CN115073383A - Synthetic method of aryl acetic acid compound - Google Patents
Synthetic method of aryl acetic acid compound Download PDFInfo
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- CN115073383A CN115073383A CN202110279325.8A CN202110279325A CN115073383A CN 115073383 A CN115073383 A CN 115073383A CN 202110279325 A CN202110279325 A CN 202110279325A CN 115073383 A CN115073383 A CN 115073383A
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- Prior art keywords
- acid compound
- acetic acid
- synthesizing
- reaction
- compound according
- Prior art date
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- -1 aryl acetic acid compound Chemical class 0.000 title claims abstract description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title claims description 71
- 238000010189 synthetic method Methods 0.000 title claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 66
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 239000002253 acid Substances 0.000 claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 14
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 11
- 238000010791 quenching Methods 0.000 claims abstract description 11
- 230000000171 quenching effect Effects 0.000 claims abstract description 11
- 239000000758 substrate Substances 0.000 claims abstract description 11
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000012298 atmosphere Substances 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 238000007865 diluting Methods 0.000 claims abstract description 3
- 229960000583 acetic acid Drugs 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 10
- 239000003208 petroleum Substances 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000012362 glacial acetic acid Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZOMQCVKHGOMNER-UHFFFAOYSA-N 2,4,5,6-tetrakis(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical group C(#N)C1=C(C(=C(C(=C1N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)C#N)N(C1=CC=CC=C1)C1=CC=CC=C1 ZOMQCVKHGOMNER-UHFFFAOYSA-N 0.000 claims description 5
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical group CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 5
- 238000003818 flash chromatography Methods 0.000 claims description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 3
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims description 2
- GCGRXVMGBHYMDA-UHFFFAOYSA-N 5-fluoro-2,4,6-tris(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical compound C1(=CC=CC=C1)N(C1=C(C#N)C(=C(C(=C1C#N)N(C1=CC=CC=C1)C1=CC=CC=C1)F)N(C1=CC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1 GCGRXVMGBHYMDA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 10
- 229910052723 transition metal Inorganic materials 0.000 abstract description 5
- 150000003624 transition metals Chemical class 0.000 abstract description 5
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000001569 carbon dioxide Substances 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- 230000009471 action Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- PYHXGXCGESYPCW-UHFFFAOYSA-N diphenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229960003424 phenylacetic acid Drugs 0.000 description 3
- 239000003279 phenylacetic acid Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 2
- MCDCIWAVBWPRSP-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)acetic acid Chemical compound C=1C=C(F)C=CC=1C(C(=O)O)C1=CC=C(F)C=C1 MCDCIWAVBWPRSP-UHFFFAOYSA-N 0.000 description 2
- SFAILOOQFZNOAU-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=C(Cl)C=CC=C1Cl SFAILOOQFZNOAU-UHFFFAOYSA-N 0.000 description 2
- GUAIAAXDEJZRBP-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=C(F)C=CC=C1Cl GUAIAAXDEJZRBP-UHFFFAOYSA-N 0.000 description 2
- IUJAAIZKRJJZGQ-UHFFFAOYSA-N 2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Cl IUJAAIZKRJJZGQ-UHFFFAOYSA-N 0.000 description 2
- QLHZKPQKYARBGT-UHFFFAOYSA-N 2-(2-cyanophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1C#N QLHZKPQKYARBGT-UHFFFAOYSA-N 0.000 description 2
- KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 2
- OCWDBDTZTFJIAQ-UHFFFAOYSA-N 2-(3-chlorophenyl)-2-phenylacetic acid Chemical compound C=1C=CC(Cl)=CC=1C(C(=O)O)C1=CC=CC=C1 OCWDBDTZTFJIAQ-UHFFFAOYSA-N 0.000 description 2
- OTGSESBEJUHCES-UHFFFAOYSA-N 2-(3-ethoxy-4-ethoxycarbonylphenyl)acetic acid Chemical compound CCOC(=O)C1=CC=C(CC(O)=O)C=C1OCC OTGSESBEJUHCES-UHFFFAOYSA-N 0.000 description 2
- YSPUGNBNEKEGKB-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-phenylacetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)C1=CC=CC=C1 YSPUGNBNEKEGKB-UHFFFAOYSA-N 0.000 description 2
- WEBXRQONNWEETE-UHFFFAOYSA-N 2-(4-cyanophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(C#N)C=C1 WEBXRQONNWEETE-UHFFFAOYSA-N 0.000 description 2
- YSVNGBYVEJEXGO-UHFFFAOYSA-N 2-(4-cyanophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(C#N)C=C1 YSVNGBYVEJEXGO-UHFFFAOYSA-N 0.000 description 2
- TXZVCDJZNRCDKW-UHFFFAOYSA-N 2-(4-methoxycarbonylphenyl)acetic acid Chemical compound COC(=O)C1=CC=C(CC(O)=O)C=C1 TXZVCDJZNRCDKW-UHFFFAOYSA-N 0.000 description 2
- XJASRMYHIKVZSP-UHFFFAOYSA-N 2-(4-methoxycarbonylphenyl)propanoic acid Chemical compound COC(=O)C1=CC=C(C(C)C(O)=O)C=C1 XJASRMYHIKVZSP-UHFFFAOYSA-N 0.000 description 2
- GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 2
- VARVNFDGRLLTCI-UHFFFAOYSA-N 2-(4-phenoxyphenyl)acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC1=CC=CC=C1 VARVNFDGRLLTCI-UHFFFAOYSA-N 0.000 description 2
- TYOCDHCKTWANIR-UHFFFAOYSA-N 2-[2-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1C(F)(F)F TYOCDHCKTWANIR-UHFFFAOYSA-N 0.000 description 2
- BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 2
- OURCOVUGQRXRTE-CQSZACIVSA-N 2-[4-(3-methylpyrazin-2-yl)phenyl]-n-[(1r)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl]acetamide Chemical compound N([C@H](C)C=1N=CC(OCC(F)(F)F)=CC=1)C(=O)CC(C=C1)=CC=C1C1=NC=CN=C1C OURCOVUGQRXRTE-CQSZACIVSA-N 0.000 description 2
- HNORVZDAANCHAY-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(C(F)(F)F)C=C1 HNORVZDAANCHAY-UHFFFAOYSA-N 0.000 description 2
- ZAOJHEOIUQVOEU-UHFFFAOYSA-N 2-[4-methoxy-2-(trifluoromethyl)phenyl]acetic acid Chemical compound COC1=CC=C(CC(O)=O)C(C(F)(F)F)=C1 ZAOJHEOIUQVOEU-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- GJMPSRSMBJLKKB-UHFFFAOYSA-N 3-methylphenylacetic acid Chemical compound CC1=CC=CC(CC(O)=O)=C1 GJMPSRSMBJLKKB-UHFFFAOYSA-N 0.000 description 2
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 2
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000005971 1-naphthylacetic acid Substances 0.000 description 1
- CJENGSVYFHIJQR-UHFFFAOYSA-N 2,2-bis(4-methoxyphenyl)-2-phenylacetic acid Chemical compound C1=CC(OC)=CC=C1C(C(O)=O)(C=1C=CC(OC)=CC=1)C1=CC=CC=C1 CJENGSVYFHIJQR-UHFFFAOYSA-N 0.000 description 1
- RUAYXHSDAMWEDR-UHFFFAOYSA-N 2-(4-tert-butylphenyl)acetic acid Chemical compound CC(C)(C)C1=CC=C(CC(O)=O)C=C1 RUAYXHSDAMWEDR-UHFFFAOYSA-N 0.000 description 1
- FNLWHBHWDXCWHV-UHFFFAOYSA-N 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetic acid Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CC(O)=O)C=C1 FNLWHBHWDXCWHV-UHFFFAOYSA-N 0.000 description 1
- QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000006713 insertion reaction Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 229960000249 pregnenolone Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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Abstract
The invention discloses aryl acetic acidThe method for synthesizing the compounds comprises the following steps: adding benzyl halide, photosensitizer and alkali into a dry reaction tube, and adding CO 2 Adding a solvent and a reducing agent in the atmosphere, reacting under the irradiation of visible light, diluting the raw materials with ethyl acetate after the reaction is finished, quenching the raw materials with a quenching agent, and then separating and purifying to obtain the arylacetic acid compound. The method is driven by visible light, and the arylacetic acid compound is efficiently synthesized under the condition of no need of a sensitive metal reagent, a transition metal reagent or a toxic and harmful reagent; the reaction condition of the scheme of the invention is mild, the range of the reaction substrate is wide, the compatibility of the functional group is wide, and the scale can be enlarged to gram-scale; the raw materials used in the invention are cheap and easily available, and the invention has good industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of an aryl acetic acid compound.
Background
At present, various aryl acetic acid compounds are industrially synthesized mainly by an aryl acetonitrile hydrolysis method, the aryl acetonitrile compounds are mainly prepared by nucleophilic substitution reaction of benzyl halide and sodium cyanide, adverse effects on environment and health of operators are possible, the synthesis needs two steps in total, and the synthesis does not conform to the concept of green chemistry. In addition, the synthesized aryl acetic acid compound can also be synthesized by the carbonyl insertion reaction of benzyl halide or similar halide and carbon monoxide under the catalysis of transition metal. The toxicity and insecurity of carbon monoxide can also limit its utility. In addition, carbon dioxide can also be used as a carbonyl source to synthesize aryl acetic acid compounds with benzyl halides or halogenated compounds. For example, arylacetic acid-based compounds can be prepared by preparing an organometallic compound such as a benzylic Grignard reagent, a zinc reagent, a lithium reagent, etc., from a benzylic halide in advance, and then reacting with carbon dioxide. However, the metal organic reagents used are sensitive to water and oxygen, have poor functional group compatibility and poor step economy. In addition to these processes, chemists have developed other processes in which carbon dioxide is involved in the synthesis of arylacetic acid compounds, such as transition metal-catalyzed processes, electrochemical processes. But problems with residual transition metal and sacrificial anodes also limit their application.
CO in the atmosphere due to the large emission of carbon dioxide 2 The concentration is continuously increased, and the global warming becomes increasingly serious. Therefore, it is of great significance to actively develop a study on rational utilization of carbon dioxide. By chemically reacting CO 2 The preparation of organic compounds as a C1 organic synthon is a very important way, and a new idea is provided for solving the greenhouse effect.
Thus, a method for synthesizing aryl acetic acid compounds capable of overcoming the above disadvantages is developed, and CO is added 2 Application to the synthesis of carboxylic acid molecules is highly desirable in the art.
Disclosure of Invention
Aiming at the prior art, the invention provides a synthesis method of an aryl acetic acid compound, which has the advantages of high yield, mild reaction conditions, low toxicity of reaction reagents, no participation of transition metals, good functional group compatibility, low cost and the like.
In order to achieve the purpose, the invention adopts the technical scheme that: the synthesis method of the aryl acetic acid compound comprises the following steps:
s1: adding benzyl halide, photosensitizer and alkali into a reaction device, and introducing CO into the reaction device 2 Replacement 3 times, then CO 2 Adding a solvent and a reducing agent under the atmosphere of (1);
s2: placing an S1 reaction device at a position 1cm away from a visible light source, stirring and reacting at room temperature for 0.1-24 h, diluting with ethyl acetate after the reaction is finished, then quenching with a quenching agent, extracting with ethyl acetate, and then spin-drying the solvent to obtain a crude product;
s3: and purifying the crude product obtained in the step S2 by flash column chromatography to obtain the aryl acetic acid compound.
On the basis of the technical scheme, the invention can be further improved as follows.
Furthermore, the structure of the benzyl halide is shown as the formula (I),
wherein Ar is aryl; r 1 And R 2 Are respectively independent hydrogen, alkyl or aryl, and X is Cl or Br.
Further, the dosage of the photosensitizer is 0.01-10 mol% of the reaction substrate; the addition amount of the alkali is 0.1-10 times equivalent of the reaction substrate; the addition amount of the reducing agent is 0.1 to 10 times equivalent of the reaction substrate.
Further, CO is in the reaction device 2 The air pressure is 0.1 atm-30 atm.
Further, the photosensitizer is 4DPAIPN, 3DPAFIPN, 4CzIPN, DPZ or Ir (ppy) 2 (dbbpy)·PF 6 。
Further, the base is at least one of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate.
Further, the reducing agent is TMEDA or Et 3 N, DIPEA or PhSiH 3 。
Further, the solvent is DMF, DMA or DMSO.
Further, the quenching agent is ethyl acetate and hydrochloric acid.
Further, eluent used for column chromatography purification in S3 is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10: 1-2: 1, and the mass fraction of the glacial acetic acid is 0.1-0.5%.
Further, the visible light source was a blue LED lamp of 30W.
In the invention, the synthesis reaction equation of the aryl acetic acid compound is as follows:
the reaction principle is shown in FIG. 1. Under the photocatalysis system, benzyl halide firstly generates a single electron transfer process with a photosensitizer in a reduction state to generate a benzyl radical. Then the benzyl radical and the photosensitizer in the reduction state are subjected to single electron reduction again to generate benzyl carbanion, and then CO is attacked 2 To form a carboxyl groupAcid negative ions are acidified to obtain the aryl acetic acid compound.
The invention has the beneficial effects that: the method is driven by visible light, and the arylacetic acid compound is efficiently synthesized under the condition of no need of a sensitive metal reagent, a transition metal reagent or other toxic and harmful reagents; the reaction condition of the scheme of the invention is mild, the range of the reaction substrate is wide, the compatibility of the functional group is wide, and the scale can be enlarged to gram scale; the raw materials used in the invention are cheap and easily available, and the invention has good industrial application prospect.
Drawings
FIG. 1 is a schematic diagram of the synthesis of arylacetic acid compounds of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
Thus, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without making any creative effort, shall fall within the protection scope of the present invention.
It is noted that relational terms such as "first" and "second," and the like, may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
The benzyl chloride is used for synthesizing the aryl acetic acid compound, and the synthetic reaction formula is shown as a formula (1).
The reaction comprises the following steps:
s1: to a dry Schlenk tube (10mL) with a stirrer added, reaction substrate 1(0.2mmol, 1.0 equiv.), photosensitizer 4DPAIPN (0.004mmol,2 mol%) and base lithium tert-butoxide (0.6mmol, 3.0 equiv.);
s3: replace Schlenk tube with CO 3 times 2 ；
S4: in CO 2 Solvent DMF (2mL) and reducing agent TMEDA (0.12mmol, 0.6 equiv.) were added under atmosphere;
s5: placing a Schlenk tube at a position 1cm away from a 30W blue LED light source, and stirring and reacting for 8 hours at room temperature (25-30 ℃);
s6: quenching the reaction by using 2mL of ethyl acetate and 2mL of 2N hydrochloric acid, extracting for 3 times by using the ethyl acetate, and directly concentrating and spin-drying an organic phase to obtain a crude product;
s7: and purifying the crude product by using flash column chromatography to obtain a pure required product, wherein an eluent used for purifying the chromatographic column is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10: 1-2: 1, and the mass fraction of the glacial acetic acid is 0.1-0.5%. The product was obtained as follows:
example 2
Synthesizing TTA-A8 precursor from benzyl chloride, wherein the synthetic reaction formula is shown as formula (2).
The reaction comprises the following steps:
s1: to a dry Schlenk tube (10mL) with a stir bar, add the reaction substrate 1ak (0.2mmol, 1.0 equiv.), the photosensitizer 4DPAIPN (0.004mmol,2 mol%) and the base lithium tert-butoxide (0.6mmol, 3.0 equiv);
s3: replace Schlenk tube with CO 3 times 2 ；
S4: in CO 2 Solvent DMF (2mL) and reducing agent TMEDA (0.12mmol, 0.6 equiv.) were added under atmosphere;
s5: placing a Schlenk tube at a position 1cm away from a 30W blue LED light source, and stirring and reacting for 6 hours at room temperature (25-30 ℃);
s6: and after the reaction is finished, adding 3 equivalents of methyl iodide under nitrogen flow, and reacting for 3 hours at the temperature of 50-75 ℃.
S7: after the reaction is finished, quenching the mixture by using water, extracting the mixture for 3 times by using ethyl acetate, and directly concentrating and spin-drying an organic phase to obtain a crude product;
s8: and purifying the crude product by flash column chromatography to obtain a pure required product, wherein an eluent used for purifying the chromatographic column is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10: 1.
The product 2ak is a product of further methyl esterification of the corresponding carboxylic acid TTA-A8 precursor, intended to facilitate isolation and purification.
Example 3
The benzyl bromide is used for synthesizing the aryl acetic acid compound, and the synthetic reaction formula is shown as a formula (3).
The reaction comprises the following steps:
s1: to a dry Schlenk tube (10mL) with a stirring bar was added reaction substrate 3(0.2mmol, 1.0 mm)Amount), photosensitizer 4DPAIPN (0.002mmol,1 mol%) and alkali Cs 2 CO 3 (0.4mmol, 2.0 equiv);
s3: replace Schlenk tube with CO 3 times 2 ；
S4: in CO 2 Solvent DMF (2mL) and reducing agent TMEDA (0.12mmol, 0.6 equiv.) were added under atmosphere;
s5: placing a Schlenk tube at a position 1cm away from a 30W blue LED light source, and stirring and reacting for 8 hours at room temperature (25-30 ℃);
s6: quenching the reaction by using 2mL of ethyl acetate and 2mL of 2N hydrochloric acid, extracting for 3 times by using the ethyl acetate, and directly concentrating and spin-drying an organic phase to obtain a crude product;
s7: and purifying the crude product by using flash column chromatography to obtain a pure required product, wherein an eluent used for purifying the chromatographic column is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10: 1-2: 1, and the mass fraction of the glacial acetic acid is 0.1-0.5%. The product was obtained as follows:
the structural characterization constants of the synthesized aryl acetic acid compound are as follows:
2- (4-Phenylphenyl) acetic acid (2a)
13 C NMR(101MHz,DMSO-d 6 )δ173.14,140.38,138.95,134.72,130.42,129.36,127.76,127.01,126.98,40.70；
LRMS(ESI-)[M-H] - calculated m/z for[C 14 H 11 O 2 ] - :211.24,found:210.98.
2- (4'- (tert-butyl) - [1,1' -diphenyl ] -4-substituted) acetic acid (2b)
13 C NMR(101MHz,DMSO-d 6 )δ173.16,150.17,138.84,137.53,134.40,130.36,126.79,126.67,126.12,40.71,34.66,31.54；
LRMS(ESI-)[M-H] - calculated m/z for[C 18 H 19 O 2 ] - :267.14,found:267.01.
2- (4'- (trifluoromethyl) - [1,1' -diphenyl ] -4-substituted) acetic acid (2c)
13 C NMR(101MHz,DMSO-d 6 )δ173.02,144.36(d,J＝1.6Hz),137.33,135.88,130.62,128.15(q,J＝31.7Hz),127.75,127.33,126.17(q,J＝3.8Hz),124.82(q,J＝273.0Hz),40.68；
19 F NMR(376MHz,DMSO-d 6 )δ-60.93；
LRMS(ESI-)[M-H] - calculated m/z for[C 15 H 10 F 3 O 2 ] - :279.06,found:278.89.
2- (4- (methoxycarbonyl) phenyl) acetic acid (2d)
13 C NMR(101MHz,CDCl 3 )δ176.93,166.86,138.31,129.91,129.47,129.22,52.18,40.93；
LRMS(ESI-)[M-H] - calculated m/z for[C 10 H 9 O 4 ] - :193.05,found:192.95.
2- (4- (trifluoromethyl) phenyl) acetic acid (2e)
13 C NMR(101MHz,DMSO-d 6 )δ172.58,140.35(d,J＝1.3Hz),130.78,127.76(q,J＝31.8Hz),125.44(q,J＝3.8Hz),124.80(q,J＝272.0Hz),40.65；
19 F NMR(376MHz,DMSO-d 6 ):δ-60.89；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 F 3 O 2 ] - :203.04,found:202.99.
2- (4-cyanophenyl) acetic acid (2f)
13 C NMR(101MHz,DMSO-d 6 )δ172.34,141.36,132.51,131.09,119.33,109.92,40.84；LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 NO 2 ] - :160.04,found:160.10.
2- [4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] acetic acid (2g)
13 C NMR(101MHz,DMSO-d 6 ) Delta 172.85,138.91,134.84,129.37,84.01,41.28,25.09 (note: carbon signal associated with boron atom cannot be scanned);
LRMS(ESI-)[M-H] - calculated m/z for[C 14 H 18 BO 4 ] - :261.13,found:260.96；
2- (4-chlorophenyl) acetic acid (2h)
13 C NMR(101MHz,DMSO-d 6 )δ172.85,134.53,131.77,131.72,128.56,40.19；
LRMS(ESI-)[M-H] - calculated m/z for[C 8 H 6 ClO 2 ] - :169.01,171.00,found:169.03,171.03.
2- (4-bromophenyl) acetic acid (2i)
1 H NMR(400MHz,CDCl 3 )2j, delta 7.47-7.42 (m,2H), 7.17-7.11 (m,2H),3.58(s, 2H); phenylacetic acid, delta 7.36-7.26 (m,0.42H),3.64(s, 0.14H);
13 C NMR(101MHz,CDCl 3 )2j delta 177.35,132.14,131.75,131.10,121.46, 40.40; phenylacetic acid delta 129.36,128.65,127.37,41.05 (not: 2carbon signals of 2-phenyl acetic acid not detected for bits low concentration);
LRMS(ESI-)[M-H] - calculated m/z for[C 8 H 6 BrO 2 ] - :212.96,214.95,found:212.98,214.90.
2- (4-methylphenyl) acetic acid (2j)
13 C NMR(101MHz,DMSO-d 6 )δ173.29,136.00,132.39,129.64,129.22,40.74,21.08；LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 9 O 2 ] - :149.06,found:148.91.
2- (4-Phenoxyphenyl) acetic acid (2k)
13 C NMR(101MHz,CDCl 3 )δ177.86,156.97,156.62,130.71,129.76,127.90,123.38,119.01,118.85,40.26；
LRMS(ESI-)[M-H] - calculated m/z for[C 14 H 11 O 3 ] - :227.07,found:227.05.
2- (4-tert-butylphenyl) acetic acid (2l)
13 C NMR(101MHz,DMSO-d 6 )δ172.90,148.87,132.04,129.03,125.01,40.29,34.15,31.19；
LRMS(ESI-)[M-H] - calculated m/z for[C 12 H 15 O 2 ] - :191.11,found:191.10.
2- (4-methoxyphenyl) acetic acid (2m)
13 C NMR(101MHz,DMSO-d 6 )δ173.45,158.43,130.79,127.37,114.07,55.43,40.19；LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 9 O 3 ] - :165.06,found:165.11.
2- (4'- (trifluoromethyl) - [1,1' -diphenyl ] -3-substituted) acetic acid (2n)
13 C NMR(101MHz,DMSO-d 6 )δ173.08,144.48(d,J＝1.4Hz),138.95,136.42,130.01,129.48,128.65,128.26(q,J＝31.9Hz),127.88,126.22(q,J＝3.8Hz),125.76,124.81(q,J＝272.4Hz),40.95；
19 F NMR(376MHz,DMSO-d 6 )δ-60.90；
LRMS(ESI-)[M-H] - calculated m/z for[C 15 H 10 F 3 O 2 ] - :279.06,found:279.02.
2- (3-trifluoromethylphenyl) acetic acid (2o)
13 C NMR(101MHz,DMSO-d 6 )δ172.28,136.53,133.78(d,J＝1.4Hz),129.20,128.94(q,J＝31.3Hz),126.09(q,J＝3.9Hz),124.29(q,J＝272.3Hz),123.36(q,J＝3.9Hz),39.96；
19 F NMR(376MHz,DMSO-d 6 )δ-61.05；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 F 3 O 2 ] - :203.03,found:203.04.
2- (3-methylphenyl) acetic acid (2p)
13 C NMR(101MHz,DMSO-d 6 )δ173.19,137.70,135.36,130.40,128.57,127.62,126.84,41.15,21.37；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 9 O 2 ] - :149.06,found:149.18.
2- (3-bromophenyl) acetic acid (2q)
1 H NMR(400MHz,CDCl 3 )2q, delta 7.46-7.37 (m,2H), 7.22-7.15 (m,2H),3.60(s, 2H); phenylacetic acid, delta 7.35-7.25 (m,0.34H),3.64(s, 0.12H);
13 C NMR(101MHz,CDCl 3 )2q delta 176.97,135.33,132.43,130.52,130.13,128.07,122.56, 40.53; phenylacetic acid delta 129.36,128.65,127.36,41.03 (note: phenylacetic acid by-product too small ratio, two carbon signals can not be found);
LRMS(ESI-)[M-H] - calculated m/z for[C 8 H 6 BrO 2 ] - :212.96,214.95,found:212.97,214.94.
2-chlorophenyl acetic acid (2r)
13 C NMR(101MHz,DMSO-d 6 )δ171.96,134.15,133.76,132.62,129.43,129.17,127.54,39.09；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 F 3 O 2 ] - :169.01,171.01,found:169.05,171.02.
2- (2- (trifluoromethyl) phenyl) acetic acid (2s)
13 C NMR(101MHz,DMSO-d 6 )δ172.15,133.81,133.73(q,J＝1.9Hz),132.81,127.91,127.89(q,J＝28.8Hz),126.09(q,J＝5.8Hz),124.88(q,J＝273.8Hz),38.27(d,J＝1.7Hz)；
19 F NMR(376MHz,DMSO-d 6 )δ-58.75；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 F 3 O 2 ] - :203.03,found:202.95.
2- (2 cyanophenyl) acetic acid (2t)
13 C NMR(101MHz,Methanol-d 4 )δ171.23,137.67,131.95,131.56,129.91,126.68,116.37,112.24,38.02；
LRMS(ESI-)[M-H] - calculated m/z for[C 9 H 6 NO 2 ] - :160.04,found:159.92.
1-Naphthylacetic acid (2u)
13 C NMR(101MHz,DMSO-d 6 )δ173.21,133.75,132.31,132.10,128.87,128.43,127.82,126.59,126.13,125.96,124.46,38.92；
LRMS(ESI-)[M-H] - calculated m/z for[C 12 H 9 O 2 ] - :185.06,found:185.05.
2-chloro-6-fluorophenylacetic acid (2v)
13 C NMR(101MHz,DMSO-d 6 )δ170.93,161.43(d,J＝247.0Hz),135.20(d,J＝5.8Hz),130.04(d,J＝9.7Hz),125.57(d,J＝3.4Hz),121.96(d,J＝19.0Hz),114.64(d,J＝22.6Hz),32.20(d,J＝3.1Hz)；
19 F NMR(376MHz,DMSO-d 6 )δ-112.64；
LRMS(ESI-)[M-H] - calculated m/z for[C 8 H 5 ClFO 2 ] - :187.00,188.99,found:187.06,189.06.
2, 6-Dichlorophenylacetic acid (2w)
13 C NMR(101MHz,DMSO-d 6 )δ170.69,135.70,132.06,130.00,128.62,36.97；
LRMS(ESI-)[M-H] - calculated m/z for[C 8 H 5 Cl 2 O 2 ] - :202.97,204.96,found:203.01,204.95.
2- (2-methyl- [1,1' -diphenyl ] -3-substituted) acetic acid (2x)
13 C NMR(101MHz,DMSO-d 6 )δ172.66,141.98,141.80,134.64,133.91,129.74,129.16,128.47,128.23,126.87,125.45,39.49,16.53；
HRMS(ESI-)[M-H] - calculated m/z for[C 15 H 13 O 2 ] - :225.0921,found:225.0924.
2- (4- (N, N-dipropylsulfonyl) phenyl) acetic acid (2y)
13 C NMR(101MHz,DMSO-d 6 )δ172.49,140.38,138.11,130.82,127.16,50.23,40.65,22.19,11.41；
HRMS(ESI-)[M-COOH] - calculated m/z for[C 13 H 20 NO 2 S] - 254.1220, found 254.1225 pregnenolone carboxylic acid derivatives (2z)
13 C NMR(101MHz,DMSO-d 6 )δ208.98,172.57,165.41,141.06,139.86,130.24,129.53,128.82,122.59,74.36,62.98,56.43,49.72,43.70,40.93,38.31,38.08,36.93,36.59,31.73,31.68,31.66,27.81,24.45,22.62,21.01,19.43,13.36；
HRMS(ESI-)[M-COOH] - calculated m/z for[C 29 H 37 O 3 ] - :433.2748,found:433.2746.
Cholesterol carboxylic acid derivative (2aa)
13 C NMR(101MHz,CDCl 3 )δ176.90,165.70,139.57,138.10,129.91,129.89,129.38,122.81,74.63,56.66,56.09,49.99,42.29,40.95,39.70,39.50,38.16,36.99,36.62,36.16,35.80,31.91,31.84,28.24,28.01,27.84,24.28,23.82,22.84,22.57,21.03,19.37,18.71,11.85；
HRMS(ESI-)[M-COOH] - calculated m/z for[C 35 H 51 O 2 ] - :503.3895,found:503.3891.
2, 2-Diphenylacetic acid (2ab)
13 C NMR(101MHz,DMSO-d 6 )δ173.85,139.97,128.92,128.83,127.28,56.66；
LRMS(ESI-)[M-COOH] - calculated m/z for[C 13 H 11 ] - :167.09,found:167.26.
2, 2-bis (4-fluorophenyl) acetic acid (2ac)
13 C NMR(101MHz,DMSO-d 6 )δ173.75,161.58(d,J＝243.3Hz),136.13(d,J＝3.1Hz),130.78(d,J＝8.2Hz),115.65(d,J＝21.3Hz),54.83；
19 F NMR(376MHz,DMSO-d 6 )δ-115.85；
LRMS(ESI-)[M-H] - calculated m/z for[C 14 H 9 F 2 O 2 ] - :247.06,found:246.89.
2- (3-chlorophenyl) -2-phenylacetic acid (2ad)
LRMS(ESI-)[M-COOH] - calculated m/z for[C 13 H 10 Cl] - :201.05,203.04,found:201.15,203.11.
2- (4-chlorophenyl) -2-phenylacetic acid (2ae)
1 H NMR(400MHz,DMSO-d 6 )δ12.84(s,1H),7.38–7.25(m,8H),7.24–7.19(m,1H),5.07(s,1H)；
13 C NMRδ173.61,139.68,139.06,132.00,130.86,128.97,128.83,128.76,127.43,55.89；
LRMS(ESI-)[M-COOH] - calculated m/z for[C 13 H 10 Cl] - :201.05,203.04,found:201.21,203.10.
2- (4-cyanophenyl) propionic acid (2af)
13 C NMR(101MHz,DMSO-d 6 )δ174.97,147.31,132.81,129.13,119.23,110.10,45.14,18.56；
LRMS(ESI-)[M-H] - calculated m/z for[C 10 H 8 NO 2 ] - :174.06,found:173.82.
2- (4- (methoxycarbonyl) phenyl) propanoic acid (2ag)
13 C NMR(101MHz,DMSO-d 6 )δ175.21,166.48,147.15,129.79,128.59,128.35,52.52,45.08,18.70；
LRMS(ESI-)[M-COOH] - calculated m/z for[C 10 H 11 O 2 ] - :163.08,found:163.12.
2- (4-isobutylphenyl) propionic acid (2ah)
13 C NMR(101MHz,CDCl 3 )δ180.85,140.83,136.97,129.37,127.26,45.01,44.97,30.16,22.38,18.09；
HRMS(ESI-)[M-H] - calculated m/z for[C 13 H 17 O 2 ] - :205.1234,found:205.1243.
2- (2-fluoro- [1,1' -diphenyl ] -4-substituted) propionic acid (2ai)
13 C NMR(101MHz,CDCl 3 )δ180.17,159.67(d,J＝248.4Hz),140.92(d,J＝7.7Hz),135.39(d,J＝1.2Hz),130.88(d,J＝4.0Hz),128.94(d,J＝3.0Hz),128.44,128.13(d,J＝13.6Hz),127.70,123.67(d,J＝3.4Hz),115.36(d,J＝23.7Hz),44.84,17.99； 19 F NMR(376MHz,CDCl 3 )δ-117.39；
HRMS(ESI-)[M-COOH] - calculated m/z for[C 15 H 12 FO 2 ] - :199.0929,found:199.0925.
2,2-bis(4-methoxyphenyl)-2-phenylacetic acid(2aj)
13 C NMR(101MHz,CDCl 3 )δ179.97,158.53,142.99,134.69,131.59,130.28,127.85,127.15,113.14,66.12,55.33；
LRMS(ESI-)[M-H] - calculated m/z for[C 21 H 19 O 2 ] - :303.14,found:303.25.
2- (4- (3-methylpyrazine-2-substituted) phenyl) acetic acid methyl ester (2ak)
13 C NMR(101MHz,CDCl 3 )δ171.71,153.61,151.77,142.14,141.56,137.44,134.63,129.34,129.17,52.12,40.94,23.21；
HRMS(ESI-)[M+H] + calculated m/z for[C 14 H 15 N 2 O 2 ] + :243.1128,found:243.1125.
2- (4 '-methyl- [1,1' -diphenyl ] -4-substituted) acetic acid (4a)
13 C NMR(101MHz,DMSO-d 6 )δ173.17,138.85,137.48,137.03,134.38,130.36,129.95,126.81,126.71,40.71,21.09；
LRMS(ESI-)[M-H] - calculated m/z for[C 15 H 13 O 2 ] - :225.09,found:225.08.
2- (3 '-methoxy- [1,1' -diphenyl ] -4-substituted) acetic acid (4b)
7.53(m,2H),7.37–7.26(m,3H),7.20–7.12(m,2H),6.89(ddd,J＝8.2,2.6,0.9Hz,1H),3.78(s,3H),3.58(s,2H)；
13 C NMR(101MHz,DMSO-d 6 )δ173.13,160.16,141.90,138.84,134.87,130.40,130.36,127.09,119.33,113.33,112.50,55.52,40.71；
LRMS(ESI-)[M-H] - calculated m/z for[C 15 H 13 O 3 ] - :241.09,found:241.01.
2- (2 '-cyano- [1,1' -diphenyl ] -4-substituted) acetic acid (4c)
13 C NMR(101MHz,DMSO-d 6 )δ173.00,144.75,136.54,136.17,134.31,133.98,130.52,130.26,129.00,128.56,119.07,110.51,40.72；
HRMS(ESI-)[M-COOH] - calculated m/z for[C 14 H 10 N] - :192.0819,found:192.0820.
2- (3, 5-bistrifluoromethyl) phenyl) acetic acid (4d)
(s,1H),3.85(s,2H)；
13 C NMR(101MHz,DMSO-d 6 )δ172.32,139.08,131.11(d,J＝4.1Hz),130.32(q,J＝32.7Hz),123.83(q,J＝272.6Hz),120.75(p,J＝3.9Hz),39.75；
19 F NMR(376MHz,DMSO-d 6 )δ-61.36；
LRMS(ESI-)[M-H] - calculated m/z for[C 10 H 5 F 6 O 2 ] - :271.02,found:271.06.
2- (4-methoxy-2-trifluoromethylphenyl) acetic acid (4e)
13 C NMR(101MHz,DMSO-d 6 )δ172.49,158.47,135.23,128.83(q,J＝29.6Hz),125.36(q,J＝1.8Hz),124.57(q,J＝274.0Hz),118.02,111.62(q,J＝5.7Hz),55.96,37.42(d,J＝2.2Hz)；
19 F NMR(376MHz,DMSO-d 6 )δ-59.00；
LRMS(ESI-)[M-H] - calculated m/z for[C 10 H 8 F 3 O 3 ] - :233.04,found:233.06.
2- (3-ethoxy-4-ethoxycarbonylphenyl) acetic acid (4f)
13 C NMR(101MHz,CDCl 3 )δ176.64,166.31,158.60,138.80,131.81,121.07,119.67,114.31,64.60,60.81,41.20,14.64,14.24；
HRMS(ESI-)[M-H] + calculated m/z for[C 13 H 15 O 5 ] - :251.0925,found:251.0929.
While the embodiments of the invention have been described in detail in connection with the drawings, the invention should not be construed as limited to the scope of the patent. Various modifications and changes may be made by those skilled in the art without inventive step within the scope of the appended claims.
Claims (10)
1. A synthetic method of an aryl acetic acid compound is characterized by comprising the following steps:
s1: the benzyl halide is photosensitiveAdding agent and alkali into a reaction device, and using CO for the reaction device 2 Replacement 3 times, then CO 2 Adding a solvent and a reducing agent under the atmosphere of (1);
s2: placing an S1 reaction device at a position 1cm away from a visible light source, stirring and reacting at room temperature for 0.1-24 h, diluting with ethyl acetate after the reaction is finished, then quenching with a quenching agent, extracting with ethyl acetate, and then spin-drying the solvent to obtain a crude product;
s3: and purifying the crude product obtained in the step S2 by flash column chromatography to obtain the aryl acetic acid compound.
2. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the structure of the benzyl halide is shown as a formula (I),
wherein Ar is aryl; r 1 And R 2 Are respectively independent hydrogen, alkyl or aryl, and X is Cl or Br.
3. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the dosage of the photosensitizer is 0.01-10 mol% of the reaction substrate; the addition amount of the alkali is 0.1-10 times equivalent of the reaction substrate; the addition amount of the reducing agent is 0.1-10 times equivalent of the reaction substrate.
4. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: CO in the reaction apparatus 2 The air pressure is 0.1 atm-30 atm.
5. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the photosensitizer is 4DPAIPN, 3DPAFIPN, 4CzIPN, DPZ or Ir (ppy) 2 (dbbpy)·PF 6 。
6. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the alkali is at least one of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate and cesium carbonate.
7. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the reducing agent is TMEDA and Et 3 N, DIPEA or PhSiH 3 。
8. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the solvent is DMF, DMA or DMSO.
9. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the quenching agent is ethyl acetate and hydrochloric acid.
10. The method for synthesizing an arylacetic acid compound according to claim 1, wherein: the eluent used for column chromatography purification in S3 is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, the volume ratio of the petroleum ether to the ethyl acetate in the mixture is 10: 1-2: 1, and the mass fraction of the glacial acetic acid is 0.1-0.5%.
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