Method for synthesizing 1, 3-thiaselenium pentane compound

Abstract

The invention discloses a method for synthesizing a 1, 3-thiaselenium pentane compound, and belongs to the technical field of organic compound synthesis. The synthesis method comprises the following steps: adding an acyl chloride compound and potassium selenide into a solvent, generating seleno isocyanate in situ, adding 1, 4-pyrithione ylionium salt into a reaction system, and reacting under stirring and heating conditions to obtain a reaction solution; performing reduced-pressure solvent concentration on the reaction liquid to obtain a crude product; and carrying out column chromatography separation and purification on the crude product to obtain the 1, 3-thiaselenium pentane compound. According to the present invention, the 1, 3-thiaselenium pentane compound can be synthesized under the loose and mild condition so as to achieve the simple, efficient, low-cost and high-universality synthesis of the 1, 3-thiaselenium pentane compound.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic compound synthesis, and particularly relates to a method for synthesizing 1, 3-selenolane compounds. BACKGROUND

[0002] 1, 3-selenolane compounds are five-membered heterocyclic compounds containing sulfur (S) and selenium (Se), and their unique electronic structure and chemical properties make them have potential application value in many fields. The skeleton of 1, 3-selenolane is widely present in biology, medicine, pharmacy and material science. Some selenium heterocyclic compounds have the activity similar to glutathione peroxidase (GPx), and can effectively alleviate oxidative stress related diseases such as cardiovascular disease, ischemic stroke, Parkinson's disease and Alzheimer's disease. Selenium heterocyclic and functional compounds are considered as potential anticancer drugs, and show anti-depression and anti-viral activity, including anti-HIV and anti-SARS-CoV-2 activity. Ebselen is an anti-inflammatory drug with neuroprotective and glutathione peroxidase-like properties, and is undergoing clinical trials in many fields, including the treatment of COVID-19. Thin film composites containing linear and branched polymers with 1, 3-selenolane structure show photoconductive properties and can be used as effective recording media. The materials of 1, 3-diselenolane derivatives and analogs show magnetic, conductive and optical properties, and 1, 3-diselenolane derivatives and analogs have obtained a large number of technical applications.

[0003] Although the synthesis method of 1, 3-selenolane has been diversified, there are still difficulties such as region selectivity control, side reaction inhibition and structure modification. In 2008, Degl'Innocent et al. used bis(trimethylsilyl) selenide (HMDSS) and epoxide substrates to catalyze TBAF to synthesize β-functionalized diselenide with high selectivity, but it needs to rely on α-bromoalkyl ether capture to derive 1, 3-selenolane, which is complicated. In 2009-2010, Potapov and Amosova groups respectively constructed the selenolane skeleton by the reaction of selenium dihalide (SeBr2 / SeCl2) and divinyl sulfide, but faced problems such as multiple by-products (such as dehydrohalogenation products), poor diastereoselectivity (isomer ratio only 6:1 or 2:1) and low yield (such as the final product yield in the chlorination system is only 36%). In 2012, Koketsu group synthesized 2-imino derivatives by iodocyclization / acid cyclization tandem reaction of isoselenocyanate and allyl mercaptan, but it needs multi-step transformation. In 2018, Punniyamurthy developed [3+2] cycloaddition, although the condition is mild, but the substrate is limited to isothio / selenocyanate, and the universality is insufficient. In 2019, Tanini's selenyl Michael addition can construct heterocycle through intramolecular cyclization, but it needs to prepare β- functionalized selenols precursors, and the activation of olefins / alkynes relies on Al2O3 catalysis. In summary, the prior art has the following problems: (1) the use of highly active reagents (such as selenium halide) leads to side reactions; (2) the difficulty in regulating the regio- and stereo-selectivity; (3) the low efficiency of multi-step synthesis; (4) the limited scope of substrates. Therefore, it is very important to develop a one-step reaction for efficiently constructing 1, 3-thiaselenolane skeleton. SUMMARY

[0004] To solve the problem of efficiently constructing 1, 3-thiaselenolane skeleton, the present application provides a method for synthesizing 1, 3-thiaselenolane compound, which comprises the following steps: in-situ generating isoselenocyanate from acyl chloride compound and potassium selenocyanate, and then realizing the efficient construction of 1, 3-thiaselenolane compound through [3+2] cascade cycloaddition reaction of isoselenocyanate and 1, 4-pyridine sulfonium ylide under relatively mild conditions.

[0005] The method for synthesizing 1, 3-thiaselenolane compound provided by the present application comprises the following steps: (1) adding acyl chloride compound and potassium selenocyanate into a solvent to generate seleno-isocyanate in-situ, then adding 1, 4-pyridine sulfonium ylide into the reaction system, stirring and reacting under heating to obtain a reaction liquid.

[0006] (2) after the reaction is completed, the reaction liquid is concentrated under reduced pressure to obtain a crude product.

[0007] (3) the crude product is separated and purified by column chromatography to obtain 1, 3-thiaselenolane compound.

[0008] The acyl chloride compound has the following structure: wherein R 1 is phenyl or the following groups: 2-chlorophenyl, 2-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethoxyphenyl, 4-methoxyphenyl, 4-nitrophenyl, 3, 5-ditrifluoromethylphenyl, 2-furyl, 2-thienyl; The 1, 4-pyridine sulfonium ylide has the following structure: wherein R 2 is ethoxycarbonyl, methoxycarbonyl, R 3 is ethoxycarbonyl, methoxycarbonyl or 4-fluorobenzoyl.

[0009] Preferably, the solvent in step (1) is one of dichloromethane, N, N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone, 1, 2-dichloroethane and 1, 4-dioxane; more preferably, dichloromethane (DCM).

[0010] Preferably, the acyl chloride compound, potassium selenocyanate and 1, 4-pyridine sulfunium salt in step (1) of the present application are added in an amount of 0.1 mmol / mL based on the volume of the solvent.

[0011] Preferably, the base in step (1) of the present application is one of triethylamine, diisopropylethylamine, 4-dimethylaminopyridine and 1, 4-diazabicyclo[2.2.2]octane, and more preferably, it is triethylamine.

[0012] Preferably, the heating temperature in step (1) of the present application is 40℃.

[0013] Preferably, in step (1) of the present application, thin layer chromatography is used to detect the reaction, and the reaction is determined to be completed when the reaction substrate is completely consumed.

[0014] Preferably, in step (1) of the present application, in the column chromatography separation and purification, silica gel powder (200-300 mesh) is used as the stationary phase, and petroleum ether and ethyl acetate are used as the mobile phase in a volume ratio of 50:1→10:1 for gradient elution to obtain the product.

[0015] The reaction equation for synthesizing the 1, 3-thiaselepenetane compound according to the present application is as follows: .

[0016] The present application has the following beneficial effects: The method for synthesizing the 1, 3-thiaselepenetane compound according to the present application has good reaction selectivity, and the product purity can reach a high level. Meanwhile, the raw materials are cheap and easy to obtain, the utilization rate of the raw materials is high, waste can be effectively reduced, and the synthesis cost can be saved. In the synthesis reaction process of the present application, no metal catalyst is used, so the reaction will not produce wastewater or inorganic pollutants containing metal ions, effectively reducing the difficulty of environmental protection treatment of the reaction substances, and the synthesis method of the present application has environmental friendliness. The synthesis method of the present application is simple, does not require strict anhydrous and anaerobic operation, is easy to implement, has good universality, has low cost, and is suitable for industrialized popularization and application. DETAILED DESCRIPTION

[0017] The present application will be further described in detail below in combination with specific examples, but the scope of protection of the present application is not limited to the content described.

[0018] The reagents and raw materials used in the present application are commercially available.

[0019] Example 1 In this example, 1, 3-thiaselepenetane compound 2-(benzimidoyl)-1, 3-thiaselepenetane-4, 5-dicarboxylic acid diethyl ester was synthesized by the following method, and the reaction equation is as follows: .

[0020] After adding acetone (2 mL) to a reaction tube equipped with 18-crown-6 (1 mg, 2 mol%) and potassium selenocyanate (28.8 mg, 0.2 mmol, 1 equiv), the reaction tube was moved to an ice bath and benzoyl chloride (28.1 mg, 0.2 mmol, 1 equiv) was added dropwise with stirring. After the dropwise addition was completed, the reaction tube was moved to room temperature and reacted for 2 h. After the reaction was completed, the solvent acetone was removed under reduced pressure, and the reaction mixture was heated to 40 °C and refluxed for 6 h after adding the corresponding 1, 4-pyridine sulfonium salt (0.2 mmol, 1 equiv), DCM (2 mL), and triethylamine (50 mg, 0.5 equiv) to the reaction tube. After the reaction was completed (monitored by TLC), the solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (PE:EA = 50:1→10:1) to obtain the corresponding substituted 1, 3-thiaselelopentane compound in a separation yield of 65%.

[0021] The 1, 3-thiaselelopentane compound 2-(benzoylimino)-1, 3-thiaselelozole-4, 5-dicarboxylic acid diethyl ester synthesized in this example was a white solid with a m.p. of 96-100 °C and a yield of 65%, which belongs to one of the 1, 3-thiaselelopentane compounds.

[0022] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.41 - 8.35 (m, 2H), 7.64 - 7.58 (m, 1H), 7.55 - 7.49 (m, 2H), 4.40 (qd, J = 7.1, 2.0 Hz, 4H), 1.40 (td, J = 7.2, 1.2 Hz, 6H). J = 7.1, 2.0 Hz, 4H), 1.40 (td, J = 7.2, 1.2 Hz,6H).

[0023] 13 C NMR (100 MHz, CDCl3) δ 185.0, 174.5, 162.3, 160.1, 134.4, 133.7, 130.7, 130.5, 128.8, 63.4, 63.1, 14.2, 14.1.

[0024] Example 2 This example uses the same method as Example 1 to synthesize a 1, 3-thiaselelopentane compound, except that o-chlorobenzoyl chloride is used as the substrate in this example.

[0025] The 2-(2-chlorobenzimidoyl)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a light yellow solid with a yield of 31% and a m.p. of 100-103°C, and has the following structural formula: .

[0026] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 7.8, 1.8 Hz, 1H), 7.54 - 7.43 (m, 2H), 7.39 (td, J = 7.4, 1.5 Hz, 1H), 4.40 (q, J = 7.1, 4H), 1.39 (t, J = 7.2, 6H).

[0027] 13 C NMR (100 MHz, CDCl3) δ 186.0, 173.7, 162.0, 160.1, 135.0, 133.2, 133.0, 131.7, 126.8, 63.5, 63.2, 14.2, 14.1.

[0028] Example 3 This example uses the same method as Example 1 to synthesize 1,3-thiaselenolane compounds, except that in this example, o-bromobenzoyl chloride is used as the substrate.

[0029] The 2-(2-bromobenzimidoyl)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a white solid with a yield of 11% and a m.p. of 89-93°C, and has the following structural formula: .

[0030] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.25 (dd, J = 7.7, 1.9 Hz, 1H), 7.73 (dd, J =7.9, 1.3 Hz, 1H), 7.44 (td, J = 7.5, 1.3 Hz, 1H), 7.37 (td, J = 7.6, 1.9 Hz, 1H),4.40 (q, J= 7.1 Hz, 4H), 1.39 (t, J = 7.2, 6H).

[0031] 13 C NMR (100 MHz, CDC13) δ 184.2, 161.7, 136.8, 130.2, 126.1, 120.7, 120.4, 117.1, 63.5, 63.2, 14.2, 14.1.

[0032] Example 4 This example employs the same method as Example 1 to synthesize 1, 3- thiaselelopentane compound, the difference is that in this example, (3-fluorobenzoyl chloride is used as the substrate.

[0033] The 2-(3-fluorobenzoylimino)-1, 3-thiaselelopentane synthesized in this example is a white solid, the yield is 32%, m.p. 125-129°C, the structural formula is as follows: .

[0034] The data of the product synthesized in this example are: 1 H NMR (400 MHz, CDC13) δ 8.20-7.96 (m, 2H), 7.52-7.42 (m, 1H), 7.32-7.26 (m, 1H), 4.41 (q, J = 7.1 Hz, 4H), 1.39 (t, J = 7.2 Hz, 6H).

[0035] 13C NMR (100 MHz, CDC13) δ 184.2, 161.7, 136.8, 130.2, 126.1, 120.7, 120.4, 117.1, 63.5, 63.2, 14.2, 14.1.

[0036] 19 F NMR (376 MHz, CDC13) δ -112.31.

[0037] Example 5 This example employs the same method as Example 1 to synthesize 1, 3- thiaselelopentane compound, the difference is that in this example, (3-fluorobenzoyl chloride is used as the substrate.

[0038] The 2-(3-chlorobenzimidoyl)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a white solid with a yield of 52% and a m.p. of 113-117°C, and has the following structural formula: .

[0039] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDC13) δ 8.35 (t, J = 1.9 Hz, 1H), 8.24 (dt, J = 7.7, 1.4Hz, 1H), 7.56 (ddd, J = 8.0, 2.3, 1.2 Hz, 1H), 7.45 (t, J = 7.9 Hz, 1H), 4.41 (q, J = 7.1 Hz, 4H), 1.39 (t, J = 7.1 Hz, 6H).

[0040] 13 C NMR (100 MHz, CDC13) δ 186.2, 173.4, 162.1, 160.0, 136.2, 134.9, 133.5, 130.5, 130.1, 128.5, 63.5, 63.2, 14.2, 14.1.

[0041] Example 6 This example uses the same method as Example 1 to synthesize 1,3-thiaselenolane compounds, except that in this example, m-bromobenzoyl chloride is used as the substrate.

[0042] The 2-(3-bromobenzimidoyl)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a white solid with a yield of 58% and a m.p. of 110-112°C, and has the following structural formula: .

[0043] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDC13) δ 8.35 (t, J = 1.9 Hz, 1H), 8.24 (dt, J = 7.7, 1.4Hz, 1H), 7.56 (ddd, J= 7.9, 2.1, 1.1 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 4.41 (q, J = 7.2 Hz, 4H), 1.39 (t, J = 7.1 Hz, 6H).

[0044] 13 C NMR (100 MHz, CDCl3) δ 184.3, 173.0, 136.5, 136.2, 133.4, 130.2, 129.0, 122.8, 63.5, 14.1.

[0045] Example 7 This embodiment uses the same method as Example 1 to synthesize 1,3-thiaselenopentane compounds, the difference being that in this embodiment, m-methoxybenzoyl chloride is used as the substrate.

[0046] The 2-(3-methoxybenzoimino)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a pale yellow liquid with a yield of 43%, and its structural formula is as follows: .

[0047] The data for the synthesized product in this embodiment are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.99 (dt, J = 7.7, 1.3 Hz, 1H), 7.87 (dd, J =2.8, 1.5 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.17-7.12 (m, 1H), 4.40 (q, J = 7.2Hz, 4H), 3.89 (s, 3H), 1.39 (t, J = 7.1 Hz, 6H).

[0048] 13 C NMR(100 MHz, CDCl3) δ 185.1, 174.4, 162.2, 160.1, 160.0, 135.7,129.8, 123.4, 123.2, 120.6, 114.3, 63.4, 63.1, 55.6, 14.2, 14.1.

[0049] Example 8 The same method as in Example 1 was used to synthesize 1, 3-thiaselenolane compound in this example, except that p-chlorobenzoyl chloride was used as the substrate in this example.

[0050] The 2-(4-chlorobenzoylimino)-1, 3-thiaselenazole-4, 5-dicarboxylic diethyl ester synthesized in this example was a white solid with a yield of 29% and a melting point of 88-90°C, and the structural formula was as follows: .

[0051] The data of the product synthesized in this example were as follows: 1 H NMR (400 MHz, CDCl3) δ 8.33 - 8.27 (m, 2H), 7.51 - 7.44 (m, 2H), 4.40 (q, J = 7.1 Hz, 4H), 1.39 (t, J = 7.1 Hz, 6H).

[0052] 13 C NMR (100 MHz, CDCl3) δ 185.7, 173.6, 162.2, 160.0, 140.0, 132.9, 131.9, 129.1, 63.5, 63.2, 14.2, 14.1.

[0053] Example 9 The same method as in Example 1 was used to synthesize 1, 3-thiaselenolane compound in this example, except that p-chlorobenzoyl chloride was used as the substrate in this example.

[0054] The 2-(4-chlorobenzoylimino)-1, 3-thiaselenazole-4, 5-dicarboxylic diethyl ester synthesized in this example was a white solid with a yield of 29% and a melting point of 88-90°C, and the structural formula was as follows: .

[0055] The data of the product synthesized in this example were as follows: 1 H NMR (400 MHz, CDCl3) δ 8.33 - 8.27 (m, 2H), 7.51 - 7.44 (m, 2H), 4.40 (q, J = 7.1 Hz, 4H), 1.39 (t, J = 7.1 Hz, 6H). J

[0056] 13 ​C NMR (100 MHz, CDC13) δ 185.9, 173.3, 162.2, 160.0, 153.1, 132.8, 132.5, 120.5, 63.5, 63.2, 14.2, 14.1.

[0057] Example 10 This example synthesizes 1, 3-thiaselelopentane compound by using the same method as in Example 1, except that p-methoxy benzoyl chloride is used as the substrate in this example.

[0058] The 2-(4-methoxy benzoyl imino)-1, 3-thiaselelopentane synthesized in this example is a colorless oil with a yield of 38%, and its structural formula is as follows: .

[0059] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDC13) δ 8.45 - 8.41 (m, 2H), 8.18 - 8.14 (m, 2H), 4.41 (q, J = 7.2 Hz, 4H), 3.96 (s, 3H), 1.40 (t, J = 7.2 Hz, 6H).

[0060] 13 C NMR (100 MHz, CDC13) δ 186.4, 173.8, 166.6, 162.2, 162.2, 138.1, 134.3, 130.4, 129.9, 63.5, 63.2, 52.6, 14.2, 14.1.

[0061] Example 11 This example synthesizes 1, 3-thiaselelopentane compound by using the same method as in Example 1, except that p-nitro benzoyl chloride is used as the substrate in this example.

[0062] The 2-(4-nitro benzoyl imino)-1, 3-thiaselelopentane synthesized in this example is a yellow solid with a yield of 11%, m.p. 69-70°C, and its structural formula is as follows: .

[0063] The data of the product synthesized in this example are as follows: 1H NMR (400 MHz, CDC13) δ 8.56 - 8.51 (m, 2H), 8.37 - 8.32 (m, 2H), 4.42 (q, J = 7.1 Hz, 4H), 1.40 (t, J = 7.2 Hz, 6H)。

[0064] 13 C NMR (100 MHz, CDC13) δ 187.6, 172.8, 159.8, 150.6, 139.7, 131.4, 123.9, 63.6, 63.3, 14.2, 14.1.

[0065] Example 12 This example synthesizes 1, 3-selenadiazole compound using the same method as Example 1, with the difference that in this example, m-bistrifluoromethyl benzoyl chloride is used as the substrate.

[0066] This example synthesizes 2-(3, 5-bistrifluoromethyl benzoyl) imino)-1, 3-selenadiazole-4, 5-dicarboxylic acid diethyl ester as a yellow oil with a yield of 31%, and the structural formula is as follows: .

[0067] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDC13) δ 8.56 - 8.51 (m, 2H), 8.37 - 8.32 (m, 2H), 4.42 (q, J = 7.1 Hz, 4H), 1.40 (t, J = 7.2 Hz, 6H)。

[0068] 13 C NMR (100 MHz, CDC13) δ 187.6, 172.8, 159.8, 150.6, 139.7, 131.4, 123.9, 63.6, 63.3, 14.2, 14.1.

[0069] Example 13 This example synthesizes 1, 3-selenadiazole compound using the same method as Example 1, with the difference that in this example, 2-furanyl formyl chloride is used as the substrate.

[0070] The 2-(2-furanylimino)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a yellow oil with a yield of 64%, and has the following structural formula: .

[0071] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.72 - 7.68 (m, 1H), 7.49 (ddd, J = 5.8, 2.9,1.1 Hz, 1H), 6.59 (dt, J = 3.2, 1.5 Hz, 1H), 4.43 - 4.34 (m, 4H), 1.38 (t, J =7.2 Hz, 6H)。

[0072] 13 C NMR (100 MHz, CDCl3) δ 184.9, 165.3, 162.1, 160.0, 150.1, 147.9, 120.2, 112.8, 112.8, 63.4, 63.1, 14.1, 14.1.

[0073] Example 14 This example uses the same method as Example 1 to synthesize 1, 3-thiaselenolane compounds, the difference is that in this example, 2-thiophenyl formyl chloride is used as the substrate.

[0074] The 2-(2-thiophenylimino)-1,3-thiaselenazole-4,5-dicarboxylic acid diethyl ester synthesized in this example is a yellow solid with a yield of 63%, m.p. 91-92°C, and has the following structural formula: .

[0075] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.07 (dd, J = 3.8, 1.3 Hz, 1H), 7.69 (dd, J =4.9, 1.3 Hz, 1H), 7.18 (dd, J = 4.9, 3.8 Hz, 1H), 4.39 (q, J = 7.1 Hz, 4H), 1.38(t, J = 7.1 Hz, 6H).

[0076] 13 C NMR (100 MHz, CDC13) δ 184.3, 169.2, 162.1, 160.0, 140.3, 134.5, 134.5, 128.7, 63.4, 63.1, 14.2, 14.1.

[0077] Example 15 This example employs the same method as Example 1 to synthesize 1, 3- thiaphenylselenolane compound, the difference is that in this example, methoxy acyl substituted 1, 4-sulfur ylide is used as the substrate.

[0078] The 2-(benzoylimino)-1, 3-thiaphenylselenazole-4, 5-dimethyl ester synthesized in this example is white solid, the yield is 60%, m.p. 116-119°C, and the structural formula is as follows: .

[0079] The data of the product synthesized in this example are as follows: 1 H NMR (400 MHz, CDC13) δ 8.41 - 8.34 (m, 2H), 7.64 - 7.58 (m, 1H), 7.51 (dd, J = 8.3, 6.9 Hz, 2H), 3.99 - 3.91 (m, 6H).

[0080] 13 C NMR (100 MHz, CDC13) δ 184.8, 174.6, 162.8, 160.6, 134.3, 133.7, 130.7, 130.6, 128.8, 128.8, 53.9, 53.8.

[0081] Example 16 This example employs the same method as Example 1 to synthesize 1, 3- thiaphenylselenolane compound, the difference is that in this example, p-fluorobenzoyl substituted 1, 4-sulfur ylide is used as the substrate.

[0082] The 2-(benzoylimino)-5-(4-fluorobenzoyl)-1, 3-thiaphenylselenazole-4- methyl ester synthesized in this example is yellow oil, the yield is 44%, and the structural formula is as follows: .

[0083] The data of the product synthesized in this example are as follows: 1H NMR (400 MHz, CDC13) δ 8.39 (dt, J = 7.1, 1.4 Hz, 2H), 7.97 (ddt, J =6.9, 5.3, 2.7 Hz, 2H), 7.65 – 7.59 (m, 1H), 7.52 (dd, J = 8.3, 6.9 Hz, 2H),7.23 – 7.17 (m, 2H), 4.15 (q, J = 7.1 Hz, 2H), 1.13 (t, J = 7.1 Hz, 3H)。

[0084] 13 C NMR (100 MHz, CDC13) δ 187.8, 174.5, 160.8, 134.4, 133.7, 132.3, 130.8, 130.6, 128.8, 116.6, 63.0, 13.9.

[0085] The present application can realize the efficient construction of 1, 3-thiaselepenetane derivatives under the condition of dichloromethane reflux through the [3+2] cascade cycloaddition reaction of isoselenocyanate generated in situ from formyl chloride compound and potassium selenocyanate with 1, 4-pyridine sulfonium ylide under the catalysis of base. After systematic condition optimization, the reaction shows good applicability to substrates containing different substituents and heterocyclic structures, and the synthesis method is simple in operation and mild in condition, and the 1, 3-thiaselepenetane skeleton is efficiently constructed with potassium selenocyanate as raw material, thereby providing a green and efficient path for the synthesis of such compounds.

[0086] The above has described the embodiments of the present application, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and changes are obvious to those skilled in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles, practical application, or improvement of technology in the market of the embodiments, or to enable other ordinary skilled persons in the art to understand the embodiments disclosed herein.

Claims

1. A method of synthesizing a 1, 3-thiaselenolane compound, characterized by, The method comprises the following steps: (1) adding an acyl chloride compound and potassium selenocyanate into a solvent to generate seleno-isocyanate in situ, then adding 1, 4-pyridine sulfonium ylide into the reaction system, and performing reaction under the action of a base and heating; (2) after the reaction is completed, the reaction liquid is concentrated under reduced pressure to obtain a crude product; (3) the crude product is separated and purified by column chromatography to obtain a 1, 3-thiaselepenetane compound. The acyl chloride compound has the structural formula: wherein R 1 is phenyl or the following groups: 2-chlorophenyl, 2-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethoxyphenyl, 4-methoxyacetylphenyl, 4-nitrophenyl, 3,5-bistrifluoromethylphenyl, 2-furyl, or 2-thienyl; The 1, 4-pyridine sulfinium salt has the structural formula: wherein R 2 is ethoxycarbonyl, methoxycarbonyl, R 3 is ethoxycarbonyl, methoxycarbonyl, or 4-fluorobenzoyl.

2. The method of synthesizing 1, 3-thiaselenolane compounds according to claim 1, characterized by, The solvent in step (1) is one of dichloromethane, N, N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone, 1, 2-dichloroethane and 1, 4-dioxane.

3. The method of synthesizing 1, 3-thiaselenolane compound according to claim 1, wherein, The adding amount of the acyl chloride compound, potassium selenocyanate and 1, 4-pyridine sulfonium ylide in step (1) is 0.1 mmol / mL based on the volume of the solvent.

4. The method for synthesizing 1,3-thiaselenopentane compound according to claim 1, characterized in that, The base in step (1) is one of triethylamine, diisopropyl ethylamine, 4-dimethylamino pyridine and 1, 4-diazabicyclo [2.2.2] octane.

5. The method of synthesizing 1, 3-thiaselenolane compound according to claim 1, wherein, In step (1), the heating condition is 40°C.

6. The method of synthesizing 1, 3-thiaselenolane compounds according to claim 1, wherein, In step (2), the completion of the reaction is detected by using thin layer chromatography, and the reaction is determined to be completed when the reaction substrate is completely consumed.

7. The method of synthesizing 1, 3-thiaselenolane compound according to claim 1, wherein, In step (3), in the column chromatography separation and purification, silica gel powder is used as the stationary phase, petroleum ether and ethyl acetate are used as the mobile phase at a volume ratio of 50:1 to 10:1, and the product is obtained by gradient elution.

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