PROCESS FOR THE PREPARATION OF 2, 2-DIFLUOROBENZO-1,3-
DIOXOLECARBOXYLIC ACID
Field of the invention
The present invention relates to the process for preparing 2,2-difluorobenzo-1,3-dioxole
carboxylic acid of Formula I.
Background of the invention
Difluorobenzodioxolecarboxylic acids play an important role as precursors for the
preparation of medicaments and crop protection agents.
O
O
F
F
COOH
Formula I
The U.S Patent No. 7,524,976 describes a process for the preparation of difluorobenzo-1,3-
dioxole-5-carboxylic acid by reacting 2, 2-difluorobenzo-1,3-dioxoles with hydrogen fluoride
in the presence of boron trifluoride followed by hydrolysis in aqueous acidic or alkaline
medium. Owing to the toxicity of boron trifluoride, this process is unpracticable for
industrial use. Additionally, the yield is low and the process uses 2 moles of 2,2-
difluorobenzo-1,3-benzodioxole to produce one mole of carboxylic acid.
Another process of preparation of difluorobenzo-1, 3-dioxole-5-carboxylic acid is described
in the U.S Patent No. 4,895,871. The process involves reacting 5-bromo-2, 2 difluoro-1, 3-
benzodioxole with n-butyl lithium followed by quenching with carbon dioxide and aqueous
acidic workup. The process operates at a temperature as low as -78 degree Celsius and
employs butylated lithium which is costly. Additionally, there is handling difficulty and
hence industrially unfavourable.
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Thus, there is a need in the art to provide simple, cost-effective and industrially scalable
process for the preparation of compound of Formula I.
Summary of the Invention
The present invention provides a process for the preparation of compounds of Formula I,
comprising;
a) contacting a compound of Formula II with magnesium to obtain a reaction mixture,
b) contacting the reaction mixture of step a) with a source of carbon-dioxide to obtain a
compound of Formula I, and
O
O
F
F
X
wherein X represents a chlorine, bromine or iodine.
Formula II
c) isolating the compound of Formula I from step b).
O
O
F
F
COOH
Formula I
Detailed Description of the Invention
The present invention provides a process for the preparation of compounds of Formula I,
comprising;
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a) contacting a compound of Formula II with magnesium to obtain a reaction mixture,
b) contacting the reaction mixture of step a) with a source of carbon-dioxide to obtain a
compound of Formula I, and
O
O
F
F
X
wherein X represents a chlorine, bromine or iodine.
Formula II
c) isolating the compound of Formula I from step b).
O
O
F
F
COOH
Formula I
The compound of Formula II may be prepared by any method known in the art, for example,
method known in Indian patent application No. 2611/DEL/2014.
The carbon-dioxide may be in the form of dry ice or in gaseous form. The source of carbondioxide
is selected from an alkali metal carbonate or an alkaline earth metal carbonate. The
carbon-dioxide may be generated from alkali metal carbonate or alkaline earth metal
carbonate in combination with mineral acids selected from hydrochloric acid or sulphuric
acid. The alkali metal in alkali metal carbonate is selected from sodium and potassium. The
alkaline earth metal in alkaline earth metal carbonate is selected from magnesium, calcium,
strontium and barium.
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The step a) may take place in the presence of mineral acids. The mineral acid may be selected from the group consisting of hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid, and hydrofluoric acid, or mixture thereof.
The step a) may be carried out in the presence of an organic solvent. The organic solvent is selected from an ether solvent. The ether solvent may be selected from the group consisting of cyclopentyl methyl ether, di-tertiary-butyl ether, diethyl ether, diethylene glycol diethyl ether, diglyme, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4-dioxane, ethyl tertiary-butyl ether, methoxyethane, 2-(2-methoxyethoxy)ethanol, methyl tertiary-butyl ether, 2-methyltetrahydrofuran, morpholine, and tetrahydropyran or a mixture thereof.
The step a) may be carried at a temperature of about 0oC to about 65oC. The step a) may be aided by stirring the contents. The step a) may take place for about 6 hours to about 12 hours.
The term ‘about’ refers to a variation of 10% on the higher and lower side of specified parameter.
The compound of Formula I is isolated from step b). The compound of Formula I may be isolated by a method selected from the group consisting of filtration, evaporation, concentration, crystallization and re-crystallization or combination thereof.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example
Preparation of 2,2-difluorobenzo-1,3-dioxole-5-carboxylic acid
Magnesium turnings (11.12g, 0.464mol) and anhydrous tetrahydrofuran (600 ml) were placed in a round-bottomed flask fitted with a mechanical stirrer, reflux condenser, pressure equalizing addition funnel and drying tube. 5-Bromo-2,2-difluoro-1,3-benzodioxole (100g) was added to the flask under nitrogen atmosphere. The temperature of the reaction mass was raised to 40°C during initiation. Upon initiation, remaining 5-Bromo-2,2-difluoro-1,3-benzodioxole (100g) was added drop-wise to the reaction mass. The temperature of the
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reaction mass was maintained below 40°C. The progress of the reaction was monitored by gas chromatography. The reaction mass was then cooled to 0°C and carbon-dioxide gas was passed for 2 hours at 0°C. The raction was monitored by liquid chromatography for completion. The reaction mass was quenched with 10% HCl (230g). The organic layer was separated, concentrated to obtain solid. The solid was washed with water (50g) and dichloromethane (50g), filtered and dried at 60°C under 50mmHg for 2 hours to obtain the title compound.
Yield (%): 70
Purity (%): 99 (by liquid chromatography)

We claim:
1. A process for the preparation of a compound of Formula I, comprising;
a) contacting a compound of Formula II with magnesium to obtain a reaction mixture,
b) contacting the reaction mixture of step a) with a source of carbon-dioxide to obtain a
compound of Formula I, and
O
O
F
F
X
wherein X represents a chlorine, bromine or iodine.
Formula II
c) isolating the compound of Formula I from step b).
O
O
F
F
COOH
Formula I
2. The process as claimed in claim 1, wherein the source of carbon-dioxide is selected
from an alkali metal carbonate or an alkaline earth metal carbonate.
3. The process as claimed in claim 2, wherein the carbon-dioxide is generated from
alkali metal carbonate or alkaline earth metal carbonate in combination with mineral
acids selected from hydrochloric acid or sulphuric acid.
4. The process as claimed in claim 2 or 3, wherein the alkali metal in alkali metal
carbonate is selected from sodium and potassium.
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5. The process as claimed in claim 2 or 3, wherein the alkaline earth metal in alkaline earth metal carbonate is selected from magnesium, calcium, strontium and barium.
6. The process as claimed in claim 1, wherein the step a) takes place in the presence of mineral acids.
7. The process as claimed in claim 1, wherein the mineral acid is selected from the group consisting of hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid, and hydrofluoric acid, or mixture thereof.
8. The process as claimed in claim 1, wherein the step a) is carried out in the presence of an ether solvent selected from the group consisting of cyclopentyl methyl ether, di-tertiary-butyl ether, diethyl ether, diethylene glycol diethyl ether, diglyme, diisopropyl ether, dimethoxyethane, dimethoxymethane, 1,4-dioxane, ethyl tertiary-butyl ether, methoxyethane, 2-(2-methoxyethoxy)ethanol, methyl tertiary-butyl ether, 2-methyltetrahydrofuran, morpholine, and tetrahydropyran or a mixture thereof.
9. The process as claimed in claim 1, wherein the step a) is carried at a temperature in the range of 0oC to 65oC.
10. The process as claimed in claim 1, wherein the compound of Formula I is isolated from step b) by a method selected from the group consisting of filtration, evaporation, concentration, crystallization and re-crystallization or combination thereof.