2g of N-arylpyrazoles (FIG. 8 for the scheme):
adding a magnetic stirrer and iodine (5.0 mol% and 2.5mg) into a 25mL reaction tube, weighing 1g (0.20mmol and 35.2mg) of N-aryl-3-pyrazolidinone compound, adding the N-aryl-3-pyrazolidinone compound, adding dimethyl sulfoxide solvent (2.0mL) for dissolving, covering a reaction tube cover, transferring the reaction tube cover into a 100 ℃ oil bath kettle, and reacting for 18 hours under the reaction condition of air(thin layer chromatography monitoring). After 1g of the raw material completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio) to obtain 2g of an N-arylpyrazole compound (28.0mg, yield 80%).1H NMR(400MHz,DMSO-d6):δ10.00(s,1H),7.71(d,J＝2.4Hz,1H),7.34-7.32(m,1H),7.29-7.25(m,3H),5.73(d,J＝2.4Hz,1H),2.27(s,3H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.1,139.9,132.2,132.0,131.3,127.2,126.6,125.2,92.5,18.3.
Example 8
Synthesis of N-arylpyrazoles 2h (FIG. 9 for the synthetic scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinones were weighed for 1h (0.20mmol, 39.2mg) and added, and then dissolved by adding dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and reacted for 20 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw materials are completely reacted for 1 hour, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound for 2 hours (32.0mg, yield 82%).1H NMR(400MHz,DMSO-d6):δ10.22(s,1H),7.86(d,J＝2.6Hz,1H),7.63-7.60(m,1H),7.54-7.52(m,1H),7.47-7.43(m,1H),7.40-7.35(m,1H),5.80(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.6,137.8,133.1,130.7,128.5,128.2,127.3,126.6,93.6.
Example 9
Synthesis of N-arylpyrazoles 2i (see fig. 10 for synthesis scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl was weighedThe 3-pyrazolidinone compound 1i (0.20mmol, 39.2mg) is added, then dimethyl sulfoxide solvent (2.0mL) is added for dissolution, a reaction tube cover is covered, the reaction tube cover is transferred to a 100 ℃ oil bath pot, and the reaction is carried out for 20 hours under the reaction condition of air (monitoring by thin layer chromatography). After the raw material 1i completely reacts, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2i (33.4mg, 86%).1H NMR(400MHz,DMSO-d6):δ10.42(s,1H),8.32(d,J＝2.4Hz,1H),7.77-7.76(m,1H),7.67-7.64(m,1H),7.46-7.42(m,1H),7.23-7.20(m,1H),5.85(d,J＝2.4Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ163.0,141.0,133.9,131.1,129.1,124.2,116.4,115.2,95.3.
Example 10
Synthesis of N-arylpyrazoles 2j (FIG. 11 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone 1j (0.20mmol, 48.0mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 18 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1j completely reacts, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2j (26.4mg, yield 55%).1H NMR(400MHz,DMSO-d6):δ10.42(s,1H),8.31(d,J＝2.6Hz,1H),7.90-7.89(m,1H),7.71-7.68(m,1H),7.40-7.34(m,2H),5.85(d,J＝2.6Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ163.0,141.1,131.4,129.1,127.1,122.4,119.2,115.5,95.3.
Example 11
Synthesis of N-arylpyrazoles 2k (synthesis scheme see fig. 12):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone 1k (0.20mmol, 46.0mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 24 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the reaction of the raw material 1k is completed, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2k (28.4mg, yield 62%).1H NMR(400MHz,DMSO-d6):δ10.30(s,1H),7.90(d,J＝2.4Hz,1H),7.82-7.81(m,1H),7.54-7.53(m,2H),5.82(d,J＝2.4Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.8,136.9,133.2,131.8,130.1,128.34,128.32,127.4,94.0.
Example 12
Synthesis of N-arylpyrazoles 2l (FIG. 13 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), 1l (0.20mmol, 42.6mg) of N-aryl-3-pyrazolidinone was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 18 hours under the reaction conditions of air (monitoring by thin layer chromatography). After 1l of the raw material completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio) to obtain 2l of the N-arylpyrazole compound (25.2mg, yield 60%).1H NMR(400MHz,DMSO-d6):δ10.37(s,1H),8.37(d,J＝2.4Hz,1H),8.14-8.13(m,1H),8.00-7.95(m,2H),7.93-7.90(m,2H),7.55-7.51(m,1H),7.47-7.43(m,1H),5.87(d,J＝2.4Hz,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.9,137.4,133.4,130.5,129.3,128.8,127.7,127.6,127.0,125.2,117.0,113.1,94.7.
Example 13
Synthesis of N-arylpyrazoles 2m (FIG. 14 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), 1m (0.20mmol, 38.6mg) of N-aryl-3-pyrazolidinone was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 22 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1m completely reacted, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) was added, ethyl acetate (5.0mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, the solvent was evaporated to dryness, and then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate 5:1, volume ratio) to obtain N-arylpyrazole compound 2m (22.0mg, yield 58%).1H NMR(400MHz,DMSO-d6):δ10.29(s,1H),8.24(d,J＝2.6Hz,1H),7.33-7.29(m,1H),7.26-7.24(m,2H),6.76-6.73(m,1H),5.80(d,J＝2.4Hz,1H),3.80(s,3H)；13C{1H}NMR(100MHz,DMSO-d6):δ162.6,160.1,141.0,130.3,128.7,110.3,108.9,102.5,94.5,55.3.
Example 14
Synthesis of N-arylpyrazoles 2N (see fig. 15 for synthesis scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (10.0 mol%, 5.0mg), and N-aryl-3-pyrazolidinone compound 1N (0.20mmol, 35.2mg) was weighed and added, and then dissolved in dimethyl sulfoxide solvent (2.0mL), and the reaction tube was covered with a lid and transferred to a 100 ℃ oil bath and allowed to react for 24 hours under the reaction conditions of air (monitoring by thin layer chromatography). After the raw material 1n completely reacts, the reaction tube is cooled to room temperature, then saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is subjected to column chromatographyChromatography (eluent, petroleum ether: ethyl acetate: 5:1 by volume) gave N-arylpyrazole compound 2N (26.0mg, yield 74%).1H NMR(400MHz,DMSO-d6):δ10.21(s,1H),8.04(d,J＝1.0Hz,1H),7.62-7.59(m,2H),7.41-7.36(m,2H),7.14-7.10(m,1H),1.90(d,J＝1.0Hz,3H)；13C{1H}NMR(100MHz,DMSO-d6):δ161.5,139.9,129.4,126.6,124.0,116.1,103.3,7.1.
Example 15
Synthesis of N-arylpyrazoles 2o (FIG. 16 for the scheme):
a25 mL reaction tube was charged with a magnetic stirrer and iodine (5.0 mol%, 2.5mg), and N-aryl-3-pyrazolidinone compound 1o (0.20mmol, 47.6mg) was weighed and added, followed by addition of dimethyl sulfoxide solvent (2.0mL) for dissolution, covering the reaction tube lid, transferring it to a 120 ℃ oil bath, and reacting under air reaction conditions for 24 hours (monitoring by thin layer chromatography). After the reaction of the raw material 1o is completed, the reaction tube is cooled to room temperature, then a saturated sodium thiosulfate solution (5.0mL) is added, ethyl acetate (5.0mL) is extracted for 3 times, an organic layer solution is taken, anhydrous sodium sulfate is dried, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate: 5:1, volume ratio) to obtain the N-arylpyrazole compound 2o (24.2mg, yield 51%).1H NMR(400MHz,DMSO-d6):δ10.22(s,1H),7.35-7.32(m,5H),7.27-7.24(m,1H),7.22-7.19(m,2H),7.16-7.14(m,2H),5.93(s,1H)；13C{1H}NMR(100MHz,DMSO-d6):δ161.8,143.2,139.9,130.4,128.9,128.6,128.4,126.6,124.6,94.3.
The N-arylpyrazole compound synthesized by the invention can be used for synthesizing bactericides or pharmaceutical intermediates, for example, the compound 2d can be used for synthesizing the pyrazole bactericides pyraclotrobin, and a synthetic route diagram is shown in figure 17.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.

Claims (7)

1. An iodine-promoted method for preparing N-aryl pyrazole compounds, which is characterized by comprising the following steps: the N-aryl-3-pyrazolidinone compound is used as an initial raw material, dimethyl sulfoxide is used as a reaction solvent, iodine is used as a catalyst, and the N-aryl-3-pyrazolidinone compound is subjected to dehydroaromatization under the reaction condition of 100-120 ℃ to prepare the N-aryl pyrazole compound.
2. The iodine-promoted process for preparing N-arylpyrazoles according to claim 1, wherein the structural formula of the N-aryl-3-pyrazolidinone compound is shown in formula 1, and R in formula 1 is1H, 2-Me, 2, 4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF3；R2H or Ph; r3H or Me;
Figure FDA0003529819370000011
3. the iodine-promoted process for preparing N-arylpyrazoles according to claim 1, wherein the structural formula of the N-arylpyrazoles is shown in formula 2, and R in formula 2 is1H, 2-Me, 2, 4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF3；R2H or Ph; r3H or Me;
Figure FDA0003529819370000012
4. the iodine-promoted process for preparing N-arylpyrazoles of claim 1, wherein the reaction time is 18-24 hours.
5. The iodine-promoted process for producing N-arylpyrazoles according to claim 1, wherein the mass ratio of N-aryl-3-pyrazolidinone compound to iodine is (32.4-48.0): (2.5-5.0).
6. The iodine-promoted process for preparing N-arylpyrazoles according to claim 1, wherein the reaction is carried out in an air atmosphere.
7. The iodine-promoted method for preparing N-arylpyrazoles according to claim 1, further comprising the steps of extraction, drying and column chromatography separation after the reaction at 120 ℃ of 100 ℃.
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