Preparation method of C2 substituted 2H-benzothiazole acylation derivative

A technology of benzothiazolyl and benzothiazole, which is applied in the field of preparation of C2-substituted 2H-benzothiazole acylation derivatives, can solve the problems of cumbersome post-processing, long reaction time and high reaction temperature, and achieves good product yield , The catalytic system is simple, and the reaction repeatability is good.

Active Publication Date: 2020-11-10
ZHEJIANG UNIV OF TECH
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AI Technical Summary

Problems solved by technology

According to literature reports, 2 H There are many methods for C2 acylation of benzothiazole, which are mainly divided into the following three categories: (1) Nucleophilic addition of metallated benzothiazole and electrophile (J. Med. Chem., 2010, 53 , 7251, Chem.-Eur. J., 2010, 16,3304, J. Med. Chem., 2008, 51, 717), but due to the high reactivity of lithium salt and the control of low temperature, this kind of method has caused certain limitations
(2) C2 acylated benzothiazoles are obtained by direct acylation of carbonyl reactants (J. Org. Chem., 2013, 78, 2792, J. Org. Chem., 2015, 80, 11065). This type of method generally adopts Aryl ketones are used as carbonyl sources (Adv. Synth. Catal. 2014, 356, 2445, Tetrahedron Lett., 2013, 54, 3838), which greatly limits their application in the field of synthesis
(3) Oxidative coupling from 2-aminothiophenol to heterocycles of various substrates (Org. Lett., 2012, 14, 4414, Green Chem., 2018, 20, 4638), but such methods still exist Some defects, such as high reaction temperature, long reaction time and cumbersome post-processing

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  • Preparation method of C2 substituted 2H-benzothiazole acylation derivative
  • Preparation method of C2 substituted 2H-benzothiazole acylation derivative
  • Preparation method of C2 substituted 2H-benzothiazole acylation derivative

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Experimental program
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Embodiment 1

[0018] Example 1 Synthesis of derivative Ia (n=0, (R)n=hydrogen)

[0019] Weigh 2 H -Benzothiazole (0.5 mmol, 67.6 mg), toluene (9.0 mmol, 829.3 mg), and K 2 S 2 o 8 (2.0mmol, 540.6 mg) in a 25 mL Schlenk reaction tube, stirred at 120 °C, monitored by TLC, the reaction was completed after about 12 h, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent (volume ratio of petroleum ether-ethyl acetate mixed solvent of 1:10) to obtain a yellow solid, namely derivative Ia. The yield is 85%.

[0020] The reaction mechanism of this embodiment is as follows:

[0021]

[0022] of the compound 1 H NMR and 13 C NMR analysis data are described below,

[0023] 1 H NMR (500 MHz, CDCl 3 ) δ 8.58 (dd, J = 8.5, 1.5 Hz, 2H), 8.28 – 8.25 (m,1H), 8.06 – 8.03 (m, 1H), 7.71 – 7.67 (m, 1H), 7.62 – 7.56 (m, 4H). 13 C NMR (125 MHz, CDCl 3 ) δ 185.21, 167.01, 153.85, 136.93, 134.84, 133.83, 131.27,...

Embodiment 2

[0025] Example 2 Synthesis of derivative Ib (n=1, (R)n=p-methyl)

[0026] Weigh 2 H -Benzothiazole (0.5 mmol, 67.6 mg), p-xylene (7.5 mmol, 795.6 mg), and K 2 S 2 o 8 (1.0 mmol, 270.3 mg) in a 25 mL Schlenk reaction tube, stirred at 110 °C, monitored by TLC, after about 10 h, the reaction was completed, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent was The petroleum ether-ethyl acetate mixed solvent of volume ratio 1: 10) obtains yellow solid, i.e. derivative Ib. Yield 89%.

[0027] of the compound 1 H NMR and 13 C NMR analysis data are described below,

[0028] 1 H NMR (500 MHz, CDCl 3 ) δ 8.50 (d, J= 8.0 Hz, 2H), 8.28 – 8.24 (m, 1H),8.05 – 8.02 (m, 1H), 7.58 (dtd, J = 15.0, 7.0, 1.5 Hz, 2H), 7.38 (d, J = 8.0Hz, 2H), 2.49 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 184.64, 167.35, 153.81, 144.81, 136.84, 132.36, 131.34, 129.15, 127.34, 126.76, 125.54, 122.02, 21.71.

[...

Embodiment 3

[0030] Example 3 Synthesis of derivative Ic (n=2, (R)n=3, 5-dimethyl)

[0031] Weigh 2 H -Benzothiazole (0.5 mmol, 67.6 mg), mesitylene (7.5 mmol, 900.7 mg), and K 2 S 2 o 8 (1.0 mmol, 270.3 mg) in a 25 mL Schlenk reaction tube, stirred at 110 °C, monitored by TLC, after about 10 h, the reaction was completed, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent was A volume ratio of 1:10 petroleum ether-ethyl acetate mixed solvent) to obtain a yellow solid, namely the derivative Ic. The yield is 85%.

[0032] of the compound 1 H NMR and 13 C NMR analysis data are described below,

[0033] 1 H NMR (500 MHz, CDCl 3 ) δ 8.24 (d, J = 8.0 Hz, 1H), 8.10 (s, 2H), 7.98 (d, J = 8.0 Hz, 1H), 7.57-7.49 (m, 2H), 7.27 (s, 1H), 2.41 (d, J = 0.5 Hz, 6H). 13 C NMR (125 MHz, CDCl 3 ) δ 185.82, 167.24, 153.86, 138.01, 136.92, 135.62, 135.07, 128.84, 127.45, 126.75, 125.62, 122.02, 21.25.

[...

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Abstract

The invention discloses a preparation method of a C2 substituted 2Hbenzothiazole acylation derivative. The preparation method comprises the following steps: mixing 2Hbenzothiazole with substituted methyl benzene, adding an oxidizing agent K2S2O8, reacting in an air atmosphere, carrying out TLC (Thin Layer Chromatography) monitoring until the reaction is finished, and separating and purifying the reaction solution to obtain the C2 substituted 2Hbenzothiazole acylation derivative. By the adoption of the technology, K2S2O8 serves as an oxidizing agent, the C2-substituted 2Hbenzothiazole acylationderivative is synthesized through a heating reaction in the air atmosphere, and the method is simple in catalytic system, good in product yield, wide in substrate range and suitable for application and popularization.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a C2-substituted 2 H - A process for the preparation of acylated derivatives of benzothiazole. Background technique [0002] Benzothiazole and its derivatives have good biological activity and high structural diversity, and are important drug synthesis intermediates, which have broad application prospects in the fields of medicine and pesticides. In the field of medicine, it has antibacterial (Eur. J.Med. Chem., 2010, 45, 1323), anti-inflammatory and analgesic (Aech. Pharm., 2018, 193, 249), anti-cancer (Eur.J. Med. Chem., 54 , 447) and other pharmacological activities; in the field of pesticides, it has insecticidal (Pharmazie, 2003, 58,527), bactericidal (Molecules, 1997, 2, 36), herbicidal (Bioorg. Med. Chem. Lett., 2016, 26, 1854) , Antiviral (Chin. J. Org. Chem., 2007, 27, 279) and other biological activities. It can be seen that benzothiazole and its derivative...

Claims

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Application Information

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IPC IPC(8): C07D277/64
CPCC07D277/64Y02A50/30
Inventor 翁建全孔瑶蕾杨佳林
Owner ZHEJIANG UNIV OF TECH
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