IL95496A - Process for the preparation of fluoropyridines - Google Patents
Process for the preparation of fluoropyridinesInfo
- Publication number
- IL95496A IL95496A IL9549690A IL9549690A IL95496A IL 95496 A IL95496 A IL 95496A IL 9549690 A IL9549690 A IL 9549690A IL 9549690 A IL9549690 A IL 9549690A IL 95496 A IL95496 A IL 95496A
- Authority
- IL
- Israel
- Prior art keywords
- process according
- compound
- fluoropyridine
- dichloro
- chloropyridine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 35
- 150000005754 fluoropyridines Chemical class 0.000 title description 8
- 238000002360 preparation method Methods 0.000 title description 6
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 21
- -1 fluoropyridine compound Chemical class 0.000 claims description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- DNDPLEAVNVOOQZ-UHFFFAOYSA-N 2,3,4,5,6-pentachloropyridine Chemical compound ClC1=NC(Cl)=C(Cl)C(Cl)=C1Cl DNDPLEAVNVOOQZ-UHFFFAOYSA-N 0.000 claims description 9
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 8
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 8
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000000010 aprotic solvent Substances 0.000 claims description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 239000006227 byproduct Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- AYTUSKIZXVPKBR-UHFFFAOYSA-N 3,5-dichloro-2,6-difluoropyridine Chemical compound FC1=NC(F)=C(Cl)C=C1Cl AYTUSKIZXVPKBR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- FATBKZJZAHWCSL-UHFFFAOYSA-N 2,3,5,6-tetrachloropyridine Chemical compound ClC1=CC(Cl)=C(Cl)N=C1Cl FATBKZJZAHWCSL-UHFFFAOYSA-N 0.000 claims 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 5
- 150000005753 chloropyridines Chemical class 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 150000003222 pyridines Chemical class 0.000 description 4
- PKSORSNCSXBXOT-UHFFFAOYSA-N 3,5-dichloro-2,4,6-trifluoropyridine Chemical compound FC1=NC(F)=C(Cl)C(F)=C1Cl PKSORSNCSXBXOT-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- KVNQWVYYVLCZKK-UHFFFAOYSA-N 2,6-dichloro-4-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(Cl)=NC(Cl)=C1 KVNQWVYYVLCZKK-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 2
- 229910001515 alkali metal fluoride Inorganic materials 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 229910001507 metal halide Inorganic materials 0.000 description 2
- 150000005309 metal halides Chemical class 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000012808 vapor phase Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- RSGHPPLWWQAFEW-UHFFFAOYSA-N 2,3,4-trichloro-6-methylpyridine Chemical compound CC1=CC(Cl)=C(Cl)C(Cl)=N1 RSGHPPLWWQAFEW-UHFFFAOYSA-N 0.000 description 1
- CNLIIAKAAMFCJG-UHFFFAOYSA-N 2,3,5-trichloropyridine Chemical compound ClC1=CN=C(Cl)C(Cl)=C1 CNLIIAKAAMFCJG-UHFFFAOYSA-N 0.000 description 1
- FBYWJUJLCBETOZ-UHFFFAOYSA-N 2,3,5-trifluoro-4-methylpyridine Chemical compound CC1=C(F)C=NC(F)=C1F FBYWJUJLCBETOZ-UHFFFAOYSA-N 0.000 description 1
- RYCXDGINNLHAIA-UHFFFAOYSA-N 2,4-dichloro-6-(difluoromethyl)pyridine Chemical compound FC(F)C1=CC(Cl)=CC(Cl)=N1 RYCXDGINNLHAIA-UHFFFAOYSA-N 0.000 description 1
- BTUKLHWINORBTN-UHFFFAOYSA-N 2,6-dichloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC(Cl)=N1 BTUKLHWINORBTN-UHFFFAOYSA-N 0.000 description 1
- XARXFSMGFLTPED-UHFFFAOYSA-N 2,6-difluoro-4-(trifluoromethyl)pyridine Chemical compound FC1=CC(C(F)(F)F)=CC(F)=N1 XARXFSMGFLTPED-UHFFFAOYSA-N 0.000 description 1
- BAMJLRZKCSLZHA-UHFFFAOYSA-N 2,6-difluoropyridine-3-carbonitrile Chemical compound FC1=CC=C(C#N)C(F)=N1 BAMJLRZKCSLZHA-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- XOUHUCXTEKWSMO-UHFFFAOYSA-N 3,4,5-trichloro-2,6-difluoropyridine Chemical compound FC1=NC(F)=C(Cl)C(Cl)=C1Cl XOUHUCXTEKWSMO-UHFFFAOYSA-N 0.000 description 1
- MPVAKPXIHLBLAV-UHFFFAOYSA-N 3,5-dichloro-4,6-difluoropyridine-2-carbonitrile Chemical compound FC1=NC(C#N)=C(Cl)C(F)=C1Cl MPVAKPXIHLBLAV-UHFFFAOYSA-N 0.000 description 1
- PVMNPAUTCMBOMO-UHFFFAOYSA-N 4-chloropyridine Chemical compound ClC1=CC=NC=C1 PVMNPAUTCMBOMO-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229920002313 fluoropolymer Polymers 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 238000006042 reductive dechlorination reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Description
PROCESS FOR THE PREPARATION OF FLUOROPYRIDINES ABSTRACT Fluoropyridine compounds having a fluoro substituent in at least one of the 2-, 4-, and 6--positions are prepared by treatment of an appropriate 2-, 4-, or 6-chloropyridine compound with excess hydrogen fluoride in a dipolar, aprotic solvent at an elevated temperature and super-atmospheric pressure. Thus, 3,5-dichloro-2,4,6-trifluoropyridine is prepared by heating a mixture of pentachloropyridine, N-methyl-2--pyrrolidinone , and hydrogen fluoride at about 220°C and about 900 kiloPascals of pressure. 6,595-F - 1 - 95496/2 FLUORINATION WITH HYDROGEN FLUORIDE The present invention relates to a process for preparing fluoropyridines from chloropyridines by treatment with hydrogen fluoride.
Fluoropyridines, such as 3 , 5-dichloro-2 , 4 , 6--trifluoropyridine, are valuable intermediates useful in the preparation of herbicides, insecticides, fungicides, fixed dyes, and other end use products. Certain of these compounds are taught to be preparable from the corresponding chloropyridines by exchange with alkali metal fluorides, either in a melt or in certain dipolar, aprotic solvents. Israeli Patent No. 33214, for example, teaches such a process employing potassium fluoride, a dipolar solvent, and a small amount of water. Certain of them are also taught to be preparable from the corresponding chloropyridines by exchange with hydrogen fluoride, either in the vapor phase or neat. For example, Israeli Patent No. 33799 teaches a vapor phase process employing an aluminum or chromium catalyst and British Patent Application No. 1,272,475 teaches a liquid phase process using excess hydrogen fluoride as the solvent. None of these methods are entirely satisfactory, however. Methods employing an alkali metal fluoride produce an alkali metal chloride as a by-product which must be disposed of, sold, or recycled. Known methods employing hydrogen fluoride are slow, require metal halide or carbon catalysts, and produce only low yields of the desired fluoropyridines. -2- It has now been found that fluoropyridine compounds can be prepared in good yield and at a reasonable reaction rate by combining chloropyridine compounds and hydrogen fluoride in a dipolar, aprotic solvent at an elevated temperature and an elevated pressure .
The invention includes a process which comprises preparing a fluoropyridine compound of the general formula wherein X2, X3, X4, X5, and X6 each independently represent F, CI, CF3, CHF2, CN, H, or CH3 with the provisos that at least one of X2, X4, and X^ represents F and no more than two of X2, X3, 4, X5, and X6 represent H or CH3, characterized by heating a mixture of a chloropyridine compound of the same general formula wherein X2, x3, XH, x5, and χ6 each independently represent F, CI, CF3, CHF2, CN, H, or CH3 with the provisos that at least one of χ2, χ , and χ6 represents CI and no more than two of X2, X3, X4, X5, and X6 represent H or CH^, 6,595-F -2- -3- hydrogen fluoride, and a dipolar, aprotic solvent to a temperature of between 160°C and 300°C and a pressure of between 100 kiloPascals and 7,000 kiloPascals for a sufficient amount of time to exchange at least one chlorine substituent in a 2-, 4-, or 6-position with fluorine and, optionally, recovering the fluoropyridine compound .
Preferred chloropyridine starting materials include pentachloropyridine , 2 , 3 > 5 , 6-tetrachloro-pyridine, and 2 , 6-dichloro-4-( trifluoromethyl )pyridine . Preferred dipolar, aprotic solvents include N-methyl-2--pyrrolidinone .
The fluoropyridine products obtained, such as 3 » 5-dichloro- , 4 , 6-trifluoropyridine , 3>5-dichloro-2,6--difluoropyridine , and 2,6-difluoro-M-( tri luoromethyl)-pyridine, which are useful as chemical intermediates for the preparation of a variety of valuable compounds, are produced in the process in good yield and in a reasonable amount of time without the generation of an alkali metal chloride by-product. The process, additionally obviates the need for catalysts, such as metal halides and activated carbon, that are often employed in hydrogen fluoride exchange reactions.
The process of the present invention is applicable to the preparation of a range of fluoropyridine compounds of the general formula 6,595-F -3- -4- wherein X2, χ3, χ5, and Χ^ each independently represent F, CI, CF3, CHF2> CN, H, or CH3 with the provisos that at least one of X2, x^, and ^ represents F and no more than two of X2, X3, 4, X5, and X6 represent H or CH3. Such compounds can be characterized as pyridines possessing at least one fluoro substituent in a 2-, 4-, or 6-position and possessing at least three total electron withdrawing substituents selected from F, CI, CF3, CHF2, and CN. Examples of fluoropyridine products preparable by the process include 3 , 5-dichloro--2, , 6-t ifluoropy idine, 2,4-difluoro-3>5,6-trichloro-pyridine, 2,6-difluoro-3 , , -trichloropyridine , 3,5-di-chloro-2, 6-difluoropyridine, 2,6-difluoro-4-( trifluoro-methyl ) pyridine , 2 , 6-difluoro-5-cyanopyridine , 4-methyl--2, 3 ,5-trifluoropyridine, 2 , -difluoro-6-(difluoro-methy1 ) pyridine , 3 , 5-dichloro-2 , 6-difluoro-4-( trifluoro-methyDpyridine, and 3 , 5-dichloro-4 , 6-difluoro-2-cyano-pyridine. A preferred product of the process is 3,5-di-chloro-2, ,6-trifluoropyridine.
The starting material chloropyridine compounds to which the process is applicable have the general formula 6,595-F -4- -5- wherein X2, 3, ch independently represent F, CI, CF3, CHF2, CN, H, or CH3 with the provisos that at least one of 2, X^, and X^ represents CI and no more than two of X2, X3, X4, X5, and X6 represent H or CH3. Such compounds can be characterized as pyridines possessing at least one chloro substituent in a 2-, 4-, or 6-position and possessing at least three total electron withdrawing substituents selected from F, CI, C 3, CHF2> and CN. Examples of chloropyridine starting materials include pentachloropyridine , 2, 6-difluoro-3 > , 5-trichloropyridine , 2 , 3 > 5 , 6-tetra-chloropyridine , 2 , 3 » , 5-tetrachloropyridine , 2,3>4,6--tetrachloropyridine , 2,3, 5-trichloropyridine, 2, 6-dichloro-4-cyanopyridine , 2,3, 4-trichloro-6-methyl-pyridine , 2 , 4-dichloro-6-( difluoromethyl ) pyridine , 2 , 3 ,6-trichloro-5-( t ifluorome hyl ) pyridine , 2, 6-di-chloro-4-(trifluoromethyl)pyridine, and 2-cyano-4,6--dichloro-3 > 5-difluoropy idine .
The process of the present invention requires a dipolar, aprotic solvent. This class of solvents is well known in the art and includes solvents such as N,N-dimethylformamide, Ν,Ν-dimethylacetamide , N-methyl--2-pyrrolidinone , 1 , 3-dimethyl-2-imidazolidinone , sulfolane, dimethyl sulfoxide, and hexamethylphosphor-amide. N-methyl-2-pyrrolidinone is a preferred solvent. A sufficient amount of solvent is generally employed to 6,595-F -5- -6- dissolve the starting chloropyridine compound at higher temperatures. Generally, a ratio of solvent to chloropyridine compound of 1:1 to 20:1 is suitable.
The hydrogen fluoride is generally employed in excess. Typically, 2 to 50 moles of hydrogen fluoride are employed for every chloro substituent exchanged. Thus, for example, to prepare 3 , 5-dichloro-2 , , 6-tri-fluoropyridine from pentachloropyridine 6 to 150 moles of hydrogen fluoride are generally employed for every mole of pentachloropyridine. Three to 40 moles are generally preferred.
The process is conducted by heating a mixture of the starting chloropyridine, a dipolar, aprotic solvent, and hydrogen fluoride at a sufficiently high temperature, under a sufficiently high pressure, and for a sufficient amount of time to exchange at least one chloro substituent in the 2-, 4-, or 6-position to a fluoro substituent in substantial conversion.
Temperatures of 160°C to 300°C are usually suitable and temperatures of 200°C to 250°C are generally preferred. Pressures of 100 to 7,000 kiloPascals are usually suitable and pressures of 300 to 3,600 kiloPascals are generally preferred. Pressures above those naturally attained in the system are generally achieved by adding an inert gas, such as nitrogen or argon.
When a substantial amount of the desired fluoropyridine compound has formed it can be recovered by conventional means. Methods involving distillation are often preferred. Since each of the reactants and products is volatile, separations are readily made by distillation. It is also appropriate to dilute with 6,595-F -6- water and separate the fluoropyridine as an insoluble liquid or solid.
It is possible, and in some instances preferable, to conduct the process in such a manner that the hydrogen chloride formed as a by-product distills from the reaction mixture as it forms. A reactor equipped with a f actionating distillation column capable of operating under pressure is required to accomplish this. When this embodiment of the invention is employed, it is possible to use less of an excess of hydrogen fluoride than when the hydrogen chloride is left in the mixture. Thus, it is preferred to employ 5 to HQ moles of hydrogen fluoride for every chloro substituent exchanged if the hydrogen chloride is not removed but only 3 to 10 if it is.
It is further possible, and in some instances preferable, to conduct the process in such a manner that the product fluoropyridine as well as the by-product hydrogen chloride is removed from the reaction mixture as it forms. In this embodiment of the process a more volatile portion of the reaction mixture is continuously removed from the mixture by distillation. The distillate obtained is fractionally distilled to separate and recover the desired fluoropyridine product and separate the hydrogen chloride by-product from the hydrogen fluoride reactants, any chloropyridine reactant or intermediate, and any solvent present in the distillate. The reactants, intermediates, and solvents are continuously returned to the reactor for further processing. 6,595-F -7- -8- The process can be conducted in either a batch mode or a continuous mode.
The process can be carried out in any reactor that is compatible with the reactants and products and is capable of super-atmospheric pressure operation.
Materials of construction resistant to corrosion by hydrogen chloride and hydrogen fluoride, are generally employed. Reactors coated with a fluorinated polymer, such as polytetrafluoroethylene , are especially useful for the process. When a metal that is too susceptible to corrosion by hydrogen chloride or hydrogen fluoride is employed, reductive dechlorination is a significant side reaction.
The following example is presented to illustrate the process of the invention. It should not be construed as limiting.
Example 1 - Preparation of 3 , 5-Dichloro-2 , 4 , 6-trifluoro-pyridine and 2 , 6-Difluoro-3 , 4 , 5-trichloropyridine From Pentachloropyridine A 250 milliliter polytetrafluoroethylene lined reactor equipped with stirring and heating means was employed. Pentachloropyridine (15.5 grams, 0.0616 mole), hydrogen fluoride (98.2 grams, 4.91 moles) and N-methyl-2-pyrrolidinone (124 grams) were placed in the reactor and heated with stirring at about 220°C.
Nitrogen gas was introduced to increase the pressure to about 900 kiloPascals . The reactor contents were sampled at intervals and the samples were analyzed by gas-liquid chromatography. The results are given in the following table: 6,595-F -8- -9- 3 ,5-Dichloro- Monofluoro- Difluoro- 2,4,6- Run Pentachloro- tetrachloro- trichloro- trifluoro- Time, pyridine, pyridines , pyridines* , pyridine , Hours Percent Percent Percent Percent 0.0 99.6 0.0 0.0 0.0 0.5 43.8 42.1 2.6 0.8 4.5 3.9 48.5 38.6 5.4 7.5 2.0 35.8 47.3 9.0 13.5 0.7 20.5 58.7 15.5 26.0 0.0 7.3 42.2 36.4 30.5 0.0 6.1 46.2 42.8 *A mixture of isomers in which 2 , 6-difluoro-3 » 4 , 5-trichloro--pyridine is predominant. 20 25 30 36,595-F -9-
Claims (10)
1. A process which comprises preparing a fluoropyridine compound of the general formula X' wherein X2, X3, X4, X5, and X6 each independently represent F, CI, CF3, CHF2, CN, H, or CH3 with the provisos that at least one of 2, X4, and X^ represents F and no more than two of X2, X3, X4, X5, and X6 represent H or CH3 characterized by heating a mixture of a chloropyridine compound of the same general formula wherein X2, X3, X4, X5, and X6 each independently represent F, CI, CF3, CHF2, CN, H, or CH3 with the provisos that at least one of X2, X4, and X^ represents CI and no more than two of X2, X3, X4, X5, and X6 represent H or CI^, 6,595-F -10- -11- hydrogen fluoride, and a dipolar, aprotic solvent to a temperature of between 160°C and 300°C and a pressure of between 100 and 7,000 kiloPascals for a sufficient amount of time to exchange at least one chlorine substituent in a 2-, 4-, or 6-position with fluorine and, optionally, recovering the fluoropyridine compound.
2. A process according to Claim 1 wherein the chloropyridine compound is pentachloropyridine or 2,3,5 , 6-tetrachloropyridine.
3. A process according to Claim 1 wherein the fluoropyridine compound is 3 » 5-dichloro-2 , 4 , 6-trifluoropyridine, 2,6-difluoro-3 > 4 , 5-trichloropyridine, or 3 , 5-dichloro-2 , 6-difluoropyridine .
4. A process according to Claim 2 wherein the chloropyridine compound is pentachloropyridine and the fluoropyridine compound is 3 » 5-dichloro-2 , , 6-trifluoropyridine .
5. A process according to any one of Claims 1 to 4 wherein the temperature is 200°C to 250°C.
6. A process according to any one of Claims 1 to 4 wherein the pressure is 300 to 3>600 kiloPascals.
7. A process according to any one of Claims 1 to 4 wherein the solvent is N-methyl-2-pyrrolidinone .
8. A process according to any one of Claims 1 to 4 wherein the hydrogen chloride by-product is removed as it forms by distillation.
9. A process according to any one of Claims 1 to 4 wherein the fluoropyridine compound is recovered. 6,595-F -11- -12-
10. A process according to Claim 9 wherein the fluoropyridine compound is recovered continuously by distillation . 36,595-F -12-
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/399,748 US4999432A (en) | 1989-08-28 | 1989-08-28 | Fluorination with hydrogen fluoride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL95496A0 IL95496A0 (en) | 1991-06-30 |
| IL95496A true IL95496A (en) | 1994-04-12 |
Family
ID=23580800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9549690A IL95496A (en) | 1989-08-28 | 1990-08-27 | Process for the preparation of fluoropyridines |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4999432A (en) |
| EP (1) | EP0415498A3 (en) |
| JP (1) | JPH03163062A (en) |
| AU (1) | AU6138090A (en) |
| CA (1) | CA2024032A1 (en) |
| HU (1) | HUT54985A (en) |
| IL (1) | IL95496A (en) |
| RU (1) | RU1838300C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5315043A (en) * | 1992-02-05 | 1994-05-24 | E. I. Du Pont De Nemours And Company | Aromatic nucleophilic fluorination |
| CA2714065A1 (en) * | 2008-02-05 | 2009-08-13 | Arysta Lifescience North America, Llc | Solid formulation of low melting active compound |
| TWI520943B (en) * | 2011-01-25 | 2016-02-11 | 陶氏農業科學公司 | Process for the preparation of 4-amino-3-chloro-5-fluoro-6-(substituted)picolinates |
| CN108017574B (en) * | 2017-12-20 | 2019-03-08 | 江苏中旗科技股份有限公司 | A kind of method for continuous production of fluroxypyr intermediate 3,5-dichloro-2,4,6-trifluoropyridine |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1234543A (en) * | 1969-02-25 | 1971-06-03 | ||
| GB1272475A (en) * | 1969-05-30 | 1972-04-26 | Ici Ltd | Manufacture of fluoropyridines |
| US4480102A (en) * | 1982-07-23 | 1984-10-30 | The Dow Chemical Company | 2,3-Difluoro-5-(trifluoromethyl)pyridine and methods of making and using the same |
| US4590279A (en) * | 1982-11-26 | 1986-05-20 | The Dow Chemical Company | Preparation of (trifluoromethyl)pyridines under liquid phase conditions |
| US4650875A (en) * | 1983-05-09 | 1987-03-17 | The Dow Chemical Company | Preparation of (trifluoromethyl)pyridines |
| US4547577A (en) * | 1984-06-08 | 1985-10-15 | The Dow Chemical Company | Preparation of (trifluoromethyl)pyridines |
| US4831148A (en) * | 1984-10-10 | 1989-05-16 | Ciba-Geigy Corporation | Process for the preparation of fluorinated pyridine derivatives |
| GB8504268D0 (en) * | 1985-02-19 | 1985-03-20 | Shell Int Research | Preparation of fluorinated pyridines |
| US4680406A (en) * | 1985-10-15 | 1987-07-14 | The Dow Chemical Company | Process for fluorinating halogenated organo-compounds |
| US4746744A (en) * | 1986-10-22 | 1988-05-24 | The Dow Chemical Company | Method of preparation of 3,5-dichloro-2,4,6-trifluoropyridine |
| US4782161A (en) * | 1987-10-21 | 1988-11-01 | The Dow Chemical Company | Preparation of fluoropyridines |
-
1989
- 1989-08-28 US US07/399,748 patent/US4999432A/en not_active Expired - Lifetime
-
1990
- 1990-08-24 HU HU905329A patent/HUT54985A/en unknown
- 1990-08-27 CA CA002024032A patent/CA2024032A1/en not_active Abandoned
- 1990-08-27 EP EP19900202288 patent/EP0415498A3/en not_active Withdrawn
- 1990-08-27 IL IL9549690A patent/IL95496A/en not_active IP Right Cessation
- 1990-08-27 RU SU904830817A patent/RU1838300C/en active
- 1990-08-27 JP JP2222659A patent/JPH03163062A/en active Pending
- 1990-08-27 AU AU61380/90A patent/AU6138090A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IL95496A0 (en) | 1991-06-30 |
| EP0415498A3 (en) | 1991-08-07 |
| HU905329D0 (en) | 1991-02-28 |
| AU6138090A (en) | 1991-02-28 |
| JPH03163062A (en) | 1991-07-15 |
| RU1838300C (en) | 1993-08-30 |
| CA2024032A1 (en) | 1991-03-01 |
| US4999432A (en) | 1991-03-12 |
| EP0415498A2 (en) | 1991-03-06 |
| HUT54985A (en) | 1991-04-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RH | Patent void |