FIELD OF THE INVENTION
The present invention provides a process for preparation of 5-amino substituted phenyltriazolone of formula I.

Formula I
wherein X is selected from halogens.

BACKGROUND OF THE INVENTION
The present invention provides a process for preparing 5-amino substituted phenyltriazolone, specifically 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one, a key intermediate for preparing herbicide like sulfentrazone.
There are several methods known in the art for preparation of 5-amino substituted phenyltriazolone derivatives.
Chinese patent application No. 109748878 discloses a process for preparation of 2-(2,4-dichloro-5-aminophenyl)-4-(difluoromethyl)-2,4-dihydro-5-methyl-3H-1,2,4-triazole-3-one by reductive hydrolysis of 1-(2,4-dichloro-5-azidobenzene)-4-difluoromethyl-2,4-dihydro-5-methyl-3H-1,2,4-triazol-3-one using methanol and Pd/C catalyst.
Chinese patent application No. 104326992 discloses a preparation of 1-(5-amino-2,4-dichlorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4-triazolin-5-one by reacting 1-(5-nitro-2,4-dichlorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4-triazolin-5-one with Pd/C and methanol at 0.5MPa and 60? for 2 hours. The patent application condemns the use of Raney Nickel as a hydrogenation catalyst for safety reasons.
The use of palladium in hydrogenation gives low yield and requires high temperature that further increases the chances of degradation of product and thereby makes the process less efficient at commercial scale.
Thus, there is a need to develop a process to overcome the drawbacks of the processes known in the art.
The present invention provides a process for preparation of 5-amino substituted phenyltriazolone derivatives with higher selectivity for desired product and is a greener, more efficient, safer, and more reliable process at industrial scale.

OBJECT OF THE INVENTION
The main object of the present invention provides a simple, safe, and commercially viable process for preparation of 5-amino substituted phenyltriazolone derivatives in good yield and selectivity.

SUMMARY OF THE INVENTION
The present invention provides a process for preparation of a compound of formula I,

Formula I
wherein X is selected from halogens,
comprising a step of hydrogenating 5-nitro substituted phenyltriazolone of formula II,

Formula II
wherein X is selected from halogens,
using transition metal catalyst in a solvent to obtain the compound of formula I, wherein the hydrogenation is carried out at a temperature of 40 to 45°C and wherein the hydrogenation is performed in a continuous flow mode.

DESCRIPTION OF DRAWING
Figure 1 describes a continuous flow reactor.
A continuous flow reactor consists of a cylindrical reactor R1 packed with Raney nickel catalyst viz. equipped with dosing pumps P1 and control valve P2 having pressure gauge P. P1 and P2 are used to introduce a compound of formula II and hydrogen gas respectively, P2 is further connected with mass flow controller MFC. The reactor is further equipped with pressure gauge P and a back pressure regulator B1. The back pressure regulator is further connected with a sample collector and an outlet for product collection.

DETAILED DESCRIPTION OF THE INVENTION
In an embodiment of the present invention, the transition metal catalyst is selected from palladium on carbon, platinum on carbon and Raney nickel or the like. The molar ratio of catalyst may be selected in the range from 0.05 to 0.3.
In a preferred embodiment, the hydrogenation is performed using Raney nickel that contains nickel in the range from 70-95% and more preferably 80-90%.
In another embodiment, weight% of the catalyst with respect to the compound of formula II is in the range of 1-10% and more preferably in the range of 5-10%.
In another embodiment of the present invention, the solvent is either water or an alcohol selected from a group consisting of methanol, ethanol, propanol, isopropyl alcohol, butanol and tert-butanol or the like and a mixture thereof.
In an embodiment, the solution of compound of formula-II in a solvent and hydrogen gas are purged continuously through catalytic fixed bed of Raney Nickel.
In another embodiment, the process of the present invention is carried out in a continuous flow reactor. In continuous flow reactor, the feed of compound of formula II and hydrogen gas are continuously and simultaneously supplied to the flow reactor containing the catalyst bed, and pure compound having no unwanted impurities, is continuously separated from the continuous flow reactor.
In another embodiment of the present invention, the continuous flow reactor includes: a catalyst bed R1 packed with Raney Nickel, first input flow line for carrying compound of formula II; a second input flow line for carrying the hydrogen, the input flow lines are equipped with a pressure pumps P1 and hydrogen pressure regulator P2 and a pressure gauge P and a back pressure regulator B1, a junction at which the first and second input flow lines converge and at which the first and second input loads mix to form the reaction mixture; an internal reactor filled with catalytic bed, through which the reaction mixture is configured to flow, located at or downstream from the first junction; and a first output flow line for carrying an output load from the internal reactor.
The present invention for preparation of the compound of formula I has following advantages over the known methods:
1. The use of mild reaction condition in form of using low temperature range prevents degradation of product and improves yield significantly.
2. The mode of addition of reactant and reagent used in the reaction positively affects the product selectivity. The present inventors observed an improvement in the selectivity with slow and continuous addition of hydrogen to the reaction mixture.
3. Use of continuous flow reactor for the reaction to get 100% conversion, minimizes the impurity and thereby increases the selectivity towards the desired product significantly.
4. The process of present invention helps in efficient recycling and recovery of solvents.
5. The process of present invention is safe at commercial scale.
In another embodiment, the solvent used in the reaction are recovered, recycled and reused.
In specific embodiment, 2-(2,4-dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one is hydrogenated using molecular hydrogen in presence of Raney nickel in an alcohol solvent in a continuous flow reactor to obtain 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one).
In another specific embodiment, 2-(2,4-dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one is hydrogenated using molecular hydrogen in presence of Raney nickel in an alcohol solvent in a continuous flow reactor to obtain 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one), having 0 to 0.1% of 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities.
The hydrogenation is carried out at a temperature range of 25°C to 35°C. The low temperature range prevents the degradation of product and improves yield significantly.
In another embodiment, hydrogenation of formula II using Raney nickel catalyst in presence of solvent to obtain a compound of formula I may be carried out in a batch mode.
In another embodiment, the Raney nickel used in the reaction is advantageously increases product selectivity.
The purity of isolated compound of formula I is greater than 90% and preferably greater than 95% and more preferably in the range of 99-99.9%.
The yield of compound of formula I is greater than 85% and preferably in the range of 90-98%.
As used herein, the compound of formula II may be prepared by any method known in the art or may be obtained commercially.
The compound of formula I is isolated by any method known in the art, for example, chemical separation, extraction, acid-base neutralization, distillation, evaporation, column chromatography and filtration or a mixture thereof.
The completion of the reaction may be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC), liquid chromatography (LC) and alike.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
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: Preparation of 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) using Raney nickel catalyst in a batch mode:
2-(2,4-Dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one (3.0 g), Raney nickel (0.20 g) and methanol (57 g) were charged in 100 mL SS-316 autoclave reactor under the nitrogen gas atmosphere. The reaction mass was heated to 25-30°C and hydrogen gas was passed to reactor at 5 kg/cm2 pressure. The reaction completion was monitored by gas chromatography. After reaction completion, the reaction mass was filtered to remove the catalyst and isolated the desired product (Yield: 93-95%; 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities: 0.2-0.5%).
Example 2: Preparation of 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) using 10% Pd/C catalyst in a batch mode:
2-(2,4-Dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one (2.0 g), Pd/C (10%, 0.20 g) and methanol (20 g) were charged in 100 mL SS-316 autoclave reactor. The reaction mass was heated to 30°C and hydrogen gas was passed to reactor at 1 kg/cm2 pressure. The reaction mass was analysed by gas chromatography. After reaction completion, the reaction mass was filtered to remove the catalyst and the desired product was isolated (Yield: 50%; 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities: 0.2-0.5%).
Example 3: Preparation of 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) using 5% Pd/C catalyst in a batch mode:
2-(2,4-Dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one (2.0 g), Pd/C (5%, 0.10 g) and methanol (20 g) were charged in 100 mL SS-316 autoclave reactor. The reaction mass was heated to 30°C and hydrogen gas was passed to reactor at 1 kg/cm2 pressure. The reaction mass was analysed by gas chromatography. After reaction completion, the reaction mass was filtered to remove the catalyst and the desired product was isolated (Yield: 52%; 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities: 3.2-6.0%).
Example 4: Preparation of 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) using Pt/C catalyst in a batch mode:
2-(2,4-Dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one (2.0 g), Pt/C (1.5%, 0.20 g) and methanol (20 g) were charged in 100 mL SS-316 autoclave reactor. The reaction mass was heated to 30°C and hydrogen gas was passed to reactor at 1 kg/cm2 pressure. The reaction mass was analysed by gas chromatography. After reaction completion, the reaction mass was filtered to remove the catalyst and the desired product was isolated (Yield: 54%; 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities: 3.0-5.5%).
Example 5: Preparation of 2-(5-amino-2,4-dichlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) using Raney nickel catalyst in a continuous mode:
A solution of 2-(2,4-dichloro-5-nitrophenyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one (5.0 g) in ethanol (100 ml) was passed through Raney nickel (2.25 g) and hydrogen at 3 kg/cm2 pressure in continuous flow reactor. The reaction mas was heated to 40-45°C and residence time was 45 seconds. The reaction mass was analysed by gas chromatography. After reaction completion, the product was isolated (Yield: 95-98%; 2-(5-amino-2-chlorophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) and 2-(5-aminophenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one) impurities: 0.01%).

SRF LIMITED NO. OF SHEETS: 1
APPLICATION NO.: 202111043830 SHEET NO. 1 OF 1

Figure 1: Flow reactor.

CLAIMS:

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

Formula I
wherein X is selected from halogens,
comprising a step of hydrogenating 5-nitro substituted phenyltriazolone of formula II,

Formula II
wherein X is selected from halogens,
using transition metal catalyst in a solvent to obtain the compound of formula I, wherein the hydrogenation is carried out at a temperature of 40 to 45°C and wherein the hydrogenation is performed in a continuous flow mode.
2. The process as claimed in claim 1, wherein the transition metal catalyst used is selected from palladium on carbon, platinum on carbon and Raney nickel.
3. The process as claimed in claim 2, wherein the hydrogenation is performed using Raney nickel that contains nickel in the range from 70-95%.
4. The process as claimed in claim 1, wherein the solution of compound of formula-II in a solvent and hydrogen gas are purged continuously through catalytic fixed bed.
5. The process as claimed in claim 1, wherein the solvent used is either water or an alcohol; is selected from a group consisting of methanol, ethanol, propanol, isopropyl alcohol, butanol and tert-butanol or the like.
6. The process as claimed in claim 1, wherein the process of the present invention is carried out in a continuous flow reactor as illustrated in Figure 1.
7. The process as claimed in claim 1, wherein the process of the present invention can be carried out in a batch mode.
8. The process as claimed in claim 1, wherein the solvent used in the reaction are recovered, recycled and reused.
9. The process as claimed in claim 1, wherein the yield of compound of formula I is greater than 85% and preferably greater than 90%.