JP7448969B2 - N-シクロプロピルメチルアニリン系化合物の調製方法 - Google Patents
N-シクロプロピルメチルアニリン系化合物の調製方法 Download PDFInfo
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- JP7448969B2 JP7448969B2 JP2021195992A JP2021195992A JP7448969B2 JP 7448969 B2 JP7448969 B2 JP 7448969B2 JP 2021195992 A JP2021195992 A JP 2021195992A JP 2021195992 A JP2021195992 A JP 2021195992A JP 7448969 B2 JP7448969 B2 JP 7448969B2
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- cyclopropylmethylaniline
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- 238000000034 method Methods 0.000 title claims description 35
- UYFBSIJFMJLIAZ-UHFFFAOYSA-N n-(cyclopropylmethyl)aniline Chemical class C1CC1CNC1=CC=CC=C1 UYFBSIJFMJLIAZ-UHFFFAOYSA-N 0.000 title claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 33
- -1 N-cyclopropylmethylaniline compound Chemical class 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- 239000003054 catalyst Substances 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 claims description 20
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 238000005984 hydrogenation reaction Methods 0.000 claims description 10
- 235000019260 propionic acid Nutrition 0.000 claims description 10
- 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 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000007868 Raney catalyst Substances 0.000 claims description 2
- 235000011054 acetic acid Nutrition 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 239000005456 alcohol based solvent Substances 0.000 claims 1
- 239000003759 ester based solvent Substances 0.000 claims 1
- 239000004210 ether based solvent Substances 0.000 claims 1
- 239000000706 filtrate Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000012512 characterization method Methods 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 6
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 4
- 238000005580 one pot reaction Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- DIEURQHPYHTDQS-UHFFFAOYSA-N C1(CC1)CNC=1C(=C(C(=O)OC(C)C)C=CC=1)F Chemical compound C1(CC1)CNC=1C(=C(C(=O)OC(C)C)C=CC=1)F DIEURQHPYHTDQS-UHFFFAOYSA-N 0.000 description 2
- IINDERHJCHTMAE-UHFFFAOYSA-N C1(CC1)CNC=1C(=C(C(=O)OCC)C=CC=1)F Chemical compound C1(CC1)CNC=1C(=C(C(=O)OCC)C=CC=1)F IINDERHJCHTMAE-UHFFFAOYSA-N 0.000 description 2
- GBQYLFCKFLNUBH-UHFFFAOYSA-N C1(CC1)CNC=1C(=C(C(=O)OCCC)C=CC=1)F Chemical compound C1(CC1)CNC=1C(=C(C(=O)OCCC)C=CC=1)F GBQYLFCKFLNUBH-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 238000007281 aminoalkylation reaction Methods 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000002917 insecticide Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- ZNGHATPBZTZUQQ-UHFFFAOYSA-N methyl 3-(cyclopropylmethylamino)-2-fluorobenzoate Chemical compound FC1=C(C(=O)OC)C=CC=C1NCC1CC1 ZNGHATPBZTZUQQ-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940090181 propyl acetate Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- FKTXDTWDCPTPHK-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical group FC(F)(F)[C](F)C(F)(F)F FKTXDTWDCPTPHK-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- NEJSBVQRQLMNFH-UHFFFAOYSA-N 2-fluoro-n-methyl-3-nitrobenzamide Chemical compound CNC(=O)C1=CC=CC([N+]([O-])=O)=C1F NEJSBVQRQLMNFH-UHFFFAOYSA-N 0.000 description 1
- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- BXVSKBBMPWRRSP-UHFFFAOYSA-N N-[2-chloro-6-(difluoromethoxy)-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-2-fluoro-3-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC2=C(Cl)C=C(C=C2OC(F)F)C(F)(C(F)(F)F)C(F)(F)F)=C1F BXVSKBBMPWRRSP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 101150013568 US16 gene Proteins 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- MFXTZNGCDRNCKK-UHFFFAOYSA-N ethyl 2-fluoro-3-nitrobenzoate Chemical compound CCOC(=O)C1=CC=CC([N+]([O-])=O)=C1F MFXTZNGCDRNCKK-UHFFFAOYSA-N 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- NUKZAGXMHTUAFE-UHFFFAOYSA-N hexanoic acid methyl ester Natural products CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 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
- 239000004615 ingredient Substances 0.000 description 1
- VEKYKLDXYNUERO-UHFFFAOYSA-N methyl 2-fluoro-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1F VEKYKLDXYNUERO-UHFFFAOYSA-N 0.000 description 1
- PRIGHYHJLGBCAE-UHFFFAOYSA-N n-[2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethoxy)phenyl]-2-fluoro-3-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC=2C(=CC(=CC=2Br)C(F)(C(F)(F)F)C(F)(F)F)OC(F)(F)F)=C1F PRIGHYHJLGBCAE-UHFFFAOYSA-N 0.000 description 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- JGFCWNALDDSHOG-UHFFFAOYSA-N propan-2-yl 2-fluoro-3-nitrobenzoate Chemical compound CC(C)OC(C(C=CC=C1[N+]([O-])=O)=C1F)=O JGFCWNALDDSHOG-UHFFFAOYSA-N 0.000 description 1
- KEBHKUSIAFUCCB-UHFFFAOYSA-N propyl 2-fluoro-3-nitrobenzoate Chemical compound CCCOC(C(C=CC=C1[N+]([O-])=O)=C1F)=O KEBHKUSIAFUCCB-UHFFFAOYSA-N 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
(ただし、Rは、アルコキシ基、アルキルアミノ基、または置換アニリノ基(
)である。)
このうち、ホウ素試薬(トリアセトキシ水素化ホウ素ナトリウム)、トリフルオロ酢は高価であり、更に、反応中に大量の二置換化合物が生成され、収率が高くない。
式IIで示される化合物およびシクロプロパンカルボキシアルデヒドを原料として、酸および触媒の作用下で水素化反応を行い、式Iで示される前記N-シクロプロピルメチルアニリン系化合物を取得するステップを含み、反応式は以下のとおりである、
(ただし、Rは、アルコキシ基、アルキルアミノ基、または式IIIで示される置換アニリノ基から選ばれる。)
(ただし、Rの限定範囲は請求項1と一致し、式IIで示される化合物とシクロプロパンカルボキシアルデヒドとのモル比は1:(0.5~3)であり、式IIで示される化合物と酸との質量比は1:(0.01~0.6)であり、式IIで示される化合物と触媒との質量比は1:(0.001~0.05)であり、式IIで示される化合物と溶媒との質量比は1:(2~10)である。)
LC/MS [M+1]:m/z=224。
1H NMR(400 MHz, CDCl3)データは以下のとおりである(δ[ppm])。7.18-7.15 (m, 1H), 7.05-7.01(m, 1H), 6.85-6.82 (m, 1H), 4.21 (br s, 1H), 3.93 (s, 3H), 3.01 (d, J = 5.6 Hz, 2H), 1.15-1.12 (m, 1H), 0.62-0.58 (m, 2H), 0.30-0.25 (m, 2H)。
LC/MS [M+1]:m/z=238。
LC/MS [M+1]:m/z=252。
LC/MS [M+1]:m/z=521。
1H NMR(400 MHz, DMSO-d6)データは以下のとおりである(δ[ppm])。10.18 (s, 1H), 8.12-8.07 (m, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.92 (s, 1H), 7.10 (t, J = 7.9 Hz, 1H), 6.94 (t, J = 8.2 Hz, 1H), 6.90-6.82 (m, 1H), 5.82-5.72 (m, 1H), 3.03 (t, J = 6.2 Hz, 2H), 1.12-1.08 (m, 1H), 0.50-0.42 (m, 2H), 0.24 (q, J = 4.4 Hz, 2H)。
LC/MS [M+1]:m/z=647。
1H NMR(400 MHz, DMSO-d6)データは以下のとおりである(δ[ppm])。10.53 (s, 1H), 8.41 (s, 1H), 7.97 (s, 1H), 7.11 (m, 1H), 6.96-6.91 (m, 1H), 6.84-6.81 (m, 1H), 5.79-5.75 (m, 1H), 3.04 (t, J = 6.2 Hz, 2H), 1.15-1.07 (m, 1H), 0.49-0.44 (m, 2H), 0.28-0.24 (m, 2H)。
LC/MS [M+1]:m/z=598。
1H NMR(400 MHz, DMSO-d6)データは以下のとおりである(δ[ppm])。1H NMR (400 MHz, DMSO-d6) 10.01 (s, 1H), 7.66 (s, 1H), 7.30 (s, 1H), 7.09 (t, J = 72.0 Hz, 1H), 6.85 (t, J = 7.8 Hz, 1H), 6.69 (t, J = 7.7 Hz, 1H), 6.56 (t, J = 6.2 Hz, 1H), 5.47 (s, 1H), 2.79 (t, J = 5.7 Hz, 2H), 0.90-0.80 (m, 1H), 0.24-0.18 (m, 2H), 0.01 (q, J = 4.9 Hz, 2H)。
LC/MS [M+1]:m/z=616。
1H NMR(400 MHz, DMSO-d6)データは以下のとおりである(δ[ppm])。10.53 (s, 1H), 8.10 (s, 1H), 7.78 (s, 1H), 7.13-7.07 (m, 1H), 6.96-6.91 (m, 1H), 6.78-6.75 (m, 1H),5.78-5.74 (m, 1H), 3.03 (t, J = 6.2 Hz, 2H), 0.98-0.90 (m, 1H), 0.26-0.22 (m, 2H), 0.16-0.12 (m, 2H)。
Claims (16)
- 前記Rは、C1~C6アルコキシ基から選ばれるいずれか1種であることを特徴とする、請求項1に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記Rは、メトキシ基、エトキシ基、プロポキシ基、またはイソプロポキシ基であることを特徴とする、請求項2に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記Rは、C1~C6アルキルアミノ基から選ばれるいずれか1種であることを特徴とする、請求項1に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記Rは、メチルアミノ基であることを特徴とする、請求項4に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記水素化反応は溶媒中に行われ、前記溶媒は、アルコール系溶媒、エステル系溶媒、エーテル系溶媒、ハロゲン化炭化水素系溶媒、またはベンゼン系溶媒のうちのいずれか1種または少なくとも2種の組み合わせを含むことを特徴とする、請求項1~6のいずれか一項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記溶媒は、メタノール、エタノール、酢酸エチル、またはトルエンのうちのいずれか1種または少なくとも2種の組み合わせであることを特徴とする、請求項7に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記酸は、無機酸または有機酸を含むことを特徴とする、請求項1~8のいずれか一項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記酸は、ギ酸、酢酸、プロピオン酸、塩酸、または硫酸のうちのいずれか1種または少なくとも2種の組み合わせであることを特徴とする、請求項9に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記酸は、酢酸および/またはプロピオン酸であることを特徴とする、請求項9に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記触媒は、白金炭素であることを特徴とする、請求項1~11のいずれか1項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記IIで示される化合物とシクロプロパンカルボキシアルデヒドとのモル比は1:(0.5~3)であり、
前記式IIで示される化合物と酸との質量比は1:(0.01~0.6)であり、
前記式IIで示される化合物と触媒との質量比は1:(0.001~0.05)であり、
前記式IIで示される化合物と溶媒との質量比は1:(2~10)であることを特徴とする、請求項1~12のいずれか1項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。 - 前記水素化反応の温度は30~150℃であり、時間は8~20hであることを特徴とする、請求項1~13のいずれか1項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 前記水素化反応において、水素ガスが通気された後の圧力を0.2~5.0MPaに制御することを特徴とする請求項1~14のいずれか1項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
- 式IIで示される化合物およびシクロプロパンカルボキシアルデヒドを原料として、酸および触媒の作用下で30~150℃にて水素化反応を8~20h行い、圧力を0.2~5.0MPaに制御し、式Iで示される前記N-シクロプロピルメチルアニリン系化合物を取得するステップを含み、反応式は以下のとおりである、
(ただし、Rの限定範囲は請求項1と一致し、式IIで示される化合物とシクロプロパンカルボキシアルデヒドとのモル比は1:(0.5~3)であり、式IIで示される化合物と酸との質量比は1:(0.01~0.6)であり、式IIで示される化合物と触媒との質量比は1:(0.001~0.05)であり、式IIで示される化合物と溶媒との質量比は1:(2~10)である。)
ことを特徴とする、請求項1~15のいずれか1項に記載のN-シクロプロピルメチルアニリン系化合物の調製方法。
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US20200178525A1 (en) | 2018-06-26 | 2020-06-11 | Cac Shanghai International Trading Co., Ltd. | M-diamide compound and preparation method thereof and use thereof |
US10844005B1 (en) | 2019-10-25 | 2020-11-24 | Chang Sha Jia Qiao Biotech Co., Ltd. | Method for preparing an N-cyclopropylmethyl aniline compound |
WO2021073373A1 (en) | 2019-10-15 | 2021-04-22 | Cac Nantong Chemical Co., Ltd. | Amide compounds and preparation method therefor and use thereof |
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