CN115521258B - Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof - Google Patents

Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof Download PDF

Info

Publication number
CN115521258B
CN115521258B CN202211294338.3A CN202211294338A CN115521258B CN 115521258 B CN115521258 B CN 115521258B CN 202211294338 A CN202211294338 A CN 202211294338A CN 115521258 B CN115521258 B CN 115521258B
Authority
CN
China
Prior art keywords
azole
acetophenone
alpha
reaction
mmol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202211294338.3A
Other languages
Chinese (zh)
Other versions
CN115521258A (en
Inventor
沈佳斌
沈超
郑凯
陈超
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang Shuren University
Original Assignee
Zhejiang Shuren University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang Shuren University filed Critical Zhejiang Shuren University
Priority to CN202211294338.3A priority Critical patent/CN115521258B/en
Publication of CN115521258A publication Critical patent/CN115521258A/en
Application granted granted Critical
Publication of CN115521258B publication Critical patent/CN115521258B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D231/16—Halogen atoms or nitro radicals
    • 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
    • C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to an alpha-alkoxy acetophenone derivative and a synthesis method thereof. The invention takes the low-cost and easily available azole acetophenone and alcohol as raw materials, and obtains a series of alpha-alkoxy azole acetophenone derivatives with high selectivity and high yield through C-H activation reaction under mild conditions.

Description

Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof
Technical Field
The invention belongs to the technical field of synthesis of pharmaceutical chemical intermediates, and particularly relates to an alpha-alkoxyl azole acetophenone derivative and a synthesis method thereof.
Background
The azole compound widely exists in the nature, and is widely applied to the fields of medicines, antibacterial, insecticidal and functional materials because of strong physiological activity and unique functions; the research finds that: azoletophenone is a main active group in certain drug molecules, and the compounds are paid attention to by the scientific community because of obvious curative effects on antifungal, anti-HIV, lung cancer, depression, new crown diseases and the like. Such as voriconazole (voriconazole), a second-generation triazole antifungal agent that acts on severe fungal infections; a broad-spectrum antifungal agent fluconazole (Fluconazole) for the treatment of fungal infections; itraconazole (Itraconazole), a highly potent broad-spectrum antifungal agent, and the like. The application value of the azole acetophenone compounds and the derivatives thereof in the field of medicine research is reflected. However, how to construct the alpha-alkoxyzolacetophenone derivatives in one step under green, simple and mild reaction conditions has been a research difficulty in the field of organic synthesis.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a simple and efficient alpha-alkoxyl azole acetophenone derivative and a synthesis method thereof.
The invention adopts the technical scheme that:
an alpha-alkoxyl azole acetophenone derivative has the structural formula shown as follows:
Wherein R 1 is one of hydrogen, C1-C6 alkyl, halogen, C1-C6 alkoxy, cyano, aryl and nitro; r 2 is one of hydrogen, aryl, nitro, halogen and alkyl; r 3 is one of alkyl, alkenyl, alkynyl and aryl.
Preferably, R 3 is one of trifluoroethyl, 2-bromoethyl, ethyl, butenyl and isopropyl.
The invention also provides a synthesis method of the alpha-alkoxy acetophenone derivatives, which comprises the steps of taking the azole acetophenone compounds shown in the structural formula (I) and the alcohol compounds shown in the formula (II) as raw materials, adding copper salt as a metal catalyst into an organic solvent, reacting under the photocatalysis condition to obtain the alpha-alkoxy acetophenone derivatives,
The synthetic route is as follows:
preferably, the molar ratio of the azole acetophenone compound to the alcohol compound is 1:2 to 15, preferably 1:5.
Preferably, the copper salt is any one of copper chloride, copper acetate, copper triflate, copper bromide, copper iodide, copper oxide, cuprous oxide or copper tetrafluoroborate tetraacetonitrile; the mol ratio of copper salt to azole acetophenone compound is 0.01-0.5: 1, preferably 0.02:1, the reaction time is 1 to 10 hours, preferably 3 to 6 hours.
Preferably, the organic solvent is any one of dichloromethane, 1, 2-dichloroethane, ethanol, acetonitrile, N-dimethylformamide, tetrahydrofuran and dimethyl sulfoxide, and the feeding mass ratio of the organic solvent to the azole acetophenone compound is 10-100: 1, preferably 15 to 50:1.
Preferably, the photocatalyst adopted in the photocatalysis process is any one of cerium chloride, acid red 94, rhodamine B, eosin Y, 9-fluorenone and 9-mesityl-10-methylacridine perchlorate, and the molar ratio of the photocatalyst to the azolyl acetophenone is 0.01-0.5: 1, preferably 0.02:1.
Preferably, the azole acetophenone compound shown in the formula (I), the alcohol compound shown in the formula (II), the metal catalyst and the photocatalyst are placed in a reaction bottle, an organic solvent is added, a blue LED lamp is used as a light source, stirring reaction is carried out for 3-6 hours at normal temperature, saturated sodium bicarbonate aqueous solution is added after the reaction is finished for quenching reaction, an organic extractant is added for extraction and layering, and the organic layer is dried by anhydrous magnesium sulfate or anhydrous sodium sulfate, filtered and purified by a column to obtain a pale yellow solid alpha-alkoxy azole acetophenone derivative product.
Preferably, the organic extractant is ethyl acetate or dichloromethane.
The invention has the beneficial effects that:
The invention takes the low-cost and easily available azole acetophenone and alcohol as raw materials, and obtains a series of alpha-alkoxy azole acetophenone derivatives with high selectivity and high yield through C-H activation reaction under mild conditions.
Detailed Description
The invention will be further illustrated with reference to specific examples, but the scope of the invention is not limited thereto. Those skilled in the art can and should appreciate that any simple changes or substitutions based on the true spirit of the invention should fall within the scope of the invention as hereinafter claimed.
Example 1
4-Chloropyrazoles acetophenone (2.20 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added to a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring reaction at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.02g, wherein the yield is 95%, and the melting point is high 82-84℃.1H NMR(500MHz,CDCl3)δ7.96(dd,J＝8.4,1.4Hz,2H),7.74(s,1H),7.64(t,J＝7.5Hz,1H),7.55(s,1H),7.50(t,J＝7.9Hz,2H),6.72(s,1H),4.06–3.90(m2H);13C NMR(126MHz,CDCl3)δ187.96,139.65,134.66,133.27,129.04,129.02,127.31,123.18(q,J＝278.7Hz),113.32,88.25,65.31(q,J＝35.4Hz);19F NMR(471MHz,CDCl3)δ-73.76;HRMS(ESI+):Calculated for C13H10ClF3N2O2Na:[M+Na]+341.0281,Found 341.0266.
Example 2
Pyrazole acetophenone (1.86 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added into a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, and the mixture was stirred at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:15, v/v) to obtain a light yellow solid target product 2.67g, wherein the yield is 94%, and the melting point is high 78-81℃.1H NMR(500MHz,CDCl3)δ7.99–7.92(m,2H),7.74(s,1H),7.64–7.59(m,2H),7.47(t,J＝7.7Hz,2H),6.84(s,1H),6.46(s,1H),4.11–3.85(m,2H);13C NMR(126MHz,CDCl3)δ188.51,141.15,134.40,133.53,129.38,128.94,123.32(q,J＝278.5Hz),108.74,64.99(q,J＝35.3Hz);19F NMR(471MHz,CDCl3)δ-73.73;HRMS(ESI+):Calculated for C13H11F3N2O2Na:[M+Na]+307.0670,Found 307.0674.
Example 3
4-Methylpyrazolacetophenone (2.00 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added into a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring reaction at normal temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 2.83g, wherein the yield is 95%, and the melting point is high 72-74℃.1H NMR(500MHz,CDCl3)δ8.00–7.92(m,2H),7.60(t,J＝7.4Hz,1H),7.51–7.42(m,4H),6.74(s,1H),4.04–3.88(m,2H),2.08(s,3H);13C NMR(126MHz,CDCl3)δ188.68,141.95,134.31,133.61,128.93,128.90,127.51,123.40(q,J＝278.5Hz),119.32,87.42,64.81(q,J＝35.4Hz),8.98;19F NMR(471MHz,CDCl3)δ-73.83;HRMS(ESI+):Calculated for C14H13F3N2O2Na:[M+Na]+321.0827,Found 321.0824.
Example 4
3, 5-Diphenylpyrazole acetophenone (3.38 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added into a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, and the mixture was stirred at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 4.10g, wherein the yield is 94%, and the melting point is high 82-84℃.1H NMR(500MHz,CDCl3)δ7.72(dd,J＝7.5,2.0Hz,2H),7.61–7.48(m,9H),7.42–7.34(m,5H),6.52(s,1H),4.49–4.32(m,2H);13C NMR(126MHz,CDCl3)δ13C NMR(126MHz,CDCl3)δ161.99,153.55,148.05,133.95,133.71,132.12,130.52,130.30,129.03,128.74,128.69,128.50,128.19,128.16,123.20(q,J＝278.8Hz),85.79,64.64(q,J＝35.4Hz);19F NMR(471MHz,CDCl3)δ-73.56;HRMS(ESI+):Calculated for C25H19F3N2O2 Na:[M+Na]+459.1296,Found 459.1299.
Example 5
3,4, 5-Tribromopyrazole acetophenone (4.20 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added into a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, and the mixture was stirred at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 4.97g, wherein the yield is 96%, and the melting point is high 72-74℃.1H NMR(500MHz,CDCl3)δ7.93–7.78(m,2H),7.61(t,J＝7.4Hz,1H),7.47(t,J＝7.7Hz,2H),6.74(s,1H),4.16(m,2H);13C NMR(126MHz,CDCl3)δ187.61,134.43,133.29,131.34,128.98,128.86,123.13(q,J＝278.6Hz),117.58,103.46,88.27,65.33(q,J＝35.5Hz);19F NMR(471MHz,CDCl3)δ-73.99;HRMS(ESI+):Calculated for C13H8Br3F3N2O2Na:[M+Na]+540.7986,Found 540.7984.
Example 6
4-Methylpyrazolacetophenone (2.34 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added into a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.02g, wherein the yield is 91%, and the melting point is high 72-74℃.1H NMR(500MHz,CDCl3)δ7.92–7.83(m,2H),7.73(s,1H),7.53(s,1H),7.28(d,J＝8.0Hz,2H),6.70(s,1H),3.97(m,2H),2.42(s,3H);13C NMR(126MHz,CDCl3)δ187.51,145.96,139.55,130.75,129.75,129.15,127.30,123.21(q,J＝278.5Hz),113.20,88.20,65.28(q,J＝35.4Hz),21.83;19F NMR(471MHz,CDCl3)δ-73.77;HRMS(ESI+):Calculated for C14H12ClF3N2O2Na:[M+Na]+355.0437,Found 355.0434.
Example 7
4-Chloropyrazoles-4-methoxyacetophenone (2.50 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added to a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.34g, wherein the yield is 96%, and the melting point is high 76-78℃.1H NMR(500MHz,CDCl3)δ7.95(d,J＝9.0Hz,2H),7.74(s,1H),7.54(d,J＝0.6Hz,1H),6.95(d,J＝9.0Hz,2H),6.68(s,1H),4.03–3.89(m,2H),3.88(s,3H);13C NMR(126MHz,CDCl3)δ186.29,164.72,139.50,131.56,127.30,126.15,123.23(q,J＝278.5Hz),114.32,113.15,88.20,65.26(q,J＝35.3Hz),55.63;19F NMR(471MHz,CDCl3)δ-73.73;HRMS(ESI+):Calculated for C14H12ClF3N2O3Na:[M+Na]+371.0386,Found 371.0388.
Example 8
4-Chloropyrazoles-3-methoxyacetophenone (2.50 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added to a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.24g, wherein the yield is 93%, and the melting point is high 84-87℃.1H NMR(500MHz,CDCl3)δ7.73(s,1H),7.54(s,1H),7.53–7.48(m,2H),7.39(t,J＝8.0Hz,1H),7.20–7.15(m,1H),6.70(s,1H),3.97(m,2H),3.85(s,3H);13C NMR(126MHz,CDCl3)δ187.80,160.03,139.65,134.52,130.03,127.27,123.20(d,J＝278.8Hz),121.48,121.47,113.33,113.03,88.27,65.27(q,J＝35.5Hz),55.50;19F NMR(471MHz,CDCl3)δ-73.73;HRMS(ESI+):Calculated for C14H12ClF3N2O3Na:[M+Na]+371.0386,Found 371.0384.
Example 9
4-Chloropyrazoles-3-fluoroacetophenone (2.38 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added to a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.16g, wherein the yield is 94%, and the melting point is high 70-72℃.1H NMR(500MHz,CDCl3)δ7.73(m,2H),7.67(d,J＝9.2Hz,1H),7.55(s,1H),7.48(td,J＝8.0,5.4Hz,1H),7.34(td,J＝7.9,2.2Hz,1H),6.66(s,1H),4.04–3.90(m,2H);13C NMR(126MHz,CDCl3)δ186.98,162.82(d,J＝249.3Hz),139.83,135.20(d,J＝6.7Hz),130.77(d,J＝7.5Hz),127.29,124.76(d,J＝3.1Hz),124.23,121.80(d,J＝21.4Hz),115.86(d,J＝23.1Hz),113.53,88.41,65.31(q,J＝35.5Hz);19F NMR(471MHz,CDCl3)δ-73.74,-110.47;HRMS(ESI+):Calculated for C13H9ClF4N2O2Na:[M+Na]+359.0186,Found 359.0187.
Example 10
4-Chloropyrazoles-2-fluoroacetophenone (2.38 g,10 mmol), 2-trifluoroethanol (5.00 g,50 mmol), copper chloride (26 mg,0.2 mmol) and cerium chloride (49 mg,0.2 mmol) were added to a reaction flask, acetonitrile (50 g) was added for dissolution, and a common blue LED lamp was used as a light source, followed by stirring at room temperature for 3 hours. After the reaction is finished, adding saturated sodium bicarbonate aqueous solution (50 g) to quench the reaction, adding dichloromethane (50 g), fully stirring, standing for layering, drying an organic layer by anhydrous magnesium sulfate, filtering, concentrating to obtain a brown crude product, purifying the crude product by a column method (eluent: ethyl acetate/petroleum ether=1:20, v/v) to obtain a light yellow solid target product 3.12g, wherein the yield is 93%, and the melting point is high 70-72℃.1H NMR(500MHz,CDCl3)δ7.94(td,J＝7.5,1.8Hz,1H),7.73(s,1H),7.67–7.58(m,1H),7.51(s,1H),7.31(td,J＝7.7,1.1Hz,1H),7.17(m,1H),6.59(s,1H),4.01(m,2H);13C NMR(126MHz,CDCl3)δ186.93,161.78(d,J＝254.5Hz),139.42,136.30(d,J＝9.6Hz),131.58(d,J＝2.4Hz),127.87,125.12(d,J＝3.2Hz),123.16(d,J＝278.3Hz),122.22,116.64(d,J＝23.7Hz),112.89,91.12(d,J＝8.7Hz),66.42(q,J＝35.5,Hz);19F NMR(471MHz,CDCl3)δ-74.26,-110.26;HRMS(ESI+):Calculated for C13H9ClF4N2O2Na:[M+Na]+359.0186,Found 359.0188.
Example 11
The experimental procedure of example 11 was repeated for example 1, except that "the amount of 2, 2-trifluoroethanol charged was replaced with 10mmol so that the molar ratio of 4-chloropyrazole acetophenone to 2, 2-trifluoroethanol was 1:1", other operations were carried out in the same manner as in example 1, to finally obtain 1.81g of a pale yellow solid target product, yield 57%.
Example 12
The experimental procedure of example 12 example 1 was repeated except that "the amount of 2, 2-trifluoroethanol fed was replaced by 100mmol so that the molar ratio of 4-chloropyrazole acetophenone was 1:10", other operations were carried out in the same manner as in example 1, to finally obtain 2.99g of a pale yellow solid target product, with a yield of 94%.
Example 13
The procedure of example 13 was repeated except that "the dichloromethane reaction solvent was replaced with an ethyl acetate reaction solvent of the same quality", and the other operations were the same as in example 1, to finally obtain 2.87g of a pale yellow solid target product, with a yield of 90%.
Example 14
Experimental procedure of example 14 example 1 was repeated except that "the photocatalyst cerium chloride was replaced with eosin Y", and the other operations were the same as in example 1, to finally obtain 2.86g of a pale yellow solid target product, with a yield of 90%.
The novel alpha-alkoxyl azole acetophenone derivative obtained by the embodiment of the invention has potential application prospect in the fields of pharmaceutical chemicals, materials, dyes and the like.
It should be noted that the description of the present application is merely an example of implementation forms of the inventive concept, and the scope of protection of the present application should not be construed as being limited to the specific forms set forth in the embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit of the application.

Claims (3)

1. A method for synthesizing alpha-alkoxyl azole acetophenone derivatives is characterized in that: placing an azole acetophenone compound shown in a formula (I), an alcohol compound shown in a formula (II), a metal catalyst and a photocatalyst in a reaction bottle, adding an organic solvent, taking a blue LED lamp as a light source, stirring at normal temperature for reaction for 3-6 hours, adding a saturated sodium bicarbonate aqueous solution for quenching reaction after the reaction is finished, adding an organic extractant for extraction and layering, and drying, filtering and purifying an organic layer by anhydrous magnesium sulfate or anhydrous sodium sulfate to obtain a pale yellow solid alpha-alkoxy azole acetophenone derivative product; the structural formula of the alpha-alkoxyl azole acetophenone derivatives is as follows:
；
；
Wherein R 1 is one of hydrogen, C1-C6 alkyl, halogen, C1-C6 alkoxy, cyano and nitro; r 2 is one of hydrogen, nitro and halogen; r 3 is trifluoroethyl;
Wherein the metal catalyst is copper chloride, and the photocatalyst is cerium chloride; the mol ratio of the azole acetophenone compound to the alcohol compound is 1:2 to 15, the molar ratio of the metal catalyst to the azole acetophenone compound is 0.01 to 0.5:1, the mole ratio of the photocatalyst to the azolyl acetophenone is 0.01-0.5: 1.
2. The method for synthesizing the alpha-alkoxyzoletophenone derivative according to claim 1, wherein the method comprises the steps of: the organic solvent is any one of dichloromethane, 1, 2-dichloroethane, ethanol, acetonitrile, N-dimethylformamide, tetrahydrofuran and dimethyl sulfoxide, and the feeding mass ratio of the organic solvent to the azole acetophenone compound is 10-100: 1.
3. The method for synthesizing the alpha-alkoxyzoletophenone derivative according to claim 1, wherein the method comprises the steps of: the organic extractant is ethyl acetate or dichloromethane.
CN202211294338.3A 2022-10-21 2022-10-21 Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof Active CN115521258B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211294338.3A CN115521258B (en) 2022-10-21 2022-10-21 Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211294338.3A CN115521258B (en) 2022-10-21 2022-10-21 Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof

Publications (2)

Publication Number Publication Date
CN115521258A CN115521258A (en) 2022-12-27
CN115521258B true CN115521258B (en) 2024-04-30

Family

ID=84703639

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211294338.3A Active CN115521258B (en) 2022-10-21 2022-10-21 Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof

Country Status (1)

Country Link
CN (1) CN115521258B (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62201872A (en) * 1986-02-28 1987-09-05 Shionogi & Co Ltd Azolylpropanol derivative and antifungal agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Masaru OGATA’等.Synthesis and oral anti-fungal activity of novel 1,3-bis-(azolyl)-2-arylpropan-2-ols.《Eur. J. Med. Chem.》.1989,第24卷137-143. *

Also Published As

Publication number Publication date
CN115521258A (en) 2022-12-27

Similar Documents

Publication Publication Date Title
JPH0216315B2 (en)
CN105541844B (en) Simple preparation method of high-purity linagliptin
CN102036983A (en) Process for the preparation of 5-(2-amino-pyrimidin-4-yl)-2-aryl-1h-pyrrole-3-carboxamides
JP5924479B2 (en) Method for producing β-dihydrofuran-derived compound, β-dihydrofuran-derived compound or β-tetrahydrofuran-derived compound, and method for producing β-glycoside compound
CN115521258B (en) Alpha-alkoxyl azole acetophenone derivatives and synthesis method thereof
CN111269156B (en) Synthesis method of 1,2, 4-tricarbonyl sulfoxide ylide compound
WO2022156025A1 (en) SYNTHESIS METHOD FOR 4-(2,2,2-TRICHLOROETHYL)-β-LACTAM DERIVATIVE
JP7393325B2 (en) Method for preparing pyrimidone compounds
CN109776407B (en) Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof
KR930005059B1 (en) Preparation of beta-ketoesters useful in preparing quinolone antibiotics
CN105646327A (en) 2-perfluoroalkyl indole derivative and synthesis method thereof
JPH04244041A (en) Process for producing halogenomethyl ketone especially 1,1,1-trifluoroacetone
CN112645896B (en) Method for synthesizing 4-aryl isoxazole derivative
CN111423353B (en) Polysubstituted N-arylpyrrole compound and preparation method thereof
CN115521257B (en) Alpha-substituted azole acetophenone derivatives and synthesis method thereof
CN104910033A (en) Method for preparing 5-aminolevulinic acid hydrochloride
CN108675986B (en) 1,2, 4-triazole pyridinium compound, preparation method and application
CN112174877B (en) Preparation method of 2, 4-diaryl-6-trifluoromethylpyridine derivative
CN115353514B (en) Fluoro-pyridopyrimidinone compounds and synthesis method thereof
CN110746336B (en) Green preparation method of N-methyl-2-cyano-3-arylpyrrole compound
CN108191778B (en) Method for preparing 2, 3-dichloro quinoxaline derivative by one-pot boiling
JP5711669B2 (en) Method for producing spiroketal derivative
CN111718295B (en) Preparation method of high-purity milrinone
CN116903471A (en) Monofluoro/difluoro oxo allyl ester compound and preparation method thereof
CN113582933A (en) Preparation method of medical intermediate 4-chloro-5-cyanopyrimidine

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant