A method for electrochemical synthesis of sulfoxide or sulfone compounds

Abstract

The present invention belongs to the field of organic synthesis technology, and in particular to a method for electrochemical synthesis of sulfoxide or sulfone compounds. It includes at least one of the following reaction routes: Reaction route 1: dissolving sulfide in an aqueous electrolyte solution, and electrolyzing under the condition of a cell voltage of 2.8-3.2V to obtain a sulfoxide compound; Reaction route 2: dissolving sulfide in an aqueous electrolyte solution, and electrolyzing under the condition of a voltage of 5.0-10.0V to obtain a sulfone compound. The present invention provides a method for electrochemical synthesis of sulfoxide and sulfone compounds using water as an oxygen source, mild conditions, and pollution-free. The synthesis method has good selectivity, high yield, and good application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to an electrochemical synthesis method for sulfoxide or sulfone compounds. Background Art

[0002] Sulfoxides and sulfone compounds are components of many drug backbones, natural products, and important ligands. Many widely used clinical drugs, such as anti-ulcer drugs, cardiotonic drugs, anti-vasodilators, and antibacterial and insecticides, contain sulfoxide or sulfone structures. Traditional synthesis methods for sulfoxide and sulfone compounds fall into two main categories: 1. cross-coupling reactions; 2. sulfide oxidation. Compared to cross-coupling, oxidation is a more direct, simpler, and more atom-economical method, making it more widely used in industrial production. However, current sulfide oxidation methods often require toxic and hazardous oxidants such as peracids and high-valent iodine salts, which are environmentally unfriendly, require complex post-processing steps, generate waste, and generally suffer from poor selectivity (sulfone byproducts are easily generated when oxidizing to sulfoxides, and incomplete conversion of sulfoxide products occurs when oxidizing to sulfones). Developing a mild, clean, efficient, and highly selective sulfide oxidation method is of great significance.

[0003] Electrochemical anodic oxidation has many advantages over traditional oxidation in the synthesis of organic compounds: Compared with traditional oxidation reactions, electrochemical oxidation reactions have the potential to achieve direct electron transfer between substrates, thus providing a new approach for oxidation reactions without waste emissions and achieving ideal atomic utilization. In addition to the potential to achieve oxidation reactions without the addition of chemical oxidants or other additives, electrochemical anodic oxidation can also precisely regulate the current / voltage to achieve the oxidation voltage required for the electrolytic system reaction, thereby accurately oxidizing the corresponding compounds and hopefully achieving highly selective organic reactions. At the same time, by precisely controlling the reaction current / voltage, uncontrollable situations such as violent heat release or sudden acceleration during the reaction can be avoided, thereby ensuring the safe and stable progress of the corresponding chemical reaction, which is particularly important in large-scale industrial production.

[0004] There have been some attempts at electrochemical synthesis of sulfoxides and sulfone compounds. The Chinese invention patent "CN108103522B A method for electrocatalytic oxidation of sulfide molecular oxygen to produce sulfoxides and sulfone compounds" provides a method for preparing sulfones and sulfoxides by electrochemical oxidation of sulfide. However, the ionic liquid and titanium-based nano-membrane electrode materials used in this method are complex to prepare and have high costs; and it uses oxygen as an oxidant, and the pressure needs to be maintained at 0.1-1.0Mpa during the reaction. Oxygen as an oxidant has certain limitations and dangers in industrial production, and pressure maintenance equipment will increase equipment costs. Therefore, the development of a safer and lower-cost electrochemical synthesis process for sulfoxides and sulfone compounds remains an urgent problem to be solved in this field. Summary of the Invention

[0005] In view of the problems of the prior art, the present invention provides an electrochemical synthesis method for sulfoxide or sulfone compounds, aiming to provide a safer and more economical electrochemical synthesis process for sulfoxide and sulfone compounds.

[0006] A method for electrochemically synthesizing sulfoxide or sulfone compounds, comprising at least one of the following reaction routes:

[0007] Reaction route 1: dissolving the sulfide in an aqueous electrolyte solution and electrolyzing it at a cell voltage of 2.8V-3.2V to obtain a sulfoxide compound;

[0008] Reaction route 2: dissolving the sulfide in an aqueous electrolyte solution and performing electrolysis at a cell voltage of 5.0-10.0 V to obtain a sulfone compound.

[0009] Preferably, the thioether structural formula is The structural formula of the sulfoxide compound is The sulfone compound is

[0010] Wherein, R1 and R2 are independently selected to be substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C6-C 10 Aryl, wherein the substituent is selected from halogen, C6-C 10 Aryl or C1-C 10 Alkoxy.

[0011] Preferably, in reaction route 1, the solvent of the electrolyte solution is a mixture of water and acetonitrile in a volume ratio of 5:1-1:2.

[0012] Preferably, in reaction route 1, the electrolyte solution contains 0.1M-0.15M electrolyte, and the electrolyte is selected from at least one of tetrabutylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate or tetrabutylammonium periodate.

[0013] Preferably, in reaction route 1, the ratio of the sulfide to the electrolyte solution is 0.4 mol:3 L.

[0014] Preferably, in reaction route 1, the electrolysis adopts constant voltage electrolysis.

[0015] Preferably, in reaction route 2, the solvent of the electrolyte solution is a mixture of water and acetonitrile in a volume ratio of 1:5-1:2.

[0016] Preferably, in reaction route 2, the electrolyte solution contains 0.02-0.05M electrolyte, and the electrolyte is selected from at least one of tetrabutylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate, and tetrabutylammonium periodate.

[0017] Preferably, in reaction route 2, the ratio of the sulfide to the electrolyte solution is 0.4 mol:3 L.

[0018] Preferably, in the second reaction route, the electrolysis is performed by constant current electrolysis, and the electrolytic cell is a U-shaped tube with a diameter of 29mm-32mm and a length of 10cm-15cm as an undivided electrolytic cell, and the electrode sheet size is 1.5cm 2 The anode is made of carbon cloth, the cathode is a platinum sheet, the electrode spacing is 7-10mm, and the current is constant at 5-8mA.

[0019] The present invention provides a new, scientific and rational method for the selective oxidation of sulfides, which can selectively produce sulfoxide or sulfone products with various substituents. The beneficial effects of the present invention include:

[0020] 1. Using water as the oxygen source, the oxidation of sulfides is achieved through electrochemistry, avoiding the use of oxidants or large amounts of oxygen, making it cleaner, safer, and more environmentally friendly;

[0021] 2. The reaction is regulated by controlling the voltage / current, so that the oxidation proceeds with high selectivity and a single target product is obtained with good selectivity;

[0022] 3. The reaction does not produce waste. The solvent and tetrabutylammonium tetrafluoroborate electrolyte used in the reaction can be recycled and reused. Hydrogen, which has economic value, is the only by-product.

[0023] 4. By optimizing and screening the reaction conditions such as reaction current, voltage, electrolyte solution system, and water ratio, the target compound is obtained with a high yield. The product prepared by the method of the present invention is easy to purify.

[0024] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0025] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. DETAILED DESCRIPTION

[0026] The reagents and materials used in the following examples, unless otherwise specified, are commercially available.

[0027] It should be noted that, in the following examples, the expression of yield is expressed in two ways: GC yield and isolation yield. The definition of GC yield is the percentage value calculated after the chromatographic peak of a certain component is analyzed by a chromatographic instrument, and the definition of isolation yield is the actual yield of the product obtained after separation of the reaction mixture. The reason for using two yield expression methods in the examples is that the isolation yield is data that can better reflect the true yield of the product. It is calculated after the compound is completely separated and purified. However, some experimental groups may suffer losses during the separation and purification process, resulting in low yields. Therefore, the yields of these experimental groups are expressed using GC yield.

[0028] Example 1

[0029] This embodiment provides an electrochemical synthesis method for sulfone and sulfoxide compounds, and the reaction is as follows:

[0030]

[0031] In this embodiment, R1 and R2 are both phenyl groups.

[0032] Reaction conditions:

[0033] Reaction route 1: Dissolve diphenyl sulfide 1 (0.4 mmol) and tetrabutylammonium tetrafluoroborate (0.1 M) in a mixture of water and acetonitrile at a ratio of 5:1 (3 mL in total), place in a non-diaphragm electrolytic cell, and place a carbon cloth (1.5 cm 2 ) anode and platinum sheet (1.5cm 2 ) cathode, and electrolysis was carried out at room temperature at a constant cell voltage of 3.0 V for 6-11 hours. The sulfoxide (labeled as 2a) was obtained as a single product with a GC yield of 89% and an isolated yield of 77%.

[0034] Reaction route 2:

[0035] Diphenyl sulfide 1 (0.4 mmol) and tetrabutylammonium tetrafluoroborate (0.02 M) were dissolved in a mixture of water and acetonitrile at a ratio of 1:5 (3 mL in total), and the mixture was placed in a non-diaphragm electrolytic cell. A carbon cloth (0.2 cm × 1.5 cm) was placed. 2 ) anode and platinum sheet (0.2cm×1.5cm2 ) cathode, and electrolysis was conducted at room temperature at a current of 5 mA (under the conditions of this example, the cell voltage range was 5.0-10.0 V) for 6-12 hours. The sulfone (labeled as 3a) was obtained as a single product in an isolated yield of 72%.

[0036] Example 2

[0037] The reaction conditions of this example are the same as those of Example 1, except that the substituent of the thioether is replaced. The reaction products and yields are as follows:

[0038] Table 1 Reaction products and yields

[0039]

[0040]

[0041] a: GC yield; b: isolation yield.

[0042] The characterization experimental data for the products of Example 1 and Example 2 are as follows:

[0043]

[0044] Sulfinyldibenzene(2a)

[0045] 1 H NMR (400MHz, CDCl3, TMS) δppm 7.65-7.63(m,4H),7.47-7.42(m,6H)

[0046] 13 C NMR (100MHz, CDCl3, TMS) δppm 145.7,131.2,129.4,124.9

[0047] HRMS m / z(ESI):calcd.for[C 12 H 10 OS+H] + :203.0525Found:203.0533.

[0048]

[0049] (Benzylsulfinyl)benzene(2b)

[0050] 1 H NMR (400MHz, CDCl3, TMS) δppm 7.47-7.36(m,5H),7.29-7.21(m,3H),6.98-6.96(m,2H),4.00-3.97(m,2H)

[0051] 13 C NMR(100MHz,CDCl3,TMS)δppm 142.8,131.2,130.6,129.2,128.9,128.4,128.2,124.4,63.6

[0052] HRMS m / z(ESI):calcd.for[C 13 H 12 OS+H] + :217.0682 Found:217.0679。

[0053]

[0054] 1-Chloro-4-(methylsulfinyl)benzene(2c)

[0055] 1 H NMR(400MHz,CDCl3,TMS)δppm 7.54-7.51(m,2H),7.45-7.42(m,2H),2.65(s,3H)

[0056] 13 C NMR(100MHz,CDCl3,TMS)δppm 144.2,137.1,129.6,124.9,44.0

[0057] HRMS m / z(ESI):calcd.for[C7H7ClOS+H] + :174.9979 Found:174.9980。

[0058]

[0059] (Sulfinylbis(methylene))dibenzene(2d)

[0060] 1 H NMR(400MHz,CDCl3,TMS)δppm 7.40-7.34(m,3H),7.30-7.28(m,2H),3.94-3.86(m,2H)

[0061] 13 C NMR(100MHz,CDCl3,TMS)δppm 130.2,129.0,128.4,57.3

[0062] HRMS m / z(ESI):calcd.for[C14 H 14 OS+H] + :231.0838 Found:231.0839。

[0063]

[0064] 4,4'-Sulfinylbis(methoxybenzene)(2e)

[0065] 1 H NMR(400MHz,CDCl3,TMS)δppm 7.53(d,J=8.8Hz,4H),6.95(d,J=8.8Hz,4H),3.82(s,6H)

[0066] 13 C NMR(100MHz,CDCl3,TMS)δppm 161.8,137.0,126.9,114.7,55.5

[0067] HRMS m / z(ESI):calcd.for[C 14 H 14 O3S+H] + :263.0742 Found:263.0746。

[0068]

[0069] 1-Bromo-4-(methylsulfinyl)benzene(2f)

[0070] 1 H NMR(100MHz,CDCl3,TMS)δ7.60(d,J=8.4Hz,2H),7.46(d,J=8.4Hz,2H),2.65(s,3H);

[0071] 13 C NMR(100MHz,CDCl3,TMS)δ144.9,132.5,125.3,125.1,44.0.

[0072] HRMS m / z(ESI):calcd.for[C7H7BrOS+H] + :218.9474 Found:218.9471。

[0073]

[0074] 1-Iodo-4-(methylsulfinyl)benzene(2g)

[0075] 1 H NMR(400MHz,CDCl3,TMS)δ7.88(dt,J=8.8,2.1Hz,2H),7.39(dt,J=8.8,2.2Hz,2H),2.71(s,3H);

[0076] 13 C NMR(100MHz,CDCl3,TMS)δ145.9,138.6,125.3,97.5,44.1

[0077] HRMS m / z(ESI):calcd.for[C7H7IOS+Na] + :288.9154 Found:288.9159。

[0078]

[0079] Sulfonyldibenzene(3a)

[0080] 1 H NMR(400MHz,CDCl3,TMS)δ7.94(d,J=7.0Hz,4H),7.57-7.53(m,2H),7.51-7.47(m,4H);

[0081] 13 C NMR(100MHz,CDCl3,TMS)δ141.7,133.3,129.4,127.7.

[0082] HRMS m / z(ESI):calcd.for[C 12 H 10 O2S+H] + :219.0474 Found:219.0477。

[0083]

[0084] (benzylsulfonyl)benzene(3b)

[0085] 1 H NMR(400MHz,CDCl3,TMS)δ7.64-7.58(m,3H),7.45(t,J=7.6Hz,2H),7.34-7.24(m,3H),7.08(d,J=7.3Hz,2H),4.31(s,2H);

[0086] 13 C NMR(100MHz,CDCl3,TMS)δ137.9,133.8,130.9,129.0,128.9,128.8,128.7,128.2,63.0

[0087] HRMS m / z(ESI):calcd.for[C 13 H 12 O2S+H] + :233.0631 Found:233.0635。

[0088]

[0089] 1-Chloro-4-(methylsulfonyl)benzene(3c)

[0090] 1 H NMR(400MHz,CDCl3,TMS)δ7.86(d,J=8.5Hz,2H),7.53(d,J=8.4Hz,2H),3.03(s,3H);

[0091] 13 C NMR(100MHz,CDCl3,TMS)δ140.5,139.1,129.8,129.0,44.6.

[0092] HRMS m / z(ESI):calcd.for[C7H7ClO2S+Na] + :212.9747 Found:212.9755。

[0093]

[0094] (Sulfonylbis(methylene))dibenzene(3d)

[0095] 1 H NMR(400MHz,CDCl3,TMS):δ7.44–7.36(m,10H),4.13(s,4H)

[0096] 13 C NMR(100MHz,CDCl3,TMS):δ130.8,130.8,129.0,128.9,127.5,58.0

[0097] HRMS m / z(ESI):calcd.for[C 14 H14 O2S+H] + :247.0787 Found:247.0790.

[0098]

[0099] 4,4'-sulfonylbis(methylbenzene)(3e)

[0100] 1 H NMR (400MHz, CDCl3, TMS) δ7.81 (d, J = 8.0Hz, 4H), 7.28 (d, J = 8.0Hz, 4H), 2.38 (s, 6H);

[0101] 13 C NMR (100MHz, CDCl3, TMS) δ143.9,139.0,129.8,127.5,21.5.

[0102] HRMS m / z(ESI):calcd.for[C 14 H 14 O4S+H] + :279.0686Found:279.0680.

[0103] The technical solution of the present invention is further illustrated by experiments below.

[0104] Experimental Example 1 Condition Screening Experiment

[0105] 1. Experimental Methods

[0106] This experimental example used the oxidation of diphenyl sulfide to sulfoxide or sulfone as a template reaction. Conditions such as the amount of water, solvent ratio, electrolyte, reaction time, current, and voltage were screened and optimized. Unspecified experimental steps and conditions within each experimental group were performed as described in Example 1.

[0107] 2. Experimental Results

[0108] During the electrochemical oxidation of sulfides, it was found that under constant current electrolysis, the sulfone product was readily obtained, while the sulfoxide product was not obtained in high yield. This may be because the voltage under constant current conditions was not consistently maintained at a low level, causing the oxidation product to remain in the sulfoxide. When performing electrolysis under constant voltage conditions, screening the reaction cell voltage revealed that electrolysis at around 3.0 V produced essentially the only product oxidized to the sulfoxide. When screening the solvent ratio, only trace amounts of product were detected in pure water. Adjusting the acetonitrile:water ratio to 1:5 did not significantly change the reaction yield. Further reductions in the acetonitrile dosage resulted in poor dissolution of the reactants. Therefore, the following conditions were ultimately selected for the oxidation of sulfides to sulfoxides: diphenyl sulfide 1a (0.4 mmol) and tetrabutylammonium tetrafluoroborate (0.1 M) were dissolved in a 5:1 mixture of water and acetonitrile (3 mL total). The solution was placed in an unpartitioned electrolytic cell, and a carbon cloth (1.5 cm) was placed. 2 ) anode and platinum sheet (1.5cm 2 ) cathode, and electrolysis was performed at room temperature at a constant cell voltage of 3.0 V for 10 hours. The isolated yield of 2a was 77%.

[0109] Table 2 Screening and optimization of conditions: oxidation of 1a to 2a

[0110]

[0111]

[0112] Experimental results for the oxidation of sulfides to sulfones demonstrated that the reaction performed better under constant current conditions compared to constant cell voltage electrolysis (Table 3, entries 1 and 2 compared with entries 3 and 4, respectively). Attempts to perform the reaction in pure water yielded only trace amounts of product (Table 3, entry 2). Subsequently, current selection revealed that yields remained essentially unchanged at 5-6 mA (Table 2, entries 3-4).

[0113] Therefore, the following conditions were finally selected: diphenyl sulfide 1a (0.4 mmol) and tetrabutylammonium tetrafluoroborate (0.02 M) were dissolved in a mixture of water and acetonitrile at a ratio of 1:5 (3 mL in total), placed in an undivided electrolytic cell, and a carbon cloth (1.5 cm 2 ) anode and platinum sheet (1.5cm 2 ) cathode, and electrolysis was performed at room temperature at a constant current of 5 mA for 12 h. The isolated yield of 3a was 72%.

[0114] Table 3 Screening and optimization of conditions: oxidation of 1a to 3a

[0115]

[0116] The above examples show that the present invention provides a mild, pollution-free electrochemical synthesis method for sulfoxide and sulfone compounds using water as an oxygen source. The synthesis method of the present invention has good selectivity, high yield, and good application prospects.

Claims

1. A method for electrochemical synthesis of sulfoxide or sulfone compounds, characterized in that: Includes at least one of the following reaction routes: Reaction route 1: dissolving the sulfide in an aqueous electrolyte solution and electrolyzing it at a cell voltage of 2.8V-3.2V to obtain a sulfoxide compound; In reaction route 1, the solvent of the electrolyte solution is a mixture of water and acetonitrile in a volume ratio of 5:1-1:2; the electrolysis adopts constant voltage electrolysis; the ratio of the sulfide to the electrolyte solution is 0.4 mol:3 L; the electrolysis uses only water as the oxygen source; Reaction route 2: dissolving the sulfide in an aqueous electrolyte solution and electrolyzing it at a cell voltage of 5.0-10.0 V to obtain a sulfone compound; In reaction route 2, the solvent of the electrolyte solution is a mixture of water and acetonitrile in a volume ratio of 1:5-1:2; the electrolysis adopts constant current electrolysis, and the current is constant at 5-8 mA; the ratio of the sulfide to the electrolyte solution is 0.4 mol:3L; and the electrolysis uses only water as the oxygen source; The sulfide structural formula is , the sulfoxide compound structural formula is , the sulfone compound is ; Wherein, R1 and R2 are independently selected to be substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C6-C 10 Aryl, wherein the substituent is selected from halogen, C6-C 10 Aryl or C1-C 10 Alkoxy.

2. The electrochemical synthesis method according to claim 1, characterized in that: In reaction route 1, the electrolyte solution contains 0.1 M to 0.15 M of an electrolyte, and the electrolyte is selected from at least one of tetrabutylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate, and tetrabutylammonium periodate.

3. The electrochemical synthesis method according to claim 1, characterized in that: In reaction route 2, the electrolyte solution contains 0.02-0.05 M electrolyte, and the electrolyte is selected from at least one of tetrabutylammonium tetrafluoroborate, tetraethylammonium hexafluorophosphate, and tetrabutylammonium periodate.

4. The electrochemical synthesis method according to claim 1, characterized in that: In the second reaction route, the electrolytic cell is a U-shaped tube with a diameter of 29 mm to 32 mm and a length of 10 cm to 15 cm. The size of the electrode sheet is 1.5 cm. 2 The anode is made of carbon cloth, the cathode is made of platinum sheet, and the distance between the electrodes is 7-10 mm.

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