WO2019109936A1 - 一种高选择性地制备2,3-二氯-5-三氟甲基吡啶的方法 - Google Patents

一种高选择性地制备2,3-二氯-5-三氟甲基吡啶的方法 Download PDF

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WO2019109936A1
WO2019109936A1 PCT/CN2018/119312 CN2018119312W WO2019109936A1 WO 2019109936 A1 WO2019109936 A1 WO 2019109936A1 CN 2018119312 W CN2018119312 W CN 2018119312W WO 2019109936 A1 WO2019109936 A1 WO 2019109936A1
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Prior art keywords
trifluoromethylpyridine
catalyst
dichloro
reaction
producing
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PCT/CN2018/119312
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English (en)
French (fr)
Inventor
于万金
林胜达
刘敏洋
刘武灿
张建君
陈先进
Original Assignee
浙江省化工研究院有限公司
浙江蓝天环保高科技股份有限公司
中化蓝天集团有限公司
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Priority claimed from CN201711275197.XA external-priority patent/CN109879802B/zh
Priority claimed from CN201810020465.1A external-priority patent/CN110003098B/zh
Priority claimed from CN201810009301.9A external-priority patent/CN110003097B/zh
Priority claimed from CN201810009294.2A external-priority patent/CN110003096B/zh
Application filed by 浙江省化工研究院有限公司, 浙江蓝天环保高科技股份有限公司, 中化蓝天集团有限公司 filed Critical 浙江省化工研究院有限公司
Priority to US16/620,763 priority Critical patent/US11186546B2/en
Priority to JP2019567321A priority patent/JP6872041B2/ja
Priority to KR1020207014641A priority patent/KR102366955B1/ko
Priority to EP18886350.0A priority patent/EP3620451B1/en
Publication of WO2019109936A1 publication Critical patent/WO2019109936A1/zh
Priority to US17/478,129 priority patent/US20220002249A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Definitions

  • the invention relates to a preparation method of chlorotrifluoromethylpyridine, in particular to a preparation method of 2,3-dichloro-5-trifluoromethylpyridine.
  • Fluorine, heterocyclic and chirality are the three characteristics of modern pesticides and new drugs in the field of medicine.
  • new fluorine-containing pyridine pesticides such as acetamiprid, pyridine guanidine, chlorpyrifos and fluazinam, have the advantages of broad-spectrum systemic absorption, high efficiency, low toxicity and low pollution, and have become highly effective insecticides.
  • 2,3-Dichloro-5-trifluoromethylpyridine (2,3,5-DCTF) is a key intermediate in the production of these new pesticides and has become a hot spot in the industry.
  • European Patent EP0078410 reports that a fluidized bed is used as a reactor, 2-chloro-5-trifluoromethylpyridine and chlorine gas are chlorinated at 250 ° C under the action of FeCl 3 /AC catalyst to form 2,3- Method of dichloro-5-trifluoromethylpyridine.
  • the yield of this method can reach 74%, but the gas phase chlorination reaction has a plurality of isomers formed, so that product separation is difficult;
  • U.S. Patent No. 4,420,618 reports the preparation of 2,3-dichloro-5-trifluoromethylpyridine by atmospheric pressure liquid chlorination process, under the action of a metal chloride catalyst, 2-chloro-5-trifluoromethyl
  • the pyridine reacts with chlorine to form 2,3-dichloro-5-trifluoromethylpyridine.
  • the yield of the method is 16 to 75%, the amount of the catalyst is very large, and it is required to reach 40 to 200% of the mass of the raw material, and the chlorine gas is continuously introduced during the reaction, and the utilization efficiency of the chlorine gas is low, resulting in high production cost.
  • the gas phase chlorination method has the disadvantages of poor selectivity of 2,3-dichloro-5-trifluoromethylpyridine, many by-produced isomers, and difficulty in separation, and the liquid phase chlorination method has a large amount of catalyst.
  • the invention aims at the deficiencies of the prior art, and provides a method for preparing 2,3-dichloro-5-trifluoromethylpyridine by pressurized liquid phase chlorination, which has high selectivity of target product, high utilization rate of chlorine gas and process conditions. Mild, easy to operate and low waste.
  • 2,5-CTF 2-chloro-5-trifluoromethylpyridine
  • 2,3,5-DCTF 2,3-dichloro-5-trifluoromethylpyridine
  • 2,6,3-DCTF 2,6-dichloro-3-trifluoromethylpyridine
  • 2,3,6,5-TCTF 2,3,6-trichloro-5-trifluoromethylpyridine.
  • 2,3-CTF 2-chloro-3-trifluoromethylpyridine
  • the preparation method provided by the invention has the following chemical reaction formula:
  • a method of preparing 2,3-dichloro-5-trifluoromethylpyridine comprising:
  • the first catalyst is selected from at least one of a supported metal chloride, a supported zeolite molecular sieve, and a supported heteropolyacid,
  • the supported metal chloride has an active component selected from at least one of WCl 6 , MoCl 5 , FeCl 3 , AlCl 3 , CuCl 2 , ZnCl 2 , SnCl 4 , and SbCl 5 , and the active component is loaded.
  • the amount is 1 to 50% by weight,
  • the supported zeolite molecular sieve has a zeolite molecule selected from at least one of ZSM-5, Beta, X, Y, 5A and L type zeolite molecular sieves, and the loading amount of the zeolite molecular sieve is 1 to 50% by weight.
  • the supported heteropoly acid wherein the heteropoly acid is at least one selected from the group consisting of phosphotungstic acid, silicotungstic acid, phosphomolybdic acid, and silicomolybdic acid, and the heteropoly acid is supported in an amount of 1 to 50% by weight.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine comprises 2-chloro-5-trifluoromethylpyridine and chlorine as raw materials, and is obtained by reaction under the action of the first catalyst. , 3-dichloro-5-trifluoromethylpyridine.
  • the first catalyst used provides the dispersion of the active component by supporting a metal chloride, a zeolite molecular sieve or a heteropolyacid in a carrier, thereby making it suitable for use in 2-chloro-5-trifluoromethylpyridine and chlorine.
  • the reaction of 2,3-dichloro-5-trifluoromethylpyridine is prepared as a raw material, and the selectivity of the target compound 2,3-dichloro-5-trifluoromethylpyridine can be remarkably improved.
  • the first catalyst used in the present invention is selected from at least one of a supported metal chloride, a zeolite molecular sieve, and a heteropoly acid.
  • the active component thereof is at least one of WCl 6 , MoCl 5 , FeCl 3 , AlCl 3 , CuCl 2 , ZnCl 2 , SnCl 4 , and SbCl 5 .
  • the active component is selected from at least one of WCl 6 , MoCl 5 , ZnCl 2 , and FeCl 3 .
  • the supported metal chloride preferably has an active component loading of from 1 to 50% by weight.
  • the active component is supported in an amount of from 5 to 20% by weight.
  • the zeolite molecules are screened from at least one of ZSM-5, Beta, X, Y, 5A and L zeolite molecular sieves.
  • the zeolite molecule is screened from at least one of ZSM-5, Beta, and L.
  • the zeolite molecular sieve has a Si/Al ratio which satisfies the smooth progress of the reaction.
  • the zeolite molecular sieve has a Si/Al ratio of 200 or less, and the equilibrium cation is at least one selected from the group consisting of H+, an alkali metal ion, an alkaline earth metal ion, a transition metal ion, and a rare earth metal ion.
  • the supported zeolite molecular sieve the loading amount of the zeolite molecular sieve is preferably from 1 to 50% by weight.
  • the zeolite molecular sieve is loaded in an amount of 5 to 20% by weight.
  • the heteropolyacid is at least one selected from the group consisting of phosphotungstic acid, silicotungstic acid, phosphomolybdic acid, and silicomolybdic acid.
  • the supported amount of the heteropoly acid in the supported heteropoly acid is preferably from 1 to 50% by weight.
  • the heteropoly acid is supported in an amount of 5 to 20% by weight.
  • the carrier used in the first catalyst of the present invention is preferably at least one selected from the group consisting of silica, alumina, titania, zirconia, activated carbon, silicon carbide, and mesoporous molecular sieves.
  • the amount of the catalyst is sufficient for the reaction to proceed smoothly.
  • the first catalyst is used in an amount of from 0.1 to 30% by weight based on the mass of the 2-chloro-5-trifluoromethylpyridine.
  • the first catalyst is used in an amount of 5 to 20% by weight based on the mass of 2-chloro-5-trifluoromethylpyridine.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine provided by the invention provides that the ratio of the raw material chlorine gas to 2-chloro-5-trifluoromethylpyridine satisfies the smooth progress of the reaction.
  • the molar ratio of the chlorine gas to 2-chloro-5-trifluoromethylpyridine is from 0.5 to 10:1.
  • the molar ratio of the chlorine gas to 2-chloro-5-trifluoromethylpyridine is from 1 to 3:1.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine provided by the present invention is required to satisfy the reaction pressure.
  • the reaction pressure is from 0.5 to 5.0 MPa.
  • reaction pressure is 1.0 to 2.0 MPa.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine provided by the invention has the reaction temperature satisfied to make the reaction proceed smoothly.
  • the reaction temperature is from 100 to 150 °C.
  • the process for preparing 2,3-dichloro-5-trifluoromethylpyridine provided by the present invention is preferably carried out in an autoclave.
  • the high pressure reactor is preferably made of a material selected from the group consisting of 316L, Monel, Inconel or Hastelloy.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine provided by the invention can be added with an alkali solution after the reaction is completed, and then separated to obtain 2,3-dichloro-5-trifluoromethyl. Pyridine.
  • the lye may be an organic base and/or an inorganic base.
  • the organic base is preferably at least one selected from the group consisting of dimethylamine, diethylamine, triethylamine, dipropylamine, and tripropylamine.
  • the inorganic base is preferably at least one selected from the group consisting of NaOH, Na 2 CO 3 , NaHCO 3 , KOH, K 2 CO 3 , KHCO 3 and ammonia water.
  • the 2,3-dichloro-5-trifluoromethylpyridine prepared by the present invention can be qualitatively analyzed by GC-MS and quantitatively analyzed by gas chromatography internal standard method.
  • i represents 2,3,5-DCTF, 2,6,3-DCTF and 2,3,6,5-TCTF and the like.
  • the method for preparing 2,3-dichloro-5-trifluoromethylpyridine has the following advantages over the prior art: the selectivity of the target product 2,3-dichloro-5-trifluoromethylpyridine And the yield is high, can reach more than 90%; the amount of catalyst is small, and the reactant is easy to be separated, and the catalyst can be recycled; the organic solvent is not needed, the cost is low, and the chlorine gas is used efficiently.
  • the present invention also provides a method for preparing the following 2-chloro-5-trifluoromethylpyridine.
  • a method for preparing 2-chloro-5-trifluoromethylpyridine comprising:
  • Chlorofluorination reaction Under the action of a chlorofluorination catalyst, the chlorofluorination temperature is maintained at 150-320 ° C, and 3-methylpyridine, chlorine gas and hydrogen fluoride are introduced into the chlorofluorination reaction zone to obtain 3-3. a mixture of fluoromethylpyridine;
  • chlorination reaction maintaining a chlorination temperature of 220 to 380 ° C under the action of a chlorination catalyst, and passing the mixed gas containing 3-trifluoromethylpyridine obtained in the step (1) into the chlorination reaction zone to obtain 2 -Chloro-5-trifluoromethylpyridine
  • the chlorination catalyst being selected from the group consisting of fluorides, oxides, hydroxides, carbonates or chlorides of magnesium, calcium and strontium, supported on activated carbon, alumina or fluorinated Palladium catalyst on aluminum.
  • the above preparation method provided by the present invention is a two-stage reaction comprising a chlorofluorination reaction step and a chlorination reaction step. Among them, in the chlorofluorination reaction step, a chlorofluorination catalyst is used.
  • the chlorofluorination catalyst may be a chlorofluorination catalyst commonly used in the art.
  • the chlorofluorination catalyst comprises a main catalyst, a first cocatalyst and a second cocatalyst, the main catalyst being selected from at least one of aluminum, magnesium and chromium, the first cocatalyst It is at least one selected from the group consisting of iron, cobalt, manganese, nickel, copper, cerium, and zinc, and the second promoter is at least one selected from the group consisting of ruthenium, osmium, iridium, calcium, sodium, and potassium.
  • the main catalyst is selected from aluminum and/or chromium
  • the first promoter is at least one selected from the group consisting of iron, nickel and copper
  • the second promoter is selected from the group consisting of ruthenium. At least one of strontium, barium and calcium.
  • the ratio between the main catalyst, the first promoter, and the second promoter may be such that the reaction proceeds smoothly.
  • the molar ratio between the main catalyst, the first promoter and the second promoter is from 50 to 95:5 to 42:0.3 to 8.
  • the molar ratio between the main catalyst, the first promoter and the second promoter is from 75 to 90:10 to 20:1 to 5.
  • the ratio of the raw material 3-methylpyridine, chlorine gas and hydrogen fluoride in the chlorofluorination reaction step is satisfactory for the reaction to proceed smoothly.
  • the molar ratio between the 3-methylpyridine, chlorine gas and hydrogen fluoride is from 1:0.1 to 50:1 to 30.
  • the molar ratio between the 3-methylpyridine, chlorine gas and hydrogen fluoride is from 1:4 to 10:3 to 12.
  • the raw material 3-methylpyridine may be directly added to the reaction as a gas, or may be added as a mixed gas after being diluted with an inert gas.
  • the 3-methylpyridine is a mixed gas diluted with an inert gas.
  • the ratio of the 3-methylpyridine in the mixed gas diluted with the inert gas satisfies the smooth progress of the reaction.
  • the molar ratio of the 3-methylpyridine to the mixed gas is 1:0.5 to 50.
  • the molar ratio of the 3-methylpyridine to the mixed gas is 1:5-20.
  • the chlorofluorination reaction step in the preparation method provided by the present invention, in the step (1), the chlorofluorination reaction step, the contact time of the raw material 3-methylpyridine, chlorine gas and hydrogen fluoride with the chlorofluorination catalyst is satisfied to allow the reaction to proceed smoothly.
  • the contact time of the 3-methylpyridine, chlorine gas and hydrogen fluoride with the chlorofluorination catalyst is from 0.5 to 40 s.
  • the contact time of the 3-methylpyridine, chlorine gas and hydrogen fluoride with the chlorofluorination catalyst is from 1.5 to 20 s.
  • the chlorination catalyst used is selected from the group consisting of magnesium, calcium, strontium fluoride, oxide, hydroxide, carbonate or chloride, and is supported on activated carbon.
  • the fluoride, oxide, hydroxide, carbonate and chloride of magnesium, calcium and barium may be magnesium fluoride, calcium fluoride, barium fluoride, magnesium oxide, calcium oxide, barium oxide or hydroxide.
  • the supported palladium catalyst supported on activated carbon, alumina or aluminum fluoride may be a supported palladium catalyst supported on activated carbon, a supported palladium catalyst supported on alumina, and a load supported on aluminum fluoride.
  • Type palladium catalyst a supported palladium catalyst supported on activated carbon, a supported palladium catalyst supported on alumina, and a load supported on aluminum fluoride.
  • the chlorination catalyst is selected from the group consisting of magnesium, calcium fluoride, oxide or chloride, supported palladium catalyst supported on activated carbon or aluminum fluoride.
  • the contact time of the mixed gas containing 3-trifluoromethylpyridine with the chlorination catalyst is such that the reaction proceeds smoothly.
  • the contact time of the mixed gas containing 3-trifluoromethylpyridine with the chlorination catalyst is from 0.5 to 40 s.
  • the contact time of the mixed gas containing 3-trifluoromethylpyridine with the chlorination catalyst is from 1.5 to 20 s.
  • the preparation method provided by the invention is a two-stage method comprising a chlorofluorination reaction step and a chlorination reaction step, and the temperature control between the two steps has an influence on the reaction result.
  • the chlorofluorination temperature is 150 to 320 ° C and the chlorination temperature is 220 to 380 ° C.
  • the chlorofluorination temperature is 220 to 260 ° C, and the chlorination temperature is 270 to 320 ° C.
  • the preparation method provided by the present invention is preferably carried out in a fixed bed or a fluidized bed reactor.
  • the formula for calculating the yield of each compound is as follows:
  • i represents three substances such as 3-TF, 2,5-CTF, 2,3-CTF, 2,6,3-DCTF, and other products include insufficient side chain methyl chloride fluorination, excessive chlorination on the ring, etc. By-products, as well as substances lost during the experiment. Since the conversion of 3-methylpyridine in each of the following examples is 100% under the given reaction conditions, in the present invention, the yield of the product i is the selectivity of the product i.
  • the target product 2-chloro-5-trifluoromethyl is improved by designing and using a chlorofluorination catalyst and a chlorination catalyst as compared with the prior art.
  • the selectivity and yield of the pyridine, 2-chloro-5-trifluoromethylpyridine selectivity and yield up to 76.7%; the gas from the first reaction zone directly enters the second reaction zone reaction without cooling
  • the invention also provides the following method for preparing 2-chloro-5-trifluoromethylpyridine, which has high raw material conversion rate, high target product selectivity, low reaction temperature, low energy consumption, simple separation, no need to use organic solvent, Initiator and photochlorination reactor equipment.
  • the invention provides a preparation method of 2-chloro-5-trifluoromethylpyridine, and the chemical reaction formula is as follows:
  • a method for preparing 2-chloro-5-trifluoromethylpyridine comprising:
  • the second catalyst is selected from at least one of ZSM-5, 5A, ⁇ and 13X molecular sieves,
  • the ZSM-5 molecular sieve has a Si/Al of 50 to 300, and the equilibrium cation is at least one selected from the group consisting of H + , Na + , K + , and Ca 2+ .
  • the preparation method provided by the present invention uses a catalyst selected from at least one of ZSM-5, 5A, ⁇ and 13X molecular sieves.
  • the Si/Al is 50-300, and the equilibrium cation is at least one selected from the group consisting of H + , Na + , K + , and Ca 2+ . .
  • the ZSM-5 molecular sieve has a Si/Al of 80 to 200, and the equilibrium cation is at least one selected from the group consisting of H+, Na +, and K + .
  • the reaction temperature is satisfied so that the reaction proceeds smoothly.
  • the reaction temperature is from 150 to 350 °C.
  • reaction temperature is 200 to 300 °C.
  • the molar ratio of 3-trifluoromethylpyridine to chlorine gas is sufficient for the reaction to proceed smoothly.
  • the molar ratio of the 3-trifluoromethylpyridine to chlorine is 1:0.1-20.
  • the molar ratio of the 3-trifluoromethylpyridine to chlorine is 1:0.5-5.
  • the contact time of the 3-trifluoromethylpyridine and the chlorine gas in the catalyst bed is satisfied so that the reaction proceeds smoothly.
  • the contact time of the 3-trifluoromethylpyridine and chlorine in the catalyst bed is from 0.5 to 100 s.
  • the contact time of the 3-trifluoromethylpyridine and chlorine in the catalyst bed is from 15 to 70 s.
  • the preparation method provided by the present invention can be carried out in a fixed bed or a fluidized bed reactor.
  • the reaction is carried out in a fluidized bed reactor.
  • the material of the reactor may be a quartz tube or an Inconel alloy.
  • the above preparation method of 2-chloro-5-trifluoromethylpyridine has the following advantages compared with the prior art: the target product 2-chloro-5-trifluoromethylpyridine has high selectivity and high atomic utilization rate; The trifluoromethylpyridine is directly fed without the use of an organic diluent, and does not require additional vaporization and separation of the diluent; the reaction temperature is low and the energy consumption is small.
  • the invention further provides a preparation method of 2-chloro-5-trifluoromethylpyridine, which has high conversion rate of raw materials, high selectivity of target product, low reaction temperature, low energy consumption, simple separation, no need to use organic solvent, and initiation Characteristics of the agent and photochlorination reactor equipment.
  • the invention provides a preparation method of 2-chloro-5-trifluoromethylpyridine, and the chemical reaction formula is as follows:
  • a method for preparing 2-chloro-5-trifluoromethylpyridine comprising:
  • the third catalyst is selected from the group consisting of fluorides, oxides, hydroxides, carbonates or chlorides of magnesium, calcium, strontium, supported palladium catalysts supported on activated carbon, alumina or aluminum fluoride.
  • the third catalyst used is selected from the group consisting of magnesium, calcium, barium fluoride, oxide, hydroxide, carbonate or chloride, and the load supported on activated carbon, alumina or aluminum fluoride.
  • Type palladium catalyst is selected from the group consisting of magnesium, calcium, barium fluoride, oxide, hydroxide, carbonate or chloride, and the load supported on activated carbon, alumina or aluminum fluoride.
  • the fluoride, oxide, hydroxide, carbonate and chloride of magnesium, calcium and barium may be magnesium fluoride, calcium fluoride, barium fluoride, magnesium oxide, calcium oxide, barium oxide or hydroxide.
  • the supported palladium catalyst supported on activated carbon, alumina or aluminum fluoride may be a supported palladium catalyst supported on activated carbon, a supported palladium catalyst supported on alumina, and a load supported on aluminum fluoride.
  • Type palladium catalyst a supported palladium catalyst supported on activated carbon, a supported palladium catalyst supported on alumina, and a load supported on aluminum fluoride.
  • the third catalyst is selected from the group consisting of magnesium, calcium fluoride, oxide or chloride, and palladium catalyst supported on activated carbon or aluminum fluoride.
  • the third catalyst used is a supported palladium catalyst supported on activated carbon, alumina or aluminum fluoride
  • the mass percentage of palladium in the catalyst satisfies the smooth progress of the reaction.
  • the mass percentage of the palladium in the catalyst is from 0.1 to 10% by weight.
  • the mass percentage of the palladium in the catalyst is from 0.5 to 3% by weight.
  • the activation pretreatment is carried out before use.
  • the activation pretreatment may be an activation pretreatment of the supported palladium catalyst at a temperature of 120 to 350 ° C using nitrogen gas and/or chlorine gas.
  • the reaction temperature is satisfied so that the reaction proceeds smoothly.
  • the reaction temperature is from 220 to 360 °C.
  • reaction temperature is 270 to 320 °C.
  • the molar ratio of 3-trifluoromethylpyridine to chlorine gas is sufficient for the reaction to proceed smoothly.
  • the molar ratio of the 3-trifluoromethylpyridine to chlorine is 1:0.1-50.
  • the molar ratio of the 3-trifluoromethylpyridine to chlorine is 1:4-10.
  • the contact time of the 3-trifluoromethylpyridine and the chlorine gas in the catalyst bed is satisfied so that the reaction proceeds smoothly.
  • the contact time of the 3-trifluoromethylpyridine and chlorine in the catalyst bed is from 1 to 60 s.
  • the contact time of the 3-trifluoromethylpyridine and chlorine in the catalyst bed is 5 to 30 s.
  • the preparation method provided by the present invention can be carried out in a fixed bed or a fluidized bed reactor.
  • the reaction is carried out in a fluidized bed reactor.
  • the prepared product is washed with water, alkali washed and distilled to obtain an oily product, that is, 2-chloro-5-trifluoromethylpyridine.
  • the yield of the target product in the present invention is the selectivity of the target product.
  • the target product 2-chloro-5-trifluoromethylpyridine has high selectivity and high atomic utilization rate;
  • the direct feeding of 3-trifluoromethylpyridine does not require the use of an organic diluent, and does not require additional vaporization and separation of the diluent; the reaction temperature is low and the energy consumption is small.
  • Example 1 The reaction temperature in Example 1 was lowered from 150 ° C to 100 ° C, and the remaining reaction conditions and product treatment methods were the same as in Example 1. The final obtained oily product after drying was 91.2 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% MoCl 5 /AC (activated carbon supported MoCl 5 , loading 15wt%, 12g), The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 97.9 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% FeCl 3 /AC (activated carbon supported FeCl 3 , loading 15wt%, 12g), The remaining reaction conditions and product processing methods were the same as in Example 1.
  • the resulting oily product after drying was 107.2 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% CuCl 2 /AC (activated carbon supported CuCl 2 , loading 15wt%, 12g), The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 100.9 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% CuCl/AC (activated carbon supported CuCl, loading 15wt%, 12g), and the rest of the reaction
  • the conditions and product processing methods are the same as in the first embodiment.
  • the final obtained oily product after drying was 98.1 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15 wt%, 12 g) in Example 1 was changed to 15% ZnCl 2 /AC (activated carbon supported ZnCl 2 , loading 15 wt%, 12 g), The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 100.7 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15 wt%, 12 g) in Example 1 was changed to 15% AlCl 3 /AC (activated carbon supported AlCl 3 , loading 15 wt%, 12 g), The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 105.2 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • the resulting oily product after drying was 103.5 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% HPW/AC (activated carbon supported phosphotungstic acid, loading 15wt%, 12g), The remaining reaction conditions and product processing methods were the same as in Example 1.
  • the resulting oily product after drying was 106.8 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% HSiW/AC (activated carbon supported silicotungstic acid, loading 15wt%, 12g), The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 93.2 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , loading 15wt%, 12g) in Example 1 was replaced by 15% HPW/TiO 2 (TiO 2 supported phosphotungstic acid, loading 15wt%, 12g The remaining reaction conditions and product processing methods were the same as in Example 1. The final obtained oily product after drying was 93.2 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 The amount of chlorine gas introduced in Example 1 was increased from 37.5 g (0.5 mol) to 71.0 g (1.0 mol), and the remaining reaction conditions and product treatment methods were the same as in Example 1. The final obtained oily product after drying was 108.7 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • Example 1 15% WCl 6 /AC (activated carbon supported WCl 6 , 15% by weight, 12 g) was changed to WCl 6 (no load, 1.8 g), and the remaining reaction conditions and product treatment methods were the same as in Example 1.
  • the final obtained oily product after drying was 98.2 g.
  • the conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1. Comparing with Example 1, it can be seen that when the active component is not supported on AC, not only the conversion of 2-chloro-5-trifluoromethylpyridine is decreased from 99.9% to 65.2%, but also the target product 2,3-dichloro. The selectivity of 5-5-trifluoromethylpyridine was also significantly reduced from 92.1% to 65.7%. It can be seen that loading the metal chloride on a carrier with a high specific surface area can significantly improve its catalytic performance.
  • Example 1 The reaction temperature in Example 1 was raised from 150 ° C to 200 ° C, and the remaining reaction conditions and product treatment methods were the same as in Example 1. The resulting oily product after drying was 109.5 g. The conversion of 2-chloro-5-trifluoromethylpyridine and the selectivity and yield of the chlorination reaction product are shown in Table 1.
  • the inner diameter of the furnace is 30mm and the height is 600mm.
  • the upper and lower sections are separately temperature controlled.
  • the upper section is the chlorofluorination reaction zone and the lower section is the chlorination reaction zone.
  • the inner diameter of the reaction tube is 19mm and the length is 700mm.
  • the material is stainless steel.
  • the height of the upper and lower catalysts is 140mm, and the upper and lower catalyst beds are in the constant temperature zone of the upper and lower sections.
  • the chlorofluorination catalyst bed consists of 55.5% MgF 2 -40.0% Co 2 O 3 -0.55% CeO 2 (55.5%, 40%, 0.5% is the atomic mole percentage of the metal, which is the number of moles of metal atoms of each component and the metal atom
  • the ratio of the total number of moles, the composition of the chlorofluorination catalyst is expressed by the molar ratio of metal atoms, the composition of the catalyst of the same formula, and the catalyst is formed into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the chlorination catalyst bed consists of 1% Pd/activated carbon (1% is the mass ratio of metal palladium in the calcined catalyst, and the composition of the supported chlorination catalyst is expressed by the ratio of the mass of the metal atom to the total mass of the catalyst.
  • the composition of the catalyst is the same as that of the catalyst, and the catalyst is molded into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the chlorofluorination reaction zone was heated to 235 ° C and the chlorination reaction zone was heated to 290 ° C.
  • the feed rate of anhydrous hydrogen fluoride is controlled to be 10.00 g/h (0.500 mol/h), and the catalyst is activated by introducing HF for 3 h, and then 3-methylpyridine vaporized with nitrogen as a carrier gas and chlorine gas are introduced into the reaction tube. .
  • the flow control of 3-methylpyridine was 4.00g/h (0.043mol/h), the flow rate of chlorine gas was controlled to 7.7L/h (0.344mol/h), and the flow rate of nitrogen gas was maintained at 12.0L/h (0.536mol). /h).
  • the contact time of all the starting reaction materials with the chlorofluorination catalyst bed and the chlorination catalyst bed catalyst was 4.5 s, and the reaction was carried out for 8 hours.
  • the off-gas leaving the reaction tube is passed to a water wash column and an alkali wash column to condense.
  • the obtained oil layer was separated, neutralized with ammonia, and subjected to steam distillation to obtain an oily product.
  • the obtained oily product was dried over anhydrous sodium sulfate and weighed to a mass of 63.04 g, and quantitatively analyzed by gas chromatography internal standard method.
  • the mass content of 2,5-CTF was 70.8%, and the reaction yield was 71.5% (based on 3 -MP calculation, the same below).
  • the upper part of the reaction tube described in Example 1 was filled with 55.5% MgF2-40% ZnO-0.5% K2O catalyst, and the catalyst was formed into a cylinder having a diameter of 3 mm and a height of 4 mm, and the lower stage was filled with 2% Pd/activated carbon catalyst, catalyst. It is formed into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the chlorofluorination reaction zone was heated to 265 ° C and the chlorination reaction zone was heated to 320 ° C.
  • the feed rate of anhydrous hydrogen fluoride is controlled to be 10.00 g/h (0.500 mol/h), and the catalyst is activated by passing HF for 3 h, and then the 3-methylpyridine vaporized with nitrogen as a carrier gas and chlorine gas are introduced into the reaction tube.
  • the flow control of 3-methylpyridine was 4.00g/h (0.043mol/h), the flow rate of chlorine gas was controlled to 7.7L/h (0.344mol/h), and the flow rate of nitrogen gas was maintained at 12.0L/h (0.536mol). /h).
  • Example 1 The treatment of the off-gas leaving the reaction tube was as in Example 1. 64.35 g of an oily product was obtained, which was subjected to gas chromatography, and the mass content of 2,5-CTF was 65.7%, and the reaction yield was 67.8%.
  • the upper portion of the reaction tube described in Example 14 was filled with 77.0% MgF 2 -20.0% Bi 2 O 3 -2.0% Na 2 O catalyst, and the catalyst was molded into a cylinder having a diameter of 3 mm and a height of 4 mm, and the lower stage was filled with MgF 2 .
  • the catalyst was formed into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the chlorofluorination reaction zone was heated to 220 ° C and the chlorination reaction zone was heated to 280 °C.
  • the feed rate of anhydrous hydrogen fluoride is controlled to be 10.00 g/h (0.500 mol/h), and the catalyst is activated by passing HF for 3 h, and then the 3-methylpyridine vaporized with nitrogen as a carrier gas and chlorine gas are introduced into the reaction tube.
  • the flow control of 3-methylpyridine was 4.00g/h (0.043mol/h), the flow rate of chlorine gas was controlled to 7.7L/h (0.344mol/h), and the flow rate of nitrogen gas was maintained at 12.0L/h (0.536mol). /h).
  • Example 14 The treatment of the off-gas leaving the reaction tube was as in Example 14. 61.94 g of an oily product was obtained and subjected to gas chromatography analysis. The mass content of 2,5-CTF was 77.2%, and the reaction yield was 76.7%.
  • the upper part of the reaction tube described in Example 14 was filled with 85.0% CrF 3 -10.0% CuO-5.0% La 2 O 3 catalyst, and the catalyst was formed into a cylinder having a diameter of 3 mm and a height of 4 mm, and the lower stage was filled with MgO catalyst, catalyst. It is formed into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the chlorofluorination reaction zone was heated to 235 ° C and the chlorination reaction zone was heated to 300 ° C.
  • the feed rate of anhydrous hydrogen fluoride was controlled to 10.32 g/h (0.516 mol/h), and the catalyst was activated by passing HF for 3 h, and then the 3-methylpyridine vaporized with nitrogen as a carrier gas and chlorine gas were introduced into the reaction tube. in.
  • the flow rate of 3-methylpyridine was 4.00g/h (0.043mol/h)
  • the flow rate of chlorine gas was 8.7L/h (0.387mol/h)
  • the flow rate of nitrogen gas was kept at 12.0L/h (0.536mol). /h).
  • the treatment of the off-gas leaving the reaction tube was as in Example 1. 40.50 g of an oily product was obtained, which was subjected to gas chromatography, and the mass content of 2,5-CTF was 69.7%, and the reaction yield was 74.5%.
  • Example 18 All operating conditions were the same as in Example 16 except for the catalyst.
  • 90.0% CrF3-8.0% Fe2O3-2.0% La2O3 catalyst was packed in the upper part of the reaction tube, and BaCl2 catalyst was filled in the lower stage; in Example 19, 90.0% AlF 3 -8.0% NiO- was filled in the upper part of the reaction tube. 2.0% BaO catalyst, the lower stage is filled with CaCl 2 catalyst; in Example 20, the upper part of the reaction tube is filled with 90.0% CrF 3 -8.0% NiO-2.0% Na 2 O catalyst, and the lower stage is filled with 1.5% Pd / activated carbon catalyst.
  • the furnace has an inner diameter of 35 mm and a height of 500 mm, and the upper and lower sections are respectively temperature-controlled.
  • the lower section is the chlorofluorination reaction zone and the upper section is the chlorination reaction zone.
  • the reaction tube is made of Incon, and the inner diameter of the reaction tube is 30 mm and the length is 600 mm.
  • the lower part of the reaction tube was filled with 60 mL of 85% AlF3-10% Mn2O3-5% BaO (average particle size 0.15 mm) chlorofluorination catalyst, the static bed height was 89 mm, and the upper part of the reaction tube was filled with 60 mL of 1% Pd/activated carbon (average The particle size is 0.15 mm) chlorination catalyst, and the static bed height is 89 mm.
  • a distribution plate is placed at the bottom of the reactor and in the middle of the reactor for distributing the gas stream and isolating the supported catalyst. After fluidizing at 235 ° C for 1 h with nitrogen, the catalyst was fluorinated by passing HF for 4 h at a feed rate of 8.59 g/h (0.430 mol/h).
  • 3-methylpyridine vaporized with nitrogen as a carrier gas and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-methylpyridine was 4.00 g/h (0.043 mol/h)
  • the flow rate of chlorine gas was controlled to 5.77 L/h (0.258 mol/h)
  • the flow rate of nitrogen gas was maintained at 9.62 L/h (0.430 mol). /h).
  • the off-gas leaving the reaction tube is passed to a water wash column and an alkali wash column to condense.
  • the obtained oil layer was separated, neutralized with ammonia, and subjected to steam distillation to obtain an oily product.
  • the obtained oily product was dried over anhydrous sodium sulfate and weighed 166.49 g, and quantitatively analyzed by gas chromatography internal standard method.
  • the mass content of 2,5-CTF was 67.3%, and the reaction yield was 73.9%.
  • Example 21 The other conditions were the same as in Example 21 except that the catalyst was different.
  • the lower part of the reaction tube was filled with 60 mL of 90% AlF3-9% ZnCl 2 -1% CaO (average particle size of 0.15 mm) chlorofluorination catalyst, and the upper stage was filled with 60 mL of 1% Pd/Al 2 O 3 (average particle size of 0.15 mm). Chlorination catalyst.
  • the product was treated and analyzed in the same manner as in Example 21 to obtain 158.90 g of an oily product.
  • the mass content of 2,5-CTF was 68.8%, and the reaction yield was 72.1%.
  • a stainless steel tube having a reaction tube inner diameter of 25 mm and a length of 800 mm was used as a fixed bed reactor, and a volume of 40 mL of HZSM-5 (representing H+ is a balanced cation) molecular sieve having a particle size of 5-10 mesh Si/Al of 100 was filled.
  • the reaction line was connected and purged with nitrogen gas, and the flow rate of nitrogen was 100 mL/min.
  • the reaction furnace was heated to 290 ° C at a heating rate of 5 ° C / min. After the catalyst bed reached the reaction temperature, the nitrogen purge was stopped, and the chlorine gas purge was changed, and 3-trifluoromethyl was continuously introduced into the fixed bed reactor.
  • the base pyridine starts the reaction.
  • the molar ratio of the reaction starting material 3-trifluoromethylpyridine to chlorine gas was 1:2, and the contact time of the reaction mass in the catalyst bed was 30.9 s.
  • the reaction product was condensed in an ice water bath and collected in a collection flask to give an oil. After the completion of the reaction, the oil was washed with water to remove acid, dried over anhydrous sodium sulfate, and then subjected to distillation. The fraction was subjected to qualitative analysis by GC-MS, and the fraction composition was quantitatively analyzed by gas chromatography internal standard method.
  • reaction results were: 3-trifluoromethylpyridine conversion rate of 98.7%, and 2-chloro-5-trifluoromethylpyridine selectivity of 93.8%.
  • Example 23 The conditions were the same as in Example 23 except for the catalyst, and the catalyst used was a 5A molecular sieve.
  • Example 23 The conditions were the same as in Example 23 except for the catalyst, and the catalyst used was a 13X molecular sieve.
  • reaction results were: the conversion of 3-trifluoromethylpyridine was 91.5%, and the selectivity of 2-chloro-5-trifluoromethylpyridine was 88.3%.
  • Example 23 The conditions were the same as in Example 23 except for the catalyst, and the catalyst used was a ⁇ molecular sieve.
  • Example 23 The conditions were the same as in Example 23 except for the reaction temperature, and the reaction temperature was 350 °C.
  • the reaction tube is made of Incon, and the inner diameter of the reaction tube is 30 mm and the length is 400 mm.
  • the reaction tube was filled with 60 mL of HZSM-5 molecular sieve catalyst with an average particle diameter of 0.15 mm and a Si/Al ratio of 100, and the mixture was heated at 235 ° C for 1 h with nitrogen gas, and then heated to 290 ° C at a heating rate of 5 ° C / min. After reaching the reaction temperature, the nitrogen purge was stopped, and the chlorine gas purge was passed, and 3-trifluoromethylpyridine was continuously introduced into the fixed bed reactor to start the reaction.
  • the molar ratio of the reaction starting material 3-trifluoromethylpyridine to chlorine gas was 1:2, and the contact time of the reaction mass in the catalyst bed was 58.5 s.
  • the reaction product was condensed in an ice water bath and collected in a collection flask to give an oil. After the completion of the reaction, the oil was washed with water to remove acid, dried over anhydrous sodium sulfate, and then subjected to distillation. The fraction was subjected to qualitative analysis by GC-MS, and the fraction composition was quantitatively analyzed by gas chromatography internal standard method.
  • reaction results were: a conversion of 3-trifluoromethylpyridine of 97.9% and a selectivity of 2-chloro-5-trifluoromethylpyridine of 94.5%.
  • the reaction was carried out as follows: the conversion of 3-trifluoromethylpyridine was 99.0%, and the selectivity of 2-chloro-5-trifluoromethylpyridine was 90.1%.
  • reaction results were: 3-trifluoromethylpyridine conversion rate was 95.7%, and 2-chloro-5-trifluoromethylpyridine selectivity was 92.5%.
  • reaction results were: 3-trifluoromethylpyridine conversion rate was 92.3%, and 2-chloro-5-trifluoromethylpyridine selectivity was 92.0%.
  • reaction results were: 3-trifluoromethylpyridine conversion rate was 94.4%, and 2-chloro-5-trifluoromethylpyridine selectivity was 88.1%.
  • reaction results were as follows: 3-trifluoromethylpyridine conversion was 98.5%, and 2-chloro-5-trifluoromethylpyridine selectivity was 85.2%.
  • the catalyst of Example 23 was changed to HZSM-5 molecular sieve having Si/Al of 22, and the other conditions were unchanged.
  • the reaction temperature was controlled at 250 ° C, and the remaining operating conditions were in accordance with Example 23.
  • the reaction result was: the conversion of 3-trifluoromethylpyridine was 96.2%, and the selectivity of the target product 2-chloro-5-trifluoromethylpyridine was only 20.2%.
  • the furnace has an inner diameter of 30 mm and a height of 600 mm.
  • the reaction tube has an inner diameter of 19 mm and a length of 700 mm. It is made of stainless steel and has a catalyst loading height of 140 mm.
  • the catalyst bed consists of 1% Pd/activated carbon (1% is the mass ratio of metal palladium in the calcined catalyst, and the composition of the supported chlorination catalyst is expressed by the ratio of the mass of the metal atom to the total mass of the catalyst.
  • the catalyst composition is such that the catalyst is formed into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the reaction zone was heated to 290 ° C, and vaporized 3-trifluoromethylpyridine and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-trifluoromethylpyridine was controlled to 6.33 g/h (0.043 mol/h), and the flow rate of chlorine gas was controlled to be 7.7 L/h (0.344 mol/h).
  • the off-gas leaving the reaction tube is passed to a water wash column and an alkali wash column to condense.
  • the obtained oil layer was separated, neutralized with ammonia, and subjected to steam distillation to obtain an oily product.
  • the obtained oily product was dried over anhydrous sodium sulfate and weighed to a mass of 66.28 g, which was quantitatively analyzed by gas chromatography internal standard method.
  • the mass content of 2-chloro-5-trifluoromethylpyridine was 88.7%, and the yield was 94.1% (calculated relative to 3-trifluoromethylpyridine, the same below).
  • the reaction tube described in Example 34 was filled with a 2% Pd/activated carbon catalyst, and the catalyst was molded into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the reaction zone was heated to 320 °C.
  • the vaporized 3-trifluoromethylpyridine and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-trifluoromethylpyridine was controlled to 6.33 g/h (0.043 mol/h), and the flow rate of chlorine gas was controlled to be 7.7 L/h (0.344 mol/h).
  • the tail gas leaving the reaction tube was treated in the same manner as in Example 34 to obtain 67.59 g of an oily product which was subjected to gas chromatography.
  • the mass content of 2-chloro-5-trifluoromethylpyridine was 84.8%, and the yield was 91.7%.
  • the reaction tube described in Example 34 was filled with a MgF 2 catalyst, and the catalyst was molded into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the reaction zone was heated to 280 °C.
  • the vaporized 3-trifluoromethylpyridine and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-trifluoromethylpyridine was controlled to 6.33 g/h (0.043 mol/h), and the flow rate of chlorine gas was controlled to be 7.7 L/h (0.344 mol/h).
  • the off-gas from the reaction tube was treated in the same manner as in Example 34 to obtain 65.86 g of an oily product, which was subjected to gas chromatography analysis.
  • the mass content of 2-chloro-5-trifluoromethylpyridine was 87.8%, and the yield was 92.5%.
  • the reaction tube described in Example 34 was filled with a MgO catalyst, and the catalyst was molded into a cylinder having a diameter of 3 mm and a height of 4 mm.
  • the reaction zone was heated to 300 °C.
  • the vaporized 3-trifluoromethylpyridine and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-trifluoromethylpyridine was 6.33 g/h (0.043 mol/h), and the flow rate of chlorine gas was 8.7 L/h (0.387 mol/h).
  • Example 34 The treatment of the off-gas leaving the reaction tube was as in Example 34. 48.49 g of an oily product was obtained, which was subjected to gas chromatography, and the mass content of 2-chloro-5-trifluoromethylpyridine was 86.7%, and the yield was 89.6%.
  • Example 38 a BaCl 2 catalyst was packed in the reaction tube; in Example 39, a CaCl 2 catalyst was packed in the reaction tube; and in Example 40, a 1.5% Pd/activated carbon catalyst was packed in the reaction tube.
  • the reaction yielded 66.25g, 61.49g and 64.57g of oily products respectively, and analyzed by gas chromatography.
  • the mass contents of 2-chloro-5-trifluoromethylpyridine were 85.0%, 89.5% and 89.8%, respectively.
  • the yields were respectively 90.1%, 88.0%, 92.8%.
  • the furnace has an inner diameter of 35 mm and a height of 500 mm.
  • the reaction tube is made of Incon, and the inner diameter of the reaction tube is 30 mm and the length is 600 mm.
  • the reaction tube was filled with 60 mL of 1% Pd/activated carbon (average particle size of 0.15 mm) chlorination catalyst, and the static bed height was 89 mm. After fluidizing at 235 ° C for 1 h with nitrogen, vaporized 3-trifluoromethylpyridine and chlorine gas were introduced into the reaction tube.
  • the flow rate of 3-trifluoromethylpyridine was 6.33 g/h (0.043 mol/h), the flow rate of chlorine gas was controlled to 5.77 L/h (0.258 mol/h), and the flow rate of nitrogen gas was maintained at 9.62 L/h ( 0.430 mol/h).
  • the off-gas leaving the reaction tube is passed to a water wash column and an alkali wash column to condense.
  • the obtained oil layer was separated, neutralized with ammonia, and subjected to steam distillation to obtain an oily product.
  • the obtained oily product was dried over anhydrous sodium sulfate and weighed to 185.88 g, and quantitatively analyzed by gas chromatography internal standard method. The mass content of 2-chloro-5-trifluoromethylpyridine was 95.8%, and the yield was 94.9%.
  • Example 41 The other conditions were the same as in Example 41 except that the catalyst was different.
  • the reaction tube was filled with 60 mL of a 1% Pd/Al 2 O 3 (average particle diameter of 0.15 mm) chlorination catalyst.
  • the product was treated and analyzed in the same manner as in Example 3.8 to give 179.69 g of an oily product.
  • the mass fraction of 2-chloro-5-trifluoromethylpyridine was determined to be 94.6% and the yield was 90.7%.
  • the yield and selectivity of the target product 2,3-dichloro-5-trifluoromethylpyridine are remarkably improved.
  • the selectivity of 2,3-dichloro-5-trifluoromethylpyridine can be substantially at least 82%.
  • the method provided by the invention not only reduces the unit consumption of the product, reduces the separation cost, but also has a reaction temperature much lower than 400 ° C, which can significantly reduce energy consumption and improve safety.

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Abstract

本发明公开了一种制备2,3-二氯-5-三氟甲基吡啶的方法，在100～150℃温度和0.5～5.0MPa压力下，在选自负载型金属氯化物、负载型沸石分子筛和负载型杂多酸中的至少一种的催化剂作用下，2-氯-5-三氟甲基吡啶和氯气反应得到2,3-二氯-5-三氟甲基吡啶。本发明提供的制备方法具有目标产物选择性高、氯气利用率高、工艺条件温和、操作简单和三废量少的优点。本发明还公开了相比现有技术能够降低单耗、降低分离成本、提高安全性的制备备2-氯-5-三氟甲基吡啶的制备方法。

Description

一种高选择性地制备2,3-二氯-5-三氟甲基吡啶的方法 技术领域
本发明涉及一种氯代三氟甲基吡啶的制备方法，尤其是涉及一种2,3-二氯-5-三氟甲基吡啶的制备方法。
背景技术
含氟、杂环、手性是现代农药和医药领域新药的三大特征。近年来，含氟吡啶类新型农药，如啶虫隆、啶蜱脲、盖草能和氟啶胺等，具有广谱内吸、高效低毒、污染小等优点，已成为高效杀虫剂、除草剂和杀菌剂的骨干品种。2,3-二氯-5-三氟甲基吡啶(2,3,5-DCTF)是生产这些新型农药的关键中间体，已成为业内人士关注的热点。
对于2,3-二氯-5-三氟甲基吡啶的合成，现有技术中有以下公开：
(1)欧洲专利EP0078410报道了以流化床为反应器、2-氯-5-三氟甲基吡啶和氯气在FeCl 3/AC催化剂作用下、于250℃发生氯化反应生成2,3-二氯-5-三氟甲基吡啶的方法。此方法的收率能够达到74％，但气相氯化反应有多种异构体生成，以致产物分离困难；
(2)美国专利US4420618报道了常压液相氯化工艺制备2,3-二氯-5-三氟甲基吡啶的方法，在金属氯化物催化剂作用下，2-氯-5-三氟甲基吡啶与氯气反应生成2,3-二氯-5-三氟甲基吡啶。此方法的收率为16～75％，催化剂用量非常大，需要达到原料质量的40～200％，且反应过程中需要不断通入氯气，氯气利用效率低，导致生产成本高。
公开的现有技术中，气相氯化法存在2,3-二氯-5-三氟甲基吡啶选择性差、副产异构体多、分离困难的缺点，液相氯化法存在催化剂用量大、氯气利用率低的缺点。因此，有必要对2,3-二氯-5-三氟甲基吡啶的制备方法做进一步改进。
发明内容
本发明针对现有技术的不足，提供一种加压液相氯化制备2,3-二氯-5-三氟甲基吡啶的方法，具有目标产物选择性高、氯气利用率高、工艺条件温和、操作简单和三废量少的特点。
本发明所述的原料和产物的名称及缩写如下：
2,5-CTF：2-氯-5-三氟甲基吡啶(2-chloro-5-trifluoromethylpyridine)；
3,5-CTF：3-氯-5-三氟甲基吡啶(3-chloro-5-trifluoromethylpyridine)；
2,3,5-DCTF：2,3-二氯-5-三氟甲基吡啶(2,3-dichloro-5-trifluoromethylpyridine)；
2,6,3-DCTF：2,6-二氯-3-三氟甲基吡啶(2,6-dichloro-3-trifluoromethylpyridine)；
2,3,6,5-TCTF:2,3,6-三氯-5-三氟甲基吡啶(2,3,6-trichloro-5-trifluoromethylpyridine)。
3-TF:3-三氟甲基吡啶(3-trifluoromethylpyridine)；
3-MP:3-甲基吡啶(3-methylpyridine)；
2,3-CTF:2-氯-3-三氟甲基吡啶(2-chloro-3-trifluoromethylpyridine)；
本发明提供的制备方法，其化学反应式如下：
Figure PCTCN2018119312-appb-000001
本发明提供如下技术方案：
一种制备2,3-二氯-5-三氟甲基吡啶的方法，所述方法包括：
在100～150℃温度和0.5～5.0MPa压力下，在第一催化剂作用下，2-氯-5-三氟甲基吡啶和氯气反应得到2,3-二氯-5-三氟甲基吡啶；
所述第一催化剂选自负载型金属氯化物、负载型沸石分子筛和负载型杂多酸中的至少一种，
所述负载型金属氯化物，其活性组分选自WCl 6、MoCl 5、FeCl 3、AlCl 3、CuCl 2、ZnCl 2、SnCl 4、和SbCl 5中的至少一种，且活性组分的负载量为1～50wt％，
所述负载型沸石分子筛，其沸石分子筛选自ZSM-5、Beta、X、Y、5A和L型沸石分子筛中的至少一种，且沸石分子筛的负载量为1～50wt％，
所述负载型杂多酸，其杂多酸选自磷钨酸、硅钨酸、磷钼酸和硅钼酸中的至少一种，且杂多酸的负载量为1～50wt％。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，以2-氯-5-三氟甲基吡啶和氯气为原料，在第一催化剂作用下，经反应得到2,3-二氯-5-三氟甲基吡啶。使用的第一催化剂通过将金属氯化物、沸石分子筛或杂多酸负载在载体，来提供活性组分的分散度，从而使其适合用于以2-氯-5-三氟甲基吡啶和氯气为原料制备2,3-二氯-5-三氟甲基吡啶的反应，并且能够显著 提高目标化合物2,3-二氯-5-三氟甲基吡啶的选择性。
本发明使用的第一催化剂选自负载型金属氯化物、沸石分子筛和杂多酸中的至少一种。
当所述第一催化剂为负载型金属氯化物，其活性组分自WCl 6、MoCl 5、FeCl 3、AlCl 3、CuCl 2、ZnCl 2、SnCl 4、和SbCl 5中的至少一种。
优选的是，所述活性组分选自WCl 6、MoCl 5、ZnCl 2、FeCl 3中的至少一种。
所述负载型金属氯化物中，活性组分的负载量优选为1～50wt％。
进一步优选的是，所述活性组分的负载量为5～20wt％。
当所述第一催化剂为负载型沸石分子筛时，沸石分子筛选自ZSM-5、Beta、X、Y、5A和L型沸石分子筛中的至少一种。
优选的是，所述沸石分子筛选自ZSM-5、Beta、L中的至少一种。
所述沸石分子筛，其Si/Al比满足使反应顺利进行即可。优选的是，所述沸石分子筛的Si/Al比为200以下，且平衡阳离子选自H+、碱金属离子、碱土金属离子、过渡金属离子和稀土金属离子中的至少一种。
所述负载型沸石分子筛，沸石分子筛的负载量优选为1～50wt％。
进一步优选的是，所述沸石分子筛的负载量为5～20wt％。
当所述第一催化剂为负载型杂多酸时，杂多酸选自磷钨酸、硅钨酸、磷钼酸和硅钼酸中的至少一种。
所述负载型杂多酸中，杂多酸的负载量优选为1～50wt％。
进一步优选的是，所述杂多酸的负载量为5～20wt％。
本发明所述第一催化剂使用的载体，优选为选自二氧化硅、氧化铝、氧化钛、氧化锆、活性炭、碳化硅和介孔分子筛中的至少一种。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，催化剂的用量满足使反应顺利进行即可。
优选的是，所述第一催化剂的用量为2-氯-5-三氟甲基吡啶质量的0.1～30wt％。
进一步优选的是，所述第一催化剂的用量为2-氯-5-三氟甲基吡啶质量的5～20wt％。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，原料氯气与2-氯-5-三氟甲基吡啶的 配比满足使反应顺利进行即可。
优选的是，所述氯气与2-氯-5-三氟甲基吡啶的摩尔配比为0.5～10:1。
进一步优选的是，所述氯气与2-氯-5-三氟甲基吡啶的摩尔配比为1～3:1。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，反应压力需满足使反应顺利进行。
优选的是，所述反应压力为0.5～5.0MPa。
进一步优选的是，所述反应压力为1.0～2.0MPa。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，反应温度满足使反应顺利进行即可。
优选的是，所述反应温度为100～150℃。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，优选在高压反应釜中进行反应。所述高压反应釜，其材质优选为选自316L、蒙耐尔合金、英康合金或者哈氏合金。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，在反应结束后，可以先加入碱液，再经分离后得到2,3-二氯-5-三氟甲基吡啶。
所述碱液可以是有机碱和/或无机碱。所述有机碱，优选为选自二甲胺、二乙胺、三乙胺、二丙胺和三丙胺中的至少一种。所述无机碱，优选为选自NaOH、Na 2CO 3、NaHCO 3、KOH、K 2CO 3、KHCO 3和氨水中的至少一种。
本发明制备的2,3-二氯-5-三氟甲基吡啶可以用GC-MS进行定性分析，用气相色谱内标法进行定量分析。
本发明所述的2-氯-5-三氟甲基吡啶的转化率和产物的2,3-二氯-5-三氟甲基吡啶选择性及和收率的计算公式如下：
(1)2,5-CTF转化率：X2,5-CTF＝反应中消耗的2,5-CTF摩尔数/加入到反应器中的2,5-CTF摩尔数×100％；
(2)产物i选择性：Si＝产物i的摩尔数/反应中消耗的2,5-CTF摩尔数×100％；
(3)产物i收率：Yi＝X 2,5-CTF×S i＝产物i的摩尔数/加入到反应器中的2,5-CTF摩尔数×100％，
其中i代表2,3,5-DCTF、2,6,3-DCTF和2,3,6,5-TCTF等产物。
本发明提供的制备2,3-二氯-5-三氟甲基吡啶的方法，相比现有技术具有如下优势：目标 产物2,3-二氯-5-三氟甲基吡啶的选择性和收率高，能够达到90％以上；催化剂用量少，且与反应物易分离，能够实现催化剂的回收利用；无需使用有机溶剂，成本低，且氯气使用效率高。
进一步地，为降低单耗、降低分离成本、提高安全性，本发明还提供以下2-氯-5-三氟甲基吡啶的制备方法。
一种2-氯-5-三氟甲基吡啶的制备方法，所述方法为两段法，包括：
(1)氯氟化反应：在氯氟化催化剂作用下，保持氯氟化温度为150～320℃，使3-甲基吡啶、氯气和氟化氢通入氯氟化反应区域，得到包含3-三氟甲基吡啶的混合气；
(2)氯化反应：在氯化催化剂作用下，保持氯化温度220～380℃，将步骤(1)得到的包含3-三氟甲基吡啶的混合气通入氯化反应区域，得到2-氯-5-三氟甲基吡啶，所述氯化催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的钯催化剂。
本发明提供的上述制备方法，为两段法反应，包括氯氟化反应步骤和氯化反应步骤。其中在氯氟化反应步骤中，需使用氯氟化催化剂。
所述氯氟化催化剂，可以是本领域常用的氯氟化催化剂。
作为一种优选的方式，所述氯氟化催化剂包括主催化剂、第一助催化剂和第二助催化剂，所述主催化剂选自铝、镁和铬中的至少一种，所述第一助催化剂选自铁、钴、锰、镍、铜、铋和锌中的至少一种，所述第二助催化剂选自镧、铈、钡、钙、钠和钾中的至少一种。
作为进一步优选的方式，所述氯氟化催化剂中，主催化剂选自铝和/或铬，第一助催化剂选自铁、镍和铜中的至少一种，所述第二助催化剂选自镧、钡和钙中的至少一种。
所述氯氟化催化剂中，主催化剂、第一助催化剂和第二助催化剂三者之间的配比满足使反应顺利进行即可。
优选的是，所述主催化剂、第一助催化剂和第二助催化剂三者之间的摩尔比为50～95:5～42:0.3～8。
进一步优选的是，所述主催化剂、第一助催化剂和第二助催化剂三者之间的摩尔比为75～90:10～20:1～5。
本发明提供的制备方法，步骤(1)氯氟化反应步骤中，原料3-甲基吡啶、氯气和氟化氢之间的配比，满足使反应顺利进行即可。
优选的是，所述3-甲基吡啶、氯气和氟化氢三者之间的摩尔配比为1:0.1～50:1～30。
进一步优选的是，所述3-甲基吡啶、氯气和氟化氢三者之间的摩尔配比为1:4～10:3～12。
其中原料3-甲基吡啶，可以直接以气体的形式加入反应，也可以经惰性气体稀释后以混合气体的形式加入反应。
优选的是，所述3-甲基吡啶为经惰性气体稀释后的混合气体。
其中3-甲基吡啶在经惰性气体稀释后的混合气体中的比例，满足使反应顺利进行即可。
优选的是，所述3-甲基吡啶与混合气体的摩尔配比为1:0.5～50。
进一步优选的是，所述3-甲基吡啶与混合气体摩尔配比为1:5～20。
本发明提供的制备方法，步骤(1)氯氟化反应步骤中，原料3-甲基吡啶、氯气和氟化氢与氯氟化催化剂的接触时间满足使反应顺利进行即可。
优选的是，所述3-甲基吡啶、氯气和氟化氢与氯氟化催化剂的接触时间为0.5～40s。
进一步优选的是，所述3-甲基吡啶、氯气和氟化氢与氯氟化催化剂的接触时间为1.5～20s。
本发明提供的制备方法，步骤(2)氯化反应中，使用的氯化催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的钯催化剂。
所述镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐和氯化物，可以是氟化镁、氟化钙、氟化钡、氧化镁、氧化钙、氧化钡、氢氧化镁、氢氧化钙、氢氧化钡、碳酸镁、碳酸钙、碳酸钡、氯化镁、氯化钙、氯化钡。
所述负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂，可以是负载在活性炭上的负载型钯催化剂、负载在氧化铝上的负载型钯催化剂、负载在氟化铝上的负载型钯催化剂。
优选的是，所述氯化催化剂选自镁、钙的氟化物、氧化物或氯化物，负载在活性炭或氟化铝上的负载型钯催化剂。
本发明提供的制备方法，步骤(2)氯化反应步骤中，包含3-三氟甲基吡啶的混合气与氯化催化剂的接触时间满足使反应顺利进行即可。
优选的是，所述包含3-三氟甲基吡啶的混合气与氯化催化剂的接触时间为0.5～40s。
进一步优选的是，所述包含3-三氟甲基吡啶的混合气与氯化催化剂的接触时间为1.5～20s。
本发明提供的制备方法，为两段式方法，包括氯氟化反应步骤和氯化反应步骤，两个步骤之间的温度控制对反应结果有影响。
优选的是，所述氯氟化温度为150～320℃、氯化温度220～380℃。
进一步优选的是，所述氯氟化温度为220～260℃、氯化温度270～320℃。
本发明提供的制备方法，优选在固定床或者流化床反应器中进行。
本发明提供的制备方法，各化合物收率的计算公式如下：
产物i的收率：Y i＝(m i/M i)/(m 3-MP/M 3-MP)*100％，
其它产物的收率：Y其它＝(1-ΣY i)*100％，
其中i代表3-TF,2,5-CTF,2,3-CTF,2,6,3-DCTF等四种物质，其它产物包括侧链甲基氯氟化不充分、环上过度氯化等副产物，以及实验过程中损失的物质。由于在所给反应条件下，以下各实施例中3-甲基吡啶的转化率均为100％，所以在本发明中，产物i的收率即为产物i的选择性。
以上2-氯-5-三氟甲基吡啶的制备方法中，相比以往具有如下优势，通过设计并使用氯氟化催化剂和氯化催化剂，提高了目标产物2-氯-5-三氟甲基吡啶的选择性和收率，2-氯-5-三氟甲基吡啶的选择性和收率高达76.7％；第一段反应区域出来的气体直接进入第二段反应区域反应，不需要冷却、分离、再汽化的操作，操作简单，能耗降低；通过两段式反应，各段反应温度低，副产物含量少。
本发明还提供了以下的制备2-氯-5-三氟甲基吡啶的方法，具有原料转化率高、目标产物选择性高、反应温度低、能耗低、分离简单、无需使用有机溶剂、引发剂和光氯化反应器设备等特点。
本发明提供2-氯-5-三氟甲基吡啶的制备方法，化学反应式如下：
Figure PCTCN2018119312-appb-000002
本发明提供如下技术方案：
一种2-氯-5-三氟甲基吡啶的制备方法，所述方法包括：
在第二催化剂存在下，保持反应温度为150～350℃，使3-三氟甲基吡啶和氯气气相反应，得到2-氯-5-三氟甲基吡啶；
所述第二催化剂选自ZSM-5、5A、β和13X分子筛中的至少一种，
所述ZSM-5分子筛，其Si/Al为50～300、平衡阳离子选自H +、Na +、K +、Ca 2+中的至少一种。
本发明提供的制备方法，使用的催化剂选自ZSM-5、5A、β和13X分子筛中的至少一种。
当所述第二催化剂为ZSM-5分子筛时，作为一种优选的方式，其Si/Al为50～300、平衡阳离子选自H +、Na +、K +、Ca 2+中的至少一种。
作为进一步优选的方式，所述ZSM-5分子筛，其Si/Al为80～200、平衡阳离子选自H+、Na +和K +中的至少一种。
本发明提供的制备方法，反应温度满足使反应顺利进行即可。
优选的是，所述反应温度为150～350℃。
进一步优选的是，所述反应温度为200～300℃。
本发明提供的制备方法，3-三氟甲基吡啶与氯气的摩尔配比满足使反应顺利进行即可。
优选的是，所述3-三氟甲基吡啶与氯气的摩尔配比为1:0.1～20。
进一步优选的是，所述3-三氟甲基吡啶与氯气的摩尔配比为1:0.5～5。
本发明提供的制备方法，3-三氟甲基吡啶和氯气在催化剂床层的接触时间满足使反应顺利进行即可。
优选的是，所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为0.5～100s。
进一步优选的是，所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为15～70s。
本发明提供的制备方法，所述反应可以在固定床或流化床反应器中进行。
优选的是，所述反应在流化床反应器中进行。
反应器的材质，可以是石英管和Inconel合金等。
以上2-氯-5-三氟甲基吡啶的制备方法中，相比以往具有如下优势：目标产物2-氯-5-三氟 甲基吡啶的选择性高，原子利用率高；原料3-三氟甲基吡啶直接进料，不需使用有机稀释剂，不需要对稀释剂进行额外的汽化与分离；反应温度低，能耗小。
本发明再提供一种2-氯-5-三氟甲基吡啶的制备方法，具有原料转化率高、目标产物选择性高、反应温度低、能耗低、分离简单、无需使用有机溶剂、引发剂和光氯化反应器设备等特点。
本发明提供2-氯-5-三氟甲基吡啶的制备方法，化学反应式如下：
Figure PCTCN2018119312-appb-000003
本发明提供如下技术方案：
一种2-氯-5-三氟甲基吡啶的制备方法，所述方法包括：
在第三催化剂存在下，保持反应温度为220～360℃，使3-三氟甲基吡啶和氯气气相通过催化剂床层，得到2-氯-5-三氟甲基吡啶；
所述第三催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂。
本发明提供的制备方法，使用的第三催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂。
所述镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐和氯化物，可以是氟化镁、氟化钙、氟化钡、氧化镁、氧化钙、氧化钡、氢氧化镁、氢氧化钙、氢氧化钡、碳酸镁、碳酸钙、碳酸钡、氯化镁、氯化钙、氯化钡。
所述负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂，可以是负载在活性炭上的负载型钯催化剂、负载在氧化铝上的负载型钯催化剂、负载在氟化铝上的负载型钯催化剂。
作为一种优选的方式，所述第三催化剂选自镁、钙的氟化物、氧化物或氯化物、负载在活性炭或氟化铝上的钯催化剂。
当使用的第三催化剂为负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂时，钯在催化剂中的质量百分比满足使反应顺利进行即可。
优选的是，所述钯在催化剂中的质量百分比为0.1～10wt％。
进一步优选的是，所述钯在催化剂中的质量百分比为0.5～3wt％。
当使用的第三催化剂为负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂时，作为一种优选的方式，在使用前进行活化预处理。
所述活化预处理，可是使用氮气和/或氯气在120～350℃的温度下对负载型钯催化剂进行活化预处理。
本发明提供的制备方法，反应温度满足使反应顺利进行即可。
优选的是，所述反应温度为220～360℃。
进一步优选的是，所述反应温度为270～320℃。
本发明提供的制备方法，3-三氟甲基吡啶与氯气的摩尔配比满足使反应顺利进行即可。
优选的是，所述3-三氟甲基吡啶与氯气的摩尔配比为1:0.1～50。
进一步优选的是，所述3-三氟甲基吡啶与氯气的摩尔配比为1:4～10。
本发明提供的制备方法，3-三氟甲基吡啶和氯气在催化剂床层的接触时间满足使反应顺利进行即可。
优选的是，所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为1～60s。
进一步优选的是，所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为5～30s。
本发明提供的制备方法，所述反应可以在固定床或流化床反应器中进行。
优选的是，所述反应在流化床反应器中进行。
本发明提供的制备方法，制备得到的产品经水洗、碱洗及蒸馏以得到油状产品，即2-氯-5-三氟甲基吡啶。
由于在所给反应条件下，以下实施例中3-三氟甲基吡啶的转化率均为100％，所以在本发明中目标产物的收率即为目标产物的选择性。
以上方法中，相比以往制备2-氯-5-三氟甲基吡啶的方法，具有如下优势：目标产物2-氯-5-三氟甲基吡啶的选择性高，原子利用率高；原料3-三氟甲基吡啶直接进料，不需使用有机稀释剂，不需要对稀释剂进行额外的汽化与分离；反应温度低，能耗小。
具体实施方式
下面结合具体实施例来对本发明进行进一步说明，但并不将本发明局限于这些具体实施 方式。本领域技术人员应该认识到，本发明涵盖了权利要求书范围内所可能包括的所有备选方案、改进方案和等效方案。
实施例1
将2-氯-5-三氟甲基吡啶(90.8g，0.5mol)和15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)加入到250mL高压反应釜(Inconel合金)中，装好釜盖后，充入2MPa氮气保压2h，对反应釜进行试漏，确认反应物不漏气后，将其放入冰乙醇浴中进行冷却，当反应釜冷却至0℃以后，从反应釜气相管中向反应釜内充入约37.5g氯气(0.5mol)，然后将反应釜放入带磁力搅拌的加热套中，在搅拌条件下将反应体系加热至150℃，此时反应体系压力约为2.0MPa，在该温度下连续反应20h。反应结束后，待反应体系温度降至室温时，从液相管中向反应釜通氮气置换30min(置换出来的尾气通入到碱洗瓶中进行吸收、中和)，打开反应釜，通过过滤的方式将催化剂和产品分离，并向产品中加入10wt％的NaOH溶液中和，萃取、分液得到油状产品。所得到的油状产品用无水硫酸钠干燥之后称量质量为107.0g，用GC-MS进行定性分析，用气相色谱内标法进行定量分析。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例2
将实施例1中的反应温度由150℃降低至100℃，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为91.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例3
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％MoCl 5/AC(活性炭负载的MoCl 5，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为97.9g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例4
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％FeCl 3/AC(活性炭负载的FeCl 3，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相 同。最终所得干燥后油状产品质量为107.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例5
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％CuCl 2/AC(活性炭负载的CuCl 2，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为100.9g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例6
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％CuCl/AC(活性炭负载的CuCl，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为98.1g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例7
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％ZnCl 2/AC(活性炭负载的ZnCl 2，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为100.7g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例8
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％AlCl 3/AC(活性炭负载的AlCl 3，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为105.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例9
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15wt％NaY/AC(活性炭负载的NaY沸石分子筛，载量15wt％，NaY的Si/Al＝5.4，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为103.5g。2-氯 -5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例10
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％HPW/AC(活性炭负载的磷钨酸，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为106.8g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例11
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％HSiW/AC(活性炭负载的硅钨酸，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为93.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例12
将实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成15％HPW/TiO 2(TiO 2负载的磷钨酸，载量为15wt％，12g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为93.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
实施例13
将实施例1中氯气通入量有37.5g(0.5mol)增加至71.0g(1.0mol)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为108.7g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
对比实施例1
实施例1中15％WCl 6/AC(活性炭负载的WCl 6，载量为15wt％，12g)换成WCl 6(不负载，1.8g)，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为98.2g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。与实施例1比较可知，当活性组分不负载在AC上时，不仅2-氯-5-三氟甲基吡啶的转化率从99.9％下降至65.2％，而且目标产物2,3-二氯-5-三氟甲基吡啶的选择性也有了明显的降低，从92.1％降低至 65.7％。可见将金属氯化物负载在高比表面积的载体上能够显著提高其催化性能。
对比实施例2
将实施例1中的反应温度由150℃升高至200℃，其余反应条件和产品处理方法与实施例1相同。最终所得干燥后油状产品质量为109.5g。2-氯-5-三氟甲基吡啶转化率及氯化反应产物的选择性和收率见表1。
表1
Figure PCTCN2018119312-appb-000004
实施例14
加热炉炉膛内径为30mm，高度为600mm，上下两段分别控温。上段为氯氟化反应区域，下段为氯化反应区域。反应管内径19mm、长度为700mm，材质不锈钢，上下两段催化剂装填高度均为140mm，且保证上下两段催化剂床层分别在上下两段加热炉的恒温区内。氯氟化催化剂床层由55.5％MgF 2-40.0％Co 2O 3-0.55％CeO 2(55.5％、40％、0.5％为金属原子摩尔百分比，是各组分的金属原子摩尔数与金属原子的摩尔数总和的比值，氯氟化催化剂的组成均用 金属原子的摩尔比表示，下同)的催化剂组成，催化剂成型为直径是3mm高度是4mm的圆柱体。氯化催化剂床层由1％Pd/活性炭(1％为金属钯在焙烧后的催化剂中的质量占比，负载型的氯化催化剂的组成均用金属原子的质量占催化剂总质量的比值表示，下同)的催化剂组成，催化剂成型为直径是3mm高度是4mm的圆柱体。
将氯氟化反应区域加热到235℃，氯化反应区域加热到290℃。控制无水氟化氢的进料速度为10.00g/h(0.500mol/h)，通入HF 3h来活化催化剂，之后将以氮气为载气汽化过的3-甲基吡啶和氯气通入反应管中。其中，3-甲基吡啶的流量控制为4.00g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)，氮气的流量保持为12.0L/h(0.536mol/h)。反应物摩尔投料比为3-甲基吡啶:氯气:氟化氢:氮气＝1:8:11.6:12.5。所有起始反应物料与氯氟化催化剂床层及氯化催化剂床层催化剂的接触时间均为4.5s，反应8h。
离开反应管的尾气通入水洗塔和碱洗塔冷凝。将所得到的油层分离出来后用氨水中和，并进行水蒸气蒸馏以得到油状产品。所得到的油状产品用无水硫酸钠干燥之后称量质量为63.04g，用气相色谱内标法进行定量分析，2,5-CTF的质量含量为70.8％，反应收率为71.5％(基于3-MP计算，下同)。
实施例15
在实施例1中所述的反应管内上段填装55.5％MgF2-40％ZnO-0.5％K2O催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体，下段填装2％Pd/活性炭催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。
将氯氟化反应区域加热到265℃，氯化反应区域加热到320℃。控制无水氟化氢的进料速度为10.00g/h(0.500mol/h)，通入HF 3h来活化催化剂，之后将以氮气为载气气化过的3-甲基吡啶和氯气通入反应管中。其中，3-甲基吡啶的流量控制为4.00g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)，氮气的流量保持为12.0L/h(0.536mol/h)。反应物摩尔投料比为3-甲基吡啶:氯气:氟化氢:氮气＝1:8:11.6:12.5，所有起始反应物料与氯氟化催化剂床层及氯化催化剂床层催化剂的接触时间均为4.5s，反应8h。
离开反应管的尾气的处理方式如实施例1。得到64.35g油状产品，对其进行气相色谱分析，2,5-CTF的质量含量为65.7％，反应收率为67.8％。
实施例16
在实施例14中所述的反应管内上段填装77.0％MgF 2-20.0％Bi 2O 3-2.0％Na 2O催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体，下段填装MgF 2催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。
将氯氟化反应区域加热到220℃，氯化反应区域加热到280℃。控制无水氟化氢的进料速度为10.00g/h(0.500mol/h)，通入HF 3h来活化催化剂，之后将以氮气为载气气化过的3-甲基吡啶和氯气通入反应管中。其中，3-甲基吡啶的流量控制为4.00g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)，氮气的流量保持为12.0L/h(0.536mol/h)。反应物摩尔投料比为3-甲基吡啶:氯气:氟化氢:氮气＝1:8:11.6:12.5，所有起始反应物料与氯氟化催化剂床层及氯化催化剂床层催化剂的接触时间均为4.5s，反应8h。
离开反应管的尾气的处理方式如实施例14。得到61.94g油状产品，对其进行气相色谱分析，2,5-CTF的质量含量为77.2％，反应收率为76.7％。
实施例17
在实施例14中所述的反应管内上段填装85.0％CrF 3-10.0％CuO-5.0％La 2O 3催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体，下段填装MgO催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。
将氯氟化反应区域加热到235℃，氯化反应区域加热到300℃。控制无水氟化氢的进料速度为10.32g/h(0.516mol/h)，通入HF 3h来活化催化剂，之后将以氮气为载气气化过的3-甲基吡啶和氯气通入反应管中。其中，3-甲基吡啶的流量控制为4.00g/h(0.043mol/h)，氯气的流量控制为8.7L/h(0.387mol/h)，氮气的流量保持为12.0L/h(0.536mol/h)。反应物摩尔投料比为3-甲基吡啶:氯气:氟化氢:氮气＝1:9:12:12.5，所有起始反应物料与氯氟化催化剂床层及氯化催化剂床层催化剂的接触时间均为4.0s，反应6h。
离开反应管的尾气的处理方式如实施例1。得到40.50g油状产品，对其进行气相色谱分析，2,5-CTF的质量含量为69.7％，反应收率为74.5％。
实施例18～20
除了催化剂外，所有操作条件与实施例16相同。实施例18中，在反应管内上段填装 90.0％CrF3-8.0％Fe2O3-2.0％La2O3催化剂，下段填装BaCl2催化剂；实施例19中，在反应管内上段填装90.0％AlF 3-8.0％NiO-2.0％BaO催化剂，下段填装CaCl 2催化剂；实施例20中，在反应管内上段填装90.0％CrF 3-8.0％NiO-2.0％Na 2O催化剂，下段填装1.5％Pd/活性炭催化剂。
反应分别得到64.30g、65.34g、64.80g油状产品，对其进行气相色谱分析，2,5-CTF的质量含量分别为73.2％、69.9％、73.3％，反应收率分别为75.5％、73.2％、76.1％。
实施例21
加热炉炉膛内径为35mm，高度为500mm，上下两段分别控温。下段为氯氟化反应区域，上段为氯化反应区域。反应管材质为因康合金，反应管内径30mm、长度600mm。反应管下段填装60mL 85％AlF3-10％Mn2O3-5％BaO(平均粒径为0.15mm)氯氟化催化剂，静态床层高度为89mm，反应管上段填装60mL 1％Pd/活性炭(平均粒径为0.15mm)氯化催化剂，静态床层高度为89mm。在反应器底部和反应器中部均放置分布板，用于分布气流及隔离支撑催化剂。用氮气在235℃流化1h后以8.59g/h(0.430mol/h)的进料速度通HF 4h，对催化剂进行氟化。之后将以氮气为载气汽化过的3-甲基吡啶和氯气通入反应管中。其中，3-甲基吡啶的流量控制为4.00g/h(0.043mol/h)，氯气的流量控制为5.77L/h(0.258mol/h)，氮气的流量保持为9.62L/h(0.430mol/h)。反应物摩尔投料比为3-甲基吡啶:氯气:氟化氢:氮气＝1:6:10:10，所有起始反应物料与氯氟化催化剂床层及氯化催化剂床层催化剂的接触时间均为5.5s，反应24h。
离开反应管的尾气通入水洗塔和碱洗塔冷凝。将所得到的油层分离出来后用氨水中和，并进行水蒸气蒸馏以得到油状产品。所得到的油状产品用无水硫酸钠干燥之后称量质量为166.49g，用气相色谱内标法进行定量分析，2,5-CTF的质量含量为67.3％，反应收率为73.9％。
实施例22
除了催化剂不同外，其他条件与实施例21相同。反应管下段填装60mL90％AlF3-9％ZnCl 2-1％CaO(平均粒径为0.15mm)氯氟化催化剂，上段填装60mL 1％Pd/Al 2O 3(平均粒径为0.15mm)氯化催化剂。产物处理和分析方法同实施例21，得到158.90g油状产品，2,5-CTF的质量含量为68.8％，反应收率为72.1％。
实施例23
反应管内径为25mm、长度为800mm的不锈钢管作为固定床反应器，将体积为40mL、颗粒大小为5-10目Si/Al为100的HZSM-5(表示H+为平衡阳离子)分子筛装填入固定床反应器中部，连接反应管线，通入氮气进行吹扫，氮气流量为100mL/min。反应炉以5℃/min的升温速率升温至290℃，催化剂床层到达反应温度后停止氮气吹扫，改成通入氯气吹扫，同时向固定床反应器中连续通入3-三氟甲基吡啶，开始反应。反应原料3-三氟甲基吡啶和氯气的摩尔比为1:2，反应物料在催化剂床层接触时间为30.9s。反应产物通过冰水浴冷凝后在收集瓶中汇集，得到油状物。反应结束后，油状物经过水洗碱洗除酸后，用无水硫酸钠干燥之后进行蒸馏，采用GC-MS对馏分进行定性分析，采用气相色谱内标法对馏分组成进行定量分析。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为98.7％、2-氯-5-三氟甲基吡啶的选择性为93.8％。
实施例24
除了催化剂外，其他条件与实施例23相同，所用催化剂为5A分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为89.2％、2-氯-5-三氟甲基吡啶的选择性为89.0％。
实施例25
除了催化剂外，其他条件与实施例23相同，所用催化剂为13X分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为91.5％、2-氯-5-三氟甲基吡啶的选择性为88.3％。
实施例26
除了催化剂外，其他条件与实施例23相同，所用催化剂为β分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为92.3％、2-氯-5-三氟甲基吡啶的选择性为89.2％。
实施例27
除了反应温度外，其他条件与实施例23相同，反应温度为350℃。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为99.9％、2-氯-5-三氟甲基吡啶的 选择性为87.1％。
实施例28
反应管材质为因康合金，反应管内径30mm、长度400mm。反应管中填装60mL平均粒径为0.15mm的Si/Al为100的HZSM-5分子筛催化剂，用氮气在235℃流化1h后以5℃/min的升温速率升温至290℃，催化剂床层到达反应温度后停止氮气吹扫，改成通入氯气吹扫，同时向固定床反应器中连续通入3-三氟甲基吡啶，开始反应。反应原料3-三氟甲基吡啶和氯气的摩尔比为1:2，反应物料在催化剂床层接触时间为58.5s。反应产物通过冰水浴冷凝后在收集瓶中汇集，得到油状物。反应结束后，油状物经过水洗碱洗除酸后，用无水硫酸钠干燥之后进行蒸馏，采用GC-MS对馏分进行定性分析，采用气相色谱内标法对馏分组成进行定量分析。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为97.9％、2-氯-5-三氟甲基吡啶的选择性为94.5％。
实施例29
除了催化剂外，其他条件与实施例28相同，所用催化剂为Si/Al＝50的HZSM-5分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为99.0％、2-氯-5-三氟甲基吡啶的选择性为90.1％。
实施例30
除了催化剂外，其他条件与实施例28相同，所用催化剂为Si/Al＝100的NaZSM-5(表示Na +为平衡阳离子)分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为95.7％、2-氯-5-三氟甲基吡啶的选择性为92.5％。
实施例31
除了催化剂外，其他条件与实施例28相同，所用催化剂为Si/Al＝100的KZSM-5(表示K +为平衡阳离子)分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为92.3％、2-氯-5-三氟甲基吡啶的选择性为92.0％。
实施例32
除了催化剂外，其他条件与实施例28相同，所用催化剂为Si/Al＝100的CaZSM-5(表示Ca 2+为平衡阳离子)分子筛。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为94.4％、2-氯-5-三氟甲基吡啶的选择性为88.1％。
实施例33
除了氯气配比外，其他条件与实施例23相同，原料3-三氟甲基吡啶和氯气的摩尔比为1:10。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为98.5％、2-氯-5-三氟甲基吡啶的选择性为85.2％。
对比实施例3
将实施例23中的催化剂换为Si/Al为22的HZSM-5分子筛，其它条件不变。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为99.9％、但目标产物2-氯-5-三氟甲基吡啶的选择性仅为47.3％。
对比实施例4
按照中国CN104610137中公开的FeCl 3/活性炭催化剂为催化剂，控制反应温度为250℃，其余操作条件与实施例23一致。
经定量分析后，反应结果为：3-三氟甲基吡啶转化率为96.2％，目标产物2-氯-5-三氟甲基吡啶的选择性仅为20.2％。
实施例34
加热炉炉膛内径为30mm，高度为600mm。反应管内径19mm、长度为700mm，材质不锈钢，催化剂装填高度为140mm。催化剂床层由1％Pd/活性炭(1％为金属钯在焙烧后的催化剂中的质量占比，负载型的氯化催化剂的组成均用金属原子的质量占催化剂总质量的比值表示，下同)的催化剂组成，催化剂成型为直径是3mm高度是4mm的圆柱体。反应区域加热到290℃，汽化过的3-三氟甲基吡啶和氯气通入反应管中。其中，3-三氟甲基吡啶的流量控制为6.33g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)。反应物摩尔投料比为 3-三氟甲基吡啶:氯气＝1:8，所有起始反应物料与催化剂床层的接触时间为16.5s，反应8h。
离开反应管的尾气通入水洗塔和碱洗塔冷凝。将所得到的油层分离出来后用氨水中和，并进行水蒸气蒸馏以得到油状产品。所得到的油状产品用无水硫酸钠干燥之后称量质量为66.28g，用气相色谱内标法进行定量分析，2-氯-5-三氟甲基吡啶的质量含量为88.7％，收率为94.1％(相对于3-三氟甲基吡啶计算，下同)。
实施例35
在实施例34中所述的反应管内填装2％Pd/活性炭催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。将反应区域加热到320℃。将汽化过的3-三氟甲基吡啶和氯气通入反应管中。其中，3-三氟甲基吡啶的流量控制为6.33g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)。反应物摩尔投料比为3-三氟甲基吡啶:氯气＝1:8，所有起始反应物料与催化剂床层的接触时间为16.5s，反应8h。
离开反应管的尾气的处理方式如实施例34，得到67.59g油状产品，对其进行气相色谱分析，2-氯-5-三氟甲基吡啶的质量含量为84.8％，收率为91.7％。
实施例36
在实施例34中所述的反应管内填装MgF 2催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。将反应区域加热到280℃。将汽化的3-三氟甲基吡啶和氯气通入反应管中。其中，3-三氟甲基吡啶的流量控制为6.33g/h(0.043mol/h)，氯气的流量控制为7.7L/h(0.344mol/h)。反应物摩尔投料比为3-三氟甲基吡啶:氯气＝1:8，所有起始反应物料与催化剂床层的接触时间为16.5s，反应8h。
离开反应管的尾气的处理方式如实施例34，得到65.86g油状产品，对其进行气相色谱分析，2-氯-5-三氟甲基吡啶的质量含量为87.8％，收率为92.5％。
实施例37
在实施例34中所述的反应管内填装MgO催化剂，催化剂成型为直径是3mm高度是4mm的圆柱体。将反应区域加热到300℃。将汽化过的3-三氟甲基吡啶和氯气通入反应管中。其中，3-三氟甲基吡啶的流量控制为6.33g/h(0.043mol/h)，氯气的流量控制为8.7L/h(0.387mol/h)。反应物摩尔投料比为3-三氟甲基吡啶＝1:9，所有起始反应物料与催化剂床层的接触时 间为14.8s，反应6h。
离开反应管的尾气的处理方式如实施例34。得到48.49g油状产品，对其进行气相色谱分析，2-氯-5-三氟甲基吡啶的质量含量为86.7％，收率为89.6％。
实施例38～40
除了催化剂外所有操作条件与实施例35相同。实施例38中，在反应管内填装BaCl 2催化剂；实施例39中，在反应管内填装CaCl 2催化剂；实施例40中，在反应管内填装1.5％Pd/活性炭催化剂。反应分别得到66.25g、61.49g、64.57g油状产品，对其进行气相色谱分析，2-氯-5-三氟甲基吡啶的质量含量分别为85.0％、89.5％、89.8％，收率分别为90.1％、88.0％、92.8％。
实施例41
加热炉炉膛内径为35mm，高度为500mm。反应管材质为因康合金，反应管内径30mm、长度600mm。反应管内填装60mL 1％Pd/活性炭(平均粒径为0.15mm)氯化催化剂，静态床层高度为89mm。用氮气在235℃流化1h后，将汽化过的3-三氟甲基吡啶和氯气通入反应管中。其中，3-三氟甲基吡啶的流量控制为6.33g/h(0.043mol/h)，氯气的流量控制为5.77L/h(0.258mol/h)，氮气的流量保持为9.62L/h(0.430mol/h)。反应物摩尔投料比为3-三氟甲基吡啶:氯气＝1:6，所有起始反应物料与催化剂床层的接触时间为13.5s，反应24h。
离开反应管的尾气通入水洗塔和碱洗塔冷凝。将所得到的油层分离出来后用氨水中和，并进行水蒸气蒸馏以得到油状产品。所得到的油状产品用无水硫酸钠干燥之后称量质量为185.88g，用气相色谱内标法进行定量分析，2-氯-5-三氟甲基吡啶的质量含量为95.8％，收率为94.9％。
实施例42
除了催化剂不同外，其他条件与实施例41相同。反应管内填装60mL 1％Pd/Al2O3(平均粒径为0.15mm)氯化催化剂。产物处理和分析方法同实施例3.8，得到179.69g油状产品，色谱分析2-氯-5-三氟甲基吡啶的质量含量为94.6％，收率为90.7％。
从以上本发明提供的2,3-二氯-5-三氟甲基吡啶的制备方法，显著地提高了目标产物2,3-二氯-5-三氟甲基吡啶的收率和选择性。2,3-二氯-5-三氟甲基吡啶的选择性基本上能够达到至 少82％以上。本发明提供的方法，不仅降低了产品单耗、降低分离成本，而且反应温度远低于400℃，能够显著降低能耗并提高安全性。

Claims (30)

  1. 一种制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述方法包括：
    在100～150℃温度和0.5～5.0MPa压力下，在第一催化剂作用下，2-氯-5-三氟甲基吡啶和氯气反应得到2,3-二氯-5-三氟甲基吡啶；
    所述第一催化剂选自负载型金属氯化物、负载型沸石分子筛和负载型杂多酸中的至少一种，
    所述负载型金属氯化物，其活性组分选自WCl 6、MoCl 5、FeCl 3、AlCl 3、CuCl 2、ZnCl 2、SnCl 4、和SbCl 5中的至少一种，且活性组分的负载量为1～50wt％，
    所述负载型沸石分子筛，其沸石分子筛选自ZSM-5、Beta、X、Y、5A和L型沸石分子筛中的至少一种，且沸石分子筛的负载量为1～50wt％，
    所述负载型杂多酸，其杂多酸选自磷钨酸、硅钨酸、磷钼酸和硅钼酸中的至少一种，且杂多酸的负载量为1～50wt％。
  2. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于：反应压力为1.0～2.0MPa。
  3. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述负载型金属氯化物中，其活性组分选自WCl 6、MoCl 5、ZnCl 2、FeCl 3中的至少一种，活性组分的负载量为5～20wt％。
  4. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述沸石分子筛选自ZSM-5、Beta、L中的至少一种，沸石分子筛的Si/Al比为200以下且平衡阳离子选自H +、碱金属离子、碱土金属离子、过渡金属离子和稀土金属离子中的至少一种，沸石分子筛的负载量为5％～20％。
  5. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述负载型杂多酸中，杂多酸的负载量为5％～20％。
  6. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述第一催化剂的载体选自二氧化硅、氧化铝、氧化钛、氧化锆、活性炭、碳化硅和介孔分子筛中的至少一种。
  7. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述第一催化剂 的用量为2-氯-5-三氟甲基吡啶质量的0.1～30wt％，所述氯气与2-氯-5-三氟甲基吡啶的摩尔配比为0.5～10:1。
  8. 按照权利要求7所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述第一催化剂的用量为2-氯-5-三氟甲基吡啶质量的5～20wt％，所述氯气与2-氯-5-三氟甲基吡啶的摩尔配比为1～3:1。
  9. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述反应在高压反应釜中进行，所述高压反应釜的材质选自316L、蒙耐尔合金、英康合金或者哈氏合金。
  10. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述反应结束后，先加入碱液，再经分离后得到2,3-二氯-5-三氟甲基吡啶。
  11. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述2-氯-5-三氟甲基吡啶通过以下步骤制备：
    (1)氯氟化反应：在氯氟化催化剂作用下，保持氯氟化温度为150～320℃，使3-甲基吡啶、氯气和氟化氢通入氯氟化反应区域，得到包含3-三氟甲基吡啶的混合气；
    (2)氯化反应：在氯化催化剂作用下，保持氯化温度220～380℃，将步骤(1)得到的包含3-三氟甲基吡啶的混合气通入氯化反应区域，得到2-氯-5-三氟甲基吡啶，所述氯化催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂。
  12. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述氯化催化剂选自镁、钙的氟化物、氧化物或氯化物，负载在活性炭或氟化铝上的负载型钯催化剂。
  13. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述氯氟化温度为220～260℃，氯化温度270～320℃。
  14. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述氯氟化催化剂包括主催化剂、第一助催化剂和第二助催化剂，所述主催化剂选自铝、镁和铬中的至少一种，所述第一助催化剂选自铁、钴、锰、镍、铜、铋和锌中的至少一种，所述第二助催化剂选自镧、铈、钡、钙、钠和钾中的至少一种，主催化剂、第一助催化剂和第二助催化剂三者之间的摩尔比为50～95:5～42:0.3～8。
  15. 按照权利要求14所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述氯氟化催化剂中，主催化剂选自铝和/或铬，第一助催化剂选自铁、镍和铜中的至少一种，所述第二助催化剂选自镧、钡和钙中的至少一种，主催化剂、第一助催化剂和第二助催化剂三者之间的摩尔比为75～90:10～20:1～5。
  16. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-甲基吡啶、氯气和氟化氢三者之间的摩尔配比为1:0.1～50:1～30。
  17. 按照权利要求16所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-甲基吡啶、氯气和氟化氢三者之间的摩尔配比为1:4～10:3～12。
  18. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-甲基吡啶为经惰性气体稀释后的混合气体，且3-甲基吡啶与惰性气体的摩尔配比为1:0.5～50。
  19. 按照权利要求18所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-甲基吡啶与惰性气体的摩尔配比为1:5～20。
  20. 按照权利要求11所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于：
    所述步骤(1)中，3-甲基吡啶、氯气和氟化氢与氯氟化催化剂的接触时间为0.5～40s；
    所述步骤(2)中，包含3-三氟甲基吡啶的混合气与氯化催化剂的接触时间为0.5～40s。
  21. 按照权利要求20所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于：
    所述步骤(1)中，3-甲基吡啶、氯气和氟化氢与氯氟化催化剂的接触时间为1.5～20s；
    所述步骤(2)中，包含3-三氟甲基吡啶的混合气与氯化催化剂的接触时间为1.5～20s。
  22. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述2-氯-5-三氟甲基吡啶通过以下步骤制备：
    在第二催化剂存在下，保持反应温度为150～350℃，使3-三氟甲基吡啶和氯气气相反应，得到2-氯-5-三氟甲基吡啶；
    所述第二催化剂选自ZSM-5、5A、β和13X分子筛中的至少一种，
    所述ZSM-5分子筛，其Si/Al为50～300、平衡阳离子选自H +、Na +、K +、Ca 2+中的至少一种。
  23. 按照权利要求22所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述ZSM-5 分子筛，其Si/Al为80～200、平衡阳离子选自H +、Na +和K +中的至少一种。
  24. 按照权利要求22所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述反应温度为200～300℃。
  25. 按照权利要求22所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-三氟甲基吡啶与氯气的摩尔配比为1:0.1～20。
  26. 按照权利要求25所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-三氟甲基吡啶与氯气的摩尔配比为1:0.5～5。
  27. 按照权利要求22所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为0.5～100s。
  28. 按照权利要求27所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述3-三氟甲基吡啶和氯气在催化剂床层的接触时间为15～70s。
  29. 按照权利要求1所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述2-氯-5-三氟甲基吡啶通过以下步骤制备：
    在第三催化剂存在下，保持反应温度为220～360℃，使3-三氟甲基吡啶和氯气气相通过催化剂床层，得到2-氯-5-三氟甲基吡啶；
    所述第三催化剂选自镁、钙、钡的氟化物、氧化物、氢氧化物、碳酸盐或氯化物，负载在活性炭、氧化铝或氟化铝上的负载型钯催化剂。
  30. 按照权利要求11、22或29任一所述的制备2,3-二氯-5-三氟甲基吡啶的方法，其特征在于所述反应在固定床或流化床反应器中进行。
PCT/CN2018/119312 2017-12-06 2018-12-05 一种高选择性地制备2,3-二氯-5-三氟甲基吡啶的方法 WO2019109936A1 (zh)

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