CN110590621B - Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne - Google Patents
Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne Download PDFInfo
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Abstract
The disclosure provides a method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivatives by copper-catalyzed terminal alkyne, which uses terminal alkyne and sulfinate compoundsAs raw materials, cuprous salt is used as a catalyst, and the reaction is carried out at the temperature of not less than 60 ℃ under the action of an additive; the terminal alkyne has the formula
The chemical formula of the sodium sulfinate compound is R1SO2M, the additive is one or more of difluorobromoacetic acid ethyl ester, difluoroiodoacetic acid ethyl ester, difluorochloroacetic acid ethyl ester and trifluoroacetic acid ethyl ester; wherein R is selected from aryl, substituted aryl which donates or absorbs electrons, heteroaryl which donates or absorbs electrons, C4‑C8Straight-chain or branched alkyl, R1Is selected from C1‑C5Linear alkyl or alkoxy, aryl, substituted aryl, heterocyclic radical, substituted heterocyclic radical, heteroaromatic radical, substituted heteroaromatic radical, arylamine, aliphatic amine and aromatic ether, wherein M is alkali metal. The method disclosed by the invention is simple to operate, mild in condition and free from toxic by-products.
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and relates to a method for synthesizing a 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne.
Background
The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art.
Sulfone-containing molecules have a wide range of applications in the fields of biochemistry, medicinal chemistry, materials and organic synthesis and they are widely found in natural products and drug molecules. Meanwhile, sulfonyl is also widely used as a general synthon for the synthesis of other organosulfur compounds. 1, 2-bis (arylsulfonyl) ethylene is an important organic sulfone compound, and has been valued for its useful synthetic intermediate and widely studied for synthetic applications. First, they can be synthesized as enantiomers of cyclic compounds as cycloadditions. Secondly, they act as leaving group alkenylation reactions, in which the various groups add a C-C double bond and then eliminate the sulfonyl group. Third, they are capable of rearranging the heavy structure 1, 2-sulfones to form various other organic sulfone compounds in the presence of an organic catalyst.
The organic sulphone compounds such as 1, 2-bis (arylsulfonyl) ethylene play an important role in organic chemistry theory and synthesis application, and the inventors of the present disclosure know that the prior methods for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivatives include: ottorio De Lucchi et al, 1984, reported a method of synthesizing 1, 2-bis (arylthio) ethylene by reacting 1, 2-dichloroethylene with a benzenethiol salt, followed by oxidation to obtain 1, 2-bis (arylsulfonyl) ethylene; the massahito Ochiai topic group in 1993 reported the formation of (Z) -1, 2-bis (arylsulfonyl) ethylene by nucleophilic vinyl substitution with sodium arylsulfonate using β - ((phenylsulfonyl) alkenyl) iodonium tetrafluoroborate as the starting material. In 1999, D.B.Reddy et al reported a one-pot process by condensing 1-arylsulfonyl-2, 2-dichloroethane with sodium sulfonate in aqueous ethanol. In 2001, Kataoka and his research team also developed a method for obtaining 1, 2-bis (benzenesulfonyl) ethylene by reacting an alkynyl selenium salt with sodium benzenesulfonate. In 2017, the dawndong topic group developed a solvent-dependent sulfonylation reaction of aryl ethylene bromide with sodium aryl sulfinate. (E) -1, 2-bis (arylsulfonyl) ethylene was formed in DMSO and arylethynyl sulfone was obtained in toluene. In 2018, professor Liyamin, university of Kunming science and technology, reports that copper-catalyzed decarboxylation and disulfonylation reaction of alkynoic acid and sulfinic acid is realized to construct (E) -1, 2-disulfonyl ethylene. However, in the course of research, the inventors of the present disclosure found that the following problems existed in these methods for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivatives: 1. the raw materials can not be directly obtained, and because the acetylenic acid and the acetylenic bromine are difficult to obtain by the market, the reaction steps are increased; 2. strong oxidant is needed for oxidation; 3. an inert atmosphere is needed, and the reaction conditions are harsh; 4. toxic by-products, and the like.
Disclosure of Invention
In order to solve the defects of the prior art, the purpose of the present disclosure is to provide a method for synthesizing a 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne, which can directly synthesize the 1, 2-bis (arylsulfonyl) ethylene derivative in one step by using the terminal alkyne, and has the advantages of no need of a strong oxidant, no need of an inert atmosphere, and no toxic by-products.
In order to achieve the purpose, the technical scheme of the disclosure is as follows:
a method for synthesizing 1, 2-bis (aryl sulfonyl) ethylene derivatives by catalyzing terminal alkyne with copper takes terminal alkyne and sulfinate compounds as raw materials, cuprous salt as a catalyst, and the reaction is carried out at the temperature of not less than 60 ℃ under the action of an additive;
the terminal alkyne has the formula
The chemical formula of the sodium sulfinate compound is R1SO2M, the additive is one or more of a difluoromethylene compound and ethyl trifluoroacetate, and the difluoromethylene compound is ethyl difluorobromoacetate, ethyl difluoroiodoacetate or ethyl difluorochloroacetate;
wherein R is selected from aryl, substituted aryl which donates or absorbs electrons, heteroaryl which donates or absorbs electrons, C4-C8Straight-chain or branched alkyl, R1Is selected from C1-C5Linear alkyl or alkoxy, aryl, substituted aryl, heterocyclic radical, substituted heterocyclic radical, heteroaromatic radical, substituted heteroaromatic radical, arylamine, aliphatic amine and aromatic ether, wherein M is alkali metal.
The reaction formula is as follows:
wherein R is selected from aryl, substituted aryl which donates or absorbs electrons, heteroaryl which donates or absorbs electrons, C4-C8Straight-chain or branched alkyl, R1Is selected from C1-C5Linear alkyl or alkoxy, aryl, substituted aryl, heterocyclic radical, substituted heterocyclic radical, aromatic hetero radical, substituted aromatic hetero radical, aromatic amine, fatty amine and aromatic ether. R1Is selected from C1-C5Linear or branched alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, heteroaromatic, substituted heteroaromatic.
The functionalized 1, 2-bis (arylsulfonyl) ethylene derivatives are prepared in one step by using terminal alkyne and sodium sulfinate compounds as raw materials under the catalysis of monovalent copper for the first time. The method disclosed by the invention is simple to operate, mild in condition and free from toxic by-products.
The beneficial effect of this disclosure does:
the invention provides a novel 1, 2-bis (arylsulfonyl) ethylene derivative, which is simple, convenient and efficient, and has the advantages of simple and easily obtained raw materials, no toxicity, fewer steps, mild conditions and low cost. The method provided by the disclosure is suitable for large-scale industrial production.
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 3a prepared in example 6 of this disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 2 is a drawing of Compound 3a prepared in example 6 of this disclosure13Nuclear magnetic resonance spectrum of C-NMR;
FIG. 3 is a drawing of Compound 3b prepared according to example 7 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 4 is a drawing of Compound 3b, prepared according to example 7 of the present disclosure13Nuclear magnetic resonance spectrum of C-NMR;
FIG. 5 is a drawing of Compound 3c, prepared according to example 8 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 6 is a drawing of Compound 3c, prepared according to example 8 of the present disclosure13Nuclear magnetic resonance spectrum of C-NMR;
FIG. 7 is a drawing of Compound 3d, prepared according to example 9 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 8 is a drawing of Compound 3d, prepared according to example 9 of the present disclosure13Nuclear magnetic resonance spectrum of C-NMR;
FIG. 9 is a drawing of Compound 3e, prepared according to example 10 of the present disclosure1Nuclear magnetic resonance spectrum of H-NMR;
FIG. 10 is a drawing of Compound 3e, prepared according to example 10 of the present disclosure13Nuclear magnetic resonance spectrum of C-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.
In view of the defects of the existing synthesis method of the 1, 2-bis (arylsulfonyl) ethylene derivative that raw materials are not easy to obtain, reaction conditions are harsh, toxic byproducts are generated and the like, the disclosure provides a method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne.
The typical embodiment of the disclosure provides a method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivatives by copper-catalyzed terminal alkyne, which takes terminal alkyne and sulfinate compounds as raw materials, takes monovalent copper salt as a catalyst, and reacts at the temperature of not less than 60 ℃ under the action of an additive;
the terminal alkyne has the formula
The chemical formula of the sodium sulfinate compound is R1SO2M, the additive is one or more of a difluoromethylene compound and ethyl trifluoroacetate, and the difluoromethylene compound is ethyl difluorobromoacetate, ethyl difluoroiodoacetate or ethyl difluorochloroacetate;
wherein R is selected from aryl, substituted aryl capable of electron donating or electron withdrawing, electron donating or electron withdrawingHeteroaryl of a group C4-C8Straight-chain or branched alkyl, R1Is selected from C1-C5Linear alkyl or alkoxy, aryl, substituted aryl, heterocyclic radical, substituted heterocyclic radical, heteroaromatic radical, substituted heteroaromatic radical, arylamine, aliphatic amine and aromatic ether, wherein M is alkali metal.
The reaction formula is as follows:
the functionalized 1, 2-bis (arylsulfonyl) ethylene derivatives are prepared in one step by using terminal alkyne and sodium sulfinate compounds as raw materials under the catalysis of monovalent copper for the first time. The method disclosed by the invention is simple to operate, mild in condition and free from toxic by-products.
In one or more embodiments of this embodiment, the aryl is phenyl and the electron donating or electron withdrawing substituted aryl is substituted with halo, C1-C6Straight-chain alkyl, C1-C6Branched alkyl, C1-C2Straight-chain alkoxy or C1-C2Phenyl substituted with a branched alkoxy group, said heteroaryl group containing one or more heteroatoms selected from N, O, S.
In one or more embodiments of this embodiment, the aryl group is phenyl; the electron-donating or electron-withdrawing substituted aryl is phenyl substituted by F, Cl, Br, methyl, ethyl, n-propyl, tert-butyl, n-pentyl, methoxy, ethoxy and the like; the heteroaryl group contains one or more heteroatoms selected from N, O, S.
In one or more embodiments of this embodiment, R is selected from the group consisting of phenyl, 4-methoxyphenyl, 4-bromophenyl, 4-methylphenyl, 4-ethylphenyl.
In one or more embodiments of this embodiment, R1Is selected from C1-C5Linear or branched alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, heteroaromatic, substituted heteroaromatic.
One of the embodimentsOr in various embodiments, R1Is aryl or substituted aryl.
In one or more embodiments of this embodiment, R1Is a substituted aryl group.
In one or more embodiments of this embodiment, R1Is 4-methylphenyl.
In one or more embodiments of this embodiment, M is sodium or potassium.
The cuprous salt is a compound containing cuprous such as cuprous iodide, cuprous bromide, cuprous chloride, cuprous thiophene-2-carboxylate, copper tetraacetonitrile tetrafluoroborate, cuprous sulfide, cuprous bromide dimethyl sulfide, cuprous oxide, etc. In one or more embodiments of this embodiment, the monovalent copper salt is cuprous iodide or cuprous sulfide. The catalyst can improve the conversion rate of raw materials and the yield of products. When the monovalent copper salt is cuprous iodide, the yield of the 1, 2-bis (arylsulfonyl) ethylene derivative can be further improved.
In one or more embodiments of this embodiment, the additive is ethyl difluorobromoacetate. When the additive is ethyl difluorobromoacetate, the conversion rate of raw materials and the yield of products can be improved.
In one or more embodiments of this embodiment, the reaction temperature is 60 to 120 ℃. This temperature can increase the conversion of the feedstock while increasing the yield of the product. When the reaction temperature is 100 + -8 deg.C, the conversion rate of the raw materials and the yield of the product can be further improved.
In one or more embodiments of this embodiment, the starting materials are added to a solvent and dissolved, and then reacted with the additives and catalyst by heating.
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 N, N-dimethylformamide or acetonitrile. The solvent improves the conversion rate of raw materials and simultaneously improves the yield of products. When the solvent is acetonitrile, the conversion rate of raw materials and the productThe yield of (a) is higher.
In one or more embodiments of the present disclosure, the molar ratio of the terminal alkyne, the difluoromethylene compound, and the sulfinate compound is 1-3: 1-7: 1 to 6. In the series of examples, the mol ratio of the terminal alkyne, the difluoromethylene compound and the sulfinate compound is 1: 6: 5.
in one or more embodiments of this embodiment, the amount of cuprous salt added is 10% to 50% of the total mass of the starting material.
In the series of examples, the addition amount of the cuprous salt is 20% of the total mass of the raw materials.
In one or more embodiments of this embodiment, the reaction time is 0 to 2 hours and the reaction time is not 0.
In this series of examples, the reaction time was 1. + -. 0.1 h.
In order to improve the purity of the 1, 2-bis (arylsulfonyl) ethylene derivative, in one or more examples of this embodiment, the solution after the reaction is added to an extraction solvent to extract and obtain an organic phase, the solvent in the organic phase is removed, and silica gel column chromatography is performed to obtain the 1, 2-bis (arylsulfonyl) ethylene derivative.
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 1-200: 1-3.
In this series of examples, the volume ratio of petroleum ether to ethyl acetate was 100: 3. The 1, 2-bis (arylsulfonyl) ethylene derivative with higher purity can be obtained by using the eluent.
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 (0.0550mL,0.5mmol), compound 2a, i.e., sodium p-toluenesulfinate (0.4454g, 2.5mmol), ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of 1, 2-Dichloroethane (DCE), dissolved at 100 deg.C, followed by addition of cuprous sulfide (0.0159g, 0.1mmol) to the system and stirring with heating continued for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 53% yield.
Example 2
Compound 1a, i.e., phenylacetylene (0.0550mL,0.5mmol), compound 2a, i.e., sodium p-toluenesulfinate (0.4454g, 2.5mmol), ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of 1, 2-Dichloroethane (DCE), dissolved at 100 deg.C, and then iodoidene ketone iodide (0.0190g, 0.1mmol) was added to the system, and heating and stirring were continued for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 58% yield.
Example 3
The compound 1a, i.e., phenylacetylene (0.0550mL,0.5mmol), the compound 2a, i.e., sodium p-toluenesulfinate (0.4454g, 2.5mmol), and ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of N, N-Dimethylformamide (DMF), dissolved at 100 ℃ and the mixture was then transferred to a substrateTo this was added 0.0190g (0.1 mmol) of iminoketone iodide, and the mixture was stirred for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 60% yield.
Example 4
Compound 1a, phenylacetylene (0.0550mL,0.5mmol), compound 2a, sodium p-toluenesulfinate (0.4454g, 2.5mmol), ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of acetonitrile (CH)3CN) was dissolved at 100 ℃ and, thereafter, iodoidene (0.0190g, 0.1mmol) was added to the system, followed by stirring with heating for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 85% yield.
Example 5
Compound 1a, phenylacetylene (0.0550mL,0.5mmol), compound 2a, sodium p-toluenesulfinate (0.4454g, 2.5mmol), ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of acetonitrile (CH)3CN) was dissolved at 80 ℃ and, thereafter, iodoidene (0.0190g, 0.1mmol) was added to the system, followed by stirring with heating for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 60% yield.
The reactions of examples 1 to 5 are shown below:
example 6
Compound 1a, phenylacetylene (0.0550mL,0.5mmol), compound 2a, sodium p-toluenesulfinate (0.4454g, 2.5mmol), ethyl difluorobromoacetate (0.3840mL,3.0mmol) were added to 2mL of acetonitrile (CH)3CN) at 120 ℃ and then, to the system was added iodoidene (0.0190g, 0.1mmol) and the mixture was stirred with heating for one hour. TLC detects the disappearance of the substrate and the reaction is finished. Cooling the reaction solution, pouring into 30mL of water, extracting with dichloromethane (3X 10mL), mixing organic phases, drying with anhydrous magnesium sulfate, vacuum filtering, distilling under reduced pressure to remove organic solvent to obtain viscous liquid, and performing silica gel column chromatography (eluent is V)Petroleum ether:VEthyl acetate100:3) gave compound 3a in 82% yield.
The reaction is shown as follows:
compound 3 a:
1H NMR(400MHz,CDCl3) δ 7.68(s,1H), 7.40-7.32 (m,2H), 7.32-7.22 (m,3H), 7.13-7.09 (m,6H),6.83(m, J ═ 7.8,1.4Hz,2H),2.31(d, J ═ 6.4Hz,6H), as shown in fig. 1;13C NMR(100MHz,CDCl3) As shown in fig. 2, δ 150.70, 145.74, 145.41, 137.57, 136.28, 133.13, 130.16, 130.02, 129.83, 129.75, 129.16, 128.18, 127.74, 126.98, 21.72, 21.69; HRMS (ESI) m/z calculated for C22H20O4S2[M+Na]+:435.0701,found:435.0655.
Example 7
The reaction was carried out as shown in the following formula under the same conditions as in example 6 except that 4-methoxyphenylacetylene (i.e., compound 1b) was used instead of compound 1a in example 6, to obtain compound 3b in 82% yield.
Compound 3 b:
1H NMR(400MHz,CDCl3) δ 7.71(s,1H), 7.50-7.44 (m,2H), 7.41-7.36 (m,2H), 7.24-7.17 (m,3H), 6.95-6.88 (m,2H), 6.76-6.70 (m,2H),3.81(s,3H),2.41(d, J ═ 9.4Hz,6H), as shown in fig. 3;13C NMR(100MHz,CDCl3) As shown in fig. 4, δ 151.44, 145.99, 145.75, 138.00, 136.10, 132.97, 131.67, 131.09, 129.96, 129.15, 128.21, 125.994, 124.98, 21.76; HRMS (ESI) m/z calculated for C23H22O5S2[M+Na]+:465.0806,found:465.0855.
Example 8
The reaction shown by the following formula was carried out under the same conditions as in example 6 except that 4-bromophenylacetylene (i.e., compound 1c) was used instead of compound 1a in example 6, to obtain compound 3c in a yield of 86%.
Compound 3 c:
1H NMR(400MHz,CDCl3) As shown in fig. 5, δ 7.74(s,1H),7.53 to 7.45(m,2H),7.43 to 7.30(m,4H),7.26(s,4H),6.88 to 6.72(m,2H),2.43(d, J ═ 9.8Hz,6H).13C NMR(100MHz,CDCl3) As shown in fig. 6, δ 161.09, 152.65, 145.52, 145.29, 137.37, 136.47, 133.49, 131.84, 129.77, 129.73, 129.08, 128.18, 21.71; HRMS (ESI) m/z calculated for C22H19BrO4S2[M+Na]+:512.9806,found:512.9866.
Example 9
The reaction shown by the following formula was carried out under the same conditions as in example 6 except that 4-ethylphenylacetylene (i.e., compound 1d) was used instead of compound 1a in example 6, to obtain compound 3d in a yield of 81%.
Compound 3 d:
1H NMR(400MHz,CDCl3) As shown in fig. 7, δ 7.73(s,1H),7.48 to 7.41(m,2H),7.37(d, J ═ 6.5Hz,2H),7.18(dd, J ═ 8.0,5.8Hz,4H),7.06 to 6.97(m,2H),6.87 to 6.79(m,2H),2.63(q, J ═ 7.6Hz,2H),2.40(d, J ═ 2.8Hz,6H),1.22(d, J ═ 7.7Hz,3H).13C NMR(100MHz,CDCl3) As shown in fig. 8, δ 152.95, 146.54, 145.56, 145.20, 137.60, 136.35, 133.37, 130.17, 129.70, 129.16, 128.22, 127.75, 124.10, 28.71, 21.72, 15.34; HRMS (ESI) m/z calculated for C24H24O4S2[M+Na]+:463.1014,found:463.1055.
Example 10
The reaction shown by the following formula was carried out under the same conditions as in example 6 except that 4-methylphenylacetylene (i.e., compound 1d) was used instead of compound 1a in example 6, to obtain compound 3e in 83% yield.
Compound 3e
1H NMR(400MHz,CDCl3) As shown in fig. 7, δ 7.71(s,1H),7.54 to 7.43(m,2H),7.43 to 7.33(m,2H),7.25 to 7.13(m,4H),7.01(d, J ═ 7.8Hz,2H),6.88 to 6.70(m,2H),2.40(d, J ═ 8.3Hz,6H),2.34(s,3H).13C NMR(100MHz,CDCl3) As shown in fig. 8, δ 152.87, 145.58, 145.35, 140.33, 137.37, 136.42, 133.34, 130.08, 129.72, 129.17, 128.49, 128.22, 123.95, 21.73; HRMS (ESI) m/z calculated for C23H22O4S2[M+Na]+:449.0857,found:449.0816.
Example 11
Compound 1a, i.e., phenylacetylene (0.0550mL,0.5mmol), compound 2a, i.e., sodium p-toluenesulfinate (0.4454g, 2.5mmol), was added to 2mL of 1, 2-Dichloroethane (DCE) and dissolved at 100 deg.C, followed by addition of cuprous sulfide (0.0159g, 0.1mmol) to the system and stirring with heating continued for one hour. TLC detection substrate remained, no product was found. To verify the substrate remaining, the reaction mixture 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, and the substrate was recovered as compound 1a by silica gel column chromatography (eluent was petroleum ether).
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 (25)
1. A method for synthesizing 1, 2-bis (aryl sulfonyl) ethylene derivatives by using terminal alkyne catalyzed by copper is characterized in that terminal alkyne and sulfinate compounds are used as raw materials, cuprous salt is used as a catalyst, and the reaction is carried out at the temperature of not less than 60 ℃ under the action of an additive, wherein the reaction formula is as follows:
the terminal alkyne has the formula
The sulfinate compound has the chemical formula R1SO2M, the additive is a difluoromethylene compound, and the difluoromethylene compound is ethyl difluorobromoacetate, ethyl difluoroiodoacetate or ethyl difluorochloroacetate;
wherein R is selected from aryl, electron-donating or electron-withdrawing substituted aryl, heteroaryl, R1Selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl, and M is an alkali metal.
2. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein the aryl group is phenyl, and the electron-donating or electron-withdrawing substituted aryl group is substituted by halogen or C1-C6Straight-chain alkyl, C1-C6Branched alkyl, C1-C2Straight-chain alkoxy or C1-C2Phenyl substituted with a branched alkoxy group, said heteroaryl group containing one or more heteroatoms selected from N, O, S.
3. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein the aryl group is a phenyl group; the electron-donating or electron-withdrawing substituted aryl is phenyl substituted by F, Cl, Br, methyl, ethyl, n-propyl, tert-butyl, n-pentyl, methoxy and ethoxy; the heteroaryl group contains one or more heteroatoms selected from N, O, S.
4. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein R is selected from the group consisting of phenyl, 4-methoxyphenyl, 4-bromophenyl, 4-methylphenyl, and 4-ethylphenyl.
5. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne as claimed in claim 1, wherein R is1Is 4-methylphenyl.
6. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein M is sodium or potassium.
7. The method for the synthesis of 1, 2-bis (arylsulfonyl) ethylene derivatives with copper-catalyzed terminal alkynes according to claim 1, wherein the monovalent copper salt is cuprous iodide or cuprous sulfide.
8. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne as claimed in claim 1, wherein the additive is ethyl difluorobromoacetate.
9. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne according to claim 1, wherein the reaction temperature is 60-120 ℃.
10. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein the reaction temperature is 100 ± 8 ℃.
11. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne according to claim 1, wherein the raw materials are added into a solvent to be dissolved, then an additive and a catalyst are added, and the mixture is heated to react.
12. The process for the synthesis of 1, 2-bis (arylsulfonyl) ethylene derivatives with copper-catalyzed terminal alkynes according to claim 11, wherein the solvent is N, N-dimethylformamide or acetonitrile.
13. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne according to claim 1, wherein the molar ratio of the terminal alkyne, the difluoromethylene compound and the sulfinate compound is 1-3: 1-7: 1 to 6.
14. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne in claim 1, wherein the molar ratio of the terminal alkyne to the difluoromethylene compound to the sulfinate compound is 1: 6: 5.
15. the method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne as claimed in claim 1, wherein the addition amount of the cuprous salt is 10-50% of the total mass of the raw materials.
16. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne as claimed in claim 1, wherein the addition amount of the cuprous salt is 20% of the total mass of the raw materials.
17. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne, according to claim 1, wherein the reaction time is 0-2 h and is different from 0.
18. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through the copper-catalyzed terminal alkyne in the claim 1, wherein the reaction time is 1 plus or minus 0.1 h.
19. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne according to claim 1, wherein the solution after the reaction is added into an extraction solvent to extract the solution to obtain an organic phase, the solvent in the organic phase is removed, and silica gel column chromatography is performed to obtain the 1, 2-bis (arylsulfonyl) ethylene derivative.
20. The method of claim 19, wherein the extraction solvent used for the extraction is one or more of 1, 2-dichloroethane, toluene, nitromethane, ethyl acetate, diethyl ether, n-hexane, cyclohexane, petroleum ether, and dichloromethane.
21. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne according to claim 19, wherein the extraction is performed 1 to 3 times by using 5 to 20mL of the extraction solvent each time.
22. The process for the synthesis of 1, 2-bis (arylsulfonyl) ethylene derivatives with copper-catalyzed terminal alkynes according to claim 19, wherein the organic phase obtained is dried over anhydrous magnesium sulfate and the organic solvent is removed.
23. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne of claim 19, wherein the eluent of the silica gel column chromatography is petroleum ether and ethyl acetate.
24. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne according to claim 23, wherein the volume ratio of the petroleum ether to the ethyl acetate is 1-200: 1-3.
25. The method for synthesizing the 1, 2-bis (arylsulfonyl) ethylene derivative through copper-catalyzed terminal alkyne of claim 23, wherein the volume ratio of the petroleum ether to the ethyl acetate is 100: 3.
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