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Derivatives of 4-polyfluoroalkyl-2,4-disubstituted pyrrole and preparation method thereof

A technology of disubstituted pyrrole and polyfluoroalkyl, which is applied in the preparation of oxime and organic chemistry, and can solve the problems of expensive, limited application range, and many synthesis steps.

Inactive Publication Date: 2014-04-30
EAST CHINA NORMAL UNIV
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

Although this type of method can effectively synthesize trifluoromethylpyrrole-containing compounds, there are many steps in the synthesis, which greatly limits its application range.
Recently, a new method has emerged for the synthesis of trifluoromethylpyrrole compounds. This method utilizes the condensation reaction of 4-trifluoroacetyl-1,3-oxazol-5 enolate with phosphine ylide or sulfur ylide reagent to obtain disubstituted or trisubstituted Substituted trifluoromethylpyrrole-containing compounds (Org.Lett., 2010, 12, 4776., Tetrahedron Lett. 2012, 53, 2782.), but the 4-trifluoroacetyl-1,3-oxo The azole-5-enolate substrate is unstable, and the reaction requires expensive butyllithium reagents, which also have very limited compatibility with functional groups

Method used

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  • Derivatives of 4-polyfluoroalkyl-2,4-disubstituted pyrrole and preparation method thereof
  • Derivatives of 4-polyfluoroalkyl-2,4-disubstituted pyrrole and preparation method thereof
  • Derivatives of 4-polyfluoroalkyl-2,4-disubstituted pyrrole and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The raw materials 3-trifluoromethyl-3-buten-1-ynylbenzene (0.2 mmol), hydroxylamine hydrochloride (0.3 mmol), and dichloromethane (2.0 ml) were placed in a reaction flask. Triethylamine (0.34 mmol) was added at 0° C. and stirred for 24 h, and the reaction was checked by TLC until the raw material disappeared completely. The solvent was distilled off under reduced pressure and the crude product was directly purified by flash column chromatography on silica gel (petroleum ether: ethyl acetate = 5: 1) to obtain pure product I-1 (32.1mg, 70 %).

[0043]

[0044] 1 H NMR (400MHz, CDCl 3 )δ7.47 (dd, J=7.7, 1.6Hz, 2H), 7.37-7.29 (m, 3H), 5.82 (s, 1H), 5.62 (brs, 1H), 4.03-3.90 (m, 1H), 3.45 (dd, J=13.2, 4.4Hz, 1H), 3.17 (dd, J=13.2, 9.6Hz, 1H). 19 F NMR (377MHz, CDCl 3 )δ-69.61. 13 C NMR (100MHz, CDCl 3 )δ131.97, 128.90, 128.33, 124.83 (q, J=278.0Hz), 121.73, 85.90, 80.13, 52.21, 36.20 (q, J=30.0Hz). MS (70eV): m / z (%): 229 (M + , 1.17), 46(100). HRMS calculation: ...

Embodiment 2

[0046]Starting material 1-methyl-4-(3-trifluoromethyl)-3-buten-1-ynylbenzene (0.2mmol), hydroxylamine hydrochloride (0.4mmol), 1,2-dichloroethane (2.0 ml) placed in the reaction flask. Tetramethylethylenediamine (0.44 mmol) was added at room temperature and stirred for 24 h. The reaction was detected by TLC until the raw material disappeared completely. The solvent was distilled off under reduced pressure and the crude product was directly purified by silica gel flash column chromatography (petroleum ether:ethyl acetate=10:1) to obtain pure product I-2 of fluorine-containing alkynyl-containing hydroxylamine compound (32.1mg, 66 %).

[0047]

Embodiment 3

[0049] The raw material 1-methoxy-4-(3-trifluoromethyl)-3-butene-1-ynylbenzene (0.2mmol), hydroxylamine hydrochloride (0.36mmol), and chloroform (1.6ml) were placed in in the reaction vial. Triethylenediamine (0.4 mmol) was added at 5° C. and stirred for 30 h, and the reaction was detected by TLC until the raw material disappeared completely. The solvent was distilled off under reduced pressure and the crude product was directly purified by flash column chromatography on silica gel (petroleum ether: ethyl acetate = 1: 1) to obtain pure product I-3 (38.9 mg, 75%).

[0050]

[0051] 1 H NMR (400MHz, CDCl 3 )δ7.40(d, J=8.8Hz, 2H), 6.83(d, J=8.8Hz, 2H), 5.99(brs, 2H), 4.02-3.87(m, 1H), 3.81(s, 3H), 3.43(dd, J=13.2, 4.4Hz, 1H), 3.15(dd, J=13.2, 9.6Hz, 1H). 19 FNMR (377MHz, CDCl 3 )δ-69.72. 13 C NMR (100MHz, CDCl 3 )δ160.00, 133.44, 124.83(q, J=278.0Hz), 113.92, 113.76, 85.92, 78.65, 78.61, 77.32, 77.00, 76.68, 55.25, 52.16, 36.12(q, J=30.0Hz).MS(70eV ): m / z (%): 259 (M ...

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Abstract

The invention discloses derivatives of 4-polyfluoroalkyl-2,4-disubstituted pyrroles as shown in a formula (II) and a preparation method thereof. The preparation method comprises the steps of dissolving fluorine-containing conjugated enyne, hydroxylamine hydrochloride and an alkali in an organic solvent, sufficiently reacting at a temperature ranging from 0 to the room temperature, removing the solvent, and obtaining fluorine-containing hydroxylamine compounds with an alkynyl group as shown in a formula (I) through column chromatography, next, dissolving the fluorine-containing hydroxylamine compounds with the alkynyl group in the organic solvent, cyclizing under co-catalysis of a gold catalyst and a protonic acid catalyst under the room temperature condition, removing the solvent, and obtaining the derivatives of the 4-polyfluoroalkyl-2,4-disubstituted pyrroles through column chromatography. The preparation method is capable of getting raw materials easily, high in yield, mild in reaction conditions, and simple to operate. The invention also provides the fluorine-containing hydroxylamine compounds with an alkynyl group as shown in the formula (I) and a preparation method thereof. The invention further provides a 2,4-disubstituted polyfluoroalkyl-containing pyrrole compound framework which plays an important role in synthesizing the substituted fluorine-containing pyrrole compounds.

Description

technical field [0001] The invention relates to a preparation method of polyfluoroalkyl pyrrole derivatives, in particular to a preparation method of 4-polyfluoroalkyl-2,4-disubstituted pyrrole derivatives, and belongs to the technical field of chemical substances and their preparation. Background technique [0002] It is well known that the selective introduction of fluorine atoms or fluorine-containing groups into organic molecules may lead to great changes in their chemical and physical properties, especially many fluorine-containing organic molecules have unique physiological activities, making them useful in the fields of medicine and biology Obtained more and more applications, so the synthetic research of fluorine-containing organic compound especially fluorine-containing heterocyclic compound becomes a focus of current organic synthetic chemistry research (C&ENews.2006,84,15., V.A.Petrov, Fluorinated Heterocyclic Compounds: Synthesis , Chemistry, and Applications; Jo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C239/10C07C239/12C07C239/18C07C239/14C07C251/48C07C249/04C07D333/20C07D213/42C07D209/48C07D207/33C07D207/333C07D207/337C07D207/335C07D409/04C07D401/04C07D403/06
Inventor 肖元晶曾琴张丽杨洁茹许冰张俊良
Owner EAST CHINA NORMAL UNIV
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