The present invention provides a process for preparation of chlorinated trihalomethylpyridines. These compounds are valuable intermediates for synthesis of active agrochemical and pharmaceutical ingredients.
BACKGROUND OF THE INVENTION
Chlorinated trihalomethylpyridines such as chlorinated trifluoromethylpyridines serve as important intermediates in agrochemical industry for example for synthesis of fluazinam and fluopicolide.
Several methods for preparation of chlorinated trihalomethylpyridines are known in literature.
European Patent No. 0110690B1 discloses a process for the preparation of 2,3-
dichloro-5-trifluoromethylpyridine by reacting 2,3-dichloro-5-
trichloromethylpyridine with anhydrous hydrogen fluoride in liquid phase below 250°C in presence of metal catalyst such as FeCh, FeCl3, NbCb, TaCb, WC16, SnCU, TiCU, SbF3, FeF2, FeF3, AgF, KF, CrF2 or mixtures thereof at a pressure range of 5 to 1200 psig.
It also discloses the formation of undesired impurities such as 3-chloro-2-fluoro-5-trifluoromethylpyridine, 3-chloro-2-fluoro-5-chlorodifluoromethylpyridine and 3-chloro-2-fluoro-5-dichlorofluoromethylpyridine.
This process has several drawbacks such as poor selectivity, long batch cycle time, high pressure reaction. Also, the process fails in providing any recovery process for catalyst.
United States Patent No. 4,288,599 discloses a process for chlorinating and fluorinating P-picoline in a vapour phase at 300 to 600°C in presence of a catalyst comprising a fluoride of a metal selected from the group consisting of aluminium, chromium, iron, nickel, cobalt, manganese, chromium with aluminium, iron with aluminium, manganese with aluminium, and cobalt with aluminium, yielding a

mixtures of multi-fluoromethylated chloropyridines such as 2-chloro-5-trifluoromethylpyridine, 2-chloro-3-trifluoromethyl pyridine and 2,6-dichloro-5-trifluoromethylpyridine. As per given process, it is difficult to selectively produce chlorinated trihalomethylpyridine derivatives with a good yield and purity without formation of undesired impurities.
Therefore, there is a need in the art to develop a process, that is, economical and industrially viable and overcome the drawback of existing processes.
Indian patent application IN201911033765 filed by the present inventors discloses a process for preparation of chlorinated trifluoromethylpyridines. The inventor through this invention now presents a process for chlorinated trihalomethylpyridines having higher selectivity, yield and purity with minimum undesired impurities.
OBJECT OF THE INVENTION
The main object of present invention is to provide a highly selective and a scalable process for preparation of chlorinated trihalomethylpyridines.
SUMMARY OF THE INVENTION
The present invention provides a vapour phase process for preparation of chlorinated trifluoromethylpyridine, comprising the steps of:
a) preheating chlorinated trichloromethylpyridine and a fluorinating agent; and
b) contacting the preheated chlorinated trichloromethylpyridine and the fluorinating agent in presence of a catalyst at a temperature of 300 to 400°C,
wherein the catalyst is selected from a group consisting of chromium oxide, aluminium oxide, fluorinated chromium oxide and fluorinated aluminium oxide or a mixture thereof.

DETAILED DESCRIPTION OF THE INVENTION
In an aspect, the present invention provides a vapour phase process for preparation of dichloro trifluoromethylpyridine by fluorination of dichloro trichloromethylpyridine in presence of a catalyst at a temperature in the range of 330 to 340°C.
As used herein, the dichloro trifluoromethylpyridine is selected from 2,3-dichloro-5-trifluoromethylpyridine, 2,3-dichloro-6-trifluoromethylpyridine, 2,6-dichloro-5-trifluoromethylpyridine and 2,6-dichloro-4-trifluoromethylpyridine.
As used herein, the dichloro trichloromethylpyridine is selected from 2,3-dichloro-5-trichloromethylpyridine, 2,3-dichloro-6-trichloromethylpyridine, 2,6-dichloro-5-trichloromethyl pyridine and 2,6-dichloro-4-trichloromethylpyridine.
As used herein, fluorinating agent for present invention is anhydrous hydrogen fluoride.
In an embodiment, the present invention provides a vapour phase process for preparation of 2,3-dichloro-5-trifluoromethylpyridine by fluorinating 2,3-dichloro-5-trichloromethylpyridine using anhydrous hydrogen fluoride at a temperature in the range of 300 to 340°C.
In a specific embodiment, 2,3-dichloro-5-trichlororomethylpyridine and anhydrous hydrogen fluoride are preheated at a temperature range of 250-290°C before contacting with the catalyst.
In an embodiment, fluorination is conducted in presence of diluent such as oxygen, nitrogen and argon. The presence of diluent helps in controlling carbonization.
In another embodiment, fluorination is conducted without using any diluent.
In a preferred embodiment, the preheated 2,3-dichloro-5-trichlororomethyl pyridine and anhydrous hydrogen fluoride are supplied at a rate of 1.5 g/min and the oxygen is supplied at a rate of 60 cc/min to 500 cc/min.
In an embodiment, the reaction mass obtained after fluorination is added to ice-cooled water and extracted with water immiscible solvents. The organic layer thus

obtained is distilled to obtain crude reaction mass. The crude reaction mass is then further distilled to obtain pure compound.
The water immiscible solvents are selected from a group consisting of dichloromethane, chloroform, carbon tetrachloride, toluene and xylene or a mixture thereof.
The dichloro trifluoromethylpyridine is obtained with a selectivity of greater than 90%; yield of more than 90% and purity of more than 99%.
In an embodiment, the dichloro trifluoromethylpyridine is obtained with undesired
impurities i.e., 3-chloro-2-fluoro-5-trifluoromethylpyridine, 3-chloro-2-fluoro-5-
chlorodifluoromethylpyridine and 3-chloro-2-fluoro-5-
dichlorofluoromethylpyridine below 0.5%.
In an embodiment, the dichloro trifluoromethyl pyridine is obtained with undesired
impurities i.e., 3-chloro-2-fluoro-5-trifluoromethylpyridine, 3-chloro-2-fluoro-5-
chlorodifluoromethylpyridine and 3-chloro-2-fluoro-5-
dichlorofluoromethylpyridine below 0.1%, preferably between 0.001 to 0.1%.
In another embodiment, the dichloro trifluoromethylpyridine obtained is substantially free from undesired impurities i.e., 3-chloro-2-fluoro-5-trifluoromethylpyridine, 2,3-difluoro-5-chlorodifluoromethylpyridine and 2,3-difluoro-5-dichlorofluoromethylpyridine.
In an embodiment of the present invention, the fluorination catalyst is selected from a group consisting of chromium oxide, aluminium oxide, fluorinated chromium oxide and fluorinated aluminium oxide or a mixture thereof.
In another embodiment of the present invention, the fluorination catalyst may be a mixture of activated chromium oxide and aluminium oxide.
In another embodiment of the present invention, the activation of the catalyst may be performed by heating the catalyst in anhydrous hydrogen fluoride.
In another embodiment of the present invention, the catalyst is heated with anhydrous hydrogen fluoride at a temperature of 100 to 400°C.

In another embodiment of the present invention, the heating of chromium oxide and aluminium oxide is carried out together in a reactor.
In an embodiment of the present invention, the fluorination reaction is carried out in absence of any solvent.
The "absence of solvent" refers to the process in which no solvent is used to aid the reaction. The absence of solvent reduces cost of process and generate less effluent after reaction.
In another embodiment of the present invention, the fluorination reaction may be carried out in a corrosion resistant reactor.
In another embodiment of the present invention, the corrosion resistant reactor comprised of materials which are resistant to corrosion as Hastelloy, Inconel, Monel and/or fluoropolymers linings.
In another aspect, the present invention provides a liquid phase process for preparation of dichloro trichloromethylpyridine, comprising a step of contacting monochloro trichloromethylpyridine and chlorine at a pressure selected in the range of atmosphere to 25 Kg/cm2 to obtain dichloro trichloromethylpyridine.
In an embodiment, the present invention provides a process for preparation of dichloro trichloromethylpyridine, comprising a step of contacting monochloro trichloromethylpyridine and chlorine in presence of a chlorination catalyst.
The liquid phase chlorination catalyst can be a Lewis acid catalyst selected from a group consisting of aluminium trichloride, ferric chloride, ferrous chloride, titanium tetrachloride, zinc chloride, cuprous chloride, cupric chloride, nickel chloride, zirconium chloride, aluminium chloride, lanthanum chloride, tin chloride and antimony chloride or a mixture thereof.
In an embodiment, the liquid phase chlorination reaction is carried out in an autoclave at a pressure range of atmosphere to 25 Kg/cm2.
In a preferred embodiment, the liquid phase chlorination reaction is carried out in an autoclave at a pressure range of 8-10kg/cm2.

In another aspect, the present invention provides a vapour phase process for preparation of monochloro trichloromethylpyridine, comprising the step of:
a) preheating methylpyridine and chlorine; and
b) contacting preheated methylpyridine and chlorine in presence of a diluent at a temperature selected in the range of 380 to 390°C and at a pressure selected in the range of 8 to 10Kg/cm2.
In another aspect, the present invention provides a vapour phase process for preparation of monochloro trichloromethylpyridine, comprising the step of:
a) preheating methylpyridine and chlorine; and
b) contacting preheated methylpyridine and chlorine in absence of a diluent at a temperature selected in the range of 380 to 390°C and at a pressure selected in the range of 8 to 10Kg/cm2.
The monochloro trichloromethylpyridine is selected from a group consisting of 2-chloro-5-trichloromethylpyridine and 2-chloro-6-trichloromethylpyridine.
In a preferred embodiment, methylpyridine and chlorine are preheated at a temperature range of 150-3 5 0°C.
In another embodiment, vapour phase chlorination reaction is carried out in presence of a diluent selected from nitrogen, argon, chlorinated organic solvent, fluorinated organic solvent or a mixture of chlorinated and fluorinated organic solvents.
In another embodiment, preheated methyl-pyridine and chlorine are supplied at a rate of 0.2g/min and lg/min respectively and nitrogen (diluent gas) is fed into the reactor at rate of 40cc/min as a diluent.
In another embodiment, 4 moles to 50 moles of chlorine w.r.t methylpyridine are used.
In a preferred embodiment, the spiral glass packing is used as a reaction medium in vapor phase chlorination.

The process of the present invention provides excellent catalyst life with higher product selectivity. The recycle of excess hydrogen fluoride is also possible and effluent load is very low.
The methylpyridines used as a raw material in the present invention may be prepared by known method or can be obtained commercially.
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.
The reagents used in the above process are obtained commercially.
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-chloro-5-trichloromethylpyridine
Preheated 3-methylpyridine (0.2g /min, 2.14 mmole) and chlorine (l.Og/min, 14 mmole) were fed into a one-meter glass reactor packed with spiral glass packing at 365°C for 8 hours. Nitrogen (diluent gas) was fed into the reactor at rate of 40cc/min as a diluent. Reactor outlet material was diluted with dichloromethane (DCM) and then washed with water and sodium carbonate solution. DCM layer was evaporated

to get crude product. Crude product was distilled to isolate pure 2-chloro-5-trichloromethylpyridine.
Purity: 99.5% (by GC)
Example 2: Preparation of 2-chloro-6-trichloromethylpyridine
Preheated 2-methylpyridine (0.2g /min, 2.14 mmole) and chlorine (l.Og/min, 14 mmole) were fed into a one-meter glass reactor packed with spiral glass packing at 365°C for 8 hours. Nitrogen (diluent gas) was fed into the reactor at rate of 40cc/min as a diluent. Reactor outlet material was diluted with dichloromethane (DCM) and then washed with water and sodium carbonate solution. DCM layer was evaporated to get crude product. Crude product was distilled to isolate pure 2-chloro-6-trichloromethylpyridine.
Purity: 99% (by GC)
Example 3: Preparation of 2,3-dichloro-5-trichloromethylpyridine
2-Chloro-5-(trichloromethyl)pyridine (200g, 0.86 moles) and anhydrous ferric chloride (lOg, 0.07 moles) were charged in an autoclave and heated to 150°C. Chlorine gas (154g, 2.5 moles) was added through dip line by maintaining pressure of 10 bar with pressure control valve. Vent gases scrubbed into caustic scrubber. After 20 hours, excess chlorine was vented off with nitrogen. Reaction mass was washed with water and extracted with dichloromethane. Organic layer was concentrated and distilled to isolate pure 2,3-dichloro-5-trichloromethylpyridine.
Purity: 97% (by GC)
Example 4: Preparation of 2,3-dichloro-6-trichloromethylpyridine
2-Chloro-6-trichloromethylpyridine (200g, 0.86 moles) and anhydrous ferric chloride (lOg, 0.07 moles) were charged in an autoclave and heated to 150°C. Chlorine gas (154g, 2.5 moles) was added through dip line by maintaining pressure of 10 bar with pressure control valve. Vent gases scrubbed into caustic scrubber. After 20 hours, excess chlorine was vented off with nitrogen. Reaction mass was

washed with water and extracted with dichloromethane. Organic layer was concentrated and distilled to isolate pure 2,3-dichloro-6-trichloromethylpyridine.
Purity: 98.2% (by GC)
Example 5: Preparation of 2,3-dichloro-5-trifluoromethylpyridine
Preheated 2,3-dichloro-5-trichlororomethylpyridine (1.5 g/min, 5.6 mmole) and anhydrous hydrogen fluoride (1.5 g/ min, 75 mmole) were fed into Inconel tubular reactor (length-11.8 inch, dia- 1 inch) packed with fluorinated alumina catalyst (60g) along with oxygen (60 cc/min) at 320°C. After reaction completion, reaction outlet mixture was collected in ice-cooled water. Collected mass was extracted with dichloromethane and washed with 10% potassium carbonate solution. Organic layer was concentrated and distilled to isolate pure 2,3-dichloro-5-trifluoromethyl pyridine.
Purity: 99.5% (by GC)
Example 6: Preparation of 2,3-dichloro-6-trifluoromethylpyridine
Preheated 2,3-dichloro-6-trichlororomethylpyridine (1.5 g/min, 5.6 mmole) and anhydrous hydrogen fluoride (1.5 g/ min, 75 mmole) were fed into Inconel tubular reactor (length-11.8 inch, dia- 1 inch) packed with fluorinated alumina catalyst (60g) along with oxygen (60 cc/min) at 320°C. After reaction completion, reaction outlet mixture was collected in ice-cooled water. Collected mass was extracted with dichloromethane and washed with 10% potassium carbonate solution. Organic layer was concentrated and distilled to isolate pure 2,3-dichloro-6-trifluoromethyl pyridine.
Purity: 99% (by GC)

WE CLAIM

1. A vapour phase process for preparation of chlorinated trifluoromethylpyridine,
comprising the steps of:
a) preheating chlorinated trichloromethylpyridine and a fluorinating agent; and
b) contacting the preheated chlorinated trichloromethylpyridine and the fluorinating agent in presence of a catalyst at a temperature of 300 to 400°C,
wherein the catalyst is selected from a group consisting of chromium oxide, aluminium oxide, fluorinated chromium oxide and fluorinated aluminium oxide or a mixture thereof.
2. The process as claimed in claim 1, wherein the fluorinating agent is anhydrous hydrogen fluoride.
3. The process as claimed in claim 1, wherein the fluorination is conducted in presence of a diluent selected from a group consisting of oxygen, nitrogen, and argon.
4. The process as claimed in claim 1, wherein the fluorination reaction is carried out without using any solvent.

5. The process as claimed in claim 1, wherein preparation of dichloro trichloromethylpyridine comprises a step of contacting monochloro trichloromethylpyridine and chlorine at a temperature selected in the range of 100-200°C and at a pressure selected in the range of atmosphere to 25 Kg/cm2 in liquid phase.
6. The process as claimed in claim 5, wherein preparation of monochloro trichloromethylpyridine in vapour phase comprises the step of:

a) preheating methylpyridine and chlorine; and
b) contacting preheated methylpyridine and chlorine in presence of a diluent at a temperature selected in the range of 380 to 390°C and at a pressure selected in the range of 8 to 10Kg/cm2.

7. The process as claimed in claim 6, wherein preparation of monochloro
trichloromethylpyridine is carried out using a diluent selected from a group
consisting of nitrogen, argon, chlorinated organic solvent, fluorinated organic
solvent or a mixture of chlorinated and fluorinated organic solvents.
8. The process as claimed in claim 1, wherein chlorinated trichloromethylpyridine
and fluorinating agent are preheated at a temperature range of 250-290°C before
contacting with the catalyst.
9. The process as claimed in claim 8, wherein preheated chlorinated
trichloromethylpyridine and fluorinating agent are supplied at a rate of 0.5 to 2.0
g/min and the oxygen is supplied at a rate of 60 cc/min to 500 cc/min.
10. The process as claimed in claim 1, wherein the chlorinated
trifluoromethylpyridine is selected from a group consisting of 2,3-dichloro-5-
trifluoromethylpyridine, 2,6-dichloro-5-trifluoromethyl pyridine, 2,3-dichloro-6-
trifluoromethylpyridine and 2,6-dichloro-4-trifluoromethylpyridine.