CN111018691B - 一种芳香酸的绿色合成方法 - Google Patents
一种芳香酸的绿色合成方法 Download PDFInfo
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- CN111018691B CN111018691B CN201911146553.7A CN201911146553A CN111018691B CN 111018691 B CN111018691 B CN 111018691B CN 201911146553 A CN201911146553 A CN 201911146553A CN 111018691 B CN111018691 B CN 111018691B
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 61
- -1 aryl iodine Chemical compound 0.000 claims abstract description 28
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 18
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000011630 iodine Substances 0.000 claims abstract description 13
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 13
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 54
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- UGNSMKDDFAUGFT-UHFFFAOYSA-N 4,4-dimethyl-2-phenyl-5h-1,3-oxazole Chemical compound CC1(C)COC(C=2C=CC=CC=2)=N1 UGNSMKDDFAUGFT-UHFFFAOYSA-N 0.000 claims description 17
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 17
- 235000019253 formic acid Nutrition 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 150000008065 acid anhydrides Chemical class 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 7
- 150000001503 aryl iodides Chemical class 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- XKPJKVVZOOEMPK-UHFFFAOYSA-M lithium;formate Chemical group [Li+].[O-]C=O XKPJKVVZOOEMPK-UHFFFAOYSA-M 0.000 claims description 5
- 239000004280 Sodium formate Substances 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 4
- 235000019254 sodium formate Nutrition 0.000 claims description 4
- JRTIUDXYIUKIIE-KZUMESAESA-N (1z,5z)-cycloocta-1,5-diene;nickel Chemical compound [Ni].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 JRTIUDXYIUKIIE-KZUMESAESA-N 0.000 claims description 3
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 3
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- DRZUOPCJWAJOAG-UHFFFAOYSA-N CC(=O)C.CC(=O)C.[Ni] Chemical compound CC(=O)C.CC(=O)C.[Ni] DRZUOPCJWAJOAG-UHFFFAOYSA-N 0.000 claims description 3
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 3
- 125000003172 aldehyde group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000000101 thioether group Chemical group 0.000 claims description 3
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 3
- 150000004675 formic acid derivatives Chemical class 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 85
- 150000008064 anhydrides Chemical class 0.000 abstract description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 2
- 238000003780 insertion Methods 0.000 abstract description 2
- 230000037431 insertion Effects 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 78
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 39
- 238000005160 1H NMR spectroscopy Methods 0.000 description 39
- 238000002360 preparation method Methods 0.000 description 32
- 239000000047 product Substances 0.000 description 26
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 239000011521 glass Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- RDAKCPVJSPEDON-UHFFFAOYSA-M lithium;formate;hydrate Chemical compound [Li+].O.[O-]C=O RDAKCPVJSPEDON-UHFFFAOYSA-M 0.000 description 15
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- 239000012300 argon atmosphere Substances 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 238000002390 rotary evaporation Methods 0.000 description 12
- 239000004576 sand Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 238000003860 storage Methods 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 238000004293 19F NMR spectroscopy Methods 0.000 description 4
- 159000000032 aromatic acids Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 description 2
- SHSGDXCJYVZFTP-UHFFFAOYSA-N 4-ethoxybenzoic acid Chemical compound CCOC1=CC=C(C(O)=O)C=C1 SHSGDXCJYVZFTP-UHFFFAOYSA-N 0.000 description 2
- GOUHYARYYWKXHS-UHFFFAOYSA-N 4-formylbenzoic acid Chemical compound OC(=O)C1=CC=C(C=O)C=C1 GOUHYARYYWKXHS-UHFFFAOYSA-N 0.000 description 2
- NCKJIJSEWKIXAT-QURGRASLSA-N [(e)-2-diphenylphosphanylethenyl]-diphenylphosphane Chemical group C=1C=CC=CC=1P(C=1C=CC=CC=1)/C=C/P(C=1C=CC=CC=1)C1=CC=CC=C1 NCKJIJSEWKIXAT-QURGRASLSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- KFBKRCXOTTUAFS-UHFFFAOYSA-N nickel;triphenylphosphane Chemical compound [Ni].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 KFBKRCXOTTUAFS-UHFFFAOYSA-N 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- VPHHJAOJUJHJKD-UHFFFAOYSA-N 3,4-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C(Cl)=C1 VPHHJAOJUJHJKD-UHFFFAOYSA-N 0.000 description 1
- UMVOQQDNEYOJOK-UHFFFAOYSA-N 3,5-dimethylbenzoic acid Chemical compound CC1=CC(C)=CC(C(O)=O)=C1 UMVOQQDNEYOJOK-UHFFFAOYSA-N 0.000 description 1
- MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 1
- FQXQBFUUVCDIRK-UHFFFAOYSA-N 3-trifluoromethylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(F)(F)F)=C1 FQXQBFUUVCDIRK-UHFFFAOYSA-N 0.000 description 1
- IYDKBQIEOBXLTP-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C(O)=O)C=C1 IYDKBQIEOBXLTP-UHFFFAOYSA-N 0.000 description 1
- SOQWSEWRMYFXRL-UHFFFAOYSA-N 4-(4-methylphenyl)sulfonyloxybenzoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC=C(C(O)=O)C=C1 SOQWSEWRMYFXRL-UHFFFAOYSA-N 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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Abstract
本发明公开了一种芳香酸的绿色合成方法。所述方法包括:使用镍催化剂,在甲酸盐、酸酐、膦配体和有机溶剂存在的条件下,使芳基碘通过镍催化插羰得到芳香酸。本发明提供的方法利用廉价的镍催化剂,实现高效催化转化,反应条件温和,操作简单。
Description
技术领域
本发明涉及一种芳香酸的绿色合成方法,具体地涉及一种使用廉价的镍催化剂合成芳香酸的绿色合成方法。
背景技术
芳香酸是一类非常重要的化工产品,是许多天然产品,药物和农用化学品中常见的结构。目前,大多数芳香酸的生产往往涉及多步反应及氧化反应,存在副产物多、原子利用率低、成本高和环境污染等缺点。由芳基碘制备芳香羧酸往往是通过钯催化一氧化碳插羰的反应途径实现,毒性较大,操作困难。本发明使用廉价的镍催化剂,甲酸盐和酸酐的混合物代替一氧化碳实现芳基碘到芳香羧酸的转化,为芳香酸类化合物的合成提供了一种新的方法,符合发展绿色环境友好化学的要求。
发明内容
本发明解决的问题在于提供一种芳香酸类化合物的制备方法,不需要昂贵的Pd催化剂和CO毒性气体,且反应条件温和,对官能团兼容性较好。
为了解决上述技术问题,本申请提供如下技术方案:
一种芳香酸的制备方法,包括以下步骤:
在式1所示的任选具有取代基的芳基碘或含氮杂芳基碘、式2所示的甲酸盐、酸酐、膦配体、镍催化剂和有机溶剂存在下,通过加热实现甲酸盐和酸酐原位生成一氧化碳,然后与所述芳基碘或杂芳基碘反应得到式3所示的芳香羧酸类化合物:
在式1和式3中,Ar表示任选被选自如下各项的取代基取代的芳基基团:卤素、酯基、醛基、醚基、硫醚基、氰基、4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基、2-((叔丁氧基羰基)氨基)-3-甲氧基-3-氧代基、甲苯磺酰氧基、吡咯基、碳原子数为1-10的直链或支链烷基、碳原子数为1-10的直链或支链烷氧基、碳原子数为1-10的直链或支链卤代烷基、碳原子数为1-10的直链或支链烷硫基、碳原子数为1-10的直链或支链烷酰基,碳原子数为2-10的直链或支链烷腈基、碳原子数为6-12的芳氧基、和碳原子数为6-12的芳基,而HetAr表示任选取代的含氮杂环,含氮杂环上的取代基为卤素。
作为优选,所述的式2和式1的摩尔比为1.0-2.0。
作为优选,所述的甲酸盐选自甲酸锂和甲酸钠中的至少一种,更优选为甲酸锂,尤其优选甲酸锂一水合物。
作为优选,所述的镍催化剂选自乙酸镍(II)四水合物、双-(1,5-环辛二烯)镍、二乙酰丙酮镍、四三苯基膦镍和氯化镍中的至少一种,摩尔用量优选为所述式1的摩尔用量的5%-20%。
作为优选,所述的膦配体选自1,3-双(二苯基膦)丙烷、顺-1,2-双(二苯基膦)乙烯中的至少一种,摩尔用量优选为所述式1的摩尔用量的10%-30%。
作为优选,所述的酸酐是乙酸酐、丙酸酐、特戊酸酐、苯甲酸酐中的至少一种,摩尔用量优选为所述式1的摩尔用量的10%-50%。
作为优选,所述有机溶剂选自甲苯和四氢呋喃中的至少一种。
作为优选,反应时间为10-30小时。
作为优选,反应温度为80-110℃。
具体实施方式
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明提供一种芳香羧酸的合成方法,具体反应式如下:
具体地,在式1所示的任选一个芳基碘或含氮杂芳基碘、式2所示的甲酸盐、酸酐、膦配体、镍催化剂和有机溶剂存在下,通过加热实现甲酸盐和酸酐原位生成一氧化碳,然后与所述芳基碘或杂芳基碘反应得到式3所示的芳香羧酸类化合物。
在上述式1和式3中,I表示碘,Ar表示任选被选自如下各项的取代基取代的芳基基团:卤素、酯基、醛基、醚基、硫醚基、氰基、4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基、2-((叔丁氧基羰基)氨基)-3-甲氧基-3-氧代基、甲苯磺酰氧基、吡咯基、碳原子数为1-10(优选1-6,更优选1-4)的直链或支链烷基、碳原子数为1-10(优选1-6,更优选1-4)的直链或支链卤代烷基、碳原子数为1-10的直链或支链烷氧基、碳原子数为1-10(优选1-6,更优选1-4)的直链或支链烷硫基、碳原子数为1-10(优选1-6,更优选1-4)的直链或支链烷酰基,碳原子数为2-10(优选2-6,更优选2-4)的直链或支链烷腈基、碳原子数为6-12(优选6-10,更优选6-8)的芳氧基、或碳原子数为6-12(优选6-10,更优选6-8)的芳基,而HetAr表示任选取代的含氮杂环,含氮杂环上的取代基为卤素。
也就是说,式1所示的化合物表示任选具有一个或多个取代基的芳基碘(Ar-I)或任选具有一个或多个取代基的含氮杂芳基碘(HetAr-I)。
所述“卤素”的实例为氟、氯或溴。
所述“碳原子数为1-10的直链或支链烷基”的实例包括甲基、乙基、丙基、丁基、叔丁基、异丁基、仲丁基、庚基、辛基、壬基、癸基、等等。
所述“碳原子数为1-10的直链或支链卤代烷基”的实例包括三氟甲基、三氟乙基、氯甲基、溴甲基、二氯乙基、氯丁基、溴乙基、溴己基、氯丙基、溴辛基、等等。
所述“碳原子数为1-10的直链或支链烷氧基”的实例包括甲氧基、乙氧基、丙氧基、正丁氧基、叔丁氧基、仲丁氧基、庚氧基、辛氧基、癸氧基、等等。
所述“碳原子数为1-10的直链或支链烷硫基”的实例包括甲硫基、乙硫基、己硫基、辛硫基、等等。
所述“碳原子数为1-10的直链或支链烷酰基”的实例包括甲酰基、乙酰基、丁酰基、辛酰基、等等。
所述“碳原子数为1-10的直链或支链烷腈基”的实例包括乙腈基、丙腈基、丁腈基、异丁腈基、己腈基、等等。
所述“碳原子数为6-12的芳基”的实例包括苯基、甲苯基、乙苯基、间甲苯基、对甲苯基、等等。
所述“碳原子数为6-12的芳氧基”的实例包括苯氧基、苄氧基、苯基乙氧基、等等。
而且,申请人发现,在所述反应转化中,合理的式1与式2的摩尔比,式1与镍催化剂、膦配体、酸酐的摩尔比,以及有机溶剂、加热温度等是进行该反应尤为重要的工艺条件。发明人经过大量的实验发现:
所述的甲酸盐为甲酸锂或甲酸钠,摩尔用量为所述式1的摩尔用量的1.0-2.0,更优选1.2-1.8,还更优选1.3-1.5。所述甲酸盐更优选为甲酸锂,并且可以使用市售的甲酸锂一水合物,而且约1.5倍摩尔用量的甲酸锂一水合物是最优选的。
发明人进一步发现,如果在上述反应中添加甲酸,将大大提高反应的产率,这可以从下面相应实施例的产率比较得出。发明人不受任何理论束缚地认为,这可能原因是甲酸可作为助催化剂提高反应效率。甲酸的用量范围可以为10mol%-200mol%,优选20mol%-100mol%,更优选50mol%-60%。
所述的镍催化剂选自乙酸镍(II)四水合物、双-(1,5-环辛二烯)镍、二乙酰丙酮镍、四三苯基膦镍和氯化镍中的至少一种,更优选为乙酸镍(II)四水合物,并且摩尔用量为所述式1的摩尔用量的5%-20%,更优选10%-20%,还更优选为15%-20%。
所述的膦配体选自1,3-双(二苯基膦)丙烷、顺-1,2-双(二苯基膦)乙烯中的至少一种,更优选为1,3-双(二苯基膦)丙烷,并且摩尔用量为所述式1的摩尔用量的10%-30%,更优选为15-20%。
所述的酸酐是乙酸酐、丙酸酐、特戊酸酐或苯甲酸酐等,更优选为乙酸酐,并且摩尔用量为所述式1的摩尔用量的10%-50%,更优选为20%-30%。
所述有机溶剂选自甲苯和四氢呋喃中的至少一种,更优选为四氢呋喃。
所述反应的温度范围是80-110℃,优选为90-100℃。
所述反应的时间为10小时-30小时,优选为20-24小时。
在使用本发明的镍催化剂体系中,在使用芳基碘或含氮杂芳基碘的情况下,产率可以达到45%以上(参见表1),这充分说明本发明具有良好的工业应用前景。
本发明提供的方法,是在芳基碘或含氮杂芳基碘、甲酸盐、酸酐有机溶剂存在时,通过加热实现甲酸盐和酸酐原位生成一氧化碳,与芳基碘反应得到芳香羧酸类化合物。具有反应条件温和、操作简单,且避免了贵金属催化剂Pd的使用,为芳香羧酸的合成提供了一种新颖的方法,符合发展绿色环境友好化学的要求。
实施例
为了进一步阐明本发明,下面结合实施例对本发明优选实施方案进行描述,但是应当理解,这些描述只是为了进一步说明本发明的特征和优点,而不是对本发明权利要求的限制,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
本发明下述实施例中用于合成芳香羧酸化合物所使用到的药品分别在以下试剂公司购买:
四氢呋喃(C4H8O,99.5%)从安耐吉公司购买,甲苯(C7H8,99.5%),从国药集团购买。
甲酸锂一水合物(LiOOCH·H2O,98%)从TCI公司购买,1,3-双(二苯基膦)丙烷(dppp,98%)从Adamas公司购买。
实施例1(比较例)、使用Pd催化剂代替Ni催化剂
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、双(二亚苄基丙酮)钯(10mol%,28.7mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率10%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
从上述结果可以看出,使用Pd催化剂代替Ni催化剂,尽管也可以获得目标产物,但是其产率是非常低的,仅有10%。而且Pd催化剂还是贵金属,本发明所使用的Ni催化剂廉价且能获得更好的产率,因而具有显著的成本优势。
实施例2、不添加甲酸
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率50%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
这个实施例的结果说明,甲酸的添加不是必须的,尽管相比于本发明的较优实验条件的实施例12的结果,产率仅有50%,效果差些。
实施例3、使用NaOOCH代替LiOOCH·H2O
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸钠(0.75mmol,52mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率62%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例4、使用5mol%乙酸镍(II)四水合物
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(5mol%,6.2mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率46%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例5、使用20mol%乙酸镍(II)四水合物
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(20mol%,24.8mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率70%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例6、使用10mol%1,3-双(二苯基膦)丙烷
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(10mol%,21mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率50%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例7、使用30mol%1,3-双(二苯基膦)丙烷
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(30mol%,62mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率64%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例8、使用10mol%乙酸酐
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.05mmol,5.1mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率65%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例9、使用50mol%乙酸酐
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.25mmol,25.5mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率65%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例10、使用80℃
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在80℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率20%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例11、使用110℃
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在110℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率30%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例12、制备4-甲基苯甲酸
反应式:
具体方法如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL)中加入4-碘甲苯(0.5mmol,109mg)、甲酸锂一水合物(0.75mmol,39mg)、乙酸镍(II)四水合物(10mol%,12.4mg)和1,3-双(二苯基膦)丙烷(20mol%,41.2mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加2mL四氢呋喃,乙酸酐(0.1mmol,10.2mg)和甲酸(0.25mmol,11.6mg)。该反应体系在100℃油浴锅中加热连续搅拌24小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,用H2O淬灭反应,并用乙酸乙酯(3*10mL)萃取反应液,再将合并的有机相用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,φ30mm,有效长:500ml)层析分离得到产物。(产物为白色固体,共55.1毫克,产率81%,洗脱剂乙酸乙酯∶石油醚=1∶5~1∶2)
1H NMR(400MHz,CDCl3)δ8.01(d,J=7.8Hz,2H),7.27(d,J=7.8Hz,2H),2.42(s,3H).
13C NMR(101MHz,CDCl3)δ172.53,144.68,130.29,129.23,126.64,21.78.
实施例13、制备苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ11.57(s,1H),8.38-7.89(m,2H),7.68-7.55(m,1H),7.47(t,J=11.6,4.2Hz,2H).
13C NMR(101MHz,CDCl3)δ171.68,143.00,136.35,134.86,133.93.
实施例14、制备3-甲基苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ8.03-7.64(m,2H),7.61-7.22(m,2H),2.37(s,3H).
13C NMR(101MHz,DMSO)δ167.90,138.37,133.93,131.20,130.21,128.93,126.93,21.29.
实施例15、制备3-甲氧基苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ7.73(ddd,J=7.6,1.5,1.0Hz,1H),7.63(dd,J=2.6,1.5Hz,1H),7.39(t,J=8.0Hz,1H),7.16(ddd,J=8.3,2.7,1.0Hz,1H),3.87(s,3H).
13C NMR(101MHz,CDCl3)δ171.82,159.63,130.56,129.55,122.70,120.50,114.40,55.48.
实施例16、制备4-乙氧基苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ8.25-7.76(m,2H),7.27-6.61(m,2H),4.14(q,J=7.0Hz,2H),1.40(t,J=7.0Hz,3H).
13C NMR(101MHz,Acetone)δ166.47,162.88,131.61,122.60,114.07,63.53,14.06.
实施例17、制备4-(叔丁基)苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ8.05(d,J=8.3Hz,2H),7.49(d,J=8.4Hz,2H),1.35(s,9H).
13C NMR(101MHz,CDCl3)δ172.34,157.58,130.14,126.62,125.50,35.21,31.12.
实施例18、制备4-氯苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.20(s,1H),8.42-7.79(m,2H),7.77-7.35(m,2H).
13C NMR(101MHz,DMSO)δ171.68,143.00,136.35,134.86,133.93.
实施例19、制备3-氯苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.36(s,1H),8.36-7.76(m,2H),7.71(ddd,J=8.0,2.2,1.1Hz,1H),7.61-7.46(m,1H).
13C NMR(101MHz,DMSO)δ166.54,133.81,133.36,133.19,131.13,129.30,128.39.
实施例20、制备4-溴苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ8.28-7.84(m,2H),7.81-7.60(m,1H).
13C NMR(101MHz,Acetone)δ166.01,131.74,131.43,129.82,127.26.
实施例21、制备4-氟苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ8.31-7.79(m,2H),7.46-6.91(m,1H).
13C NMR(101MHz,Acetone)δ166.91,165.96,164.41,132.42,132.33,127.04,127.02,115.52,115.30.
19F NMR(376MHz,Acetone)δ-107.96.
实施例22、制备3-氟苯甲酸
反应式:
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ7.89(d,J=7.7Hz,1H),7.72(d,J=9.5Hz,1H),7.62-7.55(m,1H),7.48-7.39(m,1H).
13C NMR(101MHz,Acetone)δ165.67,163.77,161.34,133.06,132.98,130.61,130.53,125.57,125.54,119.88,119.67,116.12,115.90.
19F NMR(376MHz,Acetone)δ-114.14.
实施例23、制备4-(甲硫基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ8.23-7.72(m,2H),7.60-7.02(m,2H),2.56(s,3H).
13C NMR(101MHz,Acetone)δ166.60,145.59,129.96,126.62,124.85,13.69.
实施例24、制备4-(三氟甲基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.50(s,1H),8.14(d,J=7.9Hz,2H),7.88(d,J=8.3Hz,2H).
13C NMR(101MHz,DMSO)δ166.68,135.11,133.08,132.76,130.56,128.34,126.07,126.03,125.99,125.63,122.92.
19F NMR(376MHz,DMSO)δ-61.56.
实施例25、制备3-(三氟甲基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ8.40(s,1H),8.32(d,J=7.8Hz,1H),7.89(d,J=7.8Hz,1H),7.65(t,J=7.8Hz,1H).
13C NMR(101MHz,CDCl3)δ170.70,133.42,131.49,131.16,130.83,130.46,130.07,129.30,124.92,122.80,122.22.
19F NMR(376MHz,CDCl3)δ-62.87.
实施例26、制备4-甲酰基苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ11.64(s,1H),10.17(s,1H),8.24(dd,J=7.4,3.0Hz,2H),8.06(dd,J=7.5,3.1Hz,2H).
13C NMR(101MHz,Acetone)δ191.89,165.96,139.60,135.39,130.19,129.37.
实施例27、制备4-乙酰基苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ8.06(s,4H),2.63(s,3H).
13C NMR(101MHz,DMSO)δ198.24,167.13,140.30,134.99,130.03,128.82,27.51.
实施例28、制备[1,1′-联苯基]-4-羧酸
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ11.25(s,1H),8.21-8.08(m,2H),7.84-7.79(m,2H),7.77-7.72(m,2H),7.54-7.48(m,2H),7.46-7.41(m,1H).
13C NMR(101MHz,Acetone)δ166.59,145.33,139.79,130.23,129.41,129.01,128.19,127.11,126.92.
实施例29、制备4-氰基苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.60(s,1H),8.09(d,J=8.6Hz,2H),7.99(d,J=8.6Hz,2H).
13C NMR(101MHz,DMSO)δ166.54,135.32,133.16,130.40,118.67,115.53.
实施例30、制备4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)苯甲酸方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ8.11(d,J=8.2Hz,2H),7.91(d,J=8.2Hz,2H),1.36(s,12H).
13C NMR(101MHz,CDCl3)δ172.34,134.79,131.53,129.22,84.32,77.40,77.08,76.77,24.90.(one carbon signal was overlapped)
实施例31、制备4-(氰基甲基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.06(s,1H),7.97(d,J=8.4Hz,2H),7.48(d,J=8.6Hz,2H),4.17(s,2H).
13C NMR(101MHz,DMSO)δ167.37,136.75,130.57,130.39,128.77,119.30,22.89.
实施例32、制备4-(甲苯磺酰氧基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.22(s,1H),7.94(d,J=8.5Hz,2H),7.76(d,J=7.9Hz,2H),7.47(d,J=2.6Hz,2H),7.15(d,J=8.5Hz,2H),2.50(s,3H).
13C NMR(101MHz,DMSO)δ166.74,152.55,146.55,131.81,131.57,130.80,130.37,128.73,122.68,21.66.
实施例33、制备4-(苄氧基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ12.67(s,1H),7.90(d,J=8.9Hz,2H),7.59-7.24(m,5H),7.24-6.98(m,2H),5.18(s,2H).
13C NMR(101MHz,DMSO)δ167.44,162.40,136.99,131.82,128.97,128.48,128.30,123.63,115.08,69.91.
实施例34、制备3,5-二甲基苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ12.09(s,1H),7.74(s,2H),7.23(s,1H),2.37(s,6H).
13C NMR(101MHz,CDCl3)δ172.92,138.20,135.55,129.20,127.94,21.18.
实施例35、制备3,4-二氯苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,Acetone)δ8.13(d,J=2.0Hz,1H),7.98(dd,J=8.4,2.0Hz,1H),7.75(d,J=8.4Hz,1H).
13C NMR(101MHz,Acetone)δ164.82,136.65,132.20,131.36,131.03,130.92,129.32.
实施例36、制备6-氯烟酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.68(s,1H),8.90(s,1H),8.30(dd,J=8.3,2.2Hz,1H),7.67(dd,J=8.3,2.1Hz,1H).
13C NMR(101MHz,DMSO)δ170.62,159.26,156.15,145.58,131.36,129.72.
实施例37、制备6-氟烟酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ13.63(s,1H),8.77(s,1H),8.45(td,J=8.4,2.3Hz,1H),7.32(dd,J=8.3,2.3Hz,1H).
13C NMR(101MHz,DMSO)δ166.59,165.75,164.28,150.13,150.09,149.97,143.74,143.67,126.28,110.47,110.39,110.10,110.01.
实施例38、制备4-(1H-吡咯-1-基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,DMSO)δ12.97(s,1H),8.00(d,J=8.8Hz,2H),7.73(d,J=8.8Hz,2H),7.51(t,2H),6.32(t,2H).
13C NMR(101MHz,DMSO)δ167.21,143.50,131.50,127.56,119.51,119.01,111.83.
实施例39、制备4-(2-((叔丁氧基羰基)氨基)-3-甲氧基-3-氧代丙基)苯甲酸
方法同实施例12,产率见表1。
1H NMR(400MHz,CDCl3)δ8.03(d,J=8.2Hz,1H),7.24(d,J=8.3Hz,4H),5.04(d,J=7.9Hz,1H),4.64(m,J=7.7Hz,1H),3.73(s,1H),3.22(dd,J=13.7,5.8Hz,1H),3.11(dd,J=13.3,5.9Hz,1H),1.42(s,5H).
13C NMR(101MHz,CDCl3)δ172.07,171.20,155.06,142.43,130.41,129.51,128.22,80.23,54.21,52.42,38.50,28.28.
表1由芳基碘代物制备芳香羧酸及其相应的产率
工业可适用性
传统芳基卤羧基化方法需要使用Pd催化剂外加CO气体,实验操作难度大,毒性高。本发明使用廉价的镍催化剂,甲酸盐和酸酐的混合物代替一氧化碳实现芳基卤素到芳香羧酸的转化,符合发展绿色环境友好化学的要求,底物范围广及官能团兼容性好,为芳香酸类化合物的合成提供了一种新的方法,且原料和试剂易得,具有良好的工业应用前景。
Claims (9)
1.一种芳香羧酸的制备方法,所述方法包括以下步骤:
在式1所示的任选具有一个或多个取代基的芳基碘Ar-I或含氮杂芳基碘HetAr-I、式2所示的甲酸盐、酸酐、膦配体、镍催化剂、甲酸和有机溶剂存在下,通过加热实现甲酸盐和酸酐原位生成一氧化碳,然后与所述芳基碘或含氮杂芳基碘反应,得到式3所示的芳香羧酸类化合物:
在式1和式3中,Ar表示任选被选自如下各项的取代基取代的芳基基团:卤素、醛基、氰基、4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基、2-((叔丁氧基羰基)氨基)-3-甲氧基-3-氧代基、甲苯磺酰氧基、吡咯基、碳原子数为1-10的直链或支链烷基、碳原子数为1-10的直链或支链卤代烷基、碳原子数为1-10的直链或支链烷氧基、碳原子数为1-10的直链或支链烷硫基、碳原子数为1-10的直链或支链烷酰基,碳原子数为2-10的直链或支链烷腈基、碳原子数为6-12的芳氧基、和碳原子数为6-12的芳基,而HetAr表示任选取代的含氮杂芳基环,含氮杂芳基环上的取代基为卤素,
所述镍催化剂选自乙酸镍(II)四水合物、双-(1,5-环辛二烯)镍、二乙酰丙酮镍和氯化镍中的至少一种,并且,
所述膦配体为1,3-双(二苯基膦)丙烷。
2.根据权利要求1所述的方法,其中所述式2和式1的摩尔比为1.0-2.0。
3.根据权利要求1-2中任一项所述的方法,其中所述甲酸盐为甲酸锂或甲酸钠。
4.根据权利要求1所述的方法,其中,所述膦配体的摩尔用量为所述式1的摩尔用量的10%-30%。
5.根据权利要求1所述的方法,其中,所述酸酐选自乙酸酐、丙酸酐、特戊酸酐和苯甲酸酐中的至少一种,且摩尔用量为所述式1的摩尔用量的10%-50%。
6.根据权利要求1所述的方法,其中,所述有机溶剂选自甲苯和四氢呋喃中的至少一种。
7.根据权利要求1所述的方法,其中,所述镍催化剂摩尔用量为所述式1的摩尔用量的5%-20%。
9.根据权利要求1所述的方法,其中在式1和式3中,Ar表示任选被选自如下各项的取代基取代的芳基基团:醚基和硫醚基。
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