Method for separating and purifying 2-chloro-3-trifluoromethylpyridine

Abstract

A method for separating and purifying 2-chloro-3-trifluoromethylpyridine useful as an intermediate for medicines, agrochemicals, and the like is provided. The method includes: 1) in the process of producing chloro -trifluoromethylpyridine compounds by allowing a -methylpyridine compound to react with chlorine and hydrogen fluoride in a reaction apparatus, allowing a -trifluoromethylpyridine compound to react with chlorine in a reaction apparatus, or allowing a chloro -trichloromethylpyridine compound to react with hydrogen fluoride in a reaction apparatus, 2) fractionating a liquid mixture containing chloro -trifluoromethylpyridine compounds from the reaction apparatus, and 3) separating and purifying 2-chloro-3-trifluoromethylpyridine from the liquid mixture.

Claims

1. A method of producing a chloro--trifluoromethylpyridine compound of formula (II) wherein one of X.sup.2 and Y.sup.2 is Cl and the other is H or Cl: ##STR00008## comprising: 1) reacting, in a reaction apparatus, a -methylpyridine compound of formula (I) with chlorine and anhydrous HF in a vapor phase in the presence of a catalyst and an inert diluent, -trifluoromethylpyridine of formula (III) with chlorine in a vapor or liquid phase, or a chloro--trichloromethylpyridine compound of formula (IV) with anhydrous HF in a vapor phase in the presence of a catalyst and an inert diluent, ##STR00009## wherein X.sup.1 and Y.sup.1 each independently are H or Cl, and one of X.sup.2 and Y.sup.2 is Cl and the other is H or Cl; 2) fractionating a liquid mixture containing chloro--trifluoromethylpyridine compounds from the reaction apparatus, comprising 2a) fractionating 2-chloro-5-trifluoromethylpyridine by distillation, and 2b) further fractionating a liquid mixture containing 2-chloro-3-trifluoromethylpyridine by distillation, and 3) separating and purifying 2-chloro-3-trifluoromethylpyridine from the liquid mixture by crystallization, wherein the catalyst comprises at least one selected from the group consisting of fluorides of chromium, fluorides of iron, fluorides of nickel, fluorides of manganese, fluorides of cobalt, fluorides of aluminum, fluorides of gamma-alumina and ammonium fluoride.

2. The method of claim 1 comprising heating and melting the crystals containing 2-chloro-3-trifluoromethylpyridine obtained by crystallization; and further performing crystallization.

3. The method of claim 1, wherein the temperature of the reaction of the -methylpyridine compound of formula (I) with chlorine and anhydrous HF is 300-600 C., of the -trifluoromethylpyridine compound of formula (III) with chlorine in a vapor phase is 270-500 C., of the -trifluoromethylpyridine compound of formula (III) with chlorine in a liquid phase is 35-150 C., and of the chloro--trichloromethylpyridine compound of formula (IV) with anhydrous HF is 200-700 C.

4. The method of claim 1, wherein the temperature of the distillation is 90-130 C. in step 2a) and is 110-130 C. in step 2b), each under the condition of 120-147 hPa.

5. The method of claim 1, wherein the crystallization in step 3) is performed at a liquid temperature of 5-25 C.

Description

EXAMPLES

(1) The following will describe Examples of the present invention but the invention should not be construed as being limited thereto.

Example 1

(2) (1) As a reaction apparatus, an Inconel-made vertical reaction tube having a catalyst fluidized bed whose reaction portion has an inner diameter of 97.1 mm and a height of 1,570 mm was installed, one obtained by connecting two Inconel-made preheating tubes having an inner diameter of 30 mm and a length of 1,000 mm was used for raw materials and an inert diluent, and the reaction tube and the preheating tubes were covered with an electric heater and a heat-insulating material so that temperature could be controlled.

(3) One obtained by impregnating 2.2 kg of aluminum trifluoride having a particle diameter of 105 to 250 m with 277 g of anhydrous ferric chloride was placed in the catalyst packing part and heated to 200 C., and anhydrous hydrogen fluoride was introduced at a rate of 2.3 L/minute for 1 hour to activate the catalyst.

(4) After the reaction apparatus was heated to 400 C., -picoline and nitrogen gas were introduced through the preheating tube so as to be rates of 6.8 g/minute and 9.9 L/minute, respectively, as a mixed gas of about 200 C. and chlorine gas, and anhydrous hydrogen fluoride were introduced through a preheating tube so as to be rates of 7.4 L/minute and 7.4 L/minute, respectively, as a mixed gas of about 200 C., and then they were allowed to react for about 30 hours. During the time, the activated catalyst was continuously supplied and discharged at a rate of 300 g/hour. The residence time of the reaction mixture in the tube was about 3.4 seconds.

(5) A gas discharged from the reaction apparatus was allowed to pass through a water-washing column and an alkali-washing column to obtain a condensation product. Then, the condensation product was separated and neutralized with an aqueous ammonia solution to obtain 19.11 kg of an oily substance by steam distillation. By distilling the oily substance, 1.53 kg of a first fraction containing -trifluoromethylpyridine as a main component and 9.56 kg of a main fraction containing 2-chloro-5-trifluoromethylpyridine (2,5-CTF) as a main component were fractionated. The residual fraction (post fraction) after the first fraction and the main fraction were fractionated contained 3.7% of 2-chloro-5-trifluoromethylpyridine (2,5-CTF), 14.5% of 2-chloro-3-trifluoromethylpyridine (2,3-CTF), 47.7% of 2,6-dichloro-3-trifluoromethylpyridine (2,3,6-DCTF), and 34.1% of others. The % designation herein is based on the peak area ratio (GCPA %) on gas chromatographic analysis.

(6) (2) From the oily substance obtained in accordance with the method described in the above step (1), while a fraction containing 2-chloro-5-trifluoromethylpyridine (2,5-CTF) as a main component was fractionated by distillation, distillation was continued at 110 to 130 C. for the residual fraction. Upon sampling and gas chromatographic analysis, fractions after the peak area ratio of 2-chloro-3-trifluoromethylpyridine (2,3-CTF) exceeds 65% were collected. According to the operation method, about 2,400 kg of the above oily substance was distilled to obtain about 70 kg of a fraction in which the area value of 2-chloro-3-trifluoromethylpyridine (2,3-CTF) exceeded 65%.

(7) (3) A fraction (liquid mixture) (284 kg) containing 2-chloro-3-trifluoromethylpyridine (2,3-CTF) obtained in accordance with the method described in the above step (2) was transferred to a drum can (200 L) and allowed to stand to crystallize 2-chloro-3-trifluoromethylpyridine (2,3-CTF). The melting point of 2,3-CTF is 37 to 39.5 C. After crystallization was performed under an air temperature lower than the melting point for 2 hours, a nozzle and a valve were attached to the discharge port of the drum can and the drum can was tilted sideway by a drum can tumbling device, and the liquid was received in a plastic bucket (50 L). After the crystals in the drum can was heated and melted and then again crystallized, the liquid was removed by the same operation as mentioned above to obtain 189 kg of crystals of 2,3-CTF (97.5% purity).

Example 2

(8) A fraction (liquid mixture) (1,600 kg) containing 2-chloro-3-trifluoromethylpyridine (2,3-CTF) obtained in accordance with the method described in (1) and (2) of the above Example 1 was charged into a crystallization tank (200 L) and stirred at 40 to 60 C. for 30 minutes. The crystallization tank was cooled to 20 to 30 C. to crystallize 2-chloro-3-trifluoromethylpyridine (2,3-CTF). After crystal precipitation was confirmed, the whole was stirred at the same temperature for about one hour. After the stirring was finished, crystals were extracted from the bottom of the crystallization tank and the crystals were filtrated by a filtration machine (centrifuge) to obtain 528 kg of crystals of 2,3-CTF (97 to 99% purity).

Example 3

(9) A fraction (liquid mixture) containing 2-chloro-3-trifluoromethylpyridine (2,3-CTF) obtained in accordance with the method described in the (1) and (2) of the above Example 1 is charged into a continuous melt crystallization apparatus (continuous melt crystallization apparatus having a trade name KCP manufactured by Kureha Techno Engineering Co., Ltd.). The liquid mixture is cooled to about 10 C. to crystallize 2,3-CTF for several hours. Under an environment capable of maintaining the temperature, a slurry containing 2,3-CTF as crystals is filtrated on a mesh-like filter plate. The obtained crystals containing 2,3-CTF as a main component are charged into a cylindrical vessel from the lower part and are pushed up to the upper part using a screw. A heating source capable of heating to 30 to 35 C. is present at the upper part and melts a liquid impurity included in or attached to the crystals to drop it to the lower part. Purification by heat exchange (Sweat method) in the vessel is performed by repeating the operation to obtain highly pure crystals of 2,3-CTF (97 to 99% purity). The liquid filtrated through the mesh-like filter plate is used as a raw material of the production step of the liquid mixture containing 2,3-CTF and the liquid extracted from the bottom of the cylindrical vessel is again used as a raw material of the melt crystallization.

Example 4

(10) (1) As a reaction apparatus, a stainless steel-made reaction tube whose reaction part had an inner diameter of 42 mm and a length of 1,250 mm was used and a catalyst packing layer having a length of 250 mm was installed at a part 500 mm behind the inlet of the reaction tube.

(11) On the other hand, as preheating parts, a stainless steel-made preheating tube having an inner diameter of 20 mm and a length of 500 mm was used for anhydrous hydrogen fluoride and chlorine, and a stainless steel-made preheating tube having an inner diameter of 20 mm and a length of 500 mm was used for -picoline and carbon tetrachloride.

(12) The reaction tube and the preheating tubes were covered with an electric heater and a heat-insulating material so that temperature could be externally controlled, and they were installed at a slant.

(13) A blend of 0.03 mol of hydrated chromium trifluoride and 200 g of active alumina having a particle diameter of 4 to 6 mm was packed into the catalyst packing part of the reaction tube, and the reaction tube was heated to 430 C. and anhydrous hydrogen fluoride was allowed to pass through at a rate of 1 g/minute for 2 hours for activation. Thereafter, there were supplied 280 g (3 mol) of -picoline and 2,310 g (15 mol) of carbon tetrachloride preheated to 230 C. and 960 g (13.5 mol) of chlorine and 480 g (24 mol) of anhydrous hydrogen fluoride preheated to 300 C. at an almost constant flow rate for 290 minutes to perform the reaction at 430 C. in a vapor phase. The residence time of the reaction mixture in the tube was about 9 seconds.

(14) A gas discharged from the reaction tube was allowed to pass through a water-washing column and an alkali-washing column and condensed to obtain an oily substance. The oily substance was separated, collected, washed with water, and dried over sodium sulfate, and then carbon tetrachloride was distilled off under reduced pressure to obtain 420 g of an oily substance.

(15) Using the finally obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 5

(16) After 300 g of -alumina was placed in the catalyst packing layer of the reaction tube used in the above Example 4 and activated with anhydrous hydrogen fluoride in the same manner as in the case of Example 4, 465 g (5 mol) of -picoline and 3,850 g (25 mol) of carbon tetrachloride preheated to 250 C., and, 1,950 g (27.5 mol) of chlorine and 900 g (45 mol) of anhydrous hydrogen fluoride preheated to 300 C. at an almost constant flow rate for about 8 hours were supplied, and a vapor-phase reaction was carried out at a reaction temperature of 430 C. at a residence time of the reaction mixture of about 10.5 seconds.

(17) A gas discharged from the reaction tube was treated in the same manner as in the case of Example 4 to obtain 708 g of an oily substance.

(18) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 6

(19) A reaction was carried out in the same manner as in the case of Example 5 except that one obtained by supporting 0.1 mol of hydrated nickel(II) fluoride on 200 g of active carbon having a particle diameter of 2 to 4 mm was used instead of 300 g of -alumina and the activation of the alumina catalyst with anhydrous hydrogen fluoride was not performed, thereby obtaining 300 g of an oily substance.

(20) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 7

(21) As a reaction apparatus, an Inconel-made vertical reaction tube having a catalyst fluidized bed whose reaction part has an inner diameter of 82 mm and a height of 1,100 mm was installed, one obtained by connecting two Inconel-made preheating tubes having an inner diameter of 8 mm and a length of 2,000 mm was used for raw materials and an inert diluent, and the reaction tube and the preheating tubes were covered with an electric heater and a heat-insulating material so that temperature could be controlled.

(22) As a catalyst, 1.7 kg of the activated catalyst used in the above Example 4 which was pulverized and controlled to have a particle diameter of 0.18 to 0.4 mm was packed into the reaction part.

(23) The reaction apparatus was heated to 430 C., -picoline and nitrogen gas were introduced through the preheating tube so that the rates became 3.6 g/minute and 11.3 L/minute, respectively, as a mixed gas of about 200 C., and chlorine gas and anhydrous hydrogen fluoride were introduced through the preheating tube so that the rates became 2.8 L/minute and 2.5 L/minute, respectively, as a mixed gas of about 200 C. Then, they were allowed to react for about 5 hours. The residence time of the reaction mixture in the tube was about 7 seconds.

(24) A gas discharged from the reaction apparatus was treated in the same manner as in the case of Example 4 to obtain 1,680 g of an oily substance.

(25) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 8

(26) A reaction was carried out in the same manner as in the case of Example 7 for about 3 hours except that -picoline, 3-trifluoromethylpyridine and nitrogen gas were supplied so that the rates became 2.38 g/minute, 1.88 g/minute and 11.3 L/minute, respectively, and chlorine gas and anhydrous hydrogen fluoride were supplied so that the rates became 2.8 L/minute and 2.5 L/minute, respectively. The residence time of the reaction mixture in the tube was about 7 seconds.

(27) A gas discharged from the reaction apparatus was treated in the same manner as in the case of the above Example 4 to obtain 1,090 g of an oily substance.

(28) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 9

(29) Using the same reaction apparatus as in the above Example 4, a catalyst obtained by supporting 0.1 mol of cobalt(II) fluoride on 200 g of active carbon having a particle diameter of 2 to 4 mm was placed in the catalyst packing part of the reaction tube. Thereafter, 280 g (3 mol) of -picoline and 2,310 g (15 mol) of carbon tetrachloride preheated to 230 C., and, 960 g (13.5 mol) of chlorine and 480 g (24 mol) of anhydrous hydrogen fluoride preheated to 300 C. at an almost constant flow rate for 290 minutes were supplied, and a reaction was carried out at 430 C. in a vapor phase. The residence time of the reaction mixture in the tube was about 9 seconds.

(30) A gas discharged from the reaction tube was allowed to pass through a water-washing column and an alkali-washing column and condensed to obtain an oily substance. The oily substance was separated, collected, washed with water, and dried over sodium sulfate, and then carbon tetrachloride was distilled off under reduced pressure to obtain 280 g of an oily substance.

(31) Using the finally obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 10

(32) An oily substance was obtained in an amount of 340 g in the same manner as in the above Example 9 except that the catalyst was changed to manganese(III) fluoride.

(33) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.

Example 11

(34) A glass-made reaction tube having a diameter of 4 cm and a length of 70 cm, which was fitted with a thermocouple, was used. Two glass-made gas blowing tubes were inserted into the reaction tube through a preheating device. The reaction tube was covered with an electric heater and a heat-insulating material so that temperature could be externally controlled, and they were installed at a slant. One gas blowing tube was used for the introduction of a dried chlorine gas and another blowing tube was used for the introduction of a mixed gas obtained by heating and vaporizing a carbon tetrachloride solution of 3-trifluoromethylpyridine in a nitrogen gas stream. A receiver fitted with a cooling tube was installed at the outlet of the reaction tube, for collecting discharged gases. A solution in which the molar ratio of 3-trifluoromethylpyridine to carbon tetrachloride was 1/10, chlorine and nitrogen were supplied into the reaction tube at rates of 5.9 mL, 184 mL and 610 mL, respectively, per minute for 30 minutes, and thus a vapor-phase reaction was carried out at 400 C. The residence time of the gasses in the reaction tube was about 10 seconds. A liquid substance collected in the receiver was washed with a dilute aqueous solution of ammonia and then dried over sodium sulfate, and carbon tetrachloride was removed by distillation under reduced pressure to obtain 24.8 g of a yellow oily substance.

(35) Using the obtained oily substance, distillation and crystallization are performed in accordance with (2) and (3) of the above Example 1 to obtain crystals of 2,3-CTF.