A new method for electrochemically promoting carbon-sulfur bond formation

Abstract

This invention presents a novel electrochemically induced method for the synthesis of carbon-sulfur bonds. Organosulfur compounds are important targets in medicine and biology, and also crucial intermediates in organic synthesis. Therefore, the synthesis of these compounds has significant theoretical and practical value. In organic reactions involving the construction of C-S bonds, the one-step synthesis of organosulfur compounds through the functionalization of alkenes has attracted considerable interest from chemists due to its simplicity and high atom economy. Currently, developing more efficient, greener, and transition metal-free olefin functionalization reactions for the construction of C-S bonds has become a goal pursued by chemists. This novel method provides a good method for constructing carbon-sulfur bonds, thereby synthesizing more desired compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, and is a new method for electrochemically induced carbon-sulfur bond synthesis. Background Technology

[0002] Sulfur-containing compounds are widely found in various drug molecules, natural products, and bioactive molecules; therefore, the construction of CS bonds has become a very important direction in the field of organic synthesis. Electrochemical synthesis is considered the next breakthrough in green chemistry. In recent years, electrochemical synthesis has demonstrated its enormous synthetic potential in reactions such as oxidative dehydrogenation, coupling, and cyclization.

[0003] Literature review and our previous research indicate that photochemically catalyzed defluorination and cross-coupling of thiol-containing gemstone difluoroolefins can construct carbon-sulfur bonds [Junlei Wang, Binbin Huang, Chao Yang and Wujiong Xia. Chem. Commun. 2019, 55, 11103.]. However, such reactions have the following disadvantages: 1) The reaction time is extremely long, exceeding 24 hours. 2) Additional catalysts and basic additives are required.

[0004] Therefore, constructing a new, efficient, and green method for synthesizing carbon-sulfur bonds has significant academic and practical implications. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0006] In view of the problems existing in the above and / or prior art, the present invention is proposed.

[0007] Therefore, the purpose of this invention is to overcome the shortcomings of the prior art and provide a new method for electrochemically induced carbon-sulfur bond synthesis.

[0008] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a novel method for electrochemically induced carbon-sulfur bond synthesis, comprising,

[0009] The synthesis of carbon-sulfur bonds is promoted through electrocatalytic coupling reactions, and the carbon-sulfur bond substrate is obtained.

[0010] As a novel method for electrochemically induced carbon-sulfur bond synthesis as described in this invention, the electrolyte used is nBu4NBr, and its amount is 100% of gem-difluoroolefin.

[0011] As a novel method for electrochemically induced carbon-sulfur bond synthesis as described in this invention, the characteristic feature is that the battery workstation used maintains a current of 6mA.

[0012] As a novel method for electrochemically induced carbon-sulfur bond synthesis as described in this invention, the product of various carbon-sulfur bond synthesis is obtained by electrochemical catalysis of various aryl sulfur compounds, alkyl sulfur compounds, and β-phenyl substituted gemini difluoro olefin compounds.

[0013] As a novel method for electrochemically induced carbon-sulfur bond synthesis according to the present invention, the novel method for electrochemically induced carbon-sulfur bond synthesis is characterized in that: the aryl sulfur compounds and alkyl sulfur compounds are all commercially available aryl sulfur compounds and alkyl sulfur compounds.

[0014] As a novel method for electrochemically induced carbon-sulfur bond synthesis according to the present invention, the β-phenyl-substituted geminitrofluoroolefin is characterized by being obtained by reacting an aldehyde, triphenylphosphine, and sodium 2-chloro-2,2-difluoroacetate.

[0015] Beneficial effects of this invention:

[0016] This invention is simple and easy to operate. The required materials are low in toxicity, safe and environmentally friendly, have a wide range of subsequent transformations, high yield, and high reaction efficiency. Furthermore, the raw materials used in this invention are commercially available. Under mild conditions, a series of reactions yields carbon-sulfur bond synthesis substrates, which can then undergo various subsequent transformations. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0018] Figure 1 The hydrogen nuclear magnetic resonance spectrum of the product prepared in Example 1 of this invention;

[0019] Figure 2 The nuclear magnetic resonance fluorine spectrum of the product prepared in Example 1 of this invention;

[0020] Figure 3 The nuclear magnetic resonance carbon spectrum of the product prepared in Example 1 of this invention; Detailed Implementation

[0021] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0022] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0023] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0024] Example 1

[0025] The synthesis of tetra-tert-butylthiophenol replacing 1-(2,2-difluorovinyl)-4-methoxybenzene is as follows:

[0026] Place a stir bar in a 10 ml reaction flask, and add 0.1 mmol of 1-(2,2-difluorovinyl)-4-methoxybenzene and 1 eq of... n Bu4NBr and 3eq tetra-tert-butylthiophenol were added to the flask. Magnesium was used as the anode and platinum as the cathode. The current was maintained at 6mA. Under nitrogen protection, 5 mL of MeCN was added to the reaction flask and stirred for 3 h.

[0027] The product was characterized as follows: Z-isomer: ¹H NMR (600 MHz, CDCl₃): δ 7.53 (d, J = 8.6 Hz, 2H), 7.33–7.37 (m, 4H), 6.88 (d, J = 8.6 Hz, 2H), 6.71 (d, J = 16.3 Hz, 1H), 3.81 (s, 3H), 1.30 (s, 9H). isomer: 13C{1H}NMR (151MHz, CDCl3): δ159.3, 151.3 (d, J=293.7Hz), 150.9, 130.1 (d, J=3.1Hz), 129.6, 127.9, 1 26.4, 124.8, 118.2 (d, J = 32.2Hz), 113.9, 55.3, 34.6, 31.2.E-isomer: 6.24 (d, J = 32.6Hz, 1H). Both-isomers: 19F NMR (565MHz, CDCl3): δ-82.1 (d, J=16.3Hz), -88.1 (d, J=32.6Hz).

[0028] The product structural formula is:

[0029]

[0030] Example 2

[0031] The synthesis of tetra-tert-butylthiophenol substituted for 2-(2,2-difluorovinyl)naphthalene is as follows:

[0032] Place a stir bar in a 10 ml reaction flask, add 0.1 mmol of 2-(2,2-difluorovinyl)naphthalene, 1 eq of nBu4NBr and 3 eq of tetra-tert-butylthiophenol to the flask, use magnesium as the anode and platinum as the cathode, maintain the current at 6 mA, add 5 ml of MeCN to the reaction flask under nitrogen protection, and stir for 3 h.

[0033] The product was characterized as follows: Z isomer: 1H NMR (600 MHz, CDCl3): δ 7.96 (s, 1H), 7.80–7.83 (m, 4H), 7.48 (t, J = 3.9, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.37 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 16.4 Hz, 1H), 1.31 (s, 9H). isomer: 13C{1H}NMR (151MHz, CDCl3): δ153.2 (d, J=296.8Hz), 151.2, 133.3, 132.8, 130.2, 130.0 (d, J=8.8Hz), 128.4 (d, J=3.9Hz), 1 28.1, 127.9, 127.6, 127.4, 126.5, 126.3 (d, J=2.3Hz), 126.3, 118.0 (d, J=32.0Hz), 34.6, 31.2.Eisomer: 6.43 (d, J=32.6Hz, 1H).Both isomers: 19F NMR (565MHz, CDCl3): δ-79.5 (d, J=16.3Hz), -85.1 (d, J=32.4Hz).

[0034] The product structural formula is:

[0035]

[0036] Example 3

[0037] The synthesis of 1-(2,2-difluorovinyl)-4-methoxybenzene substituted with p-methylthiophenol is as follows:

[0038] Place a stir bar in a 10 ml reaction flask, and add 0.1 mmol of 1-(2,2-difluorovinyl)-4-methoxybenzene and 1 eq of... n Bu4NBr and 3 eq of p-methylthiophenol were added to the flask. Magnesium was used as the anode and platinum as the cathode. The current was maintained at 6 mA. Under nitrogen protection, 5 mL of MeCN was added to the reaction flask and stirred for 3 h.

[0039] The product was characterized as follows: Z isomer: 1H NMR (600 MHz, CDCl3): δ 7.55 (d, J = 8.7 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 7.9 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 16.4 Hz, 1H), 3.84 (s, 3H), 2.36 (s, 3H). isomer: 13C{1H}NMR (151MHz, CDCl3): δ159.3, 151.4 (d, J=293.2Hz), 137.8, 130.3, 13 0.1 (d, J=3.5Hz), 127.7, 124.8 (d, J=8.7Hz), 117.9 (d, J=32.4Hz), 113.9, 55.3, 21.1.E isomer: 6.25 (d, J=32.7Hz, 1H). Both isomers: 19F NMR (565MHz, CDCl3): δ-82.5 (d, J=16.3Hz), -88.5 (d, J=32.7Hz).

[0040] The product structural formula is:

[0041]

[0042] Example 4

[0043] The synthesis of 1-(2,2-difluorovinyl)-4-methoxybenzene substituted with p-fluorothiophenol is as follows:

[0044] Place a stir bar in a 10 ml reaction flask, and add 0.1 mmol of 1-(2,2-difluorovinyl)-4-methoxybenzene and 1 eq of... n Bu4NBr and 3 eq of p-methylthiophenol were added to the flask. Magnesium was used as the anode and platinum as the cathode. The current was maintained at 6 mA. Under nitrogen protection, 5 mL of MeCN was added to the reaction flask and stirred for 3 h.

[0045] The product was characterized as follows: Z isomer: 1H NMR (600MHz, CDCl3): δ 7.50 (d, J = 8.6Hz, 2H), 7.41–7.43 (m, 2H), 7.03 (t, J = 8.7Hz, 2H), 6.89 (d, J = 8.6Hz, 2H), 6.69 (d, J = 16.4Hz, 1H), 3.82 (s, 3H). isomer: 13C{1H}NMR (151MHz, CDCl3): δ162.6 (d, J=247.8Hz), 159.4, 132.4 (d, J=8.3Hz), 131.3 (d, J=8.6Hz), 130.1 (d, J=3.2Hz), 125.4 (d, J=266.3Hz), 118.0 (d, J=32.0Hz), 116.5 (d, J=22.3Hz), 116.3 (d, J=21.9Hz), 113.9, 55.3.E isomer: 1H NMR (600MHz, CDCl3): δ6.23 (d, J=32.6Hz, 1H). Both isomers: 19F NMR (565MHz, CDCl3): δ-83.2 (d, J=16.4Hz), -89.0 (d, J=32.5Hz), -113.5-113.9 (m).

[0046] The product structural formula is:

[0047]

Claims

1. A novel method for electrochemically promoting the synthesis of carbon-sulfur bonds, characterized by: Comprising, with β-phenyl-substituted gem-difluoro olefins and aryl sulfides as reaction substrates, to obtain carbon-sulfur bond products n Bu4NBr as electrolyte, magnesium as anode, platinum as cathode, current maintained at 6mA, carbon-sulfur bond was synthesized by coupling reaction, and carbon-sulfur bond product was obtained; The aryl-based sulfur compound includes one of tetra-tert-butyl phenylthiol, p-methyl phenylthiol, and p-fluorophenylthiol.

2. The novel method of electrochemically facilitating the carbon-sulfur bond synthesis as claimed in claim 1, wherein: The n The molar ratio of Bu4NBr to the β-phenyl substituted gem-difluoro olefin is 1:

1.

3. The novel method for electrochemically induced carbon-sulfur bond synthesis as described in claim 1, characterized in that: The beta-phenyl-substituted gem-difluoro olefin can be obtained by reacting an aldehyde, triphenylphosphine, and sodium 2-chloro-2,2-difluoroacetate.

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