Method for preparing 4-bromo-2,3,5,6-3-fluorophenylacetic acid

A technology of tetrafluorophenylacetic acid and tetrafluorobenzene, applied in the field of 4-bromo-2, can solve the problems of polluting the environment, affecting the health of operators, etc., and achieves the effect of less environmental pollution

Active Publication Date: 2009-04-29
ZHEJIANG UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The synthetic method of traditional p-bromophenylacetic acid mainly contains p-bromobenzyl cyanide bromide-hydrolysis method, oxo synthesis (GIROUX A, NADEAU C, HAN Y.Synthesis of phenylacetic acid under rhodium-catalyzed carbonylation conditions[J].Tetrahedron Let

Method used

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  • Method for preparing 4-bromo-2,3,5,6-3-fluorophenylacetic acid
  • Method for preparing 4-bromo-2,3,5,6-3-fluorophenylacetic acid

Examples

Experimental program
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Effect test

Embodiment 1

[0030] In a 250ml three-necked flask, add 1,4-dioxane 20ml and potassium tert-butoxide 40mmol (4.12g), N 2 Under protection, 40 mmol (6.4 g) of diethyl malonate and 10 ml of 1,4-dioxane were slowly added dropwise at 50 ° C. After 1 h, the stirring was continued for 0.5 h, and then 4 mmol (0.76 g) of cuprous iodide was added. Then add 20mmol (4.94g) of 2,3,4,5,6-pentafluorobromobenzene, complete the addition in 0.5h, control the temperature to react at 110°C, finish the reaction in 18 hours, wash the reactor with hydrochloric acid and water respectively, Pour into a separatory funnel for liquid separation, extract 2-3 times with ethyl acetate, discard the water phase, evaporate the organic phase to remove the solvent and ethyl acetate under reduced pressure, and obtain a red-colored liquid after refining the residue. 1 H NMR (400MHz, CDCl 3 )δ=1.30(t, J=6Hz, 6H), 4.28(q, J=6Hz, 4H), 4.97(s, 1H). 19 F NMR (376MHz, CDCl 3 ): δ=-135.32--135.21 (m, 2F), -129.23--129.12 (m, 2F).M...

Embodiment 2

[0034] In a 250ml three-necked flask, N 2 Add 4mmol (0.76g) of cuprous iodide and 40ml of 1,4-dioxane under protection. After stirring for 10min, add 40mmol (4.12g) of potassium tert-butoxide, at 50°C N 2 Slowly add 40mmol (6.4g) of diethyl malonate dropwise under protection, and drop it over 2 hours, then add 20mmol (4.94g) of 2,3,4,5,6-pentafluorobromobenzene, react under reflux, and finish in 18 hours For the reaction, wash the reactor with hydrochloric acid and water respectively, pour into a separatory funnel to separate the liquid, extract 2-3 times with ethyl acetate, discard the water phase, and evaporate the organic phase to remove the solvent and ethyl acetate under reduced pressure.

[0035] The remaining liquid from the previous step was added to 5 times of water, 12 g of 40% NaOH was added, and after reflux hydrolysis for 5 hours, the alcohol generated during the hydrolysis process was evaporated under reduced pressure.

[0036] The above solution was extracted w...

Embodiment 3

[0038] Add 30ml of 2-methyltetrahydrofuran and 20mmol of potassium tert-butoxide (2.06g) in a 250ml three-necked flask, 2 Slowly add 20mmol (3.2g) of diethyl malonate and 10ml of 2-methyltetrahydrofuran dropwise under protection. After 1h, add 2mmol (0.38g) of cuprous iodide, and then add 2,3,4,5,6- Pentafluorobromobenzene 10mmol (2.47g), react at 80°C, finish the reaction in 20 hours, wash the reactor with hydrochloric acid and water, separate the liquids in a separatory funnel, extract 2-3 times with ethyl acetate, discard The water phase was removed, and the organic phase was evaporated under reduced pressure to remove the solvent and ethyl acetate.

[0039] The remaining liquid from the previous step was added to 5 times the volume of water, 6 g of 40% NaOH was added, and after reflux hydrolysis for 3 hours, the alcohol generated during the hydrolysis process was evaporated under reduced pressure.

[0040] The above solution was extracted with ethyl acetate, the organic p...

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Abstract

The invention discloses a preparation method of 4-bromo-2, 3, 5, 6-tetrafluorobenzeneacetic acid, the structure of which is shown in formula one. The method comprises the following steps: (a) under the protection of nitrogen and a temperature ranging from 40 to 120 DEG C, 2, 3, 4, 5, 6- bromopentafluorobenzene with the structure shown in formula two and diethyl ester with the structure shown in formula three perform nucleophilic substitution with the catalysis of cuprous salt and under the effect of strong base, and an intermediate 2-(4-bromo-2, 3, 5, 6-phenyl tetrafluoride) diethyl ester with the structure shown in formula four is obtained; inorganic base and water are added to2-(4-bromo-2, 3, 5, 6-phenyl tetrafluoride) diethyl ester to perform hydrolysis under reflux condition; after complete hydrolysis, heating and decarboxylation, 4-bromo-2, 3, 5, 6-tetrafluorobenzeneacetic acid is obtained. The preparation method has the advantages that, the low toxic substance diethyl ester is used as the nucleophile, and the ethanol, a small amount of CO2 and other substances produced during the hydrolysis decarboxylation have less environment pollution, so the method has environmental advantages.

Description

(1) Technical field [0001] The invention relates to a new preparation method of 4-bromo-2,3,5,6-tetrafluorophenylacetic acid. (2) Background technology [0002] Substituted p-bromophenylacetic acid is an important class of pharmaceutical and chemical intermediates, widely used in organic and pharmaceutical synthesis, in addition to the application of pesticides and medicine, it can also be used as ink dispersant itself, and can also be used in the synthesis of coatings , dyes, liquid crystal materials, insulating polymer materials, etc. The 4-bromo-2,3,5,6-tetrafluorophenylacetic acid studied in the present invention has potential effects in intermediates such as medicine, pesticides, liquid crystal materials, etc., such as being used in the middle of drugs such as antifungal and anti-arteriosclerosis (US4243609) Synthesis of the body (synthesis of 1-amino-2,3,5,6-tetrafluorophenylacetic acid). [0003] The synthetic method of traditional p-bromophenylacetic acid mainly co...

Claims

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Application Information

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IPC IPC(8): C07C63/70C07C51/353
Inventor 俞传明苏为科郑飞何仁宝王莺妹章正秋
Owner ZHEJIANG UNIV OF TECH
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