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Synthesis method for 5-substituted benzofuran-2-carboxylic acid and derivatives thereof

A synthetic method, the technology of phenylpropanoid furan, which is applied in the direction of organic chemistry, can solve the problems of high cost, harsh production conditions, unsuitable for industrial production, etc., and achieve the effects of low production cost, good product quality and great practical value

Inactive Publication Date: 2013-12-18
CHIM LAB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0013] Therefore the synthetic method of above-mentioned bibliography all is not suitable for suitability for suitability for suitability for suitability for industrialized production because cost is on the high side, production conditions are harsh etc.

Method used

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  • Synthesis method for 5-substituted benzofuran-2-carboxylic acid and derivatives thereof
  • Synthesis method for 5-substituted benzofuran-2-carboxylic acid and derivatives thereof
  • Synthesis method for 5-substituted benzofuran-2-carboxylic acid and derivatives thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 15

[0030] The synthesis of embodiment 15-acetyl phenylpropanoid-2-carboxylate ethyl ester

[0031] Add 136.1g of p-acetylphenol and 1L of concentrated hydrochloric acid into a 2L three-neck flask, then add 300mL of 37% formaldehyde solution, and react at 50°C for 4h while stirring. After cooling to room temperature, the resulting red precipitate was filtered, washed with water, and dried to obtain 160.5 g of red solid which was 2-chloromethyl-4-acetylphenol, HPLC > 97%, crude product yield 86.9%. The crude product can be directly used in the next step without further purification, and a white analytically pure sample can be obtained by recrystallization from toluene or THF.

[0032] 1 H NMR (DMSO-d 6 , 400MHz): δ2.51(s, 3H, CH 3 ), 4.74 (s, 2H, CH 2 ), 6.98 (d, J=8.4Hz, 1H, BzH), 7.83 (d, J=8.4Hz, 1H, BzH), 8.01 (s, 1H, BzH), 10.85 (brs, 1H, OH).

[0033] 160g of 2-chloromethyl-4-acetylphenol and 227g of triphenylphosphine obtained in the previous step were stirred and reflu...

Embodiment 2

[0037]Embodiment 2 benzofuran-2, the synthesis of 5-dicarboxylate diethyl ester

[0038] Put 1L of hydrobromic acid into a 2L three-necked flask, then add 138.1g of p-acetylphenol and 68.5g of paraformaldehyde, and react at 60-70°C for 2 hours while stirring. Then cooled to room temperature, the resulting brown-red precipitate was filtered, washed with water, and dried to obtain 212.3 g of a red solid which was 2-bromomethyl-4-carboxyphenol, HPLC > 96%, and the yield of the crude product was 91.9%. The crude product can be directly used in the next step without further purification, and recrystallization from ethyl acetate or tetrahydrofuran can give a pale yellow analytically pure sample.

[0039] 1 H NMR (DMSO-d 6 , 400MHz): δ4.58(s, 2H, CH 2 ), 7.13 (d, J=8.4Hz, 1H, BzH), 7.98 (d, J=8.4Hz, 1H, BzH), 8.17 (s, 1H, BzH), 10.87 (brs, 1H, OH).

[0040] 210g of 2-bromomethyl-4-carboxyphenol and 238.5g of triphenylphosphine obtained in the previous step were refluxed in 1.5L o...

Embodiment 35

[0044] The synthesis of embodiment 35-chlorobenzofuran-2-carboxamide

[0045] Put 1L of concentrated hydrochloric acid into a 2L three-necked flask, then add 128.6g of p-chlorophenol and 77.1g of paraformaldehyde, and react at 60-70°C for 3h while stirring. Then cooled to room temperature, the resulting yellow precipitate was filtered, washed with water, and dried to obtain 147.6 g of a yellow solid which was 2-chloromethyl-4-chlorophenol, HPLC>96%, and the yield of the crude product was 83.4%. The crude product can be directly used in the next step without further purification, and a white analytically pure sample can be obtained by recrystallization from ethyl acetate or THF.

[0046] 1 H NMR (DMSO-d 6 , 400MHz): δ4.63(s, 2H, CH 2 ), 6.91 (d, J=8.0Hz, 1H, BzH), 7.38 (d, J=8.0Hz, 1H, BzH), 7.48 (s, 1H, BzH), 10.12 (brs, 1H, OH).

[0047] 145g of 2-chloromethyl-4-chlorophenol and 215g of triphenylphosphine obtained in the previous step were refluxed in 1L of toluene for 4h...

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Abstract

The invention discloses a synthesis method for 5-substituted benzofuran-2-carboxylic acid and the derivatives thereof. The synthesis method comprises the following steps of: 1) performing a chloromethylation reaction or a bromomethylation reaction on 4-substituted phenol to generate 2-halogenated methyl-4-substituted phenol; 2) reacting 2-halogenated methyl-4-substituted phenol with triphenylphosphine to generate 2-hydroxyl-5-substituted halogenated benzyltriphenyl phosphonium; 3) performing a ring-closing reaction on 2-hydroxyl-5-substituted halogenated benzyltriphenyl phosphonium and trichloroacetyl chloride in an alkaline condition to obtain 2-trichloromethyl-5-substituted benzofuran; and 4) performing alcoholysis on 2-trichloromethyl-5-substituted benzofuran in an acidic condition to obtain 5-substituted benzofuran-2-carboxylic ester, and then performing functional group conversion to obtain a series of derivatives. According to the synthesis method provided by the invention, cheap and easily-available raw materials are used, thus reducing production cost; and moreover, the synthesis method is simple and convenient in process, easy to enlarge, and high in implement value.

Description

technical field [0001] The invention relates to the technical field of synthesizing benzofuran compounds, in particular to a new synthesis method of 5-substituted benzofuran-2-carboxylic acid and derivatives thereof. Background technique [0002] Benzofuran compounds are a class of substances ubiquitous in nature. A large number of studies have shown that most benzofuran compounds have strong biological activity and important biological functions, mainly including antibacterial, cytotoxic, insecticidal, insect repellent and Inhibit histone deacetylase, etc., they can play an important role in the treatment of Alzheimer's disease, osteoporosis, cardiac arrhythmia, Parkinson's disease and tumors, and have broad application prospects in the fields of medicine and pesticides . [0003] Among the benzofuran compounds, 5-substituted benzofuran-2-carboxylic acid and its derivatives are an important branch, and they are important pharmaceutical intermediates. For example, 2,3-dihy...

Claims

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Application Information

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IPC IPC(8): C07D307/85
Inventor 李佶辉蓝玉明孙科炎徐晨申屠宝卿常东亮
Owner CHIM LAB
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