A kind of preparation method of C2 substituted 2h-benzothiazole acylation derivatives

A technology of benzothiazole acyl and benzothiazole, which is applied in the field of preparation of C2 substituted 2H-benzothiazole acylation derivatives, can solve the problems of high reaction temperature, long reaction time, cumbersome post-treatment, etc., and achieve a simple catalytic system , Good product yield, suitable for popularization and application

Active Publication Date: 2022-07-08
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

Method used

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  • A kind of preparation method of C2 substituted 2h-benzothiazole acylation derivatives
  • A kind of preparation method of C2 substituted 2h-benzothiazole acylation derivatives
  • A kind of preparation method of C2 substituted 2h-benzothiazole acylation derivatives

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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 (2.0 mmol, 540.6 mg) in a 25 mL Schlenk reaction tube, stirred at 120 °C for the reaction, 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 1:10 petroleum ether-ethyl acetate mixed solvent) to obtain a yellow solid, namely derivative Ia. Yield 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 as follows,

[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 CNMR (125 MHz, CDCl 3 ) δ 185.21, 167.01, 153.85, 136.93, 134.84, 133.83, 131....

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 for the reaction, monitored by TLC, the reaction was completed after about 10 h, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent). It is a petroleum ether-ethyl acetate mixed solvent with a volume ratio of 1:10) to obtain a yellow solid, namely the derivative Ib. Yield 89%.

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

[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 =8.0 Hz, 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....

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 for reaction, monitored by TLC, the reaction was completed after about 10 h, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent). It is a petroleum ether-ethyl acetate mixed solvent with a volume ratio of 1:10) to obtain a yellow solid, namely derivative Ic. Yield 85%.

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

[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 C2 substitution 2 H -Preparation method of benzothiazole acylated derivatives. The preparation method is as follows: 2 H - Benzothiazole is mixed with the substituted methylbenzene of the oxidant K 2 S 2 O 8 , carry out the reaction in the air atmosphere, after TLC monitoring to the end of the reaction, the reaction solution is separated and purified to obtain C2 substituted 2 H - Benzothiazole Acylated Derivatives. The present invention uses the above-mentioned technology to achieve K 2 S 2 O 8 Synthetic C2-substituted 2 for oxidizing agent, heated and reacted in air atmosphere H A new method for acylation of benzothiazole derivatives, the method has simple catalytic system, good product yield and wide substrate range, and is suitable for popularization and application.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a kind of C2 substituted 2 H - Process for the preparation of benzothiazole acylated derivatives. Background technique [0002] Benzothiazole and its derivatives have good biological activity and high structural diversity, and are important intermediates in drug synthesis, 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 de...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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