WO2023225916A1 - 由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法 - Google Patents

由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法 Download PDF

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WO2023225916A1
WO2023225916A1 PCT/CN2022/095050 CN2022095050W WO2023225916A1 WO 2023225916 A1 WO2023225916 A1 WO 2023225916A1 CN 2022095050 W CN2022095050 W CN 2022095050W WO 2023225916 A1 WO2023225916 A1 WO 2023225916A1
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compounds
hydroxychalcone
xanthate
compound
thioflavonoid
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PCT/CN2022/095050
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French (fr)
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徐凡
何诚诚
姚志刚
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苏州大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention belongs to chemical synthesis technology, and specifically relates to a method for preparing thioflavonoid compounds from hydroxychalcone compounds and xanthogenates.
  • Flavonoids widely exist in the plant kingdom, and many structural types of flavonoids have important biological activities [(a) Li, SM; Pan, MH; Lai, CS; Lo, CY; Dushenkov, S.; Ho, CT Isolation and Syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg. Med. Chem. , 2007 , 15, 3381–3389. (b) Adem, S.; Aslan, A.; Ahmed, I.; Krohn, K.; Guler, C.; Comakl ⁇ , V.; Kuzu, M.
  • 4-thioflavones As a derivative of flavonoids, 4-thioflavones not only exhibit powerful biological properties in the field of medicinal chemistry, such as anti-cancer and antibacterial properties, but also highlight many unique and valuable functions in the fields of environmental monitoring and protection [(a ) Ravishankar, D.; KA; Boateng, SY; Green, RJ; Greco, F.; Osborn, HMI Exploring quercetin and luteolin derivatives as antiangiogenic agents. Eur. J. Med. Chem ., 2015 , 97 , 259 ⁇ 274.
  • compound 1 can produce singlet oxygen and superoxide anions, which can effectively kill a variety of bacterial and fungal species and has strong antibacterial activity.
  • the photodegradation ability of compound 1 also makes it used in green pesticides.
  • Preparation; Compound 2 has strong nitric oxide inhibitory activity and can be used to develop new neuroprotective agents; Compound 3 is very sensitive to Hg 2+ , and this feature can be used to develop Hg 2+ ion-selective signaling systems in the environment.
  • the methods for preparing 4-thioflavonoids in the prior art are mainly as follows: 1 The reflux reaction of flavonoid compounds and Lawson's reagent in toluene to obtain 4-thioflavonoids; 2 Phosphorus pentasulfide is used as a sulfur source to directly thiolate the flavonoid compounds to synthesize 4-thioflavonoids. -Thioflavones; 3 4-thioflavones are prepared by the cyclosulfurization reaction of 1,3-diketones involving phosphorus chloride/water/triethylamine. In summary, the synthesis methods of 4-thioflavonoids that have been reported so far are very limited.
  • the present invention prepares sulfonate from hydroxychalcone compounds and xanthate.
  • the flavonoid compound solves the problem of using toxic reagents in the existing technology.
  • the present invention adopts the following technical solution: a method for preparing thioflavone compounds from hydroxychalcone compounds and xanthate salts.
  • the hydroxychalcone compounds and xanthate salts are reacted in a solvent to prepare thioflavonoid compounds.
  • the chemical structural formula of the hydroxychalcone compound is as follows: .
  • R is an alkyl group, such as methyl, ethyl, propyl, isopropyl, etc.
  • M is an alkali metal, such as potassium, sodium, etc.
  • R 1 is selected from hydrogen, alkyl, alkoxy or halogen
  • Ar is an aryl group, for example, Ar is a phenyl, alkylphenyl, alkoxyphenyl, halophenyl, naphthyl or heteroaryl group.
  • the solvent is water and an organic solvent, or an organic solvent;
  • the organic solvent includes dimethyl sulfoxide, N, N -dimethylformamide, 1, 3-dimethyl-2-imidazolinone, N - Methylpyrrolidone, etc.
  • the molar ratio of water to organic solvent is (0.01-2):1, preferably (0.05-1.25):1, more preferably (0.1-1):1, further preferably (0.25-1):1.
  • the reaction temperature is 100-140°C, preferably 110-130°C; the reaction time is 1-3 hours.
  • the molar ratio of the hydroxychalcone compound and the xanthate is (0.6-2):1, preferably (1.5-2):1.
  • the present invention develops the reaction of 2-hydroxychalcone and sodium ethylxanthate to synthesize a series of 4-thioflavonoid compounds with good to excellent yields.
  • This method does not require transition metal catalysis, has simple and easily available raw material sources, mild reaction conditions, can be carried out in aqueous solvents, is relatively environmentally friendly, and provides an effective new way for the preparation of 4-thioflavonoids.
  • Figure 1 is the diffraction pattern of a single crystal of 4-thioflavone 3a.
  • Xanthate can be prepared on a large scale from cheap and easily available carbon disulfide and alcohol, and its reactivity is high.
  • the present invention uses xanthate as a sulfur source to react with 2-hydroxychalcone to achieve 4-thio- Preparation of flavonoids. All raw materials of the present invention are commercially available products or are conventionally prepared according to existing methods. Specific preparation operations and tests are conventional methods. Unless otherwise specified, the yield is an isolated yield. The reaction is carried out in the air, and the solvent is of analytical grade and used directly.
  • Example 2 Based on the preparation method of Example 1, dimethyl sulfoxide is replaced with N, N -dimethylformamide, 1, 3-dimethyl-2-imidazolinone, and N -methylpyrrolidone. Keeping the rest unchanged, the yield of 4-thioflavone 3a is obtained as shown in Table 1; replacing dimethyl sulfoxide with 1, 4-dioxane, the reaction temperature is 100°C, keeping the rest unchanged, and obtaining 4-thioflavone The yield of 3a is as shown in Table 1; when dimethyl sulfoxide is replaced with toluene, the reaction temperature is 110°C, and the rest remains unchanged, the yield of 4-thioflavonoid 3a is as shown in Table 1.
  • Example 3 Add 2-hydroxychalcone (168.2 mg, 0.75 mmol) and potassium ethyl xanthate (80.2 mg, 0.5 mmol) and 2.0 mL of mixed solvent (the molar ratio of water to dimethyl sulfoxide is 0.25:1), reacted at 120°C for 2 h; after the reaction, column chromatography was performed to separate, and a brown solid was obtained with a yield of 47%.
  • Example 4 Add 2-hydroxychalcone (224.3 mg, 1 mmol), potassium isopropylxanthate (87.2 mg, 0.5 mmol) and 2.0 mL mixed solvent (water and dimethyl sulfoxide) into the reaction bottle. The molar ratio was 0.25:1), and the reaction was carried out at 120°C for 2 h; after the reaction, column chromatography was performed to separate, and a brown solid was obtained with a yield of 85%.
  • Example 5 Add 2-hydroxychalcone (224.3 mg, 1 mmol), sodium ethyl xanthate (72.1 mg, 0.5 mmol) and 2.0 mL dimethyl sulfoxide into the reaction bottle, and react at 120°C 2 h; After the reaction, column chromatography was performed to separate, and a brown solid was obtained with a yield of 58%.
  • Example 6 Reaction conditions are: 1.0 mmol 2-hydroxychalcone compound, 0.5 mmol sodium ethyl xanthate, 2.0 mL mixed solvent (molar ratio of water to dimethyl sulfoxide is 0.75:1), 120°C, react for 2 h.
  • a gram-scale reaction was carried out using 2-hydroxychalcone and sodium ethylxanthate as template substrates, and finally the preparation of 4-thioflavones was achieved under standard reaction conditions with a yield of 90%.
  • the present invention developed the reaction of 2-hydroxychalcone and sodium ethylxanthate, and synthesized a series of 4-thioflavonoid compounds with good to excellent yields.
  • This method does not require transition metal catalysis, has simple and easily available raw material sources, mild reaction conditions, can be carried out in aqueous solvents, is relatively environmentally friendly, and provides an effective new way for the preparation of 4-thioflavonoids.

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

Abstract

本发明公开了一种由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，将羟基查尔酮化合物、黄原酸盐在溶剂中反应，制备硫代黄酮化合物。鉴于4-硫代黄酮类化合物在药物和环境领域的巨大应用潜力，开发一种简便有效的方法来制备4-硫代黄酮非常必要，本发明由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物，解决了现有技术采用有毒试剂的问题。

Description

由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法 技术领域
本发明属于化学合成技术，具体涉及由羟基查尔酮化合物和黄原酸盐制备硫代黄酮化合物的方法。
 背景技术
黄酮类化合物广泛存在于植物界，其中很多结构类型的黄酮具有重要的生物活性[(a) Li, S. M.; Pan, M. H.; Lai, C. S.; Lo, C. Y.; Dushenkov, S.; Ho, C. T. Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg. Med. Chem., 2007, 15, 3381–3389. (b) Adem, S.; Aslan, A.; Ahmed, I.; Krohn, K.; Guler, C.; Comaklı, V.; Kuzu, M. Inhibitory and activating effects of some flavonoid derivativeson human pyruvate kinase isoenzyme M2. Arch. Pharm. Chem. Life Sci., 2016, 349, 132–136. (c) Spatafora, C.; Tringali, C. Natural-derived polyphenols as potential anticancer agents. Anticancer Agents Med. Chem., 2012, 12, 902−918]。4-硫代黄酮作为黄酮的衍生物，其不止在药物化学领域表现出强大的生物学特性如抗癌和抗菌等，在环境监测与保护等领域也凸显很多独特和有价值的功用[(a) Ravishankar, D.; K. A.; Boateng, S. Y.; Green, R. J.; Greco, F.; Osborn, H. M. I. Exploring quercetin and luteolin derivatives as antiangiogenic agents. Eur. J. Med. Chem., 2015, 97, 259−274. (b) Mughala, E. U.; Ayaz, M.; Hussain, Z.; Hasan, A.; Sadiq, A.; Riaz, M.; Malik, A.; Hussain, S.; Choudhary, M. I. Synthesis and antibacterial activity of substituted flavones, 4-thioflavones and 4-iminoflavones. Bioorg. Med. Chem., 2006, 14, 4704–4711.  (c)Valente, J. V.; Buntine, M. A.; Lincoln, S. F.; Ward, A. D. UV–Vis and fluorimetric Al 3+, Zn 2+, Cd 2+ and Pb 2+ complexation studies of two 3-hydroxyflavones and a 3-hydroxythioflavone. Inorganica Chim. Acta., 2007, 360, 3380–3386]。如下所示，化合物 1可以产生单线态氧和超氧阴离子，能有效杀死多种细菌和真菌物种，具有较强的抗菌活性，同时化合物 1的光降解能力也使其被运用于绿色农药的制备；化合物 2具有较强的一氧化氮抑制活性，可用于开发新型神经保护剂；化合物 3对Hg 2+十分敏感，利用此特点可开发环境中的Hg 2+离子选择性信号系统。
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现有技术制备4-硫代黄酮的方法主要为：①黄酮化合物与劳森试剂在甲苯中的回流反应，得到4-硫代黄酮；②五硫化二磷作为硫源对黄酮化合物直接进行硫代以合成4-硫代黄酮；③三氯硫磷/水/三乙胺参与的1,3-二酮的环化硫化反应，制备得到4-硫代黄酮。综上所述，目前已报道的4-硫代黄酮的合成方法非常有限，多数方法都基于对预制的黄酮的硫化反应，仅有一例使用了开环的1,3-二酮作为原料，但其所用的硫代试剂三氯硫磷剧毒，非常危险且不易获得。鉴于4-硫代黄酮结构单元的应用价值，开发以易得的链状化合物为原料的此结构单元的合成方法意义重大。
 技术问题
鉴于4-硫代黄酮类化合物在药物和环境领域的巨大应用潜力，开发一种简便有效的方法来制备4-硫代黄酮非常必要，本发明由羟基查尔酮化合物和黄原酸盐制备硫代黄酮化合物，解决了现有技术采用有毒试剂的问题。
 技术解决方案
本发明采用如下技术方案：一种由羟基查尔酮化合物和黄原酸盐制备硫代黄酮化合物的方法，将羟基查尔酮化合物、黄原酸盐在溶剂中反应，制备硫代黄酮化合物。
本发明中，羟基查尔酮化合物的化学结构式如下： 。
黄原酸盐的化学结构式如下： 。
硫代黄酮化合物的化学结构式如下： 。
上述结构式中，R为烷基，比如甲基、乙基、丙基、异丙基等；M为碱金属，比如钾、钠等；R 1选自氢、烷基、烷氧基或者卤素；Ar为芳基，比如Ar为苯基、烷基苯基、烷氧基苯基、卤代苯基、萘基或者杂芳基。
本发明中，溶剂为水和有机溶剂，或者为有机溶剂；有机溶剂包括二甲亚砜、 N, N-二甲基甲酰胺、1, 3-二甲基-2-咪唑啉酮、 N-甲基吡咯烷酮等。优选的，水、有机溶剂的摩尔比为（0.01～2）∶1，优选（0.05～1.25）∶1，再优选（0.1～1）∶1，进一步优选（0.25～1）∶1。
本发明中，反应的温度为100～140℃，优选为110～130℃；时间为1～3小时。
本发明中，羟基查尔酮化合物、黄原酸盐的摩尔比为（0.6～2）∶1，优选（1.5～2）∶1。
 有益效果
本发明开发了2-羟基查尔酮和乙基黄原酸钠的反应，以良好到优异的产率合成了一系列4-硫代黄酮化合物。该方法无需过渡金属催化，原料来源简单易得，反应条件温和，可在含水溶剂中进行，较为环境友好，为4-硫代黄酮类化合物的制备提供了一条有效的新途径。
 附图说明
图1为4-硫代黄酮3a单晶衍射图。
 本发明的实施方式
黄原酸盐可以由廉价易得的二硫化碳和醇来实现大规模制备，其反应活性较高，本发明通过使用黄原酸盐作为硫源与2-羟基查尔酮反应，实现4-硫代黄酮的制备。本发明所有原料为市售产品或者根据现有方法常规制备，具体制备操作以及测试为常规方法，如无特殊说明，产率为分离产率，反应在空气中进行，溶剂为分析纯直接使用。
实施例一： 。
向反应瓶中加入2-羟基查尔酮（112.1 mg，0.5 mmol）、乙基黄原酸钾（80.2 mg，0.5 mmol）和2.0 mL二甲亚砜（DMSO），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，经核磁共振氢谱、碳谱、单晶衍射（图 1）、高分辨质谱等一系列测试，该化合物的结构被确定为4-硫代黄酮 3a，产率为40%。
实施例二：在实施例一制备方法基础上，将二甲亚砜替换为 N, N-二甲基甲酰胺、1, 3-二甲基-2-咪唑啉酮、 N-甲基吡咯烷酮，其余不变，得到4-硫代黄酮 3a的产率如表1；将二甲亚砜替换为1, 4-二氧六环，反应温度为100℃，其余不变，得到4-硫代黄酮 3a的产率如表1；将二甲亚砜替换为甲苯，反应温度为110℃，其余不变，得到4-硫代黄酮 3a的产率如表1。
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在实施例一方法的基础上，调整反应温度，其余不变，反应产率见表2。
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实施例三：向反应瓶中加入2-羟基查尔酮（168.2 mg， 0.75 mmol）、乙基黄原酸钾（80.2 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为47%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钾（80.2 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为74%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钾（80.2 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应1 h；反应结束后进行柱层析分离，得到了棕色固体，产率为69%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钾（80.2 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应3 h；反应结束后进行柱层析分离，得到了棕色固体，产率为74%。
实施例四：向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、异丙基黄原酸钾（87.2 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为85%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钠（72.1 mg，0.5 mmol）和2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.25∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为98%。
实施例五：向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钠（72.1 mg，0.5 mmol）和2.0 mL二甲亚砜，在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为58%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钠（72.1 mg，0.5 mmol）和2.0 mL水/二甲亚砜（水、DMSO的摩尔比为0.05∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为69%。
向反应瓶中加入2-羟基查尔酮（224.3 mg，1 mmol）、乙基黄原酸钠（72.1 mg，0.5 mmol）和2.0 mL水/二甲亚砜（水、DMSO的摩尔比为1.25∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到了棕色固体，产率为89%。
实施例六：反应条件为：1.0 mmol 2-羟基查尔酮化合物，0.5 mmol乙基黄原酸钠，2.0 mL混合溶剂（水与二甲亚砜的摩尔比为0.75∶1），120 ℃，反应2 h。
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向反应瓶中加入2-羟基查尔酮化合物（底物1，1 mmol）、乙基黄原酸钠（底物2c，0.5 mmol）和2.0 mL水/二甲亚砜（水、DMSO的摩尔比为0.75∶1），在120 ℃下反应2 h；反应结束后进行柱层析分离，得到一系列4-硫代黄酮化合物，见表 3。
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。
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以2-羟基查尔酮和乙基黄原酸钠作为模板底物进行了克级规模的反应，最终在标准反应条件下以90%的产率实现了4-硫代黄酮的制备。
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向反应瓶中加入2-羟基查尔酮（13 mmol）、乙基黄原酸钠（6.5 mmol）和26.0 mL水/二甲亚砜（水、DMSO的摩尔比为0.75∶1），在120 ℃下反应2 h；反应结束后，用乙酸乙酯与水萃取反应液（6×25 mL），合并有机相并用无水硫酸钠干燥，减压除去溶剂。粗产物柱层析得到棕色固体，产率90%。
产物的结构表征如下。
。
1H NMR (400 MHz, CDCl 3) δ 8.60 (dd, J = 8.4, 1.6 Hz, 1H), 8.00 –7.98 (m, 2H), 7.79 (s, 1H), 7.75 – 7.70 (m, 1H), 7.58 – 7.51 (m, 4H), 7.45 – 7.41 (m, 1H)。
  。
1H NMR (400 MHz, CDCl 3) δ 8.40 (d, J = 0.8 Hz, 1H), 8.00 – 7.97 (m, 2H), 7.79 (s, 1H), 7.56 – 7.52 (m, 4H),7.48 – 7.46 (m, 1H), 2.49 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 7.87 – 7.85 (m, 3H), 7.68 (s, 1H), 7.48 – 7.42 (m, 3H), 7.40 – 7.38 (m, 1H), 7.24 – 7.22 (m, 1H), 3.84 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.46 (d, J = 2.4 Hz, 1H), 7.90 – 7.88 (m, 2H), 7.68 (s, 1H), 7.60 – 7.57 (m, 1H), 7.54 – 7.44 (m, 4H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.57 (d, J = 2.4 Hz, 1H), 7.85 – 7.83 (m, 2H), 7.68 – 7.66 (m, 1H), 7.64 (s, 1H),7.47 – 7.40 (m, 3H), 7.34 (d, J = 8.8 Hz, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.42 (d, J = 8.8 Hz, 1H), 7.87 – 7.86 (m, 2H), 7.58 (s, 1H), 7.49 –7.43 (m, 3H), 6.91 – 6.84 (m, 2H), 3.89 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.15 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 6.8 Hz, 2H), 7.82 (s, 1H), 7.54–7.52 (m, 3H), 7.33 (t, J = 8.0 Hz, 1H), 7.20 (d, J = 7.6 Hz, 1H), 4.03 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.48 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 7.2 Hz, 2H), 7.81 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H) 7.59 –7.53 (m, 3H), 7.35 (t, J = 8.0 Hz, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.61 (dd, J = 8.4, 1.6 Hz, 1H), 7.72 – 7.67 (m, 1H), 7.57 – 7.55 (m, 1H), 7.49 – 7.47 (m, 1H), 7.43 – 7.39 (m, 3H), 7.32 – 7.30 (m, 2H), 2.50 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.54 (dd, J = 8.4, 1.6 Hz, 1H), 7.71 – 7.70 (m, 3H), 7.68 – 7.64 (m, 1H), 7.51 – 7.49 (m, 1H), 7.37 – 7.29 (m, 3H), 2.41 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.60 (dd, J = 8.0, 1.6 Hz, 1H), 7.78 (s, 1H), 7.75 – 7.71 (m, 1H), 7.58 – 7.56 (m, 2H), 7.49 – 7.48 (m, 1H), 7.45 – 7.41 (m, 2H), 7.11 – 7.09 (m, 1H), 3.90 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.51 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.80 – 7.79 (m, 1H), 7.73 – 7.69 (m, 1H), 7.66 (s, 1H), 7.54 – 7.48 (m, 2H), 7.45 – 7.37 (m, 2H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.57 – 8.55 (m, 1H), 8.12 – 8.11 (m, 1H), 7.89 – 7.87 (m, 1H), 7.75 – 7.71 (m, 1H), 7.70 (s, 1H), 7.68 – 7.66 (m, 1H), 7.58 – 7.55 (m, 1H), 7.44 – 7.41 (m, 1H), 7.40 – 7.37 (m, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.55 (d, J = 8.4 Hz, 1H), 7.81 – 7.79 (m, 2H), 7.70 (s, 1H), 7.68 – 7.64 (m, 1H), 7.50 – 7.48 (m, 1H), 7.38 – 7.34 (m, 1H), 7.27 – 7.25 (m, 2H), 2.37 (s, 3H)。
。
1H NMR (400 MHz, CDCl 3) δ 8.53 (dd, J = 8.0, 1.2 Hz, 1H), 7.84 – 7.81 (m, 2H), 7.65 – 7.61 (m, 2H), 7.46 – 7.44 (m, 1H), 7.36 – 7.32 (m, 1H), 6.94 – 6.91 (m, 2H), 3.82 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.54 (d, J = 8.0 Hz, 1H), 7.96 – 7.94 (m, 2H), 7.74 (s, 1H), 7.67 – 7.59 (m, 5H), 7.51 – 7.49 (m, 1H), 7.44 – 7.42 (m, 2H), 7.39 – 7.33 (m, 2H)。
。
1H NMR (400 MHz, CDCl 3) δ 8.364 – 8.361 (m, 1H), 7.92 – 7.87 (m, 2H), 7.70 (s, 1H), 7.50 – 7.47 (m, 1H), 7.41 – 7.39 (m, 1H), 7.01 – 6.96 (m, 2H), 3.87 (s, 3H), 2.45 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.51 – 8.50 (m, 1H), 7.88 – 7.86 (m, 2H), 7.67 (s, 1H), 7.61–7.58 (m, 1H), 7.46 – 7.44 (m, 1H), 7.00 – 6.98 (m, 2H), 3.88 (s, 3H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.61 (dd, J = 8.4, 1.2 Hz, 1H), 8.53 (s, 1H), 7.98 – 7.95 (m, 3H), 7.91 – 7.87 (m, 2H), 7.76 – 7.72 (m, 1H), 7.63 – 7.61 (m, 1H), 7.60 – 7.55 (m, 2H), 7.45 – 7.41 (m, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.65 (d, J = 8.0 Hz, 1H), 8.15 – 8.13 (m, 1H), 8.00 – 7.98 (m, 1H), 7.92 – 7.91 (m, 1H), 7.79 – 7.77 (m, 1H), 7.71 – 7.68 (m, 1H), 7.61 (s, 1H), 7.55 – 7.48 (m, 4H), 7.44 – 7.41 (m, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.57 (d, J = 8.0 Hz, 1H), 8.081 – 8.077 (m, 1H), 7.71 – 7.65 (m, 1H), 7.61 (s, 1H), 7.52 – 7.49 (m, 2H), 7.46 – 7.44 (m, 1H), 7.41 –7.37 (m, 1H)。
 。
1H NMR (400 MHz, CDCl 3) δ 8.57 (dd, J = 8.0, 1.2 Hz, 1H), 7.71 – 7.66 (m, 3H), 7.49 – 7.47 (m, 1H), 7.41 – 7.38 (m, 1H), 7.224 – 7.216 (m, 1H), 6.63 – 6.62 (m, 1H)。
小结：本发明开发了2-羟基查尔酮和乙基黄原酸钠的反应，以良好到优异的产率合成了一系列4-硫代黄酮化合物。该方法无需过渡金属催化，原料来源简单易得，反应条件温和，可在含水溶剂中进行，较为环境友好，为4-硫代黄酮类化合物的制备提供了一条有效的新途径。

Claims (10)

  1. 一种由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，将羟基查尔酮化合物、黄原酸盐在溶剂中反应，制备硫代黄酮化合物。
  2. 根据权利要求1所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，羟基查尔酮化合物的化学结构式如下：
    黄原酸盐的化学结构式如下：
    硫代黄酮化合物的化学结构式如下：
    。
  3. 根据权利要求2所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，R为烷基；M为碱金属；R 1选自氢、烷基、烷氧基或者卤素；Ar为芳基。
  4. 根据权利要求1所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，溶剂为有机溶剂，或者水和有机溶剂的混合溶剂。
  5. 根据权利要求4所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，有机溶剂包括二甲亚砜、 N, N-二甲基甲酰胺、1, 3-二甲基-2-咪唑啉酮、 N-甲基吡咯烷酮。
  6. 根据权利要求4所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，水、有机溶剂的摩尔比为（0.01～2）∶1。
  7. 根据权利要求1所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，反应的温度为100～140℃，时间为1～3小时。
  8. 根据权利要求1所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法，其特征在于，羟基查尔酮化合物、黄原酸盐的摩尔比为（0.6～2）∶1。
  9. 根据权利要求1所述由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法制备的4-硫代黄酮化合物。
  10. 羟基查尔酮化合物和黄原酸盐在制备4-硫代黄酮化合物中的应用。
PCT/CN2022/095050 2022-05-25 2022-05-25 由羟基查尔酮化合物和黄原酸盐制备4-硫代黄酮化合物的方法 WO2023225916A1 (zh)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4924966A (zh) * 1972-06-29 1974-03-05
KR20110037416A (ko) * 2009-10-06 2011-04-13 중앙대학교 산학협력단 수은 이온 선택성을 갖는 플라본 유도체를 포함하는 센서 및 이를 이용한 수은 이온 검출방법

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4924966A (zh) * 1972-06-29 1974-03-05
KR20110037416A (ko) * 2009-10-06 2011-04-13 중앙대학교 산학협력단 수은 이온 선택성을 갖는 플라본 유도체를 포함하는 센서 및 이를 이용한 수은 이온 검출방법

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