CN110862354B - Bifunctional 1,2, 3-triazole derivative intermediate, preparation method and application - Google Patents
Bifunctional 1,2, 3-triazole derivative intermediate, preparation method and application Download PDFInfo
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- 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
Abstract
The disclosure provides a bifunctional 1,2, 3-triazole derivative intermediate, a preparation method and application thereof, the chemical structure is shown as formula I,
wherein R is selected from aryl, substituted aryl which can give or absorb electrons, heteroaryl which can give or absorb electrons, C1‑C6Straight or branched alkyl, C1‑C2A linear or branched alkoxy group; r1Is selected from C1‑C6Straight-chain or branched alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, heteroaromatic, substituted heteroaromatic. The preparation method comprises the following steps: terminal alkyne, 2,4, 6-tribromophenyl azide compound and sodium sulfinate compound are used as raw materials, and are heated to react under the action of a catalyst and an additive to obtain a bifunctional 1,2, 3-triazole derivative intermediate; the catalyst is cuprous salt and palladium-containingThe additive is a basic compound.
Description
Technical Field
The disclosure belongs to the technical field of organic synthetic chemistry, and relates to a bifunctional 1,2, 3-triazole derivative intermediate, a preparation method and application thereof.
Background
The information in this background section is only for enhancement of understanding of the general background of the disclosure and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
The 1,2, 3-triazole compound has unique chemical structural properties, is an important structural unit for constructing a heterocyclic compound, and can introduce different substituents by utilizing alkyne and azide. The 1,2, 3-triazole compound has rich physiological activity, easy preparation and strong stability, and can be widely applied to various fields. In addition, the 1,2, 3-triazole derivative plays an important role in drug synthesis, and different functional groups can be introduced to produce different drug effects. Therefore, the improvement of functional groups of triazole compounds has led to extensive research. Wherein, N-alkenyl-1, 2, 3-triazole is an important precursor of the functional group polymer, and researchers produce the electron-rich polymer on a large scale by utilizing the easy polymerization property of the triazole; the N-sulfonyl-1, 2, 3-triazole has an electron-withdrawing sulfonyl group, and has stable chemical properties and strong anti-thermolysis capability due to a special structure.
Due to the abundant biological activity and the special structure of the 1,2, 3-triazole derivative, the compound attracts the extensive attention of researchers, and the research of the compound is rapidly advanced. In 1893, Michael originally proposed a nitrogen-rich triazole ring structure; in 2002, Kizhnyaev et al, a method for producing N-vinyl-1, 2, 3-triazole derivatives by using triazole and vinyl acetate under catalysis of mercuric (II) acetate and trifluoroacetic acid; in 2007, Fokin et al reported a method for selectively preparing N-sulfonyl-1, 2, 3-triazole by using copper iodide as a catalyst and terminal alkyne and various sulfonyl azide compounds at 0 ℃; in 2009, Duan et al reported the Au (I) catalyzed addition of 1,2, 3-triazole to unactivated alkynesReacting to synthesize vinyl substituted triazole. In recent years, the research on 1,2, 3-triazole derivatives has been advanced, and in 2011, Kavitha et al report that CAN-NaN is added in a multi-step reaction3Cinnamic acid and alkyne, a method for synthesizing N-styryl triazole compounds by a one-pot method; in 2017, Sun et al reported that N was selectively prepared in a 'one-pot two-step' manner under gold catalysis1-vinyl-substituted 1,2, 3-triazole compounds; in the same year, Ramachary et al reported that 1,4, 5-substituted N-vinyl-1, 2, 3-triazole was specifically synthesized using Triazabicyldecene (TBD) as a catalyst at room temperature.
However, in the course of research, the inventors of the present disclosure found that the following problems existed in these methods for synthesizing N-substituted-1, 2, 3-triazole compounds: (1) the catalyst is expensive and the cost is high. (2) The reaction conditions are complicated, the reaction needs to be carried out in multiple steps, and the control is difficult. (3) The reaction yield is low. (4) The synthesized 1,2, 3-triazole derivative has a single functional group, and cannot exert the advantages in drug synthesis.
Disclosure of Invention
In order to solve the defects of the prior art, the purpose of the disclosure is to provide a bifunctional 1,2, 3-triazole derivative intermediate, a preparation method and an application thereof, so that two functional groups are introduced into the compound for the first time, and N can be synthesized by utilizing terminal alkyne, 2,4, 6-tribromophenyl azide and sodium sulfinate in one step1- [ (3-sulfonyl) -alkenyl]1,2, 3-triazole. The method introduces two functional groups of sulfonyl and propenyl into the 1,2, 3-triazole for the first time, so that the synthetic product has the advantage of double functional groups, and the important function of the triazole derivative in medicinal chemistry is enriched; meanwhile, the method has the advantages of low cost, mild reaction conditions, easy control and high yield, and other known important precursors of the 1,2, 3-triazole derivatives can be synthesized by the compound in one step.
In order to achieve the purpose, the technical scheme of the disclosure is as follows:
on one hand, the chemical structure of the bifunctional 1,2, 3-triazole derivative intermediate is shown as a formula I,
wherein R is selected from aryl, substituted aryl which can give or absorb electrons, heteroaryl which can give or absorb electrons, C1-C6Straight or branched alkyl, C1-C2A linear or branched alkoxy group; r1Is selected from C1-C6Straight-chain or branched alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, heteroaromatic, substituted heteroaromatic.
On the other hand, the preparation method of the bifunctional 1,2, 3-triazole derivative intermediate takes terminal alkyne, a 2,4, 6-tribromophenyl azide compound and a sodium sulfinate compound as raw materials, and the raw materials are heated and reacted under the action of a catalyst and an additive to obtain the bifunctional 1,2, 3-triazole derivative intermediate; the catalyst is cuprous salt and palladium-containing compound, and the additive is alkaline compound;
the chemical structural formula of the terminal alkyne is
The chemical structural formula of the 2,4, 6-tribromophenyl azide compound is
The chemical formula of the sodium sulfinate compound is R1SO2Na；
The chemical structural formula of the bifunctional 1,2, 3-triazole derivative intermediate is shown as
Wherein R is selected from aryl, substituted aryl which donates or absorbs electrons, heteroaryl which donates or absorbs electrons, C1-C6Straight-chain or branched alkyl, C1-C2A linear or branched alkoxy group; r1Is selected from C1-C6Straight or branched chain alkyl, aryl, substituted aryl.
In a third aspect, the bifunctional 1,2, 3-triazole derivative intermediate is applied to preparation of a 1,2, 3-triazole derivative raw material and/or a 1,2, 3-triazole derivative monomer.
In a fourth aspect, a method for synthesizing a 1,2, 3-triazole derivative monomer, heating the 1,2, 3-triazole derivative intermediate with bifunctional groups and tert-butyl peroxide (DTBP) to not less than 95 ℃, and reacting under the catalytic action of cuprous salt to generate the 1,2, 3-triazole derivative monomer;
the chemical structural formula of the 1,2, 3-triazole derivative monomer is shown as
In a fifth aspect, a method for synthesizing a 1,2, 3-triazole derivative raw material comprises the steps of heating the 1,2, 3-triazole derivative intermediate with the bifunctional group and benzoyl peroxide to not less than 75 ℃, and reacting under the catalytic action of cuprous salt to generate the 1,2, 3-triazole derivative raw material;
the chemical structural formula of the 1,2, 3-triazole derivative raw material is
The beneficial effect of this disclosure does:
the disclosure provides a method for introducing various functional groups into a 1,2, 3-triazole derivative intermediate for the first time, enriches the medicinal properties of triazole compounds, and fully exerts the advantages of the triazole compounds in the field of medicinal synthetic chemistry. The method is simple, convenient and efficient, the used raw materials and the catalyst are easy to obtain and are non-toxic, the steps are few, the cost is low, the condition is mild and controllable, and the method provided by the disclosure is suitable for large-scale production.
Meanwhile, the 1,2, 3-triazole derivative intermediate synthesized by the method is widely applied in chemical synthesis and can be used as an important precursor for synthesizing other 1,2, 3-triazole derivatives (such as 1,2, 3-triazole derivative monomers, 1,2, 3-triazole derivative raw materials and the like).
Drawings
The accompanying drawings, which are included to provide a further understanding of the disclosure, illustrate embodiments of the disclosure and together with the description serve to explain the disclosure and are not to limit the disclosure.
FIG. 1 is a drawing of Compound 4a prepared in example 4 of this disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 2 is a drawing of Compound 4b, prepared according to example 10 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 3 is a drawing of Compound 4c, prepared according to example 11 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 4 is a drawing of Compound 4d, prepared according to example 12 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 5 is a drawing of Compound 4e, prepared according to example 13 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 6 is a drawing of Compound 4f prepared according to example 14 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 7 is a drawing showing 4g of compound prepared in example 15 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 8 is a drawing of compound 4h prepared according to example 16 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 9 is a drawing of Compound 4i, prepared according to example 17 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 10 is a drawing of Compound 4j prepared according to example 18 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 11 shows the synthesis of compound 5a from compound 4a of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present disclosure. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
The disclosure provides a bifunctional 1,2, 3-triazole derivative intermediate, a preparation method and an application thereof.
The typical embodiment of the disclosure provides a bifunctional 1,2, 3-triazole derivative intermediate, the chemical structure of which is shown in formula I,
wherein R is selected from aryl, substituted aryl which can give or absorb electrons, heteroaryl which can give or absorb electrons, C1-C6Straight or branched alkyl, C1-C2A linear or branched alkoxy group; r1Is selected from C1-C6Straight-chain or branched alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, heteroaromatic, substituted heteroaromatic.
In one or more embodiments of this embodiment, the aryl group is selected from phenyl and substituted phenyl.
In this series of examples, the substituted phenyl is phenyl substituted with halogen, alkyl or alkoxy.
In this series of examples, the halogen is selected from F, Cl, Br.
In this series of examples, the alkyl group is selected from C1-C6Straight or branched chain alkyl.
In this series of examples, the alkoxy group is selected from C1-C2Straight or branched alkoxy.
In one or more embodiments of this embodiment, the C1-C6Straight chain alkaneThe radicals are selected from methyl, ethyl, n-propyl and n-butyl.
In one or more embodiments of this embodiment, the C1-C6The branched alkyl is selected from tert-butyl and n-pentyl.
In one or more embodiments of this embodiment, the C1-C2The linear or branched alkoxy is selected from methoxy and ethoxy.
In one or more embodiments of this embodiment, the heteroaryl contains one or more heteroatoms selected from N, O, S.
In one or more embodiments of this embodiment, R1Selected from phenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl and ethyl.
The other embodiment of the disclosure provides a preparation method of a bifunctional 1,2, 3-triazole derivative intermediate, which comprises the steps of taking terminal alkyne, a 2,4, 6-tribromophenyl azide compound and a sodium sulfinate compound as raw materials, and heating to react under the action of a catalyst and an additive to obtain the bifunctional 1,2, 3-triazole derivative intermediate; the catalyst is cuprous salt and palladium-containing compound, and the additive is alkaline compound;
the chemical structural formula of the terminal alkyne is
The chemical structural formula of the 2,4, 6-tribromophenyl azide compound is
The chemical formula of the sodium sulfinate compound is R1SO2Na；
The chemical structural formula of the bifunctional 1,2, 3-triazole derivative intermediate is shown as
Wherein R is selected from aryl, substituted aryl capable of electron donating or electron withdrawing, electron donating or electron withdrawingHeteroaryl of (A), C1-C6Straight-chain or branched alkyl, C1-C2A linear or branched alkoxy group; r1Is selected from C1-C6Straight or branched chain alkyl, aryl, substituted aryl.
In one or more embodiments of this embodiment, the aryl group is selected from phenyl and substituted phenyl.
In this series of examples, the substituted phenyl is phenyl substituted with halogen, alkyl or alkoxy.
In this series of examples, the halogen is selected from F, Cl, Br.
In this series of examples, the alkyl group is selected from C1-C6Straight or branched chain alkyl.
In this series of examples, the alkoxy group is selected from C1-C2Straight or branched alkoxy.
In one or more embodiments of this embodiment, the C1-C6The straight-chain alkyl is selected from methyl, ethyl, n-propyl and n-butyl.
In one or more embodiments of this embodiment, the C1-C6The branched alkyl is selected from tert-butyl and n-pentyl.
In one or more embodiments of this embodiment, the C1-C2The linear or branched alkoxy is selected from methoxy and ethoxy.
In one or more embodiments of this embodiment, the heteroaryl contains one or more heteroatoms selected from N, O, S.
In one or more embodiments of this embodiment, R1Selected from phenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl and ethyl.
The cuprous salt is a compound containing cuprous, such as cuprous iodide, cuprous bromide, cuprous chloride, cuprous thiophene-2-formate, copper tetraacetonitrile tetrafluoroborate, cuprous sulfide, cuprous dimethyl sulfide bromide, cuprous oxide, and the like. In order to increase the yield of the bifunctional 1,2, 3-triazole derivative intermediate, in one or more embodiments of this embodiment, the cuprous salt is cuprous iodide, cuprous sulfide, cuprous oxide, cuprous acetate, and cuprous thiophene-2-carboxylate. Particularly, when the cuprous salt is cuprous iodide, the yield of the bifunctional 1,2, 3-triazole derivative intermediate is higher.
The palladium-containing compounds described in this disclosure are compounds containing zero-valent palladium and divalent palladium, such as Pd (PPh)3)4、Pd(PPh3)2Cl2、PdOAC、Pd(PPh3)2Cl2And the like. In one or more embodiments of this embodiment, the palladium-containing compound is Pd (PPh)3)4. When the palladium-containing compound is Pd (PPh)3)4And the yield of the 1,2, 3-triazole derivative intermediate with the bifunctional group is higher.
The basic compound described in the present disclosure is an inorganic basic compound or an organic basic compound, such as triethylamine, DBU, NaOH, PMDETA. In one or more embodiments of this embodiment, the additive is triethylamine. When the additive is triethylamine, the conversion rate of raw materials and the yield of products can be improved.
In one or more embodiments of this embodiment, the reaction is carried out by heating to 40-80 ℃. This temperature can increase the conversion of the feedstock while increasing the yield of the product. When the reaction temperature is 60 + -8 deg.C, the conversion rate of the raw materials and the yield of the product can be further improved.
In order to mix the terminal alkyne, the 2,4, 6-tribromophenyl nitrogen compound and the sodium sulfinate uniformly, in one or more embodiments of the embodiment, the raw materials are added into a solvent to be dissolved, and are heated to react under the action of the added additive and the catalyst.
The solvent is selected from ethanol, toluene, N-Dimethylformamide (DMF), 1, 2-dichloroethane, acetonitrile (CH)3CN), 1, 4-epoxyhexaalkane, dimethyl sulfoxide (DMSO) and glycol. In one or more embodiments of this embodiment, the solvent is dimethyl sulfoxide (DMSO), acetonitrile (CH)3CN), N-Dimethylformamide (DMF), toluene, dichloromethane and methanol, and the solvent improves the conversion rate of raw materials and the yield of products. When the solvent is dimethyl sulfoxide, the solvent is,the conversion rate of raw materials and the yield of products are higher.
In one or more embodiments of the present disclosure, the molar ratio of the terminal alkyne, the 2,4, 6-tribromophenyl azide compound, and the sodium sulfinate compound is 1-3: 1-7: 1 to 6.
In the series of examples, the mol ratio of the terminal alkyne, the 2,4, 6-tribromophenyl azide compound and the sodium sulfinate compound is 1: 6: 5.
in one or more embodiments of the present disclosure, the amount of the cuprous salt added is 10 to 50% of the total mass of the raw material, and the amount of the palladium-containing compound added is 1 to 10% of the total mass of the raw material.
In the series of examples, the addition amount of the cuprous salt is 20% of the total mass of the raw material, and the addition amount of the palladium-containing compound is 2% of the total mass of the raw material.
In one or more embodiments of this embodiment, the reaction time is 0 to 5 hours, and the reaction time is not 0.
In this series of examples, the reaction time was 4. + -. 0.2 h.
In order to improve the purity of the bifunctional 1,2, 3-triazole derivative intermediate, in one or more embodiments of this embodiment, the solution after the reaction is added to an extraction solvent to extract to obtain an organic phase, the solvent in the organic phase is removed, and silica gel column chromatography is performed to obtain the bifunctional 1,2, 3-triazole derivative intermediate.
In the series of embodiments, the extraction solvent used for extraction is one or more of 1, 2-dichloroethane, toluene, nitromethane, ethyl acetate, diethyl ether, n-hexane, cyclohexane, petroleum ether or dichloromethane.
In this series of examples, the extraction solvent used for the extraction was dichloromethane.
In the series of embodiments, the extraction is performed 1-3 times, and 5-20 mL of the extraction solvent is used each time.
In this series of examples, the organic phase obtained was dried over anhydrous magnesium sulfate and the organic solvent was removed.
In the series of examples, the eluent of the silica gel column chromatography is petroleum ether and ethyl acetate.
In the series of embodiments, the volume ratio of the petroleum ether to the ethyl acetate is 1-20: 1-4.
In this series of examples, the volume ratio of petroleum ether to ethyl acetate was 10: 3. The eluent can be used for obtaining a bifunctional 1,2, 3-triazole derivative intermediate with higher purity.
The third embodiment of the disclosure provides an application of the bifunctional 1,2, 3-triazole derivative intermediate in preparing a 1,2, 3-triazole derivative raw material and/or a 1,2, 3-triazole derivative monomer.
The chemical structural formula of the 1,2, 3-triazole derivative monomer is shown as
R is selected as described above.
The chemical structural formula of the 1,2, 3-triazole derivative raw material is
R is selected as described above.
The fourth embodiment of the disclosure provides a method for synthesizing a 1,2, 3-triazole derivative monomer, wherein the bifunctional 1,2, 3-triazole derivative intermediate and tert-butyl peroxide (DTBP) are heated to not less than 95 ℃ and react under the catalytic action of a cuprous salt to generate the 1,2, 3-triazole derivative monomer;
the chemical structural formula of the 1,2, 3-triazole derivative monomer is shown as
The chemical structural formula of the tert-butyl peroxide is shown in the specification
In one or more embodiments of this embodiment, the reaction temperature is between 98 ℃ and 102 ℃.
In one or more embodiments of this embodiment, the solvent of the reaction system is dimethyl sulfoxide.
In one or more embodiments of this embodiment, the monovalent copper salt is cuprous iodide.
The fifth embodiment of the disclosure provides a method for synthesizing a 1,2, 3-triazole derivative raw material, wherein the bifunctional 1,2, 3-triazole derivative intermediate and benzoyl peroxide are heated to not less than 75 ℃ and react under the catalytic action of cuprous salt to generate the 1,2, 3-triazole derivative raw material;
the chemical structural formula of the 1,2, 3-triazole derivative raw material is
The chemical structural formula of the benzoyl peroxide is shown in the specification
In one or more embodiments of this embodiment, the reaction temperature is 78 to 82 ℃.
In one or more embodiments of this embodiment, the solvent of the reaction system is dimethyl sulfoxide.
In one or more embodiments of this embodiment, the monovalent copper salt is cuprous iodide.
In order to make the technical solutions of the present disclosure more clearly understood by those skilled in the art, the technical solutions of the present disclosure will be described in detail below with reference to specific embodiments.
Example 1
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide compound (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and cuprous chloride (0.0050g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in 52% yield.
Example 2
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous oxide (0.0072g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in a yield of 43%.
Example 3
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide compound (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃, followed by addition of cuprous iodide (0.0095g, 0.0005mmol), palladium acetate (0.0011g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in 67% yield.
Example 4
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in 92% yield.
Example 5
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of toluene, dissolved at 60 ℃ and cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in a yield of 58%.
Example 6
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of dichloromethane, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) and heated under nitrogen protection for 2 hours with stirring. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in a yield of 64%.
Example 7
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of methanol, dissolved at 60 ℃ and cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in a yield of 70%.
Example 8
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and sodium hydroxide (0.0470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in 55% yield.
Example 9
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and PMDEPA (0.5220mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4a in a yield of 48%.
The reaction formulae of examples 1 to 9 are as follows:
compound 4a:
1h NMR (400MHz, Chloroform-d) is shown in FIG. 1; HRMS (ESI) m/z calculated for C17H15N3O2S[M+Na]+:348.3798,found:348.3767.
Synthesizing the N-alkenyl-1, 2, 3-triazole derivative:
adding the compound 4a, namely the bifunctional 1,2, 3-triazole derivative intermediate (0.0380mL, 0.25mmol) and tert-butyl peroxide (0.03650g, 0.25mmol) into 2mL of DMSO solvent, dissolving at 100 ℃, then adding cuprous iodide (0.0095g, 0.005mmol) into the system, and continuing to heat and stir for 12 hours under the nitrogen protection condition. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain the N-alkenyl-1, 2, 3-triazole derivative (5a) as the product.
The reaction formula is shown as follows:
(5a)1h NMR (400MHz, CDCl3) δ 8.00(s,1H), 7.88-7.82 (m,2H), 7.45-7.39 (t, J ═ 8.3Hz,2H), 7.36-7.30 (m,1H),5.50(s,1H),4.97(s,1H),2.42(s,3H), as shown in fig. 11;
HRMS(ESI)m/zcalculatedforC11H11N3[M+Na]+:208.0851,found 208.0879.
the compound (5a) is described in the literature (for example, [1 ]]Houwenjing metal catalyzed N2-benzyl/N1-research on synthesis of 1,2, 3-triazole substituted by isopropene [ D ]]University of eastern university of Shandong, 2019; [2]Wang Z,Tao Y,Wang Z,et al.Synthesis and characterization of poly(N-vinyl-1,2,3-triazole)s derived from monomers obtained by highly efficient Wolffs cyclocondensation.[J]Polym.chem.2016:10.1039.C6PY00147E, etc.) has been reported.
Synthesizing 1,2, 3-triazole derivatives:
adding the compound 4a, namely the bifunctional 1,2, 3-triazole derivative intermediate (0.0380mL, 0.25mmol) and benzoyl peroxide (0.0605g, 0.25mmol) into 2mL of DMSO solvent, dissolving at 80 ℃, then adding cuprous iodide (0.0095g, 0.005mmol) into the system, and continuing to heat and stir for 8 hours under the condition of nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. After the reaction solution was cooled, it was poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was removed by distillation under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain the product 1,2, 3-triazole derivative (6 a).
The reaction formula is shown as follows:
(6a)1H NMR(DMSO-d6,400MHz),1drop TFA:δ15.19(s,1H),8.35(s,1H),7.87(d,J＝6.8Hz,2H),7.44(d,J＝7.2Hz,2H),7.35(d,J＝6.8Hz,1H)；HRMS(ESI)m/z for C8H8N3:[M+Na]+168.0538,found:168.0508.
the compound (6a) is described in the literature (for example, [1 ]]Quan X J,Ren Z H,Wang Y Y,et al.ChemInform Abstract:p-Toluenesulfonic Acid Mediated 1,3-Dipolar Cycloaddition of Nitroolefins with NaN3,for Synthesis of 4-Aryl-NH-1,2,3-triazoles.[J].Organic Letters,2015,46(17):393.[2]Kamijo S,Jin T,Huo Z,et al.Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a Pd(0)-Cu(I)bimetallic catalyst.[J].Cheminform,2003,34(43):7786-7787.[3]Who Zu Jun (a new species of compounds containing 1,2, 3-triazole structure) and their characterization (D)]University of west and Jiangxi, 2019, etc.).
Example 10
Compound 1b, p-fluorophenylacetylene (0.0290mL, 0.25mmol), compound 2a, 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, sodium benzenesulfonate (0.041g, 0.25mmol), triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4b in a yield of 91%.
The reaction formula is shown as follows:
compound 4b:
1H NMR(400MHz,chloroform-d) is shown in FIG. 2; HRMS (ESI) m/z calculated for C17H14FN3O2S[M+Na]+:366.0698,found:366.0687.
Example 11
Compound 1c, p-ethoxyphenylacetylene (0.0360mL, 0.25mmol), compound 2a, 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol), and stirring under nitrogen protection with heating continued for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4c in a yield of 88%.
The reaction formula is shown as follows:
compound 4c:
1h NMR (400MHz, Chloroform-d) is shown in FIG. 3; HRMS (ESI) m/z calculated for C19H19N3O3S[M+Na]+:392.0988,found:392.0988.
Example 12
Compound 1d, i.e., 1-hexyne (0.0290mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4d with a yield of 90%.
The reaction formula is shown as follows:
compound 4d:
1h NMR (400MHz, Chloroform-d) δ 7.80(dd, J ═ 7.2,1.7Hz,2H),7.62 to 7.53(m,1H),7.46(t, J ═ 7.8Hz,2H),7.41(s,1H),5.61(d, J ═ 2.0Hz,1H),5.32(d, J ═ 2.0Hz,1H),4.66(s,2H),2.77 to 2.55(m,2H),1.67 to 1.48(m,2H),1.56 to 0.97(m,3H),0.95(d, J ═ 7.2Hz,2H), as shown in fig. 4; HRMS (ESI) m/z calculated for C15H19N3O2S[M+Na]+:328.1098,found:328.1095.
Example 13
Compound 1e, i.e., benzothiophene (0.0290mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4e in 88% yield.
The reaction formula is shown as follows:
compound 4e:
1h NMR (400MHz, Chloroform-d) δ 8.20(d, J ═ 7.8Hz,1H),7.99(s,1H),7.92(d, J ═ 7.8Hz,1H), 7.88-7.78 (m,2H),7.77(s,1H),7.52(q, J ═ 7.2Hz,1H), 7.50-7.26 (m,4H),5.77(d, J ═ 2.2Hz,1H),5.42(d, J ═ 2.2Hz,1H),4.73(s,2H), as shown in fig. 5; HRMS (ESI) m/z calculated for C19H15N3O2S2[M+Na]+:404.0498,found:404.0490.
Example 14
Compound 1f, i.e., 1-heptyne (0.0330mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3a, i.e., sodium benzenesulfonate (0.041g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4f in 92% yield.
The reaction formula is shown as follows:
compound 4f:
1h NMR (400MHz, Chloroform-d) δ 7.79(d, J ═ 7.6Hz,2H),7.57(t, J ═ 7.4Hz,1H),7.45(d, J ═ 14.4Hz,3H),5.62(s,1H),5.29(s,1H),4.68(s,2H),2.61(t, J ═ 7.8Hz,2H),1.59(q, J ═ 7.4Hz,2H),1.32(td, J ═ 7.6,6.5,4.3Hz,4H),0.90(t, J ═ 6.8Hz,3H), as shown in fig. 6; HRMS (ESI) m/z calculated for C16H21N3O2S[M+Na]+:342.4098,found:342.4090.
Example 15
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3b, i.e., sodium p-toluenesulfinate (0.045g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) and heated under nitrogen protection for 2 hours with stirring. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain 4g of the compound with a yield of 90%.
The reaction formula is shown as follows:
compound 4g:
1h NMR (400MHz, Chloroform-d) δ 7.80(s,1H),7.75(d, J ═ 7.4Hz,2H),7.67(d, J ═ 8.2Hz,2H),7.44(t, J ═ 7.6Hz,2H),7.36(dd, J ═ 8.6,6.0Hz,1H),7.21(d, J ═ 8.0Hz,2H),5.72(d, J ═ 2.0Hz,1H),5.40(d, J ═ 2.0Hz,1H),4.66(s,2H),2.26(s,3H), as shown in fig. 7; HRMS (ESI) m/z calculated for C18H17N3O2S[M+Na]+:362.0898,found:362.0887.
Example 16
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3c, i.e., sodium p-fluorobenzenesulfonate (0.045g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 deg.C, followed by addition of cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) to the system, and stirring was continued under nitrogen protection for 2 hours. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to give a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to give the compound in 88 h yield.
The reaction formula is shown as follows:
compound 4h:
1h NMR (400MHz, Chloroform-d) δ 7.92(s,1H), 7.91-7.73 (m,4H), 7.52-7.40 (m,2H), 7.41-7.34 (m,1H), 7.19-7.08 (m,2H),5.74(d, J ═ 2.2Hz,1H),5.42(d, J ═ 2.2Hz,1H),4.71(s,2H), as shown in fig. 8; HRMS (ESI) m/z calculated for C17H14FN3O2S[M+Na]+:366.0698,found:366.0687.
Example 17
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3d, i.e., sodium p-chlorobenzenesulfonate (0.050g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) were added to the system, and heating and stirring were continued for 2 hours under nitrogen protection. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4i in 89% yield.
The reaction formula is shown as follows:
compound 4i:
1h NMR (400MHz, Chloroform-d) δ 7.89(s,1H),7.76(dd, J ═ 13.6,7.9Hz,4H), 7.61-7.26 (m,5H),5.73(s,1H),5.42(s,1H),4.71(s,2H), as shown in fig. 9; HRMS (ESI) m/z calculated for C17H14ClN3O2S[M+Na]+:382.0398,found:382.0403.
Example 18
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3b, i.e., sodium ethylsulfinate (0.029g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) and heated under nitrogen protection for 2 hours with stirring. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4j in a yield of 90%.
The reaction formula is shown as follows:
compound 4j:
1h NMR (400MHz, Chloroform-d) δ 8.17(s,1H),7.86(d, J ═ 7.6Hz,2H),7.45(t, J ═ 7.6Hz,2H),7.38(t, J ═ 7.2Hz,1H),5.79(d, J ═ 2.6Hz,1H),5.53(d, J ═ 2.4Hz,1H),4.57(s,2H),3.01(q, J ═ 7.4Hz,2H),1.39(t, J ═ 7.4Hz,3H), as shown in fig. 10.
Example 19
Compound 1a, i.e., phenylacetylene (0.0270mL, 0.25mmol), compound 2a, i.e., 2,4, 6-tribromophenyl azide (0.1027g, 0.25mmol), compound 3b, i.e., sodium ethylsulfinate (0.029g, 0.25mmol), and triethylamine (0.3470mL, 2.5mmol) were added to 2mL of acetonitrile, dissolved at 60 ℃ and then cuprous iodide (0.0095g, 0.005mmol), tetrakis (triphenylphosphine) palladium (0.0062g, 0.005mmol) and heated under nitrogen protection for 2 hours with stirring. TLC detects the disappearance of the substrate and the reaction is finished. The reaction solution was cooled and poured into 30mL of water, and extracted with dichloromethane (3 × 10mL), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered with suction, and then the organic solvent was distilled off under reduced pressure to obtain a viscous liquid, which was subjected to silica gel column chromatography (eluent V petroleum ether: V ethyl acetate ═ 100:3) to obtain compound 4j in a yield of 90%.
The above description is only a preferred embodiment of the present disclosure and is not intended to limit the present disclosure, and various modifications and changes may be made to the present disclosure by those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present disclosure should be included in the protection scope of the present disclosure.
Claims (22)
1. A preparation method of a bifunctional 1,2, 3-triazole derivative intermediate is characterized in that terminal alkyne, a 2,4, 6-tribromophenyl azide compound and a sodium sulfinate compound are used as raw materials, and are heated to react under the action of a catalyst and an additive to obtain the bifunctional 1,2, 3-triazole derivative intermediate; the catalyst is cuprous salt and palladium-containing compound, and the additive is alkaline compound;
the chemical structural formula of the terminal alkyne is
The chemical structural formula of the 2,4, 6-tribromophenyl azide compound is
The chemical formula of the sodium sulfinate compound is R1SO2Na；
The chemical structural formula of the bifunctional 1,2, 3-triazole derivative intermediate is shown as
Wherein R is selected from aryl, substituted aryl which donates or absorbs electrons, heteroaryl which donates or absorbs electrons, C1-C6Straight-chain or branched alkyl, C1-C2A linear or branched alkoxy group; r1Is selected from C1-C6Straight or branched chain alkyl, aryl, substituted aryl;
the cuprous salt is cuprous iodide, cuprous sulfide, cuprous oxide, cuprous acetate, and cuprous thiophene-2-formate;
the palladium-containing compound is Pd (PPh)3)4；
The additive is triethylamine.
2. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein R is selected from phenyl and substituted phenyl.
3. The method for preparing the bifunctional intermediate of 1,2, 3-triazole derivatives according to claim 2, wherein R is phenyl substituted with halogen, alkyl or alkoxy.
4. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 3, wherein the halogen is selected from F, Cl and Br.
5. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 3, wherein the alkyl is selected from C1-C6Straight or branched chain alkyl.
6. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 3, wherein the alkoxy group is selected from C1-C2Straight or branched alkoxy.
7. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein C is1-C6The straight-chain alkyl is selected from methyl, ethyl, n-propyl, n-butyl and n-pentyl.
8. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein C is1-C6The branched alkyl group is selected from t-butyl.
9. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein C is1-C2The linear or branched alkoxy is selected from methoxy and ethoxy.
10. The method for preparing the bifunctional intermediate of 1,2, 3-triazole derivatives according to claim 1, wherein the heteroaryl group comprises one or more heteroatoms selected from N, O, S.
11. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein R is R1Selected from phenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl and ethyl.
12. The method for preparing the bifunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein the cuprous iodide is cuprous salt.
13. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein the reaction is carried out by heating to 40-80 ℃.
14. The method for preparing the bifunctional intermediate of 1,2, 3-triazole derivatives according to claim 13, wherein the reaction temperature is 60 ± 8 ℃.
15. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein the raw materials are added into a solvent to be dissolved, and the mixture is heated to react under the action of an additive and a catalyst.
16. The method for preparing the bifunctional 1,2, 3-triazole derivative intermediate as claimed in claim 15, wherein the solvent is one of dimethylsulfoxide, acetonitrile, N-dimethylformamide, toluene, dichloromethane, and methanol.
17. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 16, wherein the solvent is dimethyl sulfoxide.
18. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein the molar ratio of the terminal alkyne, the 2,4, 6-tribromophenyl azide compound and the sodium sulfinate compound is 1-3: 1-7: 1 to 6.
19. The method for preparing the bifunctional 1,2, 3-triazole derivative intermediate as claimed in claim 1, wherein the amount of cuprous salt is 10-50% of the total mass of the raw materials, and the amount of palladium-containing compound is 1-10% of the total mass of the raw materials.
20. The method for preparing the difunctional 1,2, 3-triazole derivative intermediate of claim 1, wherein the reaction time is 0-5 h and is not 0.
21. A synthesis method of 1,2, 3-triazole derivative monomers is characterized by comprising the preparation method of the bifunctional 1,2, 3-triazole derivative intermediate according to any one of claims 1 to 20, wherein the bifunctional 1,2, 3-triazole derivative intermediate and tert-butyl peroxide are heated to a temperature of not less than 95 ℃ and react under the catalysis of cuprous salt to generate the 1,2, 3-triazole derivative monomers;
the chemical structural formula of the 1,2, 3-triazole derivative monomer is shown as
22. A method for synthesizing a 1,2, 3-triazole derivative raw material is characterized by comprising the preparation method of the bifunctional 1,2, 3-triazole derivative intermediate according to any one of claims 1 to 20, wherein the bifunctional 1,2, 3-triazole derivative intermediate and benzoyl peroxide are heated to a temperature of not less than 75 ℃ and react under the catalysis of cuprous salt to generate the 1,2, 3-triazole derivative raw material;
the chemical structural formula of the 1,2, 3-triazole derivative raw material is
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