Multi-substituted pyrazole and its preparation method

A multi-substitution, pyrazole technology, applied in the direction of organic chemistry, can solve the problems of difficult synthesis of fully substituted pyrazole derivatives, poor chemoselectivity, high substrate toxicity, etc., to achieve rich product types, less dosage, and economical reaction Effect

Active Publication Date: 2020-09-08
SUZHOU UNIV
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  • Abstract
  • Description
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Problems solved by technology

For example: the most commonly used strategy is to prepare polysubstituted pyrazoles by reacting hydrazine with 1,3-dicarbonyl compounds or acetylene ketones as a substrate, but the substrate is highly toxic and has disadvantages such as poor chemoselectivity; the more direct method is 1, 3-Dipoles and alkynes undergo cycloaddition reactions to prepare polysubstituted pyrazoles. Both electron-rich diazo compounds and electron-deficient diazo compounds can be used as dipole substrates. The reaction is often initiated by Lewis acid or heat, and the resulting product Generally, it is a simple cyclization product or rearrangement product; enyne and hydrazine undergo C-N bond coupling / hydroammination series process to prepare pyrazole, but there is a problem of complex substrates
[0003] Moreover, it is difficult to synthesize fully substituted pyrazole derivatives in one step using existing synthetic methods

Method used

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  • Multi-substituted pyrazole and its preparation method
  • Multi-substituted pyrazole and its preparation method
  • Multi-substituted pyrazole and its preparation method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031]

[0032] 4-Nitrobenzenetetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0 mL), compound 1a (0.3 mmol, 52.1 mg), compound 2a (0.72 mmol, 86.5 mg) were successively charged into the reaction vial . Then the system was magnetically stirred and reacted at 40°C in air for 12 hours, quenched with ethyl acetate, removed the solvent with a rotary evaporator, adsorbed on silica gel, and the product 3a was obtained by simple column chromatography with a yield of 89% %. The main test data of the obtained product are as follows. It can be seen from the analysis that the actual synthesized product is consistent with the theoretical analysis.

[0033] 1 H NMR (400 MHz, CDCl 3 ) δ 5.28 (s, 2H), 4.32 (qd, J = 7.1, 3.2 Hz,4H), 4.28 – 4.23 (m, 2H), 4.16 (q, J = 7.1 Hz, 2H), 1.34 – 1.23 (m, 9H), 1.19(t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) 13C NMR (101 MHz, CDCL3) Δ166.29, 162.85, 159.98, 157.85, 139.64, 131.67, 121.79, 62.01, 61.79,61.50, 54.13, 13.85, 13...

Embodiment 2

[0037]

[0038] 4-Nitrobenzenetetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0 mL), compound 1b (0.3 mmol, 43.5 mg), compound 2a (0.72 mmol, 86.5 mg) were successively charged into the reaction vial . Then the system was magnetically stirred and reacted at 40°C in air for 12 hours, quenched with ethyl acetate, removed the solvent with a rotary evaporator, adsorbed on silica gel, and the product 3b / 3b` was obtained by simple column chromatography. The rate is 79%. The main test data of the obtained product are as follows. It can be seen from the analysis that the actual synthesized product is consistent with the theoretical analysis.

[0039] 1 H NMR (400 MHz, CDCl 3) δ 5.29 (s, 2H), 4.34 (m, 2H), 4.17 (m, 2H), 3.87 (s, 3H), 3.82 (s, 3H), 1.30 (m ,3H), 1.21 (m, 3H) . 13 C NMR (101 MHz, CDCl 3 ) δ 166.22, 166.20, 163.30, 163.23, 160.44, 159.96, 158.29, 157.75,139.81, 139.43, 131.94, 131.61, 121.55, 121.48, 62.13, 61.97, 61.63, 54.21,54.17, 52.79, 52.77...

Embodiment 3

[0041]

[0042] 4-Nitrobenzenetetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0 mL), compound 1c (0.3 mmol, 30.1 mg), compound 2a (0.72 mmol, 86.5 mg) were successively charged into the reaction vial . Then the system was magnetically stirred and reacted at 40°C in air for 12 hours, quenched with ethyl acetate, removed the solvent with a rotary evaporator, adsorbed on silica gel, and the product 3c / 3c` was obtained by simple column chromatography. The rate is 71%. The main test data of the obtained product are as follows. It can be seen from the analysis that the actual synthesized product is consistent with the theoretical analysis.

[0043] 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 (s, 1H), 5.39 (s, 2H), 4.42 (q, J = 7.1Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 4.27 – 4.19 (m, 2H), 1.39 (m, 6H), 1.28(m, 3H). 13 C NMR (101 MHz, CDCl 3 ) Δ 169.61, 166.93, 161.26, 159.03, 142.87,134.32, 113.81, 68.09, 61.84, 61.58, 61.26, 60.94, 54.09, 14.08,14.00, 13.98. HRMS (ESI-T...

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Abstract

The invention discloses a method for preparing polysubstituted pyrazoles, and develops a new catalytic system for aryl diazonium salts, using alkynoate and diazo ester derivatives as reaction substrates, using toluene as solvent, through cyclization / N ‑H insertion reaction to prepare polysubstituted pyrazoles. The method used in the present invention has the following characteristics: economical reaction, wider substrate universality, mild reaction conditions, can be carried out in the air, less catalyst consumption, convenient post-treatment, and is beneficial to product purification and industrial application. At the same time, the raw materials such as reactants and catalysts used in the present invention are cheap and easy to obtain, the reaction composition is reasonable, no ligand is needed, the reaction steps are few, and only one step reaction can achieve excellent yield, which meets the requirements and requirements of contemporary green chemistry and medicinal chemistry. direction.

Description

technical field [0001] The invention relates to a polysubstituted pyrazole and a preparation method thereof, belonging to the technical field of organic synthesis. Background technique [0002] Polysubstituted pyrazole is a very valuable five-membered nitrogen-containing heterocyclic skeleton with good biological activity. Its derivatives are not only widely used in insecticides and herbicides, but also have antitumor, anti-inflammatory, antibacterial, anti- Psychiatry and other applications, so it plays an important role in the fields of pesticides and medicine. At present, there are various methods for preparing polysubstituted pyrazoles, each with its own advantages and disadvantages. For example: the most commonly used strategy is to prepare polysubstituted pyrazoles by reacting hydrazine with 1,3-dicarbonyl compounds or acetylene ketones as a substrate, but the substrate is highly toxic and has disadvantages such as poor chemoselectivity; the more direct method is 1, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D231/14
CPCC07D231/14
Inventor 李海燕李辉煌龙文号廉鹏程李晶晶万小兵
Owner SUZHOU UNIV
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