FIELD OF THE INVENTION
The present invention relates to the process for preparing 2,2-difluoro-1,3-benzodioxole. The present invention also relates to the process for preparing 2,2-dichloro-1,3-benzodioxole which is used as an intermediate in preparation of 2,2-difluoro-1,3-benzodioxole.
BACKGROUND OF THE INVENTION
2,2-difluoro-1,3-benzodioxole, is used as an important intermediate for synthesizing the agrochemical and pharmaceutical products.
The EP Patent No. 1,502,908 provides a process for the preparation of 2, 2-dichloro-1, 3-benzodioxole by reacting 1, 3-benzodioxole with chlorine in the presence of a radical initiator, in dichlorobenzotrifluoride as solvent. The 2,4-dichlorobenzotrifluoride used in the process as solvent has boiling point of 117oC, which is very close to the boiling point of 2,2-difluoro-1,3-benzodioxole (130oC). Thus, there arises a difficulty in the separation of product from solvent.
The inventors of the present invention have found a process for the preparation of fluorinated derivatives of ethers that overcome the drawbacks of the existing processes.
OBJECT OF THE INVENTION
The main object of the present invention is to provide an industrially advantageous, efficient and safe process for the preparation of 2,2-difluoro-1,3-benzodioxole.
SUMMARY OF THE INVENTION
The first aspect of the present invention relates to a process for preparation of 2,2-difluoro-1,3-benzodioxole, comprising the steps of:

a) adding an aqueous solution of a base to catechol to obtain a reaction mixture 1;
b) adding reaction mixture 1 to a mixture of phase transfer catalyst and an organic solvent;
c) heating the step b) to obtain 1,3-benzodioxole;
e) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole
f) venting out the hydrochloric acid formed;
g) reacting hydrogen fluoride with 2,2-dichloro-1,3-benzodioxole in presence of benzotrifluoride;
h) venting out excess of hydrogen fluoride; and
i) isolating 2,2-difluoro-1,3-benzodioxole.
The second aspect of the present invention relates to a process for preparation of 2,2-difluoro-1,3-benzodioxole, comprising the steps of:
a) adding an aqueous solution of a base to catechol to obtain a reaction mixture 1;
b) adding reaction mixture 1 to a mixture of phase transfer catalyst and an organic solvent;
c) heating the step b) to obtain 1,3-benzodioxole;
e) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole
f) venting out the hydrochloric acid formed; and
g) converting the compound of 2,2-dichloro-1,3-benzodioxole to 2,2-difluoro-1,3-benzodioxole.
The third aspect of the present invention relates to a process for preparation of 2,2-difluoro-1,3-benzodioxole, comprising the steps of:
a) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole
b) venting out the hydrochloric acid formed;
c) reacting hydrogen fluoride with 2,2-dichloro-1,3-benzodioxole in presence of benzotrifluoride;
d) venting out excess of hydrogen fluoride; and
e) isolating 2,2-difluoro-1,3-benzodioxole.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, the term “base” refers to sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or the like.
As used herein, fluorination refers to reacting 2,2-dichloro-1,3-benzodioxole with hydrogen fluoride.
As used herein, chlorination refers to reacting 1,3-benzodioxole with chlorine.
As used herein, the term “phase transfer catalyst” refers to quaternary salts of ammonium, phosphonium or arsonium chlorides and bromides. The examples of suitable phase transfer catalyst includes tetrabutylammonium bromide (TBAB), methyltriethylammonium chloride (MTAC), triethylbenzylammonium chloride (TBAC), tetrabutylphosphonium bromide (TBPB) or the like.
As used herein, a radical initiator refers UV light, benzoyl peroxide, diacetyl peroxide, succinyl or azobisisobutyronitrile (AIBN) are suitable. Radical initiators are used in amounts of from 0 to 10 wt .-%.
As used herein, an organic solvent used in the present invention is selected from dichloromethane, chloroform, carbontetrachloride, toluene, dimethylformamide, dimethylsulfoxide, sulfolane, chlorobenzene, nitrobenzene, acetonitrile, benzotrifluoride or the like
As used herein, the term “isolating” refers to the method used to isolate the compound from the reaction mixture. The isolation is carried out using any of the process consisting of extraction, distillation, filtration, decantation, washing, dryings or combination thereof.
As used herein, the term “venting out” refers to the method of removing the gaseous compound either by heating, purging an inert gas or both.
As used herein, the term “inert gas” refers to nitrogen, helium or argon.
In an embodiment of the first aspect, the present invention provides a process for preparation of 2,2-difluoro-1,3-benzodioxole, wherein the step b) is carried out at a temperature of 100 oC to a temperature of 120 oC at a pressure of 7 to 8 Kg/cm2.
In another embodiment of the present invention, the step of “reacting 1,3-benzodioxole with chlorine” is performed by purging chlorine gas into a mixture of 1,3-benzodioxole, AIBN catalyst and benzotrifluoride at a temperature of 80oC to a temperature of 100oC.
In another embodiment of the present invention, 2,2-dichloro-1,3-benzodioxole is not isolated and its reaction mixture with benzotrifluoride is carried forward to the next step.
In another embodiment of the present invention, the step of “reacting hydrogen fluoride with 2,2-dichloro-1,3-benzodioxole” is performed by adding hydrogen fluoride to a mixture of a 2,2-dichloro-1,3-benzodioxole and benzotrifluoride at a temperature of 0oC to a temperature of 10oC.
In another embodiment of the present invention, the unreacted hydrogen fluoride is vented out either by heating or by purging an inert gas and additionally by washing the reaction mixture with an aqueous solution of sodium bicarbonate.
EXAMPLES
Example 1: Preparation of 1,3-Benzodioxole
Tetrabutyl ammonium bromide (0.026 moles) in dichloromethane (5 moles) was added in the pressure reactor vessel at room temperature and heated to 105°C-110°C. The pressure raised up to 7-8 Kg/cm2. A mixture of catechol (1 mole) and sodium hydroxide (2.0 moles of sodium hydroxide dissolved in 20.0 moles of water), was dosed through pump to the pressure reactor for 3 hours. The pressure was raised to 7-8 Kg/cm2. The reaction mass was heated and maintained for 1.0 hours at 110°C. The pressure was gradually decreased from 8 to 4 Kg/cm2. The reaction mass was cooled down to 25-30°C. The resultant mass was filtered through Buckner funnel using Celite bed. The filtered mass was taken for layer separation. The product was washed using dichloromethane (5.0 moles). The combined crude organic layer was taken for distillation. The crude organic layer was distilled at atmospheric condition to remove dichloromethane followed by distillation at reduced pressure to obtain the titled product.
Yield: 80%
Purity: 95%
Example 2: Preparation of 1,3-Benzodioxole
Tetrabutyl phosphonium bromide (0.026 moles) in carbon tetrachloride (5 moles) was added in the pressure reactor vessel at room temperature and heated to 105°C-110°C. The pressure raised up to 7-8 Kg/cm2. A mixture of catechol (1 mole) and sodium hydroxide (2.0 moles of sodium hydroxide dissolved in 20.0 moles of water), was dosed through pump to the pressure reactor for 3 hours. The pressure was raised to 7-8 Kg/cm2. The reaction mass was heated and maintained for 1.0 hours at 110°C. The pressure was gradually decreased from 8 to 4 Kg/cm2. The reaction mass was cooled down to 25-30°C. The resultant mass was filtered through buckner funnel using celite bed. The filtered mass was taken for layer separation. The product was washed using dichloromethane (5.0 moles). The combined crude organic layer was taken for distillation. The crude organic layer was distilled at atmospheric condition to remove dichloromethane followed by distillation at reduced pressure to obtain the titled product.
Comparative Example: Preparation of 1,3-Benzodioxole
Dichloromethane (1.56 g., 100 ml.) and TBAB (0.02 moles) are placed in an autoclave, and to this mixture is added catechol (0.2 moles) and caustic soda (0.6 moles) in flake form, with agitation, at 80° C. After the reaction is completed, the titled compound is recovered by following the procedure described in Example 1, that is, the organic phase is separated, and excess methylene chloride is distilled off and recycled.
Yield: 60%
Purity: 65%
Example 3: Preparation of 2,2-dichloro-1,3-bendodioxole
Chlorine (2.05 moles) was added to a mixture of 1,3-bendodioxole (1.0 mole) in benzotrifluoride (2.0 moles) and AIBN (0.05%) at 85-95°C for 3 hours and the mass was stirred at the same temperature for one hour for reaction completion. Then the reaction mass was cooled to room temperature and the nitrogen gas was passed to remove unreacted dissolved chlorine and hydrogen chloride. The crude 2,2-dichloro-1,3-bendodioxole in benzotrifluoride is taken as such to next step.
Yield: 88%
Purity: 97%
Example 4: Preparation of 2,2-dichloro-1,3-bendodioxole
Chlorine (2.05 moles) was added to a mixture of 1,3-bendodioxole (1.0 mole) in benzotrifluoride (2.0 moles) and benzoyl peroxide (0.05moles) at 80-90°C for 2 hours and the mass was stirred at the same temperature for one hour for reaction completion. Then the reaction mass was cooled to room temperature and the nitrogen gas was passed to remove unreacted dissolved chlorine and hydrogen chloride.
The crude 2,2-dichloro-1,3-bendodioxole in benzotrifluoride is taken as such to next step.
Yield: 88%
Purity: 97%
Comparative Example: Preparation of 2,2-dichloro-1,3-bendodioxole
In a stirred apparatus with a chlorine inlet, metering, intensive condenser and gas outlet, solution of AIBN (0.05%) in 1,3-bendodioxole (1.0 mole) and chlorine (2.05 moles) are simultaneously introduced in the reactor. After termination of the dosage was blown at 130°C with nitrogen. The titled compound was distilled out.
Yield: 66%
Purity: 74%
Example 5: Preparation of 2,2-difluoro-1,3-bendodioxole
2,2-dichloro-1,3-bendodioxole (2.0 moles) was continuously added to hydrogen fluoride (4.0 moles) in an autoclave at a temperature of 0°C for 2-3 hours. After completion of the addition, the reaction mass was stirred at 0°C for an hour to achieve complete conversion. The excess hydrogen fluoride was vented off by heating the mass up to 80° and the adhered hydrogen fluoride was removed by washing with sodium by carbonate solution. Then the reaction mass was distilled through two meter distillation column under vacuum to get the product.
Yield: 86%
Purity: 94%

WE CLAIM:
1. A process for preparation of 2,2-difluoro-1,3-benzodioxole,
comprising the steps of:
a) adding an aqueous solution of a base to catechol to obtain a reaction mixture 1;
b) adding reaction mixture 1 to a mixture of phase transfer catalyst and an organic solvent;
c) heating the step b) to obtain 1,3-benzodioxole;
d) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole;
e) venting out the hydrochloric acid formed;
f) reacting hydrogen fluoride with 2,2-dichloro-1,3-benzodioxole in presence of benzotrifluoride;
g) venting out excess of hydrogen fluoride; and
h) isolating 2,2-difluoro-1,3-benzodioxole.
2. A process for preparation of 2,2-difluoro-1,3-benzodioxole,
comprising the steps of:
a) adding an aqueous solution of a base to catechol to obtain a reaction mixture 1;
b) adding reaction mixture 1 to a mixture of phase transfer catalyst and an organic solvent;
c) heating the step b) to obtain 1,3-benzodioxole;
d) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole;
e) venting out the hydrochloric acid formed; and
f) converting the compound of 2,2-difluoro-1,3-benzodioxole to 2,2-difluoro-1,3-benzodioxole.

3. A process for preparation of 2,2-difluoro-1,3-benzodioxole,
comprising the steps of:
a) reacting 1,3-benzodioxole with chlorine in presence of benzotrifluoride and a radical initiator to obtain 2,2-dichloro-1,3-benzodioxole;
b) venting out the hydrochloric acid formed;
c) reacting hydrogen fluoride with the compound of 2,2-dichloro-1,3-benzodioxole in presence of benzotrifluoride;
d) venting out excess of hydrogen fluoride; and
e) isolating 2,2-difluoro-1,3-benzodioxole.
4. The process as claimed in claims 1-2, wherein the base used in step a) is selected from a group consisting of sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate or a mixture thereof.
5. The process as claimed in claims 1-2, wherein the phase transfer catalyst used in step b) is selected from quaternary salts of ammonium, phosphonium or arsonium chlorides and bromides.
6. The process as claimed in claims 1-2, wherein the step b) is carried out at a temperature of 100oC to 120oC and at a pressure of 7 to 8 Kg/cm2.
7. The process as claimed in claims 1-3, wherein the step of chlorination is carried out at a temperature of 80oC to 100oC.
8. The process as claimed in claims 1 and 3, wherein the step of fluorination is carried out at a temperature of 0oC to 10oC.
9. The process as claimed in claims 1-3, wherein the radical initiator is selected from the group consisting of UV light, benzoyl peroxide, diacetyl peroxide, succinyl, azobisisobutyronitrile or the like.
10. The process as claimed in claims 1-2, wherein the organic solvent is selected from the group consisting of dichloromethane, chloroform, carbontetrachloride, toluene, dimethylformamide, dimethylsulfoxide, sulfolane, chlorobenzene, nitrobenzene, acetonitrile, benzotrifluoride or the like.