A method for anti-Markovnikov hydro-selenation of aryl vinylenes
By using deionized water as a solvent under argon, the arylethylene compound and benzeneselenol are subjected to anti-martensite addition, which solves the problem that the anti-martensite hydroselenization reaction of arylethylene is difficult to carry out efficiently in non-toxic solvents, and achieves high yield and environmentally friendly production of anti-martensite hydroselenization products.
Patent Information
- Application Number
- CN202510513647.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-23
- Publication Date
- 2025-07-04
- Estimated Expiration
- 2045-04-23
AI Technical Summary
In the prior art, the anti-Markanine hydroselenization reaction of arylethylene is difficult to carry out efficiently in non-toxic solvents, and requires the participation of light or catalysts, and the environment is unfriendly.
In an argon environment, deionized water is used as a solvent, arylethylene compounds and benzeneselenol undergo an anti-martensite addition reaction to form an anti-martensite hydroselenization product, which is carried out through a free radical process, avoiding the use of metals or photocatalysts.
It has achieved high yield of anti-Markanine hydroselenization products, mild reaction conditions, environmentally friendly, easy to obtain raw materials, and good regional selectivity, providing a simple, effective and atomic economic new way.
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Figure CN120040327B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for anti-Markovnikov hydroselenation of aryl vinylenes. Background Art
[0002] Organic selenium compounds are widely used in the fields of synthetic chemistry, pharmaceutical chemistry, material science, etc. Among various strategies for constructing C-Se bonds, the hydroselenation reaction of carbon-carbon double bonds is the simplest, most direct and atom-economic method. In the reported hydroselenation reactions of carbon-carbon double bonds, the double bonds mainly come from activated olefins, including α,β-unsaturated carbonyl compounds, N-vinyl lactams, α,β-unsaturated thioamides, allenes, etc., while there is very little research on the hydroselenation reaction of aryl vinylenes, which are important representative substances of carbon-carbon double bonds.
[0003] In 2022, the research group of Yang Xiaohui carried out the reaction of rhodium-catalyzed styrene and benzeneselenol. Through the use of chiral ligands, the reaction can generate Markovnikov addition products with high stereoselectivity and regioselectivity. Two years later, the research group of Yang Xiaohui developed a photo-promoted reaction of styrene and benzeneselenol, which highly regioselectively generated anti-Markovnikov addition products, and disclosed that the presence of light and diphenyl diselenide is the decisive factor for the smooth occurrence of the anti-Markovnikov reaction. In 2025, the research group of Zhou Yunbing used Hantzsch ester as a hydrogen donor and carried out the hydroselenation of olefins with diselenide as the selenium source under green light. The electronic effect of diselenide greatly affects the regioselectivity of the hydroselenation reaction.
[0004] To sum up, in the hydroselenation reaction of styrene, the Markovnikov addition product is relatively easy to obtain, which is consistent with the regioselectivity of the hydroselenation reaction of activated carbon-carbon double bonds; conversely, the anti-Markovnikov addition product is difficult to obtain and requires the participation of light initiation, catalysts and a greatly excessive hydrogen donor reagent. Particularly noteworthy is that all the above-reported Markovnikov or anti-Markovnikov hydroselenation reactions of aryl vinylenes are carried out in chlorinated solvents (dichloromethane or dichloroethane) with certain toxicity, and the reaction conditions are extremely unfriendly to the environment. Therefore, it is of great significance to develop a method for anti-Markovnikov hydroselenation of aryl vinylenes with simple operation and friendly reaction conditions. Summary of the Invention
[0005] Aiming at the deficiencies in the prior art, the present invention provides a method for anti-Markovnikov hydroselenation of aryl vinylenes. In an argon atmosphere, an aryl vinyl compound and benzeneselenol are mixed and reacted in a deionized water solvent, and anti-Markovnikov addition is carried out via a free radical process to form an anti-Markovnikov hydroselenation product with a high yield; without metal or photocatalysis, without any additives, the raw materials are simple and easy to obtain, the reaction is green and mild, with good regioselectivity, carried out under deionized water conditions, environmentally friendly, and provides a simple, effective and atom-economic new route for the hydroselenation of olefins.
[0006] To solve the above technical problems, a first aspect of the present invention provides a method for anti-Markovnikov hydroselenation of aryl vinylenes, comprising the following steps:
[0007] The reaction flask is deoxygenated by a protective gas, and using deionized water as a solvent, the aryl vinyl compound and benzeneselenol undergo an anti-Markovnikov addition reaction to obtain an anti-Markovnikov hydroselenation product;
[0008] The general structural formula of the aryl vinyl compound is: ;
[0009] The general structural formula of the anti-Markovnikov hydroselenation product is: ;
[0010] Wherein, R is selected from hydrogen, methyl or cyclopropyl.
[0011] In the present invention, using deionized water as a solvent, under a protective atmosphere, the aryl vinyl compound and benzeneselenol are mixed in deionized water, and an anti-Markovnikov addition reaction is carried out via a free radical process to form an anti-Markovnikov hydroselenation product with high yield; at the same time, the anti-Markovnikov hydroselenation method of the present invention does not require metal or photocatalysis, does not require any additives, the raw materials are simple and easily available, the reaction is green and mild, has good regioselectivity, is carried out under deionized water conditions, is environmentally friendly, and provides a simple, effective and atom-economic new route for the hydroselenation of olefins.
[0012] Further, the aryl vinyl compound is:
[0013]
[0014] Further, the anti-Markovnikov hydroselenation product is:
[0015]
[0016] Further, the molar ratio of the aryl vinyl compound to benzeneselenol is (1 - 1.5):(1 - 1.5).
[0017] Further, the concentration of the aryl vinyl compound in the solvent is 0.375 - 7.5 mol / L.
[0018] Further, the concentration of benzeneselenol in the solvent is 0.25 - 5 mol / L.
[0019] Further, the protective gas is argon or nitrogen.
[0020] Further, the temperature of the reaction is 5 - 70 °C.
[0021] Further, the reaction time is 0.5 - 9 h.
[0022] The second aspect of the present invention provides an anti-Markovnikov hydroselenylation product obtained by the method described in the first aspect.
[0023] Advantages of the present invention:
[0024] Using deionized water as a solvent, under an argon atmosphere, the aryl vinyl compound and benzeneselenol undergo anti-Markovnikov addition via a radical process to form an anti-Markovnikov hydroselenylation product with a high yield.
[0025] The anti-Markovnikov hydroselenylation method of the present invention does not require metal or photocatalysis, does not require any additives, has simple and easily available raw materials, has a green and mild reaction, good regioselectivity, is carried out under deionized water conditions, is environmentally friendly, and provides a simple, effective and atom-economic new route for the hydroselenylation of olefins. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] In order to more clearly illustrate the technical solutions of the present invention, the drawings required for use in the examples will be briefly introduced below. Obviously, the drawings in the following description are only examples of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.
[0027] Figure 1 It is a reaction mechanism diagram of the anti-Markovnikov hydroselenylation method of the aryl vinyl of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0028] The technical solutions of the present invention will be clearly and completely described below in conjunction with the specific embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.
[0029] Example 1
[0030] This example relates to an anti-Markovnikov hydroselenylation method of aryl vinyl, which includes the following steps:
[0031] The reaction flask was deoxygenated by a protective gas. Deionized water (1 mL), styrene (0.75 mmol), and benzeneselenol (0.5 mmol) were added to the reaction flask. After stirring evenly, it was placed in an oil bath at 50 °C for heating for 6 h. After the reaction was completed, it was transferred with a small amount of ethyl acetate, and then separated by flash column chromatography to obtain a colorless and transparent oily substance. The structure of this oily substance was characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry, and was determined to be the anti-Markovnikov hydroselenylation product phenyl(phenylethyl)selane. The reaction formula is:
[0032] .
[0033] Among them, 1 1H NMR (400 MHz, CDCl3) δ 7.50 - 7.47 (m, 2H), 7.28 - 7.14 (m, 8H), 3.14 - 3.10 (m, 2H), 2.99 - 2.95 (m, 2H). 13 13C NMR (100 MHz, CDCl3) δ141.1, 132.7, 130.3, 129.2, 128.6, 128.5, 127.0, 126.5, 36.7, 28.8. HRMS (EI)m / z: calcd for C 14 H 14 Se [M] + 262.0261, found 262.0265。
[0034] Example 2
[0035] On the basis of Example 1, the reaction temperature and / or reaction time were adjusted to carry out the anti - Markovnikov hydro - selenation of aryl ethylene. The isolated yields of the products with different reaction temperatures and times in Example 1 and Example 2 are shown in Table 1. It can be seen that under the reaction conditions of Examples 1 - 2 of the present invention, relatively high isolated yields were obtained. Among them, the yield was the highest when the reaction temperature was 50 °C and the time was 6 h, reaching 90%.
[0036] Table 1
[0037]
[0038] Example 3
[0039] On the basis of Example 1, the solvent dosage and the molar ratio of the substrate feed were adjusted to carry out the anti - Markovnikov hydro - selenation of aryl ethylene. Referring to Table 2, the amount of benzeneselenol in serial numbers 1 - 3 was 0.5 mmol, and the amount of styrene in serial numbers 4 - 6 was 0.5 mmol. The isolated yields of the products with different solvent addition amounts and substrate feed ratios in Example 1 and Example 3 are shown in Table 2. It can be seen that under the reaction conditions of Examples 1 and 3 of the present invention, relatively high isolated yields were obtained. Among them, the yield was the highest under the reaction conditions of a solvent dosage of 1 mL, a styrene amount of 0.5 mmol, and a benzeneselenol amount of 0.6 - 0.75 mmol, reaching 95%.
[0040] Table 2
[0041]
[0042] Example 4
[0043] The difference between this example and Example 1 lies in that the addition amount of styrene is 0.5 mmol and the addition amount of phenylselenol is 0.6 mmol, and other steps and parameters remain unchanged.
[0044] In addition, the reaction substrate phenylselenol (labeled as 2) remains unchanged, and the reaction substrate styrene is replaced with the aryl vinyl compound substrate in Table 3 (labeled as 1). The corresponding product (labeled as 3) and the product separation yield are shown in Table 3. The reaction general formula is:
[0045] 。
[0046] Table 3
[0047]
[0048] As can be seen from Table 3, in the examples of the present invention, the reaction substrates all undergo anti-Markovnikov addition with phenylselenol in deionized water solvent to form anti-Markovnikov hydroselenation products, and have good yields. Among them, the highest yield reaches 99%.
[0049] Among them, Characterization shows that: 1 H NMR (400 MHz, CDCl3) δ 7.79 - 7.74 (m, 3H), 7.59 - 7.50 (m, 3H), 7.46 - 7.39 (m, 2H), 7.29 - 7.20 (m, 4H), 3.23 - 3.18 (m, 2H), 3.15 - 3.11 (m, 2H). 13 C NMR (100 MHz, CDCl3) δ 138.5, 133.6, 132.8, 132.3, 130.3, 129.2, 128.2, 127.8, 127.6, 127.1, 127.0, 126.8, 126.2, 125.5, 36.9, 28.7. HRMS (EI) m / z: calcd for C 18 H 16 Se [M] + 312.0417, found 312.0415.
[0050] Characterization: 11H NMR (400 MHz, CDCl3) δ 8.50 - 8.48 (m, 2H), 7.52 - 7.48 (m, 2H), 7.29 - 7.25 (m, 3H), 7.09 - 7.08 (m, 2H), 3.14 - 3.10 (m, 2H), 2.99 - 2.95 (m, 2H). 13 13C NMR (100 MHz, CDCl3) δ 149.9, 149.7, 133.1, 129.6, 129.3, 127.3, 123.8, 35.8, 27.3. HRMS (EI) m / z: calcd for C 13 H 13 NSe [M] + 263.0213, found 263.0209.
[0051] Characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.42 - 7.39 (m, 2H), 7.31 - 7.26 (m, 2H), 7.22 - 7.16 (m, 6H), 3.40 (dd, J J = 11.6, 6.4 Hz, 1H), 3.28 (dd, J J = 11.6, 8.0 Hz, 1H), 2.18 - 2.12 (m, 1H), 1.13 - 1.04 (m, 1H), 0.64 - 0.57 (m, 1H), 0.44 - 0.37 (m, 1H), 0.30 - 0.24 (m, 1H), 0.10 - 0.04 (m, 1H). 13 13C NMR (100 MHz, CDCl3) δ 144.2, 132.3, 131.3, 129.0, 128.4, 127.6, 126.7, 126.6, 51.1, 35.2, 17.5, 6.1, 4.2. HRMS (ASAP) m / z: calcd for C 17 H 18 Se [M + H] + 303.0652, found 303.0662。
[0052] Comparative Example 1
[0053] The difference between this comparative example and Example 1 is that the solvent was replaced with tetrahydrofuran, and other conditions and steps remained unchanged. The yield of the anti - Markovnikov hydro - selenation product obtained was only 27%.
[0054] Comparative Example 2
[0055] The difference between this comparative example and Example 1 is that the solvent was replaced with ethanol, and other conditions and steps remained unchanged. The yield of the anti-Markovnikov hydroselenation product was only 10%.
[0056] Comparative Example 3
[0057] The difference between this comparative example and Example 1 is that the solvent was replaced with n-butyl ether, and other conditions and steps remained unchanged. The yield of the anti-Markovnikov hydroselenation product was only 26%.
[0058] Comparative Example 4
[0059] The difference between this comparative example and Example 1 is that the solvent was replaced with dichloroethane, and other conditions and steps remained unchanged. The yield of the anti-Markovnikov hydroselenation product was only 68%, and dichloroethane has strong toxicity.
[0060] Comparative Example 5
[0061] The difference between this comparative example and Example 1 is that the solvent was replaced with chloroform, and other conditions and steps remained unchanged. The yield of the anti-Markovnikov hydroselenation product was only 42%, and chloroform has relatively high toxicity.
[0062] From the comparison between Comparative Examples 1-5 and Example 1, it can be seen that the method of the present invention has better anti-Markovnikov addition selectivity for aryl vinyl compounds and benzeneselenol only in deionized water solvent.
[0063] Comparative Example 6
[0064] The difference between this comparative example and Example 4 is that styrene was replaced with cyclohexene, and other conditions and steps remained unchanged. The reaction did not proceed at all.
[0065] Comparative Example 7
[0066] The difference between this comparative example and Example 4 is that styrene was replaced with 1-octene, and other conditions and steps remained unchanged. The reaction did not proceed at all.
[0067] From the comparison between Comparative Examples 6-7 and Example 4, it can be seen that the method of the present invention is only feasible for aryl olefins.
[0068] From the comparison between the above comparative examples and examples, it can be seen that the method of the present invention has excellent anti-Markovnikov addition selectivity only when the solvent is deionized water and the reaction substrate is aryl ethylene. The reaction proceeds through a radical process: when the reaction flask is deoxygenated by a protective gas, trace amounts of oxygen remaining in the reaction flask convert benzeneselenol (labeled 2) into benzeneselenyl cation radical, which is converted into benzeneselenyl radical I under the action of water. Subsequently, the generated benzeneselenyl radical undergoes a radical addition reaction with styrene (labeled 1a) to form a benzyl radical intermediate II. Intermediate II abstracts the hydrogen in benzeneselenol to generate the final product phenylphenylethyl selenide (labeled 3a) and regenerates benzeneselenyl radical I, specifically as Figure 1 shown.
[0069] In summary, the present invention uses deionized water as the solvent, and under a protective atmosphere, mixes an aryl ethylene compound and benzeneselenol in deionized water, and undergoes an anti-Markovnikov addition through a radical process to form an anti-Markovnikov hydroselenation product with a high yield. At the same time, the anti-Markovnikov hydroselenation method of the present invention does not require metal or photocatalysis, the raw materials are simple and easily available, the reaction is green and mild, has good regioselectivity, is carried out under deionized water conditions, is environmentally friendly, and provides a simple, effective and atom-economic new route for the hydroselenation of olefins.
[0070] The present invention has been described in detail above in combination with specific embodiments and exemplary examples, but these descriptions should not be construed as limiting the present invention. Those skilled in the art understand that without departing from the spirit and scope of the present invention, various equivalent substitutions, modifications or improvements can be made to the technical solutions and their implementation manners of the present invention, and these all fall within the scope of the present invention. The protection scope of the present invention is subject to the appended claims.
Claims
1. A method for anti-Markovnikov hydroselenation of aryl vinylenes, characterized in that, Including the following steps: The reaction flask is deoxygenated with a protective gas. Using deionized water as a solvent, an anti-Markovnikov addition reaction between an aryl vinyl compound and benzeneselenol is carried out to obtain an anti-Markovnikov hydro-selenation product; The general structural formula of the aryl vinyl compound is as follows: The general structural formula of the anti-Markovnikov hydrogen selenide product is as follows: wherein, R is selected from hydrogen, methyl or cyclopropyl.
2. The anti-Markovnikov hydro-selenation method of aryl ethylene according to claim 1, characterized in that, The aryl vinyl compound is:
3. The anti-Markovnikov hydroselenation method of aryl ethylene according to claim 1, characterized in that, The anti-Markovnikov hydro-selenation product is:
4. The anti-Markovnikov hydroselenation method of aryl ethylene according to claim 1, wherein The molar ratio of the aryl vinyl compound to benzeneselenol is (1 - 1.5):(1 - 1.5).
5. The anti-Markovnikov hydroselenation method of aryl ethylene according to claim 1, wherein The concentration of the aryl vinyl compound in the solvent is 0.375 - 7.5 mol / L.
6. The anti-Markovnikov hydroselenation method of aryl ethylene according to claim 1, characterized in that, The concentration of benzeneselenol in the solvent is 0.25 - 5 mol / L.
7. The anti-Markovnikov hydro-selenation method of aryl ethylene according to claim 1, wherein The protective gas is argon or nitrogen.
8. The anti-Markovnikov hydroselenation method of aryl ethylene according to claim 1, characterized in that, The temperature of the reaction is 5 - 70 °C.
9. The anti-Markovnikov hydro-selenation method of aryl ethylene according to claim 1, characterized in that, The reaction time is 0.5 - 9 h.