CN114874144A - Process for preparing 4-bromo-N-arylpyrazole compound - Google Patents

Process for preparing 4-bromo-N-arylpyrazole compound Download PDF

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CN114874144A
CN114874144A CN202210315851.XA CN202210315851A CN114874144A CN 114874144 A CN114874144 A CN 114874144A CN 202210315851 A CN202210315851 A CN 202210315851A CN 114874144 A CN114874144 A CN 114874144A
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bromo
compound
pyrazolidinones
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段玉莲
李登科
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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
    • 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
    • C07D231/26—1-Phenyl-3-methyl-5- pyrazolones, unsubstituted or substituted on the phenyl ring
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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Abstract

The scheme discloses a process for preparing a 4-bromo-N-arylpyrazole compound, which comprises the following steps: in an organic solvent dimethyl sulfoxide (DMSO), taking an N-aryl-3-pyrazolidone compound as a raw material, and reacting with N-bromosuccinimide (NBS) under the heating condition of 95-105 ℃ in air to obtain a 4-bromo-N-arylpyrazole compound.

Description

Process for preparing 4-bromo-N-arylpyrazole compound
Technical Field
The scheme belongs to the technical field of synthesis of N-aryl pyrazole compounds, and particularly relates to a process for preparing 4-bromo N-aryl pyrazole compounds.
Background
N-arylpyrazoles have been widely used in the fields of medicines, pesticides, and materials due to their unique chemical structures and properties, and thus have received much attention from scientists. For example, the pesticide fipronil is found by Bayer company, has a broad insecticidal spectrum and can control lepidoptera pests such as vegetables and cotton; the medicine celecoxib (Celebrex) is used for relieving symptoms and signs of osteoarthritis, relieving symptoms and signs of adult rheumatoid arthritis and treating acute adult pain.
Many methods have been developed for the synthesis of N-arylpyrazoles, the most common of which are the preparation strategies: obtained by the cyclocondensation of N-arylhydrazines with 1, 3-dicarbonyl compounds or the like, but this process is generally accompanied by the formation of a mixture of two regioselective isomers for asymmetric 1, 3-diketones. Therefore, the development of a pyrazole compound with cheap and easily obtained raw materials, simple steps, convenient operation, mild conditions and high efficiency is always a hotspot concerned by organic chemistry and pharmacy workers.
Disclosure of Invention
The scheme aims to overcome at least one defect (deficiency) of the prior art and provides a method for preparing a 4-bromo N-aryl pyrazole compound, the bromo pyrazole derivative is synthesized by dehydroaromatization/bromination of N-aryl-3-pyrazolidone, the reaction condition is mild, the operation steps and the post-treatment process are simple, and the yield is high.
In order to solve the technical problem, the following technical scheme is adopted:
a process for preparing 4-bromo-N-arylpyrazole compounds comprises the following steps: in an organic solvent dimethyl sulfoxide (DMSO), taking an N-aryl-3-pyrazolidone compound as a raw material, and reacting with N-bromosuccinimide (NBS) under the heating condition of 95-105 ℃ in air to obtain a 4-bromo-N-arylpyrazole compound.
Preferably, the reaction route of the process is as follows:
Figure BDA0003568977140000011
wherein, the formula (1) is the N-aryl-3-pyrazolidinone compound, and the formula (2) is the 4-bromo-N-arylpyrazole compound; in the formula (1) or the formula (2), R 1 Is hydrogen, halogen, alkyl, haloalkyl or alkoxy, preferably hydrogen, halogen, methyl, halomethyl or methoxy, R 2 Is hydrogen or phenyl.
Preferably, the 4-bromo N-arylpyrazole compound is selected from the group consisting of 3-hydroxy-4-bromo-N-arylpyrazole, 3-hydroxy-4-bromo-N-p-tolylpyrazole, 3-hydroxy-4-bromo-N-p-fluorophenylpyrazole, 3-hydroxy-4-bromo-N-p-chlorophenylpyrazole, 3-hydroxy-4-bromo-N-p-bromophenylpyrazole, 3-hydroxy-4-bromo-N- [4- (trifluoromethyl) phenyl ] pyrazole, 3-hydroxy-4-bromo-N- (2-methylphenyl) pyrazole, 3-hydroxy-4-bromo-N- (2-chlorophenyl) pyrazole, N-bromo-N-phenylpyrazole, N-bromo-4-phenylpyrazole, N-bromo-N- (2-chlorophenyl) pyrazole, N-bromo-4-hydroxy-4-phenylpyrazole, N-phenylpyrazole, and N-phenylpyrazole, 3-hydroxy-4-bromo-N- (3-chlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-bromophenyl) pyrazole, 3-hydroxy-4-bromo-N- (2, 4-dichlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-methoxyphenyl) pyrazole, or 3-hydroxy-4-bromo-N, 5-diphenylpyrazole; the N-aryl-3-pyrazolidinones are selected from the group consisting of N-aryl-3-pyrazolidinones, N-p-tolyl-3-pyrazolidinones, N-p-fluorophenyl-3-pyrazolidinones, N-p-chlorophenyl-3-pyrazolidinones, N-p-bromophenyl-3-pyrazolidinones, N- [4- (trifluoromethyl) phenyl ] -3-pyrazolidinones, N- (2-methylphenyl) -3-pyrazolidinones, N- (2-chlorophenyl) -3-pyrazolidinones, N- (3-bromophenyl) -3-pyrazolidinones, N- (2, 4-dichlorophenyl) -3-pyrazolidinone, N- (3-methoxyphenyl) -3-pyrazolidinone or N, 5-diphenyl-3-pyrazolidinone.
Preferably, the above process comprises the steps of:
s1, dissolving an N-aryl-3-pyrazolidinone compound and N-bromosuccinimide by using an organic solvent dimethyl sulfoxide;
s2, reacting the mixture obtained in the step S1 under the heating condition of 95-105 ℃ in air until the reaction is complete;
and S3, cooling the crude product obtained in the step S2 to room temperature, extracting with water and ethyl acetate, drying the organic layer solution, evaporating the solvent to dryness, and performing column chromatography separation.
More preferably, in step S1, the amount of N-bromosuccinimide is 1.1 to 1.3 equivalents, and most preferably 1.2 equivalents, based on the molar amount of the N-aryl-3-pyrazolidinone compound.
More preferably, in step S2, the end point of the reaction is monitored by thin layer chromatography.
More preferably, in step S3, the organic layer solution is dried with anhydrous sodium sulfate.
Compared with the prior art, the beneficial effect of this scheme does:
the method has the advantages of cheap and easily-obtained raw materials, mild reaction conditions, good functional group compatibility, simple operation steps and post-treatment process and high efficiency; the reaction does not need any transition metal catalyst and other complex reaction conditions, thereby avoiding the pollution of the medicine caused by the introduction of harmful metal impurities into medicinal bioactive molecules; meanwhile, bromine atoms are introduced to the pyrazole ring through aromatization and bromination reactions, and the product can be further applied to metal-catalyzed coupling reactions and halogen/metal exchange reactions, is easy to derivatization, synthesizes N-arylpyrazole compounds with diversified structures, and provides a research basis for the research on the medicinal chemistry and the biological activity of related molecules.
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FIG. 1 is nuclear magnetic resonance of Compound 2a 1 H NMR spectrum.
FIG. 2 is nuclear magnetic resonance of Compound 2a 13 C NMR spectrum.
FIG. 3 is nuclear magnetic resonance of Compound 2b 1 H NMR spectrum.
FIG. 4 nuclear magnetic resonance of Compound 2b 13 C NMR spectrum.
FIG. 5 nuclear magnetic resonance of Compound 2c 1 H NMR spectrum.
FIG. 6 NMR of Compound 2c 13 C NMR spectrum.
FIG. 7 NMR of Compound 2d 1 H NMR spectrum.
FIG. 8 is nuclear magnetic resonance of Compound 2d 13 C NMR spectrum.
FIG. 9 NMR of Compound 2e 1 H NMR spectrum.
FIG. 10 shows NMR of Compound 2e 13 C NMR spectrum.
FIG. 11 is nuclear magnetic resonance of Compound 2f 1 H NMR spectrum.
FIG. 12 NMR of Compound 2f 13 C NMR spectrum.
FIG. 13 NMR of Compound 2g 1 H NMR spectrum.
FIG. 14 NMR of Compound 2g 13 C NMR spectrum.
FIG. 15 NMR of Compound 2h 1 H NMR spectrum.
FIG. 16 NMR of Compound 2h 13 C NMR spectrum.
FIG. 17 is nuclear magnetic resonance of Compound 2i 1 H NMR spectrum.
FIG. 18 NMR of Compound 2i 13 C NMR spectrum.
FIG. 19 is nuclear magnetic resonance of Compound 2j 1 H NMR spectrum.
FIG. 20 is a compound2j nuclear magnetic resonance 13 C NMR spectrum.
FIG. 21 NMR of Compound 2k 1 H NMR spectrum.
FIG. 22 is a nuclear magnetic co-ordination of Compound 2k 13 C NMR spectrum.
FIG. 23 NMR of Compound 2l 1 H NMR spectrum.
FIG. 24 NMR of Compound 2l 13 C NMR spectrum.
FIG. 25 shows NMR of Compound 2m 1 H NMR spectrum.
FIG. 26 is nuclear magnetic resonance of Compound 2m 13 C NMR spectrum.
Detailed Description
As described above, the present invention provides a process for producing a 4-bromo N-arylpyrazole compound represented by the formula (2): in an organic solvent dimethyl sulfoxide (DMSO), taking an N-aryl-3-pyrazolidone compound shown in a formula (1) as a raw material, and reacting with N-bromosuccinimide (NBS) in the presence of air at a heating temperature of 95-105 ℃ (namely 100 +/-5 ℃) to obtain a 4-bromo N-arylpyrazole compound shown in a formula (2); the reaction route is as follows:
Figure BDA0003568977140000041
in the formula (1) or the formula (2), R 1 Is hydrogen, halogen, alkyl, haloalkyl or alkoxy, preferably hydrogen, halogen, methyl, halomethyl or methoxy; r 2 Is hydrogen or phenyl.
In a preferred embodiment of this embodiment, the 4-bromo N-arylpyrazole compound of formula (2) is selected from the group consisting of 3-hydroxy-4-bromo-N-arylpyrazole, 3-hydroxy-4-bromo-N-p-tolylpyrazole, 3-hydroxy-4-bromo-N-p-fluorophenylpyrazole, 3-hydroxy-4-bromo-N-p-chlorophenylpyrazole, 3-hydroxy-4-bromo-N-p-bromophenylpyrazole, 3-hydroxy-4-bromo-N- [4- (trifluoromethyl) phenyl ] pyrazole, 3-hydroxy-4-bromo-N- (2-methylphenyl) pyrazole, 3-hydroxy-4-bromo-N- (2-chlorophenyl) pyrazole, N-bromo-N-phenylpyrazole, N-bromo-N-p-fluorophenylpyrazole, N-bromo-4-chloro-phenyl-3-4-bromo-4-N- (2-chlorophenyl) pyrazole, N-chloro-phenyl-pyrazole, p-bromo-fluorophenylpyrazole, p-fluorophenylpyrazole, and optionally substituted or mixtures thereof, 3-hydroxy-4-bromo-N- (3-chlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-bromophenyl) pyrazole, 3-hydroxy-4-bromo-N- (2, 4-dichlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-methoxyphenyl) pyrazole, or 3-hydroxy-4-bromo-N, 5-diphenylpyrazole; the N-aryl-3-pyrazolidinones of formula (1) are selected from the group consisting of N-aryl-3-pyrazolidinones, N-p-tolyl-3-pyrazolidinones, N-p-fluorophenyl-3-pyrazolidinones, N-p-chlorophenyl-3-pyrazolidinones, N-p-bromophenyl-3-pyrazolidinones, N- [4- (trifluoromethyl) phenyl ] -3-pyrazolidinones, N- (2-methylphenyl) -3-pyrazolidinones, N- (2-chlorophenyl) -3-pyrazolidinones, N- (3-bromophenyl) -3-pyrazolidinones, N-p-tolyl-3-pyrazolidinones, N-p-chlorophenyl-3-pyrazolidinones, N- (3-bromophenyl) -3-pyrazolidinones, N-methyl-3-pyrazolidinones, N-methyl-3-yl-pyrazolidinones, N-methyl-3-methyl-3-pyrazolidinones, N-methyl-ethyl-methyl-ethyl-methyl-ethyl-3-ethyl, N- (2, 4-dichlorophenyl) -3-pyrazolidinone, N- (3-methoxyphenyl) -3-pyrazolidinone or N, 5-diphenyl-3-pyrazolidinone.
The process comprises the following steps:
s1, dissolving an N-aryl-3-pyrazolidinone compound and N-bromosuccinimide by using an organic solvent dimethyl sulfoxide;
s2, reacting the mixture obtained in the step S1 under the heating condition of 95-105 ℃ in air until the reaction is complete;
and S3, cooling the crude product obtained in the step S2 to room temperature, extracting with water and ethyl acetate, drying the organic layer solution, evaporating the solvent, and performing column chromatography separation (eluent, petroleum ether, ethyl acetate (5/1-3/1), and Rf (0.20-0.35)).
In a preferred embodiment of this embodiment, in step S1, the amount of N-bromosuccinimide is 1.1 to 1.3 equivalents, and most preferably 1.2 equivalents, based on the molar amount of the N-aryl-3-pyrazolidinone compound.
In a preferred embodiment of this embodiment, step S2 is performed by monitoring the end point of the reaction by thin layer chromatography.
In a preferred embodiment of this embodiment, the organic layer solution is dried with anhydrous sodium sulfate in step S3.
In a preferred embodiment of this embodiment, the reaction route of the above process is:
Figure BDA0003568977140000042
wherein, formula (1), formula (2) and R 1 、R 2 As defined above.
The method comprises the following steps:
s1, dissolving an N-aryl-3-pyrazolidinone compound and 1.2 equivalent of N-bromosuccinimide by using an organic solvent dimethyl sulfoxide;
s2, reacting the mixture obtained in the step S1 for 24 hours under the heating condition of air and 100 ℃, and monitoring the reaction completion through thin layer chromatography;
s3, cooling the crude product obtained in the step S2 to room temperature, extracting with water and ethyl acetate for 3 times, drying the organic layer solution with anhydrous sodium sulfate, evaporating the solvent to dryness, and performing column chromatography separation (eluent, petroleum ether: ethyl acetate).
In order to make the technical solution better understood by those skilled in the art, the present solution is further described in detail with reference to the specific embodiments below. The process methods used in the examples are all conventional methods unless otherwise specified; the materials used, unless otherwise specified, are commercially available.
Among them, the compound 1a, the compound 1b, the compound 1c, the compound 1d, the compound 1e, the compound 1f, the compound 1g, the compound 1h, the compound 1i, the compound 1j, the compound 1k, the compound 1l, the compound 1m, N-bromosuccinimide (NBS), and a dimethyl sulfoxide solvent (DMSO) are known.
Example 1
Preparation of 4-bromo-N-arylpyrazole compound 2a
The reaction route is as follows:
Figure BDA0003568977140000051
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 32.4mg (0.20mmol) of compound 1a were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, and the reaction tube was covered, transferred to a 100 ℃ oil bath, and reacted under air reaction conditions for 24 hours (monitored by thin layer chromatography). After the compound 1a completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 34.2mg of the compound 2a with a yield of 71%.
By means of H 1 The structure of the compound 2a obtained as described above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 1: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.06(s,1H),8.54(s,1H),7.69-7.67(m,2H),7.46-7.42(m,2H),7.23-7.19(m, 1H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2a obtained above, the results of which are shown in FIG. 2: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.5,139.4,129.6,128.6,125.4,116.8,82.1. As can be seen from FIGS. 1-2, the compound 2a obtained is 3-hydroxy-4-bromo-N-arylpyrazole.
Example 2
Preparation of 4-bromo-N-arylpyrazole compound 2b
The reaction route is as follows:
Figure BDA0003568977140000061
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 35.2mg (0.20mmol) of compound 1b were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, and the reaction tube was covered and transferred to a 100 ℃ oil bath pan and reacted for 24 hours under reaction conditions of air (monitoring by thin layer chromatography). After the compound 1b completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract 3 times, the 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) to give 38.4mg of the compound with a yield of 76%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2b obtained above, the results of which are shown in FIG. 3: 1 H NMR(400MHz,DMSO-d 6 ):δ10.99(br,s,1H),8.48(s1H),7.56-7.54(m,2H),7.25-7.23(m,2H),2.30(s, 3H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2b obtained above, the results of which are shown in FIG. 4: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.3,137.2,134.6,129.9,128.3,116.8,81.5,20.4. As can be seen from FIGS. 3to 4, the obtained compound 2b was 3-hydroxy-4-bromo-N-p-tolylpyrazole.
Example 3
Preparation of 4-bromo-N-arylpyrazole compound 2c
The reaction route is as follows:
Figure BDA0003568977140000062
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 36.0mg (0.20mmol) of compound 1c were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1c completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 35.2mg of the compound with a yield of 68%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2c obtained above, the results of which are shown in FIG. 5: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.07(br, s,1H),8.52(s,1H),7.72-7.67(m,2H),7.33-7.27(m, 2H); by C 13 The structure of the compound 2c obtained above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 6: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.7(d,J C-F ＝240.4Hz),159.6,136.0(d,J C-F ＝2.3Hz),128.7,118.8(d,J C-F ＝8.3Hz),116.3(d,J C-F ＝22.8Hz),82.1； 19 F NMR(376MHz,DMSO-d 6 ) -117.73to-117.80(m, 1F). From fig. 5 >6 it can be seen that compound 2c obtained is 3-hydroxy-4-bromo-N-p-fluorophenylpyrazole.
Example 4
Preparation of 4-bromo-N-arylpyrazole compound 2d
The reaction route is as follows:
Figure BDA0003568977140000071
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 39.3mg (0.20mmol) of compound 1d were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1d completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 40.0mg of the compound with a yield of 73%.
By means of H 1 The structure of the compound 2d obtained above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 7: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.16(br, s,1H),8.58(s,1H),7.71-7.67(m,2H),7.52-7.48(m, 2H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2d obtained above, the results of which are shown in FIG. 8: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.7,138.2,129.4,129.2,128.8,118.3,82.7. As can be seen from FIGS. 7 to 8, the obtained compound 2d is 3-hydroxy-4-bromo-N-p-chlorophenyl pyrazole.
Example 5
Preparation of 4-bromo-N-arylpyrazole compound 2e
The reaction route is as follows:
Figure BDA0003568977140000081
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 48.2mg (0.20mmol) of compound 1e were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1e completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 33.0mg of the compound with a yield of 52%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2e obtained above, the results of which are shown in FIG. 9: 1 H NMR(400MHz,DMSO-d 6 ) δ 11.12(br, s,1H),8.56(s,1H),7.63(s, 4H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2e obtained above, the results of which are shown in FIG. 10: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.7,138.5,132.3,128.7,118.7,117.3,82.7. As can be seen from FIGS. 9 to 10, the obtained compound 2e was 3-hydroxy-4-bromo-N-p-bromophenylpyrazole.
Example 6
Preparation of 4-bromo-N-arylpyrazole compound 2f
The reaction route is as follows:
Figure BDA0003568977140000082
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 46.0mg (0.20mmol) of compound 1f were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, and the reaction tube was covered and transferred to a 100 ℃ oil bath pan and reacted for 24 hours under reaction conditions of air (monitoring by thin layer chromatography). After the compound 1f completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 39.2mg of the compound with a yield of 64%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2f obtained above, the results of which are shown in FIG. 11: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.35(br, s,1H),8.72(s,1H),7.89-7.87(m,2H),7.82-7.80(m, 2H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2f obtained above, the results of which are shown in FIG. 12: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):160.6,142.5,129.8,127.3(q,J C-F ＝3.7Hz),125.5(q,J C-F ＝32.0Hz),124.7(q,J C-F ＝270.0Hz),117.2,84.3； 19 F NMR(376MHz,DMSO-d 6 ) 60.49(s, 3F). As can be seen from FIGS. 11 to 12, the obtained compound 2f is 3-hydroxy-4-bromo-N- [4- (trifluoromethyl) phenyl]A pyrazole.
Example 7
Preparation of 2g of 4-bromo-N-arylpyrazole compound
The reaction route is as follows:
Figure BDA0003568977140000091
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 35.2mg (0.20mmol) of 1g of the compound were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After 1g of the compound had reacted completely, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added and extracted 3 times, the 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) to give 40.0mg of the compound in 79% yield.
By means of H 1 The structure of 2g of the compound obtained above was confirmed by-NMR (Bruker FT-NMR), and the results are shown in the figure13, and: 1 H NMR(400MHz,DMSO-d 6 ) Delta 10.76(s,1H),8.04(s,1H),7.36-7.33(m,1H),7.32-7.29(m,3H),2.26(s, 3H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of 2g of the compound obtained above, the results of which are shown in FIG. 14: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):158.9,139.5,132.3,132.1,131.4,127.8,126.8,125.4,80.0,18.1. As can be seen from FIGS. 13 to 14, 2g of the obtained compound was 3-hydroxy-4-bromo-N- (2-methylphenyl) pyrazole.
Example 8
Preparation of 4-bromo-N-arylpyrazole compound for 2h
The reaction route is as follows:
Figure BDA0003568977140000092
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 39.3mg (0.20mmol) of the compound were weighed and added for 1 hour, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, and the reaction tube was covered, transferred to a 100 ℃ oil bath, and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound completely reacts for 1h, the reaction tube is cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate are added for extraction for 3 times, an organic layer solution is taken, dried by anhydrous sodium sulfate, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate) to obtain 43.8mg of the compound with the yield of 80%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2h obtained above, the results of which are shown in FIG. 15: 1 H NMR(400MHz,DMSO-d 6 ) Delta 10.98(s,1H),8.15(s,1H),7.65-7.63(m,1H),7.55-7.52(m,1H),7.49-7.41(m, 2H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2h obtained above, the results of which are shown in FIG. 16: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.4,137.5,132.9,130.6,129.4,128.3,127.7,127.4,81.0. As can be seen from FIGS. 15 to 16, the obtained compound 2h is 3-hydroxy-4-bromo-N- (2-chlorophenyl) pyrazole.
Example 9
Preparation of 4-bromo-N-arylpyrazole compound 2i
The reaction route is as follows:
Figure BDA0003568977140000101
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 39.3mg (0.20mmol) of compound 1i were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1i completely reacts, the reaction tube is cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate are added for extraction for 3 times, an organic layer solution is taken, dried by anhydrous sodium sulfate, the solvent is evaporated to dryness, and then the crude product is separated by column chromatography (eluent, petroleum ether: ethyl acetate) to obtain 44.8mg of the compound with the yield of 82%.
By means of H 1 The structure of the compound 2i obtained above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 17: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.23(br, s,1H),8.63(s,1H),7.77-7.76(m,1H),7.67-7.64(m,1H),7.49-7.44(m,1H),7.28-7.25(m, 1H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2i obtained above, the results of which are shown in FIG. 18: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.8,140.4,134.0,131.3,129.1,124.9,116.4,115.2,83.1. As can be seen from FIGS. 17 to 18, the obtained compound 2i was 3-hydroxy-4-bromo-N- (3-chlorophenyl) pyrazole.
Example 10
Preparation of 4-bromo-N-arylpyrazole compound 2j
The reaction route is as follows:
Figure BDA0003568977140000111
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS) and 48.2mg (0.20mmol) of compound 1j were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1j completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 44.6mg of the compound with a yield of 70%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2j obtained above, the results of which are shown in FIG. 19: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.22(br, s,1H),8.63(s,1H),7.90(s,1H),7.71-7.68(m,1H),7.41-7.39(m, 2H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2j obtained above, the results of which are shown in FIG. 20: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.8,140.5,131.5,129.1,127.8,122.4,119.2,115.6,83.1. As can be seen from FIGS. 19 to 20, the obtained compound 2j was 3-hydroxy-4-bromo-N- (3-bromophenyl) pyrazole.
Example 11
Preparation of 4-bromo-N-arylpyrazole compound 2k
The reaction route is as follows:
Figure BDA0003568977140000112
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 46.2mg (0.20mmol) of compound 1k were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, the reaction tube cap was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1k completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 40.0mg of the compound with a yield of 65%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2k obtained above, the results of which are shown in FIG. 21: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.07(s,1H),8.18(s,1H),7.85(s,1H),7.57-7.56(m, 2H); by C 13 The structure of the compound 2k obtained above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 22: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.6,136.5,133.0,132.7,130.1,128.7,128.40,128.36,81.5. As can be seen from FIGS. 21 to 22, the obtained compound 2k was 3-hydroxy-4-bromo-N- (2, 4-dichlorophenyl) pyrazole.
Example 12
Preparation of 4-bromo-N-arylpyrazole compound 2l
The reaction route is as follows:
Figure BDA0003568977140000121
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 38.4mg (0.20mmol) of 1L of the compound were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added to dissolve, the reaction tube was covered, and the reaction tube was transferred to a 100 ℃ oil bath and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the reaction of 1l of the compound was completed, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract 3 times, the 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) to give 29.6mg of the compound with a yield of 55%.
By the use of H 1 -NMR (Bruker FT-NMR) confirmed the structure of 2l of the compound obtained above, the results of which are shown in FIG. 23: 1 H NMR(400MHz,DMSO-d 6 ):δ11.07(s,1H),8.58(s,1H),7.38-7.32(m,1H),7.27-7.25(m,2H) 6.80-6.78(m,1H),3.79(s, 3H); by C 13 -NMR (Bruker FT-NMR) confirmed the structure of 2l of the compound obtained above, the results of which are shown in FIG. 24: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):160.2,159.4,140.5,130.4,128.7,111.1,108.8,102.4,82.1,55.4. As can be seen from FIGS. 23 to 24, 2l of the obtained compound was 3-hydroxy-4-bromo-N- (3-methoxyphenyl) pyrazole.
Example 13
Preparation of 4-bromo-N-arylpyrazole compound 2m
The reaction route is as follows:
Figure BDA0003568977140000122
in a 25mL reaction tube, a magnetic stirrer was added, 42.7mg (1.2equiv) of N-bromosuccinimide (NBS), 47.7mg (0.20mmol) of compound 1m were weighed and added, and then 2.0mL of dimethyl sulfoxide solvent was added for dissolution, and the reaction tube was covered and transferred to a 100 ℃ oil bath pan and reacted for 24 hours under the reaction condition of air (monitoring by thin layer chromatography). After the compound 1m completely reacted, the reaction tube was cooled to room temperature, then 5.0mL of water and 5.0mL of ethyl acetate were added to extract for 3 times, the 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) to give 46.8mg of the compound with a yield of 74%.
By means of H 1 -NMR (Bruker FT-NMR) confirmed the structure of the compound 2m obtained above, the results of which are shown in FIG. 25: 1 H NMR(400MHz,DMSO-d 6 ) Delta 11.02(s,1H),7.42-7.39(m,3H),7.33-7.22(m,5H),7.14-7.12(m, 2H); by C 13 The structure of the compound 2m obtained above was confirmed by NMR (Bruker FT-NMR), and the results are shown in FIG. 26: 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):159.0,140.7,139.6,129.7,129.1,129.0,128.8,128.7,126.9,124.3,82.5. As can be seen from FIGS. 25 to 26, the obtained compound 2m is 3-hydroxy-4-bromo-N, 5-diphenylpyrazole.
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. It will be apparent to those skilled in the art that other variations and modifications may be made in the foregoing description, and it is not necessary or necessary to exhaustively enumerate all embodiments herein. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims (10)

1. A process for preparing 4-bromo-N-arylpyrazole compounds is characterized in that N-aryl-3-pyrazolidinone compounds are used as raw materials and react with N-bromo-succinimide in an organic solvent dimethyl sulfoxide under the heating condition of 95-105 ℃ in air to prepare the 4-bromo-N-arylpyrazole compounds.
2. The process of claim 1, wherein the reaction scheme is as follows:
Figure FDA0003568977130000011
wherein, the formula (1) is the N-aryl-3-pyrazolidinone compound, and the formula (2) is the 4-bromo-N-arylpyrazole compound; in the formula (1) or the formula (2), R 1 Is hydrogen, halogen, alkyl, haloalkyl or alkoxy, R 2 Is hydrogen or phenyl.
3. The process of claim 2, wherein R is 1 Is hydrogen, halogen, methyl, halomethyl or methoxy.
4. The process according to claim 1, wherein the 4-bromo N-arylpyrazole compound is selected from the group consisting of 3-hydroxy-4-bromo-N-arylpyrazole, 3-hydroxy-4-bromo-N-p-tolylpyrazole, 3-hydroxy-4-bromo-N-p-fluorophenylpyrazole, 3-hydroxy-4-bromo-N-p-chlorophenylpyrazole, 3-hydroxy-4-bromo-N-p-bromophenylpyrazole, 3-hydroxy-4-bromo-N- [4- (trifluoromethyl) phenyl ] pyrazole, 3-hydroxy-4-bromo-N- (2-methylphenyl) pyrazole, 3-hydroxy-4-bromo-N- (2-chlorophenyl) pyrazole, N-bromo-p-fluorophenylpyrazole, N-bromo-4-chloro-4-phenylpyrazole, N-bromo-4-phenylpyrazole, and mixtures thereof, 3-hydroxy-4-bromo-N- (3-chlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-bromophenyl) pyrazole, 3-hydroxy-4-bromo-N- (2, 4-dichlorophenyl) pyrazole, 3-hydroxy-4-bromo-N- (3-methoxyphenyl) pyrazole, or 3-hydroxy-4-bromo-N, 5-diphenylpyrazole.
5. The process according to claim 4, wherein said N-aryl-3-pyrazolidinones are selected from the group consisting of N-aryl-3-pyrazolidinones, N-p-tolyl-3-pyrazolidinones, N-p-fluorophenyl-3-pyrazolidinones, N-p-chlorophenyl-3-pyrazolidinones, N-p-bromophenyl-3-pyrazolidinones, N- [4- (trifluoromethyl) phenyl ] -3-pyrazolidinones, N- (2-methylphenyl) -3-pyrazolidinones, N- (2-chlorophenyl) -3-pyrazolidinones, N- (3-bromophenyl) -3-pyrazolidinones, N-p-bromophenyl-3-pyrazolidinones, N-p-fluorophenyl-3-pyrazolidinones, N-p-chlorophenyl-3-pyrazolidinones, N- (3-bromophenyl) -3-pyrazolidinones, N-pyrazolidinones, and N-methyl-3-pyrazolidinones, N- (2, 4-dichlorophenyl) -3-pyrazolidinone, N- (3-methoxyphenyl) -3-pyrazolidinone or N, 5-diphenyl-3-pyrazolidinone.
6. The process according to claim 1, characterized in that it comprises the following steps:
s1, dissolving an N-aryl-3-pyrazolidinone compound and N-bromosuccinimide by using an organic solvent dimethyl sulfoxide;
s2, reacting the mixture obtained in the step S1 under the heating condition of 95-105 ℃ in air until the reaction is complete;
and S3, cooling the crude product obtained in the step S2 to room temperature, extracting with water and ethyl acetate, drying the organic layer solution, evaporating the solvent to dryness, and performing column chromatography separation.
7. The process according to claim 1, wherein in step S1, the N-bromosuccinimide is added in an amount of 1.1 to 1.3 equivalents based on the molar amount of the N-aryl-3-pyrazolidinone compound.
8. The process according to claim 7, wherein in step S1, the N-bromosuccinimide is added in an amount of 1.2 equivalents based on the molar amount of the N-aryl-3-pyrazolidinone compound.
9. The process of claim 1, wherein in step S2, the end point of the reaction is monitored by thin layer chromatography.
10. The process of claim 1, wherein in step S3, the organic layer solution is dried with anhydrous sodium sulfate.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1228075A (en) * 1996-06-20 1999-09-08 孟山都公司 Process for preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity
CN102285963A (en) * 2010-06-21 2011-12-21 中国中化股份有限公司 3-methoxy pyrazolecarboxamide compound and application thereof
CN104774179A (en) * 2014-01-12 2015-07-15 上海师范大学 Halogenated alkenyl pyrazole compound and preparation method thereof
CN105037342A (en) * 2015-08-07 2015-11-11 华中农业大学 Pyrazole ether compound with herbicidal activity and application thereof
CN107722044A (en) * 2016-08-11 2018-02-23 中国科学院广州生物医药与健康研究院 The spiral shell Buprofezin of 2 ketone of indoles 3 or thiazolone compound and its application

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1228075A (en) * 1996-06-20 1999-09-08 孟山都公司 Process for preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity
CN102285963A (en) * 2010-06-21 2011-12-21 中国中化股份有限公司 3-methoxy pyrazolecarboxamide compound and application thereof
CN104774179A (en) * 2014-01-12 2015-07-15 上海师范大学 Halogenated alkenyl pyrazole compound and preparation method thereof
CN105037342A (en) * 2015-08-07 2015-11-11 华中农业大学 Pyrazole ether compound with herbicidal activity and application thereof
CN107722044A (en) * 2016-08-11 2018-02-23 中国科学院广州生物医药与健康研究院 The spiral shell Buprofezin of 2 ketone of indoles 3 or thiazolone compound and its application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BROGDEN, PETER J. ET AL.: "Synthesis and reactions of some spiro[2H-chromen-2, 1\'-cycloalkanes]", 《J. CHEM. SOC. PERKIN TRANS. I》, pages 827 - 830 *
SHANGUANG YANG ET AL.: "A novel one-pot approach to oxidative aromatization and bromination of pyrazolidin-3-one with HBr-H2O2 system", 《HETEROCYCL. COMMUN.》, vol. 24, no. 3, pages 165 - 169 *
王呈谕 等: "基于细胞色素氧化酶CYP2D6 的何首乌肝细胞毒性及相关成分研究", 《中国药物警戒》, vol. 18, no. 3, pages 220 - 239 *

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