CN114656389A - Synthesis method of 1-phenylpyrrolidine - Google Patents
Synthesis method of 1-phenylpyrrolidine Download PDFInfo
- Publication number
- CN114656389A CN114656389A CN202210448626.3A CN202210448626A CN114656389A CN 114656389 A CN114656389 A CN 114656389A CN 202210448626 A CN202210448626 A CN 202210448626A CN 114656389 A CN114656389 A CN 114656389A
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- CN
- China
- Prior art keywords
- phenylpyrrolidine
- copper
- nitro compound
- aromatic nitro
- synthesizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- VDQQJMHXZCMNMU-UHFFFAOYSA-N 1-phenylpyrrolidine Chemical compound C1CCCN1C1=CC=CC=C1 VDQQJMHXZCMNMU-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 69
- 238000006243 chemical reaction Methods 0.000 claims abstract description 55
- -1 aromatic nitro compound Chemical class 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 22
- 239000012074 organic phase Substances 0.000 claims abstract description 22
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 238000004440 column chromatography Methods 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- FSQYJJHVABILHQ-UHFFFAOYSA-N 4-(4-methylphenyl)sulfonyloxybutyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCCCOS(=O)(=O)C1=CC=C(C)C=C1 FSQYJJHVABILHQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012153 distilled water Substances 0.000 claims abstract description 12
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 11
- 238000001035 drying Methods 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000011259 mixed solution Substances 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- 239000003208 petroleum Substances 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- 230000002194 synthesizing effect Effects 0.000 claims description 11
- 239000003480 eluent Substances 0.000 claims description 10
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 6
- JJLJMEJHUUYSSY-UHFFFAOYSA-L copper(II) hydroxide Inorganic materials [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 claims description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 3
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 3
- AEJIMXVJZFYIHN-UHFFFAOYSA-N copper;dihydrate Chemical compound O.O.[Cu] AEJIMXVJZFYIHN-UHFFFAOYSA-N 0.000 claims description 3
- QYCVHILLJSYYBD-UHFFFAOYSA-L copper;oxalate Chemical compound [Cu+2].[O-]C(=O)C([O-])=O QYCVHILLJSYYBD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims description 3
- OXFZSJOUPRCPJO-UHFFFAOYSA-N copper ethyl 3-oxobutanoate Chemical compound [Cu+2].CCOC(=O)[CH-]C(C)=O.CCOC(=O)[CH-]C(C)=O OXFZSJOUPRCPJO-UHFFFAOYSA-N 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- SFAIGHZDVQCLIO-UHFFFAOYSA-L copper;2,2,2-trifluoroacetate;hydrate Chemical compound O.[Cu+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F SFAIGHZDVQCLIO-UHFFFAOYSA-L 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 15
- 239000000543 intermediate Substances 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 239000007788 liquid Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 14
- 239000002994 raw material Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 150000001500 aryl chlorides Chemical class 0.000 description 2
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- GYQYAJJFPNQOOW-UHFFFAOYSA-N gilteritinib Chemical compound N1=C(NC2CCOCC2)C(CC)=NC(C(N)=O)=C1NC(C=C1OC)=CC=C1N(CC1)CCC1N1CCN(C)CC1 GYQYAJJFPNQOOW-UHFFFAOYSA-N 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
- DPQIAEJLCJLSJK-UHFFFAOYSA-N 1-(4-chlorophenyl)pyrrolidine Chemical compound C1=CC(Cl)=CC=C1N1CCCC1 DPQIAEJLCJLSJK-UHFFFAOYSA-N 0.000 description 1
- IIYRJYZDFOBAKW-UHFFFAOYSA-N 1-(4-fluorophenyl)pyrrolidine Chemical compound C1=CC(F)=CC=C1N1CCCC1 IIYRJYZDFOBAKW-UHFFFAOYSA-N 0.000 description 1
- STRWKFUEXQHMFW-UHFFFAOYSA-N 1-(4-methylphenyl)pyrrolidine Chemical compound C1=CC(C)=CC=C1N1CCCC1 STRWKFUEXQHMFW-UHFFFAOYSA-N 0.000 description 1
- XAIOGMOTJLWPAJ-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]pyrrolidine Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCCC1 XAIOGMOTJLWPAJ-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- XKYLCLMYQDFGKO-UHFFFAOYSA-N 1-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(C(F)(F)F)C=C1 XKYLCLMYQDFGKO-UHFFFAOYSA-N 0.000 description 1
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 1
- SZBGQDXLNMELTB-UHFFFAOYSA-N 4-fluoro-n-methyl-n-[1-[4-(2-methylpyrazol-3-yl)phthalazin-1-yl]piperidin-4-yl]-2-(trifluoromethyl)benzamide Chemical compound C=1C=C(F)C=C(C(F)(F)F)C=1C(=O)N(C)C(CC1)CCN1C(C1=CC=CC=C11)=NN=C1C1=CC=NN1C SZBGQDXLNMELTB-UHFFFAOYSA-N 0.000 description 1
- UGSNXXVWQXTDNA-UHFFFAOYSA-N 4-methyl-2-[4-(5-methyl-2-sulfophenyl)butyl]benzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C(CCCCC=2C(=CC=C(C)C=2)S(O)(=O)=O)=C1 UGSNXXVWQXTDNA-UHFFFAOYSA-N 0.000 description 1
- NKJIFDNZPGLLSH-UHFFFAOYSA-N 4-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C=C1 NKJIFDNZPGLLSH-UHFFFAOYSA-N 0.000 description 1
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 1
- ZNMSYUCZLWETII-UHFFFAOYSA-N 4-pyrrolidin-1-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCCC1 ZNMSYUCZLWETII-UHFFFAOYSA-N 0.000 description 1
- AILRADAXUVEEIR-UHFFFAOYSA-N 5-chloro-4-n-(2-dimethylphosphorylphenyl)-2-n-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1P(C)(C)=O AILRADAXUVEEIR-UHFFFAOYSA-N 0.000 description 1
- NOVKHIQVXQKSRL-UHFFFAOYSA-N 5-nitro-1-benzothiophene Chemical compound [O-][N+](=O)C1=CC=C2SC=CC2=C1 NOVKHIQVXQKSRL-UHFFFAOYSA-N 0.000 description 1
- MXKZSCXYMSXOAO-UHFFFAOYSA-N 7-nitroquinoline Chemical compound C1=CC=NC2=CC([N+](=O)[O-])=CC=C21 MXKZSCXYMSXOAO-UHFFFAOYSA-N 0.000 description 1
- LFAINLHFUYHZSV-UHFFFAOYSA-N 8-pyrrolidin-1-ylquinoline Chemical compound C1CCCN1C1=CC=CC2=CC=CN=C12 LFAINLHFUYHZSV-UHFFFAOYSA-N 0.000 description 1
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 229940122531 Anaplastic lymphoma kinase inhibitor Drugs 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 241001169121 Gabriella Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 229910021205 NaH2PO2 Inorganic materials 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229950004272 brigatinib Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- BYUYRWRYAISPPF-UHFFFAOYSA-N cyclobutyloxycyclobutane Chemical compound C1CCC1OC1CCC1 BYUYRWRYAISPPF-UHFFFAOYSA-N 0.000 description 1
- LEUIUWYZAHKPSE-UHFFFAOYSA-L disodium;butane-1,4-disulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)CCCCS([O-])(=O)=O LEUIUWYZAHKPSE-UHFFFAOYSA-L 0.000 description 1
- 229950006304 gilteritinib Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- WIJZXSAJMHAVGX-DHLKQENFSA-N ivosidenib Chemical compound FC1=CN=CC(N([C@H](C(=O)NC2CC(F)(F)C2)C=2C(=CC=CC=2)Cl)C(=O)[C@H]2N(C(=O)CC2)C=2N=CC=C(C=2)C#N)=C1 WIJZXSAJMHAVGX-DHLKQENFSA-N 0.000 description 1
- 229950010738 ivosidenib Drugs 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 150000003142 primary aromatic amines Chemical class 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229950000062 taladegib Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 229930004006 tropane Natural products 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention belongs to the technical field of preparation of organic synthesis intermediates, and particularly relates to a synthesis method of 1-phenylpyrrolidine. The synthesis method specifically comprises the following steps: sequentially adding a catalyst Cu (II), zinc powder and an organic solvent into a dry schlenk reaction tube under the nitrogen atmosphere, then adding an aromatic nitro compound and 1, 4-butanediyl bis (4-methylbenzenesulfonate), reacting for 8 hours at 50-80 ℃, adding a mixed solution of distilled water and ethyl acetate into a reaction solution after the aromatic nitro compound is completely converted, extracting, combining organic phases, adding anhydrous magnesium sulfate for drying, concentrating an organic phase at 40 ℃, and performing column chromatography to obtain a target product 1-phenylpyrrolidine. The method is simple, low in cost and high in yield, and can synthesize the 1-phenylpyrrolidine through one-step reaction, so that the existing synthesis technology is widened.
Description
Technical Field
The invention belongs to the technical field of preparation of organic synthesis intermediates, and particularly relates to a method for preparing an organic intermediate 1-phenylpyrrolidine by using an aromatic nitro compound and 1, 4-butanediyl bis (4-methylbenzenesulfonate) as substrates.
Background
1-phenylpyrrolidine is an important organic synthesis intermediate, and is widely applied to a plurality of fields of scientific research, drug synthesis, alkaloid synthesis, chemical production and the like. Widely exists in natural alkaloid, tropane drug molecules and new drug lead compounds. Meanwhile, the compound is also a commonly used synthetic building block in drug synthesis, and is often applied to the total synthesis research of other natural products with wide biological activity. Therefore, the N-aryl substituted nitrogen heterocyclic ring similar to the 1-phenyl pyrrolidine has high application value in organic synthesis and pharmaceutical research.
At present, 1-phenyl pyrrolidine and derivatives thereof are found to have wide physiological activity, can be used as a biological enzyme inhibitor or have anticancer effect. Some of the related compounds found to be of widespread interest in pharmaceutical research are exemplified by the following: taladegib (a) approved for the treatment of locally advanced basal cell carcinoma; the first clinical validation of the enzyme inhibitor ividh 1 (ivosidenib) (b) was obtained in human trials; the new generation of anaplastic lymphoma kinase inhibitor Brigatinib (C) has strong curative effect on ALK positive non-small cell lung cancer patients. In addition, gilteritinib (d) may improve survival in some patients with acute myeloid leukemia.
Currently, 1-phenylpyrrolidine can be synthesized by the following method.
1) Reduction reaction of phenyl-2-pyrrolidone with diisobutyl aluminum borohydride: first, synthesis of diisobutyl aluminum borohydride from diisobutyl aluminum hydride (DIBAL) and borane dimethyl sulfide (BMS) is required, and 1-phenyl-2-pyrrolidone (1 equivalent), diisobutyl aluminum borohydride (1.1 equivalent) and anhydrous THF are mixed at 0 deg.C. Once all the hydride was added, the ice bath was removed and the reaction mixture was heatedAnd continuously stirring the reaction mixture for 1 hour under the argon atmosphere, and performing post-treatment to obtain the product. Diisobutyl aluminum borohydride (iBu) used in the method2AlBH4Cannot be purchased directly, requires complex synthesis steps, and requires reaction at 0 ℃ under an argon atmosphere, with harsh reaction conditions. Reference: gabriella Amberchan, Rachel a. snelling, Enrique Moya, j. org. chem.2021,86,6207.
2) Deoxyamination of aniline with cyclic ethers: the reaction first requires reacting aniline, cyclobutylether, I2、NaH2PO2Adding the product into a closed reaction tube, reacting for 11h at 160 ℃, and separating to obtain the 1-phenylpyrrolidine, wherein the reaction temperature of 160 ℃ is very strict, the yield is greatly reduced when the temperature is slightly reduced, and the byproduct is HI which has strong corrosivity and complex treatment process. Reference: ying Lin, Dongyang Li, jingjingzhang, Zhi Tang, New j. chem.,2021,45,21011.
3) C-N cross-coupling reaction of phenylboronic acid with N-heterocyclic compound: the reaction adopts a novel nano particle as a catalyst, and uses phenylboronic acid, an N-heterocyclic compound and K3PO4The target product can be obtained by reacting distilled water and the catalyst at 60 ℃ for a period of time, but the synthesis of the nano particles required by the reaction is complex, and the metal cobalt used in the catalyst has strong toxicity and complex operation process. Reference: seyyedeh Amerehne Alavi G, Mohammad Ali Nasseri, Milad Kazemnejadi, New J. chem.,2021,45,7741.
4) Nickel catalyzed coupling amination of aryl chlorides with amides: the reaction is carried out under a nitrogen atmosphere maintained at 35 ℃ and the solvents toluene, aryl chloride, amide, Ni (COD) are added to the reaction tube2、Apr·HCl、KOtBu and H2And O is reacted for 24 hours. The reaction is kept in a nitrogen atmosphere at required time, and the used solvent toluene is a controlled drug, so that the conditions are strict. Reference: jinpeng Li, Changyu Huang, Daheng Wen, Qingshu Zheng, org. lett.2021,23,687.
5) Hydrodehalogenation of aryl halides: the reaction is carried out under nitrogen atmosphere, and 2-iodine-1-Phenyl-pyrrolidine, catalyst, trace potassium, KOtBu, a solvent is prepared by dimethyl sulfoxide and dioxane according to a certain proportion, and the reaction lasts for 24 hours. The reaction needs nitrogen protection and is used in pressure pipes, active potassium metal is used in raw materials, the reaction risk is high, the used substrate needs to be synthesized by self, the reaction is not easy to obtain, and the reaction is not easy to operate. Reference: bhagat Singh, jasimulddin Ahmed, Amit Biswas, Rupankar Paira, j.org.chem.2021,86,7242.
In summary, although 1-phenylpyrrolidine is an important organic synthesis intermediate, the existing synthetic methods are all reactions using primary aromatic amine as raw material or reductive amination using dicarbonyl compound, but the methods have limitations on the functional tolerance of the substrate, high requirements on conditions and complex operation, and are not suitable for industrial production. Therefore, it is very important to develop a new synthetic method.
Disclosure of Invention
The invention aims to provide a method for synthesizing 1-phenylpyrrolidine, which is simple, low in cost, high in yield, capable of synthesizing the 1-phenylpyrrolidine through one-step reaction and widens the existing synthesis technology.
In order to realize the purpose, the invention adopts the technical scheme that:
a method for synthesizing 1-phenylpyrrolidine specifically comprises the following steps: sequentially adding a catalyst Cu (II), zinc powder and an organic solvent into a dry schlenk reaction tube in a nitrogen atmosphere, then adding an aromatic nitro compound and 1, 4-butanediyl bis (4-methylbenzenesulfonate), reacting for 8 hours at 50-80 ℃, adding a mixed solution of distilled water and ethyl acetate into a reaction solution after the aromatic nitro compound is completely converted, extracting, combining organic phases, adding anhydrous magnesium sulfate for drying, concentrating an organic phase at 40 ℃, and performing column chromatography to obtain a target product 1-phenylpyrrolidine.
Further, the aromatic nitro compound is nitrobenzene or heteroaryl benzene.
Further, the structural formula of the nitrobenzene is shown as
The structural formula of the heteroaryl benzene is shown in the specification
Wherein R is1Is hydrogen, halogen, alkyl, aryl, -OMe, -CHO, -CN, -SCH3Either one or both of them, but not limited to these groups.
Further, the molar ratio of the 1, 4-butanediyl bis (4-methylbenzenesulfonate) to the aromatic nitro compound is 2-3: 1.
Further, the catalyst cu (II) is one of copper sulfate (II), copper (II) oxalate, copper (II) chloride, copper (II) nitrate, copper (II) bromide, copper (II) trifluoromethanesulfonate, copper (II) hydroxide, copper (II) ethylacetoacetate, and copper (II) trifluoroacetate hydrate, but is not limited to the above catalyst cu (II).
Furthermore, the dosage of the catalyst Cu (II) is 3-5 mol% of the aromatic nitro compound.
Further, the organic solvent is Toluene, 1,4-Dioxane, THF, DMSO, CH3CN, NMP and DMF, but not limited to the organic solvent.
Further, the dosage of the organic solvent is 1-4 mL of the organic solvent per millimole of the aromatic nitro compound.
Furthermore, the molar ratio of the zinc powder to the aromatic nitro compound is 1.5:1, and the zinc powder is used for reducing nitrobenzene or heteroaryl benzene.
Further, the eluent for column chromatography is a mixture of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 50: 1.
When one of the reaction substrates is nitrobenzene, the reaction equation of the present invention is as follows:
wherein R is1The substituent group may be hydrogen, halogen, alkyl, aryl, or the like, but is not limited thereto. For use in the inventionNitrobenzene is commercially available in a variety of substituents; x is 3-5, Y is 1.5, T is 50-80, and formula A is a target product 1-phenylpyrrolidine.
When one of the reaction substrates is a heteroaryl benzene
In the present invention, the reaction equation is similar to the above reaction equation, and the benzene ring of nitrobenzene in the above reaction equation may be replaced with a nitrogen heterocycle.
Compared with the prior art, the invention has the beneficial effects that:
1. the raw materials in the method are cheap and easy to obtain, and the method meets the requirement of industrial production.
2. The method has no complex intermediate links in the reaction, and has lower requirements on experimental operation level.
3. The method of the invention uses nitrobenzene as raw material to synthesize the target product, and widens the synthesis method of 1-phenyl-pyrrolidine.
Detailed Description
The technical solutions and effects of the present invention will be further described with reference to specific examples, but the scope of the present invention is not limited thereto.
In the reaction equations of the following examples, I represents nitrobenzene or heteroarylbenzene, and II represents 1, 4-butanediyl bis (4-methylbenzenesulfonate).
Example 1
This example 1-Synthesis of phenylpyrrolidine 1:
to a dry 25mL schlenk reaction tube were added copper (II) chloride [2mg, 0.015mmol ], zinc powder (49mg, 0.75mmol), DMF (2mL) as a solvent, nitrobenzene (51. mu.L, 0.5mmol), 1, 4-butanediyl bis (4-methylbenzenesulfonate) (321. mu.L, 1mmol) in this order under a nitrogen atmosphere. Reacting for 8h on a heater with the rotating speed of 360rpm and the temperature of 65 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and separating by column chromatography, wherein the eluent is (ethyl acetate/petroleum ether is 50/1), so that the product is obtained as a pale yellow liquid with the yield of 67mg and 94%.
1H NMR(400MHz,CDCl3)δ7.17–7.13(m,2H),6.59–6.56(t,1H),6.50–6.48(d,2H),3.22–3.18(m,4H),1.93–1.90(m,4H).13C{1H}NMR(100MHz,CDCl3)δ147.5,128.3,114.5,110.3,46.1,24.2.Ms(EI):m/z＝147.5[M]+.
Example 2
Synthesis of example 1- (p-tolyl) pyrrolidine 2:
to a dry 25mL schlenk reaction flask, copper (II) [4mg, 0.025mmol ], zinc powder (49mg, 0.75mmol), solvent Toluene (0.5mL), p-nitrotoluene (69mg,0.5mmol), 1, 4-butanediyl bis (4-methylbenzenesulfonate) (468. mu.L, 1.5mmol) were added in this order under a nitrogen atmosphere. Reacting for 8h on a heater with the rotation speed of 200rpm and the temperature of 50 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phases, and performing column chromatography to obtain a product, namely a light yellow liquid 76mg with the yield of 94%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1H NMR(400MHz,CDCl3)δ7.01(d,2H),6.54(d,2H),3.25(t,4H),2.27(s,3H),2.05–1.94(m,4H).13C{1H}NMR(100MHz,CDCl3)δ146.7,129.5,124.3,111.6,47.5,25.3,20.5.Ms(EI):m/z＝161.5[M]+.
Example 3
This example synthesis of 1- (4-fluorophenyl) pyrrolidine 3:
to a dry 25mL schlenk reaction vessel, under nitrogen, were added copper (II) oxalate [3.8mg, 0.025mmol ], zinc powder (49mg, 0.75mmol), solvent NMP (2mL), 4-fluoronitrobenzene (70.5mg, 0.5mmol), 1, 4-butanediyl bis (4-methylbenzenesulfonate) (468. mu.L, 1.5mmol) in that order. Reacting for 8h on a heater with the rotation speed of 150rpm and the temperature of 80 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and performing column chromatography to obtain a product, namely a pale yellow liquid of 77.6mg and the yield of 94%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1HNMR(400MHz,CDCl3)δ7.01–6.84(m,2H),6.57–6.48(m,2H),3.23(t,4H),2.03–1.95(m,4H).13C{1H}NMR(100MHz,CDCl3)δ155.1,144.5,115.4,112.1,48.7,25.6.19F NMR(376MHz,CDCl3)δ-130.93.Ms(EI):m/z＝165.5[M]+.
Example 4
This example synthesis of 1- (4-chlorophenyl) pyrrolidine 4:
to a dry 25mL schlenk reaction flask, copper (II) nitrate [2.80mg, 0.015mmol ], zinc powder (49mg, 0.75mmol), solvent DMSO (2mL), 4-chloronitrobenzene (79mg, 0.5mmol), 1, 4-butanediyl bis (4-methylbenzenesulfonate) (312. mu.L, 1mmol) were added in this order under a nitrogen atmosphere. Reacting for 8h on a heater with the rotation speed of 150rpm and the temperature of 70 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and performing column chromatography to obtain a product, namely a pale yellow liquid 87mg and the yield of 96%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1H NMR(400MHz,CDCl3)δ7.24–7.11(m,2H),6.54–6.42(m,2H),3.24(t,4H),2.01–1.95(m,4H).13C{1H}NMR(100MHz,CDCl3)δ146.5,128.2,120.8,112.3,47.4,25.4.Ms(EI):m/z＝181.3[M]+.
Example 5
Synthesis of 4- (pyrrolidin-1-yl) benzonitrile 5 of this example:
to a dry 25mL schlenk reaction flask, copper (II) hydroxide [1.46mg, 0.015mmol ], zinc powder (49mg, 0.75mmol), solvent 1,4-Dioxane (1mL), p-nitrobenzonitrile (74mg, 0.5mmol), 1, 4-butanedisulfonate (312. mu.L, 1mmol) were added sequentially under a nitrogen atmosphere. Reacting for 8h on a heater with the rotation speed of 150rpm and the temperature of 70 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and performing column chromatography to obtain a product, namely a light yellow liquid 82mg with the yield of 95%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1H NMR(400MHz,CDCl3)δ7.46–7.41(m,2H),6.53(d,2H),3.34–3.21(m,4H),2.13–1.96(m,4H).13C{1H}NMR(100MHz,CDCl3)δ150.3,133.4,121.5,111.3,96.3,47.7,25.5.Ms(EI):m/z＝172.6[M]+.
Example 6
This example synthesis of 1- (4- (trifluoromethyl) phenyl) pyrrolidine 6:
to a dry 25mL schlenk reaction flask, anhydrous copper (II) acetate [2.72mg, 0.015mmol ] was added in sequence under nitrogen]Zinc powder (49mg, 0.75mmol), solvent CH3CN (2mL), 4-Nitro-trifluorotoluene (95.6mg, 0.5mmol), 1, 4-butanediyl bis (4-methylbenzene)Sulfonate) (468. mu.L, 1.5 mmol). Reacting for 8h on a heater with the rotation speed of 200rpm and the temperature of 70 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and performing column chromatography to obtain a product, namely a light yellow liquid 104mg with the yield of 97%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1H NMR(400MHz,CDCl3)δ7.43(d,2H),6.54(d,2H),3.33(t,4H),2.02(td,4H).13C{1H}NMR(100MHz,CDCl3)δ148.4,125.5(q,),124.2,115.3,109.5,46.3,24.7.19F NMR(376MHz,CDCl3)δ-60.55.Ms(EI):m/z＝215.3[M]+.
Example 7
This example synthesis of 8- (1-pyrrolidinyl) -quinoline 7:
to a dry 25mL schlenk reaction flask, copper (II) trifluoromethanesulfonate [5.42mg, 0.015mmol ], zinc powder (49mg, 0.75mmol), solvent THF (2mL), 7-nitroquinoline (87mg, 0.5mmol), 1, 4-butanediylbis (4-methylbenzenesulfonate) (468. mu.L, 1.5mmol) were added in this order under a nitrogen atmosphere. Reacting for 8 hours on a heater with the rotation speed of 200rpm and the temperature of 80 ℃, detecting that the raw materials completely react by TLC (thin layer chromatography), stopping the reaction, extracting the reaction mixed solution for a plurality of times by using a mixed solution of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phases, and performing column chromatography to obtain a light yellow liquid 92mg of a product with the yield of 93 percent, wherein the eluent is (ethyl acetate/petroleum ether: 50/1).
1HNMR(400MHz,CDCl3)δ8.77–8.74(m,1H),8.05–8.01(m,1H),7.42–7.25(m,2H),7.18–7.14(m,1H),6.84–6.81(m,1H),3.74–3.72(m,4H),2.06–1.92(m,4H).13C{1H}NMR(100MHz,CDCl3)δ146.5,141.3,135.4,129.5,127.1,120.5,116.5,111.2,52.3,25.3.Ms(EI):m/z＝198.3[M]+.
Example 8
This example synthesis of 5-pyrrolobenzo [ b ] thiophene 8:
to a dry 25mL schlenk reaction flask, copper (II) bromide [3.35mg, 0.015mmol ], zinc powder (49mg, 0.75mmol), solvent N-methylpyrrolidone (2mL), 5-nitrobenzothiophene (89.6mg, 0.5mmol), 1, 4-butanediyl bis (4-methylbenzenesulfonate) (468. mu.L, 1.5mmol) were added in this order under a nitrogen atmosphere. Reacting for 8h on a heater with the rotation speed of 200rpm and the temperature of 80 ℃, detecting that the raw materials completely react by TLC, stopping the reaction, extracting the reaction mixed liquid for a plurality of times by using a mixed liquid of distilled water and ethyl acetate with the volume ratio of 1:2, combining organic phases, drying by using anhydrous magnesium sulfate, concentrating the organic phase, and performing column chromatography to obtain a product, namely a light yellow liquid 116mg with the yield of 96%, wherein the eluent is ethyl acetate/petroleum ether (50/1).
1H NMR(400MHz,CDCl3)δ7.65(d,1H),7.33(d,1H),7.14(d,1H),6.94(d,1H),6.78–6.73(m,1H),3.38–3.23(m,4H),2.08–1.92(m,4H).13C{1H}NMR(100MHz,CDCl3)δ146.1,141.3,127.5,126.4,123.7,112.9,112.3,104.5,48.3,25.7.Ms(EI):m/z＝203.3[M]+.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. A synthetic method of 1-phenyl pyrrolidine is characterized by comprising the following steps: sequentially adding a catalyst Cu (II), zinc powder and an organic solvent into a dry schlenk reaction tube under the nitrogen atmosphere, then adding an aromatic nitro compound and 1, 4-butanediyl bis (4-methylbenzenesulfonate), reacting for 8 hours at 50-80 ℃, adding a mixed solution of distilled water and ethyl acetate into a reaction solution after the aromatic nitro compound is completely converted, extracting, combining organic phases, adding anhydrous magnesium sulfate for drying, concentrating an organic phase at 40 ℃, and performing column chromatography to obtain a target product 1-phenylpyrrolidine.
2. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the aromatic nitro compound is nitrobenzene or heteroaryl benzene.
3. The method for synthesizing 1-phenylpyrrolidine according to claim 2, wherein the structural formula of the nitrobenzene is
The structural formula of the heteroaryl benzene is shown in the specification
Wherein R is1Is hydrogen, halogen, alkyl, aryl, -OMe, -CHO, -CN, -SCH3Either one or both of them, but not limited to these groups.
4. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the molar ratio of 1, 4-butanediyl bis (4-methylbenzenesulfonate) to the aromatic nitro compound is 2-3: 1.
5. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the catalyst cu (II) is one of copper (II) sulfate, copper (II) oxalate, copper (II) chloride, copper (II) nitrate, copper (II) bromide, copper (II) trifluoromethanesulfonate, copper (II) hydroxide, copper (II) ethylacetoacetate, and copper (II) trifluoroacetate hydrate, but not limited to the above catalyst cu (II).
6. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the amount of the catalyst Cu (II) is 3-5 mol% of the aromatic nitro compound.
7. The method of claim 1, wherein the organic solvent is Toluene, 1,4-Dioxane, THF, DMSO, CH3CN, NMP and DMF, but not limited to the organic solvent.
8. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the amount of the organic solvent is 1-4 mL per millimole of the aromatic nitro compound.
9. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the molar ratio of the zinc powder to the aromatic nitro compound is 1.5: 1.
10. The method for synthesizing 1-phenylpyrrolidine according to claim 1, wherein the eluent for the column chromatography is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 50: 1.
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