CN100564360C - The method for preparing the 2-cyanopyridine - Google Patents
The method for preparing the 2-cyanopyridine Download PDFInfo
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- CN100564360C CN100564360C CNB2005100882205A CN200510088220A CN100564360C CN 100564360 C CN100564360 C CN 100564360C CN B2005100882205 A CNB2005100882205 A CN B2005100882205A CN 200510088220 A CN200510088220 A CN 200510088220A CN 100564360 C CN100564360 C CN 100564360C
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- cyanide
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- 238000000034 method Methods 0.000 title claims abstract description 59
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims abstract description 13
- -1 alkali metal cyanide Chemical class 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical group N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract description 3
- ICAIHGOJRDCMHE-UHFFFAOYSA-O ammonium cyanide Chemical compound [NH4+].N#[C-] ICAIHGOJRDCMHE-UHFFFAOYSA-O 0.000 claims abstract description 3
- 239000003125 aqueous solvent Substances 0.000 claims abstract description 3
- 230000031709 bromination Effects 0.000 claims description 7
- 238000005893 bromination reaction Methods 0.000 claims description 7
- 238000005660 chlorination reaction Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003444 phase transfer catalyst Substances 0.000 claims description 2
- 150000004714 phosphonium salts Chemical class 0.000 claims description 2
- 150000005621 tetraalkylammonium salts Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 238000005695 dehalogenation reaction Methods 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910001513 alkali metal bromide Inorganic materials 0.000 description 2
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940107816 ammonium iodide Drugs 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 2
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229950006389 thiodiglycol Drugs 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
- LUGYGMMZVFJFEQ-UHFFFAOYSA-N 2-bromo-6-chloro-N-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-N-methylbenzamide Chemical compound ClC=1C(=NC=C(C1)C(F)(F)F)N(C(C1=C(C=CC=C1Cl)Br)=O)C LUGYGMMZVFJFEQ-UHFFFAOYSA-N 0.000 description 1
- YYAJIRPBIZIZJE-UHFFFAOYSA-N 2-chloro-N-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-6-fluoro-N-methylbenzamide Chemical compound ClC=1C(=NC=C(C1)C(F)(F)F)N(C(C1=C(C=CC=C1F)Cl)=O)C YYAJIRPBIZIZJE-UHFFFAOYSA-N 0.000 description 1
- XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- NTKVWOTYTNWGRK-UHFFFAOYSA-N P.Br.Br.Br Chemical compound P.Br.Br.Br NTKVWOTYTNWGRK-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
- OCBHHZMJRVXXQK-UHFFFAOYSA-M benzyl-dimethyl-tetradecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 OCBHHZMJRVXXQK-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000006298 dechlorination reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- VICYBMUVWHJEFT-UHFFFAOYSA-N dodecyltrimethylammonium ion Chemical compound CCCCCCCCCCCC[N+](C)(C)C VICYBMUVWHJEFT-UHFFFAOYSA-N 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- YCOZIPAWZNQLMR-UHFFFAOYSA-N heptane - octane Natural products CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910001512 metal fluoride Inorganic materials 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- XDXKSZZAKNNKSG-UHFFFAOYSA-N n-methyloctanamide Chemical compound CCCCCCCC(=O)NC XDXKSZZAKNNKSG-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229960004839 potassium iodide Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YODZTKMDCQEPHD-UHFFFAOYSA-N thiodiglycol Chemical compound OCCSCCO YODZTKMDCQEPHD-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
The present invention relates to the method for compound shown in the general formula (II); the preparation method of compound shown in the general formula (II); this method is included in aqueous solvent or solvent-free down with the compound shown in cyanide source and the catalyst treatment general formula (III); wherein; X is a halogen; each Y can be the same or different; be halogen, haloalkyl, carbalkoxy or alkyl sulphonyl; and n is 0～3, and described cyanide source is prussic acid, alkali metal cyanide, alkaline-earth metal prussiate or the optional ammonium cyanide that replaces.
Description
The application is that international application no is PCT/EP01/10984, international filing date be the pct international patent application in August 21 calendar year 2001 to enter the national applications of China after the stage number be 01814622.8, denomination of invention is divided an application for the Chinese patent application of " method for preparing 2-aminoethyl pyridine ".
Technical field
The present invention relates to prepare 2-aminomethyl-pyridine (especially 2-aminomethyl-3-chloro-5-5-flumethiazine), and preparation is used for the novel method of 2-cyanopyridine of their preparation process, and above-claimed cpd can be used as intermediate and is used to prepare sterilant.
Background technology
The known catalytic reduction reaction that carries out cyanopyridine can provide aminomethyl-pyridine.But when the cyanopyridine compound contained extra halogen atom, described reduction reaction can become complicated because of the competition dehalogenation reaction.Show " Hydrogenation Methods " (Best Synthetic Series at P.N.Rylander, AcademicPress publishes), (1985), mention in the 148th page, when the dehalogenation reaction is carried out in hope, usually select palladium as catalyzer, and platinum and rhodium are inoperative comparatively speaking, therefore are usually used in hydrogenation when needs keep halogen.
Compare with above-mentioned prior art, we find to use palladium catalyst in the reduction reaction of the cyanopyridine that contains extra halogen atom, can obtain good especially effect.We have researched and developed the novel method for preparing the 2-aminomethyl-pyridine that contains extra halogen atom, the dehalogenation reaction of minimum degree wherein only occurs, and go for plant-scale process.
Announced that at present many being used for introduce method on the pyridine molecule 2-position with cyano group.These are usually directed in for example especially replacement of bromine or fluorine of halogen in methyl-sulphoxide or the dimethyl formamide of polar solvent.And, many methods that begin from active N-pyridine oxide or N-alkyl pyridine are arranged.Many methods in these cyaniding routes are all used the heavy metal reagent that contains copper or nickel.For example, EP0034917 disclosed from its 2-bromine analogue by under 120 ℃, dimethyl formamide and cuprous cyanide react and prepare 2-cyano group-3-chloro-5-5-flumethiazine.
But there are one or more shortcomings in many in these prior art methods, comprise that productive rate is low, use heavy metal that can produce poisonous liquid effluent or the polar solvent that uses very difficult recovery.And, relate to the method that forms N-pyridine oxide or N-alkyl pyridine and comprise several steps.These shortcomings are just crucial more for being amplified to technical scale.
Publication No. is the cyanogenation that 117970 English Patent has disclosed 2-halogen pyridine compounds and activator and cyanide source in polar solvent, avoids many above-mentioned shortcomings thus.But, still belong to and need recycle activator and aprotic solvent, so that the cost of technical scale process is reduced to minimum this method.
Summary of the invention
Now, we researched and developed a kind of alternative, be applicable on the technical scale process improving one's methods of preparation 2-cyanopyridine.
First aspect of the present invention provides the method (A) for preparing the compound or its salt shown in general formula (I):
Wherein, this method comprises the catalytic hydrogenation of compound or its salt shown in the general formula (II):
Wherein, X is a halogen, and each Y can be the same or different, and be halogen, haloalkyl, carbalkoxy or alkyl sulphonyl, and n is 0～3.
In the present invention, halogen is meant fluorine, chlorine or bromine atom.Preferred halogen atom is the chlorine atom.
Haloalkyl typically refers to the C that replaces with one or more halogen atoms
1～C
6Moieties.For example, described C
1～C
6Moieties can be methyl, ethyl, n-propyl or sec.-propyl, is preferably methyl.Described C
1～C
6Moieties should use one or more chlorine atoms or fluorine atom to replace.Preferred haloalkyl is a trifluoromethyl.
Carbalkoxy is C normally
1～C
6Carbalkoxy is as methoxycarbonyl, ethoxycarbonyl, n-propyl base or isopropyl ester base.
Alkyl sulphonyl is C normally
1～C
6Alkyl sulphonyl, wherein C
1～C
6The definition of part as mentioned above.
X is preferably the chlorine atom.
Y is preferably halogen or haloalkyl (being more preferably trifluoromethyl).
Compound (II) is preferably 3-chloro-2-cyano group-5-5-flumethiazine.
Described catalyzer contains the metal that is selected from palladium, platinum, ruthenium, nickel and cobalt usually.Amount of metal in the catalyzer that uses (for example be carried on usually charcoal on) with respect to the amount of compound shown in the general formula (II), is generally 0.05～0.7 weight %, is preferably 0.05-0.3 weight %, more preferably 0.1～0.2 weight %.Preferred catalyzer contains palladium, for example the fine palladium on inert support such as charcoal.Find that this can provide suitable speed of response and minimum side reaction.Therefore, when compound shown in the general formula (II) is 3-chloro-2-cyano group-5-5-flumethiazine, use method of the present invention can make the dechlorination reaction minimum.Other appropriate catalyst example comprises the oxide compound that contains above-mentioned metal or the catalyzer of other compound.
Described method is carried out in having the solvent of for example alcohol (as methyl alcohol, ethanol, propyl alcohol or butanols), ester (as ethyl acetate) or ether (as tetrahydrofuran (THF)) usually.Preferred alcohols solvent (most preferably methyl alcohol).Described method should be carried out under the condition that has strong acid example hydrochloric acid, Hydrogen bromide, sulfuric acid or phosphoric acid (being preferably hydrochloric acid).The poisoning of catalyst that the existence of acid can help prevent the amino because of product shown in the general formula (I) to cause also can prevent the coupling of amino intermediate, and known this point also exists in the catalytic hydrogenation of nitrile.
Described reaction conditions generally includes and adds all reagent in the suitable reaction vessel and stir, and for example, at 0～60 ℃, is preferably under 20～30 ℃ the temperature.An advantage again of described method just is to use low pressure, uses 1～4 atmospheric hydrogen pressure (described method should be carried out under 1 normal atmosphere) usually.
Described reaction is randomly carried out existing under the condition of catalytic inhibitor, can further improve reaction preference by the amount that reduces the dehalogenation reaction that exists as side reaction.This catalytic inhibitor is known in present technique, for example, show " Hydrogenation Methods " (Best SyntheticSeries as P.N.Rylander, Academic Press publishes), (1985), the 125-126 page or leaf is described, comprise alkali-metal bromide or iodide such as Potassium Bromide and potassiumiodide, brometo de amonio or ammonium iodide, hydrogen bromide or hydrogen iodide, phosphide such as triphenyl phosphite, Hypophosporous Acid, 50, phosphorous acid or alkyl Hypophosporous Acid, 50, thiodiglycol (2, the 2-thiodiglycol), thiocarbamide or sulphur.Described catalytic inhibitor should be selected from alkali-metal bromide or iodide, brometo de amonio or ammonium iodide and hydrogen iodide.
The present invention provides the productive rate of preparation 2-aminomethyl-pyridine thus and selectivity is high and method easily.
Especially be convenient to prepare compound with shown in the general formula (I) of the form of salt especially hydrochloride.When as the intermediate of preparation during sterilant, described salt can directly carry out next step reactions steps, separates and need not carry out corresponding unhindered amina in advance.Therefore can in single reactor, carry out the preparation and the subsequent reaction thereof of described salt easily.Especially preferred salt is 2-aminomethyl-3-chloro-5-5-flumethiazine.
According to a feature more of the present invention, the method (B) of the compound of preparation shown in above-mentioned general formula (II) is provided, wherein this method is included in aqueous solvent or solvent-free down with the compound shown in cyanide source and the catalyst treatment general formula (III):
Wherein, X, Y and n's is civilian as defined above described, and described cyanide source is prussic acid, alkali metal cyanide, alkaline-earth metal prussiate or the optional ammonium cyanide that replaces.
Described catalyzer is phase-transfer catalyst normally, for example tetraalkylammonium salt such as zephiran chloride trimethyl ammonium, chlorination three capryloyl ammonium methyls, chlorination four Shens base ammonium, bromination four n-propyl ammoniums, chlorination dodecyl trimethyl ammonium, chlorination tetra-n-butyl ammonium, bromination tetra-n-butyl ammonium, bromination four n-octyl ammoniums or bromination n-tetradecane base trimethyl ammonium; Or Si Wan Ji phosphonium salt such as bromination tetra-n-butyl phosphorus or tetraphenylphosphonibromide bromide phosphorus; Or its crown ether or do not have ring analogues such as TDA-1 (three [2-(2-methoxy ethoxy) ethyl] amine); Or amine such as 4-Dimethylamino pyridine.
Described catalyzer should be selected from chlorination three capryloyl ammonium methyls and bromination four n-octyl ammoniums.
Catalyst consumption is generally about 0.01～10 mole of %, is preferably about 0.1～5 mole of %, more preferably about 1～5 mole of %.
Compound (III) is preferably 3-chloro-2-fluoro-5-5-flumethiazine.
Aforesaid method of the present invention (B) is the method that productive rate is high, be used to prepare the 2-cyanopyridine, and it can be operated under moderate temperature, and the shortcoming of many prior art methods can not occur.Especially method of the present invention does not need the prussiate of heavy metal prussiate such as copper or nickel, can produce poisonous liquid effluent and be difficult to reclaim when they are used for technical scale.The waste water that the inventive method (B) produces can be easy to handle.
In addition, described method need not prepare active N-pyridine oxide or N-alkyl pyridine for high conversion, and this point is essential in many prior art methods.The inventive method (B) does not need activator such as 4-Dimethylamino pyridine, has therefore removed extra recovery and circulation step from.Another advantage of the inventive method (B) be in reaction not with an organic solvent, therefore removed from and reclaimed expensive solvent such as methyl-sulphoxide.
Described cyanide source is preferably sodium cyanide or potassium cyanide, is preferably potassium cyanide.The consumption of cyanide source is about 1.0～2.0 molar equivalents (but if the words of needs can be used more) usually, is preferably 1.0～1.5 molar equivalents, is more preferably 1.0～1.1 molar equivalents.
Described reaction should make water carry out as solvent usually, but also can carry out under the condition of not using solvent.
Described reaction conditions is usually included in 10～60 ℃, is preferably to add all reagent in the suitable reaction vessel under 20～40 ℃ the temperature and stir.
Therefore, the invention provides productive rate method high, that be used to prepare the 2-cyanopyridine (B).Because described reaction uses medium temperature of reaction, all need only is simply and not expensive reactor and downstream processing equipment.And because described reagent is easy to obtain, described method operates also not expensive.In addition, the waste water of present method generation is also handled easily.
According to a feature more of the present invention, described method (B) and (A) can combine is by the compound shown in the compound general formula (I) shown in the general formula (III).
According to a feature more of the present invention; described method (A) or described combining method (B) and (A) then carry out step (C) afterwards again, it comprises that with the benzoylation compound shown in the general formula (IV) above-claimed cpd (I) being carried out acidylate provides the compound shown in the logical formula V:
Wherein, L is a leavings group; R
1And R
2Represent identical or different halogens separately; And m is 0,1 or 2.
L is preferably the chlorine atom.
Compound shown in the logical formula V is important pesticide active ingredient, is for example disclosed in International Patent Publication No. W WO99/42447.
Compound shown in the preferred logical formula V is:
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2, the 6-dichloro-benzamide
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2, the 6-difluorobenzamide
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2-chloro-6-fluorobenzamide
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2, the 3-difluorobenzamide
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2,4, the 6-benzamide trifluoroacetate
* methyl N-[(3-chloro-5-trifluoromethyl-2-pyridyl)]-2-bromo-6-chlorobenzamide
In International Patent Publication No. W WO 99/42447, disclosed step (C).
According to a feature more of the present invention, described method (B) or described combining method (B) and (A) or (B), (A) and (C) can be used in combination with step (D) more early, it comprises that the compound shown in the mutual-through type (VI) fluoridizes:
Wherein, X, the definition of Y and n is as mentioned above.
Described step (D) under 50～150 ℃ temperature, is used suitable fluorizating agent such as alkaline metal fluoride cpd usually in aprotic solvent such as methyl-sulphoxide or tetramethylene sulfone, be preferably Potassium monofluoride or Sodium Fluoride and carry out.
The general formula (1) and the compound shown in (2) that are made by the invention described above method are being particularly useful in the fungi activity 2-pyridyl methylamine derivative shown in the preparation general formula (5), below are its reaction scheme:
Further specify the present invention by following preparation embodiment.
Embodiment
Embodiment 1 (method A)
Under 20 ℃, 1 normal atmosphere hydrogen, stir the mixture of the palladium (metallic palladium is 5.1 milligrams) on 3-chloro-2-cyano group-5-5-flumethiazine (5.1 gram) and 5% charcoal and methyl alcohol and concentrated hydrochloric acid (2.5 milliliters) mixed.After 4 hours, judge that with high efficiency liquid chromatography hplc described reaction carries out fully.By the described mixture of diatomite filtration, water and methanol wash, and the hydrochloride of evaporation formation 2-aminomethyl-3-chloro-5-5-flumethiazine, productive rate is 95～97%, NMR is (at D
2O) in, 4.6 (s, 2H), 8.35 (s, 1H), 8.9 (s, 1H).
Embodiment 2 (method B)
Under 30 ℃, water (215 gram) solution with potassium cyanide (71.6 gram) in 1 hour joins in the stirring the mixture of 3-chloro-2-fluoro-5-5-flumethiazine (199.5 gram) and Aliquat 336 (chlorination three capryloyl methylamine, 12.1 grams).Under this temperature, continue to stir 4 hours, and be lower than 1% up to the amount of the initial fluorochemical that records with hplc.Isolate lower organic phase and with sodium chloride aqueous solution washing again in 15mbar, 90 ℃ of distillations down, make 3-chloro-2-cyano group-5-5-flumethiazine (185.8 grams, productive rate is 90%).This degree of purity of production is 98%.
Embodiment 3 (method B)
Under 20～25 ℃, solid sodium cyanide (0.29 gram) is added in the stirring the mixture of 3-chloro-2-fluoro-5-5-flumethiazine (0.8 gram) and Tetrabutylammonium bromide (0.06 gram), and stir and made 3-chloro-2-cyano group-5-5-flumethiazine (0.68 gram, the productive rate that records with hplc is 82%) in 23 hours.
The embodiment of step (D)
Under 110 ℃ with 2,3-two chloro-5-5-flumethiazines (800 gram) add in the stirring the mixture of anhydrous potassium fluoride (320 gram) and anhydrous dimethyl sulfoxide, heated 2 hours down at 120 ℃ then, and under reduced pressure, carry out fractionation, make 3-chloro-2-fluoro-5-5-flumethiazine (685 gram), productive rate is 92% (purity is 98%).
Claims (8)
1. the preparation method of compound shown in the general formula (II),
This method is included in aqueous solvent or solvent-free down with compound shown in cyanide source and the catalyst treatment general formula (III):
Wherein, X is a halogen; each Y can be the same or different; be halogen, haloalkyl, carbalkoxy or alkyl sulphonyl; and n is 0～3; and described cyanide source is prussic acid, alkali metal cyanide, alkaline-earth metal prussiate or ammonium cyanide, and described catalyzer is tetraalkylammonium salt or Si Wan Ji phosphonium salt phase-transfer catalyst.
2. the described method of claim 1 is characterized in that described catalyzer is selected from chlorination three capryloyl ammonium methyls and bromination four n-octyl ammoniums.
3. the described method of claim 1 is characterized in that described catalyst consumption is 0.01～10 mole of %.
4. the described method of claim 1 is characterized in that described cyanide source is a potassium cyanide.
5. the described method of claim 1, the consumption that it is characterized in that described cyanide source is 1.0～2.0 molar equivalents.
6. the described method of claim 1 is characterized in that described solvent is a water.
7. the described method of claim 1 is characterized in that temperature is 10～60 ℃.
8. the described method of claim 1 is characterized in that the compound shown in the general formula (III) is a 3-chloro-2-fluoro-5-5-flumethiazine.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0021066.6 | 2000-08-25 | ||
| GB0021066A GB0021066D0 (en) | 2000-08-25 | 2000-08-25 | Novel process |
| GB0025616.4 | 2000-10-19 | ||
| EP01420128.9 | 2001-06-07 |
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| CNB018146228A Division CN100368400C (en) | 2000-08-25 | 2001-08-21 | Process for the preparation of 2-aminomriordan peter dominic ethylpyridines |
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| CN100564360C true CN100564360C (en) | 2009-12-02 |
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| EP3088390A1 (en) * | 2015-04-30 | 2016-11-02 | Bayer CropScience AG | Catalytic hydrogenation of substituted cyanopyridines |
| CN106243027B (en) * | 2016-07-28 | 2019-03-05 | 南京红太阳生物化学有限责任公司 | A kind of preparation method of 3,6- dichloro-2-pyridyl carboxylic acid |
| CN107286087B (en) * | 2017-04-16 | 2020-01-07 | 内蒙古佳瑞米精细化工有限公司 | Synthetic method of 2-cyano-3-chloro-5-trifluoromethylpyridine |
| CN111170932A (en) * | 2020-01-13 | 2020-05-19 | 大连九信精细化工有限公司 | Preparation method of 2-aminomethyl-5-trifluoromethyl pyridine salt |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4367336A (en) * | 1980-02-21 | 1983-01-04 | Ishihara Sangyo Kaisha, Ltd. | 2-Substituted-5-trifluoromethylpyridines and process for producing the same |
| US4766219A (en) * | 1985-06-03 | 1988-08-23 | The Dow Chemical Company | Preparation of 2-cyano-6-chloropyridine compounds |
| US4851539A (en) * | 1982-06-18 | 1989-07-25 | The Dow Chemical Company | 2,3-Difluoropyridine and 3-fluoro-2-pyridinyloxyphenol compounds |
| WO1992018487A1 (en) * | 1991-04-15 | 1992-10-29 | Zeneca Limited | Substituted-2-phenyl-3-methoxypropenoates as fungicides |
-
2000
- 2000-08-25 GB GB0021066A patent/GB0021066D0/en not_active Ceased
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2001
- 2001-08-21 CN CNB2005100882205A patent/CN100564360C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4367336A (en) * | 1980-02-21 | 1983-01-04 | Ishihara Sangyo Kaisha, Ltd. | 2-Substituted-5-trifluoromethylpyridines and process for producing the same |
| US4851539A (en) * | 1982-06-18 | 1989-07-25 | The Dow Chemical Company | 2,3-Difluoropyridine and 3-fluoro-2-pyridinyloxyphenol compounds |
| US4766219A (en) * | 1985-06-03 | 1988-08-23 | The Dow Chemical Company | Preparation of 2-cyano-6-chloropyridine compounds |
| WO1992018487A1 (en) * | 1991-04-15 | 1992-10-29 | Zeneca Limited | Substituted-2-phenyl-3-methoxypropenoates as fungicides |
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| GB0021066D0 (en) | 2000-10-11 |
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