WO1996020164A1 - Procede de production de derive de 2-(2-hydroxymethylphenyl)acetamide et intermediaire utilise pour sa production - Google Patents
Procede de production de derive de 2-(2-hydroxymethylphenyl)acetamide et intermediaire utilise pour sa production Download PDFInfo
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- WO1996020164A1 WO1996020164A1 PCT/JP1995/002621 JP9502621W WO9620164A1 WO 1996020164 A1 WO1996020164 A1 WO 1996020164A1 JP 9502621 W JP9502621 W JP 9502621W WO 9620164 A1 WO9620164 A1 WO 9620164A1
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 15
- YWRSQOLTKJVEIN-UHFFFAOYSA-N 2-[2-(hydroxymethyl)phenyl]acetamide Chemical class NC(=O)CC1=CC=CC=C1CO YWRSQOLTKJVEIN-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 239000000203 mixture Substances 0.000 claims abstract description 72
- 125000006239 protecting group Chemical group 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- -1 triaralkylnyl Chemical group 0.000 claims description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000011777 magnesium Substances 0.000 claims description 11
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 11
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 229910052749 magnesium Inorganic materials 0.000 claims description 10
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 7
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 5
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 5
- 239000007818 Grignard reagent Substances 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 150000004795 grignard reagents Chemical class 0.000 claims description 4
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 4
- 238000010306 acid treatment Methods 0.000 claims description 3
- 125000005107 alkyl diaryl silyl group Chemical group 0.000 claims description 3
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 125000005429 oxyalkyl group Chemical group 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- IVIIAEVMQHEPAY-UHFFFAOYSA-N tridodecyl phosphite Chemical group CCCCCCCCCCCCOP(OCCCCCCCCCCCC)OCCCCCCCCCCCC IVIIAEVMQHEPAY-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- 239000000284 extract Substances 0.000 description 18
- 238000010898 silica gel chromatography Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 150000002430 hydrocarbons Chemical class 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- YKECSFNZQGAHFU-UHFFFAOYSA-N 2-iminoacetamide Chemical compound NC(=O)C=N YKECSFNZQGAHFU-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- JRMAQQQTXDJDNC-UHFFFAOYSA-M 2-ethoxy-2-oxoacetate Chemical compound CCOC(=O)C([O-])=O JRMAQQQTXDJDNC-UHFFFAOYSA-M 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- 238000006317 isomerization reaction Methods 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 4
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000000417 fungicide Substances 0.000 description 4
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 4
- CEAJFNBWKBTRQE-UHFFFAOYSA-N methanamine;methanol Chemical compound NC.OC CEAJFNBWKBTRQE-UHFFFAOYSA-N 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 4
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- IOWGHQGLUMEZKG-UHFFFAOYSA-N (2-bromophenyl)methanol Chemical compound OCC1=CC=CC=C1Br IOWGHQGLUMEZKG-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000005046 Chlorosilane Substances 0.000 description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 230000000855 fungicidal effect Effects 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910000103 lithium hydride Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000004210 ether based solvent Substances 0.000 description 2
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 description 2
- 150000004692 metal hydroxides Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- CZVBTOGZRGRJSC-UHFFFAOYSA-N 2,5-dichloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(Cl)=CN=C1Cl CZVBTOGZRGRJSC-UHFFFAOYSA-N 0.000 description 1
- 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
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- RTKKOPXYLQWHBJ-UHFFFAOYSA-N 2-[(2-bromophenyl)methoxy]oxane Chemical compound BrC1=CC=CC=C1COC1OCCCC1 RTKKOPXYLQWHBJ-UHFFFAOYSA-N 0.000 description 1
- YOWQWFMSQCOSBA-UHFFFAOYSA-N 2-methoxypropene Chemical compound COC(C)=C YOWQWFMSQCOSBA-UHFFFAOYSA-N 0.000 description 1
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
- FMQUUOZOHJGBLK-UHFFFAOYSA-N 2-phenylethyl 2-oxoacetate Chemical compound O=CC(=O)OCCC1=CC=CC=C1 FMQUUOZOHJGBLK-UHFFFAOYSA-N 0.000 description 1
- DGBGIIPEHWOEQZ-UHFFFAOYSA-N 2-phenylmethoxyoxane Chemical compound C=1C=CC=CC=1COC1CCCCO1 DGBGIIPEHWOEQZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BTOJSYRZQZOMOK-UHFFFAOYSA-N 4-chloro-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=NC(Cl)=C2C=C1 BTOJSYRZQZOMOK-UHFFFAOYSA-N 0.000 description 1
- STBGWNRZMPCVTG-UHFFFAOYSA-N 4h-thiopyran Chemical compound C1C=CSC=C1 STBGWNRZMPCVTG-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000004258 Ethoxyquin Substances 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- LOMVENUNSWAXEN-UHFFFAOYSA-N Methyl oxalate Chemical compound COC(=O)C(=O)OC LOMVENUNSWAXEN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 239000005858 Triflumizole Substances 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005104 aryl silyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 description 1
- 229940093500 ethoxyquin Drugs 0.000 description 1
- 235000019285 ethoxyquin Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- OTCKNHQTLOBDDD-UHFFFAOYSA-K gold(3+);triacetate Chemical compound [Au+3].CC([O-])=O.CC([O-])=O.CC([O-])=O OTCKNHQTLOBDDD-UHFFFAOYSA-K 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 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
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 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
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- HSMVPDGQOIQYSR-KGENOOAVSA-N triflumizole Chemical compound C1=CN=CN1C(/COCCC)=N/C1=CC=C(Cl)C=C1C(F)(F)F HSMVPDGQOIQYSR-KGENOOAVSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/56—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having carbon atoms of carboxamide groups bound to carbon atoms of carboxyl groups, e.g. oxamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/12—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/17—Unsaturated ethers containing halogen
- C07C43/174—Unsaturated ethers containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention relates to a method for producing a 2- (2-hydroxymethylphenyl) acetamide derivative and an intermediate for the production thereof.
- the present invention relates to a 2- (2-hydroxymethylphenyl) acetamide derivative, which is an intermediate for producing an alkoxyiminoacetic acid amide compound useful as an agricultural fungicide,
- the present invention relates to a method for producing (hydroxymethylphenyl) -1-alkoxy (or hydroxy) iminoacetamide and intermediates for producing the same.
- 2- (2-Hydroxymethylphenyl) 1-2-alkoxy (or hydroxy) iminoacetamide is an important intermediate for the production of alkoxyminoacetamido derivatives useful as agricultural fungicides ( Japanese Patent Application Laid-Open (JP-A) Nos. 3-246628 and 4-182641).
- Examples of the method for producing the intermediate include a method in which 2- (2-methylphenyl) -12-alkoxyiminoacetic acid ester is reacted with a gold acetate salt and then with an amine (Japanese Patent Laid-Open No. 3-246628).
- An object of the present invention is to provide an industrially advantageous method for producing 2- (2-hydroxymethylphenyl) -12-alkoxy (or hydroxy) iminoacetamide. Further, another object of the present invention is to provide an intermediate for producing 2- (2-hydroxymethylphenyl) -12-alkoxy (or hydroxy) iminoacetamide. Disclosure of the invention
- the present inventors have conducted intensive studies to achieve the above object, and as a result, have found that 2- (2-hydroxymethylphenyl) -12-alkoxy (or hydroxy) iminoacetamide has a hydroxymethyl group.
- the present inventors have found that a compound having a protected hydroxyl group can be obtained by subjecting the compound to a hydroxyl group deprotection reaction, thereby completing the present invention.
- the present invention provides a compound represented by the general formula (II):
- R 1 and R 2 are the same or different and each is a hydrogen or an alkyl group, R is a hydrogen or an alkyl group, P is a hydroxyl-protecting group, is an E-form, a Z-form or a mixture thereof.
- the protecting group (P) for the hydroxyl group of the compound represented by the general formula (I) is removed:
- R 3 represents an alkyl group, and the other symbols have the same meanings as described above].
- the compound represented by the general formula ( ⁇ ) is a compound represented by the general formula (IV)
- R is as defined above
- the present invention further provides a compound represented by the general formula (ID) contained in the general formulas ( ⁇ ) and (IV):
- R 1 and R 2 are the same or different, hydrogen or an alkyl radical, R is hydrogen or an alkyl radical, [rho 2 is Ararukiru group, trialkoyl kill silyl group, preparative Ria Lal Kill silyl group, an alkyl di ⁇ reel Silyl group, alkoxyal A kill group, an alkoxyalkoxyalkyl group, an alkylthioalkyl group, a tetrahydrodrobilanyl group, a tetrahydrothiopyranyl group, a tetrahydrofuranyl group, a tetrahydrothiofuranyl group or an aralkyloxyalkyl group,
- R the alkyl group represented by RR 2 and R 3, for example 1 to 8 carbon atoms, and preferably c specifically include an alkyl group having 1 to 6 carbon atoms, such as methyl, Echiru , Propyl, isobutyl, sec-butyl, t-butyl and the like. Of these, methyl is preferred.
- Hydroxyl protecting groups represented by P and P 2 include, for example, T.W.Green3 ⁇ 4 '. Green), ⁇ Protective Groups in Organic Sy'nthesis'', P. 1-11-1, John Willy & Sons (19981); CB Reese, "Protective 'Groups'in' Organic '' Ethers listed in Chemistry (Protective Groups in Organic Chemistry), edited by JF McOmie, pp. 95-143, Plenum Press (1973), etc. Protection of normal hydroxyl groups such as type protecting groups and acetal type protecting groups
- ether type protecting group for example, an alkyl 'group (eg, - 6 alkyl group, preferably a C physician 4 alkyl groups such as methyl, Echiru, propyl, t one-butyl, etc.), an alkenyl group (e.g., C 2 - 6 alkenyl group, preferably a C 2-4 alkenyl group, such as Ariru)
- Ararukiru group e.g., substituted or unsubstituted C 6 - 10 7 reels primary alkyl groups, such as benzyl, p- main Bok Kishibenjiru, triflumizole We methylpropenylmethyl etc.
- trialkylsilyl group e.g., tri-C 1-6 alkylsilyl, e.g.
- alkyl di ⁇ reel silyl group e.g., d-6 alkyl distearate C 6 -!
- Arylsilyl such as t-butyldiphenylsilyl, etc.
- triaralkylsilyl group eg, tribenzylsilyl, etc.
- acetal-type protecting group examples include, for example, an alkoxyalkyl group (eg, c 1-4 alkoxy-1 C 1-4 alkyl, for example, methoxymethyl, 11-ethoxyquinethyl, 1-methyl-1-methoxyl), an alkoxyalkoxyalkyl group ( examples, C physician 4 alkoxy one C physician 4 alkoxy one C physician 4 alkyl, such as main Bok carboxymethyl eth Kin methyl), alkylthioalkyl (e.g., d alkylthio one c 1-4 alkyl, for example methylthiomethyl, etc.), Te Jewishi Drobilanyl group (eg, tetrahydridopyran-1-yl, 4-methoxytetrahydrodropyran-4-yl, etc.), tetrahydridothiopyranyl group (eg, tetrahydridothiopyran-2-yl, etc.), tetrahydrofurany
- protecting groups that can be removed by acid treatment are preferred.
- a protecting group which can be more removed and is stable under a Grignard reagent (eg, a compound ( ⁇ ) described below) synthesis reaction conditions or basic conditions is preferable.
- Specific examples of preferred protecting groups include an aralkyl group (eg, triphenylmethyl), a trialkylsilyl group (eg, t-butyldimethylsilyl, triisopropylsilyl, etc.), a triaralkylsilyl group (eg, tribenzyl Silyl, etc.), alkoxyalkyl groups (eg, methoxymethyl, 11-ethoxyl, 11-methyl-1-methoxyl, etc.), tetrahydrobiranyl groups (eg, tetrahydropyran-12-yl, etc.), tetrahydrothiopyranyl groups (eg, For example, a tetrahydrochlorothiofuran-2-yl group,
- the compounds represented by the general formulas (II) and (II-1) and the general formula (II-12) described below include E-isomer and Z-isomer. These compounds may be in any of the E-form, the Z-form or a mixture thereof, unless otherwise specified. In the above general formula, this is shown using a wavy line ( ⁇ ).
- the compounds represented by the general formulas U), (I-11), (I-12) and (II-11) may form a salt, and specific examples of such a salt include an alkali metal Salts (eg, sodium salt, potassium salt, lithium salt, etc.).
- alkali metal Salts eg, sodium salt, potassium salt, lithium salt, etc.
- Preferred examples of the compound represented by the general formula (I) include a compound in which R is a hydrogen atom or a methyl group, and a compound in which R 1 and R 2 are a hydrogen atom; and a compound in which R is a hydrogen atom or a methyl group; And a compound wherein one of R 2 is a hydrogen atom and the other is a methyl group.
- R is a hydrogen atom or a methyl group
- the desired compound represented by the general formula (I) (hereinafter sometimes referred to as compound (I), and the same applies to other compounds) is a compound in which R is a hydrogen atom (I-11) , And R are alkyl groups (I-12).
- the compound (I-11) can be produced according to the following scheme 1, and the compound (I-12) can be produced according to the scheme 3 or 4.
- the compound (I-11) can be obtained by removing the hydroxyl-protecting group (P) of the compound (II-1).
- the isomerization to the E-isomer proceeds at the same time as the removal of the protecting group for the hydroxyl group, so there is no need for a separate isomerization step to the E-isomer, and a high-purity compound (1-1) is obtained Can be obtained at a rate.
- the protecting group of a hydroxyl group is an alkyl group (eg, t-butyl, etc.), an alkenyl group (eg, aryl, etc.), an aralkyl group (eg, trif-X-methyl, etc.), a trialkylsilyl group (eg, , T-butyldimethylsilyl, triisopropylsilyl, etc.), alkyldiarylsilyl group (eg, tbutyldiphenylsilyl, etc.), triaralkylsilyl group (eg, tribenzylsilyl, etc.), alkoxyalkyl ( For example, methoxymethyl, 1-ethoxyethyl, 1-methyl-11-methoxethyl, alkoxyalkoxyalkyl (for example, methoxyethoxyquinmethyl), alkylthioalkyl (for example, methylthiomethyl), tetrahydrobi
- acids examples include, for example, hydrohalic acids (eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), hydrogen halides (eg, hydrogen chloride, hydrogen bromide, hydrogen iodide, etc.), Inorganic acids such as boric acid, phosphoric acid and sulfuric acid; sulfonic acids (eg, aliphatic sulfonic acids such as trifluoromethanesulfonic acid and aromatic sulfonic acids such as toluenesulfonic acid); carboxylic acids (eg, acetic acid, Trifluoroacetic acid, etc.), silica gel, Lewis acid [eg, aluminum halide (eg, aluminum chloride, etc.), zinc chloride, titanium tetrachloride, etc.]. One or more suitable acids are appropriately selected from these and used. Can be used.
- hydrohalic acids eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.
- hydrogen halides
- the amount of acid used is trace to 1 equivalent.
- carboxylic acids may be used as the solvent.
- Solvents that can be used include, for example, hydrocarbons (eg, benzene, toluene, quinylene, etc.), halogenated hydrocarbons (eg, dichloromethane, 1.2 dichloroethane, etc.), ethers (eg, tetrahydrofuran, dioxane, etc.) And alcohols (eg, methanol, ethanol, etc.), nitriles (eg, acetate nitrile, etc.), water, and a mixed solvent thereof.
- the reaction temperature is one 80 to 150 ° C
- c reaction time is preferably one 10 to 80 ° C is 1 minute to 3 hours, preferably 5 minutes to 1 hour.
- the protecting group is a substituted silyl, for example, under basic conditions (eg, sodium hydroxide / hydrated ethanol, etc.) or fluorine anion (eg, n—Bu 4 N, F ⁇ , C 5 H 5 N + HF- etc.).
- basic conditions eg, sodium hydroxide / hydrated ethanol, etc.
- fluorine anion eg, n—Bu 4 N, F ⁇ , C 5 H 5 N + HF- etc.
- the thus-obtained compound (1-1) has a more preferable content of the E-form, and thus can be used in the next step as a reaction solution or as a crude product. If necessary, it can be purified by a conventional method (eg, column chromatography, recrystallization, etc.) and used in the next step.
- a conventional method eg, column chromatography, recrystallization, etc.
- Compound (II-11) that can be used as a starting material for this reaction can be preferably produced according to the following scheme 2.
- the compound (II-1) can be produced by reacting the compound (IV) with hydroxyylamine and / or a salt thereof in a suitable solvent.
- Hydroxylyamine is used in 1 to 4 equivalents, preferably 1 to 3 equivalents, relative to compound (IV).
- Examples of the salt of hydroxylamine include mineral salts such as hydrochloride and sulfate.
- the reaction is carried out by neutralizing with a base so that the protecting group for the hydroxyl group is not eliminated.
- Bases that can be used include, for example, metal hydroxides (eg, sodium hydroxide, potassium hydroxide, etc.), metal carbonates (eg, sodium carbonate, potassium carbonate, etc.), metal alkoxides (eg, , Sodium methoxide, sodium ethoxide, etc.), amides (eg, pyridin), etc., in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the salt of hydroquinamine. .
- metal hydroxides eg, sodium hydroxide, potassium hydroxide, etc.
- metal carbonates eg, sodium carbonate, potassium carbonate, etc.
- metal alkoxides eg, , Sodium methoxide, sodium ethoxide, etc.
- Solvents that can be used include, for example, hydrocarbons (eg, benzene, toluene, xylene, etc.), halogenated hydrocarbons (eg, chloroform, 1,2-dichloroethane, etc.), ethers (eg, tetrahydrofuran) , Dioxane, etc.), alcohols (eg, methanol, ethanol, n-propanol, isopropanol, etc.), water and a mixed solvent thereof.
- hydrocarbons eg, benzene, toluene, xylene, etc.
- halogenated hydrocarbons eg, chloroform, 1,2-dichloroethane, etc.
- ethers eg, tetrahydrofuran
- Dioxane Dioxane
- alcohols eg, methanol, ethanol, n-propanol, isopropanol, etc.
- the reaction temperature is from 0 to 150 ° C, preferably from 20 to 100 ° C.
- the reaction time is usually about 15 minutes to 24 hours.
- the obtained compound (II-11) can be used in the next step after purification by a reaction method or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.).
- compound (I-12) can be produced according to the following scheme 3. Wear.
- compound (I-12) can be produced by reacting compound (1-1) with an alkylating agent in an appropriate solvent in the presence of a base to carry out alkylation.
- alkylating agent examples include dialkyl sulfates (eg, dimethyl sulfate, diethyl sulfate, etc .; 6 alkyl sulfates), alkyl halides (eg, C 1-6 such as methyl chloride, methyl bromide, methyl iodide, etc.). Alkyl halide, etc.).
- the amount of the alkylating agent to be used is 1 to 10 mol, preferably 1 to 1.5 mol, per 1 mol of compound (1-1).
- solvent examples include ketones (eg, acetone, ethyl methyl ketone, etc.), ethers (eg, tetrahydrofuran, dioxane, etc.), hydrocarbons (eg, toluene, benzene, hexane, cyclohexane). Etc.), halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, etc.), alcohols (eg, methanol, ethanol, etc.), water, etc. c These solvents may be used alone or in combination. be able to.
- ketones eg, acetone, ethyl methyl ketone, etc.
- ethers eg, tetrahydrofuran, dioxane, etc.
- hydrocarbons eg, toluene, benzene, hexane, cyclohexane.
- Etc. halogenated hydrocarbons
- Examples of the base include metal carbonates (eg, sodium carbonate, carbonated lime, etc.), metal hydroxides (eg, sodium hydroxide, lithium hydroxide, hydroxide) Lithium hydride, etc.) and metal hydrides (eg, sodium hydride, lithium hydride, etc.).
- the amount of the base to be used is 1-10 mol, preferably 1-2 mol, per 1 mol of compound (I-11).
- phase transfer catalyst examples include quaternary ammonium salts [eg, tetraalkylammonium halides (eg, tetrabutylammonium chloride, tetrabutylammonium bromide, etc.), tetraalkylammonium hydroxide sulfate (eg, tetrabutylammonium halide, etc.).
- quaternary ammonium salts eg, tetraalkylammonium halides (eg, tetrabutylammonium chloride, tetrabutylammonium bromide, etc.), tetraalkylammonium hydroxide sulfate (eg, tetrabutylammonium halide, etc.).
- amines eg, tris (3,6-dioxaheptyl) amine, etc.
- the amount of the phase transfer catalyst to be used is 0.01 to 1 mol
- the reaction temperature is usually from 20 to 100 ° C, preferably from 0 to 50 ° C, and the reaction time is usually from 1 to 24 hours.
- the obtained compound (I-12) can be used in the next step after being purified as a reaction solution or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.).
- compound (1-2) can also be produced according to scheme 4 below.
- the compound (I-12) can be produced by removing the hydroxyl-protecting group (P) of the compound (II-2).
- the isomerization to the E-isomer proceeds at the same time as the removal of the protecting group (P) for the hydroxyl group, so that a separate isomerization step to the E-isomer is not required, and the high-purity compound (I-I ) Can be obtained in high yield.
- This reaction can be performed under the same reaction conditions as in the reaction of Scheme 1.
- the obtained compound (I-12) can be used in the next step after being purified as a reaction solution or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.).
- the compound (II-12) can be produced by reacting the compound (IV-11) with the compound (III-11) and / or a salt thereof.
- the salt of the compound (III-11) include the same salts as those of the hydroxylamine in Scheme 2.
- This reaction can be carried out under the same reaction conditions as in the reaction of Scheme 2.
- the obtained compound (II-2) can be used in the next step after being purified as it is or as a crude reaction solution, or by a conventional method (eg, column chromatography, recrystallization, etc.).
- the compound ( ⁇ ) can be produced by reacting the compound (VI) with the compound (V).
- halogen atom represented by L examples include fluorine, chlorine, bromine, and iodine. Of these, chlorine or bromine is preferred.
- Examples of the alkoxy group represented by L include an alkoxy group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxyquin, and propoxy.
- Compound (V) is not diluted with a solvent, or is diluted with an appropriate solvent and added dropwise to compound (VI) or introduced as a gas.
- the compound (V) is used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, based on the compound (VI).
- the compound ( ⁇ ) is a monoketoacid halide, 2 to 6 equivalents are used. preferable.
- the solvent include hydrocarbons (eg, benzene, toluene, xylene, etc.), halogenated carbon Hydrogens (eg, dichloromethane, 1,2-dichloroethane, etc.), ethers (eg, tetrahydrofuran. Dioxane, etc.), alcohols (eg, methanol, ethanol, etc.), water, and their mixed solvents No.
- hydrocarbons eg, benzene, toluene, xylene, etc.
- halogenated carbon Hydrogens eg, dichloromethane, 1,2-dichloroethane, etc.
- ethers eg, tetrahydrofuran. Dioxane, etc.
- alcohols eg, methanol, ethanol, etc.
- water and their mixed solvents No.
- the compound (V) is dropped or introduced at a temperature of from 75 to 50 ° (preferably from 160 to 30 ° C, for from 5 minutes to 2 hours, preferably from 15 minutes to 1 hour. Then, the reaction is carried out at 50 to 100 ° C., preferably at 130 to 60 ° C., for 1 minute to 5 hours, preferably for 10 minutes to 2 hours to obtain compound (IV).
- the obtained compound (7 [pi) is the the reaction mixture or the crude product, or a conventional method (e.g., column chromatography, recrystallization, etc.) to give it you to use in the next step.
- a conventional method e.g., column chromatography, recrystallization, etc.
- compound (VI) can be produced by reacting compound (VII) with compound (VII).
- halogen atom represented by X include fluorine, chlorine, bromine, and iodine. Among these, chlorine, bromine or iodine are preferred c
- the addition is carried out at a temperature of from 100 to 50 ° C, preferably from 170 to 30 ° C. C, for 5 minutes to 2 hours, preferably for 15 minutes to 1 hour. Then, the reaction is carried out at 100 to 50 ° C, preferably 180 to 30 ° C, for 5 minutes to 2 hours, preferably for 15 minutes to 1 hour.
- Examples of the solvent include ether solvents such as THF, getyl ether, dibutyl ether and the like, and hydrocarbon solvents such as toluene.
- Examples of the compound (VII) include oxalyl halides such as oxalyl chloride and oxalyl bromide, oxalic esters such as dimethyl oxalate and getyl oxalate, and oxalic esters such as methyloxalyl chloride and ethyl oxalyl chloride. Alkyloxalyl chlorides and the like.
- the compound (VII) may be reacted with the compound (VIII) without adding the solvent or by diluting the compound (VIII) with an appropriate solvent.
- the solvent and reaction conditions can be the same as described above.
- the compound (VI) thus obtained is ⁇ -keto acid halide
- it can be used in the next step as a reaction solution.
- ⁇ -keto acid ester it can be used in the next step after purification as a reaction solution or crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.) c
- compound (VI) is a monoketo acid ester, as an alternative, it may be produced by reacting compound (VII) with compound (VIII) in which Mg X is replaced by Li. Can be.
- L is preferably an alkoxy group.
- compound ⁇ ' ⁇ can be produced by reacting compound (IX) with magnesium in a suitable solvent.
- the compound (IX) is reacted with 1-4 equivalents, preferably 1-2 equivalents, of magnesium.
- ether solvents such as dry THF, getyl ether, dibutyl ether and the like. These may be used alone or may be a hydrocarbon (eg, toluene, etc.), an amine (eg, triethylamine, etc.). Such May be used as a mixed solvent with other solvents.
- the reaction temperature ranges from room temperature to 150 ° C., preferably from 40 to 100 ° C.
- the reaction time is 10 minutes to 48 hours, preferably 30 minutes to 6 hours.
- iodine dibromoethane, ethylpromide, etc.
- the amount is from 0.001 to 0.4 equivalent, preferably from 0.005 to 0.2 equivalent.
- the compound (II) in which MgX is replaced with Li can be produced by reacting compound (IX) with metallic lithium or alkyllithiums (eg, n-butyllithium, etc.).
- metallic lithium or alkyllithiums eg, n-butyllithium, etc.
- the obtained compound (VIII) can be used in the next step as a reaction solution or as a crude product.
- compound (II) can be produced by protecting the hydroxyl group of commercially available compound (X) with an appropriate protecting group.
- Hydroxyl protection includes, for example, T. W. Green, 'Protective Groups' in 'Organic Synthesis'
- the compound (IX) protected by tetrahydrobiranil, tetrahydrotiobiranil, tetrahydrofuranyl, tetrahydrothiofuranyl, 1-ethoxyl and 1-methyl-1-methoxyl corresponds to the corresponding olefin It is obtained by reacting compound (X) in the presence of an acid catalyst in a suitable solvent or without a solvent.
- the corresponding olefins are 3.4-dihydro 2H-pyran, 2,3-dihydro 4H-thiin, dihydrofuran, dihydrothiofuran, ethyl vinyl ether, and 2-methoxypropene, respectively, which are commercially available products. It can be used or manufactured by a known method.
- the amount of the olefin used is 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to compound (X).
- the acid catalyst examples include hydrogen chloride, oxylin chloride, p-toluenesulfonic acid, ⁇ -toluenesulfonic acid pyridin salt, montmorillonite, bistrimethylsulfuric acid, acetic acid, p-toluenesulfonic acid polyvinylpyridinium Trifluoroacetic acid, boron trifluoride etherate (BF 3 ⁇ ⁇ Et 2 ), and an acidic ion exchange resin.
- a non-alcoholic solvent can be used.
- hydrocarbons eg, benzene, toluene, xylene, etc.
- halogenated hydrocarbons eg, chloroform, dichloromethane, etc.
- ethers eg, getyl Ether, tetrahydrofuran, dioxane, etc.
- esters eg, ethyl acetate, etc.
- N-dimethylformamide e.g, N-dimethylformamide
- the reaction temperature is 130 to 100 ° C, preferably 0 to 60 ° C.
- the reaction time is usually about 15 minutes to 24 hours.
- the silyl ether type compound ( ⁇ ) can be obtained by reacting the compound (X) with a suitable silylating agent. In general, it is obtained by reacting compound (X) with chlorosilane as a silylating agent in the presence of a base in a suitable solvent.
- Chlorosilane can be used as a commercially available product or produced by a known method.
- Chlorsilane is used in an amount of 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to compound (X).
- Bases that can be used include organic bases (eg, ⁇ , ⁇ -dimethylaniline, pyridine, triethylamine, imidazole, etc.), metal carbonates (eg, sodium carbonate, potassium carbonate, etc.), metal hydrides (eg, Examples include sodium hydride, lithium hydride, etc., metal bicarbonates (eg, sodium bicarbonate, potassium bicarbonate, etc.), and the like.
- One or more equivalents, preferably one to two equivalents are used. can do.
- Solvents that can be used include hydrocarbons (eg, hexane, benzene, toluene, xylene, etc.), halogenated hydrocarbons (eg, chloroform, dichloromethane, methane, etc.), ethers (eg, getyl) Ethers, tetrahydrofuran, dioxane, etc.), ketones (eg, acetone, methyl ethyl ketone, etc.), nitriles (eg, acetonitrile, etc.), ⁇ , ⁇ -dimethylformamide, dimethylsulfo And a mixed solvent thereof.
- hydrocarbons eg, hexane, benzene, toluene, xylene, etc.
- halogenated hydrocarbons eg, chloroform, dichloromethane, methane, etc.
- ethers eg, getyl
- Ethers eg, t
- the reaction temperature is from 120 to 100 ° C, preferably from 0 to 60 ° C.
- the reaction time is 5 minutes to 30 hours, preferably 30 minutes to 15 hours.
- the compound (IX) protected by methoxymethyl or trifuunylmethyl and the compound (IX) protected by tetrahydrofuranyl or 1-ethoxyxetil described above can be obtained by adding the corresponding halide to the compound (X) in the presence of a base. It is obtained by reacting with
- Corresponding halides are halomethyl methyl ether, trimethyl methyl halide, 2-halotetrahydrofuran, and 1-haloethyl ether, respectively, which are either commercially available products or produced by known methods. be able to.
- Chloride or bromide can be used as halide.
- the compound ( ⁇ ) protected by methoxymethyl described above can be obtained by reacting the compound (X) with dimethoxymethane in the presence of a suitable catalyst (eg, phosphorus pentoxide, etc.).
- a suitable catalyst eg, phosphorus pentoxide, etc.
- Solvents and reaction conditions that can be used are the same as those for the above-mentioned reaction between olefin and compound (X).
- the obtained compound (IX) can be used in the next step as a crude product or purified by a conventional method (eg, column chromatography, recrystallization, etc.).
- X represents a halogen atom
- P 1 represents an aralkyl group, a triaralkylsilyl group, an alkoxyalkyl group, an alkoxyalkoxyalkyl group, an alkylthioalkyl group, a tetrahydrovinylyl group, a tetrahydrothiovinylyl group, and a tetrahydrofuranyl group.
- a tetrahydrothiofuranyl group or an aralkyloxyalkyl group is a novel compound and is included in the present invention.
- Specific examples of the groups represented by P 1, include the same groups as exemplified by P.
- the compound (I-12) obtained by the reactions of Schemes 3 and 4 can be converted into an alkoxyiminoacetic amide compound (XI) having excellent bactericidal activity and useful as an agricultural bactericide according to, for example, Scheme 10 below. It can be easily converted (see Japanese Patent Application Laid-Open No. 3-246628 and Japanese Patent Application Laid-Open No. 4-182461), and is useful as an intermediate for the production thereof.
- compound (XI) can be obtained by reacting compound (XII) with compound (I-12). Can be.
- the radical represented by A includes a substituted or unsubstituted radical,
- the heterocyclic group for example, at least one selected from nitrogen, oxygen, and sulfur
- Heterocyclic groups containing one heteroatom as a ring-constituting atom such as pyridyl, pyrimidinyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, isooxazolyl, isothiazolyl, quinolyl And so on.
- preferred substituents include, for example, methyl, trifluoromethyl, trichloromethyl, a fluorine atom, a chlorine atom, and methoxy.
- the mixture was dropped at a temperature of not more than 160 ° C for 15 minutes into a mixture of 50 milliliters of THF, and then stirred at a temperature of 160 to 170 ° C for 1 hour.
- To the reaction solution was added 11.65 g (0.15 mol) of a 40% methanol solution of methylamine, and the temperature was further raised from 150 ° C to room temperature in 1 hour.
- the reaction mixture was extracted with 500 milliliters of water, 300 milliliters of ether, and then 300 milliliters of dichloromethane.
- a mixture of (0.01 mol) and 8 milliliters of dry THF was added dropwise at 50-60 ° C over 20 minutes. After the dropwise addition, the mixture was stirred at 50 to 60 ° C for 1 hour, and then cooled to room temperature. After cooling, the mixture was added dropwise to a mixture of 1.90 g (0.015 mol) of oxalyl chloride and 30 ml of dry THF at 150 ° C or less for 15 minutes, and then stirred at 160-170 ° C for 40 minutes. did. 4.66 g (0.06 mol) of a 40% methylamine methanol solution was added to the reaction solution, and the mixture was further stirred at 120 to 110 ° C for 30 minutes.
- the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a crude product of 2- [2- (1-ethoxyquinethyl) oxymethyl] phenyl 2-hydroxymino-methylacetamide.
- 4 g of methanol and 0.05 g (0.0002 mol) of pyridinium p-toluenesulfonate were added, and the mixture was stirred under reflux for 30 minutes. After the reaction, the residue obtained by concentration under reduced pressure was added with 4 milliliters of acetone, and subsequently, 0.41 g (0.003 mol) of lithium carbonate and 0.30 g (0.0024 mol) of dimethyl sulfate were added by cooling on ice.
- Methoxyamine hydrochloride 7 Dissolve 2 g (0.09 mol) of ⁇ in 60 ml of methanol, then add 19.68 g (0.102 mol) of 28% sodium methoxide methanol solution on ice. To the suspension added under the same control, 15.92 g (0.06 mol) of 2- [2-((1-ethoxyquinethyl) oxymethyl ⁇ phenyl] -N-methyl-12-oxoacetamide was added to 60 milliliters of methanol. After the reaction, the methanol was concentrated under reduced pressure by about half, then 400 milliliters of water was added, and the mixture was extracted twice with 200 milliliters of dichloromethane.
- an alkoxyiminoacetic acid amide compound used as an agricultural fungicide is used.
- An economically and industrially advantageous method for producing 2- (2-hydroxymethylphenyl) -12-alkoxy (or hydroxy) iminoacetamide derivative useful as an intermediate for production, and an intermediate for production used therefor Is provided.
- an alkoxyiminoacetic acid amide compound useful as an agricultural fungicide obtained from compound (I) in a short process is a compound having a more excellent bactericidal action, and thus compound (I) can be obtained in E form. Is preferred.
- the isomerization to the E-isomer proceeds at the same time as the deprotection of the protecting group for the hydroxyl group. Highly pure E-isomer of (I) can be obtained, and its industrial utility is high.
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Description
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Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP95941835A EP0801054B1 (en) | 1994-12-26 | 1995-12-21 | Process for producing 2-(2-hydroxymethylphenyl)acetamide derivative and intermediate for the production thereof |
DK95941835T DK0801054T3 (da) | 1994-12-26 | 1995-12-21 | Fremgangsmåde til fremstilling af 2-(2-hydroxymethylphenyl)acetamidderivater og mellemprodukter til fremstilling deraf |
DE69517201T DE69517201T2 (de) | 1994-12-26 | 1995-12-21 | Verfahren zur herstellung von 2-(2-hydroxymethylphenyl)acetamid-derivaten und zwischenprodukte zur herstellung |
AU43145/96A AU4314596A (en) | 1994-12-26 | 1995-12-21 | Process for producing 2-(2-hydroxymethylphenyl)acetamide derivative and intermediate for the production thereof |
AT95941835T ATE193281T1 (de) | 1994-12-26 | 1995-12-21 | Verfahren zur herstellung von 2-(2- hydroxymethylphenyl)acetamid-derivaten und zwischenprodukte zur herstellung |
KR1019970704375A KR980700956A (ko) | 1994-12-26 | 1995-12-21 | 2-(2-하이드록시메틸페닐)아세트아미드 유도체의 제조방법 및 그의 제조를 위한 중간체(process for producing 2-(2-hydroxymethylphenyl)acetamide derivative and int ermediate for the production thereof) |
US08/849,218 US5856573A (en) | 1994-12-26 | 1995-12-21 | Process for producing 2-(2-hydroxymethylphenyl)acetamide derivative and intermediate for the production thereof |
GR20000401153T GR3033503T3 (en) | 1994-12-26 | 2000-05-25 | Process for producing 2-(2-hydroxymethylphenyl)acetamide derivative and intermediate for the production thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6/322130 | 1994-12-26 | ||
JP32213094 | 1994-12-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996020164A1 true WO1996020164A1 (fr) | 1996-07-04 |
Family
ID=18140271
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1995/002621 WO1996020164A1 (fr) | 1994-12-26 | 1995-12-21 | Procede de production de derive de 2-(2-hydroxymethylphenyl)acetamide et intermediaire utilise pour sa production |
Country Status (13)
Country | Link |
---|---|
US (2) | US5856573A (ja) |
EP (1) | EP0801054B1 (ja) |
KR (1) | KR980700956A (ja) |
CN (1) | CN1082046C (ja) |
AT (1) | ATE193281T1 (ja) |
AU (1) | AU4314596A (ja) |
DE (1) | DE69517201T2 (ja) |
DK (1) | DK0801054T3 (ja) |
ES (1) | ES2148587T3 (ja) |
GR (1) | GR3033503T3 (ja) |
PT (1) | PT801054E (ja) |
TW (1) | TW363957B (ja) |
WO (1) | WO1996020164A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0858997A1 (en) * | 1995-10-18 | 1998-08-19 | Zeneca Limited | Fungicides |
US6211202B1 (en) | 1997-11-14 | 2001-04-03 | Dow Agrosciences Llc | 2-methoxyimino-2-(pyridinyloxymethyl) phenyl acetamides with substituted ketal derivatives on the pyridine ring |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6369083B1 (en) | 1998-09-16 | 2002-04-09 | Dow Agrosciences Llc | 2-methoxyimino-2 (pyrinyloxymethyl) phenyl acetamides with polyether derivatives on the pyridine ring |
WO2000015616A1 (en) | 1998-09-16 | 2000-03-23 | Dow Agrosciences Llc | 2-methoxyimino-2-(pyridinyloxymethyl)phenyl acetamides with (derivatised) hydroxyalkyl derivatives on the pyridine ring |
BR9915968A (pt) * | 1998-09-16 | 2001-08-28 | Dow Agrosciences Llc | Acetamidas de 2-metoxiimino- 2-(piridiniloximetil)fenila com anéis heterocìclicos de 5 elementos no anel de piridina como fungicidas |
KR20020067549A (ko) | 1999-12-15 | 2002-08-22 | 다우 아그로사이언시즈 엘엘씨 | 살진균 활성을 갖는 피리딘 유도체, 이의 제조방법 및이의 사용 방법 |
CN105503642B (zh) * | 2015-12-17 | 2017-09-15 | 湖南科技大学 | N‑取代‑2‑(2‑羟基苄基)氨基乙酰胺类化合物及其制备和用途 |
GB201910037D0 (en) | 2019-07-12 | 2019-08-28 | Syngenta Crop Protection Ag | Microbiocidal compounds |
GB202006386D0 (en) | 2020-04-30 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal Compounds |
GB202006480D0 (en) | 2020-05-01 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal compounds |
GB202014840D0 (en) | 2020-09-21 | 2020-11-04 | Syngenta Crop Protection Ag | Microbiocidal compounds |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS4920324A (ja) * | 1972-06-19 | 1974-02-22 | ||
JPH04501418A (ja) * | 1988-10-25 | 1992-03-12 | イーストマン ケミカル カンパニー | ビアリール化合物の製造 |
JPH07233143A (ja) * | 1994-02-21 | 1995-09-05 | Taisho Pharmaceut Co Ltd | プロスタグランジン誘導体およびその使用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4030038A1 (de) * | 1990-09-22 | 1992-03-26 | Basf Ag | Ortho-substituierte phenylessigsaeureamide |
JP3121061B2 (ja) * | 1991-10-04 | 2000-12-25 | 塩野義製薬株式会社 | アルコキシイミノアセトアミド類製造用中間体の製造法およびそれに用いる中間体 |
US5258551A (en) * | 1991-12-18 | 1993-11-02 | Shionogi & Co., Ltd. | Process for producing α-ketoamide derivative |
US5506358A (en) * | 1993-03-16 | 1996-04-09 | Shionogi & Co., Ltd. | Process for producing alkoxyiminoacetamide compounds |
-
1995
- 1995-12-21 ES ES95941835T patent/ES2148587T3/es not_active Expired - Lifetime
- 1995-12-21 WO PCT/JP1995/002621 patent/WO1996020164A1/ja not_active Application Discontinuation
- 1995-12-21 US US08/849,218 patent/US5856573A/en not_active Expired - Fee Related
- 1995-12-21 DK DK95941835T patent/DK0801054T3/da active
- 1995-12-21 KR KR1019970704375A patent/KR980700956A/ko not_active Application Discontinuation
- 1995-12-21 DE DE69517201T patent/DE69517201T2/de not_active Expired - Fee Related
- 1995-12-21 CN CN95197669A patent/CN1082046C/zh not_active Expired - Fee Related
- 1995-12-21 PT PT95941835T patent/PT801054E/pt unknown
- 1995-12-21 AU AU43145/96A patent/AU4314596A/en not_active Abandoned
- 1995-12-21 EP EP95941835A patent/EP0801054B1/en not_active Expired - Lifetime
- 1995-12-21 AT AT95941835T patent/ATE193281T1/de not_active IP Right Cessation
- 1995-12-23 TW TW084113831A patent/TW363957B/zh active
-
1998
- 1998-10-16 US US09/174,256 patent/US6147231A/en not_active Expired - Fee Related
-
2000
- 2000-05-25 GR GR20000401153T patent/GR3033503T3/el not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4920324A (ja) * | 1972-06-19 | 1974-02-22 | ||
JPH04501418A (ja) * | 1988-10-25 | 1992-03-12 | イーストマン ケミカル カンパニー | ビアリール化合物の製造 |
JPH07233143A (ja) * | 1994-02-21 | 1995-09-05 | Taisho Pharmaceut Co Ltd | プロスタグランジン誘導体およびその使用 |
Non-Patent Citations (15)
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0858997A1 (en) * | 1995-10-18 | 1998-08-19 | Zeneca Limited | Fungicides |
US6211202B1 (en) | 1997-11-14 | 2001-04-03 | Dow Agrosciences Llc | 2-methoxyimino-2-(pyridinyloxymethyl) phenyl acetamides with substituted ketal derivatives on the pyridine ring |
Also Published As
Publication number | Publication date |
---|---|
DK0801054T3 (da) | 2000-08-07 |
EP0801054A4 (en) | 1998-12-23 |
KR980700956A (ko) | 1998-04-30 |
CN1082046C (zh) | 2002-04-03 |
DE69517201D1 (de) | 2000-06-29 |
ATE193281T1 (de) | 2000-06-15 |
GR3033503T3 (en) | 2000-09-29 |
CN1175244A (zh) | 1998-03-04 |
PT801054E (pt) | 2000-08-31 |
EP0801054B1 (en) | 2000-05-24 |
AU4314596A (en) | 1996-07-19 |
TW363957B (en) | 1999-07-11 |
ES2148587T3 (es) | 2000-10-16 |
US5856573A (en) | 1999-01-05 |
DE69517201T2 (de) | 2000-09-28 |
US6147231A (en) | 2000-11-14 |
EP0801054A1 (en) | 1997-10-15 |
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