PROCESS FOR THE PREPARATION OF 2-CHLORO-6-TRIFLUOROMETHYL PYRIDINE
Field of the invention
The present invention provides a process for the preparation of 2-chloro-6-trifluoromethylpyridine of Formula I.
Background of the invention The 2-chloro-6-trifluoromethylpyridine is a key intermediate in the synthesis of pesticides, insecticides, herbicides and the like. It is also widely used in organic synthesis, pharmaceuticals and dye.
The U.S. Patent No. 4,563,529 provides a process for producing trifluoromethylpyridine, by reacting a pyridine derivative selected from α-picoline, γ-picoline and a lutidine with chlorine and anhydrous hydrogen fluoride at a temperature of 300°C to 600°C in vapour phase in the presence of a diluent and a catalyst comprising a fluoride of a metallic element selected from aluminum, chromium, iron, nickel, manganese, cobalt and copper to obtain α-trifluoromethylpyridine, γ-trifluoromethylpyridine, a bis(trifluoromethyl)pyridine and chlorides thereof which have 1 to 3 chlorine atoms in its pyridine nucleus. This process is not industrially viable due to simultaneous handling of multiple volatile reactants such as chlorine, anhydrous hydrogen fluoride and catalyst. Since, the process involves one-pot synthesis resulting in numerous by-products and hence the separation of the by-products is very difficult and thus selectivity is also low. The process produces 6-chloro-2-trifluoromethyl pyridine with a low yield ranging from 37.4% to 48.3% by gas chromatography.
The Chinese patent application No. 101081831 provides a process of preparing 2-chloro-6-trifluoromethylpyridine by reacting 2-chloro-6-methylpyridine with chlorine gas in organic solvent, and in the presence of a catalyst under 800-2000W UV light irradiation, to obtain 2-chloro-6-trichloromethylpyridine. Fluorinating the 2-chloro-6-trichloromethylpyridine 2
with 15 to 30 fold hydrogen fluoride at 1600°C to 1850°C for 15h to 30h in the presence of
a catalyst selected from antimony pentachloride or antimony pentafluoride to provide 2-
chloro-6-trifluoromethylpyridine. The fluorination step requires a longer duration and use
of an autoclave or expensive antimony trifluoride. Therefore, it is not satisfactory as an
industrial process.
The present invention provides a process for the preparation of 2-chloro-6-
trifluoromethylpyridine which is simple, easy to perform and industrially doable. The
present invention provides 2-chloro-6-trifluoromethylpyridine with high yield.
Summary of the invention
The present invention provides a process for the preparation of 2-chloro-6-trifluoromethyl
pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-6-
trifluoromethyl pyridine of Formula I, and
Cl N CF3
Formula I
Cl N CCl 3
Formula II
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
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a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II having purity greater
than 98.0% with anhydrous hydrogen fluoride in the presence of a fluorination
catalyst to obtain 2-chloro-6-trifluoromethyl pyridine of Formula I, and
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of chromia-alumina or chromia to obtain 2-
chloro-6-trifluoromethyl pyridine of Formula I, and
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-6-
trifluoromethyl pyridine of Formula I, and
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) is carried out in the absence of a solvent.
Detailed description of the invention
The present invention provides a process for the preparation of 2-chloro-6-trifluoromethyl
pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-
6-trifluoromethyl pyridine of Formula I, and
Cl N CF3
4
Formula I
Cl N CCl 3
Formula II
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a),
wherein the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II having purity
greater than 98.0% with anhydrous hydrogen fluoride in the presence of a
fluorination catalyst to obtain 2-chloro-6-trifluoromethyl pyridine of Formula I,
and
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a),
wherein the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of chromia-alumina or chromia to obtain 2-
chloro-6-trifluoromethyl pyridine of Formula I, and
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a),
wherein the step a) takes place in a vapour phase.
The present invention also provides a process for the preparation of 2-chloro-6-
trifluoromethyl pyridine of Formula I, comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-
6-trifluoromethyl pyridine of Formula I, and
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b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein the step a) is carried out in the absence of a solvent.
The compound of Formula II may be obtained commercially or can be prepared by any of the methods known in the art.
The fluorination catalyst is selected from oxides or fluorides of one or more of chromium, manganese, iron, cobalt, aluminium or nickel or mixtures thereof. The catalyst may be used either unsupported or supported, supported materials may be selected from aluminium fluoride, alumina, silica-alumina.
The process of the present invention is solvent-free. The process of the present invention is continuous.
The amount of anhydrous hydrogen fluoride is usually in the range of 3 to 20 moles per mole of the 2-chloro-6-trichloromethyl pyridine. The process of the present invention is carried out at a temperature in the range of from about 3000C to 4000C, for example, from about 3300C to 3800C.
In usual, gaseous materials containing the fluorinated products as main component, the unreacted anhydrous hydrogen fluoride, the intermediates, hydrogen chloride as a by-product are discharged from the reaction tube. The trifluoromethylpyridines are obtained as a liquid mixture through a desired cooling and condensing device. In the liquid mixture, there are contained 2-chloro-6-trifluoromethylpyridine, 2-chloro-6-(chloro-difluoro-methyl)pyridine, 2-chloro-6-(dichloro-fluoro-methyl)pyridine, 2-fluoro-6-trifluoromethylpyridine.
The unwanted intermediates and by-products, such as 2-chloro-6-(chloro-difluoromethyl)-pyridine, 2-chloro-6-(dichloro-fluoromethyl)-pyridine, 2-fluoro-6-trifluoromethylpyridine may be converted to 2-chloro-6-trifluoromethylpyridine by recyclization. Further, the 2-chloro-6-trifluoromethylpyridine may be isolated from the reaction mixture by the methods known in the art, for example, filtration, decantation, layer separation, precipitation, distillation and evaporation or a mixture thereof. 6
The 2-chloro-6-trifluoromethylpyridine prepared by virtue of the process of present invention is pure to greater than 97.0%, preferably greater than 97.5% by GC.
The term ‘about’ refers to a variation of 10% on the higher and lower side of specified parameter.
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 examples are 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-6-trifluoromethyl pyridine
2-chloro-6-trichloromethyl pyridine (100 g, 0.43 moles, feed rate - 0.47 g/min), anhydrous hydrogen fluoride (149 g, 7.45 moles, feed rate 0.7 g/min) and nitrogen (feed rate - 80cc /min) were fed into a tubular reactor packed with pre-activated chromia-alumina catalyst (154g) at 350°C. The outlet material from the reactor was collected in ice-cooled water and was extracted with dichloromethane. The dichloromethane layer was then washed with 10% potassium hydroxide solution. The organic layer was separated out and concentrated to obtain 56.0 g of title compound.
Yield (%): 70.0
Purity (by GC analysis): 97.5%

We claim:
1. A process for the preparation of 2-chloro-6-trifluoromethyl pyridine of Formula I,
comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-6-
trifluoromethyl pyridine of Formula I, and
Cl N CF3
Formula I
Cl N CCl 3
Formula II
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
2. A process for the preparation of 2-chloro-6-trifluoromethyl pyridine of Formula I,
comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II having purity greater
than 98.0% with anhydrous hydrogen fluoride in the presence of a fluorination
catalyst to obtain 2-chloro-6-trifluoromethyl pyridine of Formula I, and
Cl N CF3
Formula I
Cl N CCl 3
Formula II
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b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
3. A process for the preparation of 2-chloro-6-trifluoromethyl pyridine of Formula I,
comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of chromia-alumina or chromia to obtain 2-
chloro-6-trifluoromethyl pyridine of Formula I, and
Cl N CF3
Formula I
Cl N CCl 3
Formula II
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) takes place in a vapour phase.
4. The process as claimed in claim 1, 2 or 3, wherein step a) takes place at a temperature
range of 300oC to 400oC.
5. The process as claimed in claim 1, 2 or 3, wherein the anhydrous hydrogen fluoride in
step a) is reacted in an amount in the range of 3 to 20 moles per mole of the 2-chloro-6-
trichloromethyl pyridine.
6. A process for the preparation of 2-chloro-6-trifluoromethyl pyridine of Formula I,
comprising;
a) reacting 2-chloro-6-trichloromethyl pyridine of Formula II with anhydrous
hydrogen fluoride in the presence of a fluorination catalyst to obtain 2-chloro-6-
trifluoromethyl pyridine of Formula I, and
Cl N CF3
Formula I
9
Cl N CCl 3
Formula II
b) isolating 2-chloro-6-trifluoromethyl pyridine of Formula I from the step a), wherein
the step a) is carried out in the absence of a solvent.
7. The process as claimed in claim 1, 2 or 6, wherein fluorination catalyst is selected from
oxides or fluorides of one or more of chromium, manganese, iron, cobalt, aluminium or
nickel or mixture thereof.
8. The process as claimed in claim 1, 2, 3 or 6, wherein compound of Formula I is isolated
using filtration, decantation, layer separation, precipitation, distillation and evaporation or
a mixture thereof.