Preparation method of terminal alkyne based pyrazol compound

A technology for pyrazoles and compounds, which is applied in the field of preparation of pyrazoles, can solve the problems of harsh reaction conditions, poor functional group compatibility, poor atom economy and the like, and achieves the effects of short synthesis route, mild conditions and easy industrialization.

Inactive Publication Date: 2013-05-08
DALIAN UNIV OF TECH
View PDF3 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of method has the following disadvantages: using strong acid or strong base as a catalyst; harsh reaction conditions; poor functional group compatibility, etc.
Although a series of other pyrazole ring synthesis methods have been developed [see: (a) Rueping, M.; Bootwicha, T.; Baars H.; Sugiono, E.Beilstein J.Org.Chem.2011,7,1680. (b) Yoshizawa, K.; Shioiri, T. Tetrahedron Lett. 2006, 47, 4943. (c) Xu, L.-W.; Li, L.; Xia, C.-G.; Zhao, P.- Q.Helv.Chim.Acta.2004,87,3080.(d)Eddarir,S.;Cotelle,N.;Bakkour,Y.;Rolando,C.Tetrahedron Lett.2003,44,5359.], but these methods There are disadvantages such as the need for special compounds as raw materials, harsh reaction conditions, and poor atom economy.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of terminal alkyne based pyrazol compound
  • Preparation method of terminal alkyne based pyrazol compound
  • Preparation method of terminal alkyne based pyrazol compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: Synthesis of 5-Benzyl-3-phenyl-1H-pyrazole (3a)

[0036]

[0037] Accurately weigh phenylacetylene (61.3mg, 0.6mmol) and cuprous iodide (5.7mg, 0.03mmol) into a 25mL Schlenk bottle, add refined ethanol (3.0mL), and place at 90°C Expose to air in an oil bath for 8h. The reaction temperature was lowered to 50°C, and then 85% hydrazine aqueous solution (45.2 μL, 1.2 mmol) was accurately measured, added to the above reaction solution, and the temperature was raised to 60°C to continue the reaction for 20 h. After the reaction, add 10 mL of water to the reaction solution, extract 3 times with 3×10 mL of ethyl acetate, combine the organic phases, dry with anhydrous sodium sulfate for 1 h, remove the solvent under reduced pressure, and use petroleum ether / ethyl acetate as the eluent Reagent, silica gel column separation, 5-benzyl-3-phenylpyrazole yield is 80%. 1 H NMR (400MHz, CDCl 3 )δ7.68(d,J=7.2Hz,2H),7.38–7.24(m,8H),6.35(s,1H),4.01(s,2H); 13 C NMR (100MHz...

Embodiment 2

[0038] Example 2: Synthesis of 5-(4-Methylbenzyl)-3-(p-tolyl)-1H-pyrazole (3b)

[0039]

[0040] Accurately weigh 4-methylphenylacetylene (69.7mg, 0.6mmol), cuprous bromide (4.3mg, 0.03mmol), and add them to a 25mL Schlenk bottle in turn, add refined cyclohexane (3.0mL) , placed in a 90°C oil bath and exposed to air for 8h. The reaction temperature was lowered to 50°C, and then 85% hydrazine aqueous solution (67.8 μL, 1.8 mmol) was accurately measured and added to the above reaction solution, and the temperature was raised to 100°C to continue the reaction for 15 h. After the reaction, add 10 mL of water to the reaction solution, extract 3 times with 3×10 mL of ethyl acetate, combine the organic phases, dry with anhydrous sodium sulfate for 1 h, remove the solvent under reduced pressure, and use petroleum ether / ethyl acetate as the eluent Reagent, silica gel column separation, 5-(4-methylbenzyl)-3-(4-methylphenyl) pyrazole yield is 78%. 1 H NMR (400MHz, CDCl3 )δ9.74(s,1H)...

Embodiment 3

[0041] Example 3: Synthesis of 5-(3-Methylbenzyl)-3-(m-tolyl)-1H-pyrazole (3c)

[0042]

[0043] Accurately weigh 3-methylphenylacetylene (69.7mg, 0.6mmol) and cuprous chloride (3.0mg, 0.03mmol), and add them to a 25mL Schlenk bottle in turn, add refined toluene (3.0mL), and set Expose to air in 90°C oil bath for 8h. The reaction temperature was lowered to 50°C, and then 85% hydrazine aqueous solution (45.2 μL, 1.2 mmol) was accurately measured and added to the above reaction solution, and the temperature was raised to 120°C to continue the reaction for 20 h. After the reaction, add 10 mL of water to the reaction solution, extract 3 times with 3×10 mL of ethyl acetate, combine the organic phases, dry with anhydrous sodium sulfate for 1 h, remove the solvent under reduced pressure, and use petroleum ether / ethyl acetate as the eluent Reagent, silica gel column separation, 5-(3-methylbenzyl)-3-(3-methylphenyl) pyrazole yield is 80%. 1 H NMR (400MHz, CDCl 3 )δ9.49(s,1H),7.53...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the field of medical chemical industry intermediates and related chemical technologies, relates to a preparation method of a pyrazol compound and a related chemical technology, and in particular provides a method for synthesizing a novel pyrazol compound based on terminal alkyne. The preparation method is characterized in that the terminal alkyne and hydrazine are used as raw materials, and the novel pyrazol compound is synthetized in two steps by one boiler under the catalysis of Cu. The invention mainly provides the novel pyrazol ring synthetic method which has the advantages of being mild in reaction condition, excellent in functional group compatibility, wide in substrate scope, environment-friendly and the like. Because the pyrazol ring is an important biological active group and is used very widely in the medicine field, the preparation method provided by the invention has relatively high application value and social economic benefits.

Description

technical field [0001] The invention relates to the field of pharmaceutical and chemical intermediates and related chemical technologies, and relates to a preparation method of pyrazole compounds based on terminal alkyne and hydrazine as raw materials. Background technique [0002] Pyrazole compounds are a class of important biologically active molecules, which have a very wide range of applications in many fields. Pharmaceutical active molecules containing pyrazole rings, especially in medicine and pesticides, have shown excellent performance, so the synthesis of pyrazole compounds is one of the current research hotspots. The classic method for the synthesis of pyrazole rings is the cycloaddition of hydrazine and 1,3-dicarbonyl compounds or α,β-unsaturated carbonyl compounds [see: Krishnakumar, B.; Velmurugan, R.; Swaminathan, M. Catal. Commun. 2011, 12, 375.]. However, this type of method has the following disadvantages: using strong acid or strong base as a catalyst; ha...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12C07D409/14C07D401/14
Inventor 包明冯秀娟于晓强王良广
Owner DALIAN UNIV OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products