CN111909112B - Preparation method of C2 substituted 2H-benzothiazole acylated derivative - Google Patents
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Abstract
The invention discloses a C2 substituted 2HA process for the preparation of acylated derivatives of benzothiazole. The preparation method comprises the following steps: will 2HMixing benzothiazole with substituted methylbenzene, adding oxidant K2S2O8The reaction is carried out in an air atmosphere, TLC monitoring is carried out until the reaction is finished, and the reaction solution is separated and purified to obtain C2 substituted 2H-benzothiazole acylated derivatives. The invention adopts the technology and uses K2S2O8Synthesis of C2 substitution 2 as an oxidizing agent by reaction with heating in an air atmosphereHThe method for preparing the benzothiazole acylation derivatives has the advantages of simple catalytic system, good product yield, wide substrate range and suitability for popularization and application.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to C2 substituted 2HA process for the preparation of acylated derivatives of benzothiazole.
Background
The benzothiazole and the derivative thereof have good biological activity and high structural diversity, are important drug synthesis intermediates, and have wide application prospects in the fields of medicines, pesticides and the like. In the pharmaceutical field, the compound has pharmacological activities such as antibacterial (eur. j. med. chem., 2010, 45, 1323), anti-inflammatory and analgesic (aech. pharm., 2018, 193, 249), anticancer (eur. j. med. chem., 54, 447), and the like; in the field of pesticides, they have biological activities such as insecticidal (Pharmazie, 2003, 58, 527), bactericidal (fungi, 1997, 2, 36), herbicidal (bioorg, med, chem, lett, 2016, 26, 1854), antiviral (china, j, org, chem, 2007, 27, 279), and the like. Therefore, benzothiazole and derivatives thereof become one of the important leaders for the creation of new medicines. In particular C2 acylated benzothiazoles are of high therapeutic activity and good pharmaceutical properties and are of interest, for example herbicidal properties (bioorg. med. chem. lett., 2016, 26, 1854), anti-cancer properties (j. med. chem., 2012, 55, 2469), enzymatic protein inhibitory properties (j. med. chem., 2014, 57, 10198, eur. j. med. chem., 2013, 68, 372).
2HThe acylation reaction of benzothiazole C2 is referred to as being at 2HReaction of introduction of an acyl group at position C2 of benzothiazole. According to the literature report, 2HThe methods for realizing the acylation of C2 by benzothiazole are many and mainly divided into the following three types: (1) by nucleophilic addition of metallated benzothiazoles to electrophiles (j. med. chem., 2010, 53, 7251, chem. -eur. j., 2010, 16, 3304, j. med. chem., 2008, 51, 717), but this type of approach is limited by the high reactivity, low temperature control of lithium salts. (2) Direct acylation from the carbonyl reactant gives C2 acylated benzothiazoles (j. org. chem., 2013, 78, 2792, j. org. chem., 2015, 80, 11065), which generally employ aryl ketones as carbonyl sources (adv. synth. cat. 2014, 356, 2445, Tetrahedron lett., 2013, 54, 3838), which greatly limits their application in the field of synthesis. (3) Oxidative coupling from heterocycles of 2-aminothiophenols with various substrates (org. lett., 2012, 14, 4414, Green chem., 2018, 20, 4638), however, this type of method still has some drawbacks, such as higher reaction temperature, long reaction time and cumbersome post-treatment. Therefore, it is important to search for a synthesis method with mild reaction conditions, simple operation and high product yield.
Disclosure of Invention
In view of the above problems in the prior art, the present invention is directed to providing a C2 substituted 2HA process for the preparation of acylated derivatives of benzothiazole.
One C2 substitution 2HA preparation method of (E) -benzothiazole acylated derivative, which is characterized in that 2 shown as a formula (II) is addedH-benzothiazoles andmixing the substituted methylbenzene shown as the formula (III), and adding an oxidant K2S2O8Carrying out reaction in air atmosphere, monitoring by TLC till the reaction is finished, and separating and purifying reaction liquid to obtain C2 substituted 2 shown in formula (I)H-a benzothiazole acylated derivative;
in the formula (I) and the formula (III), H on a methyl benzene ring is mono-substituted, multi-substituted or not substituted by a substituent R; n is an integer of 0-3, and n represents the number of substituent groups R on the methylbenzene ring; when n =0, it represents that H on the methylphenyl ring is unsubstituted; when n =1, represents that H on the methylphenyl ring is monosubstituted with a substituent R; when n = 2-3, the H on the methyl benzene ring is replaced by a substituent R in multiple times, and the substituent R on different substitution positions is the same or different; the substituent R is hydrogen, methyl or halogen.
One C2 substitution 2HA process for producing a benzothiazole acylated derivative, characterized in that in the formulae (I) and (III), n = an integer of 0 to 3.
One C2 substitution 2H-a process for the preparation of acylated derivatives of benzothiazole, characterized in that in the formulae (I) and (III) R is methyl, chlorine, bromine or fluorine.
One C2 substitution 2HA preparation method of a benzothiazole acylation derivative, which is characterized in that benzothiazole shown in a formula (II), substituted methylbenzene shown in a formula (III) and an oxidant K2S2O8The amount ratio of the feeding materials is 1: 5.0-50.0: 1.0-8.0, preferably 1: 15.0-25.0: 2.0-5.0.
One C2 substitution 2H-a process for the preparation of acylated derivatives of benzothiazole, characterized in that the reaction temperature is 100-130 ℃, preferably 110-125 ℃; the reaction time is 8 to 24 hours, preferably 10 to 15 hours.
One C2 substitution 2HProcess for the preparation of acylated derivatives of benzothiazole, characterised in that the reaction mixture is purified and separatedThe method comprises the following steps: after the reaction is finished, concentrating the reaction solution to remove the solvent, and carrying out column chromatography separation on the concentrated solution to obtain C2 substituted 2 shown in the formula (I)HAnd (3) benzothiazole acylation derivatives, wherein an eluant adopted by column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1-0.05: 0.1.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a new medicine composition with K2S2O8Synthesis of C2 substitution 2 as an oxidizing agent by reaction with heating in an air atmosphereHThe method has the advantages of simple catalytic system, good product yield, wide substrate range and good reaction repeatability, and is suitable for popularization and application.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
In the following examples, the structural formulae of the derivatives Ia to Il are shown in the formula (I), and the specific types of the substituents (R) n are respectively disclosed in the corresponding examples.
Example 1 synthesis of derivative Ia (n =0, (R) n = hydrogen)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), toluene (9.0 mmol, 829.3 mg), and K2S2O8(2.0 mmol, 540.6 mg) in a 25 mL Schlenk reaction tube, stirring at 120 ℃ for reaction, monitoring by TLC, after about 12 h, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (eluent is a petroleum ether-ethyl acetate mixed solvent with the volume ratio of 1: 10) to obtain a yellow solid, namely the derivative Ia. The yield thereof was found to be 85%.
The reaction mechanism of this example is as follows:
of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) 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). 13C NMR (125 MHz, CDCl3) δ 185.21, 167.01, 153.85, 136.93, 134.84, 133.83, 131.27, 128.46, 127.54, 126.85, 125.64, 122.11.
HRMS (ESI) calcd C14H10NOS [M+H]+ 240.30, found 240.46。
example 2 synthesis of derivative Ib (n =1, (R) n = p-methyl)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), p-xylene (7.5 mmol, 795.6 mg), and K2S2O8(1.0 mmol, 270.3 mg) in a 25 mL Schlenk reaction tube, stirring at 110 ℃ for reaction, monitoring by TLC, after about 10 h, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 10) to obtain a yellow solid, namely the derivative Ib. The yield thereof was found to be 89%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) 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). 13C NMR (125 MHz, CDCl3) 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.
HRMS (ESI) calcd C15H12NOS [M+H]+ 254.32, found 254.38。
example 3 synthesis of derivative Ic (n =2, (R) n = 3, 5-dimethyl)
Weighing 2H-benzothiazole (0.5 mmol, 67.6 mg),Mesitylene (7.5 mmol, 900.7 mg), and K2S2O8(1.0 mmol, 270.3 mg) was put in a 25 mL Schlenk reaction tube, stirred at 110 ℃ for reaction, 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 mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 1: 10) to give a yellow solid, i.e., derivative Ic. The yield thereof was found to be 85%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ8.24 (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). 13C NMR (125 MHz, CDCl3) 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.
HRMS (ESI) calcd C16H14NOS [M+H]+ 268.35, found 268.38。
example 4 Synthesis of derivative Id (n =1, (R) n = p-chloro)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), p-chlorotoluene (12.5 mmol, 1582.3 mg), and K2S2O8(2.5 mmol, 675.8 mg) in a 25 mL Schlenk reaction tube, stirring the mixture at 125 ℃, monitoring by TLC, after about 15 h, finishing the reaction, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 10) to obtain a yellow solid, namely the derivative Id. The yield thereof was found to be 81%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.61 – 8.56 (m, 2H), 8.26 (d, J = 7.5 Hz, 1H), 8.06 – 8.03 (m, 1H), 7.64 – 7.54 (m, 4H). 13C NMR (125 MHz, CDCl3) δ183.85, 166.72, 153.77, 140.52, 137.02, 133.11, 132.62, 128.76, 127.73, 126.93, 125.77, 122.11.
HRMS (ESI) calcd C14H9ClNOS [M+H]+ 275.74 found 275.69。
example 5 synthesis of derivative Ie (n =1, (R) n = m-chloro)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), m-chlorotoluene (12.5 mmol, 1582.3 mg), and K2S2O8(2.5 mmol, 675.8 mg) in a 25 mL Schlenk reaction tube, stirring at 125 deg.C for reaction, monitoring by TLC, after about 15 h, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 1: 10) to obtain a yellow solid, namely derivative Ie. The yield thereof was found to be 78%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ8.65 (d, J = 0.8 Hz, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.23(d, J = 9.0 Hz, 1H), 8.00 (d, J = 8.5 Hz, 1H), 7.63-7.47 (4H, m). 13C NMR (125 MHz, CDCl3) δ 183.93, 166.41, 153.79, 137.01, 136.39,134.68, 133.74, 131.13, 129.73, 129.43, 127.78, 127.03, 125.76, 122.11.
HRMS (ESI) calcd C14H9ClNOS [M+H]+ 275.74, found 275.77。
example 6 synthesis of derivative If (n =1, (R) n = o-chloro)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), o-chlorotoluene (12.5 mmol, 1582.3 mg), and K2S2O8(2.5 mmol, 675.8 mg) in a 25 mL Schlenk reaction tube, stirring at 125 deg.C for reaction, monitoring by TLC, after about 15 h, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 1: 10) to obtain a yellow solid, namely derivative If. The yield thereof was found to be 75%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ8.19-8.17 (m, 1H), 8.03-8.01 (m, 1H), 7.78-7.76 (m, 1H), 7.56-7.48 (m, 4H), 7.43-7.41 (m, 1H). 13C NMR (125 MHz, CDCl3) δ187.52, 165.78, 153.61, 137.34, 135.91, 132.41, 132.34, 130.68, 130.44, 127.91, 127.02, 126.43, 125.79.
HRMS (ESI) calcd C14H9ClNOS [M+H]+ 275.74, found 275.77。
example 7 synthesis of derivative Ig (n =1, (R) n = p-bromo)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), para-bromotoluene (10 mmol, 1699.7 mg), and K2S2O8(2.0 mmol, 540.64 mg) was placed in a 25 mL Schlenk reaction tube and stirred at 110 deg.C for about 13 h, after TLC monitoring, 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 mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 1: 20) to obtain a yellow solid, i.e., derivative Ig. The yield thereof was found to be 82%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.48 (d, J = 8.5 Hz, 2H), 8.25 (d, J = 1.0 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.62-7.54 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 184.12, 166.71, 153.82, 137.03, 133.64, 132.69, 131.81, 129.43, 127.74, 127.02, 125.71, 122.14.
HRMS (ESI) calcd C14H9BrNOS [M+H]+ 317.95, found 317.78。
example 8 synthesis of derivative Ih (n =1, (R) n = m-bromo)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), m-bromotoluene (10 mmol, 1699.7 mg), and K2S2O8(2.0 mmol, 540.64 mg) was placed in a 25 mL Schlenk reaction tube, stirred at 110 ℃ for reaction, monitored by TLC, and after about 13 hours, the reaction was complete and the reaction mixture was concentratedRemoving the solvent, and performing column chromatography separation on the concentrated solution (eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 20) to obtain a yellow solid, namely the derivative Ih. The yield thereof was found to be 80%.
Of the compound1H NMR and13the C NMR analysis data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.73 (d, J = 1.5 Hz, 1H), 8.57 (d, J = 7.5 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.91 (d, J = 8.5 Hz, 1H), 7.79 (t, J = 8.5 Hz, 1H), 7.59-7.51 (m, 2H), 7.44 (t, J = 8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 183.71, 166.32, 153.71, 137.04, 136.49, 133.91, 129.91, 129.79, 127.84, 127.02, 125.84, 122.63, 122.12.
HRMS (ESI) calcd C14H9BrNOS [M+H]+ 317.95, found 317.94。
example 9 Synthesis of derivative Ii (n =1, (R) n = ortho-bromo)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), o-bromotoluene (10 mmol, 1699.7 mg), and K2S2O8(2.0 mmol, 540.64 mg) was put into a 25 mL Schlenk reaction tube, stirred at 110 ℃ for reaction, monitored by TLC, after about 13 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 mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 1: 20) to obtain a yellow solid, i.e., derivative Ii. The yield thereof was found to be 79%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.18 (d, J = 6.0 Hz, 1H), 8.06 (d, J = 5.0 Hz, 1H), 7.75 (t, J = 7.0 Hz, 2H), 7.57 (t, J = 3.0 Hz, 2H), 7.51 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 188.22, 165.63, 153.61, 138.04, 137.41, 133.58, 132.29, 130.63, 127.91, 127.01, 125.91, 122.29, 120.51.
HRMS (ESI) calcd C14H8BrNOS [M+H]+ 317.95, found 317.88。
example 10 synthesis of derivative Ij (n =1, (R) n = p-fluoro)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), p-fluorotoluene (10 mmol, 1100.5 mg), and K2S2O8(2.0 mmol, 540.64 mg) in a 25 mL Schlenk reaction tube, stirring at 110 ℃ for reaction, monitoring by TLC, after about 12 h, concentrating the reaction solution to remove the solvent, and separating the concentrated solution by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 20) to obtain a yellow solid, namely the derivative Ij. The yield thereof was found to be 80%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.81 (q, J = 4.0 Hz, 2H), 8.37 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.70-7.63 (m, 2H), 7.33 (q, J = 7.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 183.41, 167.33, 165.13, 153.78, 136.91, 134.11, 131.23, 127.64, 125.63, 122.12, 115.73.
HRMS (ESI) calcd C14H9FNOS [M+H]+ 258.04, found 258.34。
example 11 synthesis of derivative Ik (n =1, (R) n = m-fluoro)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), p-fluorotoluene (10 mmol, 1100.5 mg), and K2S2O8(2.0 mmol, 540.64 mg) is put into a 25 mL Schlenk reaction tube, stirred at 110 ℃ for reaction, monitored by TLC, after about 12 h, the reaction is finished, the reaction solution is concentrated to remove the solvent, and the concentrated solution is separated by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 20) to obtain a yellow solid, namely the derivative Ik. The yield thereof was found to be 75%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ 8.37 (d, J = 7.6 Hz, 1H), 8.33-8.30 (m, 1H), 8.23 (d, J = 7.5 Hz, 1H), 7.99 (t, J = 7.5 Hz, 1H), 7.59-7.49 (m, 3H), 7.37-7.32 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 183.82, 166.51, 163.74, 161.22, 153.81, 137.01, 130.13, 127.84, 127.02, 125.78, 122.11, 120.91, 118.14.
HRMS (ESI) calcd C14H9FNOS [M+H]+ 258.04, found 258.28。
example 12 Synthesis of derivative Il (n =1, (R) n = ortho-fluorine)
Weighing 2HBenzothiazole (0.5 mmol, 67.6 mg), o-fluorotoluene (10 mmol, 1100.5 mg), and K2S2O8(2.0 mmol, 540.64 mg) is put in a 25 mL Schlenk reaction tube, stirred for reaction at 110 ℃, monitored by TLC, after about 12 h, the reaction is finished, the reaction solution is concentrated to remove the solvent, and the concentrated solution is separated by column chromatography (the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 1: 20) to obtain a yellow solid, namely the derivative Il. The yield thereof was found to be 70%.
Of the compound1H NMR and13the C NMR analytical data are as follows,
1H NMR (500 MHz, CDCl3) δ8.15 (d, J = 6.0 Hz, 1H), 8.00 (q, J = 2.5 Hz, 2H), 7.56-7.50 (m, 3H), 7.27 (t, J = 6.0 Hz, 1H), 7.16 (t, J = 7.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 185.22, 166.14, 162.14, 160.13, 153.62, 137.21, 134.33, 127.83, 127.01, 125.68, 124.83,123.91, 116.63.
HRMS (ESI) calcd C14H9FNOS [M+H]+ 258.04, found 258.15。
the statements in this specification merely set forth a list of implementations of the inventive concept and the scope of the present invention should not be construed as limited to the particular forms set forth in the examples.
Claims (9)
1. C2 substituted 2HA preparation method of (E) -benzothiazole acylated derivative, which is characterized in that 2 shown as a formula (II) is addedH-benzothiazoles andmixing the substituted methylbenzene shown as the formula (III), and adding an oxidant K2S2O8Carrying out reaction in air atmosphere, monitoring by TLC till the reaction is finished, and separating and purifying reaction liquid to obtain C2 substituted 2 shown in formula (I)H-a benzothiazole acylated derivative;
in the formula (I) and the formula (III), H on a methyl benzene ring is mono-substituted, multi-substituted or not substituted by a substituent R; n is an integer of 0-3, and n represents the number of substituent groups R on the methylbenzene ring; when n =0, it represents that H on the methylphenyl ring is unsubstituted; when n =1, represents that H on the methylphenyl ring is monosubstituted with a substituent R; when n = 2-3, the H on the methyl benzene ring is replaced by a substituent R in multiple times, and the substituent R on different substitution positions is the same or different; the substituent R is hydrogen, methyl or halogen.
2. A C2 substitution 2 according to claim 1HA process for the preparation of acylated derivatives of benzothiazole, characterized in that in formula (I) and formula (III) R is methyl, chloro, bromo or fluoro.
3. A C2 substitution 2 according to claim 1HA process for the preparation of acylated derivatives of benzothiazole, characterized in that (R) n is hydrogen, p-methyl, 3, 5-dimethyl, p-chloro, m-chloro, o-chloro, p-bromo, m-bromo, o-bromo, p-fluoro, m-fluoro, o-fluoro.
4. A C2 substitution 2 according to claim 1HA preparation method of a benzothiazole acylation derivative, which is characterized in that benzothiazole shown in a formula (II), substituted methylbenzene shown in a formula (III) and an oxidant K2S2O8The amount ratio of the feeding materials is 1: 5.0-50.0: 1.0-8.0.
5. A C2 substitution according to claim 12H-a process for the preparation of acylated derivatives of benzothiazole, characterized in that the reaction temperature is 100-130 ℃; the reaction time is 8-24 hours.
6. A C2 substitution 2 according to claim 1HThe preparation method of the benzothiazole acylated derivative is characterized in that the method for separating and purifying the reaction liquid comprises the following steps: after the reaction is finished, concentrating the reaction solution to remove the solvent, and carrying out column chromatography separation on the concentrated solution to obtain C2 substituted 2 shown in the formula (I)HAnd (3) benzothiazole acylation derivatives, wherein an eluant adopted by column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1-0.05: 0.1.
7. A C2 substitution 2 according to claim 1HA preparation method of a benzothiazole acylation derivative, which is characterized in that benzothiazole shown in a formula (II), substituted methylbenzene shown in a formula (III) and an oxidant K2S2O8The amount of the feed material is 1: 15.0-25.0: 2.0-5.0.
8. A C2 substitution 2 according to claim 1H-a process for the preparation of acylated derivatives of benzothiazole, characterized in that the reaction temperature is 110-125 ℃; the reaction time is 10-15 hours.
9. A C2 substituted 2 according to any one of claims 1 to 8H-a process for the preparation of acylated derivatives of benzothiazole, characterized in that the reaction is carried out in a Schlenk reaction tube.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102977050A (en) * | 2012-11-20 | 2013-03-20 | 浙江工业大学 | Method for synthesizing 2-benzothiazolyl dimethylacetal and 2-benzothiazol formaldehyde |
| CN105646343A (en) * | 2016-01-30 | 2016-06-08 | 湖南大学 | Method for synthesizing aza-aryl-phenolic-ketone compound |
| CN107216242A (en) * | 2017-07-07 | 2017-09-29 | 南京师范大学 | A kind of method of iron catalysis oxidation alkyl aromatic compound synthesis aromatic aldehyde, arone and aromatic ester |
| CN108640807A (en) * | 2018-04-25 | 2018-10-12 | 哈尔滨工业大学 | A kind of preparation method of formylated Hete rocyclic derivatives |
| CN111039893A (en) * | 2020-01-19 | 2020-04-21 | 浙江工业大学 | Preparation method of substituted benzothiazole C2 arylation derivative |
-
2020
- 2020-08-24 CN CN202010855527.8A patent/CN111909112B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102977050A (en) * | 2012-11-20 | 2013-03-20 | 浙江工业大学 | Method for synthesizing 2-benzothiazolyl dimethylacetal and 2-benzothiazol formaldehyde |
| CN105646343A (en) * | 2016-01-30 | 2016-06-08 | 湖南大学 | Method for synthesizing aza-aryl-phenolic-ketone compound |
| CN107216242A (en) * | 2017-07-07 | 2017-09-29 | 南京师范大学 | A kind of method of iron catalysis oxidation alkyl aromatic compound synthesis aromatic aldehyde, arone and aromatic ester |
| CN108640807A (en) * | 2018-04-25 | 2018-10-12 | 哈尔滨工业大学 | A kind of preparation method of formylated Hete rocyclic derivatives |
| CN111039893A (en) * | 2020-01-19 | 2020-04-21 | 浙江工业大学 | Preparation method of substituted benzothiazole C2 arylation derivative |
Non-Patent Citations (6)
| Title |
|---|
| "2-位官能团化合成2-取代苯并噻唑的研究进展";戴小强 等;《有机化学》;20171231;第37卷;第1924-1938页 * |
| "Acyl Radicals from Terminal Alkynes: Photoredox-Catalyzed Acylation of Heteroarenes";Shaista Sultan，et al.;《Chem. Eur. J.》;20180629;第24卷;第10617-10620页 * |
| "An Electrophilic Approach to the Palladium-Catalyzed Carbonylative C-H Functionalization of Heterocycles";Jevgenijs Tjutrins，et al.;《J. Am. Chem. Soc.》;20150831;第137卷;第12050-12054页 * |
| "Design and Synthesis of 2-Acylbenzothiazoles via In Situ Cross-Trapping Strategy from Benzothiazoles with Aryl Ketones";Qinghe Gao，et al.;《J. Org. Chem.》;20130220;第78卷;第2792-2797页 * |
| "Metal-, Photocatalyst-, and Light-Free Direct C-H Acylation and Carbamoylation of Heterocycles";Matthew T. Westwood，et al.;《Org. Lett.》;20190809;第21卷;第7119-7123页 * |
| "可见光诱导的无过渡金属催化交叉脱氢偶联反应研究进展";孔瑶蕾 等;《有机化学》;20190605;第39卷;第3065-3083页 * |
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