CN114456117B - Iodine-promoted method for preparing N-aryl pyrazole compound - Google Patents

Iodine-promoted method for preparing N-aryl pyrazole compound Download PDF

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CN114456117B
CN114456117B CN202210202175.5A CN202210202175A CN114456117B CN 114456117 B CN114456117 B CN 114456117B CN 202210202175 A CN202210202175 A CN 202210202175A CN 114456117 B CN114456117 B CN 114456117B
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iodine
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CN114456117A (en
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李登科
沈先福
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Qujing Normal University
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Qujing Normal University
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    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms

Abstract

The invention discloses a method for preparing an N-aryl pyrazole compound by iodine promotion, 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, and the N-aryl-3-pyrazolidinone compound is subjected to dehydroaromatization under the reaction condition of 100-120 ℃ to prepare a series of N-aryl pyrazoles compounds with novel structures, which can be directly used and used as substrates in other reactions, and the adopted reaction conditions are mild, the operation steps and the post-treatment process are simple, and the product yield is higher and is 51% -88%.

Description

Iodine-promoted method for preparing N-aryl pyrazole compound
Technical Field
Relates to the technical field of organic synthesis, in particular to a method for preparing N-aryl pyrazole compounds by iodine promotion.
Background
Currently, more than half of the drug molecules belong to the class of nitrogen-containing heterocyclic compounds. Pyrazole compounds are taken 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. For example, celecoxib (Celebrex) for alleviating symptoms and signs of osteoarthritis, alleviating symptoms and signs of rheumatoid arthritis in adults, treating acute pain in adults; rimonabant (Acomplia), the first type 1 cannabinoid receptor (CB 1) inhibitor type weight loss drug worldwide, has insulin sensitization and lipid metabolism disorder ameliorating effects.
Many methods for synthesizing N-arylpyrazoles have been developed, among which synthesis of N-arylpyrazoles is most common by a ring condensation reaction of N-arylhydrazine with 1, 3-dicarbonyl compounds or their alternatives. However, this process is generally a mixture of two regioselective isomers for the asymmetric 1, 3-diketones. An alternative is to catalyze the N-arylation of 1-hydropyrazoles, which, however, in the case of asymmetric pyrazoles as starting materials, also face regioselectivity problems, since pyrazoles can act as tautomers, thus giving rise to dual nucleophilicity. In addition, the existing N-aryl pyrazole compound synthesis method is mainly carried out under the protection of inert gas at higher temperature and metal participation and long reaction time, 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-aryl pyrazole compounds, which has mild reaction conditions and simple operation steps and post-treatment processes, solves the problems in the prior art, improves the yield, and is suitable for preparing a large amount of N-aryl pyrazole compounds.
In order to achieve the above object, the present invention provides the following solutions:
the invention provides a method for preparing an N-aryl pyrazole compound by iodine promotion, which comprises the following steps: n-aryl-3-pyrazolidinone compound is taken as an initial raw material, dimethyl sulfoxide (DMSO) is taken as a reaction solvent, iodine is taken as a catalyst, and dehydrogenation aromatization is carried out on the N-aryl-3-pyrazolidinone compound under the reaction condition of 100-120 ℃ to prepare the N-aryl pyrazole compound.
The invention provides a preparation method of N-aryl pyrazole compounds, which takes easily obtained N-aryl-3-pyrazolidinone compounds (32.4 mg-48.0 mg) as a starting material, dimethyl sulfoxide (DMSO) as a reaction solvent, iodine (2.5-5.0 mg) as a catalyst, and the N-aryl-3-pyrazolidinone compounds react for 18-24 hours (monitored by thin layer chromatography) at 100-120 ℃ under the air condition, so that a series of N-aryl pyrazole compounds with novel structures are obtained in a green and efficient manner. The product prepared by the method can be directly used, can also be used as a substrate for other reactions, has mild reaction conditions, simple operation steps and post-treatment processes, and has high product yield of 51-88%.
Further, the N-aryl-3-pyrazolidinylThe structural formula of the compound is shown in formula 1, R in formula 1 1 =h, 2-Me, 2,4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF 3 ；R 2 =h or Ph; r is R 3 =h or Me;
further, the structural formula of the N-aryl pyrazole compound is shown as formula 2, wherein R in formula 2 1 =h, 2-Me, 2,4-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-C, 4-Br or 4-CF 3 ；R 2 =h or Ph; r is R 3 =h or Me;
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 iodine is (32.4-48.0): (2.5-5.0).
Further, the reaction was carried out under an air atmosphere.
Further, after the reaction is finished at 100-120 ℃, the method also comprises the processes of extraction, drying and column chromatography separation.
Further, after the reaction was completed, the reaction mixture was cooled to room temperature, then saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and 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 an N-arylpyrazole compound (yield: 51% -88%).
The N-aryl pyrazole 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 mass preparation 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.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a reaction scheme of the preparation method of the present invention;
FIG. 2 is a synthetic scheme for N-arylpyrazoles 2a of example 1;
FIG. 3 is a synthetic scheme for N-arylpyrazole compound 2b of example 2;
FIG. 4 is a synthetic scheme for N-arylpyrazoles 2c of example 3;
FIG. 5 is a synthetic scheme for N-arylpyrazoles 2d of example 4;
FIG. 6 is a synthetic scheme for N-arylpyrazoles 2e of example 5;
FIG. 7 is a synthetic scheme for N-arylpyrazoles 2f of example 6;
FIG. 8 is a synthetic scheme showing the synthesis of 2g of N-arylpyrazoles of example 7;
FIG. 9 is a synthetic scheme for N-arylpyrazoles 2h of example 8;
FIG. 10 is a synthetic scheme for N-arylpyrazoles 2i of example 9;
FIG. 11 is a synthetic scheme for N-arylpyrazoles 2j of example 10;
FIG. 12 is a synthetic scheme for N-arylpyrazole compound 2k of example 11;
FIG. 13 is a synthetic scheme showing the synthesis of 2l of the N-arylpyrazoles of example 12;
FIG. 14 is a synthetic scheme for N-arylpyrazoles 2m of example 13;
FIG. 15 is a synthetic scheme for N-arylpyrazoles 2N of example 14;
FIG. 16 is a synthetic scheme for N-arylpyrazole compound 2o of example 15;
FIG. 17 is a circuit diagram of compound 2d for synthesizing the pyrazole fungicide Pyraclostrobin.
Detailed Description
Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions 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. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, 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 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 invention described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present invention. The specification and examples of the present invention are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
The reaction route diagram of the preparation method of the invention is shown in figure 1.
Example 1
Synthesis of N-arylpyrazole Compound 2a (synthetic scheme see FIG. 2):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1a (0.20 mmol,32.4 mg) was weighed and added, dimethyl sulfoxide solvent (2.0 mL) was then added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the raw material 1a was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2a (28.3 mg, yield 88%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.7,139.8,129.4,128.5,124.6,116.8,94.4.
Example 2
Synthesis of N-arylpyrazole Compound 2b (synthetic scheme see FIG. 3):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1b (0.20 mmol,35.2 mg) was weighed and added, followed by dissolution in dimethyl sulfoxide solvent (2.0 mL), covering the reaction tube, transferring it to an oil bath at 100℃and reacting for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the raw material 1b is completed, the reaction tube is cooled to room temperature, and then is added withSaturated sodium thiosulfate solution (5.0 mL) was added, extraction was performed 3 times with ethyl acetate (5.0 mL), the organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated off, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2b (30.0 mg, yield 86%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.5,137.7,133.8,129.8,128.2,116.8,94.0,20.4.
Example 3
Synthesis of N-arylpyrazole Compound 2c (synthetic scheme see FIG. 4):
into a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1c (0.20 mmol,36.0 mg) was weighed and then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted under the reaction condition of air for 20 hours (monitored by thin layer chromatography). After the reaction of the raw material 1c was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2c (22.0 mg, yield 62%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.8,159.3(d,J C-F ＝239.5Hz),136.5(d,J C-F ＝2.6Hz),128.7,118.6(d,J C-F ＝8.2Hz),116.1(d,J C-F ＝22.7Hz),94.4； 19 F NMR(376MHz,DMSO-d 6 ):δ-118.77to-118.84(m,1F).
Example 4
Synthesis of N-arylpyrazole 2d (synthetic scheme see FIG. 5):
into a 25mL reaction tube, a magnetic stirrer and iodine were added(5.0 mol%,2.5 mg) N-aryl-3-pyrazolidinone 1d (0.20 mmol,39.2 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted for 18 hours under air reaction conditions (monitored by thin layer chromatography). After the reaction of the starting material 1d was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2d (33.8 mg, yield 87%). . 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.9,138.7,129.3,128.8,128.5,118.3,95.0.
Example 5
Synthesis of N-arylpyrazole Compound 2e (synthetic scheme see FIG. 6):
into a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1e (0.20 mmol,48.0 mg) was weighed and then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted under the reaction condition of air for 22 hours (monitored by thin layer chromatography). After the reaction of the raw material 1e was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2e (27.2 mg, yield 57%). The reason for the lower yield of compound 2 e: part of the raw materials are decomposed during the reaction. 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.9,139.1,132.2,128.8,118.7,116.6,95.0.
Example 6
Synthesis of N-arylpyrazole Compound 2f (synthetic scheme see FIG. 7):
into a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1f (0.20 mmol,46.0 mg) was weighed and added, followed by dissolution in dimethyl sulfoxide solvent (2.0 mL), covering the reaction tube, transferring it to an oil bath at 100℃and reacting for 24 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the raw material 1f was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2f (34.0 mg, yield 75%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ163.4,142.6,129.4,126.8(q,J C-F ＝3.8Hz),124.5(q,J C-F ＝32.0Hz),124.4(q,J C-F ＝269.8Hz),116.8,96.0； 19 F NMR(376MHz,DMSO-d 6 ):δ-60.39(s,3F).
Example 7
Synthesis of N-arylpyrazoles 2g (synthetic scheme see FIG. 8):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, 1g (0.20 mmol,35.2 mg) of N-aryl-3-pyrazolidinone was weighed and added, followed by dissolution in dimethyl sulfoxide solvent (2.0 mL), covering the reaction tube, transferring it to an oil bath at 100℃and reacting for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of 1g of the raw material was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to obtain N-arylpyrazole2g of the compound (28.0 mg, yield 80%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):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 (synthetic scheme see FIG. 9):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone was weighed for 1h (0.20 mmol,39.2 mg) and then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted for 20 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the starting material 1h was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give an N-arylpyrazole compound for 2h (32.0 mg, yield 82%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ162.6,137.8,133.1,130.7,128.5,128.2,127.3,126.6,93.6.
Example 9
Synthesis of N-arylpyrazole Compound 2i (synthetic scheme see FIG. 10):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1i (0.20 mmol,39.2 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted for 20 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the starting material 1i was completed, the reaction tube was cooled to room temperature, and then a saturated sodium thiosulfate solution (5.0mL), ethyl acetate (5.0 mL), drying the organic layer solution, evaporating the solvent, and separating the crude product by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2i (33.4 mg, 86%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ163.0,141.0,133.9,131.1,129.1,124.2,116.4,115.2,95.3.
Example 10
Synthesis of N-arylpyrazole Compound 2j (synthetic scheme see FIG. 11):
into a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1j (0.20 mmol,48.0 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of the raw material 1j was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2j (26.4 mg, yield 55%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ163.0,141.1,131.4,129.1,127.1,122.4,119.2,115.5,95.3.
Example 11
Synthesis of N-arylpyrazole Compound 2k (synthetic scheme see FIG. 12):
into a 25mL reaction tube, magnetic stirring bar and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1k (0.20 mmol,46.0 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped,this was transferred to a 100 ℃ oil bath and reacted for 24 hours under air reaction conditions (monitored by thin layer chromatography). After the reaction of the raw material 1k was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2k (28.4 mg, yield 62%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):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 (synthetic scheme see FIG. 13):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, 1l (0.20 mmol,42.6 mg) of N-aryl-3-pyrazolidinone was weighed and added, followed by dissolution in dimethyl sulfoxide solvent (2.0 mL), covering the reaction tube, transferring it to an oil bath at 100℃and reacting for 18 hours under the reaction condition of air (monitored by thin layer chromatography). After the reaction of 1l of the starting material was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, extraction was performed 3 times with ethyl acetate (5.0 mL), an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give 2l of N-arylpyrazoles (25.2 mg, yield 60%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):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 (synthetic scheme see FIG. 14):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1m (0.20 mmol,38.6 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted under the reaction condition of air for 22 hours (monitored by thin layer chromatography). After the reaction of the starting material 1m was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2m (22.0 mg, yield 58%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):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-arylpyrazole Compound 2N (synthetic scheme see FIG. 15):
into a 25mL reaction tube, a magnetic stirrer and iodine (10.0 mol%,5.0 mg) were added, N-aryl-3-pyrazolidinone 1N (0.20 mmol,35.2 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 100℃and reacted under the reaction condition of air for 24 hours (monitored by thin layer chromatography). After the reaction of the raw material 1N was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2N (26.0 mg, yield 74%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ161.5,139.9,129.4,126.6,124.0,116.1,103.3,7.1.
Example 15
Synthesis of N-arylpyrazoles 2o (synthetic scheme see FIG. 16):
in a 25mL reaction tube, a magnetic stirrer and iodine (5.0 mol%,2.5 mg) were added, N-aryl-3-pyrazolidinone 1o (0.20 mmol,47.6 mg) was weighed and added, then dimethyl sulfoxide solvent (2.0 mL) was added for dissolution, the reaction tube was capped, transferred to an oil bath at 120℃and reacted under the reaction condition of air for 24 hours (monitored by thin layer chromatography). After the reaction of the starting material 1o was completed, the reaction tube was cooled to room temperature, then a saturated sodium thiosulfate solution (5.0 mL) was added, ethyl acetate (5.0 mL) was extracted 3 times, an organic layer solution was taken, dried over anhydrous sodium sulfate, and the solvent was evaporated, then the crude product was separated by column chromatography (eluent, petroleum ether: ethyl acetate=5:1, volume ratio) to give N-arylpyrazoles 2o (24.2 mg, yield 51%). 1 H NMR(400MHz,DMSO-d 6 ):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)； 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ161.8,143.2,139.9,130.4,128.9,128.6,128.4,126.6,124.6,94.3.
The N-aryl pyrazole compound synthesized by the invention can be used for synthesizing bactericides or drug intermediates, for example, the compound 2d can be used for synthesizing the pyrazole bactericides Pyraclostrobin, and the synthetic route diagram is shown in figure 17.
The above embodiments are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solutions of the present invention should fall within the protection scope defined by the claims of the present invention without departing from the design spirit of the present invention.

Claims (2)

1. A method for preparing an N-arylpyrazole compound with iodine promotion, comprising the steps of: the N-aryl-3-pyrazolidinone compound is taken as an initial raw material, dimethyl sulfoxide is taken as a reaction solvent, iodine is taken as a catalyst, the reaction is carried out for 18 to 24 hours at the temperature of 100 to 120 ℃, and the N-aryl-3-pyrazolidinone compound is subjected to dehydroaromatization to prepare the N-aryl pyrazole compound;
the structural formula of the N-aryl-3-pyrazolidinone compound is shown as formula 1, R in formula 1 1 =h, 2-Me, 3-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-Br or 4-CF 3 ；R 2 =h or Ph; r is R 3 =h or Me;
the structural formula of the N-aryl pyrazole compound is shown in formula 2, R in formula 2 1 =h, 2-Me, 3-Cl, 3-Br, 3-OMe, 4-Me, 4-F, 4-Br or 4-CF 3 ；R 2 =h or Ph; r is R 3 =h or Me;
2；
the mass ratio of the N-aryl-3-pyrazolidinone compound to iodine is (32.4-48.0): (2.5-5.0);
the reaction was carried out under an air atmosphere.
2. The method for preparing N-arylpyrazoles by iodine according to claim 1, wherein the method further comprises the steps of extraction, drying and column chromatography separation after the reaction is finished at 100-120 ℃.
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