CN116554056A - 一种具有多官能团化的环己烷化合物及其制备方法 - Google Patents
一种具有多官能团化的环己烷化合物及其制备方法 Download PDFInfo
- Publication number
- CN116554056A CN116554056A CN202310529406.8A CN202310529406A CN116554056A CN 116554056 A CN116554056 A CN 116554056A CN 202310529406 A CN202310529406 A CN 202310529406A CN 116554056 A CN116554056 A CN 116554056A
- Authority
- CN
- China
- Prior art keywords
- cyclohexane compound
- malononitrile
- compound
- cyclohexane
- solvent
- 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.)
- Pending
Links
- -1 Cyclohexane compound Chemical class 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 125000000524 functional group Chemical group 0.000 title claims 2
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000003054 catalyst Substances 0.000 claims abstract description 23
- 239000002994 raw material Substances 0.000 claims abstract description 23
- 150000002576 ketones Chemical class 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- 239000012038 nucleophile Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 54
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 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
- 239000003960 organic solvent Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- MFIGJRRHGZYPDD-UHFFFAOYSA-N n,n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)NCCNC(C)C MFIGJRRHGZYPDD-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000007306 functionalization reaction Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 150000001934 cyclohexanes Chemical class 0.000 abstract description 5
- 238000005580 one pot reaction Methods 0.000 abstract description 4
- 238000005815 base catalysis Methods 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 49
- 239000000243 solution Substances 0.000 description 19
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 15
- 238000001514 detection method Methods 0.000 description 15
- 239000011259 mixed solution Substances 0.000 description 15
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 238000004809 thin layer chromatography Methods 0.000 description 15
- 239000000463 material Substances 0.000 description 12
- 238000000926 separation method Methods 0.000 description 4
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 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 description 3
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 2
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 2
- 238000006352 cycloaddition reaction Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- VUNOFAIHSALQQH-UHFFFAOYSA-N Ethyl menthane carboxamide Chemical compound CCNC(=O)C1CC(C)CCC1C(C)C VUNOFAIHSALQQH-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000006668 aldol addition reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- ZLQHJDFXKLKCEE-UHFFFAOYSA-N ethyl 4-(4-bromophenyl)-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=C(Br)C=C1 ZLQHJDFXKLKCEE-UHFFFAOYSA-N 0.000 description 1
- HEMDRKHHUFUGRF-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=C(F)C=C1 HEMDRKHHUFUGRF-UHFFFAOYSA-N 0.000 description 1
- XNQHIPSJGRPIIW-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=C(OC)C=C1 XNQHIPSJGRPIIW-UHFFFAOYSA-N 0.000 description 1
- ACXLBHHUHSJENU-UHFFFAOYSA-N ethyl 4-oxo-4-phenylbut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=CC=C1 ACXLBHHUHSJENU-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种具有多官能团化的环己烷化合物及其制备方法,属于有机化学合成方法技术领域,该化合物以双亲核试剂丙二腈和两分子α,β‑不饱和酮为原料,以碱性物质为催化剂,在溶剂中于0‑50℃的温度下反应1‑48h,然后通过柱层析纯化,制备得到。本发明示例的一种具有多官能团化的环己烷化合物及其制备方法,利用碱催化来进行制备,实现了多步串联“一锅法”合成环己烷化合物。
Description
技术领域
本发明涉及有机化学合成方法技术领域,特别是涉及一种具有多官能团化的环己烷化合物及其制备方法。
背景技术
多官能团化的环己烷骨架作为一类独特的结构单元广泛存在于药物分子和天然产物中。如环萜类的薄荷醇(参照Xu,L.;Han,Y.;Chen,X.;Aierken,A.;Wen,H.;Zheng,W.;Wang,H.;Lu,X.;Zhao,Z.;Ma,C.;Liang,P.;Yang,W.;Yang,S.;Yang,F.Nat Common,2020,11,3790.)、姜科植物郁金中的榄香烯化合物(参照Iglesias,D.B.;Teijón.P.H.;González,R.R.;Fernández-Mateos,A.Eur.J.Org.Chem.2018,4926.)、第三代铂类抗癌药物奥沙利铂(参照Horasawa,S.;Kaneko,A.;Kotani,D.;Nakashima,S.;Bando,H.;Yoshino,T.Ann.Oncol.2018,29,ix32)。另外,该类骨架还在不对称催化中作为手性催化剂和手性配体表现出重要应用优势,如Trost配体被广泛应用于多种有机或金属不对称催化反应,且获得优异的对映选择性(参照Trost,B.M.;Fandrick,D.R.;Dinh,D.C.J.Am.Chem.Soc.2005,127,14186.)。此外,在化工行业,环己烷骨架衍生物也有广泛应用,如环保增塑剂环己烷-1,2-二甲酸二异辛酯(参照McMurray,J.W.;Zhou,Y.;Luo,H.-M.;Qu,J.Polymers,2017,667,55.)和凉味剂N-乙基-2-异丙基-5-甲基环己烷甲酰胺(参照Serra,S.;Fuganti,C.;Gatti,F.G.Eur.J.Org.Chem.2008,1031.)等。由此可见,多取代环己烷骨架是多种生物活性分子和工业用品的“优势基础单元”,如何高效便捷构建此类化合物成为有机合成的一大热点。
目前,针对该类骨架的合成主要是通过两组分环加成方式得到,如[4+2],[3+3]和[5+1]环加成反应[参照a)Huang,X.-F.;Liu,Z.-M.;Geng,Z.-C.;Zhang,S.-Y.;Wang,Y.;Wang,X.-W.Org.Biomol.Chem.2012,10,8794;b)Reyes,E.;Jiang,H.;Milelli,A.;Elaner,P.;Hazell,R.;K.A.Angew.Chem.;Int.Ed.2007,119,9362;c)Ma,W.;Fang,J.;Ren,J.;Wang,Z.Org.Lett.2015,15,4180;d)Akhtar,W.M.;Armstrong,R.J.;Frost,J.R.;Stevenson,N.G.;Donohoe,T.J.J.Am.Chem.Soc.2018,140,11916.]。而对于三组分串联方式来构建这类化合物的研究还有待进一步开发,其中通过三组分[2+2+2]串联反应合成环已烷化合物有少量的报道[参照a)Mao,Z.;Jia,Y.;Xu,Z.;Wang,R.Adv.Synth.Catal.2012,354,1401;b)Kuan,H.-H.;Chien,C.-H.;Chen,K.Org.Lett.2013,15,2880.]。而对于历经更具挑战性的[1+2+3]多组分串联“一锅法”途径来制备该类骨架还鲜有报道。因此,发展一种操作简便、催化高效、经济性好,且高化学选择性的化学方法来合成具有多官能团化的环己烷化合物,无论在科学研究还是工业应用领域中都将具有广阔的应用前景。
发明内容
为了解决上述现有技术中的不足,本发明的目的是提供一种具有多官能团化的环己烷化合物及其制备方法,利用碱催化来进行制备,实现了多步串联“一锅法”合成环己烷化合物。
本发明解决其技术问题所采用的技术方案为:
提供了一种具有多官能团化的环己烷化合物,该化合物以双亲核试剂丙二腈和两分子α,β-不饱和酮为原料,以碱性物质为催化剂,在溶剂中反应制得。
具体的,反应方程式如下:
进一步的,双亲核试剂丙二腈:α,β-不饱和酮的投料摩尔比为1:1~5。
进一步的,催化剂碱的用量是5mol%-20mol%。
进一步的,该化合物的结构通式为:
进一步的,所述双亲核试剂的结构式为
R1和/或R2任意选自CN、CO2Me、CO2Et、NO2、PhCO、CO2tBu中的一种。
优选的,所述双亲核试剂的结构式为
进一步的,α,β-不饱和酮的结构式为:
其中,R3选自Me、Et、tBu、iPr、-CH2Ph、-C6H5中的任意一种。
进一步的,R4选自烷基、芳杂环、取代的芳基中的一种;
其中R5、R6、R7、R8、R9选自H、F、Cl、Br、I、CN、NO2、CF3、Me、OMe、3,5-CF3、3,5-OMe、CO2Me中的任意一种。
进一步的,所述碱性物质为碳酸钾、碳酸钠、碳酸铯、碳酸氢钠、三乙胺、二异丙基乙二胺、4-二甲氨基吡啶(DMAP)、1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)、三乙烯二胺(DABCO)以及手性叔胺如奎宁、奎尼丁、辛可宁、辛可尼丁中的任意一种。
进一步的,所述溶剂为有机溶剂或水;
或者,所述的有机溶剂为二氯甲烷、甲苯、四氢呋喃、三氯甲烷、乙醚、三氟甲苯、乙腈、二甲苯、1,4-二氧六环、叔丁基甲醚、甲醇、乙醇中的一种或多种。
优选的,所述双亲核试剂丙二腈、α,β-不饱和酮和DBU的投料摩尔比为1:2.1:0.05;
双亲核试剂丙二腈的反应浓度为0.01~0.2mol/L,优选0.05mol/L。
优选的,溶剂使用1,4-二氧六环和甲醇的混合液作为反应溶剂。
本发明所提到的烷基,烷氧基,除特别说明外,均推荐为碳数1~10的基团,特别推荐碳数1~3的基团。本发明所提到的芳基,除特别说明外,均指苯基和萘取代基,特别推荐苯基,所述杂环为C5~C10的含氮、氧、硫的杂环取代基。
一种具有多官能团化的环己烷化合物的制备方法,将双亲核试剂丙二腈、两分子α,β-不饱和酮以及碱性物质加入至溶剂中,于0-50℃的温度下反应1-48h,然后通过柱层析纯化,制备得到。
具体的,柱层析分离纯化所用的洗脱剂为极性溶剂和非极性溶剂的混合溶剂,优选乙酸乙酯-石油醚混合溶剂。
与现有技术相比,本发明的有益效果在于:
本发明示例的具有多官能团化的环己烷化合物及其制备方法,以丙二腈为代表的双亲核试剂和两分子α,β-不饱和酮为原料,以碱为催化剂反应制得,高效、高化学选择性地通过Michael/Michael/Aldol加成多步串联“一锅法”合成一系列多官能团化的环己烷骨架化合物,具有催化剂用量较少、原料易得、反应条件温和、操作简便易行、底物适用范围广泛、区域和非对映选择性优异等诸多优点。
具体实施方式
下面结合实施例对本申请作进一步的详细说明。可以理解的是,此处所描述的具体实施例仅仅用于解释相关发明,而非对该发明的限定。
需要说明的是,在不冲突的情况下,本申请中的实施例及实施例中的特征可以相互组合。
实施例1:
以丙二腈和3-(苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(苯甲酰基)丙烯酸乙酯2a(42.8mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3a,性状为白色固体,产率为94%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.68–7.66(m,2H),7.50–7.47(m,1H),7.34–7.31(m,4H),7.16–7.14(m,2H),7.08–7.05(m,1H),5.06(d,J=2.4Hz,1H),4.52(d,J=11.4Hz,1H),4.35–4.27(m,2H),4.05–4.00(m,1H),3.93(d,J=12.0Hz,1H),3.80(dd,J=12.6Hz,4.2Hz,1H),3.77–3.71(m,1H),2.43(dd,J=14.4Hz,3.6Hz,1H),2.36–2.31(m,1H),1.32(t,J=7.2Hz,3H),0.98(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)201.5,168.7,167.5,142.2,136.4,134.3,128.6,128.5,128.4,128.3,127.9,124.4,113.9,112.3,73.6,63.0,62.6,48.9,47.7,45.6,38.6,37.0,13.9,13.3。
实施例2:
以丙二腈和3-(3-甲基-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(3-甲基-苯甲酰基)丙烯酸乙酯2b(45.8mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3b,性状为白色固体,产率为91%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.48(d,J=8.4Hz,1H),7.42(s,1H),7.28(d,J=7.2Hz,1H),7.22(t,J=7.8Hz,1H),7.11–7.10(m,2H),7.04(t,J=7.8Hz,1H),6.87(d,J=7.8Hz,1H),4.97(d,J=2.4Hz,1H),4.48(d,J=12.0Hz,1H),4.35–4.27(m,2H),4.06–4.00(m,1H),3.92(d,J=11.4Hz,1H),3.84–3.73(m,2H),2.42(dd,J=15.0Hz,3.6Hz,1H),2.34–2.29(m,4H),2.18(s,3H),1.32(t,J=7.2Hz,3H),0.98(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)201.7,168.8,167.6,142.2,138.4,138.2,136.6,135.0,128.7,128.6,128.4,128.3,125.8,125.2,121.5,113.9,112.2,73.5,63.0,62.6,48.9,47.8,45.6,38.6,36.9,21.3,21.2,14.0,13.4。
实施例3:
以丙二腈和3-(4-甲基-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-甲基-苯甲酰基)丙烯酸乙酯2c(45.8mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3c,性状为白色固体,产率为92%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.60(d,J=8.4Hz,2H),7.22(d,J=7.8Hz,2H),7.14(d,J=7.8Hz,2H),6.97(d,J=7.8Hz,2H),5.24(d,J=2.4Hz,1H),4.47(d,J=11.4Hz,1H),4.34–4.26(m,2H),4.01–3.96(m,1H),3.88(d,J=11.4Hz,1H),3.77(dd,J=12.6Hz,3.6Hz,1H),3.68–3.63(m,1H),2.40(dd,J=14.4Hz,3.6Hz,1H),2.35(s,3H),2.30–2.25(m,1H),2.17(s,3H),1.31(t,J=7.2Hz,3H),0.95(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.9,168.8,167.6,145.7,139.7,137.7,133.9,129.4,129.2,128.6,124.3,113.9,112.2,73.6,62.8,62.6,49.0,47.2,45.6,39.0,37.0,21.7,20.8,14.0,13.4。
实施例4:
以丙二腈和3-(4-甲氧基-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-甲氧基-苯甲酰基)丙烯酸乙酯2d(49.1mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3d,性状为白色固体,产率为85%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.71(d,J=8.4Hz,2H),7.26(d,J=9.0Hz,2H),6.81(d,J=9.0Hz,2H),6.70(d,J=9.0Hz,2H),5.37(d,J=3.0Hz,1H),4.42(d,J=12.0Hz,1H),4.33–4.28(m,2H),4.03–3.97(m,1H),3.86(d,J=12.0Hz,1H),3.83(s,3H),3.77(dd,J=12.6Hz,3.6Hz,1H),3.72–3.68(m,4H),2.39(dd,J=14.4Hz,3.6Hz,1H),2.30–2.25(m,1H),1.31(t,J=7.2Hz,3H),0.97(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)199.5,168.8,167.6,164.6,159.0,134.8,131.1,129.3,125.7,113.9,113.8,113.7,112.2,73.4,62.8,62.5,55.6,55.2,49.0,47.0,45.6,39.0,37.0,14.0,13.4。
实施例5:
以丙二腈和3-(3-溴-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(3-溴-苯甲酰基)丙烯酸乙酯2e(59.0mg0.21 mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3e,性状为白色固体,产率为83%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.71(t,J=1.8Hz,1H),7.61(d,J=7.8Hz,1.8Hz,2H),7.45(d,J=1.8Hz,1H),7.26–7.19(m,3H),7.03(t,J=7.8Hz,1H),4.62(d,J=3.0Hz,1H),4.37–4.30(m,3H),4.19–4.13(m,1H),3.98–3.93(m,2H),3.80(dd,J=12.6Hz,3.6Hz,1H),2.43(dd,J=14.4Hz,3.6Hz,1H),2.30–2.25(m,1H),1.33(t,J=7.2Hz,3H),1.12(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.4,168.5,167.4,144.1,138.1,137.1,131.3,131.1,130.1,130.0,128.0,127.1,123.1,123.1,123.0,113.6,112.0,73.1,63.5,62.8,48.8,48.5,45.6,38.1,36.8,14.0,13.5。
实施例6:
以丙二腈和3-(4-氟-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-氟-苯甲酰基)丙烯酸乙酯2f(46.6mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3f,性状为白色固体,产率为86%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.73–7.71(m,2H),7.30–7.27(m,2H),7.03–7.00(m,2H),6.86–6.83(m,2H),7.03(t,J=7.8Hz,1H),4.96(d,J=3.0Hz,1H),4.41(d,J=12.0Hz,1H),4.37–4.28(m,3H),4.13–4.08(m,1H),3.92(d,J=12.0Hz,1H),3.89–3.84(m,1H),3.80(dd,J=12.6Hz,3.6Hz,1H),2.42(dd,J=15.0Hz,3.6Hz,1H),2.31–2.26(m,1H),1.33(t,J=7.2Hz,3H),1.05(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.0,168.6,167.5,166.3(d,1JFC=257.0Hz),162.2(d,1JFC=246.6Hz),138.0(d,4JFC=3.2Hz),132.8(d,4JFC=6.0Hz),131.3(d,3JFC=9.8Hz),126.4(d,3JFC=8.1Hz),116.0(d,2JFC=22.1Hz),115.5(d,2JFC=21.3Hz),113.6,112.1,73.3,63.2,62.7,48.9,48.0,45.6,38.6,36.9,13.9,13.5。
实施例7:
以丙二腈和3-(4-氯-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-氯-苯甲酰基)丙烯酸乙酯2g(50.0mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3g,性状为白色固体,产率为91%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.62(d,J=8.4Hz,2H),7.33(d,J=8.4Hz,2H),7.24(d,J=9.0Hz,2H),7.14(d,J=8.4Hz,2H),4.95(d,J=2.4Hz,1H),4.39(d,J=12.0Hz,1H),4.35–4.29(m,2H),4.13–4.07(m,1H),3.91(d,J=12.0Hz,1H),3.87–3.81(m,1H),3.78(dd,J=12.6Hz,3.6Hz,1H),2.40(dd,J=14.4Hz,3.6Hz,1H),2.28–2.23(m,1H),1.33(t,J=7.2Hz,3H),1.06(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.3,168.5,167.4,141.4,140.7,134.6,134.2,129.8,129.1,128.8,125.9,113.6,112.0,73.3,63.3,62.8,48.9,47.7,45.5,38.5,36.9,13.9,13.5。
实施例8:
以丙二腈和3-(4-溴-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-溴-苯甲酰基)丙烯酸乙酯2g(59.0mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3h,性状为白色固体,产率为88%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.54–7.50(m,4H),7.31–7.29(m,2H),7.19–7.18(m,2H),4.93(d,J=2.4Hz,1H),4.38(d,J=11.4Hz,1H),4.36–4.29(m,2H),4.13–4.07(m,1H),3.91(d,J=12.0Hz,1H),3.86–3.77(m,2H),2.40(dd,J=14.4Hz,3.6Hz,1H),2.28–2.23(m,1H),1.32(t,J=7.2Hz,3H),1.06(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.5,168.5,167.4,141.3,135.0,132.1,131.8,130.2,129.8,126.2,122.3,113.6,112.0,73.3,63.3,62.8,48.9,47.7,45.5,38.5,36.9,13.9,13.5。
实施例9:
以丙二腈和3-(4-碘-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-碘-苯甲酰基)丙烯酸乙酯2i(69.3mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3i,性状为白色固体,产率为81%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.73(d,J=8.4Hz,2H),7.49(d,J=8.4Hz,2H),7.35(d,J=8.4Hz,2H),7.04(d,J=8.4Hz,2H),4.89(d,J=2.4Hz,1H),4.36–4.27(m,3H),4.12–4.07(m,1H),3.90(d,J=12.0Hz,1H),3.85–3.76(m,2H),2.40(dd,J=14.4Hz,3.6Hz,1H),2.26–2.21(m,1H),1.32(t,J=7.2Hz,3H),1.06(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.9,168.5,167.4,141.9,138.1,137.7,135.5,129.5,126.4,113.6,112.0,103.2,94.0,73.4,63.3,62.7,48.8,47.6,45.5,38.3,36.9,13.9,13.5。
实施例10:
以丙二腈和3-(4-硝基-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-硝基-苯甲酰基)丙烯酸乙酯2j(52.3mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3j,性状为白色固体,产率为84%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)8.18(d,J=9.0Hz,2H),8.03(d,J=9.0Hz,2H),7.85(d,J=9.0Hz,2H),7.54(d,J=9.0Hz,2H),4.78(d,J=3.0Hz,1H),4.51(d,J=12.0Hz,1H),4.39–4.30(m,2H),4.24–4.18(m,1H),4.03(d,J=12.0Hz,1H),4.00–3.95(m,1H),3.84(dd,J=12.6Hz,3.6Hz,1H),2.46(dd,J=14.4Hz,3.6Hz,1H),2.35–2.30(m,1H),1.34(t,J=7.2Hz,3H),1.16(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)200.3,168.2,167.3,150.8,148.7,147.6,140.4,129.5,125.8,123.9,113.3,111.9,73.5,63.9,63.0,49.1,48.4,45.5,38.0,36.7,13.9,13.5。
实施例11:
以丙二腈和3-(4-三氟甲基-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-三氟甲基-苯甲酰基)丙烯酸乙酯2k(57.1mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3k,性状为白色固体,产率为84%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.71(d,J=7.8Hz,2H),7.56(d,J=8.4Hz,2H),7.42–7.37(m,4H),4.60(d,J=2.4Hz,1H),4.45(d,J=12.0Hz,1H),4.38–4.29(m,2H),4.22–4.17(m,1H),4.02–3.93(m,2H),3.85–3.82(m,1H),2.46(dd,J=14.4Hz,3.6Hz,1H),2.36–2.31(m,1H),1.33(t,J=7.2Hz,3H),1.13(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)201.1,168.4,167.5,145.7,139.2,135.3(q,2JFC=33.0Hz),130.6(q,2JFC=32.7Hz),128.8,125.6(t,3JFC=3.9Hz),125.5(t,3JFC=3.9Hz),125.1,123.3(q,1JFC=270.8Hz),123.1(q,1JFC=271.2Hz),113.5,112.0,73.4,63.6,62.9,49.1,48.8,45.5,38.0,36.8,13.9,13.5。
实施例12:
以丙二腈和3-(2-呋喃甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(4-三氟甲基-苯甲酰基)丙烯酸乙酯2l(40.7mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3l,性状为白色固体,产率为77%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.58(d,J=1.2Hz,1H),7.20(dd,J=3.6Hz,1.2Hz,1H),7.17(d,J=1.8Hz,1H),6.50(dd,J=3.6Hz,1.8Hz,1H),6.20(dd,J=3.6Hz,1.2Hz,1H),6.15–6.14(m,1H),4.65(d,J=2.4Hz,1H),4.37–4.29(m,2H),4.22(d,J=12.6Hz,1H),4.17–4.11(m,1H),4.04–3.98(m,1H),3.86(d,J=12.0Hz,1H),3.71(dd,J=12.6Hz,4.2Hz,1H),2.51–2.47(m,1H),2.43–2.38(m,1H),1.34(t,J=7.2Hz,3H),1.08(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)187.9,168.4,167.1,154.5,151.7,148.4,142.3,120.1,110.5,106.8,70.9,63.1,62.7,48.0,47.6,44.9,36.6,35.9,13.9,13.4。
实施例13:
以丙二腈和3-(3,5-二氟-苯甲酰基)丙烯酸乙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-(3,5-二氟-苯甲酰基)丙烯酸乙酯2m(50.4mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3m,性状为白色固体,产率为87%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.20(d,J=5.4Hz,2H),6.98(t,J=7.8Hz,1H),6.84(d,J=5.4Hz,2H),6.57(t,J=8.4Hz,1H),4.58(s,1H),4.38–4.30(m,2H),4.25–4.20(m,2H),4.06–4.01(m,1H),3.95(d,J=12.0Hz,1H),3.79(dd,J=13.2Hz,3.6Hz,1H),2.45(dd,J=14.4Hz,3.6Hz,1H),2.25(t,J=13.8Hz,1H),1.34(t,J=7.2Hz,3H),1.19(t,J=7.2Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)199.2(t,4JFC=2.6Hz),168.2,167.2,163.0(d,1JFC=249.9Hz),162.5(d,1JFC=249.9Hz),162.2(d,1JFC=251.3Hz),162.1(d,1JFC=251.1Hz),146.0(t,3JFC=7.8Hz),139.2(t,3JFC=7.8Hz),113.4,111.8,111.4(d,2JFC=26.5Hz),111.3(d,2JFC=15.0Hz),109.7(t,2JFC=25.1Hz),108.1(d,2JFC=26.7Hz),108.0(d,2JFC=15.6Hz),103.7(t,2JFC=25.1Hz),73.1(t,4JFC=2.2Hz),63.7,62.9,48.9,48.7,45.5,37.8,36.7,13.9,13.5。
实施例14:
以丙二腈和3-苯甲酰基丙烯酸异丙酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-苯甲酰基丙烯酸异丙酯2n(45.8mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3n,性状为白色固体,产率为87%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.68–7.66(m,2H),7.48–7.45(m,1H),7.32–7.29(m,4H),7.15–7.12(m,2H),7.06–7.04(m,1H),5.21–5.15(m,1H),4.97(d,J=3.0Hz,1H),4.86–4.80(m,1H),4.50(d,J=12.0Hz,1H),3.89(d,J=12.0Hz,1H),3.76(dd,J=12.0Hz,3.6Hz,1H),2.41(dd,J=14.4Hz,3.6Hz,1H),2.35–2.30(m,1H),1.33(d,J=6.6Hz,3H),1.28(d,J=6.0Hz,3H),1.12(d,J=6.6Hz,3H),0.90(d,J=6.0Hz,3H)。
13C NMR(150MHz,CDCl3):δ(ppm)201.7,168.2,167.0,142.2,136.5,134.2,128.6,128.5,128.4,127.9,124.5,113.9,112.2,73.6,71.8,70.8,49.0,47.9,45.7,38.4,37.1,21.6,21.5,21.3,20.8。
实施例15:
以丙二腈和3-苯甲酰基丙烯酸苄酯为原料,反应式和实验步骤如下:
在10mL反应试管中,依次加入丙二腈1(6.6mg,0.1mmol),3-苯甲酰基丙烯酸异丙酯2o(55.9mg,0.21mmol),催化剂DBU(0.8μL,0.005mmol),1,4二氧六环和甲醇的混合溶液2mL,其比例为4:1,之后放置在5℃下搅拌至薄层层析检测原料1消失。然后浓缩反应液,硅胶柱层析分离得到产物3o,性状为白色固体,产率为81%,dr>19:1。其数据表征如下:
1H NMR(600MHz,CDCl3):δ(ppm)7.56–7.54(m,2H),7.46–7.43(m,1H),7.36–7.33(m,5H),7.28–7.21(m,7H),7.13–7.10(m,2H),7.07–7.02(m,3H),5.25(dd,J=19.2Hz,12.6Hz,2H),5.02–5.00(m,2H),4.62(d,J=12.0Hz,1H),4.52(d,J=12.0Hz,1H),3.98(d,J=12.0Hz,1H),3.84(dd,J=12.6Hz,3.6Hz,1H),2.44–2.40(m,1H),2.36–2.31(m,1H)。
13C NMR(150MHz,CDCl3):δ(ppm)201.3,168.7,167.5,142.0,136.2,134.4,134.2,133.4,128.9,128.8,128.8,128.7,128.7,128.7,128.6,128.6,128.6,128.5,128.5,128.5,128.4,128.4,128.2,128.0,124.4,113.7,112.0,73.6,68.6,68.3,48.9,47.8,45.7,38.4,36.9。
本领域技术人员应当理解,本申请中所涉及的发明范围,并不限于上述技术特征的特定组合而成的技术方案,同时也应涵盖在不脱离所述发明构思的情况下,由上述技术特征或其等同特征进行任意组合而形成的其它技术方案。例如上述特征与本申请中公开的(但不限于)具有类似功能的技术特征进行互相替换而形成的技术方案。
Claims (10)
1.一种具有多官能团化的环己烷化合物,其特征在于,该化合物以双亲核试剂丙二腈和两分子α,β-不饱和酮为原料,以碱性物质为催化剂,在溶剂中反应制得。
2.根据权利要求1所述的一种具有多官能团化的环己烷化合物,其特征在于,双亲核试剂丙二腈:α,β-不饱和酮的投料摩尔比为1:1~5。
3.根据权利要求1所述的一种具有多官能团化的环己烷化合物,其特征在于,催化剂碱的用量是5mol%-20mol%。
4.根据权利要求1所述的一种具有多官能团化的环己烷化合物,其特征在于,该化合物的结构通式为:
5.根据权利要求4所述的一种具有多官能团化的环己烷化合物,其特征在于,所述双亲核试剂的结构式为
R1和/或R2选自CN、CO2Me、CO2Et、NO2、PhCO、CO2tBu中的一种。
6.根据权利要求4所述的一种具有多官能团化的环己烷化合物,其特征在于,α,β-不饱和酮的结构式为:
其中,R3选自Me、Et、tBu、iPr、-CH2Ph、-C6H5中的任意一种。
7.根据权利要求6所述的一种具有多官能团化的环己烷化合物,其特征在于,R4选自烷基、芳杂环、取代的芳基中的一种;
其中R5、R6、R7、R8、R9选自H、F、Cl、Br、I、CN、NO2、CF3、Me、OMe、3,5-CF3、3,5-OMe、CO2Me中的任意一种。
8.根据权利要求1所述的一种具有多官能团化的环己烷化合物,其特征在于,所述碱性物质为碳酸钾、碳酸钠、碳酸铯、碳酸氢钠、三乙胺、二异丙基乙二胺、4-二甲氨基吡啶、1,8-二氮杂双环[5.4.0]十一碳-7-烯、三乙烯二胺以及手性叔胺中的任意一种。
9.根据权利要求1所述的一种具有多官能团化的环己烷化合物,其特征在于,所述溶剂为有机溶剂或水;
或者,所述的有机溶剂为二氯甲烷、甲苯、四氢呋喃、三氯甲烷、乙醚、三氟甲苯、乙腈、二甲苯、1,4-二氧六环、叔丁基甲醚、甲醇、乙醇中的一种或多种。
10.一种权利要求1-9任一项所述的具有多官能团化的环己烷化合物的制备方法,其特征在于,将双亲核试剂丙二腈、两分子α,β-不饱和酮以及碱性物质加入至溶剂中,于0-50℃的温度下反应1-48h,然后通过柱层析纯化,制备得到。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310529406.8A CN116554056A (zh) | 2023-05-11 | 2023-05-11 | 一种具有多官能团化的环己烷化合物及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310529406.8A CN116554056A (zh) | 2023-05-11 | 2023-05-11 | 一种具有多官能团化的环己烷化合物及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116554056A true CN116554056A (zh) | 2023-08-08 |
Family
ID=87494174
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310529406.8A Pending CN116554056A (zh) | 2023-05-11 | 2023-05-11 | 一种具有多官能团化的环己烷化合物及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116554056A (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180141964A1 (en) * | 2015-07-23 | 2018-05-24 | East China Normal University | Functionalized cyanosilane and synthesis method and use thereof |
-
2023
- 2023-05-11 CN CN202310529406.8A patent/CN116554056A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180141964A1 (en) * | 2015-07-23 | 2018-05-24 | East China Normal University | Functionalized cyanosilane and synthesis method and use thereof |
Non-Patent Citations (3)
Title |
---|
ABDELKARIM CHAOUIKI等: "Electrochemical behavior and interfacial bonding mechanism of new synthesized carbocyclic inhibitor for exceptional corrosion resistance of steel alloy:DFTB, MD and experimental approaches", 《ARABIAN JOURNAL OF CHEMISTRY》, vol. 15, 3 October 2022 (2022-10-03), pages 104323 * |
B. NARAYANA等: "3-(4-Fluorobenzoyl)-4-(4-fluorophenyl)-4-hydroxy-2, 6-diphenylcyclohexane- 1, 1-dicarbonitrile", 《ACTA CRYST.》, vol. 70, 31 December 2014 (2014-12-31), pages 736 * |
刁晓菊等: "无溶剂合成1, 3, 5-三芳基-2-芳酰基环己醇衍生物和晶体结构", 《有机化学》, vol. 31, no. 7, 31 December 2011 (2011-12-31), pages 1064 - 1068 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2018103509A1 (zh) | 含连续季碳中心环丙烷氨基磷酸酯类化合物的合成方法 | |
CN114437103B (zh) | 一种通过金催化的不对称环加成反应合成手性四氢苯并氧杂卓类化合物的方法 | |
CN108033928A (zh) | 一种合成2-三氟甲基恶唑化合物的方法 | |
CN104788360B (zh) | 3‑砜基螺环三烯酮类化合物及其制备方法 | |
CN102911105B (zh) | 一种3-芳酰基吲哚化合物的合成方法 | |
CN111925356A (zh) | 手性喹啉-咪唑啉配体的合成方法及其应用 | |
CN108976243A (zh) | 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 | |
CN101735134A (zh) | 一种手性3-羟基吡咯酮类化合物及其制备方法与应用 | |
CN108794357A (zh) | 一种n-二氟甲基腙类化合物及其合成方法 | |
CN102942511B (zh) | 一种环戊二烯的制备方法 | |
CN102702218B (zh) | 含手性螺环骨架结构的双噁唑啉配体化合物及其制备方法和应用 | |
CN104193620A (zh) | 肼活化空气氧制备ɑ-羟基-β-二羰基化合物的方法 | |
CN103664821B (zh) | 一种基于邻氨基苯硫酚环化的苯并噻唑类化合物制备方法 | |
CN102731450A (zh) | 一种苯并呋喃或吲哚的制备方法 | |
CN106187825B (zh) | 一种n,n‑二酰胺基取代腙衍生物及合成方法 | |
CN116554056A (zh) | 一种具有多官能团化的环己烷化合物及其制备方法 | |
CN115215796B (zh) | 一种3-酰基喹啉类化合物的合成方法 | |
CN105732648B (zh) | 一种吡咯并呋喃的含氮杂环化合物及合成方法 | |
Wen et al. | Asymmetric pinacol coupling reaction catalyzed by dipeptide-type Schiff bases | |
CN105085563B (zh) | 一种支链烯丙基化合物、制备方法及应用 | |
CN116283868A (zh) | 一种螺[苯并呋喃-环己烯]类化合物的合成方法 | |
CN113845481B (zh) | 一种4,4-二甲基-4,5-二氢哒嗪-3-酮的合成方法 | |
CN106831474B (zh) | 一种含α-芳基-α,β-二氨基酸酯衍生物及其合成方法和应用 | |
CN106883188B (zh) | 一种5-氢-1, 4-苯并二氮杂卓类化合物及其合成方法 | |
CN109851540B (zh) | 芳氧功能化脯氨醇手性配体作为催化剂的应用 |
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 |