CN107445835A - 一种1,2‑二氢环丁烯并[a]萘衍生物及其前体的合成方法 - Google Patents
一种1,2‑二氢环丁烯并[a]萘衍生物及其前体的合成方法 Download PDFInfo
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- 239000002243 precursor Substances 0.000 title abstract description 6
- 150000002790 naphthalenes Chemical class 0.000 title abstract description 5
- 150000001930 cyclobutanes Chemical class 0.000 title abstract 3
- 238000010189 synthetic method Methods 0.000 title abstract 3
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 32
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 229930192474 thiophene Natural products 0.000 claims description 16
- -1 tetrafluoroborate Chemical compound 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical group I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- IIFFFBSAXDNJHX-UHFFFAOYSA-N 2-methyl-n,n-bis(2-methylpropyl)propan-1-amine Chemical compound CC(C)CN(CC(C)C)CC(C)C IIFFFBSAXDNJHX-UHFFFAOYSA-N 0.000 claims description 4
- DORMTBIPKNPJPY-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.IC1=CC=CC=C1 DORMTBIPKNPJPY-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229940043279 diisopropylamine Drugs 0.000 claims description 4
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 4
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-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 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 claims description 3
- FIYYMXYOBLWYQO-UHFFFAOYSA-N ortho-iodylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I(=O)=O FIYYMXYOBLWYQO-UHFFFAOYSA-N 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
- PCRAJOWHMTYSKR-UHFFFAOYSA-N iodobenzene;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.IC1=CC=CC=C1 PCRAJOWHMTYSKR-UHFFFAOYSA-N 0.000 claims description 2
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 abstract description 16
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- AOWPVIWVMWUSBD-RNFRBKRXSA-N [(3r)-3-hydroxybutyl] (3r)-3-hydroxybutanoate Chemical compound C[C@@H](O)CCOC(=O)C[C@@H](C)O AOWPVIWVMWUSBD-RNFRBKRXSA-N 0.000 abstract 3
- 239000000126 substance Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000197 pyrolysis Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 2
- QIMMUPPBPVKWKM-UHFFFAOYSA-N 2-methylnaphthalene Chemical compound C1=CC=CC2=CC(C)=CC=C21 QIMMUPPBPVKWKM-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NXZJVSTVFDJMLY-UHFFFAOYSA-N benzaldehyde;ethynylbenzene Chemical compound C#CC1=CC=CC=C1.O=CC1=CC=CC=C1 NXZJVSTVFDJMLY-UHFFFAOYSA-N 0.000 description 2
- RYJXPRUXQSAMQE-UHFFFAOYSA-N buta-1,2,3-trien-1-one Chemical compound C=C=C=C=O RYJXPRUXQSAMQE-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N vinyl-ethylene Natural products C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- FCZFPMKLLXTSNP-UHFFFAOYSA-N CCOC(C=N)=O Chemical compound CCOC(C=N)=O FCZFPMKLLXTSNP-UHFFFAOYSA-N 0.000 description 1
- SVVQOWJQNHYENN-UHFFFAOYSA-M O1CCCC1.[Br-].C(#C)[Mg+] Chemical compound O1CCCC1.[Br-].C(#C)[Mg+] SVVQOWJQNHYENN-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007265 chloromethylation reaction Methods 0.000 description 1
- CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- IFPHDUVGLXEIOQ-UHFFFAOYSA-N ortho-iodosylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I=O IFPHDUVGLXEIOQ-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical compound [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- 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
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- 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
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及有机合成化学领域,具体涉及一种—1,2‑二氢环丁烯并[a]萘衍生物及其前体的合成方法。本发明提供了一种联烯炔酮酯的合成方法,该方法首次合成苯环连接的联烯炔酮酯,联烯炔酮酯是合成1,2‑二氢环丁烯并[a]萘的前体,具有简便,高效,反应条件温和,绿色环保,低成本低能耗等优点。
Description
技术领域
本发明涉及有机合成化学领域,具体涉及一种—1,2-二氢环丁烯并[a]萘衍生物及其前体的合成方法。
背景技术
1,2-二氢环丁烯并[a]萘在医药、农药中具有重要的应用。萘衍生物在杀虫剂中具有显著的特性,若在稠合上环丁烯具有潜在的生物活性。该方发成功稳定环丁烯结构,为新药的发展创造了可筛选的化合物库。
CN 103626621专利名称为1,2-二氢环丁烯并[a]萘合成新方法,该方法通过2-甲基萘氯甲基化,热解关环等步骤合成1,2-二氢环丁烯并[a]萘,其步骤过于复杂繁琐,原料中使用盐酸对设备腐蚀性较强。反应高温裂解温度高达700-800℃,温度太高实施性低且危险系数大。且热解过程中产生废酸(盐酸)腐蚀性较强。
目前,合成1,2-二氢环丁烯并[a]萘的方法较少且条件严格,后处理繁琐,底物范围窄。需要一种适宜工业应用的生产方法。
发明内容:
本发明旨在解决上述问题,提供一种利于工业应用的生产方法。
本发明提供了一种合成炔酮联烯酯的方法,可高效定向构筑1,2-二氢环丁烯并[a]萘骨架。
本发明的技术方案为:
本发明提供一种制备式2化合物的方法,其特征在于,该方法在有机溶
剂中,碱和氧化剂存在下,氮气条件下,将式1化合物与苯亚磺酸钠和N-碘
代丁二酰亚胺、反应制备式2化合物,反应式如下:
其中,
R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;;
R3为C1-C5烷基。
进一步的,上述制备式2化合物的反应中,所述的碱为三乙胺、二异丙胺、三异丁胺、三正丁胺、DBU;有机溶剂选自乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇中的一种或几种;氧化剂为醋酸碘苯,叔丁基过氧化氢、二叔丁基过氧化物、叔丁基过氧苯甲酸酯、三氟乙酸碘苯中的一种或几种。
进一步的,所述的式1化合物是由式3化合物制备得到,是在有机溶剂中,式3化合物与2-碘酰基苯甲酸制备式1化合物,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;
所述的有机溶剂为乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇中的一种或几种。
进一步的,所述的式3化合物是由式4化合物制备得到,是在有机溶剂中,碱、催化剂存在下,式4化合物与重氮乙酸乙酯反应,制备式3化合物,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
进一步的,所述的式3化合物的制备方法中,所述的催化剂为碘化亚铜、氯化亚铜、溴化亚酮、氰化亚铜、醋酸亚铜、三氟甲基磺酸亚铜、四氟硼酸亚铜、六氟磷酸四(乙腈)合亚铜;有机溶剂为乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇;碱为三乙胺、二异丙胺、三异丁胺、三正丁胺、DBU。
进一步的,所述的式4化合物是由式5化合物制备得到,是将式5化合物溶于有机溶剂,-10℃~0℃条件下,加入乙炔基溴化镁有机溶剂,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
进一步的,所述的式4化合物的制备方法中,所述的有机溶剂为四氢呋喃。
进一步的,所述的式5化合物是由式6化合物与式7化合物制备得到,是在有机溶剂中,催化剂存在下,氮气条件下,反应温度为40~80℃反应制备得到,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
进一步的,上述式5化合物的制备方法中,所述的催化剂为碘化亚铜、双(三苯基膦)二氯化钯;有机溶剂为三乙胺,反应温度优选为60~70℃。
另一方面,本发明提供了式2化合物、式3化合物、式1化合物:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;
R3为C1-C5烷基;
进一步的,所述的R1为H、OMe、Me、Cl;R2为H、OMe、Me、Cl、Br、Et、t-Bu、噻吩;R3为甲基、乙基、丙基。
进一步的,在上述制备方法中,所述的R1为H、OMe、Me、Cl;R2为H、OMe、Me、Cl、Br、Et、t-Bu、噻吩;R3为甲基、乙基、丙基。
发明详述:
炔酮联烯酯和1,2-二氢环丁烯并[a]萘衍生物的合成及提纯方法
邻溴苯甲醛与苯乙炔用双(三苯基膦)二氯化钯碘化亚铜作催化剂三乙胺作溶剂氮气条件下60℃反应得到2-苯乙炔基苯甲醛。
将2-苯乙炔基苯甲醛溶于无水四氢呋喃,0℃缓慢加入乙炔基溴化镁四氢呋喃溶液(0.5mol/L)室温搅拌2h。用饱和氯化铵溶液淬灭,乙酸乙酯萃取,无水硫酸镁干燥,浓缩得到1,6-二炔醇。
1,6-二炔醇和重氮乙酸乙酯在碘化亚铜催化下,乙腈作溶剂,三乙胺作碱,室温反应后,抽滤,滤液通过硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=10:1,得到1,7-联烯炔醇。
炔醇联烯酯,2-碘酰基苯甲酸和乙腈作溶剂瓶80℃反应后,抽滤除去固体。滤液用硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=5:1。得到炔酮联烯酯。
用炔酮联烯酯,苯亚磺酸钠和N-碘代丁二酰亚胺醋酸碘苯做氧化剂三乙胺做碱乙腈作溶剂氮气条件下,室温反应1小时可得到多取代1,2-二氢环丁烯并[a]萘的衍生物。
有益效果:
该方法首次合成苯环连接的联烯炔酮酯,联烯炔酮酯是合成1,2-二氢环丁烯并[a]萘的前体,具有简便,高效,反应条件温和,绿色环保,低成本低能耗等优点。
实施例1:
以1a为例(其他取代基条件相同):
邻溴苯甲醛(9.3g 50mmol),苯乙炔(5.355g 52.5mmol)和三乙胺200ml在氮气条件下注入500ml史莱克管,其次向体系中加入双三苯基膦二氯化钯(0.702g1mmol)和碘化亚铜(0.190g 1mmol),60℃搅拌4h,通过硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=50:1,得到2-苯炔基苯甲醛(10.094g 98%)。
2-苯炔基苯甲醛(10.094g 49mmol)和无水四氢呋喃50ml加入到500ml圆底烧瓶0℃搅拌,缓慢加入乙炔基溴化镁四氢呋喃溶液(0.5mol/L)150ml,加入完毕后室温搅拌2h。用饱和氯化铵溶液淬灭,乙酸乙酯萃取,无水硫酸镁干燥,浓缩得到1,6-二炔醇(10.564g98%)。
1,6-二炔醇(10.564g 48mmol),重氮乙酸乙酯(5.7g 50mmol)和无水乙腈100ml在氮气条件下加入到250ml史莱克管,加入碘化亚铜(0.914g 4.8mol),三乙胺14ml室温搅拌搅拌1h。通过硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=10:1,得到1,6-联烯炔醇(13.737g 90%)
炔醇联烯酯(13.737g 43.7mmol),2-碘酰基苯甲酸(18.354g 65.5mmol)和乙腈100ml加入到250mml圆底烧瓶80℃搅拌2h,抽滤除去固体。滤液用硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=5:1。得到炔酮联烯酯1a(12.704g 92%)。
炔酮联烯酯1a(0.063g 0.2mmol),对甲苯亚磺酸钠(0.178g 1mmol),醋酸碘苯(0.193g 0.6mmol)和NIS(0.067g 0.3mmol)氮气条件下乙腈作溶剂室温搅拌1h,抽滤,滤液用硅胶柱层析法,洗脱剂为石油醚:乙酸乙酯=5:1得到目标产物2a(0.105g 70%)
实施例2:
按照实施例1中方法,其中各步反应条件及溶剂不变,只是将方面详述中的R1、
R2取代基改变,炔酮联烯酯产率不同,表1为炔酮联烯酯产率的产率:
表1
黄色固体熔点113.5-114.8℃
1H NMR(400MHz,CDCl3)δ8.38–8.31(m,1H),8.05-8.02(m,1H),7.87–7.79(m,2H),7.64-7.59(m,1H),7.58–7.45(m,4H),6.31(s,1H),4.93(s,1H),4.21(q,J=7.2Hz,2H),1.23(t,J=7.2Hz,3H).
黄色固体熔点156.1-157.5.8℃
1H NMR(400MHz,CDCl3)δ8.35(d,J=8.0Hz,1H),7.98(d,J=7.6Hz,1H),7.78(d,J=8.4Hz,2H),7.68–7.61(m,1H),7.6.-7.56(m,1H),7.50(d,J=8.4Hz,2H),6.33(s,1H),4.93(s,1H),4.22(q,J=7.2Hz,2H),1.24(t,J=7.2Hz,3H).
黄色固体熔点122.7-124.1℃
1H NMR(400MHz,CDCl3)δ8.42(d,J=6.8Hz,1H),8.10-8.06(dt,J=8.0,4.1Hz,2H),8.04-8.02(m,1H)7.79(d,J=8.4Hz,2H),7.37(d,J=8.0Hz,2H),6.42(s,1H),4.98(s,1H),4.25(q,J=7.2Hz,2H),2.48(s,3H),1.27(t,J=7.2Hz,3H).
黄色固体熔点116.8-118.0℃
1H NMR(400MHz,CDCl3)δ8.25(d,J=8.1Hz,1H),7.83–7.76(m,3H),7.35(dd,J=8.1,0.9Hz,1H),7.04(d,J=8.9Hz,2H),6.26(s,1H),4.88(s,1H),4.21(q,J=7.1Hz,2H),3.89(s,3H),2.48(s,3H),1.23(t,J=7.1Hz,3H).
黄褐色固体熔点107.9-109.3℃
1H NMR(400MHz,CDCl3)δ8.36(d,J=8.0Hz,1H),8.13(d,J=8.0Hz,1H),7.73(d,J=5.2Hz,1H),7.67-7.65(m,1H),7.60(d,J=4.0Hz,1H),7.56(t,J=7.6Hz,1H),7.25–7.19(m,1H),6.33(s,1H),4.92(s,1H),4.25(q,J=7.2Hz,2H),1.27(t,J=7.2Hz,3H).
白色固体
1H NMR(400MHz,CDCl3)δ8.20(d,J=8.4Hz,1H),7.93(d,J=8.0Hz,1H),7.88(d,J=8.0Hz,2H),7.67(d,J=8.0Hz,3H),7.62-7.58(m,3H),7.39(s,2H),7.07-7.04(m,4H),4.73(s,1H),3.73(q,J=6.8Hz,2H),2.49(s,3H),2.35(s,3H),0.81(t,J=6.8Hz,3H).
Claims (12)
1.一种制备式2化合物的方法,其特征在于,该方法在有机溶剂中,碱和氧化剂存在下,氮气条件下,将式1化合物与苯亚磺酸钠和N-碘代丁二酰亚胺、反应制备式2化合物,反应式如下:
其中,
R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;
R3为C1-C5烷基。
2.根据权利要求1所述的方法,其特征在于,所述的碱为三乙胺、二异丙胺、三异丁胺、三正丁胺、DBU中的一种或几种;有机溶剂选自乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇中的一种或几种;氧化剂为醋酸碘苯,叔丁基过氧化氢、二叔丁基过氧化物、叔丁基过氧苯甲酸酯、三氟乙酸碘苯中的一种或几种。
3.根据权利要求1所述的方法,其特征在于,所述的式1化合物是由式3化合物制备得到,是在有机溶剂中,式3化合物与2-碘酰基苯甲酸制备式1化合物,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;
所述的有机溶剂为乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇中的一种或几种。
4.根据权利要求3所述的方法,其特征在于,所述的式3化合物是由式4化合物制备得到,是在有机溶剂中,碱、催化剂存在下,式4化合物与重氮乙酸乙酯反应,制备式3化合物,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
5.根据权利要求4所述的制备方法,其特征在于,所述的催化剂为碘化亚铜、氯化亚铜、溴化亚酮、氰化亚铜、醋酸亚铜、三氟甲基磺酸亚铜、四氟硼酸亚铜、六氟磷酸四亚铜;有机溶剂为乙腈、1,4-二氧六环、甲苯、二氯甲烷、二氯乙烷、四氢呋喃、乙酸乙酯、甲醇;碱为三乙胺、二异丙胺、三异丁胺、三正丁胺、DBU。
6.根据权利要求4所述的方法,其特征在于,所述的式4化合物是由式5化合物制备得到,是将式5化合物溶于有机溶剂,-10℃~0℃条件下,加入乙炔基溴化镁有机溶剂,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
7.根据权利要求6所述的方法,其特征在于,所述的有机溶剂为四氢呋喃。
8.根据权利要求6所述的方法,其特征在于,所述的式5化合物是由式6化合物与式7化合物制备得到,是在有机溶剂中,催化剂存在下,氮气条件下,反应温度为40~80℃反应制备得到,其反应式如下:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩。
9.根据权利要求8所述的方法,其特征在于,所述的催化剂为碘化亚铜、双(三苯基膦)二氯化钯;有机溶剂为三乙胺,反应温度优选为60~70℃。
10.式2化合物、式3化合物、式1化合物:
其中,R1为H、C1-C5烷基氧基、C1-C5烷基、卤素;
R2为H、甲氧基、C1-C5烷基、卤素、Et、t-Bu、噻吩;
R3为C1-C5烷基。
11.根据权利要求10所述的化合物,其特征在于,所述的R1为H、OMe、Me、Cl;R2为H、OMe、Me、Cl、Br、Et、t-Bu、噻吩;R3为甲基、乙基、丙基。
12.根据权利要求1、3、4、6、8任一所述的方法,其特征在于,所述的R1为H、OMe、Me、Cl;R2为H、OMe、Me、Cl、Br、Et、t-Bu、噻吩;
R3为甲基、乙基、丙基。
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