DESC:FIELD OF DISCLOSURE
The present disclosure relates to a process for diazotizing aromatic amines. More particularly, the present disclosure relates to a process for diazotizing chlorotrifluoromethylaniline.
BACKGROUND
2-Chloro-4-trifluoromethylaniline is an important raw material in the process of preparation of the agrochemical Fipronil. 2-Chloro-4-trifluoromethylaniline is prepared by ammonolysis of 3,4-dichlorobenzotrifluoride. Unwanted regioisomer 2-chloro-5-trifluoromethylaniline is formed during this reaction.
2-Chloro-5-trifluoromethylaniline can be converted to the starting material 3,4-dichlorobenzotrifluoride so that it can be reused. Chemical transformation involved in this reaction is the conversion of amino group to chloro group. This transformation can be achieved by converting the amine to its diazonium salt and subsequent displacement with chloride.
Diazotization of primary amines is carried out in mineral acids using sodium nitrite. However some aromatic amines are either incompletely diazotized or not diazotized, resulting in poor yields of product.
GB1121211 discloses a reaction of 3-amino-4-chlorobenzotrifluoride (2-chloro-5-trifluoromethylaniline) with sodium nitrate and hydrochloric acid to yield 3,4-dichlorobenzotrifluoride. The yield was 60%.
Therefore, there is a need to provide a diazotization process for the transformation of 2-chloro-5-trifluoromethylaniline or 2-chloro-4-trifluoromethylaniline or a mixture thereof into diazonium salt and subsequent reaction with chloride that gives a relatively higher yield.
OBJECT
The object of the present disclosure, which at least one embodiment herein satisfies, is as follows:
It is an object of the present disclosure to prepare diazonium salt from 2-chloro-5-trifluoromethylaniline or 2-chloro-4-trifluoromethylaniline or a mixture thereof and further reaction of the diazonium salt with chloride to get a high yield of 3,4-dichlorobenzotrifluoride.
Other objects and advantages of the present disclosure will be more apparent from the following description when read in conjunction with the accompanying figures, which are not intended to limit the scope of the present disclosure.
SUMMARY
In accordance with the present disclosure there is provided a process for preparing 3,4-dichlorobenzotrifluoride; said process comprising of the following steps:
(a) reacting a compound selected from the group consisting of 2-chloro-5-trifluoromethylaniline, 2-chloro-4-trifluoromethylaniline and a mixture thereof with a diazotization reagent to obtain a diazo mass; and
(b) adding said diazo mass to a mixture of concentrated HCl and copper salt to obtain 3,4-dichlorobenzotrifluoride.
Typically, step (a) is carried out at a temperature ranging from 0°C to 40°C.
Typically, step (b) is carried out at a temperature ranging from 2°C to 60°C.
Typically, the diazotization reagent is at least one selected from a group consisting of nitrosyl sulphate and sodium nitrite.
Preferably, the diazotization reagent is nitrosyl sulphate.
Typically, the molar ratio of chloro-trifluoromethylaniline to the diazotization reagent ranges from 1:1 to 1:1.5.
Preferably, the molar ratio of chloro-trifluoromethylaniline to the diazotization reagent is 1:1.15.
Typically, the copper salt is selected from a group consisting of cuprous chloride, copper chloride, copper sulphate, and hydrates and solvates thereof.
Typically, the molar ratio of chloro-trifluoromethylaniline to the copper salt ranges from 1:1 to 1:1.5.
Preferably, the molar ratio of chloro-trifluoromethylaniline to the copper salt is 1:1.12.
DETAILED DESCRIPTION
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The description herein after, of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
2,6-Dichloro-4-trifluoromethylaniline is an intermediate in the synthesis of Fipronil. Improved method for the synthesis of 2,6-dichloro-4-trifluoromethylaniline has been described in co-pending Indian patent application no. 2611/MUM/2009. The method involves ammonolysis of 3,4-dichlorobenzotrifluoride to yield 2-chloro-4-trifluoromethylaniline which is further chlorinated to get 2,6-dichloro-4-trifluoromethylaniline.

2-Chloro-5-trifluoromethylaniline is the undesired regioisomer formed during above reaction.

In accordance with the present disclosure the undesired isomer 2-chloro-5-trifluoromethylaniline is converted back to 3,4-dichlorobenzotrifluoride using Sandmeyer reaction.
In accordance with the process of the present disclosure 2-chloro-5-trifluoromethylaniline or 2-chloro-4-trifluoromethylaniline or a mixture containing 2-chloro-5-trifluoromethylaniline and 2-chloro-4-trifluoromethylaniline, is treated with diazotization reagent to form a diazo mass.
In accordance with the present disclosure the diazotization of amine is carried out at a temperature ranging from 0°C to 40°C. The diazotization reagent used for this reaction is selected from a group consisting of nitrosyl sulphate and sodium nitrite. Preferably, the diazotization reagent is nitrosyl sulphate. The molar ratio of chloro-trifluoromethylaniline to diazotization reagent ranges from 1:1 to 1:1.5. It is found that when the molar ratio of chloro-trifluoromethylaniline to diazotization reagent is 1:1.15, the process provides improved yield and conversion.
In one embodiment of the present disclosure the diazo mass is added to a mixture of concentrated hydrochloric acid and a copper salt to form 3,4-dichlorobenzotrifluoride. This reaction is carried out at a temperature ranging from 2°C to 60°C. The copper salt is selected from a group consisting of cuprous chloride, copper chloride, copper sulphate, and hydrates and solvates thereof. The molar ratio of chloro-trifluoromethylaniline to the copper salt ranges from 1:1 to 1:1.5. It is found that when chloro-trifluoromethylaniline and the copper salt are used in a molar ratio of 1:1.12, the process provides improved yield and conversion.
Apart from this the reaction gives high yield and do not produce any major byproduct. This makes the process economic and environmentally friendly.
The present disclosure is further illustrated with the help of the following examples which are set forth for illustration purpose only and should not be construed to limit the disclosure in any way.
EXAMPLES:
Example-1:
195.5g (1mol) of CTFMA (chloro trifluoromethyl aniline) containing 55% of 2-chloro-4-trifluoromethylaniline and 45% of 2-chloro-5-trifluoromethylaniline was charged in a flask equipped with mechanical stirring. 560g of nitrosyl sulphate (purity = 26%) was added to the flask over a period of 2hrs maintaining the temperature in the range from 32 to 36°C and the reaction was continued at 32-36°C. After complete consumption of starting amine (2hrs), excess nitrosyl sulphate was destroyed with urea.
Another flask containing 400ml of concentrated HCl and 112g (1.12mol) of CuCl was cooled to 3°C. The above diazo mass was added to the flask at a temperature between 2-3°C over 2hrs. The reaction mass was maintained at this temperature for 1hr. Temperature of the reaction mass was raised to 30-32°C and maintained for 2hrs. The temperature was then further raised to 60°C and maintained for 2hrs at 60°C. The reaction mass was then cooled and filtered. The filtered solid was washed with water and dichloromethane. The filtrate was extracted with dichloromethane and the combined organic layer washed with water. The organic layer was concentrated to get 3,4-dichlorobenzotrifluoride.
Weight of concentrated mass = 188g; purity by GLC = 97%
Yield on purity = 85%, conversion = 100%
Example-2
195.5g (1mol) of CTFMA (chloro trifluoromethyl aniline) containing 55% of 2-chloro-4-trifluoromethylaniline and 45% of 2-chloro-5-trifluoromethylaniline was charged in a flask equipped with mechanical stirring. 560g of nitrosyl sulphate (purity = 26%) was added to the flask over a period of 2hrs maintaining the temperature between 32-36°C. The reaction was continued at 32-36°C. After complete consumption of starting material (2hrs) excess nitrosyl sulphate was destroyed with urea.
Another flask containing 400ml of concentrated HCl and 195g (1.12mol) of CuCl2.2H2O was cooled to 3°C. The diazo mass was added to flask maintaining the temperature between 2-3°C over 2hrs. The reaction was further maintained at this temperature for 1hr. The temperature was then raised to 30-32°C and maintained for 2hrs. The temperature was then further raised to 60°C and maintained for 2hrs. The reaction mass was then cooled and filtered. The filtered solid was washed with water and dichloromethane. The filtrate was then extracted with dichloromethane and the combined organic layer washed with water. The organic layer was concentrated to get 3,4-dichlorobenzotrifluoride.
Weight of concentrated mass = 151g; purity by GLC = 97%
Yield on purity = 68%, conversion = 100%
Example-3
195.5g (1mol) of CTFMA (chloro trifluoromethylaniline) containing 55% of 2-chloro-4-trifluoromethylaniline and 45% of 2-chloro-5-trifluoromethylaniline was charged in a flask equipped with mechanical stirring. 560g of nitrosyl sulphate (purity = 26%) was added to the reaction mixture over a period of 2hrs maintaining the temperature between 32-36°C and the reaction was continued at 32-36°C. After complete consumption of starting amine on TLC (2hrs), excess nitrosyl sulphate was destroyed with urea.
Another flask containing 400 ml of concentrated HCl and 195g (1.12mol) of CuSO4.5H2O was cooled to 3°C. The above diazo mass was added maintaining the temperature between 2-3°C for 2hrs. The reaction was further maintained at this temperature for 1hr. The temperature was then raised to 30-32°C and maintained for 2hrs. The temperature was then further raised to 60°C and maintained for 2hrs. The reaction mass was then cooled and filtered. The filtered solid was washed with water and dichloromethane. The filtrate was then extracted with dichloromethane and the combined organic layer washed with water. The organic layer was concentrated get 3,4-dichlorobenzotrifluoride.
Weight of concentrated mass = 166g; purity by GLC = 97%
Yield on purity = 75%, conversion = 100%
Example-4
Concentrated HCl (400 ml) was cooled to 5°C and 195.5g (1mol) of CTFMA (Chlorotrifluoromethylaniline) was added to the HCl solution while maintaining the temperature at 5°C. Sodium nitrite solution (73g dissolved in 200ml of water) was added to the above reaction mixture over 2 hrs while maintaining temperature of reaction mixture at 5°C. The reaction mixture was stirred at 5°C for 1 hr and then excess of HNO2 was destroyed using sulfamic acid to get diazo mass.
In another flask a mixture of 400ml concentrated HCl and 113g (1.12mol) of CuCl were cooled to 3°C. The above diazo mass was added to the flask at a temperature of 5°C over 2 hrs. Reaction mixture was maintained at this temperature till N2 evolution ceased. Temperature of the reaction mixture was then raised to 30°C in 3 hrs and maintained at 30°C for 30 min. Temperature of reaction mixture was then raised to 60°C in 2 hrs and maintained at 60°C for 2 hrs. Reaction mixture was cooled to 30°C and 1.2 liters of dichloromethane was added to it followed by stirring for 30min. The organic layer was separated and aqueous layer was extracted with 2 x 350 ml of dichloromethane. The combined organic layer was washed with water till neutral pH and concentrated to get 3,4-dichlorobenzotrifluoride.
Weight of concentrated mass = 167g; purity by GLC = 73.8%,
Yield on purity = 57%.

TECHNICAL ADVANCEMENTS AND ECONOMICAL SIGNIFICANCE

The technical advancements offered by the present disclosure include the realization of:
• Conversion of 2-chloro-5-trifluoromethylaniline or 2-chloro-4-trifluoromethylaniline or a mixture thereof to 3,4-dichlorobenzotrifluoride by the disclosed process provides an economic advantage by reducing the overall cost of Fipronil synthesis.
• The process is high yielding and does not generate any major byproduct.
• The overall process is environment friendly.

Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the invention as it existed anywhere before the priority date of this application.
While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the disclosure. These and other changes in the preferred steps of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,CLAIMS:1. A process for preparing 3,4-dichlorobenzotrifluoride; said process comprising of the following steps:
(a) reacting a compound selected from the group consisting of 2-chloro-5-trifluoromethylaniline, 2-chloro-4-trifluoromethylaniline and a mixture thereof with a diazotization reagent to obtain a diazo mass; and
(b) adding said diazo mass to a mixture of concentrated HCl and copper salt to obtain 3,4-dichlorobenzotrifluoride.

2. The process as claimed in claim 1, wherein the step (a) is carried out at a temperature ranging from 0°C to 40°C.

3. The process as claimed in claim 1, wherein the step (b) is carried out at a temperature ranging from 2°C to 60°C.

4. The process as claimed in claim 1, wherein the diazotization reagent is selected from a group consisting of nitrosyl sulphate and sodium nitrite.

5. The process as claimed in claim 1, wherein the diazotization reagent is nitrosyl sulphate.

6. The process as claimed in claim 1, wherein the molar ratio of chloro-trifluoromethylaniline to the diazotization reagent ranges from 1:1 to 1:1.5.

7. The process as claimed in claim 1, wherein the molar ratio of chloro-trifluoromethylaniline to the diazotization reagent is 1:1.15.
8. The process as claimed in claim 1, wherein the copper salt is selected from a group consisting of cuprous chloride, copper chloride, copper sulphate, and hydrates and solvates thereof.

9. The process as claimed in claim 1, wherein the molar ratio of chloro-trifluoromethylaniline to the copper salt ranges from 1:1 to 1:1.5.

10. The process as claimed in claim 1, wherein the molar ratio of chloro-trifluoromethylaniline to the copper salt is 1:1.12.