Preparation method of benzothiazole ether compound
By using potassium phosphate catalyst to catalyze the reaction of 2-(methanesulfonyl)benzothiazole with alcohols or phenols under mild conditions, benzothiazole ether compounds were successfully synthesized. This solved the problems of limited catalyst applicability and insufficiently mild reaction conditions in the prior art, and achieved efficient and selective compound synthesis.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SUZHOU UNIV
- Filing Date
- 2026-03-30
- Publication Date
- 2026-05-26
AI Technical Summary
In the existing technology, sodium hydroxide as a catalyst in the synthesis of benzothiazole ether compounds has limitations in its applicability to base-sensitive substrates, easily promotes side reactions, and the reaction conditions are not mild enough, resulting in low efficiency.
Using potassium phosphate as a catalyst, 2-(methanesulfonyl)benzothiazole is reacted with alcohols or phenols under mild conditions to synthesize benzothiazole ethers, extending the range to a wide range of substrates containing esters and amides.
The method achieves efficient synthesis of benzothiazole ether compounds under mild conditions with high yield, good selectivity, good compatibility with various functional groups, and simple operation, which has practical application value.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for preparing benzothiazole ether compounds. Background Technology
[0002] Benzothiazole, as a structural motif in many drugs and bioactive compounds, plays an important role in anticancer, antibacterial, antiviral, and anti-inflammatory activities. Therefore, the synthesis of benzothiazole methyl sulfone using benzothiazole as a reagent and the further optimization of reaction conditions to maintain its bioactivity still have great potential for development, especially in the pharmaceutical industry.
[0003] Sulfons are fundamental structural elements in chemical molecules and have been widely used as substrates or intermediates in organic synthesis. Due to their chemical stability and structural versatility, the application of sulfons as electrophiles in transition metal-catalyzed cross-coupling reactions has become a new field and has attracted considerable research attention. Therefore, further exploration of reactions without transition metals, without high temperatures, and under mild conditions is of great significance.
[0004] Benzothiazole methyl sulfone (2-(methanesulfonyl)benzothiazole) exhibits unique chemical properties that facilitate related reactions. Existing research has shown that sodium hydroxide can catalyze the reaction of methanol and 2-(methanesulfonyl)benzothiazole to produce 2-methoxybenzothiazole. However, sodium hydroxide's suitability as a strong base substrate is limited, restricting its application in reactions involving antibodies or base-sensitive substrates. Furthermore, it easily promotes side reactions and exhibits relatively low efficiency. Therefore, achieving efficient preparation of benzothiazole ether compounds under mild conditions is of great significance. Summary of the Invention
[0005] This invention addresses the shortcomings of existing technologies by providing a method for preparing benzothiazole ether compounds. It utilizes mild, alkaline potassium phosphate as a catalyst, which efficiently catalyzes the main reaction while effectively protecting sensitive functional groups in the substrate molecule. This successfully extends the reaction system to a wide range of substrates containing ester and amide groups, providing a significant boost to the rapid construction of small molecule libraries containing benzothiazole structures and offering new options for pharmaceutical synthesis. Furthermore, the process conditions are milder and the operation is safer.
[0006] To address the aforementioned technical problems, the first aspect of this invention provides a method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis, comprising the following steps:
[0007] In an organic solvent, 2-(methanesulfonyl)benzothiazole compounds are mixed with alcohols or phenols and reacted under the catalysis of potassium phosphate to yield benzothiazole ether compounds.
[0008] This invention uses potassium phosphate as a catalyst to react 2-(methanesulfonyl)benzothiazole compounds with alcohols or phenols as substrates to synthesize benzothiazole ether compounds. The reaction conditions are mild, the yield is high, the selectivity is good, and it has good compatibility with various functional groups. The materials are simple and readily available, and the operation is convenient. At the same time, the reaction substrates can be extended to a wide range of substrates containing ester groups, amide groups, etc., which has practical application value.
[0009] Furthermore, the 2-(methanesulfonyl)benzothiazole compound has the following structure: R1 is H, methyl, nitro, ethyl ester, trifluoromethyl, or bromine.
[0010] Furthermore, the alcohol compound is one or more of isopentyl glycol, benzyl alcohol, tetrafluoropropanol, perfluorohexylethyl alcohol, tert-butyl 3-hydroxymethylazine-1-carboxylate, and p-hydroxyphenylethanol.
[0011] Furthermore, the phenolic compound is one or more of 4-aminophenol, 2-naphthol, Boc-tyrosine methyl ester, and vitamin E.
[0012] Furthermore, the molar ratio of the 2-(methanesulfonyl)benzothiazole compound to the alcohol or phenol compound is 1:(1-3).
[0013] Furthermore, the molar ratio of the 2-(methanesulfonyl)benzothiazole compound to potassium phosphate is 1:(1-3).
[0014] Furthermore, the reaction temperature is 20-40°C.
[0015] Furthermore, the reaction time is 5-20 hours.
[0016] Furthermore, the concentration of the 2-(methanesulfonyl)benzothiazole compound in the reaction system is 0.1-1 mol / L.
[0017] The second aspect of the present invention provides benzothiazole ether compounds prepared by the method described in the first aspect.
[0018] The beneficial effects of this invention are:
[0019] This invention uses potassium phosphate as a catalyst to react 2-(methanesulfonyl)benzothiazole compounds with alcohols or phenols as substrates to synthesize benzothiazole ether compounds. The reaction conditions are mild, the yield is high, the selectivity is good, the compatibility with various functional groups is good, the materials are simple and readily available, and the operation is convenient.
[0020] This invention uses potassium phosphate as a catalyst and reacts under mild conditions, which can extend the reaction substrate to a wide range of substrates such as those containing ester groups and amide groups, and has practical application value. Detailed Implementation
[0021] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0022] Example 1
[0023] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and isopentyl glycol in the presence of potassium phosphate. The specific operation is as follows:
[0024] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of isopentyl glycol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a colorless oily liquid with a yield of 90%. The reaction formula is: .
[0025] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 1H), 7.61 (d, J =7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.21 (d, J = 7.6 Hz, 1H), 4.74 (t, J =6.7 Hz, 2H), 2.06 (t, J = 6.7 Hz, 2H), 1.31 (s, 6H); 13 C NMR (100 MHz, CDCl3)δ 172.9, 149.2, 131.8, 126.0, 123.6, 121.3, 120.8, 70.0, 69.0, 41.8, 29.8.
[0026] Example 2
[0027] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and benzyl alcohol in the presence of potassium phosphate. The specific operation is as follows:
[0028] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of benzyl alcohol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a colorless oily liquid with a yield of 86%. The reaction formula is: .
[0029] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 7.9 Hz, 1H), 7.54 (d, J =7.9 Hz, 1H), 7.42 - 7.39 (m, 2H), 7.34 - 7.25 (m, 4H), 7.14 (td, J = 7.6, 1.2Hz, 1H), 5.51 (s, 2H).; 13 C NMR (100 MHz, CDCl3) δ 172.7, 149.3, 135.2, 132.0, 128.7, 128.7, 128.5, 126.0, 123.6, 121.3, 120.9, 73.4.
[0030] Example 3
[0031] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and tetrafluoropropanol under the action of potassium phosphate. The specific operation is as follows:
[0032] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of tetrafluoropropanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a colorless oily liquid with a yield of 94%. The reaction formula is: .
[0033] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 1H), 7.52 (d, J =8.0 Hz, 1H), 7.26 (td, J = 7.8, 1.3 Hz, 1H), 7.14 (td, J = 7.7, 1.2 Hz, 1H),6.02 - 5.72 (m, 1H), 4.83 (tt, J = 12.5, 1.5 Hz, 2H); 13 C NMR (100 MHz, CDCl3)δ 171.1, 148.5, 132.4, 126.4, 124.3, 121.5, 121.4, 116.5, 114.3, 114.0,112.1, 111.7, 111.4, 109.6, 109.2, 108.9, 107.1, 106.7, 106.4, 66.5, 66.2,65.9; 19 F NMR (376 MHz, CDCl3) δ -124.18, -137.89.
[0034] Example 4
[0035] This embodiment uses 2-(methanesulfonyl)benzothiazole and perfluorohexylethyl alcohol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0036] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of perfluorohexylethyl alcohol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a colorless solid with a yield of 91%. The reaction formula is:
[0037] .
[0038] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 1H), 7.65 (d, J =8.0 Hz, 1H), 7.39 (t, J = 8.2 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 4.88 (t, J =6.6 Hz, 2H), 2.79 - 2.66 (m, 2H); 13 C NMR (100 MHz, CDCl3) δ 171.94, 149.05, 132.06, 126.10, 123.81, 121.33, 121.03, 63.18, 30.91, 30.69, 30.47; 19 F NMR (376 MHz, CDCl3) δ -80.91, -113.43, -121.91, -122.92, -123.56, -126.21.
[0039] Example 5
[0040] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and 4-aminophenol in the presence of potassium phosphate. The specific operation is as follows:
[0041] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of 4-aminophenol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a brown oily liquid with a yield of 85%. The reaction formula is as follows: .
[0042] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 1H), 7.63 (d, J =8.0 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.24 (t, J = 7.7 Hz, 1H), 7.14 - 7.10(m, 2H), 6.71 - 6.67 (m, 2H), 3.70 (s, 2H); 13 C NMR (101 MHz, CDCl3) δ 173.57,149.35, 147.12, 145.09, 132.21, 126.17, 123.75, 121.78, 121.50, 121.24,115.82.
[0043] Example 6
[0044] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and 3-hydroxymethylazetane-1-carboxylic acid tert-butyl ester under the action of potassium phosphate. The specific operation is as follows:
[0045] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of tert-butyl 3-hydroxymethylazine-1-carboxylic acid, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 98%. The reaction formula is as follows:
[0046] .
[0047] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer.
[0048] 1 H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 8.0Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.19 (t, J = 7.7 Hz, 1H), 4.66 (d, J = 6.8Hz, 2H), 4.05 (t, J = 8.5 Hz, 2H), 3.78 (dd, J = 8.9, 5.3 Hz, 2H), 3.06 -2.96 (m, 1H), 1.42 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.52, 156.23, 149.08,131.88, 126.03, 123.65, 121.28, 120.81, 79.51, 72.69, 60.31, 28.36, 27.83,14.16.
[0049] Example 7
[0050] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and 2-naphthol under the action of potassium phosphate. The specific operation is as follows:
[0051] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of 2-naphthol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature and in air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 97%. The reaction formula is:
[0052] .
[0053] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.95 – 7.85 (m, 4H), 7.82 (d, J = 8.1 Hz,1H), 7.69 (d, J = 8.0 Hz, 1H), 7.57 – 7.50 (m, 3H), 7.43 (td, J = 7.8, 1.3Hz, 1H), 7.30 (td, J = 7.7, 1.2 Hz, 1H); 13 C NMR (100 MHz, CDCl3) δ 171.98,152.34, 149.14, 133.88, 132.38, 131.62, 130.13, 127.87, 127.80, 126.86,126.29, 126.00, 124.12, 121.80, 121.33, 120.13, 117.49.
[0054] Example 8
[0055] This embodiment uses 2-(methanesulfonyl)benzothiazole and p-hydroxyphenylethanol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0056] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of p-hydroxyphenylethanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 79%. The reaction formula is:
[0057] .
[0058] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.1 Hz, 1H), 7.63 (d, J =8.5 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.26 - 7.21 (m, 5H), 3.82 (t, J = 6.6Hz, 2H), 2.85 (t, J = 6.6 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 172.3, 153.3, 149.0, 137.0, 132.2, 130.5, 126.3, 124.1, 121.6, 121.3, 120.7, 63.4, 38.6.
[0059] Example 9
[0060] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and Boc-tyrosine methyl ester in the presence of potassium phosphate. The specific operation is as follows:
[0061] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 2-(methanesulfonyl)benzothiazole, 0.6 mmol of Boc-tyrosine methyl ester, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate and filtered into a round-bottom flask. An appropriate amount of silica gel was added, and excess solvent was removed by rotary evaporation under reduced pressure. Column chromatography was then performed to obtain a white solid with a yield of 90%. The reaction formula is as follows:
[0062] .
[0063] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.1 Hz, 1H), 7.64 (d, J =7.9 Hz, 1H), 7.35 (m, J = 8.0 Hz, 1H), 7.26 (m, 3H), 7.19 (m, 2H), 5.06 (d, J= 8.3 Hz, 1H), 4.59 (q, J = 6.8 Hz, 1H), 3.71 (s, 3H), 3.17 - 3.02 (m, 2H), 1.41 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 172.2, 171.8, 155.1, 153.8, 149.1,134.3, 132.3, 130.8, 126.3, 124.1, 121.8, 121.3, 120.6, 80.1, 54.4, 52.3,37.8, 28.3.
[0064] Example 10
[0065] In this embodiment, benzothiazole ether compounds were synthesized from 2-(methanesulfonyl)benzothiazole and vitamin E in the presence of potassium phosphate. The specific operation is as follows:
[0066] In a 5 mL reaction flask, a stir bar, 2-(methanesulfonyl)benzothiazole (0.3 mmol), vitamin E (0.6 mmol), and potassium phosphate (0.6 mmol) were added. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature and in air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, ethyl acetate (10 mL) was added for dilution, the mixture was transferred to a separatory funnel, and washed with water (10 mL × 3). The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 81%. The reaction formula is:
[0067] .
[0068] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.1 Hz, 1H), 7.60 (d, J =7.9 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.23 (t, J = 8.0 Hz, 1H), 2.63 (t, J =6.8 Hz, 2H), 2.14 (d, J = 3.6 Hz, 6H), 2.11 (s, 3H), 1.83 (m, 2H), 1.61 -1.09 (m, 26H), 0.89 - 0.85 (m, 12H); 13 C NMR (101 MHz, CDCl3) δ 174.11,150.28, 149.96, 145.30, 132.36, 127.57, 126.16, 125.92, 123.89, 123.50,121.53, 121.31, 118.15, 75.46, 40.12, 39.46, 37.55, 37.50, 37.38, 32.89,32.78, 31.15, 28.06, 24.89, 24.54, 23.97, 22.80, 22.71, 21.09, 20.69, 19.84, 19.76, 13.04, 12.20, 11.98.
[0069] Example 11
[0070] This embodiment uses 6-methyl-2-(methanesulfonyl)benzothiazole and phenethyl alcohol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0071] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 6-methyl-2-(methanesulfonyl)benzothiazole, 0.6 mmol of phenylethanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 78%. The reaction formula is:
[0072] .
[0073] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.91 - 7.78 (m, 4H), 7.15 (dt, J = 8.7,4.2 Hz, 4H), 1.32 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 165.4 (dd, J = 255.0, 3.2 Hz), 134.4 (dd, J = 11.6, 8.9 Hz), 128.4 (d, J = 107.9 Hz), 116.1 (dd, J= 21.4, 14.0 Hz), 48.1, 30.2; 31 P NMR (162 MHz, CDCl3) δ 40.53.
[0074] Example 12
[0075] This embodiment uses 6-ethyl carboxylate-2-(methanesulfonyl)benzothiazole and phenethyl alcohol as raw materials to synthesize benzothiazole ether compounds via a reaction in the presence of potassium phosphate. The specific operation is as follows:
[0076] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of ethyl 6-carboxylate-2-(methanesulfonyl)benzothiazole, 0.6 mmol of phenylethanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 93%. The reaction formula is:
[0077] .
[0078] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 8.37 (s, 1H), 8.07 (dd, J = 8.5, 1.8 Hz,1H), 7.69 (d, J = 8.5 Hz, 1H), 7.32 (m, 5H), 4.80 (t, J = 7.0 Hz, 2H), 4.40(q, J = 7.1 Hz, 2H), 3.18 (t, J = 7.0 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H); 13 CNMR (100 MHz, CDCl3) δ 175.1, 166.1, 152.9, 137.2, 131.9, 129.0, 128.6,127.5, 126.8, 125.7, 123.3, 120.3, 72.6, 61.0, 35.2, 14.4.
[0079] Example 13
[0080] This embodiment uses 6-bromo-2-(methanesulfonyl)benzothiazole and phenethyl alcohol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0081] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 6-bromo-2-(methanesulfonyl)benzothiazole, 0.6 mmol of phenylethanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 71%. The reaction formula is:
[0082] .
[0083] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 1.9 Hz, 1H), 7.49 (d, J =8.56 Hz, 1H), 7.42 (dd, J = 8.6, 2.0 Hz, 1H), 7.32 – 7.20 (m, 5H), 4.73 (t, J= 7.0 Hz, 2H), 3.13 (t, J = 7.0 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 172.9,148.3, 137.3, 133.6, 129.4, 129.0, 128.7, 126.8, 123.8, 122.0, 116.3, 72.5,35.2.
[0084] Example 14
[0085] This embodiment uses 6-nitro-2-(methanesulfonyl)benzothiazole and phenethyl alcohol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0086] In a 5 mL reaction flask, a stir bar, 6-nitro-2-(methanesulfonyl)benzothiazole, phenylethanol (0.6 mmol), and potassium phosphate (0.6 mmol) were added. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature and in air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, ethyl acetate (10 mL) was added for dilution, the mixture was transferred to a separatory funnel, and washed with water (10 mL × 3). The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 80%. The reaction formula is:
[0087] .
[0088] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 2.3 Hz, 1H), 8.21 (dd, J =8.9, 2.4 Hz, 1H), 7.68 (d, J = 8.9 Hz, 1H), 7.34 – 7.24 (m, 5H), 4.81 (t, J =7.0 Hz, 2H), 3.17 (t, J = 7.0 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 176.58,154.25, 143.80, 136.99, 132.41, 129.04, 128.76, 126.98, 121.97, 120.72,117.83, 73.37, 35.18.
[0089] Example 15
[0090] This embodiment uses 6-trifluoromethyl-2-(methanesulfonyl)benzothiazole and phenethyl alcohol as raw materials to synthesize benzothiazole ether compounds in the presence of potassium phosphate. The specific operation is as follows:
[0091] In a 5 mL reaction flask, a stir bar was added, along with 0.3 mmol of 6-trifluoromethyl-2-(methanesulfonyl)benzothiazole, 0.6 mmol of phenylethanol, and 0.6 mmol of potassium phosphate. Dimethyl sulfoxide (1.5 mL) was used as the solvent. The reaction was carried out at room temperature under air for 12 hours, and TLC was used to confirm complete reaction. After the reaction, 10 mL of ethyl acetate was added to dilute the solution, which was then transferred to a separatory funnel and washed with 10 mL × 3 drops of water. The resulting organic phase was dried over anhydrous sodium sulfate, filtered into a round-bottom flask, and a suitable amount of silica gel was added. Excess solvent was removed by rotary evaporation under reduced pressure, followed by column chromatography to obtain a white solid with a yield of 89%. The reaction formula is as follows:
[0092] .
[0093] The product was dissolved in CDCl3 and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.56 (dd, J = 8.5, 1.9 Hz, 1H), 7.32 - 7.20 (m, 5H), 4.76 (t, J = 7.0 Hz, 2H), 3.14 (t, J = 7.0 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 174.81, 151.95,137.23, 132.24, 129.09, 128.75, 126.94, 126.28, 125.96, 125.75, 125.63,123.26, 123.23, 123.19, 123.15, 123.05, 120.97, 118.96, 118.92, 118.88,118.84, 72.85, 35.24; 19 F NMR (376 MHz, CDCl3) δ -61.29.
[0094] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.
Claims
1. A method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis, characterized in that, Includes the following steps: In an organic solvent, 2-(methanesulfonyl)benzothiazole compounds are mixed with alcohols or phenols and reacted under the catalysis of potassium phosphate to yield benzothiazole ether compounds.
2. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The 2-(methanesulfonyl)benzothiazole compounds have the following structures: R1 is H, methyl, nitro, ethyl ester, trifluoromethyl, or bromine.
3. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The alcohol compounds are one or more of isopentyl glycol, benzyl alcohol, tetrafluoropropanol, perfluorohexylethyl alcohol, tert-butyl 3-hydroxymethylazine-1-carboxylate, and p-hydroxyphenylethanol.
4. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The phenolic compound is one or more of 4-aminophenol, 2-naphthol, Boc-tyrosine methyl ester, and vitamin E.
5. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The molar ratio of the 2-(methanesulfonyl)benzothiazole compound to the alcohol or phenol compound is 1:(1-3).
6. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The molar ratio of the 2-(methanesulfonyl)benzothiazole compound to potassium phosphate is 1:(1-3).
7. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The reaction temperature is 20-40℃.
8. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The reaction time is 5-20 hours.
9. The method for synthesizing benzothiazole ether compounds based on potassium phosphate catalysis as described in claim 1, characterized in that, The concentration of the 2-(methanesulfonyl)benzothiazole compound in the reaction system is 0.1-1 mol / L.
10. A benzothiazole ether compound prepared by the method of any one of claims 1-9.