Description:FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

“AN IMPROVED PROCESS FOR PREPARATION OF TRIFLUOROMETHYLBENZALDEHYDES”
This patent application is a modification of the invention filed in Indian patent application No. IN201711031775 granted as Indian Patent No. IN392439

SRF LIMITED, AN INDIAN COMPANY,
SECTOR 45, BLOCK-C, UNICREST BUILDING,
GURGAON – 122003,
HARYANA (INDIA)

The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention provides an improved process for preparation of trifluoromethylbenzaldehydes.

BACKGROUND OF THE INVENTION
Trifluoromethylbenzaldehydes are useful chemical intermediates for the production of pesticides and pharmaceutical products.
Various methods for preparing trifluoromethylbenzaldehydes have been described in the prior art.
U.S. Patent No. 2,180,772 describes a process for preparation of trifluoromethylbenzaldehydes from trifluoromethylbenzalfluorides by saponification in presence of concentrated sulphuric acid at 80°C to 150°C.
The main disadvantage of this process is that the use of trifluoromethylbenzalfluoride which is prepared from trichloromethylbenzal chloride, this additional step makes the process lengthy and uneconomic.
Indian Patent No. 392439 granted to the present applicant discloses a process for preparation of trifluoromethylbenzaldehydes by hydrolysing trifluoromethylbenzal chloride to trifluoromethylbenzaldehydes using hydrolysing agent selected from a group consisting of sulphuric acid, sulphur trioxide, nitric acid, phosphoric acid, and Lewis’s acid catalyst.
It has been observed that the step of hydrolysis results in the formation of trifluoromethylbenzyl chloride as an impurity that mandates extensive distillation and results in considerable loss of yield.
The present invention aims to reduce the impurity and improve the yield of the final benzaldehyde.

OBJECT OF THE INVENTION
The main object of the present invention is to provide a simple, cost effective and an industrially applicable process for preparation of trifluoromethylbenzaldehydes that reduces the formation of corresponding benzyl chloride impurity and improves the yield of the final benzaldehyde.

SUMMARY OF THE INVENTION
In first aspect, the present invention provides a process for preparation of a compound of formula 1,

Formula 1
comprising the steps of:
a) contacting a compound of formula 2,

Formula 2
with a hydrolysing agent to obtain a mixture containing the compound of formula 1;
b) treating the mixture of step a) with an amine to isolate the compound of formula 1.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, the trifluoromethylbenzaldehydes includes 2-trifluoromethylbenzaldehyde; 3-trifluoromethylbenzaldehyde; and 4-trifluoromethylbenzaldehyde or the like.
As used herein, the “hydrolysing agent” is selected from a group consisting of sulphuric acid, sulphur trioxide, nitric acid, phosphoric acid and Lewis acid catalyst including zinc chloride, titanium chloride, boron trifluoride, tin chloride and ferric chloride or a mixture thereof. The Lewis acid catalyst is used in catalytic amount and can be recovered during the process.
The hydrolysis reaction when carried out in presence of the Lewis acid catalyst reduces the cost of the overall process by reducing the effluent load.
In a preferred embodiment of the present invention, the step of hydrolysis is carried out in the presence of sulphuric acid. In yet another preferred embodiment of the present invention, the step of hydrolysis is carried out in presence of 0.9 to 1.5 moles of sulphuric acid with respect to trifluoromethylbenzal chloride.
The hydrolysis reaction using an acid is performed by adding reaction mixture containing the acid to chilled water.
In another embodiment of the present invention, the step of hydrolysis reaction of step a) is carried out at a temperature selected in the range from 30 to 100°C.
The hydrolysis reaction is carried out at a temperature in the range from 30 to 100°C and at a pressure in the range from 3 to 60 Kg/cm2.
In another embodiment of the present invention, the mixture obtained in step a) is treated with an amine selected from a group consisting of trimethyl amine, triethyl amine, tripropyl amine, diisopropylethyl amine, tributyl amine, dimethyl amine, diethyl amine, dipropyl amine and dibutyl amine or the like.
The mixture contains corresponding benzyl chloride impurity, which is difficult to separate in distillation, owing to its close boiling point with the product.
In another embodiment of the present invention, the step b) of treatment of the mixture with an amine is carried at a temperature of 30 to 150°C.
As used herein, the mixture contains 1.0-5.0% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride and 4-trifluoromethylbenzyl chloride or the like.
In another embodiment of the present invention, the process of preparation of the compound of formula 1, comprises of:
a) hydrolysis of a compound of formula 2 to obtain a mixture 1;
b) extraction of the mixture 1 using an organic solvent;
c) neutralization of the organic layer using a base to isolate a mixture containing more than 1.0% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride and 4-trifluoromethylbenzyl chloride or the like;
d) treating the mixture with an amine to isolate pure compound of formula 1.
The base used for neutralization is selected from a group consisting of sodium carbonate, sodium bicarbonate or the like.
The organic solvent used in the extraction is the organic solvent is selected from a group consisting of dichloromethane and diethylether.
The pure compound of formula 1 has less than 0.1% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride and 4-trifluoromethylbenzyl chloride or the like. Preferably, the pure compound of formula 1 has purity of 99.8-99.95% and has 0.001 to 0.1% of benzyl chloride impurity. The pure compound of formula 1 is obtained in a yield of 90-95%.
In an embodiment of the present invention, the compound of formula 1 is isolated in a yield of 90-96% and purity of 99.5-99.9%, having 0.001-0.1% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride and 4-trifluoromethylbenzyl chloride.
As used herein, “the step of isolation” is carried out using techniques known in the art for example extraction, decantation, filtration, distillation, evaporation, column chromatography and layer separation 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.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1 (Comparative Example using sulphuric acid for hydrolysis and isolation carried out without an amine)
Sulphuric acid (94 g, 0.93 mole) was added to 1-(dichloromethyl)-3-(trifluoromethyl)benzene (200 g, 0.76 mole) in a reactor. The reaction mass was heated to a temperature of 80-90°C and water (18.7 g., 1 mole) was added using dosing pump for over 2.5 hours, while maintaining the same temperature and stirred for additional 2 hours. The progress of the reaction was monitored by GC. After completion of the reaction, the reaction mass was cooled to a temperature of 25-35°C and water (150 g.) was added over 15 minutes at 25-35°C and subsequently dichloromethane (200 g) was added. The reaction mass was stirred for 15 minutes and filtered. The layers were separated, and the aqueous layer was extracted with dichloromethane (100 g). The combined organic layer was washed with an aqueous solution of sodium bicarbonate (7%, 151 g.). The organic layer was concentrated and distilled to obtain the titled product (97% purity with 2.5% of benzyl chloride).

Example 2 (hydrolysis using sulphuric acid and isolation using an amine):
Sulphuric acid (94 g., 0.93 mole) was added to 1-(dichloromethyl)-3-(trifluoromethyl)benzene (200 g., 0.76 mole) in a reactor and was heated to a temperature of 80-90°C. Water (18.7 g., 1 mole) was added to the reaction mass using dosing pump for over 2.5 hours while maintaining the reaction at the same temperature during the water addition. The progress of the reaction was monitored by GC. After completion of the reaction, water (150 g.) was added to the reaction mass over 15 minutes while maintaining the temperature of the reaction mass at 25-35°C and subsequently dichloromethane (200 g) was added to the reaction mass and stirred the reaction mass for 15 minutes. The reaction mass was filtered, and layers were separated. The aqueous layer was extracted with dichloromethane (100 g). The combined organic layer was washed with an aqueous solution of sodium bicarbonate (7%, 151 g) and concentrated to get the crude product (97% purity with 2.5% of benzyl chloride).
Removal of 3-(trifluoromethyl)benzyl chloride impurity using triethylamine:
Triethyl amine (2.88 g, 0.03 mole) was added to the crude product (obtained in the previous example 2) and heated the reaction mass at a temperature of 95-100°C and stirred at the same temperature for 4 hours. The reaction mass was distilled to obtain the titled product (95% yield, 99.5% purity and having 0.01% of 3-trifluoromethyl benzyl chloride impurity).
Removal of 3-(trifluoromethyl)benzyl chloride impurity using diisopropyl ethylamine:
Diisopropylethylamine (3.85 g, 0.03 mole) was added to the crude product (obtained in the previous example 2) and heated the reaction mass at a temperature of 95-100°C and stirred at the same temperature for 4 hours. The reaction mass was distilled to obtain the titled product (95% yield, 99.5% purity and having 0.01% of 3-trifluoromethyl benzyl chloride impurity).
Removal of 3-(trifluoromethyl)benzyl chloride impurity using diethylamine:
Diethylamine (2.19 g, 0.03 mole) was added to the crude product (obtained in the previous example 2) and heated the reaction mass at a temperature of 95-100°C and stirred at the same temperature for 4 hours. The reaction mass was distilled to obtain the titled product (95% yield, 99.5% purity and having 0.01% of 3-trifluoromethyl benzyl chloride impurity).
Example 3 (Comparative example using ferric chloride for hydrolysis and isolation carried out without an amine)
Anhydrous ferric chloride was added to 1-(dichloromethyl)-3-(trifluoromethyl)benzene (200 g., 0.76 mole) in a reactor and heated to a temperature of 80-90°C. Water (18.7 g., 1 mole) was added using dosing pump for over 2.5 hours while maintaining the temperature to 85-90°C during the water addition. After completion of the reaction, the reaction mass was cooled to 25-35°C and water (150 g.) was added over 15 minutes at 25-35°C and subsequently dichloromethane (200 g.) was added and stirred the reaction mass for 15 minutes. The reaction mass was filtered, and the layers were separated. The aqueous layer was extracted with dichloromethane (100 g.). The combined organic layer was washed with an aqueous solution of NaHCO3 (7%, 151 g.). The organic layer was concentrated in rotary evaporator and distilled of the product gives 96% purity with 2.8% of benzyl chloride.

Example 4 (hydrolysis using ferric chloride and isolation using an amine):
The Example 3 was repeated and 3g of triethyl amine was introduced during the distillation and the product obtained was 99.8% pure with only 0.009% benzyl chloride.
Example 5 (Comparative Example using zinc chloride for hydrolysis and isolation carried out without an amine)
Zinc chloride (1.2 g., 0.009 mole) was added to 1-(dichloromethyl)-3-(trifluoromethyl)benzene (200 g., 0.76 mole) in a reactor and heated at a temperature of 80-90°C. Water (18.7 g., 1 mole) was added using dosing pump for over 2.5 hours and the temperature was maintained at 85-90°C during the water addition while maintaining the reaction mass at the same temperature for 2 hours. The progress of the reaction was monitored by GC. After completion of the reaction, the reaction mass was cooled to 25-35°C and water (150 g.) was added over 15 minutes at same temperature and subsequently dichloromethane (200 g.) was added and stirred the reaction mass for 15 minutes. The reaction mass was filtered, and layers were separated. The aqueous layer was extracted with dichloromethane (100 g.). The combined organic layer was washed with an aqueous solution of sodium bicarbonate (7%, 151 g.). The organic layer was concentrated and distilled to obtain product (97.5% purity and 2.5% of benzyl chloride).
Example 6 (hydrolysis using ferric chloride and isolation using an amine) Example 5 was repeated and 3g of triethyl amine was introduced during the distillation and the product obtained is 99.8% pure with only 0.01% benzyl chloride.
, Claims:

WE CLAIM:
1. A process for preparation of a compound of formula 1,

Formula 1
comprising the steps of:
a) contacting a compound of formula 2,

Formula 2
with a hydrolysing agent to obtain a mixture containing the compound of formula 1;
b) treating the reaction mixture of step a) with an amine to isolate the compound of formula 1.
2. The process as claimed in claim 1, wherein hydrolysing agent used in step a) is selected from a group consisting of sulphuric acid, sulphur trioxide, nitric acid, phosphoric acid and Lewis acid catalyst including zinc chloride, titanium chloride, boron trifluoride, tin chloride and ferric chloride or a mixture thereof.
3. The process as claimed in claim 1, wherein hydrolysis reaction of step a) is carried out at a temperature selected in the range from 30 to 100°C.
4. The process as claimed in claim 1, wherein an amine is selected from a group consisting of trimethyl amine, triethyl amine, tripropyl amine, diisopropylethyl amine, tributyl amine, dimethyl amine, diethyl amine, dipropyl amine and dibutyl amine.
5. The process as claimed in claim 1, wherein step b) is carried out at a temperature selected in the range from 30 to 150°C.
6. The process as claimed in claim 1, wherein the process comprises of:
a) hydrolysis of a compound of formula 2 to obtain a mixture 1;
b) extraction of the mixture 1 using an organic solvent;
c) neutralization of the organic layer using a base to isolate a mixture containing more than 1.0% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride; 4-trifluoromethylbenzyl chloride; and
d) treating the mixture with an amine to isolate pure compound of formula 1.
7. The process as claimed in claim 6, wherein the organic solvent is selected from a group consisting of dichloromethane and diethylether.

8. The process as claimed in claim 1, wherein the compound of formula 1 is isolated in a yield of 90-96% and purity of 99.5-99.9%, having 0.001-0.1% of benzyl chloride impurity selected from a group consisting of 2-trifluoromethylbenzyl chloride; 3-trifluoromethylbenzyl chloride and 4-trifluoromethylbenzyl chloride.

Dated this 31st day of October 2022.