A method for preparing a 2-sulfonyl benzothiazole compound

Abstract

The application belongs to the technical field of organic chemical synthesis, and particularly relates to a preparation method of 2-sulfonyl benzothiazole compounds. The method uses benzothiazole as a raw material, carbon tetrachloride as a chlorination reagent, and sodium tert-butoxide as an alkali. Water and a reaction solvent are added, and the reaction is carried out at room temperature for 40 minutes. Then, sodium sulfinate is added, and the reaction is carried out at 80-100 DEG C for 7-24 hours. After post-treatment, the target product is obtained. The application uses cheap and readily available benzothiazole to replace the limited source of chlorobenzothiazole as a starting material. Without transition metal and ligand, carbon tetrachloride is used as an electrophilic activation reagent to efficiently construct the target product through a one-pot two-step method. In addition, the reaction can be carried out in an air atmosphere without nitrogen protection. The method has the advantages of mild conditions, simple operation, wide substrate application range, and the like, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis, specifically relating to a method for preparing 2-sulfonylbenzothiazole compounds. Background Technology

[0002] Sulfons and their derivatives, as an important class of sulfur-containing compounds, have wide applications in medicinal chemistry, materials science, and industrial chemistry due to their excellent physicochemical properties. Benzothiazoles are an important class of heterocyclic structural units, reported to possess various biological activities such as antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, and antiparasitic effects. Sulfonylbenzothiazole compounds combine the aforementioned two structural groups, exhibiting not only unique physicochemical properties but also diverse synthetic transformation potential. In recent years, these compounds have become a research hotspot due to their potential biopharmacological activities and their value as useful intermediates in synthetic chemistry.

[0003] Traditionally, the preparation of sulfonylbenzothiazole compounds often employs a two-step method: first, thioetherification of benzothiazole with a thiol, followed by oxidation of the resulting thioether intermediate. However, this method has significant limitations: firstly, the thiol raw materials used typically have unpleasant odors and require an unfriendly operating environment; secondly, the subsequent oxidation reaction conditions may be incompatible with the sensitive functional groups contained in the molecular structure, thus limiting the substrate applicability of this method.

[0004] To overcome these shortcomings, researchers have developed various transition metal-catalyzed coupling strategies in recent years. For example, using 2-chlorobenzothiazole as a substrate, combined with aryl halides / DABSO or boric acid / DABSO, the target product can be obtained through a one-pot, two-step sulfinization process catalyzed by palladium. In addition, some literature reports the use of inexpensive nickel catalysts to achieve this type of conversion. One route involves the direct sulfinization reaction of 2-chlorobenzothiazole with sodium sulfite; another uses aryl / alkenylboronic acid with potassium metabisulfite for the conversion.

[0005] While the aforementioned catalytic methods provide a convenient route for the synthesis of sulfonylbenzothiazoles, they still generally rely on transition metal catalysts, organic ligands, and traditional organic solvents, which poses cost and environmental constraints for practical industrial applications. Although some studies have reported green sulfonation synthesis routes based on eutectic solvents and without the participation of transition metals, their starting material is still 2-chlorobenzothiazole. Compared with widely available benzothiazoles, the source of starting materials for chlorobenzothiazoles is relatively limited, which to some extent affects the practicality and economy of this route.

[0006] Therefore, developing a synthetic method that does not require the participation of transition metals or ligands and directly uses widely available benzothiazoles (rather than their chlorinated derivatives) as starting materials is of great research significance and application value. Summary of the Invention

[0007] The purpose of this invention is to provide a method for preparing 2-sulfonylbenzothiazole compounds. This method is not only mild in reaction conditions, simple in operation, and environmentally friendly, but also significantly broadens the applicable range of substrates and yields stable target products in high yield.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing a 2-sulfonylbenzothiazole compound, comprising the following steps: In an organic solvent, benzothiazole of Formula 1 is used as a raw material. A chlorinating agent, alkali and water are added and the mixture is reacted at room temperature for 40 minutes. Then sodium sulfinate of Formula 2 is added and the mixture is reacted at 80-100 °C for 7-24 hours. The resulting reaction solution is post-treated to obtain compound of Formula 3, which is a 2-sulfonylbenzothiazole compound. The molar ratio between compound benzothiazole of formula 1 and sodium sulfite of formula 2 is 1:2; The structural formula of the compound benzothiazole of formula 1 is as follows: ; The structural formula of compound 2, sodium sulfite, is as follows: ; The structural formula of compound 3 is as follows: ; In Equations 1 and 3, R 1 Selected from one of hydrogen, methyl, methoxy, hydroxy, phenyl, and fluorine; in formulas 2 and 3, R 2 It is selected from one of alkyl, phenyl, alkyl-substituted phenyl, methoxy-substituted phenyl, halogen-substituted phenyl, trifluoropropyl, cycloalkyl, and thiophene.

[0009] The above reaction formula is: .

[0010] Preferably, the alkyl group is methyl or ethyl; the alkyl-substituted phenyl group is methyl-substituted phenyl, ethyl-substituted phenyl, or 2,4,6-trimethyl-substituted phenyl; the halogen-substituted phenyl group is fluorine-substituted phenyl or chlorine-substituted phenyl; and the cycloalkyl group is one of cyclopropyl, cyclobutyl, and cyclopentyl.

[0011] Preferably, the reaction is carried out at room temperature for 40 minutes, followed by the addition of sodium sulfite, compound of formula 2, and the reaction is carried out at 100 °C for 7 hours.

[0012] Preferably, the base is t-BuONa, and the amount of base used is three times the amount of benzothiazole compound of Formula 1.

[0013] Preferably, the chlorinating agent is CCl4, and the amount of chlorinating agent used is 1.1 times the amount of benzothiazole compound of Formula 1.

[0014] Preferably, the amount of water used is three times the amount of benzothiazole compound of Formula 1.

[0015] Preferably, the organic solvent is anhydrous DMF, and the volume ratio of the solvent to the molar amount of benzothiazole of Formula 1 is 5 mL: 1 mmol.

[0016] Furthermore, after the reaction was complete, ethyl acetate was added to the reaction solution for quenching, and the mixture was washed three times with brine and extracted three times with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography. The separation and purification method was as follows: silica gel for column chromatography was added to the obtained reaction solution, and the solvent was removed by reduced pressure distillation. The pure target product was obtained by column chromatography separation.

[0017] Preferably, the purification is performed by silica gel column chromatography, and the eluent is a mixture of petroleum ether and ethyl acetate at a volume ratio of 4:1.

[0018] Compared with the prior art, the present invention has the following beneficial effects: This invention provides a novel synthetic route for 2-sulfonylbenzothiazole compounds. For the first time, it uses readily available and inexpensive benzothiazole and sodium sulfite as starting materials, directly replacing the limited-source chlorobenzothiazole, significantly reducing raw material costs and broadening the substrate applicability range. Furthermore, the entire reaction system of this invention requires no transition metal catalysts or ligands, and uses ultra-dry DMF as a solvent and carbon tetrachloride as a chlorinating agent. The reaction can be carried out efficiently at 80-100 °C under normal atmospheric pressure and air, with mild reaction conditions and simple operation, avoiding the need for stringent inert gas protection. Finally, the target products, 2-sulfonylbenzothiazole compounds prepared by this invention, are chemically stable, easy to store and subsequently applied, and have good prospects for industrialization. Detailed Implementation

[0019] The present invention will be further described in detail below with reference to the embodiments.

[0020] Example 1

[0021] Preparation of 2-p-toluenesulfonylbenzo[d]thiazole with the following structural formula

[0022] The specific preparation process is as follows: Anhydrous sodium tert-butoxide (144 mg, 1.5 mmol), ultra-dry DMF (2.5 mL), H2O (27 μL, 1.5 mmol), benzothiazole (52 μL, 0.5 mmol), and CCl4 (53.3 μL, 0.55 mmol) were added to a reaction flask and stirred at room temperature for 40 min. Then, sodium p-toluenesulfinate (178 mg, 1.0 mmol) was added, and the mixture was heated to 100 °C and reacted for 7 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added to the reaction solution to quench the reaction, and the mixture was washed three times with brine and extracted three times with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by rapid silica gel chromatography. The purification method was as follows: silica gel was added to the resulting reaction solution, and the solvent was removed by vacuum distillation. Pure 2-p-toluenesulfonylbenzo[d]thiazole was obtained by column chromatography (petroleum ether / ethyl acetate volume ratio = 4 / 1) with a yield of 71%. The structural characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 7.0 Hz, 1H), 8.03 (d, J = 6.0Hz, 2H), 7.94 (d, J = 6.8 Hz, 1H), 7.60 - 7.47 (m, 2H), 7.36 (d, J = 6.6 Hz,2H), 2.41 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 167.7, 153.0, 146.0, 137.1, 135.5, 130.3,129.1, 127.9, 127.5, 125.6, 122.3, 21.8. Example 2

[0023] Preparation of 2-((4-methoxyphenyl)sulfonyl)benzo[d]thiazole with the following structure

[0024] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium p-methoxybenzenesulfinate, and the other steps were the same as in Example 1. Pure 2-((4-methoxyphenyl)sulfonyl)benzo[d]thiazole was isolated with a yield of 71%, and the structural characterization numbers are as follows: 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 6.0 Hz, 2H), 8.17 (d, J = 8.1Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.78 (d, J =6.2 Hz, 2H), 7.61 - 7.39 (m,7H); 13 C NMR (101 MHz, CDCl3) δ 167.6, 153.1, 147.7, 139.1, 137.2, 137.0,129.7, 129.3, 129.0, 128.3, 128.0, 127.7, 127.6, 125.7, 122.4. Example 3

[0025] Preparation of 2-(phenylsulfonyl)benzo[d]thiazole with the following structure

[0026] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium benzenesulfinate, and the other steps were the same as in Example 1. Pure 2-(phenylsulfonyl)benzo[d]thiazole was isolated with a yield of 86%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.20 - 8.07 (m, 3H), 7.94 (d, J = 7.8 Hz,1H), 7.68 - 7.47 (m, 5H); 13 C NMR (101 MHz, CDCl3) δ 167.3, 152.9, 138.5, 137.1, 134.7, 129.6,129.0, 128.0, 127.6, 125.5, 122.3. Example 4

[0027] Preparation of 2-((4-ethylphenyl)sulfonyl)benzo[d]thiazole with the following structure

[0028] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium p-ethylbenzenesulfinate, and the other steps were the same as in Example 1. Pure 2-((4-ethylphenyl)sulfonyl)benzo[d]thiazole was isolated with a yield of 66%, and the structural characterization numbers are as follows: 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 9.0, 1H), 8.06 (d, J = 8.0 Hz,2H), 7.94 (d, J = 7.9, 1H), 7.60 - 7.46 (m, 2H), 7.38 (d, J = 8.4 Hz, 2H),2.70 (q, J = 8.4 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 167.8, 153.0, 152.1, 137.1, 135.7, 129.2,128.5, 127.9, 127.5, 125.6, 122.3, 29.1, 15.0. Example 5

[0029] Preparation of 2-(tris(toluenesulfonyl)benzo[d]thiazole with the following structure

[0030] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium 2,4,6-trimethylbenzenesulfinate, the temperature in Example 1 was replaced with 80 °C, and the time in Example 1 was replaced with 7 h for 24 h. All other steps were the same as in Example 1. Pure 2-(tris(trimethylbenzenesulfonyl)benzo[d]thiazole was obtained in 56% yield. The structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 9.4 Hz, 1H), 7.85 (d, J = 9.4Hz, 1H), 7.49 - 7.39 (m, 2H), 6.89 (s, 2H), 2.67 (s, 6H), 2.21 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.1, 152.7, 144.9, 141.7, 136.6, 132.6,132.5, 127.8, 127.4, 125.6, 122.2, 23.4, 21.3. Example 6

[0031] Preparation of 2-(methylsulfonyl)benzo[d]thiazole with the following structure

[0032] The sodium methanesulfonate in Example 1 was replaced with an equimolar amount of sodium p-toluenesulfonate, and the other steps were the same as in Example 1. Pure 2-(methanesulfonyl)benzo[d]thiazole was isolated with a yield of 68%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 7.8Hz, 1H), 7.67 - 7.55 (m, 2H), 3.41 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 166.5, 152.5, 136.7, 128.2, 127.8, 125.5,122.5, 42.5. Example 7

[0033] Preparation of 2-(ethylsulfonyl)benzo[d]thiazole with the following structure

[0034] The sodium ethanesulfonate in Example 1 was replaced with an equimolar amount of sodium ethanesulfonate, and the other steps were the same as in Example 1. Pure 2-(ethylsulfonyl)benzo[d]thiazole was isolated with a yield of 76%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 9.3 Hz, 1H), 8.02 (d, J = 7.8Hz, 1H), 7.68 - 7.55 (m, 2H), 3.55 (q, J = 7.3 Hz, 2H), 1.44 (t, J = 7.4 Hz,3H); 13 C NMR (101 MHz, CDCl3) δ 165.5, 152.9, 136.9, 128.2, 127.8, 125.6,122.5, 49.5, 7.3. Example 8

[0035] Preparation of 2-(cyclopropylsulfonyl)benzo[d]thiazole with the following structure

[0036] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium cyclopropanesulfinate, and the other steps were the same as in Example 1. Pure 2-(cyclopropylsulfonyl)benzo[d]thiazole was isolated with a yield of 74%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 7.9Hz, 1H), 7.65 - 7.52(m, 2H), 2.91- 2.81 (m, 1H), 1.55 - 1.48 (m, 2H), 1.20(d, J = 9.5 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 166.3, 152.9, 136.8, 128.0, 127.7, 125.6,122.4, 31.8, 6.7. Example 9

[0037] Preparation of 2-(cyclobutylsulfonyl)benzo[d]thiazole with the following structure

[0038] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium cyclobutanesulfinate, and the other steps were the same as in Example 1. Pure 2-(cyclobutylsulfonyl)benzo[d]thiazole was isolated with a yield of 72%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.0Hz, 1H), 7.64 - 7.53 (m, 2H), 4.37 - 4.26 (m, 1H), 2.78 - 2.66 (m, 2H), 2.39- 2.28 (m, 2H), 2.14 - 2.01 (m, 2H); 13 C NMR (101 MHz, CDCl3) δ 165.1, 152.9, 136.9, 128.0, 127.7, 125.5,122.4, 56.1, 22.8, 17.4. Example 10

[0039] Preparation of 2-(cyclopentylsulfonyl)benzo[d]thiazole with the following structure

[0040] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium cyclopentanesulfinate, and the other steps were the same as in Example 1. Pure 2-(cyclopentylsulfonyl)benzo[d]thiazole was isolated with a yield of 75%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 7.8Hz, 1H), 7.64 - 7.54 (m, 2H), 4.07 - 3.97 (m, 1H), 2.30 - 2.18 (m, 2H), 2.08- 1.96 (m, 2H), 1.87 - 1.76 (m, 2H), 1.72 - 1.60 (m, 2H); 13 C NMR (101 MHz, CDCl3) δ 166.1, 153.0, 136.9, 128.0, 127.7, 125.5,122.4, 63.4, 27.2, 26.1. Example 11

[0041] Preparation of 2-((4-fluorophenyl)sulfonyl)benzo[d]thiazole with the following structure

[0042] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium p-fluorobenzenesulfinate, and the other steps were the same as in Example 1. Pure 2-((4-fluorophenyl)sulfonyl)benzo[d]thiazole was isolated with a yield of 45%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.23 ​​- 8.11 (m, 3H), 7.97 (d, J = 7.9 Hz,1H), 7.62 - 7.50 (m, 2H), 7.30 - 7.21 (m, 2H); 13 C NMR (101 MHz, CDCl3) δ 167.1, 166.5 (d, J C-F = 259.5 Hz), 153.0,137.1, 134.6 (d, J C-F = 3.2 Hz), 132.1 (d, J C-F = 9.9 Hz), 127.9 (d, J C-F= 39.5Hz), 125.6, 122.4, 117.2, 117.0; 19 F NMR (376 MHz, CDCl3) δ -101.4. Example 12

[0043] Preparation of 2-((4-chlorophenyl)sulfonyl)benzo[d]thiazole with the following structure

[0044] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium p-chlorobenzenesulfinate, and the other steps were the same as in Example 1. Pure 2-((4-chlorophenyl)sulfonyl)benzo[d]thiazole was isolated with a yield of 68%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.7Hz, 2H), 7.96 (d, J = 7.8 Hz, 1H), 7.61 - 7.49 (m, 4H); 13 C NMR (101 MHz, CDCl3) δ 166.9, 153.0, 141.6, 137.1, 137.0, 130.5,130.0, 128.1, 127.7, 125.6, 122.4. Example 13

[0045] Preparation of 2-((3,3,3-trifluoropropyl)sulfonyl)benzo[d]thiazole with the following structure

[0046] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium 3,3,3-trifluoropropanesulfinate, and the other steps were the same as in Example 1. Pure 2-((3,3,3-trifluoropropyl)sulfonyl)benzo[d]thiazole was obtained in 46% yield, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 7.9Hz, 1H), 7.71 - 7.58 (m, 2H), 3.78 - 3.70 (m, 2H), 2.86 - 2.72 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 164.6, 152.6, 136.8, 128.6, 128.1, 125.3(q, J C-F = 277.9 Hz), 125.8, 122.5, 48.2 (q, J C-F = 3.2 Hz), 28.2 (q, J C-F = 31.9Hz); 19 F NMR (376 MHz, CDCl3) δ -65.9. Example 14

[0047] Preparation of 2-(2-thienylsulfonyl)benzothiazole with the following structure

[0048] The sodium p-toluenesulfinate in Example 1 was replaced with an equimolar amount of sodium thiophene-2-sulfinate, and the other steps were the same as in Example 1. Pure 2-(2-thiophenesulfonyl)benzo[d]thiazole was isolated with a yield of 35%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 9.6 Hz, 1H), 7.99 - 7.93 (m,2H), 7.82 - 7.77 (m, 1H), 7.63 - 7.52 (m, 2H), 7.20- 7.15 (m, 1H); 13 C NMR (101 MHz, CDCl3) δ 167.3, 152.9, 139.1, 137.2, 136.6, 136.3,128.6, 128.1, 127.7, 125.7, 122.4. Example 15

[0049] Preparation of 5-methyl-2-p-toluenesulfonylbenzo[d]thiazole with the following structure

[0050] The "benzothiazole" in Example 1 was replaced with an equimolar amount of "5-methylbenzo[d]thiazole", and the temperature was replaced with 80 °C instead of 100 °C in Example 1. All other steps were the same as in Example 1. Pure 5-methyl-2-p-toluenesulfonylbenzo[d]thiazole was obtained with a yield of 57%. The structural characterization numbers are as follows: 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.3 Hz, 2H), 7.92 (s, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.38 - 7.31 (m, 3H), 2.49 (s, 3H), 2.42 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 167.6, 153.4, 145.9, 137.9, 135.7, 134.2,130.3, 129.7, 129.1, 125.3, 121.7, 21.9, 21.6. Example 16

[0051] Preparation of 4-methyl-2-p-toluenesulfonylbenzo[d]thiazole with the following structure

[0052] The "benzothiazole" in Example 1 was replaced with an equimolar amount of "4-methylbenzo[d]thiazole", and the other steps were the same as in Example 1. Pure 4-methyl-2-p-toluenesulfonylbenzo[d]thiazole was isolated with a yield of 66%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.3 Hz, 2H), 7.73 (d, J = 7.8Hz, 1H), 7.41 - 7.28 (m, 4H), 2.71 (s, 3H), 2.41 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 166.1, 152.7, 145.8, 137.0, 135.9, 135.7,130.2, 129.0, 127.9, 127.8, 119.5, 21.8, 18.3. Example 17

[0053] Preparation of 5-methoxy-2-p-toluenesulfonylbenzo[d]thiazole with the following structure

[0054] The "benzothiazole" in Example 1 was replaced with an equimolar amount of "5-methoxybenzo[d]thiazole", and the 100 °C in Example 1 was replaced with 80 °C. All other steps were the same as in Example 1. Pure 5-methoxy-2-p-toluenesulfonylbenzo[d]thiazole was isolated with a yield of 82%. The structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 6.8Hz, 1H), 7.53 (s, 1H), 7.34 (d, J = 7.3 Hz, 2H), 7.13 (d, J = 8.9 Hz, 1H),3.83 (s, 3H), 2.39 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 168.3, 159.8, 154.4, 145.9, 135.6, 130.2,129.1, 128.9, 122.4, 119.1, 106.5, 55.7, 21.8. Example 18

[0055] Preparation of 2-p-toluenesulfonylbenzo[d]thiazol-6-phenol with the following structure

[0056] The "benzo[d]thiazole-6-phenol" in Example 1 was replaced with an equimolar amount of "benzo[d]thiazole-6-phenol", and the other steps were the same as in Example 1. Pure 2-p-toluenesulfonylbenzo[d]thiazole-6-phenol was obtained with a yield of 52%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 7.98 (d, J = 6.6 Hz, 1H), 7.73- 7.65 (m, 3H), 7.30 (d, J = 7.0 Hz, 2H), 7.04 (d, J = 6.4 Hz, 1H), 2.43 (s,3H); 13 C NMR (101 MHz, CDCl3) δ 155.3, 151.9, 147.2, 145.8, 134.5, 132.1,130.0, 128.6, 124.2, 121.2, 116.0, 21.8. Example 19

[0057] Preparation of 5-phenyl-2-p-toluenesulfonylbenzo[d]thiazole with the following structure

[0058] The "benzothiazole" in Example 1 was replaced with an equimolar amount of "5-phenylbenzo[d]thiazole", and the other steps were the same as in Example 1. Pure 5-phenyl-2-p-toluenesulfonylbenzo[d]thiazole was isolated with a yield of 60%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 8.06 (d, J = 6.2 Hz, 2H), 7.99 (d, J = 6.5, 1H), 7.76 (d, J = 8.6, 1H), 7.64 - 7.58 (m, 2H), 7.47 (t, J =7.6 Hz, 2H), 7.42 - 7.34 (m, 3H), 2.43 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 168.4, 153.7, 146.1, 141.3, 139.9, 135.9,135.5, 130.3, 129.2, 129.1, 128.1, 127.53, 127.46, 123.5, 122.5, 21.9. Example 20

[0059] Preparation of 6-fluoro-2-p-toluenesulfonylbenzo[d]thiazole with the following structure

[0060] The "benzothiazole" in Example 1 was replaced with an equimolar amount of "6-fluorobenzo[d]thiazole", and the other steps were the same as in Example 1. Pure 6-fluoro-2-p-toluenesulfonylbenzo[d]thiazole was isolated with a yield of 65%, and the structural characterization numbers are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.02 - 8.05 (m, 1H), 8.02 (d, J = 6.2 Hz, 2H), 7.62 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.33 - 7.24 (m, 1H),2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.5, 161.9 (d, J C-F = 251.9 Hz), 149.7,146.2, 138.4 (d, J C-F = 11.3 Hz), 135.4, 130.4, 129.2, 127.0 (d, J C-F = 9.9 Hz),117.0 (d, J C-F = 25.4 Hz), 108.4 (d, J C-F = 27.1 Hz), 21.9; 19 F NMR (376 MHz, CDCl3) δ -110.5。

Claims

1. A method for preparing a 2-sulfonylbenzothiazole compound, characterized in that, The specific steps are as follows: In an organic solvent, benzothiazole of Formula 1 is used as a raw material. A chlorinating agent, alkali and water are added and the mixture is reacted at room temperature for 40 minutes. Then sodium sulfinate of Formula 2 is added and the mixture is reacted at 80-100 °C for 7-24 hours. The resulting reaction solution is post-treated to obtain compound of Formula 3, which is a 2-sulfonylbenzothiazole compound. The molar ratio between compound benzothiazole of formula 1 and sodium sulfite of formula 2 is 1:2; The structural formula of the compound benzothiazole of formula 1 is as follows: ; The structural formula of compound 2, sodium sulfite, is as follows: ; The structural formula of compound 3 is as follows: ; In Equations 1 and 3, R 1 Selected from one of hydrogen, methyl, methoxy, hydroxy, phenyl, and fluorine; in formulas 2 and 3, R 2 It is selected from one of alkyl, phenyl, alkyl-substituted phenyl, methoxy-substituted phenyl, halogen-substituted phenyl, trifluoropropyl, cycloalkyl, and thiophene.

2. The method for preparing a 2-sulfonylbenzothiazole compound according to claim 1, characterized in that, The alkyl group is methyl or ethyl; the alkyl-substituted phenyl group is methyl-substituted phenyl, ethyl-substituted phenyl, or 2,4,6-trimethyl-substituted phenyl; the halogen-substituted phenyl group is fluorine-substituted phenyl or chlorine-substituted phenyl; the cycloalkyl group is one of cyclopropyl, cyclobutyl, and cyclopentyl.

3. The method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The reaction was carried out at room temperature for 40 minutes, followed by the addition of sodium sulfite, compound of formula 2, and the reaction was carried out at 100 °C for 7 hours.

4. The method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The base is t-BuONa, and the amount of base used is three times the amount of benzothiazole compound of formula 1.

5. A method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The chlorinating agent is CCl4, and the amount of chlorinating agent used is 1.1 times the amount of benzothiazole compound of Formula 1.

6. The method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The amount of water used is three times the amount of benzothiazole, the compound of Formula 1.

7. A method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The organic solvent is anhydrous DMF, and the volume ratio of the solvent to the molar amount of compound benzothiazole of Formula 1 is 5 mL: 1 mmol.

8. A method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, After the reaction was complete, ethyl acetate was added to the reaction solution for quenching, and the mixture was washed three times with brine and extracted three times with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography. The separation and purification method was as follows: silica gel was added to the obtained reaction solution, and the solvent was removed by reduced pressure distillation. The pure target product was obtained by column chromatography.

9. A method for preparing a 2-sulfonylbenzothiazole compound according to claim 1 or 2, characterized in that, The purification was performed by silica gel column chromatography, with the eluent being a mixture of petroleum ether and ethyl acetate at a volume ratio of 4:1.

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