CN110668973B - 一种内炔衍生物及其制备方法 - Google Patents
一种内炔衍生物及其制备方法 Download PDFInfo
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- CN110668973B CN110668973B CN201910833596.6A CN201910833596A CN110668973B CN 110668973 B CN110668973 B CN 110668973B CN 201910833596 A CN201910833596 A CN 201910833596A CN 110668973 B CN110668973 B CN 110668973B
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- 150000001345 alkine derivatives Chemical class 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- -1 alkyl saturated carbon-carbon Chemical class 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 4
- 239000010703 silicon Substances 0.000 claims abstract description 4
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims abstract description 3
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 claims abstract description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 12
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 12
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 12
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 12
- 229940071536 silver acetate Drugs 0.000 claims description 12
- 239000001632 sodium acetate Substances 0.000 claims description 12
- 235000017281 sodium acetate Nutrition 0.000 claims description 12
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- JBEPFZCYCKRHTN-UHFFFAOYSA-N C(=O)O.C12CC3CC(CC(C1)C3)C2 Chemical compound C(=O)O.C12CC3CC(CC(C1)C3)C2 JBEPFZCYCKRHTN-UHFFFAOYSA-N 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000000460 chlorine Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 2
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims 2
- 239000003513 alkali Substances 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract description 14
- 125000005233 alkylalcohol group Chemical group 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 238000001994 activation Methods 0.000 description 14
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 11
- GSRAUIACFLZSEZ-UHFFFAOYSA-N C1=CC=C(C=C1)C#CCCCCNC2=CC=CC3=C2N=CC=C3 Chemical compound C1=CC=C(C=C1)C#CCCCCNC2=CC=CC3=C2N=CC=C3 GSRAUIACFLZSEZ-UHFFFAOYSA-N 0.000 description 10
- 150000001298 alcohols Chemical class 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
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- 238000004440 column chromatography Methods 0.000 description 9
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- 238000002390 rotary evaporation Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 8
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000000967 suction filtration Methods 0.000 description 7
- ZISJRLFUNCQBBU-UHFFFAOYSA-N 1-phenyl-4-(2-phenylethynyl)benzene Chemical group C1=CC=CC=C1C#CC1=CC=C(C=2C=CC=CC=2)C=C1 ZISJRLFUNCQBBU-UHFFFAOYSA-N 0.000 description 6
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- 150000003333 secondary alcohols Chemical class 0.000 description 6
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
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- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical class ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
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- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
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- ZECJHXWYQJXFQQ-UHFFFAOYSA-L CC1=C(C)C(C)([Ir](Cl)Cl)C(C)=C1C Chemical class CC1=C(C)C(C)([Ir](Cl)Cl)C(C)=C1C ZECJHXWYQJXFQQ-UHFFFAOYSA-L 0.000 description 1
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- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 description 1
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- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
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- 125000004971 nitroalkyl group Chemical group 0.000 description 1
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- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000002097 pentamethylcyclopentadienyl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical class [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- 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
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/40—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals
- C07C15/50—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts substituted by unsaturated carbon radicals polycyclic non-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
- C07C2/86—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by condensation between a hydrocarbon and a non-hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
- C07C25/24—Halogenated aromatic hydrocarbons with unsaturated side chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/215—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring having unsaturation outside the six-membered aromatic rings
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Abstract
本发明属于有机合成的技术领域,尤其涉及一种内炔衍生物及其制备方法。本申请第一方面提供了一种内炔衍生物,所述内炔衍生物的结构式如式(Ⅰ)所示;其中,R1和R2独立的选自C1~C20的烃基、C5~C30的芳基或C5~C30的芳杂环基、或硅基如三异丙基硅基、二甲基叔丁基硅基、含环己基的氧硅醚。本发明的制备方法采用式(Ⅱ)常见易得的烷基醇衍生物与式(Ⅲ)化合物在碱性环境和氧化剂条件下,实现了基于烷基饱和碳‑碳的活化反应,以获得快速构建各种不同取代的内炔衍生物的高效方法。本发明的制备方法的底物简单易得,反应步骤少,操作简单,一锅法合成,能够实现多种内炔衍生物的高效合成。
Description
技术领域
本发明属于有机合成的技术领域,尤其涉及一种内炔衍生物及其制备方法。
背景技术
目前,饱和碳碳键在有机分子中无处不在;而对其转化具有重要的合成意义,其主要原因在于碳碳键的活化有望达到分子骨架的重组,为实现与传统合成方法完全不同的合成复杂分子提供新机遇。
然而,鉴于饱和碳碳键在热力学和动力学上的稳定性,其直接转化反应的进展主要依赖于张力环,而发展过渡金属催化的链状饱和碳碳键的活化仍具有极大挑战,其动力学原因在于:饱和碳碳键数量小于相应分子中碳氢键,且碳氢键活化与碳碳键活化往往是竞争反应;过渡金属催化剂难以靠近被大量碳氢键包裹的目标碳碳键;饱和碳碳键中的轨道导向性不利于碳碳键断裂。
现有的烷基醇的催化碳碳键活化制备内炔衍生物的反应主要集中于三级醇,难以使用一级醇衍生物或二级醇衍生物进行碳碳键活化反应,其主要原因是在金属催化下,烷氧基金属物种的竞争性β-H消除与β-C消除反应;且当使用一级醇、二级醇时,其β-H消除过程优于β-C消除步骤,从而更多的得到羰基化合物难以发生目标C-C键活化反应。
发明内容
有鉴于此,本申请提供了一种内炔衍生物及其制备方法,有效解决了现有技术中难以使用一级醇衍生物或二级醇衍生物进行催化碳碳键活化反应以制备内炔衍生物。
本申请第一方面提供了一种内炔衍生物,所述内炔衍生物的结构式如式(Ⅰ)所示;
优选的,所述式(Ⅰ)具体结构为:
需要说明的是,本申请提供的内炔衍生物的述官能团为氢、烷基(甲基、乙基、异丙基、叔丁基等)、烯烃、苯环、萘、杂芳环如呋喃、噻吩、吲哚、吡咯。
需要说明的是,本申请提供的内炔衍生物有望在含醇类天然产物后期修饰、新药和新型材料的开发、特别是利用饱和碳碳键的活化反应在聚合物(如塑料)的降解中具有良好的应用前景。
本申请第二方面提供了内炔衍生物的制备方法,包括以下步骤:
将式(Ⅱ)所示化合物和式(Ⅲ)所示化合物溶于惰性溶剂中,在氧化剂和金属催化剂的作用下,在碱性条件下进行反应,得到所述内炔衍生物衍生物;
优选的,所述金属催化剂选自醋酸钯、氯化钯、三氯化钌、二氯(对甲基异丙基苯基)钌(II)二聚体、二氯(五甲基环戊二烯基)合铑二聚体或三乙腈(五甲基环戊二烯基)二(六氟锑酸)合铑、二氯(五甲基环戊二烯基)合铱二聚体中的一种或多种。
更优选为醋酸钯。
优选的,调节所述碱性条件的碱选自自醋酸钠、醋酸铯、醋酸钾、碳酸钠、碳酸钠和磷酸钾中的一种或多种。
更优选为醋酸钠。
优选的,所述氧化剂选自醋酸银、碳酸银、三氟磺酸银、硝酸银、醋酸铜、卤化亚铜、卤化铜、三卤化铁和硝酸铁中的一种或多种。
更优选为醋酸银。
优选的,所述惰性溶剂选自甲苯、四氢呋喃、1,4-二氧六环、N,N’-二甲基甲酰胺、N,N’-二甲基乙酰胺、N-甲基吡咯烷酮、二甲亚砜、乙腈、1,2-二氯乙烷、乙醇和丙酮中的一种或多种。
更优选为1,2-二氯乙烷。
优选的,所述反应的温度为80℃~120℃;所述反应的时间为8h~36h。
更优选,所述反应的温度为100℃;所述反应的时间为8h~36h。
优选的,所述式(Ⅱ)所示化合物和式(Ⅲ)所示化合物的摩尔比为1:(1~4)。
更优选,所述式(Ⅱ)所示化合物和式(Ⅲ)所示化合物的摩尔比为1:3。
优选的,所述金属催化剂的用量为所述式(Ⅱ)所示化合物用量的1mol%~5mol%,更优选为2mol%。
优选的,碱的用量为式(Ⅱ)所示化合物用量的(5~50)mol%,更优选为15mol%;氧化剂的用量为式(Ⅱ)所示化合物用量的(10~300)mol%,更优选为30mol%。式(Ⅱ)所示化合物在惰性溶剂的浓度为0.1mol/L~3.0mol/L,优选为0.2mol/L。
本申请发现,在低级的烷基醇(例如一级醇衍生物或二级醇衍生物)分子中原位引入N-O键(形成肟醚衍生物),N-O键作为易转化的导向基协助金属催化剂中心与底物分子的靠近、作用,进而利用释放小分子(本申请中底物原位释放乙烯气体分子和硝基烷烃)作为更利于C-C活化过程的驱动力,从而得到金属有机物种,进而发生分子间偶联反应,得到目标低级的烷基醇(例如一级醇衍生物或二级醇衍生物)的高增值转化。本发明制备方法中,采用式(Ⅱ)的常见易得的烷基醇衍生物与式(Ⅲ)化合物在碱性环境和氧化剂条件下,通过金属催化剂(例如二价钯)的催化作用,实现了基于烷基饱和碳-碳的活化反应,以获得快速构建各种不同取代的内炔衍生物的高效方法,本申请通过碳碳键断裂来实现碳-碳键重组反应的新颖的合成方式;提供了催化的惰性烷基Csp3-Csp3键的活化、进而发生分子间交叉偶联的新思路。此外,本发明的制备方法的底物简单易得,反应步骤少,操作简单,一锅法合成,能够实现多种内炔衍生物的高效合成。同时本申请的化学转化具有良好的区域选择性和化学选择性。本发明制备方法对底物的适用范围非常广,其制备方法还具有良好的原子经济性。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1为本发明提供的内炔衍生物式(Ⅰ)的结构式;
图2为本发明实施例1提供的4-(辛-1-炔)-1-苯甲腈(1a)的核磁共振1H谱图;
图3为本发明实施例1提供的4-(辛-1-炔)-1-苯甲腈(1a)的核磁共振13C谱图;
图4为本发明实施例2提供的6-苯基-N-(喹啉-8-基)己-5-炔酰胺(1b)的核磁共振1H谱图;
图5为本发明实施例2提供的6-苯基-N-(喹啉-8-基)己-5-炔酰胺(1b)的核磁共振13C谱图;
图6为本发明实施例3提供的4-(苯乙炔)苯甲腈(1c)的核磁共振1H谱图;
图7为本发明实施例3提供的4-(苯乙炔)苯甲腈(1c)的核磁共振13C谱图;
图8为本发明实施例4提供的三异丙基(对甲基苯乙炔)硅(1d)的核磁共振1H谱图;
图9为本发明实施例4提供的三异丙基(对甲基苯乙炔)硅(1d)的核磁共振13C谱图;
图10为本发明实施例5提供的(E)-1-甲氧基-4-(4-苯丁基-3-烯-1-炔-1-基)苯(1e)的核磁共振1H谱图;
图11为本发明实施例5提供的(E)-1-甲氧基-4-(4-苯丁基-3-烯-1-炔-1-基)苯(1e)的核磁共振13C谱图;
图12为本发明实施例6提供的4-(苯乙炔基)-1,1′-联苯(1f)的核磁共振1H谱图;
图13为本发明实施例6提供的4-(苯乙炔基)-1,1′-联苯(1f)的核磁共振13C谱图;
图14为本发明实施例7提供的(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯(1g)的核磁共振1H谱图;
图15为本发明实施例7提供的(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯(1g)的核磁共振13C谱图;
图16为本发明实施例8提供的(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯(1h)的核磁共振1H谱图;
图17为本发明实施例8提供的(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯(1h)的核磁共振13C谱图。
具体实施方式
本发明提供了一种内炔衍生物及其制备方法,用于提供一种内炔衍生物及其制备方法,有效解决了现有技术中难以使用一级醇衍生物或二级醇衍生物进行催化碳碳键活化反应以制备内炔衍生物。
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,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。基于本发明中的实施例,本领域普通技术人员在没有做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。
其中,以下实施例所用原料均为市售或自制,下述实施例的肟醚类化合物2a、2b、2c、2d、2e、2f、2g为自制,具体参考文献(T.Kang,Y.Kim,D.Lee,Z.Wang,S.Chang,J.Am.Chem.Soc.2014,136,4141-4144;Guo K,Chen X,Guan M,et al.Direct ortho-C–HFunctionalization of Aromatic Alcohols Masked by Acetone Oxime Ether via exo-Palladacycle[J].Organic Letters,2015,17(7).);3a化合物、3b化合物、3c化合物、3d化合物、3e化合物、3f化合物为商业可得。
具体的,本申请实施例提供了内炔衍生物的具体制备方法,包括以下步骤:在空气氛围下,在反应器中依次加入式(Ⅱ)所示醇衍生物(18.3mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射式(III)所示炔烃化合物(54mg,0.3mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到式(Ⅰ)的内炔衍生物。
实施例1
本实施例提供了4-(辛-1-炔)-1-苯甲腈(1a),其制备方法如下:
4-(辛-1-炔)-1-苯甲腈(1a),其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2a(20.2mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3a(33mg,0.3mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到4-(辛-1-炔)-1-苯甲腈(1a),15.8mg,纯度为95%,产率为75%。
对4-(辛-1-炔)-1-苯甲腈(1a)进行核磁共振检测,请参阅图2至图3,结果为:1HNMR(400MHz,CDCl3)δ7.30(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),2.41(t,J=6.8Hz,2H),2.34(s,3H),1.60(t,J=7.6Hz,2H),1.49(dd,J=6.8Hz,3H),0.96(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3)δ137.4,131.4,128.9,121.1,89.6,80.6,65.3,30.9,30.4,22.0,21.4,19.1,13.6。
本实施例将醇的衍生物在过渡金属催化下实现烷基Csp3-Csp3的活化并进行后续的与末端炔的偶联反应,为以后的过渡金属催化的C-C键活化、偶联反应提供重要的理论和实验基础。
实施例2
本实施例提供了6-苯基-N-(喹啉-8-基)己-5-炔酰胺(1b),其制备方法如下:
1b全称为6-苯基-N-(喹啉-8-基)己-5-炔酰胺,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2a(17.7mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3b(47.6mg,0.2mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到6-苯基-N-(喹啉-8-基)己-5-炔酰胺(1b),21.0mg,纯度为95%,产率为67%。
对6-苯基-N-(喹啉-8-基)己-5-炔酰胺(1b)进行核磁共振检测,请参阅图4至图5,结果为:1H NMR(400MHz,CDCl3)δ9.89(brs,1H),8.79(dd,J=1.6Hz,7.2Hz,1H),8.74(dd,J=1.6Hz,4.0Hz,1H),8.13(dd,J=1.6Hz,8.0Hz,1H),7.54-7.47(m,2H),7.44-7.41(m,3H),7.29-7.25(m,3H),2.27(t,J=7.2Hz,2H),2.59(t,J=6.8Hz,2H),2.12(t,J=7.2Hz,1H).13C NMR(100MHz,CDCl3)δ206.9,171.1,148.1,128.2,127.7,127.4,123.8,121.6,121.5,116.4,89.0,81.7,36.8,30.9,24.4,18.9。
本实施例反应得到含酰胺基团的炔烃衍生物,为后续的进一步导向基协助的过渡金属催化的C-H键活化,来构建多官能团化的分子提供基础。
实施例3
本实施例提供了4-(苯乙炔)苯甲腈(1c),其制备方法如下:
1c全称为4-(苯乙炔)苯甲腈,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2a(20.2mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3c(20.4mg,0.2mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到4-(苯乙炔)苯甲腈(1c),13.2mg,纯度为95%,产率为65%。
对4-(苯乙炔)苯甲腈(1c)进行核磁共振检测,请参阅图6至图7,结果为:1H NMR(400MHz,CDCl3)δ9.60-7.55(m,6H),7.38-7.35(m,3H).13CNMR(100MHz,CDCl3)δ132.1,132.0,131.8,129.2,128.5,128.2,118.5,111.5,93.8,87.8。
实施例4
本实施例提供了三异丙基(对甲基苯乙炔)硅(1d),其制备方法如下:
1d全称为三异丙基(对甲基苯乙炔)硅,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2c(19.1mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3d(54mg,0.3mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到三异丙基(对甲基苯乙炔)硅(1d),19.3mg,纯度为95%,产率为71%。
对三异丙基(对甲基苯乙炔)硅(1d)进行核磁共振检测,请参阅图8至图9,结果为:1HNMR(400MHz,CDCl3)δ7.89(d,J=8.4Hz,2H),7.36(d,J=8.0Hz,2H),2.46(s,3H),1.03-1.02(m,21H).13C NMR(100MHz,CDCl3)δ145.2,139.2,129.9,127.3,100.8,100.1,21.8,18.3,10.9。
实施例5
本实施例提供了(E)-1-甲氧基-4-(4-苯丁基-3-烯-1-炔-1-基)苯(1e),其制备方法如下:
1e全称为(E)-1-甲氧基-4-(4-苯丁基-3-烯-1-炔-1-基)苯,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2d(19.1mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3e(41.8mg,0.2mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到炔烃化合物(1e),14.5mg,纯度为95%,产率为62%。
对(E)-1-甲氧基-4-(4-苯丁基-3-烯-1-炔-1-基)苯(1e)进行核磁共振检测,请参阅图10至图11,结果为:1H NMR(400MHz,CDCl3)δ7.34(d,J=7.6Hz,4H),7.27-7.17(m,3H),6.92(d,J=16.0Hz,1H),6.78(d,J=7.6Hz,2H),6.30(d,J=8.0Hz,1H),3.74(s,3H).13CNMR(100MHz,CDCl3)δ159.6,140.5,136.5,133.0,128.7,126.2,115.6,114.1,114.0,108.4,91.9,87.7,55.3。
实施例6
本实施例提供了4-(苯乙炔基)-1,1′-联苯(1f),其制备方法如下:
1f全称为4-(苯乙炔基)-1,1′-联苯,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2e(25.3mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3c(20.4mg,0.3mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到4-(苯乙炔基)-1,1′-联苯(1f),13.2mg,纯度为95%,产率为52%。
对4-(苯乙炔基)-1,1′-联苯(1f)进行核磁共振检测,请参阅图12至图13,结果为:1HNMR(400MHz,d6-DMSO)δ7.76-7.71(m,4H),7.65(d,J=8.0Hz,2H),7.60-7.57(m,2H),7.49(t,J=7.2Hz,2H),7.45-7.38(m,4H).13C NMR(100MHz,d6-DMSO)δ140.2,139.1,131.9,131.4,128.8,127.9,126.6,122.3,121.2,90.0,89.2。
实施例7
本实施例提供了(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯1g,其制备方法如下:
1g全称为(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯(1g),其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2f(18.5mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3f(28mg,0.2mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯(1g),14.1mg,纯度为95%,产率为69%。
对(E)-5-(4-氟苯基)戊-2-烯-4-炔酸甲酯(1g)进行核磁共振检测,请参阅图14至图15,结果为:1H NMR(400MHz,CDCl3)δ7.46-7.43(m,2H),7.02(t,J=8.4Hz,2H),6.95(d,J=12.0Hz,1H),6.28(d,J=8.0Hz,1H),3.76(s,3H).13C NMR(100MHz,CDCl3)δ166.3,163.1(d,J=5.0Hz),161.8,134.0(d,J=0.8Hz),129.6,125.1,118.3(d,J=0.4Hz),115.8(d,J=2.0Hz),97.3,86.1(d,J=0.2Hz),51.9。
实施例8
本实施例提供了(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯(1h),其制备方法如下:
1h全称为(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯,其反应式如下所示:
在空气氛围下,在反应器中依次加入醇衍生物2g(29.3mg,0.1mmol),醋酸钯(1.2mg)、醋酸钠(2.5mg)、醋酸银(11.7mg)、金刚烷甲酸(5.4mg),用注射器注射炔烃化合物3c(69.4mg,0.2mmol)的1,2-二氯乙烷(1.0mL)的溶液到反应器中置于100℃下反应12h,经薄层色谱分析确定反应结束,将反应液经硅藻土抽滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10克,展开剂为体积比为200:1至50:1的石油醚与乙酸乙酯,得到(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯(1h),16.7mg,纯度为95%,产率为57%。
对(E)-1,2,3,4,5-五氟-6-(4-苯丁基-1-烯-3-炔-1-基)苯(1h)进行核磁共振检测,请参阅图16至图17,结果为:1H NMR(400MHz,CDCl3)δ7.51–7.47(m,2H),7.37–7.34(m,3H),6.93(d,J=16.8Hz,1H),6.73(d,J=16.4Hz,1H);13C NMR(100MHz,CDCl3)δ143.0,132.5,131.7,128.9,128.5,124.98,124.96,122.7,117.34,117.27,107.5,95.1,88.2ppm。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (7)
2.根据权利要求1所述的制备方法,其特征在于,所述惰性溶剂选自甲苯、四氢呋喃、1,4-二氧六环、N,N’-二甲基甲酰胺、N,N’-二甲基乙酰胺、N-甲基吡咯烷酮、二甲亚砜、乙腈、1,2-二氯乙烷、乙醇和丙酮中的一种或多种。
3.根据权利要求1所述的制备方法,其特征在于,所述反应的温度为80℃~120℃;所述反应的时间为8h~36h。
4.根据权利要求1所述的制备方法,其特征在于,所述式(Ⅱ)所示化合物和式(Ⅲ)所示化合物的摩尔比为1:(1~4)。
5.根据权利要求1所述的制备方法,其特征在于,所述金属催化剂的用量为所述式(Ⅱ)所示化合物用量的1mol%~5mol%。
6.根据权利要求1所述的制备方法,其特征在于,所述碱的用量为式(Ⅱ)所示化合物用量的(5~50)mol%;所述氧化剂的用量为式(Ⅱ)所示化合物用量的(10~300)mol%;所述式(Ⅱ)所示化合物在惰性溶剂的浓度为0.1mol/L ~3.0mol/L。
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