A method for the transition metal-free synthesis of benzothiazole compounds

Abstract

The application belongs to the field of compound synthesis, and particularly relates to a transition metal-free synthesis method of benzothiazole compounds. The synthesis method is as follows: aromatic amine, aromatic alcohol, sulfur element, iodine element and a solvent are added into a reaction tube, and then the reaction is carried out at 140 DEG C under a nitrogen atmosphere. After the reaction is completed, the benzothiazole compound is obtained through post-treatment. The method is mild in reaction and simple in operation, and avoids the use of metal residues and toxic sulfur sources in the traditional method. The application directly reacts on the C-H bond to construct the C-S bond, and does not need to add transition metals. The reaction condition is mild, the functional group tolerance is excellent, and the application has good application prospect. The application provides an efficient and green synthesis method for the synthesis of benzothiazole compounds.

Description

Technical Field

[0001] This invention belongs to the field of compound synthesis, specifically relating to a method for synthesizing benzothiazole compounds without transition metal catalysis. Background Technology

[0002] Benzothiazoles, as a core class of sulfur-containing heterocyclic compounds, have shown irreplaceable application value in multiple fields such as biomedicine and industrial materials. In the biomedical field, benzothiazoles and their derivatives stand out due to their potent biological activity, covering a variety of pharmacological effects such as antitumor, antibacterial, anthelmintic, antidiabetic, antitrypanoid, and antioxidant effects. For example, F-DM-PBT can selectively inhibit the activity of lung cancer, colon cancer, and breast cancer cells (Eur. J. Med. Chem. 2006, 41(2), 210-218). Thioflavin T, as a potential micro-fluorescent reagent, can selectively recognize RNA G-quadruplexes and detect fibrils (Biochim. Biophys. Acta - Proteins Proteom. 2010, 1804(7), 1405-1412). Therefore, it is of certain significance to study the synthesis methods of benzothiazole compounds. This invention develops a method for synthesizing benzothiazole compounds using aromatic amines, aromatic alcohols, and elemental sulfur as substrates and iodine as a catalyst. This method is mild and simple to operate, avoiding the use of metal residues and toxic sulfur sources in traditional methods. The reaction involves key steps such as alcohol oxidation, aldehyde-amine condensation, iodine-promoted sulfur insertion, and cyclization, achieving iodine catalytic cycling. Elemental sulfur participates in the reaction as both a sulfur source and an oxidant. This provides an efficient and green synthetic method for benzothiazole compounds. Summary of the Invention

[0003] The purpose of this invention is to address the shortcomings and deficiencies of existing technologies by providing a transition metal-free method for the synthesis of benzothiazoles. This invention develops a method for synthesizing benzothiazole compounds using aromatic amines, aromatic alcohols, and elemental sulfur as substrates and elemental iodine as a catalyst. This method is mild, simple to operate, and avoids the use of metal residues and toxic sulfur sources in traditional methods. It exhibits good compatibility with benzyl alcohol derivatives containing alkyl groups, halogens, and trifluoromethyl groups; electron-donating groups in aniline derivatives favor the reaction, while strongly electron-withdrawing groups or sterically hindered groups inhibit the reaction. The reaction involves key steps such as alcohol oxidation, aldehyde-amine condensation, iodine-promoted sulfur insertion, and cyclization, achieving a catalytic cycle of iodine, with elemental sulfur participating in the reaction as both a sulfur source and oxidant. This provides an efficient and green synthetic method for the synthesis of benzothiazole compounds.

[0004] The objective of this invention is achieved through the following technical solution.

[0005] A method for synthesizing benzothiazole compounds without transition metal catalysis includes the following steps: In a reaction tube, aromatic amines, aromatic alcohols, elemental sulfur, elemental iodine catalyst, and solvent are added, and the reaction is carried out under certain temperature and atmosphere. After the reaction is completed, the benzothiazole compounds are obtained by separation and purification.

[0006] Furthermore, the chemical reaction equations for the synthesis process are shown below: ; In the formula, Ar 1 It is 2-naphthyl, 3-methylphenyl; Ar 2 It is phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 3-methylphenyl, 3-fluorophenyl, 3-trifluoromethylphenyl, 2-methylphenyl, 3,5-difluorophenyl, 2,4-difluorophenyl; Further, general formula I is 2-naphthylamine or 3-methylaniline; general formula II is benzyl alcohol, 4-methylbenzyl alcohol, 4-tert-butylbenzyl alcohol, 4-fluorophenylbenzyl alcohol, 4-trifluoromethylbenzyl alcohol, 3-methylbenzyl alcohol, 3-fluorobenzyl alcohol, 3-trifluoromethylbenzyl alcohol, 2-methylbenzyl alcohol, 3,5-difluorobenzyl alcohol, or 2,4-difluorobenzyl alcohol.

[0007] Furthermore, the catalyst is elemental iodine, sodium iodide, tetrabutylammonium iodide, hydrogen iodide, or ammonium iodide, preferably elemental iodine.

[0008] Furthermore, the oxidant is elemental sulfur.

[0009] Furthermore, the atmosphere is nitrogen, oxygen, or air, with a nitrogen atmosphere being preferred.

[0010] Furthermore, the solvent is N 1-Methylpyrrolidone, acetonitrile, dichloromethane, tetrahydrofuran, ethanol N , N -Dimethylformamide, preferred N -Methylpyrrolidone.

[0011] Further, the separation and purification operation is as follows: the reaction solution is added to ethyl acetate, washed and extracted twice with saturated NaCl solution, the upper organic phase solution is taken, dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the benzothiazole compound.

[0012] Furthermore, the molar ratio of the compound of structural formula I to the compound of structural formula II is 1:1 to 1.5, preferably 1:1.

[0013] Furthermore, the molar ratio of the compound represented by structural formula I to the compound represented by structural formula III is 1:1 to 4, preferably 1:3.

[0014] Furthermore, the molar ratio of the catalyst to the compound of Formula I is 0.05 to 1.50:1, preferably 0.05:1.

[0015] Furthermore, the stirring reaction time is 12 to 15 hours, preferably 14 hours.

[0016] Furthermore, the reaction temperature is 120–140°C, preferably 140°C.

[0017] This invention utilizes elemental iodine as a catalyst. N Using methylpyrrolidone as a solvent, at 140℃, and with aromatic amines, aromatic alcohols, and elemental sulfur as substrates, the direct cyclization reaction of naphthylamine and benzyl alcohol was achieved to synthesize benzothiazole compounds, providing an efficient and green synthetic method for the synthesis of benzothiazole compounds.

[0018] Compared with existing technologies, the present invention has the following advantages and beneficial effects: (1) This invention uses readily available aromatic alcohols and aromatic amines as raw materials, and achieves the direct conversion of benzyl alcohol and aromatic amines through a one-pot three-component reaction and cascaded cyclization, thereby directly constructing benzothiazole compounds. This method eliminates the need for intermediate separation and purification, significantly shortens the synthesis steps, improves the step economy and atom economy of the reaction, and expands the range of raw material selection; (2) This invention does not require transition metal catalysts, strong acids or bases, or additional ligands. It uses elemental sulfur as a sulfur source and oxidant, and elemental iodine as a catalyst. The reaction conditions are simple, the raw materials are readily available, and it has good functional group compatibility. Attached Figure Description

[0019] Figure 1 and Figure 2 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1, respectively.

[0020] Figure 3 and Figure 4 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2, respectively.

[0021] Figure 5 and Figure 6 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3, respectively.

[0022] Figure 7 and Figure 8 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4, respectively.

[0023] Figure 9 and Figure 10 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 5, respectively.

[0024] Figure 11 and Figure 12 These are the proton and carbon spectra of the target product obtained in Example 6, respectively.

[0025] Figure 13 and Figure 14 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 7, respectively.

[0026] Figure 15 and Figure 16 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 8, respectively.

[0027] Figure 17 and Figure 18 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 9, respectively.

[0028] Figure 19 and Figure 20 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 10, respectively.

[0029] Figure 21 and Figure 22 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 11, respectively.

[0030] Figure 23 and Figure 24 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 12, respectively. Specific implementation methods The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings, but the scope of protection and implementation of the present invention are not limited thereto.

[0031] Example 1 2-Naphthylamine (0.2 mmol), benzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate, and the mixture was washed twice with saturated NaCl solution. The upper organic phase was collected, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product in 79% yield. The proton and carbon spectra of the obtained target product are shown below. Figure 1 and Figure 2 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.16-8.14 (m, 2H), 8.12 (s, 1H), 8.10 (s,1H), 8.03 (d, J= 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.62-7.59 (m, 1H), 7.56-7.51 (m, 4H); 13 C NMR (CDCl3, 125 MHz) δ 167.2, 152.2, 133.7, 132.2, 131.1, 130.7, 129.1, 129.1, 128.1, 127.5, 127.4, 127.1, 126.0, 125.2, 121.7.

[0032] Based on the above data, the structure of the target product is inferred as follows: .

[0033] Example 2 2-Naphthylamine (0.2 mmol), 4-methylbenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 83%.

[0034] The proton and carbon spectra of the obtained target product are as follows: Figure 3 and Figure 4 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.09 (d, J = 8.5 Hz, 1H), 8.03 (t, J = 8.5Hz, 3H), 7.95 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.60-7.57 (m,1H), 7.55-7.51 (m, 1H), 7.30 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H); 13 C NMR (CDCl3, 125 MHz) δ167.4, 152.2, 141.1, 131.9, 131.0, 130.9, 129.7, 128.9, 128.1, 127.3, 127.2, 126.9, 125.8, 125.1, 121.6, 21.5.

[0035] Based on the above data, the structure of the target product is inferred as follows: .

[0036] Example 3 2-Naphthylamine (0.2 mmol), 4-tert-butylbenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 90%.

[0037] The proton and carbon spectra of the obtained target product are as follows: Figure 5 and Figure 6 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.12–8.08 (m, 3H), 8.04 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 9.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H),7.56-7.53 (m, 3H), 1.39 (s, 9H); 13 C NMR (CDCl3, 125 MHz) δ 167.3, 154.3, 152.3, 132.0, 131.0, 129.0, 128.1, 127.3, 127.1, 126.9, 126.0, 125.9, 125.2, 121.7, 35.0, 31.2.

[0038] Based on the above data, the structure of the target product is inferred as follows: .

[0039] Example 4 2-Naphthylamine (0.2 mmol), 4-fluorobenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 68%.

[0040] The proton and carbon spectra of the obtained target product are as follows: Figure 7 and Figure 8 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.12–8.07 (m, 3H), 8.00 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.61-7.58 (m, 1H), 7.56-7.53 (m, 1H), 7.19 (t, J = 7.0 Hz, 2H); 13 C NMR (CDCl3, 125 MHz) δ 165.8, 164.2(d, J = 250.0 Hz), 152.1, 132.1, 129.9 (d, J = 3.1 Hz), 129.2 (d, J = 8.6Hz), 129.0, 128.0, 127.5, 127.0, 126.0, 125.1, 121.6, 116.1 (d, J = 22.0 Hz).

[0041] Based on the above data, the structure of the target product is inferred as follows: .

[0042] Example 5 2-Naphthylamine (0.2 mmol), 4-(trifluoromethyl)benzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 61%.

[0043] The proton, carbon, and fluorine spectra of the obtained target product are as follows: Figure 9 and Figure 10 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) 1 H NMR (CDCl3, 500 MHz) δ 8.23 (d, J = 8.0 Hz, 2H), 8.10 (d, J = 9.0 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.63-7.56 (m, 2H); 13 CNMR (CDCl3, 125 MHz) δ 165.0, 152.2, 136.8, 132.2 (q, J = 32.4 Hz), 129.7 (q, J = 4.5 Hz), 129.1, 128.0, 127.8, 127.5, 127.2, 126.4, 126.1 (q, J = 3.6 Hz),125.2, 124.9, 122.8 (q, J = 270.8 Hz), 121.8.

[0044] Based on the above data, the structure of the target product is inferred as follows: .

[0045] Example 6 2-Naphthylamine (0.2 mmol), 3-methylbenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 91%.

[0046] The proton and carbon spectra of the obtained target product are as follows: Figure 11 and Figure 12 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.11 (d, J = 7.5 Hz, 1H), 8.03 (d, J = 8.0Hz, 1H), 7.99 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 7.0 Hz, 1H), 7.88 (d, J = 9.0 Hz, 1H), 7.61 (s, J = 7.0 Hz, 1H), 7.55 (s, J = 7.0 Hz, 1H), 7.41 (t, J = 7.0 Hz, 1H), 7.31 (d, J = 7.5 Hz, 1H), 2.48 (s, 3H); 13 C NMR (CDCl3, 125 MHz) δ 167.5, 152.1, 138.9, 133.5, 132.1, 131.6, 131.0, 129.0, 128.1, 127.8, 127.4, 127.1, 127.0, 126.0, 125.1, 124.6, 121.6, 21.4.

[0047] Based on the above data, the structure of the target product is inferred as follows: .

[0048] Example 7 2-Naphthylamine (0.2 mmol), 3-fluorobenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 69%.

[0049] The proton and carbon spectra of the obtained target product are as follows: Figure 13 and Figure 14 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.11 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 8.0Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.92-7.88 (m, 3H), 7.64-7.61 (m, 1H), 7.58-7.56 (m, 1H), 7.51-7.46 (m, 1H), 7.22-7.18 (m, 1H); 13 C NMR (CDCl3, 125MHz) δ 165.5 (d, J = 2.5 Hz), 163.5 (d, J = 246.1 Hz), 152.1, 135.7 (d, J =8.0 Hz), 132.4, 131.2, 130.7 (d, J = 8.1 Hz), 129.0, 128.0, 127.7, 127.2,126.3, 125.2, 123.1 (d, J = 2.8 Hz), 121.7, 117.6 (d, J = 21.5 Hz), 114.1 (d, J = 23.5 Hz).

[0050] Based on the above data, the structure of the target product is inferred as follows: .

[0051] Example 8 2-Naphthylamine (0.2 mmol), 3-(trifluoromethyl)benzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 74%.

[0052] The proton and carbon spectra of the obtained target product are as follows: Figure 15 and Figure 16 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.41 (s, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.09(d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.88(d, J = 7.5 Hz, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.63-7.54 (m, 3H); 13 C NMR (CDCl3, 125 MHz) δ 165.1, 152.1, 134.4, 132.4, 131.7 (q, J = 32.5 Hz), 131.2,130.3, 129.6, 129.0, 128.0, 127.8, 127.2, 127.1 (q, J = 3.6 Hz), 126.3,125.1, 124.0 (q, J = 3.7 Hz), 123.7 (q, J = 272.6 Hz), 121.7.

[0053] Based on the above data, the structure of the target product is inferred as follows: .

[0054] Example 9 2-Naphthylamine (0.2 mmol), 2-methylbenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 68%.

[0055] The proton and carbon spectra of the obtained target product are as follows: Figure 17 and Figure 18 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.14 (d, J = 9.0 Hz, 1H), 8.07(d, J = 8.0Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.86 (d, J = 7.5Hz, 1H), 7.63-7.60 (m, 1H), 7.58-7.55 (m, 1H), 7.42-7.33 (m, 3H). 2.72 (s,3H); 13 C NMR (CDCl3, 125 MHz) δ 167.0, 151.7, 137.2, 133.1, 132.7, 131.0, 130.5, 129.9, 129.0, 128.0, 127.3, 127.0, 126.2, 126.0, 125.3, 121.8, 21.5.

[0056] Based on the above data, the structure of the target product is inferred as follows: .

[0057] Example 10 2-Naphthylamine (0.2 mmol), 3,5-difluorobenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 71%.

[0058] The proton and carbon spectra of the obtained target product are as follows: Figure 19 and Figure 20 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.08 (d, J = 8.5 Hz, 1H), 8.02 (d, J = 8.0Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.67-7.56 (m,4H), 6.95-6.91 (m, 1H); 13 C NMR (CDCl3, 125 MHz) δ 164.2 (dd, J = 247.0, 12.5Hz), 162.2 (dd, J = 248.0, 12.5 Hz), 152.0, 136.6 (t, J = 8.8 Hz), 132.6,131.3, 129.1, 127.9 (d, J = 3.8 Hz), 127.2, 126.5, 125.2, 121.7, 110.2 (dd, J = 25.0, 7.5 Hz), 105.8 (t, J = 26.3 Hz).

[0059] Based on the above data, the structure of the target product is inferred as follows: .

[0060] Example 11 2-Naphthylamine (0.2 mmol), 2,4-difluorobenzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 61%.

[0061] The proton and carbon spectra of the obtained target product are as follows: Figure 21 and Figure 22 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.49 (dd, J = 8.5, 2.0 Hz, 1H), 8.12-8.08(m, 2H), 7.98 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.63-7.56 (m, 2H), 7.09-7.00 (m, 2H); 13 C NMR (CDCl3, 125 MHz) δ 162.5 (dd, J = 247.3, 12.6Hz), 159.2 (dd, J = 9.0, 3.8 Hz), 150.1, 132.7(d, J = 8.0 Hz), 131.1, 130.8 (dd, J = 8.8, 4.0 Hz), 129.0, 128.0, 127.5, 127.0, 126.1, 125.0, 121.5, 118.1(dd, J = 21.0, 4.4 Hz), 112.4 (dd, J = 20.8, 13.8 Hz), 104.5 (t, J = 25.0Hz).

[0062] Based on the above data, the structure of the target product is inferred as follows: .

[0063] Example 12 3-Methylaniline (0.2 mmol), benzyl alcohol (0.2 mmol), elemental sulfur (0.6 mmol), and elemental iodine (0.01 mmol) were added sequentially to the reaction tube. N 0.4 mL of methylpyrrolidone and a magnetic stir bar were reacted at 140 °C under a nitrogen atmosphere for 14 hours. After cooling to room temperature, the reaction solution was added to ethyl acetate and washed twice with saturated NaCl solution. The upper organic phase solution was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product with a yield of 64%.

[0064] The proton and carbon spectra of the obtained target product are as follows: Figure 23 and Figure 24 As shown, the NMR data are as follows: 1 H NMR (CDCl3, 500 MHz) δ 8.09–8.07 (m, 2H), 7.96 (d, J = 8.0 Hz, 1H),7.70 (s, 1H), 7.49-7.48 (m, 3H), 7.30 (d, J = 8.5 Hz, 1H), 2.50 (s, 3H); 13 CNMR (CDCl3, 125 MHz) δ 167.0, 152.2, 135.4, 135.2, 133.7, 130.8, 129.0, 127.9, 127.4, 122.7, 121.4, 21.5.

[0065] Based on the above data, the structure of the target product is inferred as follows: .

Claims

1. A method for synthesizing benzothiazole compounds without transition metal catalysis, characterized in that, Includes the following steps: ； An aromatic amine compound as shown in Formula I, an aromatic alcohol compound as shown in Formula II, a sulfur source as shown in Formula III, a catalyst, and a solvent are added to a reaction tube and reacted under a certain temperature and atmosphere. After the reaction is completed, the benzothiazole compound as shown in Formula IV is obtained by separation and purification. Wherein, Ar 1 It is 2-naphthyl, 3-methylphenyl; Ar 2 It is phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 3-methylphenyl, 3-fluorophenyl, 3-trifluoromethylphenyl, 2-methylphenyl, 3,5-difluorophenyl, 2,4-difluorophenyl; The catalyst is elemental iodine, sodium iodide, tetrabutylammonium iodide, hydrogen iodide, or ammonium iodide; The oxidant is elemental sulfur; The solvent is N 1-Methylpyrrolidone, acetonitrile, dichloromethane, tetrahydrofuran, ethanol N , N -Dimethylformamide; The sulfur source is elemental sulfur, potassium thiocyanate, anhydrous potassium sulfide, anhydrous sodium thiosulfate, or potassium persulfate.

2. The synthesis method according to claim 1, characterized in that, The separation and purification process is as follows: the reaction solution is added to ethyl acetate, washed and extracted twice with saturated NaCl solution, the upper organic phase solution is taken, dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography to obtain the benzothiazole compounds.

3. The synthesis method according to claim 1, characterized in that, The molar ratio of the compound represented by structural formula I to the compound represented by structural formula II is 1:1 to 1.

5.

4. The synthesis method according to claim 1, characterized in that, The molar ratio of the compound represented by structural formula I to the compound represented by structural formula III is 1:1 to 4.

5. The preparation method according to claim 1, characterized in that, The molar ratio of the catalyst to the compound shown in Formula I is 0.05 to 1.50:

1.

6. The synthesis method according to claim 1, characterized in that, The reaction time is 12-15 hours.

7. The synthesis method according to claim 1, characterized in that, The reaction temperature is 120~140℃.

8. The synthesis method according to claim 1, characterized in that, The reaction atmosphere is nitrogen, air, and oxygen.

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