Field of invention
The present invention provides a process for the preparation of 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline and its salts.
Background of the invention
The JP Patent No. 4126638 discloses use of expensive iodo-perfluoroalkyl as a raw material for the preparation of perfluoroalkyl substituted aniline, thus, making the process unfavourable for large scale industrial manufacturing.
The JP Publication No. 2003-335735 describes a process for the preparation of perfluoroalkyl substituted aniline by treating perfluoroalkyl chloride with substituted aniline wherein the molar ratio of perfluoroalkyl chloride used is double to that of substituted aniline. Furthermore, extremely low yield of around 30 % and extended reaction time makes the disclosed process extremely expensive and industrially unfavorable.
The high molar ratio of perfluoroalkyl chloride leads to the formation of impurity, thus resulting in extremely low yield of desired product.
Summary of the invention
The present invention provides a process for the preparation of compound of Formula I and its salts comprising:
3
Formula I
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl,
a) contacting a compound of Formula II with a compound of Formula III to obtain a
compound of Formula I, wherein the compound of Formula II and the compound of
Formula III are contacted in a ratio of 1 to 1.5 mol of the compound of Formula II to 0.5
to 1 mol of the compound of Formula III,
F
Br
F
F F
F
F
F
NH2
R1
R2 R4
R3
Formula II Formula III
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl,
b) optionally contacting the compound of Formula I with an acid to obtain a salt of
compound of Formula I, and
c) isolating the compound of Formula I from step a) or the salt of compound of Formula I
from step b).
Detailed description of the invention
4
In an aspect, the present invention provides a process for the preparation of compound of
Formula I and its salts comprising:
Formula I
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl,
a) contacting a compound of Formula II with a compound of Formula III to obtain a
compound of Formula I, wherein the compound of Formula II and the compound of
Formula III are contacted in a ratio of 1 to 1.5 mol of the compound of Formula II to 0.5
to 1 mol of the compound of Formula III,
F
Br
F
F F
F
F
F
NH2
R1
R2 R4
R3
Formula II Formula III
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl,
b) optionally contacting the compound of Formula I with an acid to obtain a salt of
compound of Formula I, and
5
c) isolating the compound of Formula I from step a) or the salt of compound of Formula I from step b).
The compounds of Formula II and Formula III may be prepared by any method known in the art or may be commercially obtained.
The compound of Formula II may be contacted with compound of Formula III at a temperature of about 10oC to about 30oC, for about 1 hour to about 4 hours.
The compound of Formula II may be contacted with compound of Formula III in the presence of phase transfer catalyst and sodium dithionate. The phase transfer catalyst may be selected from a group consisting of tetra butyl ammonium hydrogen sulfate, tetrabutyl phosphonium bromide, tetrabutyl ammonium bromide, tetrabutyl ammonium chloride and tetrabutyl phosphonium chloride.
The acid of step b) are selected from hydrochloride, hydrobromide and hydrosulfate or mixture thereof.
The compound of Formula I is isolated from step a) by evaporation, distillation and layer separation or mixture thereof.
The salt of compound of Formula I is isolated from step b) by filteration, precipitation, crystallization, evaporation and re-crystallization or mixture thereof.
The compound of Formula I may be 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline and its salt.
In another aspect, the compound of Formula I, as obtained by the present invention, has purity of about greater than 96%, preferably greater than 97.5%.
In yet another aspect, the salt of compound of Formula I, as obtained by the present invention, has purity of about greater than 97.5%.
Example:
Preparation of 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline and its salt
6
The heptafluoroisopropyl bromide (1.5 mol equivalents) was treated with mixture of 2-aminobenzotrifluoride (1.0 mol equivalents), water (45.0 mol equivalents), ethyl acetate (5.4 mol equivalents), sodium dithionite (1.0 mol equivalents) and tetrabutylammonium hydrogensulfate (0.1 mol equivalents) at 15oC-20oC. The aqueous solution of sodium carbonate was added and reaction mass was further stirred for 2 hours to 3 hours.
The organic layer was separated, washed with hydrochloric acid, aqueous sodium carbonate and water sequentially. The solvent was removed and swapped with toluene. Hydrogen chloride gas was purged into the solution and precipitated salt was filtered, washed with toluene and dried to get 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline hydrochloride.
Yield: = 83%
Purity: 97.6%

We claim:
1. A process for the preparation of compound of Formula I and its salts comprising:
Formula I
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl;
a) contacting a compound of Formula II with a compound of Formula III to obtain a
compound of Formula I, wherein the compound of Formula II and the compound of
Formula III are contacted in a ratio of 1 to 1.5 mol of the compound of Formula II to 0.5
to 1 mol of the compound of Formula III,
F
Br
F
F F
F
F
F
NH2
R1
R2 R4
R3
Formula II Formula III
wherein R1, R2, R3, R4 are independently selected from hydrogen, C1-C5 alkyl and C1-C5
perfluoroalkyl,
b) optionally contacting the compound of Formula I with an acid to obtain a salt of
compound of Formula I, and
c) isolating the compound of Formula I from step a) or the salt of compound of Formula I
from step b).
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2. The process as claimed in claim 1, wherein the compound of Formula II is contacted with the compound of Formula III at a temperature in the range of 10oC to 30oC for 1 hour to 4 hours.
3. The process as claimed in claim 1, wherein the compound of Formula II is contacted with the compound of Formula III in the presence of phase transfer catalyst and sodium dithionate.
4. The process as claimed in claim 3, wherein the phase transfer catalyst is selected from a group consisting of tetra butyl ammonium hydrogen sulfate, tetrabutyl phosphonium bromide, tetrabutyl ammonium bromide, tetrabutyl ammonium chloride and tetrabutyl phosphonium chloride.
5. The process as claimed in claim 1, wherein the acid used in step b) is selected from the group consisting of hydrochloride, hydrobromide and hydrosulfate or mixture thereof.
6. The process as claimed in claim 1, wherein the compound of Formula I is 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline or salt thereof.
7. The process as claimed in claim 1, wherein the compound of Formula I is isolated from step b) by evaporation, distillation and layer separation or mixture thereof.
8. The process as claimed in claim 1, wherein the salt of compound of Formula I is isolated from step b) by filteration, precipitation, crystallization, evaporation and re-crystallization or mixture thereof.
9. The process as claimed in claim 1, wherein the compound of Formula I, as obtained by the present invention has purity greater than 96%.
10. The process as claimed in claim 1, wherein the salt of compound of Formula I, as obtained by the present invention has purity greater than 97.5%.