Synthesis method of alpha-carbonylated selenium

Abstract

The invention belongs to the field of chemical synthesis, and particularly relates to a synthesis method of alpha-carbonylated selenium, which comprises the following steps: S1, adding phenyl selenium chloride and 5-bromoindole potassium xanthate into a reaction container, and then sequentially adding p-R-styrene, phenylsilane and acetonitrile to obtain a reaction mixture; s2, placing the mixture obtained in the step S1 on a magnetic stirrer, and performing photocatalytic reaction under blue light irradiation to obtain a photocatalytic product after the reaction is completed; and S3, extracting the photocatalytic product obtained in the step S2 with ethyl acetate, and carrying out drying, concentration and column chromatography on an organic phase to obtain the high-purity alpha-selenium carbonyl compound. According to the preparation method, 5-bromoindole potassium xanthate is taken as a catalyst, phenyl selenium chloride is taken as a selenium source, the generated intermediate realizes homocracking of S-Se bonds under the action of photocatalysis, so that the corresponding phenyl selenyl free radicals are generated, the preparation process is simple, a noble metal catalyst is not needed, the production efficiency is improved, and the production cost is reduced.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical synthesis, and particularly relates to a synthesis method of alpha-carbonyl selenium. BACKGROUND

[0002] As a member of chalcogen elements and a special heteroatom indispensable to human body, the introduction of selenium can greatly change the physical and chemical properties, medicinal properties and biological activity of a substance. Among numerous selenium-containing compounds, the synthesis of alpha-selenocarbonyl compounds has attracted extensive attention. For example, alpha, beta-unsaturated carbonyl compounds can be obtained by the oxidative deselenization of alpha-selenocarbonyl compounds through peroxide; and cyclic or ketone alpha-aryl products can be synthesized by the deselenization of alpha-selenocarbonyl compounds through a free radical pathway. Meanwhile, alpha-selenocarbonyl compounds also provide an important role for the research and development of antidepressants, antioxidants, anticancer agents and anti-inflammatory agents.

[0003] Currently, there are mainly two methods for synthesizing alpha-selenocarbonyl compounds by using phenyl selenyl chloride as a selenium source: one is the synthesis method of aldehyde or ketone enolate and phenyl selenyl chloride under the catalysis of acid or base; and the other is the synthesis method of alpha-haloketone and phenyl selenyl chloride under the catalysis of transition metal palladium (Pd) or samarium (Sm). Both of the two methods have problems of requiring specific substrates, high cost, complex reaction steps, and the like, which are not conducive to organic synthesis and pharmacological research. SUMMARY

[0004] In order to solve the problems existing in the prior art, the present application provides a synthesis method of alpha-carbonyl selenium, which uses 5-bromoindole potassium xanthate as a catalyst and phenyl selenyl chloride as a selenium source. The generated intermediate realizes homolysis of S-Se bond under the action of photocatalysis, so as to generate the corresponding phenyl selenyl radical. The preparation process is simple and does not require a noble metal catalyst, thereby improving production efficiency and reducing production cost.

[0005] The specific technical scheme adopted by the present application is as follows:

[0006] A synthesis method of alpha-carbonyl selenium, comprising the following steps:

[0007] S1, phenyl selenyl chloride and 5-bromoindole potassium xanthate are added into a reaction container, and then p-R-styrene, phenylsilane and acetonitrile are sequentially added to obtain a reaction mixture;

[0008] S2, the reaction mixture in step S1 is subjected to a photocatalytic reaction under blue light irradiation, and a photocatalytic product is obtained after the reaction is completed;

[0009] S3, the photocatalytic product obtained in step S2 is extracted with ethyl acetate, and the organic phase is dried, concentrated and subjected to column chromatography to obtain a high-purity alpha-selenocarbonyl compound.

[0010] Further, the chemical structural formula of the p-R-styrene is

[0011] Further, the para-R-styrene includes any one of styrene, p-methylstyrene, p-fluorostyrene, p-hydroxystyrene, p-tert-butylstyrene and 2-vinylnaphthalene.

[0012] Further, the amount of the catalyst 5-bromoindole potassium xanthate is 10-12 mol% of the moles of phenyl selenyl chloride.

[0013] Further, the molar ratio of the para-R-styrene, phenylsilane and phenyl selenyl chloride is 1.1-1.3:1.

[0014] Further, 4.0-6.0 mL of acetonitrile is added per mmol of the phenyl selenyl chloride.

[0015] Further, the specific step of the photocatalysis in the step S2 is that the reaction tube containing the reaction mixture is placed on a magnetic stirrer at room temperature, the reaction tube is open, a 36W blue light LED is arranged beside the reaction tube, the distance between the reaction tube and the light source is 0.5-1.5 cm, and the stirring reaction is carried out for 6-8 h to obtain the photocatalysis product.

[0016] Further, the eluent for the column chromatography includes ethyl acetate and petroleum ether in a volume ratio of 1:10-20.

[0017] The beneficial effects of the present application are:

[0018] The present application uses 5-bromoindole potassium xanthate (DTCA) as a catalyst, and phenyl selenyl chloride as a selenium source to generate a light-absorbing intermediate through S N 2 path, which realizes homolysis of S-Se bond under irradiation of 36W blue light to generate corresponding phenyl selenyl radical, and then synthesizes selenium-containing organic matter through addition with styrene compounds and capture of oxygen in the air, and high-purity alpha-selenocarbonyl compounds are obtained through extraction, concentration and column chromatography.

[0019] This xanthate effectively activates the photocatalytic method of inert substrates in the classical radical generation strategy based on different physical properties of substrates, creates a new idea for the introduction of heteroatoms, provides a mild, efficient and inexpensive method for the design and discovery of new functional molecules, and also provides a practical new means for drug research and development. The preparation process of the present application is simple and does not need noble metal catalysts, improves production efficiency and reduces production cost. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The reaction equation of the present application is as follows:

[0021] Figure 2The structural formulas and yields of the α-selenyl carbonyl compounds prepared in Examples 1-6 are shown below;

[0022] Figure 3 The 1H NMR spectrum of product 3a from Example 1;

[0023] Figure 4 The carbon spectrum of product 3a from Example 1;

[0024] Figure 5 The 3b proton NMR spectrum of the product from Example 2;

[0025] Figure 6 The 3b carbon spectrum of the product from Example 2;

[0026] Figure 7 The 3c proton spectrum of the product in Example 3;

[0027] Figure 8 The 3C carbon spectrum of the product in Example 3;

[0028] Figure 9 The 3d proton NMR spectrum of the product from Example 4;

[0029] Figure 10 The 3D carbon spectrum of the product in Example 4;

[0030] Figure 11 The 3e proton spectrum of the product from Example 5;

[0031] Figure 12 The 3e carbon spectrum of the product from Example 5;

[0032] Figure 13 The 3f proton NMR spectrum of the product from Example 6;

[0033] Figure 14 The 3f carbon spectrum of the product from Example 6;

[0034] Figure 15 The product of Example 6 is a 3f high-resolution mass spectrometer (HRMS). Detailed Implementation

[0035] The present invention will be further described below with reference to the accompanying drawings and specific embodiments:

[0037] The silica gel (200-300 mesh) and thin-layer chromatography silica gel plates (TLC) used in this invention are both domestically produced. The high-resolution mass spectrometer (HRMS) is equipped with an ESI ionization source and a Q-TOF detector. The nuclear magnetic resonance spectrometer (NMR) is a Varian Mercury plus-400 and an Agilent 600MHz DD2.

[0038] Example 1

[0039] S1, in an oven-dried 25 mL reaction tube, first add 0.3 mmol of phenyl selenyl chloride and 0.03 mmol of 5-bromoindole potassium xanthate, then quickly add 0.36 mmol of styrene, 0.36 mmol of phenylsilane, and 3.0 mL of acetonitrile in sequence, and stir to obtain a reaction mixture;

[0040] S2, at room temperature, place the reaction tube containing the mixture in an open state beside a 36W LED lamp emitting blue light, with the reaction tube being 1 cm away from the lamp, and stir to react for 6 h to obtain a photocatalytic product;

[0041] S3, extract the photocatalytic product with ethyl acetate, dry with anhydrous Na2SO4, concentrate under reduced pressure, and purify by column chromatography (ethyl acetate / petroleum ether = 1:20) to obtain 1-phenyl-2-(phenylselenyl)ethanone.

[0042] Example 2

[0043] S1, in an oven-dried 25 mL reaction tube, first add 0.3 mmol of phenyl selenyl chloride and 0.03 mmol of 5-bromoindole potassium xanthate, then quickly add 0.36 mmol of styrene, 0.36 mmol of phenylsilane, and 3.0 mL of acetonitrile in sequence, and stir to obtain a reaction mixture;

[0044] S2, at room temperature, place the reaction tube containing the mixture in an open state beside a 36W LED lamp emitting blue light, with the reaction tube being 1 cm away from the lamp, and stir to react for 6 h to obtain a photocatalytic product;

[0045] S3, extract the photocatalytic product with ethyl acetate, dry with anhydrous Na2SO4, concentrate under reduced pressure, and purify by column chromatography (ethyl acetate / petroleum ether = 1:20) to obtain 2-(phenylselenyl)-1-(p-tolyl)ethanone.

[0046] Example 3

[0047] S1, in an oven-dried 25 mL reaction tube, first add 0.3 mmol of phenyl selenyl chloride and 0.03 mmol of 5-bromoindole potassium xanthate, then quickly add 0.36 mmol of p-fluorostyrene, 0.36 mmol of phenylsilane, and 3.0 mL of acetonitrile in sequence, and stir to obtain a reaction mixture;

[0048] S2, at room temperature, place the reaction tube containing the mixture in an open state beside a 36W LED lamp emitting blue light, with the reaction tube being 1 cm away from the lamp, and stir to react for 6 h to obtain a photocatalytic product;

[0049] S3, extract the photocatalytic product with ethyl acetate, dry with anhydrous Na2SO4, concentrate under reduced pressure, and purify by column chromatography (ethyl acetate / petroleum ether = 1:20) to obtain 1-(4-fluorophenyl)-2-(phenylselenyl)ethanone.

[0050] Example 4

[0051] S1, in a 25 mL dried reaction tube, first add 0.3 mmol phenyl selenyl chloride and 0.03 mmol 5-bromoindole potassium xanthate, then quickly add 0.36 mmol p-acetoxystyrene, 0.36 mmol phenylsilane, and 3.0 mL acetonitrile in sequence, stir to get a reaction mixture;

[0052] S2, at room temperature, place the reaction tube containing the mixture in front of a 36 W LED lamp emitting blue light, the reaction tube is 1 cm away from the lamp, stir for 6 h to get a photocatalytic product;

[0053] S3, extract the photocatalytic product with ethyl acetate, dry with anhydrous Na2SO4, concentrate under reduced pressure, then purify by column chromatography (ethyl acetate / petroleum ether = 1:20) to get 4-(2-(phenylselenyl)acetyl)phenyl acetate.

[0054] Example 5

[0055] S1, in a 25 mL dried reaction tube, first add 0.3 mmol phenyl selenyl chloride and 0.03 mmol 5-bromoindole potassium xanthate, then quickly add 0.36 mmol p-tert-butylstyrene, 0.36 mmol phenylsilane, and 3.0 mL acetonitrile in sequence, stir to get a reaction mixture;

[0056] S2, at room temperature, place the reaction tube containing the mixture in front of a 36 W LED lamp emitting blue light, the reaction tube is 1 cm away from the lamp, stir for 6 h to get a photocatalytic product;

[0057] S3, extract the photocatalytic product with ethyl acetate, dry with anhydrous Na2SO4, concentrate under reduced pressure, then purify by column chromatography (ethyl acetate / petroleum ether = 1:20) to get 1-(4-tert-butylphenyl)-2-(phenylselenyl)ethanone.

[0058] Example 6

[0059] S1, in a 25 mL dried reaction tube, first add 0.3 mmol phenyl selenyl chloride and 0.03 mmol 5-bromoindole potassium xanthate, then quickly add 0.36 mmol 2-vinylnaphthalene, 0.36 mmol phenylsilane, and 3.0 mL acetonitrile in sequence, stir to get a reaction mixture;

[0060] S2, at room temperature, place the reaction tube containing the mixture in front of a 36 W LED lamp emitting blue light, the reaction tube is 1 cm away from the lamp, stir for 6 h to get a photocatalytic product;

[0061] S3, the photocatalytic product was extracted with ethyl acetate, dried with anhydrous Na2SO4, concentrated under reduced pressure, and purified by column chromatography (ethyl acetate / petroleum ether = 1:20) to obtain 1-(naphthyl)-2-(phenylselenyl)ethan-1-one.

[0062] II. Component detection

[0063] The reaction equation of the synthesis method of α-selenocarbonyl compounds in Examples 1-6 is shown in Figure 1 , the structural formula and yield of α-selenocarbonyl compounds are shown in Figure 2 , the nuclear magnetic resonance (NMR) spectrum 1 H NMR and 13 C NMR are shown in Figures 3-14 , the high resolution mass spectrum (HRMS) (ESI) m / z of product 3f of Example 6: [M+Na]+Calcd for C 18 H 14 NaOSe 349.01021; Found 349.01009, see Figure 15 .

[0064] The characterization data of the compound prepared in Example 1 are as follows:

[0065] 1-Phenyl-2-(phenylselanyl)ethan-1-one (3a) Yellow Oil.

[0066] 1 H NMR (400 MHz, CDCl3) δ / ppm = 7.88 (d, J = 7.1 Hz, 2H), 7.58-7.53 (m, 3H), 7.44 (t, J = 7.7 Hz, 2H), 7.30-7.26 (m, 3H), 4.18 (s, 2H). 13 C NMR (150 MHz, CDCl3) δ / ppm = 194.9, 135.4, 134.0, 133.2, 129.2, 129.0, 128.7, 128.6, 128.1, 32.7.

[0067] The characterization data of the compound prepared in Example 2 are as follows:

[0068] 2-(phenylselanyl)-1-(p-tolyl)ethan-1-one (3b) Yellow Oil.

[0069] 1H NMR (400 MHz, CDCI3) δ / ppm = 7.79 (d, J = 7.8 Hz, 2H), 7.55 - 7.53 (m, 2H), 7.28 - 7.22 (m, 5H), 4.16 (s, 2H), 2.41 (s, 3H). 13 C NMR (150 MHz, CDCI3) δ / ppm = 194.7, 144.2, 133.8, 132.9, 129.3, 129.2, 128.8, 128.0, 32.7, 21.7.

[0070] The compound prepared in Example 3 was characterized by the following data:

[0071] 1 -(4-fluorophenyl)-2-(phenylselanyl)ethan-1 -one (3c) Colorless Oil.

[0072] 1 H NMR (400 MHz, CDCI3) δ / ppm = 7.90 - 7.87 (m, 2H), 7.53 - 7.51 (m, 2H), 7.33 - 7.25 (m, 3H), 7.11 - 7.07 (m, 2H), 4.13 (s, 2H). 13 C NMR (150 MHz, CDCI3) δ / ppm = 193.4, 165.8 (d, J = 254.0 Hz), 164.9, 134.1, 131.8 (d, J = 2.9 Hz), 131.3 (d, J = 9.2 Hz), 129.3, 128.8, 128.2, 115.7 (d, J = 21.6 Hz), 32.5.

[0073] The compound prepared in Example 4 was characterized by the following data:

[0074] 4-(2-(phenylselanyl)acetyl)phenyl acetate (3d) Colorless Oil.

[0075] 1 H NMR (400 MHz, CDCI3) δ / ppm = 7.90 (d, J = 8.64 Hz, 2H), 7.54 - 7.51 (m, 2H), 7.30 - 7.25 (m, 3H), 7.16 (d, J = 8.6 Hz, 2H), 4.14 (s, 2H), 2.32 (s, 3H). 13C NMR (150 MHz, CDC13) δ / ppm = 193.7, 168.7, 154.4, 134.1, 132.9, 130.3, 129.3, 128.9, 128.2, 121.8, 32.6, 21.2.

[0076] The compound prepared in Example 5 was characterized by the following data:

[0077] 1-(4-(tert-butyl)phenyl)-2-(phenylselanyl)ethan-1-one (3e) Yellow Oil.

[0078] 1 H NMR (400 MHz, CDC13) δ / ppm = 7.85 - 7.81 (m, 2H), 7.57 - 7.53 (m, 2H), 7.46 - 7.44 (m, 2H), 7.30 - 7.24 (m, 3H), 4.17 (d, J = 2.76 Hz, 2H), 1.35 (d, J = 2.76 Hz, 9H). 13 C NMR (150 MHz, CDC13) δ / ppm = 194.6, 157.0, 133.9, 132.8, 129.2, 129.2, 128.6, 127.9, 125.6, 35.1, 32.7, 31.1.

[0079] The compound prepared in Example 6 was characterized by the following data:

[0080] 1-(naphthalen-2-yl)-2-(phenylselanyl)ethan-1-one (3f) Yellow Solid, m.p. = 65-67 °C.

[0081] 1 H NMR (400 MHz, CDC13) δ / ppm = 8.29 (s, 1H), 7.99 - 7.96 (m, 1H), 7.89-7.84 (m, 3H), 7.62 - 7.52 (m, 4H), 7.31 - 7.25 (m, 3H), 4.29 (s, 2H). 13 C NMR (150 MHz, CDC13) δ / ppm = 195.0, 135.6, 134.2, 132.8, 132.4, 130.5, 129.6, 129.3, 129.2, 128.6, 128.5, 128.1, 127.7, 126.7, 124.3, 32.9.

[0082] As can be seen from the yield of the α-selenocarbonyl compounds of each embodiment, the chemical synthesis method in the present application has high yield, which effectively reduces the production cost of the α-selenocarbonyl compounds.

Claims

1. A method of synthesis of an α-carbonylated selenium characterized in that, The method comprises the following steps: S1, adding phenyl selenyl chloride and 5-bromoindole potassium xanthate into a reaction container, and then adding p-R-styrene, phenylsilane and acetonitrile into the reaction container in sequence to obtain a reaction mixture; S2, performing a photocatalytic reaction on the reaction mixture in step S1 under blue light irradiation, and obtaining a photocatalytic product after the reaction is completed; S3, extracting the photocatalytic product obtained in step S2 with ethyl acetate, drying the organic phase, concentrating, and performing column chromatography to obtain a high-purity α-selenocarbonyl compound.

2. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The chemical structure of the p-R-styrene is 3. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The p-R-styrene includes any one of styrene, p-methylstyrene, p-fluorostyrene, p-hydroxystyrene, p-tert-butylstyrene and 2-vinyl naphthalene.

4. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The amount of the catalyst 5-bromoindole potassium xanthate is 10-12 mol% of the moles of phenyl selenyl chloride.

5. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The molar ratio of the p-R-styrene, phenylsilane and phenyl selenyl chloride is 1.1-1.3:

1.

6. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, 4.0-6.0 mL of acetonitrile is added per mmol of the phenyl selenyl chloride.

7. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The specific steps of the photocatalysis in step S2 are as follows: placing a reaction tube containing the reaction mixture on a magnetic stirrer at room temperature, leaving the reaction tube open, arranging a 36W blue light LED beside the reaction tube, setting the distance between the reaction tube and the light source to be 0.5-1.5 cm, and stirring and reacting for 6-8 h to obtain the photocatalytic product.

8. The method for synthesizing α-carbonyl selenide according to claim 1, characterized in that, The eluent for the column chromatography includes ethyl acetate and petroleum ether in a volume ratio of 1:10-20.

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