JP3547017B2 - Method for producing 2-aminobenzyl alcohols - Google Patents
Method for producing 2-aminobenzyl alcohols Download PDFInfo
- Publication number
- JP3547017B2 JP3547017B2 JP05258994A JP5258994A JP3547017B2 JP 3547017 B2 JP3547017 B2 JP 3547017B2 JP 05258994 A JP05258994 A JP 05258994A JP 5258994 A JP5258994 A JP 5258994A JP 3547017 B2 JP3547017 B2 JP 3547017B2
- Authority
- JP
- Japan
- Prior art keywords
- producing
- catalyst
- nitrobenzaldehyde
- formula
- aminobenzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 238000004519 manufacturing process Methods 0.000 title claims description 22
- -1 2-aminobenzyl alcohols Chemical class 0.000 title claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 claims description 8
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 239000007868 Raney catalyst Substances 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 239000003054 catalyst Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical group [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- BWRBVBFLFQKBPT-UHFFFAOYSA-N (2-nitrophenyl)methanol Chemical compound OCC1=CC=CC=C1[N+]([O-])=O BWRBVBFLFQKBPT-UHFFFAOYSA-N 0.000 description 3
- FXWFZIRWWNPPOV-UHFFFAOYSA-N 2-aminobenzaldehyde Chemical compound NC1=CC=CC=C1C=O FXWFZIRWWNPPOV-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- 239000002574 poison Substances 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- OJZQOQNSUZLSMV-UHFFFAOYSA-N (3-aminophenyl)methanol Chemical compound NC1=CC=CC(CO)=C1 OJZQOQNSUZLSMV-UHFFFAOYSA-N 0.000 description 2
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910001361 White metal Inorganic materials 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000002815 nickel Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
- 239000010969 white metal Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KWXFQMHMUVDCGC-UHFFFAOYSA-N 2,3-dimethoxy-6-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1OC KWXFQMHMUVDCGC-UHFFFAOYSA-N 0.000 description 1
- LLEKPOIFAGQDSK-UHFFFAOYSA-N 2,4-dimethoxy-6-nitrobenzaldehyde Chemical compound COC1=CC(OC)=C(C=O)C([N+]([O-])=O)=C1 LLEKPOIFAGQDSK-UHFFFAOYSA-N 0.000 description 1
- RULWBFLPUAFFGY-UHFFFAOYSA-N 2-(hydroxymethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1CO RULWBFLPUAFFGY-UHFFFAOYSA-N 0.000 description 1
- RZDOUWDCYULHJX-UHFFFAOYSA-N 2-chloro-6-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1C=O RZDOUWDCYULHJX-UHFFFAOYSA-N 0.000 description 1
- LBHWNZFYCKTRFN-UHFFFAOYSA-N 2-methyl-6-nitrobenzaldehyde Chemical compound CC1=CC=CC([N+]([O-])=O)=C1C=O LBHWNZFYCKTRFN-UHFFFAOYSA-N 0.000 description 1
- VHXOKHNXAGVMJI-UHFFFAOYSA-N 3,4-dimethoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C(C=O)C([N+]([O-])=O)=C1OC VHXOKHNXAGVMJI-UHFFFAOYSA-N 0.000 description 1
- IOHYBMYWODOPEY-UHFFFAOYSA-N 3,6-dimethoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C(OC)C([N+]([O-])=O)=C1C=O IOHYBMYWODOPEY-UHFFFAOYSA-N 0.000 description 1
- WKHILFGJMAXBNZ-UHFFFAOYSA-N 3-chloro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=C(Cl)C=CC=C1C=O WKHILFGJMAXBNZ-UHFFFAOYSA-N 0.000 description 1
- MMJHLWJXUDPLRW-UHFFFAOYSA-N 4,5-dimethyl-2-nitrobenzaldehyde Chemical compound CC1=CC(C=O)=C([N+]([O-])=O)C=C1C MMJHLWJXUDPLRW-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XLTSVKXVJZWHGB-UHFFFAOYSA-N 4-iodo-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(I)=CC=C1C=O XLTSVKXVJZWHGB-UHFFFAOYSA-N 0.000 description 1
- FDYADQPZUDULNK-UHFFFAOYSA-N 4-methyl-2-nitrobenzaldehyde Chemical compound CC1=CC=C(C=O)C([N+]([O-])=O)=C1 FDYADQPZUDULNK-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- UFRVBZVJVRHSNR-UHFFFAOYSA-N 5-bromo-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1C=O UFRVBZVJVRHSNR-UHFFFAOYSA-N 0.000 description 1
- JVVPPRRJHPQUHT-UHFFFAOYSA-N 6-chloro-3-methoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C(Cl)C(C=O)=C1[N+]([O-])=O JVVPPRRJHPQUHT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004645 aluminates Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 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
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- BDAGIHXWWSANSR-NJFSPNSNSA-N hydroxyformaldehyde Chemical compound O[14CH]=O BDAGIHXWWSANSR-NJFSPNSNSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time 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
- 150000003839 salts Chemical class 0.000 description 1
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 229910000018 strontium carbonate Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Description
【０００１】
【産業上の利用分野】
本発明は２−アミノベンジルアルコ−ル類の製造方法に関する。２−アミノベンジルアルコ−ル類は、医薬の原料として、重要な中間体である。
【従来の技術】
２−アミノベンジルアルコ−ル類の製造方法としては、
１）アントラニル酸の還元：▲１▼電解還元による方法 Ｊ．Ｃ．Ｓ．，１９４２，９８−１０２ ；Ｏｒｇａｎｉｃ Ｓｙｎｔｈｅｓｉｓ ２１，１０−１２（１９４１）▲２▼水素化リチウムアルミニウムによる還元 Ｊ．Ａ．Ｃ．Ｓ．，６９，２５４８−９（１９４７）；Ｊ．Ａ．Ｃ．Ｓ．，７２，３５８６−８（１９５０）▲３▼ソディウムディハイドロビス（２−メトキシエトキシ）アルミネートによる還元 Ｉｎｄｉａｎ Ｊ．Ｃｈｅｍ．Ｅｄｕｃ．１９７２，３（１），２３−４▲４▼ボランメチルサルファイドによる還元 Ｊ．Ｏｒｇ．Ｃｈｅｍ．１９７４，３９（２０），３０５２−４▲５▼サマリウムディヨーダイドによる還元 Ｂｕｌｌ．Ｃｈｅｍ．Ｓｏｃ．Ｊｐｎ．１９９２，６５（１１），３０４９−５４
２）アントラニル酸エステルの還元：▲１▼水素化ホウ素ナトリウムによる還元
特開昭６２−３３１３９：Ｂｕｌｌ．Ｃｈｅｍ．Ｓｏｃ．Ｊｐｎ．１９９１，６４（９），２７３０−４
３）２−ニトロベンジルアルコールの還元：▲１▼水硫化ソ−ダによる還元 Ｂｅｒ．６１Ｂ，２５５５−６６（１９２８） 水素還元 Ｕ．Ｓ．Ｓ．Ｒ．１８５，９３６
４）２−アミノベンズアルデヒドの還元：▲１▼水素還元 Ｂ，５６，２１７４
５）２−カルバモイルベンジルアルコ−ルのホフマン分解法 特開昭５６−７３０４９
等がある。
しかし、原料が高価、工程が複雑、長い、収率が低い、等問題があり、工業的な方法とはいい難い。
【０００２】
【発明が解決しようとする課題】
以上のように、従来の合成方法では、煩雑な操作を必要とし、工業的に安価に製造できるものではないので、安価な製造方法が望まれていた。
【０００３】
前記したように、アントラニル酸またはアントラニル酸エステルを還元して、２ーアミノベンジルアルコールを合成する方法は、還元剤が高価か、エーテル、テトラヒドロフラン等の危険な有機溶剤を使用するなど、工業的な方法とは言えないため、別の原料系を探す必要があった。
２ーニトロベンジルアルコールを還元する方法は、適切な還元剤を選択する必要があり、誤ると、分子内酸化還元が生じ、２ーアミノベンズアルデヒドとなる。室温で水素還元する例もあるが、２ーニトロベンジルアルコールは、市場で入手しにくい。
本発明者は市場で容易に得られる２ーニトロベンズアルデヒドの水素還元による２ーアミノベンジルアルコールの製造方法を検討した。
その結果、触媒、反応温度、反応水素圧を選択することにより、良好な収率で２ーアミノベンジルアルコールが得られることが分かり、又、式［１］で表される化合物についても、同様に反応することが分かり、本発明を完成した。
【０００４】
【課題を解決するための手段】
即ち、本発明は
（１）２−ニトロベンズアルデヒド類を還元して、２−アミノベンジルアルコール類を製造する方法において、金属触媒の存在化、水素添加することを、特徴とする２−アミノベンジルアルコール類の製造方法、
（２）２−ニトロベンズアルデヒド類が次式［１］で表される化合物であり、
【０００５】
【化３】
（式中、Ｒ１ およびＲ２ は、水素原子、アルキル基、アルコキシ基またはハロゲン原子を表わし、Ｒ１ およびＲ２ は同種であっても、異なっていてもよい。）
２−アミノベンジルアルコ−ル類が、次式［２］で表される化合物である前項（１）記載の製造方法、
【０００７】
【化４】
（式中、Ｒ１ およびＲ２ は、水素原子、アルキル基、アルコキシ基またはハロゲン原子を表わし、Ｒ１ およびＲ２ は同種であっても、異なっていてもよい。）
（３）式［１］の定義におけるＲ１ 、Ｒ２ が共に、水素原子である前項（２）記載の製造方法。
（４）金属触媒が、パラジウム、白金である前項（１）−（３）記載の２−アミノベンジルアルコ−ル類の製造方法、
（５）金属触媒が、ニッケルである前項（１）−（３）記載の２−アミノベンジルアルコ−ル類の製造方法、
（６）ニッケル金属触媒が、ラネ−ニッケルである前項（５）記載の２−アミノベンジルアルコ−ル類の製造方法、
（７）反応温度が１０−１５０℃である前項（１）−（６）記載の２−アミノベンジルアルコ−ル類の製造方法、
（８）反応温度が３０−１００℃である前項（７）記載の２−アミノベンジルアルコ−ル類の製造方法、
（９）反応温度が４０−８０℃である前項（８）記載の２−アミノベンジルアルコ−ル類の製造方法、
（１０）反応水素圧が２−２００ｋｇ／ｃｍ２ （ゲージ圧）である前項（１）−（９）記載の２−アミノベンジルアルコ−ル類の製造方法、
（１１）反応水素圧が２−５０ｋｇ／ｃｍ２ （ゲージ圧）である前項（１０）記載の２−アミノベンジルアルコ−ル類の製造方法、
（１２）３−２０ｋｇ／ｃｍ２ （ゲージ圧）である前項（１１）記載の２−アミノベンジルアルコ−ル類の製造方法、
である。
【０００９】
又Ｊ．Ｏｒｇ．Ｃｈｅｍ．１５，６５９−６１（１９５０）には、ｍ−ニトロベンズアルデヒド、ｐ−ニトロベンズアルデヒドを、アダムスのＰｔＯ２ 触媒で、水素還元して、ポリマーを得ている。
又、Ｃｈｅｍ．Ｂｅｒ．８７，２２８−３１（１９５４）には、ｍ−ニトロベンズアルデヒドを、メタノール溶剤中、ラネーニッケル触媒で、室温、水素圧６０ｋｇ／ｃｍ２ で還元して、ｍ−アミノベンジルアルコールを得ている。
しかし、これらの例より、本発明を類推することは難しい。
ｏ−体の場合は、アルデヒド基が隣のニトロ基により酸化され、カルボキシル基になり、ニトロ基が還元されアミノ基になりやすいと考えられる。
ｍ−体やｐ−体の場合は、アルデヒド基とニトロ基が離れていて、ｏ−体に比較して、影響が少ないと考えられるからである。
シッフの塩の生成速度も、相当異なると考えられる。従って、ｍ−体でスムーズに反応したからといって、ｏ−体にも直ちに適応できるとは考えにくい。
上記の二つの例は、反応条件が、詳細に記述されていないが、ｍ−体は、触媒の違いにより、大きく生成物が異なっている。アダムスのＰｔＯ２ はポリマーを、ラネーニッケルはｍ−アミノベンジルアルコールを与える。
触媒を選択する必要性は、伺い知ることができるが、直ちに、本発明を類推し得ない。本発明の触媒選択の基準とは、全くことなっている。本発明では、Ｐｔを使用することもできる。
【００１０】
Ｂ，５６，２１７４には、２ーアミノアルデヒドをデカリン中、１１５−１２０℃にて、ニッケル塩で水素還元して、２ーアミノベンジルアルコールを得ている。しかし、デカリンという特殊な溶剤を使用し、高い温度で反応させていること、ニッケル塩と本発明のニッケル金属系触媒とは本質的に異なる触媒作用を持っていることは、衆知の事実であること、アミノ基とニトロ基では、触媒に与える被毒の程度は大きく異なること等により、本反応を類推することは、困難である。ニトロ基は、触媒に強く吸着し、触媒を被毒しやすい。アミノ基の置換した構造で反応がスムーズにいったとしても、ニトロ基では、難しい場合が多い。
ニトロ基がアミノ基に還元される途中で、触媒が被毒され、次の反応（アルデヒドの還元によるアルコールの生成）が起こり難くなるからである。
従って、後記の本発明の反応が室温で反応することを、類推することは、極めて難しい。
【００１１】
以下、本発明を詳細に説明する。
式〔１〕の定義のアルキル基とは、炭素数１−６の直鎖または分岐鎖のアルキルをいう。例えばメチル、エチル。プロピル、イソプロピル、ｎ−ブチル、ｉｓｏ−ブチル、ｔｅｒｔ−ブチル、ペンチル、ヘキシル等である。アルコキシ基とはメトキシ、エトキシ、プロポキシ、ブトキシ等である。ハロゲン原子とは、塩素、臭素、ヨウ素、フッ素である。
具体的に本発明に用いられる２ーニトロベンズアルデヒド類としては、例えば前記式〔１〕で示されるものであるが、具体的には、５，６ジメトキシ−２−ニトロベンズアルデヒド、４，６ジメトキシ−２−ニトロベンズアルデヒド、３，６ジメトキシ−２−ニトロベンズアルデヒド、３，４ジメトキシ−２−ニトロベンズアルデヒド、５−ブロモ−２−ニトロベンズアルデヒド、６−クロロ−２−ニトロベンズアルデヒド、３ークロロ−２−ニトロベンズアルデヒド、４ーヨード−２−ニトロベンズアルデヒド、６ーメチル−２−ニトロベンズアルデヒド、４，５ジメチル−２−ニトロベンズアルデヒド、６ークロロ−３−メトキシ−２−ニトロベンズアルデヒド、４−メチル−２−ニトロベンズアルデヒド、３−メチル−２−ニトロベンズアルデヒド、４ーフルオロ−２−ニトロベンズアルデヒド、３ーメトキシ−２−ニトロベンズアルデヒド等を挙げることが出来る。
触媒としては、白金属系触媒、ニッケル系触媒を挙げることが出来る。
白金属系触媒としては、例えば、白金、パラジウム、ロジウム、ルテニウム等の金属を挙げることができる。該金属は、活性炭、二酸化珪素、アルミナ、硫酸バリウム、炭酸カルシウム、炭酸ストロンチウム等の担体に分散させて使用しても良い。例えば、パラジウム−カーボン、白金−カーボンが好ましい。また、該金属の酸化物も有用に使用される。例えば、酸化白金、酸化パラジウムが好ましい。
促進剤、及び又は、被毒剤を加えて、選択性を向上することも出来る。
Ｎｉ系触媒としては、漆原触媒、担体付き触媒、ホウ化ニッケル触媒、ラネーニッケル触媒を挙げることが出来る。中でもラネーニッケル触媒が好ましい。
促進剤、及び又は、被毒剤を加えて、選択性を向上することも出来る
【００１２】
触媒量は、原料の２ーニトロアルデヒドに対し、１−１００重量％、好ましくは２−４０重量％、更に好ましくは５−３０重量％である。１００重量％を越えると、初期の反応速度が速くなりすぎ、温度を制御しにくい。経済的でない。
１重量％未満では、速度が遅くなりすぎ、反応時間が２０時間を超え、経済的でない。
反応溶剤は、メタノール、エタノール、プロパノール、イソプロパノール、ブタノール等のアルコール類、蟻酸、酢酸、プロピオン酸、酪酸、等の有機酸類、
ジオキサン、テトラヒドロフラン等のエーテル類、酢酸メチル、酢酸エチル、酢酸プロピル等のエステル類、トルエン、ヘキサン、シクロヘキサン等の炭化水素類、及び水を挙げることができる。該溶剤は、単独にあるいは、二種以上混合して、使用してもよい。
【００１３】
反応温度は、１０−１５０℃、好ましくは、３０−１００℃、特に好ましくは、４０−８０℃である。１５０℃を越えると、副反応物が多くなる。１０℃未満では反応速度が遅い。
反応水素圧は、２−２００ｋｇ／ｃｍ２ （ゲージ圧）、好ましくは、２−５０ｋｇ／ｃｍ２ （ゲージ圧）、特に好ましくは、３−２０ｋｇ／ｃｍ２ （ゲージ圧）である。
【００１４】
２ーアミノベンジルアルコール類を比較的溶かさない溶剤例えば、トルエン等の溶剤を反応溶剤として、使用した場合は、熱時、触媒を分離し、適切な溶剤量に調節して、２ーアミノベンジルアルコール類を溶解、析出させ、トルエン等で洗浄し、ＬＣ面積純度９９．６％以上の２ーアミノベンジルアルコール類を得る。又、硅藻土、活性炭等で、若干の溶剤浮遊物、又は、着色物の除去操作をしても良い。
【００１５】
【実施例】
実施例によって本発明を具体的に説明するが、本発明がこれらの実施例のみに限定されるものでない。
実施例１
撹拌器、温度計を備えた５００ｃｃオートクレーブに、２−ニトロベンズアルデヒド ９０ｇ、メタノール ３００ｃｃ、ラネーニッケル（川研ファインケミカル（株）製 ＮＤＴ−９０） １８ｇ（金属）加え、水素圧 ９ｋｇ／ｃｍ２ （ゲージ圧）に保ち、室温にて、反応させると、約１時間で、３０℃に温度が上昇した。加熱を開始し、約３０分で６０℃に温度を上げ、その後、６０℃で５時間保つと水素の吸収が止まった。更に、１時間、熟成して、オートクレーブより、反応物を取り出した。静置し、上澄み液を５００ｃｃビーカに移し、減圧濾過した。濾液を、減圧ロータリーエバポレータにかけ、メタノールを留去した。残査として、２ーアミノベンジルアルコール ７１．６ｇ 粗収率 ９７．７％、融点 ８０−８２℃、液体クロマト純度 ９４．１面積％。
上記全量を４８０ｃｃのトルエンで再結晶すると、６５．９ｇ得られた。
精製品収率 ９０％、液体クロマト純度 ９９．６％。
【００２０】
【発明の効果】
２ーアミノベンジルアルコール類が、高収率、高純度、簡単な操作で、製造できる。[0001]
[Industrial applications]
The present invention relates to a method for producing 2-aminobenzyl alcohols. 2-aminobenzyl alcohols are important intermediates as raw materials for pharmaceuticals.
[Prior art]
As a method for producing 2-aminobenzyl alcohols,
1) Reduction of anthranilic acid: (1) Method by electrolytic reduction C. S. , 1942 , 98-102; Organic Synthesis 21 , 10-12 (1941) (2) Reduction with lithium aluminum hydride. A. C. S. , 69 , 2548-9 (1947); A. C. S. , 72 , 3586-8 (1950) (3) Reduction with sodium dihydrobis (2-methoxyethoxy) aluminate Chem. Educ. 1972 , 3 (1), 23-4 {4} Reduction with borane methyl sulfide Org. Chem. 1974 , 39 (20), 3052-4 <5> Reduction with samarium diiodide Bull. Chem. Soc. Jpn. 1992 , 65 (11), 3049-54
2) Reduction of anthranilate: (1) Reduction with sodium borohydride JP-A-62-33139: Bull. Chem. Soc. Jpn. 1991 , 64 (9), 2730-4
3) Reduction of 2-nitrobenzyl alcohol: {circle around (1)} Reduction with sodium hydrogen sulfide Ber. 61B , 2555-66 (1928) Hydrogen reduction U.S. S. S. R. 185,936
4) Reduction of 2-aminobenzaldehyde: (1) hydrogen reduction B, 56 , 2174
5) Hoffman decomposition method of 2-carbamoylbenzyl alcohol
Etc.
However, there are problems that the raw material is expensive, the process is complicated, long, and the yield is low.
[0002]
[Problems to be solved by the invention]
As described above, the conventional synthesis method requires complicated operations and cannot be manufactured industrially at low cost, and thus an inexpensive manufacturing method has been desired.
[0003]
As described above, the method of synthesizing 2-aminobenzyl alcohol by reducing anthranilic acid or anthranilic acid ester requires an industrial method such as using a high-priced reducing agent or using a dangerous organic solvent such as ether or tetrahydrofuran. Since it was not a method, it was necessary to find another raw material system.
In the method of reducing 2-nitrobenzyl alcohol, it is necessary to select an appropriate reducing agent, and if mistaken, intramolecular oxidation-reduction occurs, resulting in 2-aminobenzaldehyde. In some cases, hydrogen reduction is performed at room temperature, but 2-nitrobenzyl alcohol is hardly available on the market.
The present inventors have studied a method for producing 2-aminobenzyl alcohol by hydrogen reduction of 2-nitrobenzaldehyde, which is easily obtained on the market.
As a result, it was found that by selecting the catalyst, the reaction temperature, and the reaction hydrogen pressure, 2-aminobenzyl alcohol can be obtained with a good yield. The same applies to the compound represented by the formula [1]. The reaction was found to be completed, and the present invention was completed.
[0004]
[Means for Solving the Problems]
That is, the present invention provides (1) a method for producing 2-aminobenzyl alcohols by reducing 2-nitrobenzaldehydes, wherein a metal catalyst is present and hydrogenated. Manufacturing methods,
(2) 2-nitrobenzaldehydes are compounds represented by the following formula [1],
[0005]
Embedded image
(In the formula, R 1 and R 2 represent a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom, and R 1 and R 2 may be the same or different.)
The production method according to the above (1), wherein the 2-aminobenzyl alcohol is a compound represented by the following formula [2]:
[0007]
Embedded image
(In the formula, R 1 and R 2 represent a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom, and R 1 and R 2 may be the same or different.)
(3) The production method according to the above (2), wherein both R 1 and R 2 in the definition of the formula [1] are hydrogen atoms.
(4) The method for producing 2-aminobenzyl alcohols according to the above (1) to (3), wherein the metal catalyst is palladium or platinum;
(5) The method for producing 2-aminobenzyl alcohols according to the above (1) to (3), wherein the metal catalyst is nickel,
(6) the method for producing 2-aminobenzyl alcohols according to the above (5), wherein the nickel metal catalyst is Raney nickel;
(7) The method for producing 2-aminobenzyl alcohols according to (1) to (6), wherein the reaction temperature is 10 to 150 ° C.
(8) The method for producing 2-aminobenzyl alcohols according to the above (7), wherein the reaction temperature is 30-100 ° C.
(9) The method for producing 2-aminobenzyl alcohols according to (8), wherein the reaction temperature is 40 to 80 ° C.
(10) The method for producing 2-aminobenzyl alcohols according to (1) to (9), wherein the reaction hydrogen pressure is 2-200 kg / cm 2 (gauge pressure).
(11) The method for producing 2-aminobenzyl alcohols according to (10), wherein the reaction hydrogen pressure is 2 to 50 kg / cm 2 (gauge pressure).
(12) the method for producing 2-aminobenzyl alcohols according to the above (11), which is 3 to 20 kg / cm 2 (gauge pressure);
It is.
[0009]
Also, J. Org. Chem. 15 , 659-61 (1950), a polymer is obtained by hydrogen reduction of m-nitrobenzaldehyde and p-nitrobenzaldehyde with an Adams PtO 2 catalyst.
Also, Chem. Ber. 87 , 228-31 (1954), m-nitrobenzaldehyde is reduced with a Raney nickel catalyst in a methanol solvent at room temperature and a hydrogen pressure of 60 kg / cm 2 to obtain m-aminobenzyl alcohol.
However, it is difficult to infer the present invention from these examples.
In the case of the o-form, it is considered that the aldehyde group is oxidized by the adjacent nitro group to become a carboxyl group, and the nitro group is reduced to become an amino group.
This is because, in the case of the m-form or the p-form, the aldehyde group is separated from the nitro group, and it is considered that the influence is smaller than that of the o-form.
The rate of formation of Schiff's salt may also vary considerably. Therefore, it is unlikely that the m-body smoothly responds to the o-body immediately.
In the above two examples, the reaction conditions are not described in detail, but the m-isomer greatly differs in the product due to the difference in the catalyst. PtO 2 in Adams polymer, Raney nickel gives m- aminobenzyl alcohol.
Although the need to select a catalyst can be known, the present invention cannot be immediately analogized. The criteria for selecting the catalyst of the present invention are completely different. In the present invention, Pt can also be used.
[0010]
For B, 56 , 2174, 2-aminoaldehyde is obtained by reducing 2-aminoaldehyde in decalin at 115-120 ° C with hydrogen over a nickel salt. However, it is a well-known fact that a special solvent called decalin is used and reacted at a high temperature, and that the nickel salt and the nickel metal-based catalyst of the present invention have an essentially different catalytic action. In addition, it is difficult to analogize this reaction because the degree of poisoning given to the catalyst differs greatly between the amino group and the nitro group. Nitro groups are strongly adsorbed on the catalyst and are liable to poison the catalyst. Even if the reaction proceeds smoothly with an amino-substituted structure, it is often difficult with a nitro group.
This is because the catalyst is poisoned while the nitro group is reduced to the amino group, and the next reaction (the production of alcohol by the reduction of aldehyde) becomes difficult to occur.
Therefore, it is extremely difficult to infer that the reaction of the present invention described below reacts at room temperature.
[0011]
Hereinafter, the present invention will be described in detail.
The alkyl group defined in the formula [1] refers to a linear or branched alkyl having 1 to 6 carbon atoms. For example, methyl, ethyl. Propyl, isopropyl, n-butyl, iso-butyl, tert-butyl, pentyl, hexyl and the like. The alkoxy group is methoxy, ethoxy, propoxy, butoxy and the like. Halogen atoms are chlorine, bromine, iodine and fluorine.
Specific examples of the 2-nitrobenzaldehyde used in the present invention include those represented by the formula [1], and specific examples thereof include 5,6 dimethoxy-2-nitrobenzaldehyde and 4,6 dimethoxy- 2-nitrobenzaldehyde, 3,6 dimethoxy-2-nitrobenzaldehyde, 3,4 dimethoxy-2-nitrobenzaldehyde, 5-bromo-2-nitrobenzaldehyde, 6-chloro-2-nitrobenzaldehyde, 3-chloro-2-nitrobenzaldehyde 4,4-iodo-2-nitrobenzaldehyde, 6-methyl-2-nitrobenzaldehyde, 4,5 dimethyl-2-nitrobenzaldehyde, 6-chloro-3-methoxy-2-nitrobenzaldehyde, 4-methyl-2-nitrobenzaldehyde, 3- Methyl-2-nitroben Aldehyde, 4 Furuoro 2-nitrobenzaldehyde, 3 Metokishi 2-nitrobenzaldehyde and the like.
Examples of the catalyst include a white metal catalyst and a nickel catalyst.
Examples of the white metal catalyst include metals such as platinum, palladium, rhodium and ruthenium. The metal may be used by dispersing it in a carrier such as activated carbon, silicon dioxide, alumina, barium sulfate, calcium carbonate, strontium carbonate and the like. For example, palladium-carbon and platinum-carbon are preferred. Also, oxides of the metal are usefully used. For example, platinum oxide and palladium oxide are preferable.
Accelerators and / or poisons can be added to improve selectivity.
Examples of the Ni-based catalyst include Urushibara catalyst, catalyst with a carrier, nickel boride catalyst, and Raney nickel catalyst. Among them, Raney nickel catalyst is preferred.
Accelerators and / or poisons can be added to improve selectivity.
The amount of the catalyst is 1 to 100% by weight, preferably 2 to 40% by weight, and more preferably 5 to 30% by weight, based on 2-nitroaldehyde as a raw material. If it exceeds 100% by weight, the initial reaction rate becomes too fast, and it is difficult to control the temperature. Not economic.
If it is less than 1% by weight, the speed becomes too slow and the reaction time exceeds 20 hours, which is not economical.
Reaction solvents include methanol, ethanol, propanol, isopropanol, alcohols such as butanol, formic acid, acetic acid, propionic acid, butyric acid, and other organic acids,
Examples thereof include ethers such as dioxane and tetrahydrofuran, esters such as methyl acetate, ethyl acetate and propyl acetate, hydrocarbons such as toluene, hexane and cyclohexane, and water. The solvents may be used alone or as a mixture of two or more.
[0013]
The reaction temperature is from 10 to 150 ° C, preferably from 30 to 100 ° C, particularly preferably from 40 to 80 ° C. If the temperature exceeds 150 ° C., the amount of side reactants increases. If the temperature is lower than 10 ° C., the reaction rate is low.
The reaction hydrogen pressure is 2-200 kg / cm 2 (gauge pressure), preferably 2-50 kg / cm 2 (gauge pressure), and particularly preferably 3-20 kg / cm 2 (gauge pressure).
[0014]
When a solvent relatively insoluble in 2-aminobenzyl alcohol, for example, a solvent such as toluene is used as a reaction solvent, the catalyst is separated at the time of heating, and the amount of the solvent is adjusted to an appropriate amount. Are dissolved and precipitated, and washed with toluene or the like to obtain 2-aminobenzyl alcohol having an LC area purity of 99.6% or more. In addition, it is possible to remove a small amount of solvent suspended matter or colored matter with diatomaceous earth or activated carbon.
[0015]
【Example】
The present invention will be specifically described by way of examples, but the present invention is not limited to only these examples.
Example 1
In a 500 cc autoclave equipped with a stirrer and a thermometer, 90 g of 2-nitrobenzaldehyde, 300 cc of methanol and 18 g of Raney nickel (NDT-90 manufactured by Kawaken Fine Chemical Co., Ltd.) (metal) were added, and hydrogen pressure was 9 kg / cm 2 (gauge pressure). The temperature was raised to 30 ° C. in about 1 hour. Heating was started, and the temperature was raised to 60 ° C. in about 30 minutes, and then kept at 60 ° C. for 5 hours to stop hydrogen absorption. After aging for 1 hour, the reaction product was taken out of the autoclave. After standing still, the supernatant was transferred to a 500 cc beaker and filtered under reduced pressure. The filtrate was subjected to a vacuum rotary evaporator to distill off methanol. As a residue, 71.6 g of 2-aminobenzyl alcohol, a crude yield of 97.7%, a melting point of 80 to 82 ° C., and a purity of liquid chromatography of 94.1 area%.
The whole amount was recrystallized from 480 cc of toluene to obtain 65.9 g.
Purified product yield 90%, liquid chromatography purity 99.6%.
[0020]
【The invention's effect】
2-Aminobenzyl alcohols can be produced with high yield, high purity and simple operation.
Claims (2)
で表される２−ニトロベンズアルデヒド類を、ラネーニッケルの存在下、反応温度４０−８０℃、反応水素圧３−２０ｋｇ／ｃｍ2（ゲージ圧）で水素添加して還元することを特徴とする、次式［２］
で表される２−アミノベンジルアルコール類の製造方法。The following equation [1]
Wherein 2-nitrobenzaldehyde represented by the formula is reduced by hydrogenation in the presence of Raney nickel at a reaction temperature of 40-80 ° C and a reaction hydrogen pressure of 3-20 kg / cm 2 (gauge pressure). Equation [2]
A method for producing a 2-aminobenzyl alcohol represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP05258994A JP3547017B2 (en) | 1994-02-28 | 1994-02-28 | Method for producing 2-aminobenzyl alcohols |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP05258994A JP3547017B2 (en) | 1994-02-28 | 1994-02-28 | Method for producing 2-aminobenzyl alcohols |
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| Publication Number | Publication Date |
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| JPH07242603A JPH07242603A (en) | 1995-09-19 |
| JP3547017B2 true JP3547017B2 (en) | 2004-07-28 |
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| JP05258994A Expired - Fee Related JP3547017B2 (en) | 1994-02-28 | 1994-02-28 | Method for producing 2-aminobenzyl alcohols |
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| WO2025240827A1 (en) | 2024-05-16 | 2025-11-20 | Corteva Agriscience Llc | Processes related to preparation of substituted benzene derivatives as intermediates for the synthesis of pesticidal oxathiazolidines |
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