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CN106631646A - Synthetic method of (E)-4-oxo-2-butenal compound - Google Patents

Synthetic method of (E)-4-oxo-2-butenal compound Download PDF

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CN106631646A
CN106631646A CN201610735258.5A CN201610735258A CN106631646A CN 106631646 A CN106631646 A CN 106631646A CN 201610735258 A CN201610735258 A CN 201610735258A CN 106631646 A CN106631646 A CN 106631646A
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CN106631646B (en
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何艳
范学森
张新迎
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Henan Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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Abstract

本发明公开了一种(E)‑4‑氧代‑2‑丁烯醛类化合物的合成方法，属于醛类化合物的合成技术领域。本发明的技术方案要点为：将高烯丙基醇类化合物溶于有机溶剂中，然后加入亚硝酸特丁酯和氧化剂，在空气或氧气存在下于40‑100℃反应制得(E)‑4‑氧代‑2‑丁烯醛类化合物。本发明合成过程为一锅串联反应，效率高，原料易于制备，反应在100℃以下进行，条件温和，操作简便，底物的适用范围广，产物构型立体选择性高。The invention discloses a method for synthesizing ( E )-4-oxo-2-butenal compounds, which belongs to the technical field of synthesis of aldehyde compounds. The key points of the technical scheme of the present invention are: dissolving homoallyl alcohol compounds in an organic solvent, then adding tert-butyl nitrite and an oxidizing agent, and reacting at 40-100°C in the presence of air or oxygen to obtain ( E )- 4-oxo-2-butenals. The synthesis process of the invention is a one-pot series reaction with high efficiency, easy preparation of raw materials, mild conditions, easy operation, wide application range of substrates, and high stereoselectivity of product configurations.

Description

一种(E)-4-氧代-2-丁烯醛类化合物的合成方法A kind of synthetic method of (E)-4-oxo-2-butenal compound

技术领域technical field

本发明属于醛类化合物的合成技术领域，具体涉及一种(E)-4-氧代-2-丁烯醛类化合物的合成方法。The invention belongs to the technical field of synthesis of aldehyde compounds, and in particular relates to a synthesis method of (E)-4-oxo-2-butenal compounds.

背景技术Background technique

作为重要的有机合成中间体，4-氧代-2-丁烯醛类化合物在精细化工和药物化学等领域均具有广泛的应用，因此对其合成方法的研究也一直受到化学家的关注。目前，该类化合物主要通过以下途径合成：酸催化下二氢呋喃类化合物的水解、呋喃衍生物的氧化、2-丁烯-1,4-二醇类化合物的氧化以及钯催化羰基化反应等。虽然这些方法可以有效地合成4-氧代-2-丁烯醛类化合物，但仍存在一些急需解决的问题，如原料和试剂的价格昂贵、产物的构型(E型和Z型)难以控制、底物官能团的兼容性差、反应条件苛刻以及反应步骤繁琐等，这些不足之处也使得上述方法的实用性受到很大限制。有鉴于此，进一步研究并开发从易得的原料出发合成4-氧代-2-丁烯醛类化合物的简捷、高效且选择性高的绿色新方法具有重要的意义。As an important intermediate in organic synthesis, 4-oxo-2-butenal compounds are widely used in the fields of fine chemical industry and medicinal chemistry, so the research on their synthetic methods has always attracted the attention of chemists. At present, such compounds are mainly synthesized through the following routes: acid-catalyzed hydrolysis of dihydrofuran compounds, oxidation of furan derivatives, oxidation of 2-butene-1,4-diol compounds, and palladium-catalyzed carbonylation reactions, etc. . Although these methods can effectively synthesize 4-oxo-2-butenal compounds, there are still some problems that need to be solved urgently, such as the expensive price of raw materials and reagents, the configuration (E type and Z type) of the product is difficult to control , poor compatibility of substrate functional groups, harsh reaction conditions and complicated reaction steps, etc., these shortcomings also greatly limit the practicability of the above method. In view of this, it is of great significance to further study and develop a simple, efficient and highly selective green method for the synthesis of 4-oxo-2-butenal compounds from readily available raw materials.

发明内容Contents of the invention

本发明解决的技术问题是提供了一种(E)-4-氧代-2-丁烯醛类化合物的合成方法，该合成方法从简单易制备的原料出发，通过一锅串联反应直接得到(E)-4-氧代-2-丁烯醛类化合物，操作方便，条件温和，底物适用范围广，适合于工业化生产。The technical problem that the present invention solves is to provide a kind of synthetic method of (E)-4-oxo-2-butenal compound, this synthetic method starts from the raw material that is simple and easy to prepare, directly obtains ( The E)-4-oxo-2-butenal compound has the advantages of convenient operation, mild conditions, wide application range of substrates, and is suitable for industrial production.

本发明为解决上述技术问题采用如下技术方案，一种(E)-4-氧代-2-丁烯醛类化合物的合成方法，其特征在于：将高烯丙基醇类化合物1溶于有机溶剂中，然后加入亚硝酸特丁酯和氧化剂，在空气或氧气存在下于40-100℃反应制得(E)-4-氧代-2-丁烯醛类化合物2，该合成方法中的反应方程式为：In order to solve the above-mentioned technical problems, the present invention adopts the following technical scheme, a synthetic method of (E)-4-oxo-2-butenal compound, which is characterized in that: homoallyl alcohol compound 1 is dissolved in organic In the solvent, then add tert-butyl nitrite and oxidizing agent, in the presence of air or oxygen, react at 40-100 ° C to prepare (E)-4-oxo-2-butenal compound 2, the synthesis method The reaction equation is:

其中R1为1-萘基、4-吡啶基、2-噻吩基、苯基或取代苯基，该取代苯基苯环上的取代基为氟、氯、溴、甲基、三氟甲基或甲氧基中的一种或多种，取代基的位置为苯环上的邻位、间位或对位，R2为氢、烷基或苯基，R3为氢或烷基，氧化剂为四甲基哌啶氮氧化物(TEMPO)或过氧化氢(H2O2)，有机溶剂为甲苯、乙腈、1,4二氧六环或二氯乙烷。Wherein R is 1 -naphthyl, 4-pyridyl, 2-thienyl, phenyl or substituted phenyl, and the substituent on the substituted phenyl benzene ring is fluorine, chlorine, bromine, methyl, trifluoromethyl or one or more of methoxy groups, the position of the substituent is the ortho, meta or para position on the benzene ring, R2 is hydrogen , alkyl or phenyl, R3 is hydrogen or alkyl, oxidizing agent It is tetramethylpiperidine nitrogen oxide (TEMPO) or hydrogen peroxide (H 2 O 2 ), and the organic solvent is toluene, acetonitrile, 1,4 dioxane or dichloroethane.

进一步限定，所述的高烯丙基醇类化合物1与亚硝酸特丁酯的投料物质的量之比为1:1-3，所述的高烯丙基醇类化合物1与氧化剂的投料物质的量之比为1:0.5-2。It is further defined that the ratio of the amount of the homoallyl alcohol compound 1 to the feed material of tert-butyl nitrite is 1:1-3, and the feed material of the homo allyl alcohol compound 1 to the oxidant The amount ratio is 1:0.5-2.

本发明与现有技术相比具有以下优点：(1)合成过程为一锅串联反应，操作简便，效率高；(2)原料易于制备；(3)反应在100℃以下进行，条件温和，操作简便；(4)底物的适用范围广；(5)产物构型立体选择性高。因此，本发明为(E)-4-氧代-2-丁烯醛类化合物的合成提供了一种经济实用且绿色环保的新方法。Compared with the prior art, the present invention has the following advantages: (1) the synthesis process is a one-pot series reaction, which is easy to operate and high in efficiency; (2) the raw materials are easy to prepare; (3) the reaction is carried out below 100°C, with mild conditions and easy operation (4) The applicable range of the substrate is wide; (5) The stereoselectivity of the product configuration is high. Therefore, the present invention provides an economical, practical and environmentally friendly new method for the synthesis of (E)-4-oxo-2-butenal compounds.

具体实施方式detailed description

以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。The above-mentioned contents of the present invention are described in further detail below through the embodiments, but this should not be interpreted as the scope of the above-mentioned themes of the present invention being limited to the following embodiments, and all technologies realized based on the above-mentioned contents of the present invention all belong to the scope of the present invention.

实施例1Example 1

在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(DCE，3mL)，然后加入亚硝酸特丁酯(t-BuONO,TBN,1mmol,108μL)和TEMPO(1mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(54mg,68％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:7.00(dd,J1＝15.6Hz,J2＝7.6Hz,1H),7.55(t,J＝7.6Hz,2H),7.65-7.75(m,2H),7.99-8.01(m,2H),9.90(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:128.9,129.1,134.2,136.3,139.2,142.1,189.8,192.8.MS:m/z 161[MH]+。Add 1a (0.5mmol, 74mg) and dichloroethane (DCE, 3mL) to a 25mL reaction flask, then add tert-butyl nitrite (t-BuONO, TBN, 1mmol, 108μL) and TEMPO (1mmol, 78mg) . The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (54mg, 68% ). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 7.00 (dd, J 1 =15.6Hz, J 2 =7.6Hz, 1H), 7.55 (t, J = 7.6Hz, 2H), 7.65 -7.75 (m, 2H), 7.99-8.01 (m, 2H), 9.90 (d, J=7.2Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 128.9, 129.1, 134.2, 136.3, 139.2, 142.1, 189.8, 192.8. MS: m/z 161 [MH] + .

实施例2Example 2

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在空气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(40mg,50％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an air atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (40mg, 50% ).

实施例3Example 3

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氮气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(7mg,8％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C under nitrogen atmosphere for 10 hours, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (7mg, 8% ).

实施例4Example 4

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1.5mmol,162μL)和TEMPO(0.5mmol,78mg)。在空气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(39mg,48％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1.5mmol, 162μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an air atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (39mg, 48% ).

实施例5Example 5

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(0.5mmol,54μL)和TEMPO(0.5mmol,78mg)。在空气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(24mg,30％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (0.5mmol, 54μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an air atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (24mg, 30% ).

实施例6Example 6

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(1mmol,156mg)。在空气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×2)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(56mg,70％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (1mmol, 156mg) were added. The reaction was stirred at 70° C. for 10 hours under an air atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×2), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (56mg, 70% ).

实施例7Example 7

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.25mmol,39mg)。在空气气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(25mg,31％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.25mmol, 39mg) were added. The reaction was stirred at 70°C for 10 hours under an air atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtration, spin-drying, and silica gel column separation (petroleum ether/ethyl acetate = 20:1) gave the yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (25mg, 31%) .

实施例8Example 8

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和H2O2(0.5mmol,51μL,30wt％水溶液)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(4mg,5％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and H 2 O 2 (0.5mmol, 51μL , 30wt% aqueous solution). The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (4mg, 5% ).

实施例9Example 9

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和甲苯(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(47mg,58％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and toluene (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (47mg, 58% ).

实施例10Example 10

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和乙腈(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(33mg,41％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and acetonitrile (3mL) were added to a 25mL reaction vial, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (33mg, 41% ).

实施例11Example 11

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和1,4-二氧六环(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(29mg,36％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and 1,4-dioxane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg). The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (29mg, 36% ).

实施例12Example 12

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于40℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(34mg,42％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 40°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (34mg, 42% ).

实施例13Example 13

按实施例1所述的方法，在25mL的反应瓶中加入1a(0.5mmol,74mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于100℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物(E)-4-氧代-4-苯基-2-丁烯醛2a(50mg,63％)。According to the method described in Example 1, 1a (0.5mmol, 74mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 100°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product (E)-4-oxo-4-phenyl-2-butenal 2a (50mg, 63% ).

实施例14Example 14

按实施例1所述的方法，在25mL的反应瓶中加入1b(0.5mmol,113mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2b(66mg,55％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:6.75(dd,J1＝16.0Hz,J2＝7.6Hz,1H),7.35-7.47(m,4H),7.67(dd,J1＝8.0Hz,J2＝0.8Hz,1H),9.88(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:119.7,127.8,129.8,132.8,133.8,139.25,139.31,144.2,192.9,193.5.HRMS calcd for C10H8BrO2:238.9702[M+H]+,found:238.9698。According to the method described in Example 1, 1b (0.5mmol, 113mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product 2b (66 mg, 55%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 )δ: 6.75(dd, J 1 =16.0Hz, J 2 =7.6Hz, 1H), 7.35-7.47(m, 4H), 7.67(dd, J 1 ＝8.0Hz, J 2 ＝0.8Hz, 1H), 9.88(d, J＝7.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 )δ: 119.7, 127.8, 129.8, 132.8, 133.8, 139.25, 139.31, 144.2, 192.9, 193.5. HRMS calcd for C 10 H 8 BrO 2 : 238.9702 [M+H] + , found: 238.9698.

实施例15Example 15

按实施例1所述的方法，在25mL的反应瓶中加入1c(0.5mmol,83mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2c(56mg,63％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:7.01(dd,J1＝15.6Hz,J2＝7.2Hz,1H),7.34-7.39(m,1H),7.51-7.57(m,1H),7.66-7.70(m,2H),7.78(dd,J1＝7.6Hz,J2＝1.2Hz,1H),9.90(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:115.6(d,2JC-F＝22.8Hz),121.3(d,2JC-F＝21.4Hz),124.7(d,4JC-F＝3.0Hz),130.8(d,3JC-F＝7.2Hz),138.3(d,3JC-F＝6.9Hz),139.6,141.2,163.0(d,1JC-F＝247.6Hz),188.6(d,4JC-F＝2.7Hz),192.6.HRMS calcd for C10H8FO2:179.0503[M+H]+,found:179.0505。According to the method described in Example 1, 1c (0.5mmol, 83mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2c (56 mg, 63%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 7.01(dd, J 1 =15.6Hz, J 2 =7.2Hz, 1H), 7.34-7.39(m, 1H), 7.51-7.57( m, 1H), 7.66-7.70 (m, 2H), 7.78 (dd, J 1 =7.6Hz, J 2 =1.2Hz, 1H), 9.90 (d, J = 7.6Hz, 1H). 13 C NMR (100MHz ,CDCl 3 )δ: 115.6(d, 2 J CF ＝22.8Hz), 121.3(d, 2 J CF ＝21.4Hz), 124.7(d, 4 J CF ＝3.0Hz), 130.8(d, 3 J CF ＝ 7.2Hz), 138.3(d, 3 J CF ＝6.9Hz), 139.6, 141.2, 163.0(d, 1 J CF ＝247.6Hz), 188.6(d, 4 J CF ＝2.7Hz), 192.6. HRMS calcd for C 10 H 8 FO 2 : 179.0503 [M+H] + , found: 179.0505.

实施例16Example 16

按实施例1所述的方法，在25mL的反应瓶中加入1d(0.5mmol,91mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2d(64mg,66％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:7.01(dd,J1＝15.6Hz,J2＝7.2Hz,1H),7.50(t,J＝8.0Hz,1H),7.62-7.86(m,2H),7.87(d,J＝8.0Hz,1H),7.97(d,J＝1.6Hz,1H),9.90(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:126.9,128.9,130.4,134.1,135.5,137.8,139.6,141.1,188.6,192.5.HRMS calcd for C10H8ClO2:195.0207[M+H]+,found:195.0213。According to the method described in Example 1, 1d (0.5mmol, 91mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2d (64 mg, 66%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 7.01 (dd, J 1 =15.6Hz, J 2 =7.2Hz, 1H), 7.50 (t, J = 8.0Hz, 1H), 7.62 -7.86(m,2H),7.87(d,J=8.0Hz,1H),7.97(d,J=1.6Hz,1H),9.90(d,J=7.2Hz,1H). 13 C NMR(100MHz, CDCl 3 ) δ: 126.9, 128.9, 130.4, 134.1, 135.5, 137.8, 139.6, 141.1, 188.6, 192.5. HRMS calcd for C 10 H 8 ClO 2 : 195.0207[M+H] + ,found: 195.0213.

实施例17Example 17

按实施例1所述的方法，在25mL的反应瓶中加入1e(0.5mmol,81mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2e(52mg,60％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.47(s,3H),7.00(dd,J1＝16.0Hz,J2＝8.0Hz,1H),7.44-7.48(m,2H),7.73(d,J＝16.0Hz,1H),7.79-7.82(m,2H),9.91(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:21.4,126.2,128.9,129.4,130.6,135.0,136.4,139.0,142.4,190.0,193.0.HRMS calcd for C11H11O2:175.0754[M+H]+,found:175.0759。According to the method described in Example 1, 1e (0.5mmol, 81mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product 2e (52 mg, 60%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.47(s, 3H), 7.00(dd, J 1 =16.0Hz, J 2 =8.0Hz, 1H), 7.44-7.48(m, 2H), 7.73(d, J=16.0Hz, 1H), 7.79-7.82(m, 2H), 9.91(d, J=7.6Hz, 1H). 13 C NMR(100MHz, CDCl 3 )δ: 21.4, 126.2 , 128.9, 129.4, 130.6, 135.0, 136.4, 139.0, 142.4, 190.0, 193.0. HRMS calcd for C 11 H 11 O 2 : 175.0754[M+H] + ,found: 175.0759.

实施例18Example 18

按实施例1所述的方法，在25mL的反应瓶中加入1f(0.5mmol,81mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2f(63mg,72％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.39(s,3H),6.92(dd,J1＝16.0Hz,J2＝7.6Hz,1H),7.27(d,J＝8.0Hz,2H),7.65(d,J＝15.6Hz,1H),7.83(d,J＝8.8Hz,2H),9.82(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:21.8,129.1,129.8,133.8,138.9,142.4,145.4,189.2,192.9.MS:m/z 175[MH]+.HRMS calcd for C11H11O2:175.0754[M+H]+,found:175.0758。According to the method described in Example 1, 1f (0.5mmol, 81mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain 2f (63 mg, 72%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.39(s, 3H), 6.92(dd, J 1 =16.0Hz, J 2 =7.6Hz, 1H), 7.27(d, J = 8.0Hz, 2H), 7.65(d, J=15.6Hz, 1H), 7.83(d, J=8.8Hz, 2H), 9.82(d, J=7.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 )δ:21.8,129.1,129.8,133.8,138.9,142.4,145.4,189.2,192.9.MS:m/z 175[MH] + .HRMS calcd for C 11 H 11 O 2 :175.0754[M+H] + , Found: 175.0758.

实施例19Example 19

按实施例1所述的方法，在25mL的反应瓶中加入1g(0.5mmol,83mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2g(54mg,61％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:6.93(dd,J1＝15.6Hz,J2＝7.2Hz,1H),7.15(t,J＝7.6Hz,2H),7.63(d,J＝15.6Hz,1H),7.96-7.99(m,2H),9.83(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:116.3(d,2JC-F＝22.3Hz),131.7(d,3JC-F＝9.8Hz),132.7(d,4JC-F＝3.0Hz),139.2,141.6,166.4(d,1JC-F＝254.9Hz),188.1,192.7.HRMS calcd for C10H8FO2:179.0503[M+H]+,found:179.0503。According to the method described in Example 1, 1 g (0.5 mmol, 83 mg) and dichloroethane (3 mL) were added to a 25 mL reaction flask, and then TBN (1 mmol, 108 μL) and TEMPO (0.5 mmol, 78 mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. It was filtered and spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain 2 g (54 mg, 61%) of a yellow liquid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 6.93 (dd, J 1 =15.6Hz, J 2 =7.2Hz, 1H), 7.15 (t, J = 7.6Hz, 2H), 7.63 (d, J=15.6Hz, 1H), 7.96-7.99(m, 2H), 9.83(d, J=7.2Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 116.3(d, 2 J CF ＝22.3Hz), 131.7(d, 3 J CF ＝9.8Hz), 132.7(d, 4 J CF ＝3.0Hz), 139.2, 141.6, 166.4(d, 1 J CF ＝254.9Hz), 188.1, 192.7.HRMS calcd for C 10 H 8 FO 2 :179.0503[M+H] + ,found: 179.0503.

实施例20Example 20

按实施例1所述的方法，在25mL的反应瓶中加入1h(0.5mmol,104mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10:1)得黄色液体产物2h(68mg,62％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:3.95(s,3H),3.98(s,3H),6.92-7.01(m,2H),7.57(d,J＝2.0Hz,1H),7.62(dd,J1＝8.0Hz,J2＝2.0Hz,1H),7.75(d,J＝15.6Hz,1H),9.87(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:56.1,56.2,110.1,110.5,124.2,129.6,138.6,142.2,149.7,154.5,187.7,193.0.HRMS calcd forC12H13O4:221.0808[M+H]+,found:221.0812。According to the method described in Example 1, 1h (0.5mmol, 104mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10:1) to obtain 2h (68 mg, 62%) as a yellow liquid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 )δ: 3.95(s,3H),3.98(s,3H),6.92-7.01(m,2H),7.57(d,J=2.0Hz, 1H), 7.62 (dd, J 1 =8.0Hz, J 2 =2.0Hz, 1H), 7.75 (d, J = 15.6Hz, 1H), 9.87 (d, J = 7.6Hz, 1H). 13 C NMR ( 100MHz, CDCl 3 )δ:56.1,56.2,110.1,110.5,124.2,129.6,138.6,142.2,149.7,154.5,187.7,193.0. HRMS calcd for C 12 H 13 O 4 :221.0808[M+H] + ,found: 221.0812.

实施例21Example 21

按实施例1所述的方法，在25mL的反应瓶中加入1i(0.5mmol,120mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2i(76mg,60％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.45(s,3H),6.48(dd,J1＝7.6Hz,J2＝1.2Hz,1H),7.28-7.42(m,3H),7.61(d,J＝7.6Hz,1H),10.29(dd,J1＝7.6Hz,J2＝0.8Hz,1H).13C NMR(100MHz,CDCl3)δ:12.1,119.5,127.5,129.0,131.9,133.2,135.6,139.4,151.6,192.2,198.9.HRMS calcd for C11H10BrO2:252.9859[M+H]+,found:252.9865。According to the method described in Example 1, 1i (0.5mmol, 120mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2i (76 mg, 60%) as a yellow solid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 )δ: 2.45(s, 3H), 6.48(dd, J 1 =7.6Hz, J 2 =1.2Hz, 1H), 7.28-7.42(m, 3H), 7.61 (d, J = 7.6Hz, 1H), 10.29 (dd, J 1 = 7.6Hz, J 2 = 0.8Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 12.1, 119.5, 127.5 ,129.0,131.9,133.2,135.6,139.4,151.6,192.2,198.9. HRMS calcd for C 11 H 10 BrO 2 :252.9859[M+H] + ,found:252.9865.

实施例22Example 22

按实施例1所述的方法，在25mL的反应瓶中加入1j(0.5mmol,88mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2j(71mg,75％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.31(s,3H),2.36(d,J＝1.6Hz,3H),6.13(dd,J1＝7.6Hz,J2＝1.6Hz,1H),7.24-7.33(m,2H),7.47-7.51(m,2H),10.17(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:14.2,21.3,127.0,128.5,130.1,132.5,134.4,135.3,138.6,153.5,191.5,198.0.HRMS calcd for C12H13O2:189.0910[M+H]+,found:189.0911。According to the method described in Example 1, 1j (0.5mmol, 88mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2j (71 mg, 75%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.31(s, 3H), 2.36(d, J=1.6Hz, 3H), 6.13(dd, J 1 =7.6Hz, J 2 = 1.6Hz, 1H), 7.24-7.33(m, 2H), 7.47-7.51(m, 2H), 10.17(d, J=7.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 14.2, 21.3 ,127.0,128.5,130.1,132.5,134.4,135.3,138.6,153.5,191.5,198.0. HRMS calcd for C 12 H 13 O 2 :189.0910[M+H] + ,found:189.0911.

实施例23Example 23

按实施例1所述的方法，在25mL的反应瓶中加入1k(0.5mmol,90mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2k(69mg,72％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.38(d,J＝1.2Hz,3H),6.17(dd,J1＝7.2Hz,J2＝1.6Hz,1H),7.20-7.25(m,1H),7.39-7.42(m,2H),7.48(dd,J1＝6.0Hz,J2＝1.2Hz,1H),10.20(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:14.0,116.3(d,2JC-F＝22.6Hz),120.6(d,2JC-F＝21.6Hz),125.5(d,4JC-F＝3.1Hz),130.5(d,3JC-F＝7.6Hz),133.1,137.4(d,3JC-F＝5.6Hz),152.4,162.6(d,1JC-F＝247.1Hz),191.3,196.5(d,4JC-F＝2.0Hz).HRMS calcd for C11H10FO2:193.0659[M+H]+,found:193.0663。According to the method described in Example 1, 1k (0.5mmol, 90mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2k (69 mg, 72%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.38 (d, J = 1.2Hz, 3H), 6.17 (dd, J 1 = 7.2Hz, J 2 = 1.6Hz, 1H), 7.20 13 C _ NMR (100MHz, CDCl 3 ) δ: 14.0, 116.3(d, 2 J CF ＝22.6Hz), 120.6(d, 2 J CF ＝21.6Hz), 125.5(d, 4 J CF ＝3.1Hz), 130.5(d , 3 J CF ＝7.6Hz), 133.1, 137.4(d, 3 J CF ＝5.6Hz), 152.4, 162.6(d, 1 J CF ＝247.1Hz), 191.3, 196.5(d, 4 J CF ＝2.0Hz) .HRMS calcd for C 11 H 10 FO 2 : 193.0659[M+H] + ,found: 193.0663.

实施例24Example 24

按实施例1所述的方法，在25mL的反应瓶中加入1l(0.5mmol,88mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2l(77mg,74％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.38(d,J＝1.6Hz,3H),6.16(dd,J1＝7.6Hz,J2＝1.6Hz,1H),7.36(t,J＝8.0Hz,1H),7.49-7.52(m,1H),7.55-7.58(m,1H),7.67(t,J＝1.6Hz,1H),10.20(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:14.0,127.8,129.5,130.0,133.2,133.4,135.0,137.1,152.4,191.4,196.5.HRMS calcdfor C11H10ClO2:209.0364[M+H]+,found:209.0367。According to the method described in Example 1, 1 l (0.5 mmol, 88 mg) and dichloroethane (3 mL) were added to a 25 mL reaction flask, and then TBN (1 mmol, 108 μL) and TEMPO (0.5 mmol, 78 mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain 2l (77 mg, 74%) as a yellow liquid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.38 (d, J=1.6Hz, 3H), 6.16 (dd, J 1 =7.6Hz, J 2 =1.6Hz, 1H), 7.36 (t,J=8.0Hz,1H),7.49-7.52(m,1H),7.55-7.58(m,1H),7.67(t,J=1.6Hz,1H),10.20(d,J=7.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 )δ: 14.0, 127.8, 129.5, 130.0, 133.2, 133.4, 135.0, 137.1, 152.4, 191.4, 196.5. HRMS calcdfor C 11 H 10 ClO 2 : 209.0364[M+H ] + ,found:209.0367.

实施例25Example 25

按实施例1所述的方法，在25mL的反应瓶中加入1m(0.5mmol,120mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2m(98mg,78％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.36(d,J＝1.6Hz,3H),6.12(dd,J1＝7.6Hz,J2＝1.2Hz,1H),7.52-7.58(m,4H),10.17(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:14.1,128.8,131.2,132.0,132.8,134.1,152.6,191.3,196.8.HRMS calcd for C11H10BrO2:252.9859[M+H]+,found:252.9863。According to the method described in Example 1, 1m (0.5mmol, 120mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain 2m (98 mg, 78%) as a yellow solid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.36 (d, J=1.6Hz, 3H), 6.12 (dd, J 1 =7.6Hz, J 2 =1.2Hz, 1H), 7.52 -7.58(m,4H),10.17(d,J＝7.6Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ:14.1,128.8,131.2,132.0,132.8,134.1,152.6,191.3,196.8.HRMS calcd for C 11 H 10 BrO 2 : 252.9859 [M+H] + , found: 252.9863.

实施例26Example 26

按实施例1所述的方法，在25mL的反应瓶中加入1n(0.5mmol,111mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2n(100mg,85％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.42(d,J＝1.6Hz,3H),3.90(s,3H),3.93(s,3H),6.14(dd,J1＝8.0Hz,J2＝1.2Hz,1H),6.85(d,J＝8.4Hz,1H),7.36(dd,J1＝8.0Hz,J2＝2.0Hz,1H),7.42(d,J＝2.0Hz,1H),10.21(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3)δ:14.7,56.0,56.2,109.9,111.1,125.4,127.7,131.1,149.4,154.1,154.2,191.3,196.2.HRMS calcd for C13H15O4:235.0965[M+H]+,found:235.0975。According to the method described in Example 1, 1n (0.5mmol, 111mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow solid product 2n (100 mg, 85%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.42(d, J=1.6Hz, 3H), 3.90(s, 3H), 3.93(s, 3H), 6.14(dd, J 1 =8.0Hz, J 2 =1.2Hz, 1H), 6.85(d, J=8.4Hz, 1H), 7.36(dd, J 1 =8.0Hz, J 2 =2.0Hz, 1H), 7.42(d, J= 2.0Hz, 1H), 10.21 (d, J=7.6Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 14.7, 56.0, 56.2, 109.9, 111.1, 125.4, 127.7, 131.1, 149.4, 154.1, 154.2 , 191.3, 196.2. HRMS calcd for C 13 H 15 O 4 : 235.0965 [M+H] + , found: 235.0975.

实施例27Example 27

按实施例1所述的方法，在25mL的反应瓶中加入1o(0.5mmol,106mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2o(90mg,80％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.55(d,J＝1.2Hz,3H),6.28(dd,J1＝7.2Hz,J2＝1.2Hz,1H),7.49-7.59(m,4H),7.92(m,1H),8.03(d,J＝8.0Hz,1H),8.12(d,J＝8.8Hz,1H),10.32(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:13.1,124.3,125.2,126.8,127.8,128.4,128.6,130.8,132.4,133.8,134.4,135.3,153.7,192.1,200.1.HRMS calcd for C15H13O2:225.0910[M+H]+,found:225.0913。According to the method described in Example 1, 1o (0.5mmol, 106mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow liquid product 2o (90 mg, 80%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.55 (d, J = 1.2Hz, 3H), 6.28 (dd, J 1 = 7.2Hz, J 2 = 1.2Hz, 1H), 7.49 -7.59(m,4H),7.92(m,1H),8.03(d,J=8.0Hz,1H),8.12(d,J=8.8Hz,1H),10.32(d,J=7.2Hz,1H) .13 C NMR(100MHz,CDCl 3 )δ:13.1,124.3,125.2,126.8,127.8,128.4,128.6,130.8,132.4,133.8,134.4,135.3,153.7,192.1,200.1. HRMS calcd for C 15 H 13 O 2 :225.0910[M+H] + ,found:225.0913.

实施例28Example 28

按实施例1所述的方法，在25mL的反应瓶中加入1p(0.5mmol,82mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10:1)得黄色液体产物2p(52mg,59％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.47(d,J＝1.6Hz,3H),6.30(d,J＝7.2Hz,1H),7.54(dd,J1＝4.4Hz,J2＝1.6Hz,2H),8.82-8.84(m,2H),10.32(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:13.3,119.9,122.3,134.9,142.5,150.7,191.3,197.0.HRMS calcd for C10H10NO2:176.0706[M+H]+,found:176.0701。According to the method described in Example 1, 1p (0.5mmol, 82mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10:1) to obtain 2p (52 mg, 59%) as a yellow liquid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.47 (d, J=1.6Hz, 3H), 6.30 (d, J=7.2Hz, 1H), 7.54 (dd, J 1 =4.4 Hz, J 2 =1.6Hz, 2H), 8.82-8.84 (m, 2H), 10.32 (d, J = 7.2Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 13.3, 119.9, 122.3, 134.9 , 142.5, 150.7, 191.3, 197.0. HRMS calcd for C 10 H 10 NO 2 : 176.0706 [M+H] + , found: 176.0701.

实施例29Example 29

按实施例1所述的方法，在25mL的反应瓶中加入1q(0.5mmol,112mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2q(95mg,80％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:6.34(d,J＝7.6Hz,1H),7.43-7.50(m,7H),7.58-7.62(m,1H),7.91(dd,J1＝7.2Hz,J2＝1.2Hz,2H),9.84(d,J＝7.2Hz,1H).13C NMR(100MHz,CDCl3)δ:128.8,128.9,129.8,130.1,130.2,130.7,132.4,134.1,135.2,157.2,192.7,195.4.HRMS calcd for C16H13O2:237.0910[M+H]+,found:237.0908。According to the method described in Example 1, 1q (0.5mmol, 112mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain yellow liquid product 2q (95 mg, 80%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 6.34(d, J=7.6Hz, 1H), 7.43-7.50(m, 7H), 7.58-7.62(m, 1H), 7.91( dd, J 1 =7.2Hz, J 2 =1.2Hz, 2H), 9.84 (d, J = 7.2Hz, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 128.8, 128.9, 129.8, 130.1, 130.2, 130.7, 132.4, 134.1, 135.2, 157.2, 192.7, 195.4. HRMS calcd for C 16 H 13 O 2 : 237.0910[M+H] + ,found: 237.0908.

实施例30Example 30

按实施例1所述的方法，在25mL的反应瓶中加入1r(0.5mmol,121mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2r(99mg,78％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3)δ:6.33(d,J＝7.8Hz,1H),7.13-7.16(m,2H),7.46-7.48(m,5H),7.93-7.95(m,2H),9.84(d,J＝7.8Hz,1H).13C NMR(150MHz,CDCl3)δ:116.2(d,2JC-F＝21.9Hz),129.0,129.7,130.3,130.6,131.6(d,4JC-F＝2.3Hz),132.3,132.8(d,3JC-F＝9.9Hz),157.0,166.3(d,1JC-F＝258.2Hz),192.5,193.8.HRMS calcd for C16H12FO2:255.0816[M+H]+,found:255.0840。According to the method described in Example 1, 1r (0.5mmol, 121mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow solid product 2r (99 mg, 78%). The characterization data of this compound are as follows: 1 H NMR (600MHz, CDCl 3 )δ: 6.33 (d, J=7.8Hz, 1H), 7.13-7.16 (m, 2H), 7.46-7.48 (m, 5H), 7.93- 7.95(m, 2H), 9.84(d, J＝7.8Hz, 1H). 13 C NMR (150MHz, CDCl 3 ) δ: 116.2(d, 2 J CF ＝21.9Hz), 129.0, 129.7, 130.3, 130.6, 131.6(d, 4 J CF ＝2.3Hz), 132.3, 132.8(d, 3 J CF ＝9.9Hz), 157.0, 166.3(d, 1 J CF ＝258.2Hz), 192.5, 193.8. HRMS calcd for C 16 H 12 FO 2 :255.0816[M+H] + ,found: 255.0840.

实施例31Example 31

按实施例1所述的方法，在25mL的反应瓶中加入1s(0.5mmol,120mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2s(90mg,71％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.03(d,J＝1.2Hz,3H),7.30-7.37(m,2H),7.68-7.71(m,1H),7.82-7.84(m,1H),8.04(t,J＝1.6Hz,1H),9.63(s,1H).13C NMR(100MHz,CDCl3)δ:10.5,122.3,126.1,129.5,130.5,135.7,137.7,137.8,148.0,189.4,193.3.HRMS calcd for C11H10BrO2:252.9859[M+H]+,found:252.9861。According to the method described in Example 1, 1s (0.5mmol, 120mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow solid product 2s (90 mg, 71%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.03 (d, J=1.2Hz, 3H), 7.30-7.37 (m, 2H), 7.68-7.71 (m, 1H), 7.82- 7.84(m,1H),8.04(t,J＝1.6Hz,1H),9.63(s,1H). 13 C NMR(100MHz,CDCl 3 )δ:10.5,122.3,126.1,129.5,130.5,135.7,137.7 , 137.8, 148.0, 189.4, 193.3. HRMS calcd for C 11 H 10 BrO 2 : 252.9859 [M+H] + , found: 252.9861.

实施例32Example 32

按实施例1所述的方法，在25mL的反应瓶中加入1t(0.5mmol,120mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2t(88mg,70％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.08(d,J＝1.6Hz,3H),7.38(t,J＝1.6Hz,1H),7.67(dd,J1＝6.8Hz,J2＝2.0Hz,2H),7.84(dd,J1＝6.8Hz,J2＝1.6Hz,2H),9.69(s,1H).13C NMR(100MHz,CDCl3)δ:11.5,127.5,129.3,130.1,132.3,139.1,148.6,190.9,194.4.HRMS calcd for C11H10BrO2:252.9859[M+H]+,found:252.9861。According to the method described in Example 1, 1t (0.5mmol, 120mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow solid product 2t (88 mg, 70%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.08 (d, J=1.6Hz, 3H), 7.38 (t, J=1.6Hz, 1H), 7.67 (dd, J 1 =6.8 Hz, J 2 =2.0Hz, 2H), 7.84 (dd, J 1 =6.8Hz, J 2 =1.6Hz, 2H), 9.69 (s, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 11.5, 127.5, 129.3, 130.1, 132.3, 139.1, 148.6, 190.9, 194.4. HRMS calcd for C 11 H 10 BrO 2 : 252.9859[M+H] + ,found: 252.9861.

实施例33Example 33

按实施例1所述的方法，在25mL的反应瓶中加入1u(0.5mmol,115mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色液体产物2u(91mg,75％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.05(d,J＝1.6Hz,3H),7.35(d,J＝1.6Hz,1H),7.73(d,J＝8.8Hz,2H),8.02(d,J＝8.4Hz,2H),9.65(s,1H).13C NMR(150MHz,CDCl3)δ:11.6,123.5(d,1JC-F＝271.2Hz),126.4(d,4JC-F＝3.6Hz),128.9(d,3JC-F＝5.9Hz),130.9,135.1(d,2JC-F＝32.7Hz),139.8,149.4,190.8,194.2.HRMScalcd for C12H10F3O2:243.0627[M+H]+,found:243.0631。According to the method described in Example 1, 1u (0.5mmol, 115mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow liquid product 2u (91 mg, 75%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.05(d, J=1.6Hz, 3H), 7.35(d, J=1.6Hz, 1H), 7.73(d, J=8.8Hz , 2H), 8.02(d, J＝8.4Hz, 2H), 9.65(s, 1H). 13 C NMR (150MHz, CDCl 3 )δ: 11.6, 123.5(d, 1 J CF ＝271.2Hz), 126.4( d, 4 J CF ＝3.6Hz), 128.9(d, 3 J CF ＝5.9Hz), 130.9, 135.1(d, 2 J CF ＝32.7Hz), 139.8, 149.4, 190.8, 194.2. HRMScalcd for C 12 H 10 F 3 O 2 : 243.0627[M+H] + ,found: 243.0631.

实施例34Example 34

按实施例1所述的方法，在25mL的反应瓶中加入1v(0.5mmol,96mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2v(84mg,82％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.04(s,3H),3.90(s,3H),7.00(d,J＝9.6Hz,2H),7.39(d,J＝1.2Hz,1H),7.96(d,J＝9.2Hz,2H),9.68(s,1H).13C NMR(100MHz,CDCl3)δ:11.3,55.6,127.0,130.1,131.1,141.0,147.0,164.3,190.7,194.7.HRMS calcd for C12H13O3:205.0859[M+H]+,found:205.0862。According to the method described in Example 1, 1v (0.5mmol, 96mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain the yellow solid product 2v (84 mg, 82%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 )δ: 2.04(s, 3H), 3.90(s, 3H), 7.00(d, J=9.6Hz, 2H), 7.39(d, J= 1.2Hz, 1H), 7.96(d, J=9.2Hz, 2H), 9.68(s, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 11.3, 55.6, 127.0, 130.1, 131.1, 141.0, 147.0, 164.3, 190.7, 194.7. HRMS calcd for C 12 H 13 O 3 : 205.0859 [M+H] + , found: 205.0862.

实施例35Example 35

按实施例1所述的方法，在25mL的反应瓶中加入1w(0.5mmol,106mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2w(67mg,60％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.10(d,J＝1.2Hz,3H),7.34(d,J＝1.6Hz,1H),7.52-7.68(m,3H),7.90-7.94(m,2H),8.07(d,J＝8.4Hz,1H),8.77(d,J＝8.8Hz,1H),9.68(s,1H).13C NMR(100MHz,CDCl3)δ:11.3,124.5,125.5,126.9,128.6,128.7,130.0,130.2,134.0,134.1,134.8,143.0,147.4,194.9,195.0.HRMS calcd for C15H13O2:225.0910[M+H]+,found:225.0915。According to the method described in Example 1, 1w (0.5mmol, 106mg) and dichloroethane (3mL) were added to a 25mL reaction flask, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain product 2w (67 mg, 60%) as a yellow solid. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ) δ: 2.10 (d, J=1.2Hz, 3H), 7.34 (d, J=1.6Hz, 1H), 7.52-7.68 (m, 3H) ,7.90-7.94(m,2H),8.07(d,J=8.4Hz,1H),8.77(d,J=8.8Hz,1H),9.68(s,1H). 13 C NMR(100MHz,CDCl 3 ) δ:11.3,124.5,125.5,126.9,128.6,128.7,130.0,130.2,134.0,134.1,134.8,143.0,147.4,194.9,195.0.HRMS calcd for C 15 H 13 O 2 :225.0910[M+H] + found: 225.0915.

实施例36Example 36

按实施例1所述的方法，在25mL的反应瓶中加入1x(0.5mmol,84mg)和二氯乙烷(3mL)，然后加入TBN(1mmol,108μL)和TEMPO(0.5mmol,78mg)。在氧气(1atm)气氛下于70℃搅拌反应10小时，然后加入8mL饱和氯化钠溶液淬灭反应，用乙酸乙酯萃取(8mL×3)，合并有机相，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝20:1)得黄色固体产物2x(67mg,74％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ:2.18(s,3H),7.21(t,J＝4.4Hz,1H),7.37(s,1H),7.78(d,J＝4.0Hz,1H),7.82(d,J＝4.0Hz,1H),9.68(s,1H).13C NMR(100MHz,CDCl3)δ:11.4,128.6,132.9,135.5,138.4,145.0,148.9,183.4,194.7.HRMS calcd for C9H9O2S:181.0318[M+H]+,found:181.0317。According to the method described in Example 1, 1x (0.5mmol, 84mg) and dichloroethane (3mL) were added to a 25mL reaction vial, and then TBN (1mmol, 108μL) and TEMPO (0.5mmol, 78mg) were added. The reaction was stirred at 70°C for 10 hours under an oxygen (1 atm) atmosphere, then 8 mL of saturated sodium chloride solution was added to quench the reaction, extracted with ethyl acetate (8 mL×3), the organic phases were combined, and dried over anhydrous sodium sulfate. Filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=20:1) to obtain 2x (67 mg, 74%) as a yellow solid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 )δ: 2.18(s, 3H), 7.21(t, J=4.4Hz, 1H), 7.37(s, 1H), 7.78(d, J= 4.0Hz, 1H), 7.82(d, J=4.0Hz, 1H), 9.68(s, 1H). 13 C NMR (100MHz, CDCl 3 ) δ: 11.4, 128.6, 132.9, 135.5, 138.4, 145.0, 148.9, 183.4, 194.7. HRMS calcd for C 9 H 9 O 2 S: 181.0318 [M+H] + , found: 181.0317.

以上实施例描述了本发明的基本原理、主要特征及优点，本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。The above embodiments have described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What are described in the above embodiments and description are only to illustrate the principles of the present invention. Without departing from the scope of the principle of the present invention, there will be various changes and improvements in the present invention, and these changes and improvements all fall within the protection scope of the present invention.

Claims (2)

1. the synthetic method of one kind (E) -4- oxo -2- butylene aldehyde compounds, it is characterised in that：By high allyl alcohols chemical combination Thing 1 is dissolved in organic solvent, is subsequently adding nitrous acid special butyl ester and oxidant, anti-in 40-100 DEG C in the presence of air or oxygen (E) -4- oxo -2- butylene aldehyde compound 2 should be obtained, the reaction equation in the synthetic method is：
Wherein R1For 1- naphthyls, 4- pyridine radicals, 2- thienyls, phenyl or substituted-phenyl, the substituent on the substituted-phenyl phenyl ring is One or more in fluorine, chlorine, bromine, methyl, trifluoromethyl or methoxyl group, the position of substituent is ortho position, meta on phenyl ring Or contraposition, R2For hydrogen, alkyl or phenyl, R3For hydrogen or alkyl, oxidant is tetramethyl piperidine nitrogen oxides or hydrogen peroxide, is had Machine solvent is toluene, acetonitrile, 1,4 dioxane or dichloroethanes.
2. the synthetic method of (E) -4- oxos -2- butylene aldehyde compounds according to claim 1, it is characterised in that：Institute The high allyl alcohols compound 1 stated is 1 with the ratio of the amount of the material that feeds intake of nitrous acid special butyl ester:1-3, described high allyl Alcohol compound 1 is 1 with the ratio of the amount of the material that feeds intake of oxidant:0.5-2.
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CN108863750A (en) * 2018-09-10 2018-11-23 河南师范大学 A kind of 2- butene-1, the synthetic method of 4- cyclohexadione compounds
CN108976106A (en) * 2018-09-10 2018-12-11 河南师范大学 (E) synthetic method of -2- methylene -1,4- diacetyl class compound
CN109761845A (en) * 2019-02-21 2019-05-17 河南师范大学 A kind of synthetic method of N-nitroso-4-aminobutyrate compound
CN109776308A (en) * 2019-02-21 2019-05-21 河南师范大学 A kind of synthetic method of N-(3-cyanopropyl) formamide compound
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CN108863750A (en) * 2018-09-10 2018-11-23 河南师范大学 A kind of 2- butene-1, the synthetic method of 4- cyclohexadione compounds
CN108976106A (en) * 2018-09-10 2018-12-11 河南师范大学 (E) synthetic method of -2- methylene -1,4- diacetyl class compound
CN108976106B (en) * 2018-09-10 2021-02-19 河南师范大学 (E) Synthesis method of (E) -2-methylene-1, 4-butanedione compounds
CN109761845A (en) * 2019-02-21 2019-05-17 河南师范大学 A kind of synthetic method of N-nitroso-4-aminobutyrate compound
CN109776308A (en) * 2019-02-21 2019-05-21 河南师范大学 A kind of synthetic method of N-(3-cyanopropyl) formamide compound
CN109776308B (en) * 2019-02-21 2021-08-03 河南师范大学 A kind of synthetic method of N-(3-cyanopropyl) formamide compound
CN109761845B (en) * 2019-02-21 2021-08-20 河南师范大学 A kind of synthetic method of N-nitroso-4-aminobutyrate compound
CN109896989A (en) * 2019-05-06 2019-06-18 河南师范大学 A kind of synthetic method of 5- oxo -2H- aromatic ring simultaneously [g] indoles -1- oxide
CN109896989B (en) * 2019-05-06 2021-09-10 河南师范大学 Synthesis method of 5-oxo-2H-aromatic ring [ g ] indole-1-oxide

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