Synthesis method of novel sulfonyl heterocyclic compound

Abstract

The invention discloses a synthesis method of a novel sulfuryl heterocyclic compound. According to the method, sulfur dioxide released by sodium pyrosulfite is adopted as a double synthon, sulfonate free radicals and a single stable sulfur dioxide source are obtained through electrochemical oxidation of sulfur dioxide and methanol, and the sulfuryl heterocyclic compound with double-component sulfur dioxide inserted can be directly and orderly constructed without transition metal. And the method is mild in conditions, efficient and high in atom economy.

Description

Technical Field

[0001] The invention relates to a chemical synthesis technology, in particular to a method for synthesizing a novel sulfone heterocyclic compound. Background Art

[0002] Sulfone is an important functional group structure and is widely used in pharmaceuticals, agricultural chemicals and other fields.

[0003] Sulfone compounds occupy an important position in the field of medicinal chemistry due to their unique physical and chemical properties, and compounds containing sulfone groups have been widely used in clinical practice. For example: Apremilast is an oral phosphodiesterase-4 inhibitor, which is a clinical drug used to treat psoriatic arthritis in adults (J. Chem. Inf. Model. 2012, 52, 3138-3143). The drug was approved for marketing in the United States in 2014, and its annual sales in the United States reached US$1.6 billion in 2019; Remikiren is a classic drug for the early treatment of hypertension (J. Chem. Educ. 2010, 87, 1348-1349); Tazobactam is a highly effective β-lactamase inhibitor (Curr. Topics Med. Chem. 2016, 16, 1200-1216), which has a good broad-spectrum antibacterial effect, and bactam compounds can be administered in combination with many antibiotics in clinical practice to enhance the antibacterial effect of antibiotics; Dorolamide hydrochloride (Dorolamide HCl) is a carbonic anhydrase inhibitor (J.Med.Chem.1996,39,522-530), a drug for treating glaucoma. In addition, sulfonamide compounds can be used as antibacterial drugs.

[0004] Sulfone compounds are an important class of organic synthesis intermediates, which are widely present in a variety of natural compounds and synthetic bioactive molecules and have a variety of chemical and biological activities. In the past few years, various methods have been established to synthesize sulfone-containing compounds, and the free radical rule based on the sulfur dioxide insertion strategy is characterized by high efficiency and rapidity. Traditionally, there are two main strategies for the synthesis of sulfone compounds by sulfur dioxide insertion: (1) transition metal insertion of sulfur dioxide; (2) photocatalytic insertion of sulfur dioxide. However, these methods usually require the use of transition metal catalysts, pre-functionalization between metal and substrate, expensive photocatalysts, and long reaction times, making them difficult to apply in practical synthesis. In contrast, electrochemistry has the characteristics of highly controllable factors such as potential, current, and electrolyte, which provides an attractive alternative for the construction of various functional compounds. In the prior art, the method of constructing sulfone heterocyclic compounds by two-component sulfur dioxide insertion under electrochemical oxidation conditions has not been reported. This scarcity is attributed to the redox potential of sulfur dioxide, which readily donates an electron to directly generate the more stable sulfur dioxide radical anion. Therefore, ensuring the orderly addition of the two reactive intermediates generated by sulfur dioxide to olefins to form a single product is a major challenge.

[0005] In recent years, although progress has been made in the synthesis of single-component sulfone compounds, the construction of multi-fragment sulfone heterocyclic compounds remains a major challenge and difficulty in organic synthesis. Summary of the invention

[0006] The purpose of the present invention is to provide a novel method for synthesizing sulfone heterocyclic compounds in view of the deficiencies of the prior art. The method has the characteristics of simple reaction operation, mild reaction conditions, environmental friendliness, high efficiency and high atom economy.

[0007] The technical solution for achieving the purpose of the present invention is:

[0008] A method for synthesizing a novel sulfone heterocyclic compound, wherein the general synthesis formula of the novel sulfone heterocyclic compound is:

[0009]

[0010] Among them, R 1 is alkyl or halogen, and the acid is methanesulfonic acid, formic acid or acetic acid.

[0011] The synthesis process of the novel sulfone heterocyclic compound is:

[0012] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of acid are respectively added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol is added to dissolve, a carbon rod is used as an anode and a platinum sheet is used as a cathode, and a stirring reaction is carried out at 4 mA constant current at 25-30 degrees Celsius for 4 hours, and a thin layer chromatography is used to monitor the reaction progress. After the reaction is completed, the mixture is extracted with 3×5 ml of dichloromethane, the organic layer is dried with anhydrous sodium sulfate, the solvent is dried under reduced pressure, and the residue is purified by column chromatography to obtain the target product, wherein, during elution purification, silica gel, dichloromethane / methanol = 100:1.

[0013] The technical scheme adopts a mild and efficient electrochemical oxidation method to directly construct valuable new sulfone heterocyclic compounds. The technical scheme uses sulfur dioxide released by sodium pyrosulfite as a double synthon, and uses electrochemical oxidation under the action of sulfur dioxide and methanol to continuously produce two different sulfur dioxide intermediates to directly synthesize a series of new sulfone heterocyclic compounds. Specifically, the electrochemical oxidation of sulfur dioxide and methanol is used to obtain sulfonate free radicals and a single stable sulfur dioxide source.

[0014] This method has the characteristics of simple reaction operation, mild reaction conditions, environmental friendliness, high efficiency and high atom economy. DETAILED DESCRIPTION

[0015] The present invention will be further described below with reference to the embodiments, but the present invention is not limited thereto.

[0016] Embodiment 1:

[0017] Preparation and product characterization of 4-methylbenzolidine (3a):

[0018]

[0019] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked bottle, and 10 ml of ultra-dry methanol was added to dissolve. A carbon rod was used as an anode and a platinum sheet was used as a cathode. The reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3a. White solid (nuclear magnetic yield: 71%). mp90.2-92.5℃. 1H NMR(400MHz,Chloroform-d)δ7.77(m,1H),7.45(m,1H),6.98(m,1H),4.18-4.16(m,1H),4.02-4.00(m,1H),3.98(s ,3H),3.97-3.93(m,1H),3.68-3.66(m,1H),3.31-3.24(m,1H),2.87-2.80(m,1H),2.44(s,3H),2.37-2.25(m,1H). 13 C NMR(101MHz,Chloroform-d)δ160.4,137.7,134.2,132.0,125.0,121.8,115.0,56.6,50.4,48.0,40.4,25.4,21.1.HRMS(m / z)(ESI):calcd for C 12 H 17 N 2 O 5 S 2 + [M+H] + 345.0574, found 345.0578.

[0020] Embodiment 2:

[0021] Preparation and characterization of 4-ethylbenzolidine (3b):

[0022]

[0023] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of formic acid were added to a 10 ml three-necked bottle, and 10 ml of ultra-dry methanol was added to dissolve. A carbon rod was used as an anode and a platinum sheet was used as a cathode. The reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3b. White solid (nuclear magnetic yield: 65%). mp94.2-94.5℃. 11H NMR (400 MHz, Chloroform-d) δ 7.81 (m, 1H), 7.49 - 7.47 (m, 1H), 7.02 - 7.00 (m, 1H), 4.19 - 4.16 (m, 1H), 4.02 - 4.00 (m, 1H), 3.97 (s, 3H), 3.96–3.93 (m, 1H), 3.68 - 3.66 (m, 1H), 3.31 - 3.25 (m, 1H), 2.87 (s, 1H), 2.76 - 2.70 (m, 2H), 2.31 - 2.25 (m, 1H), 1.28 - 1.25 (s, 3H). 13 13C NMR (101 MHz, Chloroform-d) δ 160.5, 144.0 133.2, 132.2, 123.9, 121.9, 115.1, 56.7, 50.5, 48.1, 40.4, 28.4, 25.4, 15.1. HRMS (m / z) (ESI): calcd for C 14 H 18 NaN 2 O 5 S 2 + [M + Na] + 381.0555, found 381.0553.

[0024] Example 3:

[0025] Preparation and characterization of 4-isopropylbenzothianthrene (3c):

[0026]

[0027] 0.25 mmol of the olefin compound, 1.25 mmol of sodium metabisulfite, and 1.25 mmol of acetic acid were added to a 10 mL three-necked flask, dissolved in 10 mL of ultradry methanol. Using a carbon rod as the anode and a platinum sheet as the cathode, a constant current of 4 mA was applied, and the reaction was stirred at 25 °C for 4 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was rotary evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, eluted with dichloromethane / methanol = 100:1) to obtain the target product 3c. white solid (nuclear magnetic yield: 70%). m.p. 89.1 - 90.3 °C. 1H NMR(400MHz,Chloroform-d)δ7.84-7.83(m,1H),7.53-7.50(m,1H),7.03-7.01(m,1H),4.18-4.16(m,1H),4.00-.99(m,1H),3.97(s,3H ),3.95-3.93(m,1H),3.70-3.62(m,1H),3.31-3.25(m,1H),3.03-2.96(m,1H),2.86-2.79(m,1H),2.31-2.25(m,1H),1.28-1.26(m,6H). 13 C NMR(101MHz,Chloroform-d)δ160.5,148.6,132.2,131.9,122.5,121.9,115.2,56.6,50.4,48.1,40.4,33.9,25.4,23.7.HRMS(m / z)(ESI):calcd for C 15 H 20 NaN 2 O 5 S 2 + [M+Na] + 395.0711, found 395.0711.

[0028] Embodiment 4:

[0029] Preparation and characterization of 4-tert-butylbenzoxoltan (3d):

[0030]

[0031] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3d. White solid (nuclear magnetic yield: 78%). mp94.9-95.1℃. 1H NMR(400MHz,Chloroform-d)δ7.96(m,1H),7.68(m,1H),7.03(m,1H),4.18-4.16(m,1H),4.00-3.97(m,1H),3.96(s,3H),3.95 -3.93(m,1H),3.72-3.58(m,2H),3.31-3.25(m,1H),2.86-2.79(m,1H),2.30-2.24(m,1H),1.34(s,9H). 13 C NMR(101MHz,Chloroform-d)δ160.5,151.1,132.0,131.0,121.6,121.4,114.9,56.7,50.4,48.0,40.3,35.2,31.1,25.4.HRMS(m / z)(ESI):calcd for C 16 H 23 N 2 O 5 S 2 + [M+H] + 387.1043, found 387.1043.

[0032] Embodiment 5:

[0033] Preparation and characterization of 4-sec-butylbenzoxoltan (3e):

[0034]

[0035] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of acetic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3e. White solid (nuclear magnetic yield: 70%). mp88.7-91.0℃. 1H NMR(400MHz,Chloroform-d)δ7.76-7.75(m,1H),7.47-7.44(m,1H),7.03-7.01 (m,1H),4.17-4.15(m,1H),3.98-3.97(m,1H),3.94-3.93(m,3H),3.90-3.89(m ,1H),3.65-3.60(m,1H),3.31-3.24(m,1H),2.80-2.77(m,1H),2.71-2.66(m,1 H),2.28-2.22(m,1H),1.61-1.57(m,2H),1.24-1.22(m,3H),0.81-0.78(m,3H). 13 CNMR(101MHz,Chloroform-d)δ160.6,147.5,132.3,123.0,121.8,115.3,56.7,50.4,48.1,41.3,40.4,30.9,25.3,21.5,12.1.HRMS(m / z)(ESI):calcd for C 16 H 23 N 2 O 5 S 2 + [M+H] + 387.1043, found 387.1042.

[0036] Embodiment 6:

[0037] Preparation and characterization of 4-butylbenzoxoltan (3f):

[0038]

[0039] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite, and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked flask, and 10 ml of ultra-dry methanol was added to dissolve. A carbon rod was used as an anode and a platinum sheet was used as a cathode. The reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3f. White solid (nuclear magnetic yield: 73%). mp91.7-92.1℃. 1H NMR(400MHz,Chloroform-d)δ7.80(s,1H),7.47-7.45(m,1H),7.01-6.99(m ,1H),4.21-4.17(m,1H),4.02-4.00(m,1H),3.98(s,3H),3.95-3.94(m,1H), 3.71-3.36(m,1H),3.31-3.22(m,1H),2.88-2.81(m,1H),2.71-2.67(m,2H), 2.34-2.25(m,1H),1.64-1.60(m,2H),1.38-1.33(m,2H),0.95-0.91(m,3H). 13 C NMR(101MHz,Chloroform-d)δ160.4,142.8,133.6,132.1,124.4,121.8,115.0,56.6,50.4,48.1,40.4,35.1,33.1,25.4,22.2,13.9.HRMS(m / z)(ESI):calcd for C 16 H 22 NaN 2 O 5 S 2 + [M+Na] + 409.0864, ​​found 409.0868.

[0040] Embodiment 7:

[0041] Preparation and characterization of 4-cyclohexylbenzoxoltan (3 g):

[0042]

[0043] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain 3 g of the target product. White solid (nuclear magnetic yield: 65%). mp94.0-94.3℃. 1H NMR(400MHz,Chloroform-d)δ7.82-7.81(m,1H),7.50-7.48(m,1H),7.02-7.0 0(m,1H),4.20-4.10(m,1H),4.01-3.98(m,1H),3.96(s,3H),3.94-3.82(m,1H ),3.66-3.62(m,1H),3.30-3.24(m,1H),2.87-2.80(m,1H),2.59(s,1H),2.30 -2.24(m,1H),1.86(s,3H),1.77-1.74(m,2H),1.39-1.37(m,4H),1.25(s,1H). 13 CNMR(101MHz,Chloroform-d)δ160.5,147.8,132.2,123.5,122.8,121.8,115.1,56.6,50.4,48.1,44.1,40.4,34.1,26.8,25.9,25.4.HRMS(m / z)(ESI):calcd for C 18 H 24 NaN 2 O 5 S 2 + [M+Na] + 435.1019, found 435.1025.

[0044] Embodiment 8:

[0045] Preparation and characterization of benzoxoltan (3h):

[0046]

[0047] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3h. White solid (nuclear magnetic yield: 70%). mp87.9-88.3℃. 1H NMR(400MHz,Chloroform-d)δ7.89-7.87(m,1H),7.65-6.21(m,1H),7.45-7.41(m,1H),7.08-7.06(m,1H),4.20-4.15(m,1H),4.0 3-3.98(m,1H),3.97-3.93(m,3H),3.92-3.83(m,1H),3.70-3.62(m,1H),3.31-3.24(m,1H),2.81-2.78(m,1H),2.29-2.23(m,1H). 13 C NMR(101MHz,Chloroform-d)δ161.0,134.3,133.3,127.1,125.0,121.8,115.3,56.7,50.4,48.2,40.4,25.3.HRMS(m / z)(ESI):calcd forC 12 H 14 NaN 2 O 5 S 2 + [M+Na] + 353.0242, found 353.0237.

[0048] Embodiment 9:

[0049] Preparation and characterization of 4-fluorobenzoxoltan (3i):

[0050]

[0051] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of formic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3i. White solid (nuclear magnetic yield: 66%). mp86.4-87.3℃. 11H NMR (400 MHz, Chloroform-d) δ 7.42 - 7.40 (m, 1H), 7.37 - 7.32 (m, 1H), 7.13 - 7.09 (m, 1H), 4.20 - 4.15 (m, 1H), 4.08 - 4.01 (m, 1H), 3.97 (s, 3H), 3.89 - 3.84 (m, 1H), 3.74 - 3.66 (m, 1H), 3.36 - 3.29 (m, 1H), 2.81 - 2.78 (m, 1H), 2.30 - 2.25 (m, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 161.2, 160.0 (d, J=252.5 Hz), 130.9, 122.8 (d, J=10.1 Hz), 121.1 (d, J=20.2 Hz), 117.9 (d, J=10.1 Hz), 111.3, (d, J=20.2 Hz), 56.6, 50.4, 48.5, 40.4, 25.1. 19 19F NMR (376 MHz, Chloroform-d) δ -110.98. HRMS (m / z) (ESI): calcd for C 12 H 13 NaFN 2 O 5 S 2 + [M + Na] + 371.0143, found 371.0145.

[0052] Example 10:

[0053] Preparation and Characterization of 4-Chlorobenzosultam (3j):

[0054]

[0055] 0.25 mmol of the olefin compound, 1.25 mmol of sodium metabisulfite, and 1.25 mmol of methanesulfonic acid were added to a 10 mL three-necked flask, dissolved in 10 mL of ultra-dry methanol. Using a carbon rod as the anode and a platinum sheet as the cathode, a constant current of 4 mA was applied, and the reaction was stirred at 25 °C for 4 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was rotary evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, eluted with dichloromethane / methanol = 100:1) to obtain the target product 3j. White solid (nuclear magnetic yield: 65%). m.p. 90.8 - 92.1 °C. 1H NMR(400MHz,Chloroform-d)δ7.84(m,1H),7.59(m,1H),7.03(m,1H),4.20-4.15(m,1H),4.03-4.01(m,1H), 3.98(s,3H),3.94-3.90(m,1H),3.72-3.69(m,1H),3.34-3.27(m,1H),2.86-2.81(m,1H),2.33-2.28m,1H). 13 C NMR(101MHz,Chloroform-d)δ161.1,133.5,132.8,132.4,125.0,122.9,116.8,56.6,50.4,48.3,40.4,25.2.HRMS(m / z)(ESI):calcd for C 12 H 13 ClNaN 2 O 5 S 2 + [M+Na] + 386.9847, found 386.9850.

[0056] Embodiment 11:

[0057] Preparation and characterization of 4-bromobenzoltan (3k):

[0058]

[0059] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite, and 1.25 mmol of methanesulfonic acid were added to a 10 ml three-necked bottle, and 10 ml of ultra-dry methanol was added to dissolve. A carbon rod was used as an anode and a platinum sheet was used as a cathode. The reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3k. White solid (nuclear magnetic yield: 66%). mp91.1-92.6℃. 1H NMR(400MHz,Chloroform-d)δ8.05(m,1H),7.76-7.74(m,1H),6.98-6.96(m,1H),4.21-4.15(m,1H),4.04-4.00(m ,1H),3.98(s,3H),3.96-3.90(m,1H),3.70-3.66(m,1H),3.33-3.27(m,1H),2.88-2.84(m,1H),2.34-2.28(m,1H). 13 C NMR(101MHz,Chloroform-d)δ161.0,136.3,128.0,123.1,119.7,116.9,56.7,50.3,48.3,40.4,25.3.HRMS(m / z)(ESI):calcd for C 12 H 13 Bn 2 O 5 S 2 Na + [M+Na] + 430.9347, found 430.9347.

[0060] Embodiment 12:

[0061] Preparation and characterization of 3,5-dimethylbenzoxazolamide (3l):

[0062]

[0063] 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of acetic acid were added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol was added to dissolve, a carbon rod was used as an anode and a platinum sheet was used as a cathode, and the reaction was stirred at 4 mA constant current at 25 degrees Celsius for 4 hours. The reaction progress was monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with dichloromethane (3×5 ml). The organic layer was dried over anhydrous sodium sulfate, the solvent was dried under reduced pressure, and the residue was purified by column chromatography (silica gel, dichloromethane / methanol=100:1 elution) to obtain the target product 3l. White solid (nuclear magnetic yield: 77%). mp94.3-94.5℃. 1 H NMR (400 MHz, Acetonitrile-d 3)δ7.14(s,1H),6.95(s,1H),4.17-4.13(m,1H),3.99-3.97(m,1H),3.95(s,3H),3.92-3.86(m,1H) ,3.83(m,1H),3.63-3.61(m,1H),3.46-3.40(m,1H),2.68-2.64(m,1H),2.63(s,3H),2.40(s,3H). 13 C NMR (101 MHz, Acetonitrile-d 3 )δ160.6,144.3,137.2,135.6,131.9,130.8,114.8,57.5,50.1,49.2,40.9,25.2,21.1,19.4.HRMS(m / z)(ESI):calcd for C 14 H 18 N 2 O 5 S 2 Na + [M+Na] + 381.0550, found 381.0552.

[0064] Summary: This patent develops a transition metal catalyst-free method to synthesize valuable new sulfone heterocyclic compounds. Under mild electrochemical conditions, sulfur dioxide released from sodium pyrosulfite is used as a double synthon, and two sulfur dioxide active intermediates are continuously produced by sulfur dioxide and methanol under electrochemical oxidation conditions. A series of new sulfone heterocyclic compounds are directly synthesized, which are environmentally friendly, highly efficient and highly atom-economical.

Claims

1. A method for synthesizing a novel sulfone heterocyclic compound, characterized in that: The general synthetic formula of the novel sulfone heterocyclic compound is: Among them, R 1 is alkyl or halogen, and the acid is methanesulfonic acid, formic acid or acetic acid.

2. The method for synthesizing the novel sulfone heterocyclic compound according to claim 1, characterized in that: The synthesis process of the novel sulfone heterocyclic compound is: 0.25 mmol of olefin compound, 1.25 mmol of sodium metabisulfite and 1.25 mmol of acid are respectively added to a 10 ml three-necked bottle, 10 ml of ultra-dry methanol is added to dissolve, a carbon rod is used as an anode and a platinum sheet is used as a cathode, and a stirring reaction is carried out at 4 mA constant current at 25-30 degrees Celsius for 4 hours, and a thin layer chromatography is used to monitor the reaction progress. After the reaction is completed, the mixture is extracted with 3×5 ml of dichloromethane, the organic layer is dried with anhydrous sodium sulfate, the solvent is dried under reduced pressure, and the residue is purified by column chromatography to obtain the target product, wherein, during elution purification, silica gel, dichloromethane / methanol = 100:1.

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