Anti-Martensite hydroselenylation method of aryl ethylene

Abstract

The invention discloses a trans-Markov hydroselenylation method of aryl ethylene, which comprises the following steps: carrying out deoxidation treatment on a reaction flask through a protective gas, and carrying out trans-Markov addition reaction on an aryl ethylene compound and phenylselenol by taking deionized water as a solvent to obtain a trans-Markov hydroselenylation product; the structural general formula of the aryl ethylene compound is # imgabs0 #; the structural general formula of the anti-Martensite hydroselenylation product is # imgabs 1 #. According to the preparation method, deionized water is used as a solvent, in the argon atmosphere, the aryl ethylene compound and the phenylselenol are subjected to anti-Markov addition through the free radical process, the anti-Markov hydroselenylation product is formed, and the yield is high; metal or photocatalysis is not needed, the raw materials are simple and easy to obtain, the reaction is green and mild, the regioselectivity is good, the reaction is carried out under the deionized water condition, the method is environment-friendly, and a simple, effective and atom-economical new way is provided for hydroselenylation of olefin.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly to an anti-Markovnikov hydroselenation method of aryl vinylenes. Background Art

[0002] Organic selenium compounds are widely used in the fields of synthetic chemistry, pharmaceutical chemistry, materials 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-economical 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. However, 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. By using 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 a selenium source under green light. The electronic effect of diselenide greatly affects the regioselectivity of the hydroselenation reaction.

[0004] In summary, in the hydroselenation reaction of styrene, Markovnikov addition products are relatively easy to obtain, which is consistent with the regioselectivity of the hydroselenation reaction of activated carbon-carbon double bonds; conversely, anti-Markovnikov addition products are difficult to obtain and require the participation of light initiation, catalysts, and a large excess of hydrogen donor reagents. It is particularly noteworthy 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 simple and environmentally friendly method for the anti-Markovnikov hydroselenation of aryl vinylenes. Summary of the Invention

[0005] Aiming at the deficiencies in the prior art, the present invention provides an anti-Markovnikov hydroselenation method 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 through a free radical process to form an anti-Markovnikov hydroselenation product with a high yield; no metal or photocatalysis is required, no additives are required, the raw materials are simple and easily available, the reaction is green and mild, the regioselectivity is good, and it is carried out under deionized water conditions, which is environmentally friendly and provides a simple, effective, and atom-economical 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 hydroselenylation of aryl vinylenes, comprising the following steps: The reaction flask is deoxygenated by a protective gas. Using deionized water as a solvent, an anti-Markovnikov addition reaction is carried out between an aryl vinyl compound and benzeneselenol to obtain an anti-Markovnikov hydroselenylation product; The general structural formula of the aryl vinyl compound is: ; The general structural formula of the anti-Markovnikov hydroselenylation product is: ; Wherein, R is selected from hydrogen, methyl or cyclopropyl.

[0007] The present invention uses deionized water as a solvent. Under a protective atmosphere, an 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 hydroselenylation product with a high yield. At the same time, the anti-Markovnikov hydroselenylation 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-economical new route for the hydroselenylation of olefins.

[0008] Further, the aryl vinyl compound is:

[0009] Further, the anti-Markovnikov hydroselenylation product is:

[0010] Further, the molar ratio of the aryl vinyl compound to benzeneselenol is (1 - 1.5):(1 - 1.5).

[0011] Further, the concentration of the aryl vinyl compound in the solvent is 0.375 - 7.5 mol / L.

[0012] Further, the concentration of benzeneselenol in the solvent is 0.25 - 5 mol / L.

[0013] Further, the protective gas is argon or nitrogen.

[0014] Further, the temperature of the reaction is 5 - 70 °C.

[0015] Further, the reaction time is 0.5 - 9 h.

[0016] A second aspect of the present invention provides an anti-Markovnikov hydroselenylation product prepared by the method described in the first aspect.

[0017] Advantages of the present invention: In the present invention, deionized water is used as a solvent, and under an argon atmosphere, an aryl vinyl compound and benzeneselenol undergo anti-Markovnikov addition via a radical process to form an anti-Markovnikov hydroselenation product with a high yield.

[0018] 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only embodiments 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.

[0020] Figure 1 is the reaction mechanism diagram of the anti-Markovnikov hydroselenation method of the aryl vinyl of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0021] 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 fall within the scope of protection of the present invention.

[0022] Example 1

[0023] This example relates to an anti-Markovnikov hydroselenation method of an aryl vinyl, which includes the following steps: 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 and heated 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 oily substance was characterized by proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR) and high-resolution mass spectrometry (HRMS), and its structure was determined to be the anti-Markovnikov hydroselenation product phenyl(phenylethyl)selane. The reaction formula is: .

[0024] Among them, 1 1H NMR (400 MHz, CDCl 3) 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 C NMR (100 MHz, CDCl 3 ) 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。

[0025] Example 2

[0026] On the basis of Example 1, this example adjusted the reaction temperature and / or reaction time to conduct anti - Markovnikov hydro - selenation of aryl vinyl. The separation yields of products at 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 separation yields are obtained. Among them, the yield is the highest when the reaction temperature is 50 °C and the time is 6 h, reaching 90%.

[0027] Table 1

[0028] Example 3 On the basis of Example 1, this example adjusted the solvent dosage and the molar ratio of substrate feed to conduct anti - Markovnikov hydro - selenation of aryl vinyl. Referring to Table 2, among them, the dosage of benzeneselenol in No. 1 - 3 is 0.5 mmol, and the dosage of styrene in No. 4 - 6 is 0.5 mmol. The separation yields of products at 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 separation yields are obtained. Among them, the yield is the highest under the reaction conditions of solvent dosage of 1 mL, styrene dosage of 0.5 mmol, and benzeneselenol dosage of 0.6 - 0.75 mmol, up to 95%.

[0029] Table 2

[0030] Example 4 The difference between this example and Example 1 is that the addition amount of styrene is 0.5 mmol and the addition amount of benzeneselenol is 0.6 mmol, and other steps and parameters remain unchanged.

[0031] In addition, with the reaction substrate phenylselenol (labeled as 2) remaining unchanged, the reaction substrate styrene is replaced with the aryl vinyl compound substrate in Table 3 (labeled as 1), and the corresponding product (labeled as 3) and the isolated yield of the product are shown in Table 3. The reaction general formula is: .

[0032] Table 3

[0033] 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%.

[0034] Among them, Characterization shows that: 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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.

[0035] Characterization: 1 H NMR (400 MHz, CDCl 3 ) 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). 1313C NMR (100 MHz, CDCl 3 ) 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. Characterization: 1 1H NMR (400 MHz, CDCl 3 ) δ 7.42 - 7.39 (m, 2H), 7.31 - 7.26 (m, 2H), 7.22 - 7.16 (m, 6H), 3.40 (dd, J = 11.6, 6.4 Hz, 1H), 3.28 (dd, 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, CDCl 3 ) 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。

[0036] Comparative Example 1

[0037] 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%.

[0038] Comparative Example 2

[0039] 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 hydro - selenation product obtained was only 10%.

[0040] Comparative Example 3

[0041] 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 hydro-selenation product was only 26%.

[0042] Comparative Example 4 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 hydro-selenation product was only 68%, and dichloroethane is highly toxic.

[0043] Comparative Example 5

[0044] 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 hydro-selenation product was only 42%, and chloroform is highly toxic.

[0045] 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.

[0046] Comparative Example 6 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.

[0047] Comparative Example 7 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.

[0048] 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.

[0049] 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 vinyl. Its reaction proceeds through a radical mechanism: when the reaction flask is deoxygenated by a protective gas, trace amounts of oxygen remaining in the reaction flask convert benzeneselenol (labeled as 2) into a benzeneselenyl cation radical, which is converted into a benzeneselenyl radical I under the action of water. Subsequently, the generated benzeneselenyl radical undergoes a radical addition reaction with styrene (labeled as 1a) to form a benzyl radical intermediate II. Intermediate II abstracts the hydrogen in benzeneselenol to generate the final product phenylphenylethyl selenide (labeled as 3a) and regenerates benzeneselenyl radical I, as specifically shown in Figure 1 as shown.

[0050] In summary, in the present invention, deionized water is used as a solvent. Under a protective atmosphere, an aryl vinyl compound and benzeneselenol are mixed in deionized water, and anti-Markovnikov addition is carried out via a free 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 the condition of deionized water, is environmentally friendly, and provides a simple, effective and atom-economic new route for the hydroselenation of olefins.

[0051] 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 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 hydroselenization of arylethylene, characterized in that: The steps include: The reaction bottle is deoxygenated by using protective gas, and the aromatic vinyl compound and phenylselenol are subjected to anti-Markovnikov addition reaction with deionized water as solvent to obtain an anti-Markovnikov hydroselenation product. The general structural formula of the aromatic vinyl compound is: ; The general structural formula of the anti-Markovnikov hydroselenization product is: ; Wherein, R is selected from hydrogen, methyl or cyclopropyl.

2. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The aromatic vinyl compound is: 。 3. The anti-Markovnikov hydroselenization method of arylethylene according to claim 1, characterized in that: The anti-Markovnikov hydroselenization product is: 。 4. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The molar ratio of the arylethylene compound to phenylselenol is (1-1.5): (1-1.5).

5. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The concentration of the aromatic vinyl compound in the solvent is 0.375-7.5 mol / L.

6. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The concentration of the phenylselenol in the solvent is 0.25-5 mol / L.

7. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The protective gas is argon or nitrogen.

8. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The reaction temperature is 5-70°C.

9. The method for anti-Markovnikov hydroselenization of arylethylene according to claim 1, characterized in that: The reaction time is 0.5-9h.

10. An anti-Markovnikov hydroselenation product prepared by the method according to any one of claims 1 to 9.

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