CN111116285B - 一种高效的1-芳基-4-丁烯化合物的制备方法 - Google Patents
一种高效的1-芳基-4-丁烯化合物的制备方法 Download PDFInfo
- Publication number
- CN111116285B CN111116285B CN201911353267.8A CN201911353267A CN111116285B CN 111116285 B CN111116285 B CN 111116285B CN 201911353267 A CN201911353267 A CN 201911353267A CN 111116285 B CN111116285 B CN 111116285B
- Authority
- CN
- China
- Prior art keywords
- aryl
- aromatic hydrocarbon
- bis
- butene compound
- palladium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 26
- -1 methyl aromatic hydrocarbon Chemical class 0.000 claims abstract description 22
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims abstract description 16
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003446 ligand Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 5
- SBLSVQAUPIHUAM-UHFFFAOYSA-N 2,3-dimethylhept-6-ene-2,3-diol Chemical compound C(C=C)CC(O)(C)C(C)(C)O SBLSVQAUPIHUAM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- PRRIGGBFRPGBRY-UHFFFAOYSA-N (3-diphenylphosphanyl-1-naphthalen-1-ylnaphthalen-2-yl)-diphenylphosphane Chemical group C1=CC=CC=C1P(C=1C(=C(C=2C3=CC=CC=C3C=CC=2)C2=CC=CC=C2C=1)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 PRRIGGBFRPGBRY-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 2
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Chemical group 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 15
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- QGLVEAGMVUQOJP-UHFFFAOYSA-N prop-2-enylboronic acid Chemical compound OB(O)CC=C QGLVEAGMVUQOJP-UHFFFAOYSA-N 0.000 abstract description 10
- 239000012847 fine chemical Substances 0.000 abstract description 4
- 239000008204 material by function Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 238000001228 spectrum Methods 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- SEECMEVLHANLBS-UHFFFAOYSA-N 2-but-1-enylbenzonitrile Chemical compound CCC=CC1=CC=CC=C1C#N SEECMEVLHANLBS-UHFFFAOYSA-N 0.000 description 7
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- IAKDLHAKDXXZBW-UHFFFAOYSA-N 1-but-3-enyl-4-phenylbenzene Chemical group C1=CC(CCC=C)=CC=C1C1=CC=CC=C1 IAKDLHAKDXXZBW-UHFFFAOYSA-N 0.000 description 5
- NSXNRTMDNYHXGI-UHFFFAOYSA-N 1-but-3-enylnaphthalene Chemical compound C1=CC=C2C(CCC=C)=CC=CC2=C1 NSXNRTMDNYHXGI-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001308 synthesis method Methods 0.000 description 5
- GGGQLQPVNWFFQB-UHFFFAOYSA-N 1-but-1-enyl-2-ethylbenzene Chemical compound CCC=CC1=CC=CC=C1CC GGGQLQPVNWFFQB-UHFFFAOYSA-N 0.000 description 4
- FFWIWOGEFRVJIU-UHFFFAOYSA-N 1-but-1-enyl-2-methylbenzene Chemical compound CCC=CC1=CC=CC=C1C FFWIWOGEFRVJIU-UHFFFAOYSA-N 0.000 description 4
- NHCGITCVQSPLMS-UHFFFAOYSA-N 1-but-1-enyl-2-tert-butylbenzene Chemical compound CCC=CC1=CC=CC=C1C(C)(C)C NHCGITCVQSPLMS-UHFFFAOYSA-N 0.000 description 4
- HEZMLYMGYNMVNL-UHFFFAOYSA-N 1-but-3-enyl-3-methylnaphthalene Chemical compound CC1=CC2=CC=CC=C2C(=C1)CCC=C HEZMLYMGYNMVNL-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- NMWGVTREOAPDSN-UHFFFAOYSA-N methyl 4-but-3-enylbenzoate Chemical compound COC(=O)C1=CC=C(CCC=C)C=C1 NMWGVTREOAPDSN-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ODICZNLVJBYVOS-UHFFFAOYSA-N 1-(chloromethyl)-3-methylnaphthalene Chemical compound C1=CC=CC2=CC(C)=CC(CCl)=C21 ODICZNLVJBYVOS-UHFFFAOYSA-N 0.000 description 1
- DUBCVXSYZVTCOC-UHFFFAOYSA-N 1-(chloromethyl)-4-ethylbenzene Chemical compound CCC1=CC=C(CCl)C=C1 DUBCVXSYZVTCOC-UHFFFAOYSA-N 0.000 description 1
- DMHZDOTYAVHSEH-UHFFFAOYSA-N 1-(chloromethyl)-4-methylbenzene Chemical compound CC1=CC=C(CCl)C=C1 DMHZDOTYAVHSEH-UHFFFAOYSA-N 0.000 description 1
- HLQZCRVEEQKNMS-UHFFFAOYSA-N 1-(chloromethyl)-4-phenylbenzene Chemical group C1=CC(CCl)=CC=C1C1=CC=CC=C1 HLQZCRVEEQKNMS-UHFFFAOYSA-N 0.000 description 1
- XMWGTKZEDLCVIG-UHFFFAOYSA-N 1-(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1 XMWGTKZEDLCVIG-UHFFFAOYSA-N 0.000 description 1
- GFAULJSTUQLMCX-UHFFFAOYSA-N 1-but-3-enyl-2-methylnaphthalene Chemical compound C1=CC=CC2=C(CCC=C)C(C)=CC=C21 GFAULJSTUQLMCX-UHFFFAOYSA-N 0.000 description 1
- WAXIFMGAKWIFDQ-UHFFFAOYSA-N 1-tert-butyl-4-(chloromethyl)benzene Chemical compound CC(C)(C)C1=CC=C(CCl)C=C1 WAXIFMGAKWIFDQ-UHFFFAOYSA-N 0.000 description 1
- ZSHNOXOGXHXLAV-UHFFFAOYSA-N 2-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=CC=C1C#N ZSHNOXOGXHXLAV-UHFFFAOYSA-N 0.000 description 1
- LOQLDQJTSMKBJU-UHFFFAOYSA-N 4-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=C(C#N)C=C1 LOQLDQJTSMKBJU-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- UXRZLDREKITWRO-UHFFFAOYSA-N P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 Chemical compound P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 UXRZLDREKITWRO-UHFFFAOYSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229960001880 fosinopril sodium Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- AAHZCIWUDPKSJP-UHFFFAOYSA-N methyl 2-(chloromethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CCl AAHZCIWUDPKSJP-UHFFFAOYSA-N 0.000 description 1
- HTXZNZFHYKYBRH-UHFFFAOYSA-N methyl 4-butan-2-ylbenzoate Chemical compound CCC(C)C1=CC=C(C(=O)OC)C=C1 HTXZNZFHYKYBRH-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- TVTJZMHAIQQZTL-WATAJHSMSA-M sodium;(2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylate Chemical compound [Na+].C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C([O-])=O)CCCC1=CC=CC=C1 TVTJZMHAIQQZTL-WATAJHSMSA-M 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
-
- 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
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- C07C2531/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- C07C2531/22—Organic complexes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于精细化学品及相关化学技术领域,提供了一种高效的1‑芳基‑4‑丁烯化合物的制备方法。以含卤甲基芳烃及其衍生物为原料,在钯催化剂及配体的存在,以氟化铯作为碱,在无水有机溶剂条件下,与烯丙基硼酸频那醇酯在80℃~100℃下反应12小时,即可得到1‑芳基‑4‑丁烯化合物。本发明的有益效果是选择性高、反应条件温和、操作简便、有实现工业化的可能性,并且以较高收率得到1‑芳基‑4‑丁烯化合物;利用该方法所合成的1‑芳基‑4‑丁烯化合物可以进一步官能化得到各类化合物,应用于天然产物、功能材料及精细化学品的开发与研究。
Description
技术领域
本发明属于精细化学品及相关化学技术领域,提供了一种高效的1-芳基-4- 丁烯化合物的制备方法。
背景技术
1-芳基-4-丁烯化合物在有机化学中是一类极其重要的结构单元,其在医药、农药、染料、香料和功能材料等领域[Macromolecules2011,44,4167-4179]都有着很重要的应用价值。其中,1-苯基-4-丁烯作为核心原料,用于降压药福辛普利钠的合成。
已经报道的合成1-芳基-4-丁烯化合物的合成方法包括格式反应法[Org.Lett.2014,16,1610-1613],电催化烷基化法[Org.Lett.2017,19,2022-2025],炔烃还原法[Chem.Lett.2011,40,405-407]等。
格式反应法是最为普遍的合成方法,即先将含有烯丙基的原料与镁反应,得到格式试剂,格式试剂再与苄基卤代物发生亲核取代反应得到所需产物。不过格式试剂具有极强的亲核性,能够与氰基、硝基、羰基、酯基等敏感性官能团发生反应,使得该合成方法具有局限性,不利于药物的开发。
电催化烷基化法是使用钯催化剂在水溶液中电催化底物与含烯丙基的卤化物发生烷基化反应,该方法需要金属介导。这种方法具有耗能大、反应昂贵、重复性不高等缺点。
炔烃还原法是将含有炔烃的芳基化合物在金属催化下与氢气反应。这种方法由于大量使用氢气且压强较大,存在反应条件比较严苛且容易发生危险等缺点,且这种方法存在过度还原的风险。
近年来,钯金属催化的烯丙基偶联反应因其反应条件比较温和,反应选择性好,反应转化率高等优点逐渐受到人们的广泛关注。2017年报道了钯催化使用烯丙基硼酸频那醇酯作为底物的制备烯丙基芳基化合物的方法[Adv.Synth. Catal.2017,359,2723-2728]。该合成方法只能得到芳烃烯丙基化的产物,而涉及过渡金属钯催化的卤甲基芳香化合物与烯丙基硼化合物的直接偶联反应制备1- 芳基-4-丁烯化合物的合成方法还未见报道。
发明内容
本发明提供了一种1-芳基-4-丁烯化合物的新颖制备方法,该合成方法选择性高、反应条件温和、操作简便,并且收率较高。
本发明的技术方案:
一种高效的1-芳基-4-丁烯化合物的制备方法,以含卤甲基芳烃及其衍生物为原料,在钯催化剂及配体的存在条件下,以氟化铯作为碱,在无水有机溶剂中,与烯丙基硼酸频那醇酯在80℃~100℃下反应12小时,即得到1-芳基-4-丁烯化合物,合成路线如下:
R1选自氢、烷基、酯基、氰基、羰基、烷氧基、卤素和苯基;R1位于卤甲基芳烃的邻位、间位或对位;
X选自氯和溴;
R2、R3、R4选自氢、烷基和芳基,三者相同或不同;
含卤甲基芳烃及其衍生物与钯催化剂的摩尔比为1:0.05~1:0.1;
含卤甲基芳烃及其衍生物与烯丙基硼酸频那醇酯的摩尔比为1:2~1:5;
含卤甲基芳烃及其衍生物与氟化铯的摩尔比为1:3~1:20;
钯催化剂与配体的摩尔比为1:2~1:4;
含卤甲基芳烃及其衍生物的摩尔浓度为0.01mmol/mL~2mmol/mL。
所述的溶剂为四氢呋喃、1,2-二氯乙烷、1,4-二氧六环或氯苯。优选四氢呋喃或1,2-二氯乙烷。
所述的钯催化剂为醋酸钯、二(三苯基磷)二氯化钯、(1,5-环辛二烯)二氯化钯、[1,1'-双(二苯基膦基)二茂铁]二氯化钯中的一种或两种以上混合,优选醋酸钯或二(三苯基磷)二氯化钯。
所述的配体为4,5-双(二苯基膦)-9,9-二甲基氧杂蒽、双-(二苯膦基)-1,1'-联萘或双(2-二苯基磷苯基)醚。优选4,5-双(二苯基膦)-9,9-二甲基氧杂蒽。
分离方法包括重结晶、柱层析等。
重结晶方法使用的溶剂包括苯、乙醇、甲苯、四氢呋喃、氯仿、正己烷、丙酮、乙酸乙酯、二氯甲烷。
用柱层析方法进行产物分离时,可以使用硅胶或氧化铝作为固定相,展开剂一般为极性与非极性的混合溶剂,如乙酸乙酯-石油醚、乙酸乙酯-正己烷、二氯甲烷-石油醚、甲醇-石油醚。
本发明的有益效果是选择性高、反应条件温和、操作简便,并且收率较高;利用该方法所合成的1-芳基-4-丁烯化合物可以进一步官能化得到各类化合物,应用于天然产物、功能材料及精细化学品的开发与研究。
附图说明
图1是实施例1中对甲基-3-丁烯基苯的1H核磁谱图。
图2是实施例1中对甲基-3-丁烯基苯的13C核磁谱图。
图3是实施例2中对乙基-3-丁烯基苯的1H核磁谱图。
图4是实施例2中对乙基-3-丁烯基苯的13C核磁谱图。
图5是实施例3中对叔丁基-3-丁烯基苯的1H核磁谱图。
图6是实施例3中对叔丁基-3-丁烯基苯的13C核磁谱图。
图7是实施例4中4-(3-丁烯基)联苯的1H核磁谱图。
图8是实施例4中4-(3-丁烯基)联苯的13C核磁谱图。
图9是实施例5中邻氰基-3-丁烯基苯的1H核磁谱图。
图10是实施例5中邻氰基-3-丁烯基苯的13C核磁谱图。
图11是实施例6中对-3-丁烯基苯甲酸甲酯的1H核磁谱图。
图12是实施例6中对-3-丁烯基苯甲酸甲酯的13C核磁谱图。
图13是实施例7中的对氰基-3-丁烯基苯1H核磁谱图。
图14是实施例7中的对氰基-3-丁烯基苯13C核磁谱图。
图15是实施例8中1-(3-丁烯基)萘的1H核磁谱图。
图16是实施例8中1-(3-丁烯基)萘的13C核磁谱图。
图17是实施例9中1-(3-丁烯基)-3-甲基萘的1H核磁谱图。
图18是实施例9中1-(3-丁烯基)-3-甲基萘的13C核磁谱图。
具体实施方式
本发明所述的1-芳基-4-丁烯化合物的制备方法,具有原料价格低廉、反应步骤少、反应条件温和、便于操作和反应收率高等优点。
下面结合具体实施例,进一步阐述本发明。这些实施例仅用于说明本发明而不用于限制本发明的范围。在本领域内的技术人员对本发明所做的简单替换或改进均属于本发明所保护的技术方案之内。
实施例1:对甲基-3-丁烯基苯的合成
在25mL反应器中,加入4-甲基苄氯(0.028g,0.2mmol),烯丙基硼酸频那醇酯(0.067g,0.4mmol),醋酸钯(2.2mg,0.01mmol),氟化铯(0.091g, 0.6mmol),4,5-双二苯基膦-9,9-二甲基氧杂蒽(8.7mg,0.015mmol),80℃、氮气条件下搅拌12h。柱层析分离(硅胶,200-300目;展开剂,石油醚)得到对甲基-3-丁烯基苯0.023g,产率83%。
无色油状液体;1H NMR(400MHz,CDCl3):δ7.09(s,4H),5.92–5.80(m,1H),5.08 –4.94(m,2H),2.67(t,J=8.0Hz,2H),2.36(q,J=8.0Hz,2H),2.32(s,3H);13C NMR (100MHz,CDCl3):δ139.8,138.2,135.2,128.9,128.3,114.8,35.6,34.9,21.0.
实施例2:对乙基-3-丁烯基苯的合成
操作同实施例1,由4-乙基苄氯与烯丙基硼酸频那醇酯反应得到对乙基-3- 丁烯基苯0.024g,产率79%。
无色油状液体;1H NMR(400MHz,CDCl3):δ7.11(s,4H),5.92–5.90(m,1H),5.09 –4.95(m,2H),2.68(t,J=8.0Hz,2H),2.62(q,J=8.0Hz,2H),2.36(q,J=8.0Hz, 2H),1.22(t,J=8.0Hz,3H);13C NMR(100MHz,CDCl3):δ141.7,139.1,138.3, 128.4,127.8,114.8,35.6,34.9,28.5,15.7.
实施例3:对叔丁基-3-丁烯基苯的合成
操作同实施例1,由4-叔丁基苄氯与烯丙基硼酸频那醇酯反应得到对叔丁基 -3-丁烯基苯0.030g,产率82%。
无色油状液体;1H NMR(400MHz,CDCl3):δ7.35(d,J=8.0Hz,2H),7.18(d,J=8.0Hz,2H),5.98–5.96(m,1H),5.14–4.99(m,2H),2.76–2.69(t,J=8.0Hz,2H), 2.44–2.39(m,2H),1.36(s,9H);13C NMR(100MHz,CDCl3):δ148.6,138.8,138.3, 128.1,125.2,114.8,35.5,34.8,34.4,31.4.
实施例4:4-(3-丁烯基)联苯的合成
操作同实施例1,由4-氯甲基联苯与烯丙基硼酸频那醇酯反应得到4-(3-丁烯基)联苯0.032g,产率76%。
无色油状液体;1H NMR(400MHz,CDCl3):δ7.58(d,J=7.3Hz,2H),7.51(d,J=8.1Hz,2H),7.42(t,J=7.6Hz,2H),7.32(t,J=7.3Hz,1H),7.26(d,J=8.0Hz, 2H),5.94–5.84(m,1H),5.09–4.99(m,2H),2.77–2.73(t,J=8.0Hz,2H),2.44–2.38 (m,2H);13C NMR(100MHz,CDCl3):δ141.1,141.0,138.8,138.1,128.9,128.7, 127.1,127.0,115.1,35.5,35.0.
实施例5:邻氰基-3-丁烯基苯的合成
在25mL反应器中,加入2-氰基苄氯(0.031g,0.2mmol),烯丙基硼酸频那醇酯(0.067g,0.4mmol),醋酸钯(2.2mg,0.01mmol),氟化铯(0.091g,0.6 mmol),4,5-双二苯基膦-9,9-二甲基氧杂蒽(8.7mg,0.015mmol),80℃、氮气条件下搅拌12h。柱层析分离(硅胶,200-300目;展开剂,石油醚:乙酸乙酯=10:1)得到邻氰基-3-丁烯基苯0.023g,产率72%。
黄色油状液体;1H NMR(400MHz,CDCl3):δ7.63(d,J=7.7Hz,1H),7.53(t,J=7.2Hz,1H),7.36–7.28(m,2H),5.93–5.81(m,1H),5.10–4.99(m,2H),2.97(t,J=4.0Hz,2H),2.46(q,J=7.5Hz,2H);13C NMR(100MHz,CDCl3):δ145.6,136.7, 132.8,132.6,129.6,126.5,118.1,115.9,112.4,34.7,33.9.
实施例6:对-3-丁烯基苯甲酸甲酯的合成
操作同实施例5,由邻氯甲基苯甲酸甲酯与烯丙基硼酸频那醇酯反应得到对 -3-丁烯基苯甲酸甲酯0.027g,产率70%。
黄色油状液体;1H NMR(400MHz,CDCl3):δ7.95(d,J=7.5Hz,2H),7.25(d,J=7.7Hz,2H),5.89–5.76(m,1H),5.07–4.96(m,2H),3.90(s,3H),2.76(t,J=7.7Hz, 2H),2.38(q,J=7.1,6.4Hz,2H);13C NMR(100MHz,CDCl3):δ167.1,147.3,137.4, 129.6,128.9,127.8,115.3,51.9,35.3,35.0.
实施例7:对氰基-3-丁烯基苯的合成
操作同实施例5,由对氰基苄氯与烯丙基硼酸频那醇酯反应得到对氰基-3- 丁烯基0.026g,产率70%。
黄色油状液体;1H NMR(400MHz,CDCl3):δ7.57(d,J=7.7Hz,2H),7.28(d,J=7.6Hz,2H),5.97–5.75(m,1H),5.07–4.97(m,2H),2.77(t,J=7.6Hz,2H),2.38(q, J=7.2Hz,2H);13C NMR(100MHz,CDCl3):δ147.4,136.9,132.1,129.2,119.1, 115.7,109.7,35.4,34.8.
实施例8:1-(3-丁烯基)萘的合成
在25mL反应器中,加入1-氯甲基萘(0.035g,0.2mmol),烯丙基硼酸频那醇酯(0.067g,0.4mmol),二(三苯基膦)二氯化钯(7.1mg,0.01mmol),氟化铯(0.091g,0.6mmol),4,5-双二苯基膦-9,9-二甲基氧杂蒽(8.7mg,0.015 mmol),100℃、氮气条件下搅拌12h。柱层析分离(硅胶,200-300目;展开剂,石油醚)得到1-(3-丁烯基)萘0.026g,产率67%。
无色油状液体;1H NMR(600MHz,CDCl3):δ8.04(s,1H),7.85(s,1H),7.71(s,1H),7.49(d,J=18.5Hz,2H),7.42–7.37(m,1H),7.33(s,1H),6.00–5.90(m,1H),5.06 (dd,J=47.3,13.0Hz,2H),3.16(s,2H),2.51(s,2H);13C NMR(150MHz,CDCl3): δ138.2,137.9,128.8,126.6,125.9,125.8,125.5,125.4,123.77,114.9,34.8,32.5.
实施例9:1-(3-丁烯基)-3-甲基萘的合成
操作同实施例8,由3-甲基-1-氯甲基萘与烯丙基硼酸频那醇酯反应得到1-(3- 丁烯基)-2-甲基萘0.026g,产率65%。
无色油状液体;1H NMR(400MHz,CDCl3):δ8.05–7.99(m,1H),7.82–7.78(m,2H),7.54–7.50(m,1H),7.50–7.44(m,2H),7.22(d,J=1.7Hz,1H),6.05–5.94(m,1H), 5.18–5.04(m,2H),3.22–3.11(m,2H),2.54(d,J=11.6Hz,5H);13C NMR(100 MHz,CDCl3):δ138.3,137.7,135.0,134.2,130.0,128.3,128.1,125.5,125.4,124.8, 123.5,114.8,34.9,32.4,21.6。
Claims (2)
1.一种1-芳基-4-丁烯化合物的制备方法,其特征在于,以含卤甲基芳烃及其衍生物为原料,在钯催化剂及配体的存在条件下,以氟化铯作为碱,在无水有机溶剂中,与烯丙基硼酸频那醇酯在80℃~100℃下反应12小时,即得到1-芳基-4-丁烯化合物,合成路线如下:
R1选自氢、烷基、酯基、氰基、羰基、烷氧基、卤素和苯基;R1位于卤甲基芳烃的邻位、间位或对位;
X选自氯和溴;
R2、R3、R4选自氢、烷基和芳基,三者相同或不同;
含卤甲基芳烃及其衍生物与钯催化剂的摩尔比为1:0.05~1:0.1;
含卤甲基芳烃及其衍生物与烯丙基硼酸频那醇酯的摩尔比为1:2~1:5;
含卤甲基芳烃及其衍生物与氟化铯的摩尔比为1:3~1:20;
钯催化剂与配体的摩尔比为1:2~1:4;
含卤甲基芳烃及其衍生物的摩尔浓度为0.01mmol/mL~2mmol/mL;溶剂为四氢呋喃、1,2-二氯乙烷、1,4-二氧六环或氯苯;
配体为4,5-双(二苯基膦)-9,9-二甲基氧杂蒽、双-(二苯膦基)-1,1'-联萘或双(2-二苯基磷苯基)醚。
2.根据权利要求1所述的制备方法,其特征在于,所述的钯催化剂为醋酸钯、二(三苯基磷)二氯化钯、(1,5-环辛二烯)二氯化钯、[1,1'-双(二苯基膦基)二茂铁]二氯化钯中的一种或两种以上混合。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911353267.8A CN111116285B (zh) | 2019-12-25 | 2019-12-25 | 一种高效的1-芳基-4-丁烯化合物的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911353267.8A CN111116285B (zh) | 2019-12-25 | 2019-12-25 | 一种高效的1-芳基-4-丁烯化合物的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111116285A CN111116285A (zh) | 2020-05-08 |
CN111116285B true CN111116285B (zh) | 2021-05-07 |
Family
ID=70502472
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911353267.8A Active CN111116285B (zh) | 2019-12-25 | 2019-12-25 | 一种高效的1-芳基-4-丁烯化合物的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111116285B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114316334B (zh) * | 2021-12-09 | 2023-02-28 | 西安理工大学 | 大空间位阻侧链型聚烯烃基阴离子交换膜的制备方法 |
CN118666617A (zh) * | 2023-03-14 | 2024-09-20 | 浙江九洲药业股份有限公司 | 一种钯催化苯甲酸的衍生物间位碳氢烯烃化的方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105732253A (zh) * | 2016-01-26 | 2016-07-06 | 大连理工大学 | 一种烯丙基芳香化合物的制备方法 |
CN109879899A (zh) * | 2019-02-22 | 2019-06-14 | 华侨大学 | 一种反式三取代烯烃衍生物的制备方法 |
-
2019
- 2019-12-25 CN CN201911353267.8A patent/CN111116285B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105732253A (zh) * | 2016-01-26 | 2016-07-06 | 大连理工大学 | 一种烯丙基芳香化合物的制备方法 |
CN109879899A (zh) * | 2019-02-22 | 2019-06-14 | 华侨大学 | 一种反式三取代烯烃衍生物的制备方法 |
Non-Patent Citations (3)
Title |
---|
Introduction of Allyl and Prenyl Side-Chains into Aromatic Systems by Suzuki Cross-Coupling Reactions;Darío C. Gerbino 等;《Eur. J. Org. Chem.》;20090706;3964–3972 * |
Manganese-Catalyzed Cross-Coupling of Aryl Halides and Grignard Reagents by a Radical Mechanism;Giuseppe Antonacci 等;《Eur. J. Org. Chem.》;20171231;4758–4764 * |
Palladium-Catalyzed Regioselective Allylation of Chloromethyl(hetero)arenes with Allyl Pinacolborate;Sheng Zhang 等;《Adv. Synth. Catal.》;20170519;第359卷;2723-2728 * |
Also Published As
Publication number | Publication date |
---|---|
CN111116285A (zh) | 2020-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Marcoux et al. | Nickel‐catalyzed synthesis of phosphonium salts from aryl halides and triphenylphosphine | |
JP2004505091A (ja) | アダマンチル基を有するホスファンリガンド、その製造および接触反応におけるその使用 | |
CN111116285B (zh) | 一种高效的1-芳基-4-丁烯化合物的制备方法 | |
JPH04501418A (ja) | ビアリール化合物の製造 | |
CN104098607B (zh) | 含三环己基膦的单膦单氮杂环卡宾镍(ii)配合物及其应用 | |
CN110423217B (zh) | 一种共轭烯炔化合物的制备方法 | |
CN107973812A (zh) | 一种制备芳基硼酸新戊二醇酯类化合物的方法 | |
Aydemir et al. | Synthesis and characterizations of N, N′‐bis (diphenylphosphino)‐2‐(aminomethyl) aniline derivatives: application of a palladium (II) complex as pre‐catalyst in Heck and Suzuki cross‐coupling reactions | |
CN113979897A (zh) | 一种γ-芳基烯丙基磺酰氟化合物及其制备方法与应用 | |
CN101195641A (zh) | 新颖的膦配体、它们的制备和它们在催化反应中的用途 | |
Huo et al. | Highly Efficient Bulky α‐Diimine Palladium Complexes for Suzuki‐Miyaura Cross‐Coupling Reaction | |
CN112574244B (zh) | 一种1-苯基乙烯基硼酸酯的合成方法 | |
Correa-Ayala et al. | Dipalladium (I) complexes of ortho-and para-functionalized 1, 3-bis (aryl) triazenide ligands: Synthesis, structure and catalytic activity | |
Yu et al. | Synthesis and application of novel ionic phosphine ligands with a cobaltocenium backbone | |
CN110483571B (zh) | (1-(取代苯基)苊烯基)-二(3,5-二(三氟甲基))苯基膦化合物及其制备方法 | |
CN114085242A (zh) | 一种铁催化烷基内炔化合物的合成方法 | |
CN112299937B (zh) | 一种高效的对称二芳基乙烯化合物的制备方法 | |
CN104610002B (zh) | 一种芳香肼合成对称性联苯的方法 | |
JP5568976B2 (ja) | 多置換ホスフィン化合物及び該ホスフィン化合物を含む触媒 | |
CN114832862B (zh) | 一种偶联反应的催化组合物及其在制备异喹啉-1,3-二酮类化合物中的应用 | |
CN113801015B (zh) | 一种利用二氧化碳合成芳香羧酸化合物的方法 | |
CN114773229B (zh) | 一种1,6二烯类化合物及其制备方法与应用 | |
CN110002986B (zh) | 一种水相中分子氧氧化合成芴酮类化合物的方法 | |
CN110003062B (zh) | 一种n-苯基-n-对甲苯磺酰基二氟乙酰胺及应用 | |
CN117865773A (zh) | 一种基于钯催化脱羰偶联的二氟甲基芳烃化合物制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |