CN115677569B - 基于铁催化芳基卤代物与烷基卤代物还原偶联反应的吡啶类和取代苯类化合物合成方法 - Google Patents
基于铁催化芳基卤代物与烷基卤代物还原偶联反应的吡啶类和取代苯类化合物合成方法 Download PDFInfo
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- 150000001350 alkyl halides Chemical class 0.000 title claims abstract description 20
- 150000001502 aryl halides Chemical class 0.000 title claims abstract description 20
- 150000001555 benzenes Chemical class 0.000 title claims description 11
- 150000003222 pyridines Chemical class 0.000 title claims description 7
- 238000005859 coupling reaction Methods 0.000 title abstract description 20
- 230000009467 reduction Effects 0.000 title abstract description 15
- 238000001308 synthesis method Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- 239000003446 ligand Substances 0.000 claims description 10
- 238000006578 reductive coupling reaction Methods 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims 5
- 238000006243 chemical reaction Methods 0.000 abstract description 27
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 10
- 239000003638 chemical reducing agent Substances 0.000 abstract description 9
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 8
- 229910052723 transition metal Inorganic materials 0.000 abstract description 7
- 150000003624 transition metals Chemical class 0.000 abstract description 7
- 229910052742 iron Inorganic materials 0.000 abstract description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 abstract 1
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 238000006722 reduction reaction Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 9
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 229910021575 Iron(II) bromide Inorganic materials 0.000 description 6
- 229940046149 ferrous bromide Drugs 0.000 description 6
- GYCHYNMREWYSKH-UHFFFAOYSA-L iron(ii) bromide Chemical compound [Fe+2].[Br-].[Br-] GYCHYNMREWYSKH-UHFFFAOYSA-L 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- IBXHWLZKSOGUFS-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane;hydroiodide Chemical compound [I-].C1C(C2)CC(C3)CC2CC13[PH+](CCCC)C1(C2)CC(C3)CC2CC3C1 IBXHWLZKSOGUFS-UHFFFAOYSA-N 0.000 description 5
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- PWRBCZZQRRPXAB-UHFFFAOYSA-N 3-chloropyridine Chemical compound ClC1=CC=CN=C1 PWRBCZZQRRPXAB-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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- 239000003153 chemical reaction reagent Substances 0.000 description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical group [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 2
- NDTCXABJQNJPCF-UHFFFAOYSA-N chlorocyclopentane Chemical compound ClC1CCCC1 NDTCXABJQNJPCF-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 229960002089 ferrous chloride Drugs 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
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- 239000002904 solvent Substances 0.000 description 2
- YWWDBCBWQNCYNR-UHFFFAOYSA-N trimethylphosphine Chemical compound CP(C)C YWWDBCBWQNCYNR-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- PONXTPCRRASWKW-ZIAGYGMSSA-N (1r,2r)-1,2-diphenylethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-ZIAGYGMSSA-N 0.000 description 1
- GDIPAQOCWAFNMZ-UHFFFAOYSA-N 2-(4-methoxycarbonylpyridin-2-yl)pyridine-4-carboxylic acid Chemical compound COC(=O)C1=CC=NC(C=2N=CC=C(C=2)C(O)=O)=C1 GDIPAQOCWAFNMZ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- YKXGRCRPKIHTFM-UHFFFAOYSA-N 4-chloro-1-(4-methylphenyl)sulfonylpiperidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCC(Cl)CC1 YKXGRCRPKIHTFM-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 238000005577 Kumada cross-coupling reaction Methods 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 229960001781 ferrous sulfate Drugs 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 229910021506 iron(II) hydroxide Inorganic materials 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
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- 229910052759 nickel Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
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- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
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- 229910052763 palladium Inorganic materials 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- NZZWXABIGMMKQL-UHFFFAOYSA-N tert-butyl 4-chloropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(Cl)CC1 NZZWXABIGMMKQL-UHFFFAOYSA-N 0.000 description 1
- -1 tetramethyl ethylenediamine, tetramethyl Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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- Pyridine Compounds (AREA)
Abstract
本发明公开了一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,属于有机合成技术领域,该方法通过于均相体系中,以芳基卤代物和烷基卤代物作为反应底物和铁盐作为催化剂,同时加入配体、碱、还原剂和溶剂进行还原偶联反应,制得吡啶类化合物和取代苯类化合物。本发明首次提供一种以双联频哪醇联硼酸酯等化合物作为还原剂,铁催化的芳基卤代物和烷基卤代物的还原偶联反应,解决了现在传统过渡金属催化碳碳键偶联反应条件苛刻的问题,实现了碳氯键的断裂,高效合成了sp2‑sp3碳碳键,同时具有操作方便、原料廉价易得、反应条件温和且绿色环保、底物普适性广和产物收率高的特点。
Description
技术领域
本发明涉及有机合成技术领域,具体涉及到一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法。
背景技术
过渡金属催化的碳碳键偶联反应在有机合成领域中是非常重要的一类反应,为药物、材料等化学品的合成提供了高效的工具。目前过渡金属催化的碳碳键偶联反应的主要还是利用传统的suzuki反应、kumada反应等,需要一个亲电体(如卤代物、磺酸酯等)和一个亲核体(通常为金属试剂如镁试剂、有机硼化物等)。但是这些反应所需要的有机金属试剂通常比较昂贵,且不稳定对贮存条件要求苛刻,甚至需要现制现用,并且这些反应的反应条件也通常比较严格需要无水无氧,对操作有很高的要求,限制了这些反应的应用。
通过在反应体系中加入还原剂一步实现两个亲电试剂的碳碳键偶联,过渡金属催化的还原偶联反应迅速发展为构建碳碳键最为直接、简单、灵活的方法。芳基、烷基、烯基、烯丙基等的卤化物、磺酸酯都成功应用到还原偶联反应中。但是目前还原偶联反应的研究主要聚焦在镍、钯等昂贵过渡金属催化剂,这些金属催化剂或者价格昂贵,或者有生物毒性对药物的后期修饰有影响。因此发展绿色廉价的还原偶联反应具有非常重要的意义。
除此之外,目前过渡金属催化的还原偶联反应通常是非均相体系,需要当量或过量的锌或锰金属粉末作为还原剂,这些还原剂来源广泛,操作简单。但是由于锌、镁的溶解性问题,在反应的后处理中不易除去,而对反应的结果造成影响,限制了其使用。但目前均相的还原偶联反应却鲜有报道,尤其是反应更为惰性的芳基氯代物和烷基机氯代物的还原偶联反应更是有机合成领域内一大挑战。因此,提供一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法也就显得十分的有意义。
发明内容
针对上述不足,本发明的目的是提供一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,可有效解决现有技术中均相体系中基于铁催化的芳基卤代物与烷基卤代物的还原偶联反应研究空白的问题,同时该方法具有操作方便、原料廉价易得、反应条件温和且绿色环保、底物普适性广和产物收率高的特点。
为达上述目的,本发明采取如下的技术方案:
本发明提供一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,于均相体系中,以芳基卤代物和烷基卤代物作为反应底物和铁盐作为催化剂,同时加入配体、碱、还原剂和溶剂进行还原偶联反应,制得吡啶类化合物和取代苯类化合物。
进一步地,上述基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,包括以下步骤:
在惰性气体保护的氛围下,将芳基卤代物、烷基卤代物、铁盐、配体、碱、还原剂和溶剂加入反应装置中,于65℃~95℃温度下搅拌反应10~24小时,反应结束后对反应产物进行分离纯化,制得吡啶类化合物和取代苯类化合物;其中,烷基卤代物、芳基卤代物、铁盐、配体、碱和还原剂的摩尔比为 1~2:1~3:0.01~0.5:0.01~0.8:1~5:0.1~5。
进一步地,烷基卤代物、芳基卤代物、铁盐、配体、碱和还原剂的摩尔比为1~2:1~3:0.05~0.2:0.2~0.6:1~2:0.1~0.5,优选为2:3:0.2:0.4:1.6:0.5。
进一步地,芳基卤代物的结构通式如下所示:
其中,R为烷基、芳基、杂环基、卤素、羰基、胺基、烷氧基、硅基、取代巯基、取代烷基、取代芳基、取代杂环基或取代硼基;虚线环为杂环。
进一步地,R为链状烷基、环烷基;虚线环为五元含氧杂环。
进一步地,芳基卤代物的结构式如下所示:
进一步地,烷基卤代物的结构通式为Alkyl-Cl;其中,Alkyl为烷基。
进一步地,烷基卤代物的结构式如下所示:
进一步地,铁盐为二价铁盐。
进一步地,二价铁盐包括氢氧化亚铁、溴化亚铁、氯化亚铁、硫酸亚铁或硝酸亚铁,优选为溴化亚铁或氯化亚铁。
进一步地,配体为膦配体或有机胺配体。
进一步地,膦配体包括二(金刚烷-1-基)(丁基)膦氢碘酸盐、三苯基膦、三甲基磷、三叔丁基磷或正丁基二(1-金刚烷基)膦氢碘酸盐,优选为二(金刚烷-1- 基)(丁基)膦氢碘酸盐。
进一步地,有机胺配体包括四甲基乙二胺、四甲基甲烷二胺、2,2'-联吡啶-4,4'-二甲酸甲酯、(1R,2R)-1,2-二苯基乙二胺或乙二胺,优选为四甲基乙二胺。
进一步地,碱包括碳酸金属盐或有机碱,优选为甲醇锂或甲醇钠。
进一步地,还原剂为双联频哪醇联硼酸酯、单质锌或单质锰,优选为双联频哪醇联硼酸酯。
进一步地,反应温度为80℃,反应时间为20~24小时.
本发明的化学反应式(以最优反应条件为例)如下:
综上所述,本发明具有以下优点:
1、本发明提供一种基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,于均相体系中,以芳基卤代物和烷基卤代物作为反应底物和铁盐作为催化剂,同时加入配体、碱、还原剂和溶剂进行还原偶联反应,制得吡啶类化合物和取代苯类化合物;本发明首次提供一种以双联频哪醇联硼酸酯等化合物作为还原剂,铁催化的芳基卤代物和烷基卤代物的还原偶联反应,解决了现在传统过渡金属催化碳碳键偶联反应条件苛刻的问题,并且拓展了铁催化提供了对C-Cl键裂解的应用范围。
2、本发明以铁盐作为催化剂无毒,低成本且对环境友好,利用其对氯代芳烃和氯代烷烃的还原偶联反应,实现了碳氯键的断裂,高效合成了sp2-sp3碳碳键。
3、本发明具有操作方便、原料廉价易得、反应条件温和且绿色环保、底物普适性广和产物收率高的特点。
附图说明
图1-2为本实施例1所得产物的核磁图谱;
图3-4为本实施例2所得产物的核磁图谱;
图5-6为本实施例3所得产物的核磁图谱。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅用以解释本发明,并不用于限定本发明,即所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。
因此,以下对提供的本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围,而是仅仅表示本发明的选定实施例。基于本发明的实施例,本领域技术人员在没有做出创造性劳动的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。
实施例1
本例的反应方程式如下所示:
其中,3-氯吡啶(0.3mmol,1.5equiv),氯代环戊烷(0.2mmol,1.0equiv),溴化亚铁(0.02mmol,0.10equiv),二(金刚烷-1-基)(丁基)膦氢碘酸盐(0.04mmol, 0.20equiv),甲醇锂(1.6mmol,8.0equiv),双联频哪醇联硼酸酯(0.5mmol,2.5equiv),甲基叔丁基醚(1.5ml);得到3-环戊基吡啶,透明液体24.4mg,产率为83%,产物的核磁图谱如图2和1所示。
上述反应的具体制备过程包括以下步骤:
1)将25ml的耐压封管放入手套箱中,然后称取加入溴化亚铁,二(金刚烷-1-基)(丁基)膦氢碘酸盐,甲醇锂,双联频哪醇联硼酸酯;
2)将步骤1)中耐压封管从手套箱中取出,连接双排管,用氮气抽换气3 次,每次间隔3-5分钟,完成换气后,在处于充气的状态换一次性橡胶塞,再用氮气抽换气3次,每次间隔3-5分钟;
3)完成换气后,在处于通氮气的状态下,往步骤2)所得的耐压封管中加入3-氯吡啶,氯代环戊烷,甲基叔丁基醚,换回密封塞,放入80℃恒温搅拌器中,反应20小时;
4)将步骤3)中反应后的耐压封管从恒温搅拌器中取出,加入1ml氯化铵饱和溶液(6.95mol/L)淬灭,乙酸乙酯萃取3次,每次10ml,合并有机相,无水硫酸钠干燥,真空浓缩,并用石油醚:乙酸乙酯=5:1(v:v)作为洗脱剂,通过快速柱层析色谱洗脱得到透明液体24.4mg,产率为83%。
实施例2
本例的反应方程式如下所示:
其中,3-氯吡啶(0.3mmol,1.5equiv),4-氯哌啶-1-羧酸叔丁酯(0.2mmol,1.0equiv),溴化亚铁(0.02mmol,0.10equiv),二(金刚烷-1-基)(丁基)膦氢碘酸盐(0.04mmol,0.20equiv),甲醇锂(1.6mmol,8.0equiv),双联频哪醇联硼酸酯(0.5 mmol,2.5equiv),甲基叔丁基醚(1.5ml);得到3-环戊基吡啶,黄色固体35.2mg,产率为67%,产物的核磁图谱如图4和3所示。
本例的制备过程与实施例1相同。
实施例3
本例的反应方程式如下所示:
其中,3-氯吡啶(0.3mmol,1.5equiv),4-氯-1-甲苯磺酰哌啶(0.2mmol,1.0equiv),溴化亚铁(0.02mmol,0.10equiv),二(金刚烷-1-基)(丁基)膦氢碘酸盐(0.04mmol,0.20equiv),甲醇锂(1.6mmol,8.0equiv),双联频哪醇联硼酸酯(0.5mmol,2.5equiv),甲基叔丁基醚(1.5ml);得到3-环戊基吡啶,黄色固体34.1mg,产率为 54%,产物的核磁图谱如图6和5所示。
本例的制备过程与实施例1相同。
实施例4
本例的反应方程通式如下所示:
其中,烷基卤代物(0.2mmol,1.0equiv)的结构式如下所示:
芳基卤代物(0.4mmol,2.0equiv)的结构式如下所示:
本例所制得的产物及收率如下所示:
以上内容仅仅是对本发明内容所作的举例和说明,所属本领域的技术人员不经创造性劳动即对所描述的具体实施例做的修改或补充或采用类似的方式替代仍属本专利的保护范围。
Claims (1)
1.基于铁催化芳基卤代物与烷基卤代物还原偶联反应的合成吡啶类和取代苯类化合物方法,其特征在于,包括以下合成路径:
或
或
;
所述合成路径中P ligand为;
所述或/>或/>为0.4 mmol,2.0 equiv;所述Alkyl-Cl为0.2mmol,1.0 equiv;
所述合成路径中为:
;
所述合成路径中为:/>;
所述合成路径中为:/>、/>或/>;
所述合成路径中Alkyl-Cl为:
。
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CN1933904A (zh) * | 2004-03-23 | 2007-03-21 | 沙特基础工业公司 | 烷烃选择性转化成不饱和羧酸的催化剂组合物,其制造方法和使用方法 |
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CN1933904A (zh) * | 2004-03-23 | 2007-03-21 | 沙特基础工业公司 | 烷烃选择性转化成不饱和羧酸的催化剂组合物,其制造方法和使用方法 |
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