CN117466694A - 一种构建季碳中心的方法 - Google Patents
一种构建季碳中心的方法 Download PDFInfo
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- 229910052799 carbon Inorganic materials 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims abstract description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 claims abstract description 5
- 239000011736 potassium bicarbonate Substances 0.000 claims abstract description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 36
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000013375 chromatographic separation Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 abstract description 4
- 229940100198 alkylating agent Drugs 0.000 abstract description 4
- 150000001732 carboxylic acid derivatives Chemical group 0.000 abstract description 2
- 239000012038 nucleophile Substances 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 229910052723 transition metal Inorganic materials 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 abstract 2
- DCYGAPKNVCQNOE-UHFFFAOYSA-N 2,2,2-triphenylacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)O)C1=CC=CC=C1 DCYGAPKNVCQNOE-UHFFFAOYSA-N 0.000 abstract 1
- 229910002092 carbon dioxide Inorganic materials 0.000 abstract 1
- 239000001569 carbon dioxide Substances 0.000 abstract 1
- 230000007613 environmental effect Effects 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 238000011112 process operation Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 238000005303 weighing Methods 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- 239000000047 product Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 238000011068 loading method Methods 0.000 description 15
- 239000003208 petroleum Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 244000156473 Vallaris heynei Species 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
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- 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
- C07C1/323—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 the hetero-atom being a nitrogen atom
-
- 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
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract
本发明提供了一种构建季碳中心的方法,属于有机化学技术领域。本发明方法为:在溶剂与氮气氛围下,三苯乙酸在碳酸氢钾的作用下脱去质子,随后再脱去二氧化碳生成三苯基负离子作为亲核剂进攻作为烷基化试剂的Katritzky盐,以良好的产率得到含季碳中心的产物。本发明从稳定易制备的Katritzky盐和三级羧酸直接构建季碳中心,不需要氧化剂以及高温条件,同时避免了过渡金属的使用,工艺操作简便、反应条件要求低、对环境友好。
Description
技术领域
本发明属于有机化学技术领域,具体涉及一种构建季碳中心的方法。
背景技术
季碳立体中心的化合物结构更具有多样性和刚性,因此季碳中心广泛存在于药物、天然产物等生物活性化合物中,在生物医学、药学领域具有重要地位[参见:Hervieu,C.;Kirillova,M.S.;Suarez,T.;Muller,M.;Merino,E.;Nevado,C.Nat Chem 2021,13,327.]。例如,在2011年,美国销售额前200名的药中,有12%具有季碳手性中心。发展高效的构建季碳手性中心的方法有助于合成这些生物活性分子及其类似物,研究结构和功能的关系,从而促进新药研发。但由于受位阻拥挤、构象柔性等影响,构建季碳立体中心在有机合成中一直是一个巨大的挑战[参见:Zeng,X.P.;Cao,Z.Y.;Wang,Y.H.;Zhou,F.;Zhou,J.Chem.Rev.2016,116,7330.]。
构建季碳可以通过烷基化手段来引入碳,常见的各种烷基化试剂(如烷基卤、羧酸、酯类等)发展都比较成熟,我们选择近五年科学家研究热点的Katritzky盐作为烷基化试剂,Katritzky盐以在自然界存在广泛的胺为合成原料,是一种很好的烷基化试剂[参见:Plunkett,S.;Basch,C.H.;Santana,S.O.;Watson,M.P.J.Am.Chem.Soc.2019,141,2257.]。通过亲核取代反应,选择酸和Katritzky盐作为底物,酸脱羧后作为亲核试剂进攻Katritzky盐构建季碳中心,该反应条件环境友好、操作简单。
发明内容
针对背景所提内容,本发明的目的在于提供一种构建季碳中心的方法。
本发明反应合成路线如下:
本发明提供了一种构建季碳中心的方法,包括如下步骤::
步骤一、取Katritzky盐与2,2,2-三苯乙酸混合,再加入碳酸氢钾,混合物在氮气氛围下加至溶剂中;
步骤二、步骤一体系在室温下搅拌反应,反应结束加水淬灭,用乙酸乙酯萃取,有机层浓缩层析得到产物。
作为优选,Katritzky盐中的R1、R2基团分别为各种取代的芳基、烷基、氢。
作为优选,Katritzky盐中的R1基团是各种取代的芳基时,R2为氢。
作为优选,Katritzky盐中的R1基团是-C10H13时,R2为甲基。
作为优选,步骤一所述Katritzky盐、2,2,2-三苯乙酸和碳酸氢钾的物质的量之比为1:1:1。
作为优选,步骤一所述溶剂为0.2M的二甲基亚砜(DMSO)。
作为优选,步骤二搅拌反应时间为6h。
典型反应如下:
本发明的有益效果为:
本发明的方法反应条件温和,不需要氧化剂以及高温条件,同时避免了过渡金属的使用,从稳定易制备的Katritzky盐和三级羧酸直接构建季碳中心。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚,下面将结合实施例对本发明的技术方案进行清楚、完整地描述。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
除非另有定义,本文所使用的所有技术和科学术语与本发明技术领域的技术人员通常理解的含义相同。在本发明的说明书所使用的术语只是为了描述具体实施例的目的,并非用于限制本发明。本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。
实施例所用原料Katritzky盐的合成:
根据Watson及其同事描述的程序[参见:Plunkett,S.;Basch,C.H.;Santana,S.O.;Watson,M.P.J.Am.Chem.Soc.2019,141,2257.],将2,4,6-三苯基四氟硼酸吡啶鎓(1.0equiv)和胺(1.2equiv)加入到含有搅拌棒的Schlenk中。随后加入干燥的EtOH(1.0M),导致颜色从黄色变为黑橙色。然后搅拌混合物,并在90℃的油浴中回流加热5h。此时,将混合物冷却至室温。然后加入Et2O(15mL)并剧烈振荡,形成固体沉淀物。过滤由此获得的固体,用Et2O(2×15mL)洗涤,并在高真空下干燥。如果吡啶鎓盐未能沉淀,则进行快速柱色谱,用DCM/丙酮混合物洗脱。
实施例1
称取(48.5mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到28.2mg产物/>(石油醚:乙酸乙酯=50:1),产率84%,1H NMR(400MHz,CDCl3)δ7.2–7.1(m,15H),7.0(t,J=7.4Hz,1H),7.0(t,J=7.5Hz,2H),6.6(d,J=7.6Hz,2H),3.9(s,2H)。
实施例2
称取(49.2mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到25.8mg产物(石油醚:乙酸乙酯=50:1),产率74%,1H NMR(400MHz,CDCl3)δ7.2(dd,J=4.4,1.2Hz,11H),7.2–7.1(m,3H),7.2–7.1(m,1H),6.8(d,J=7.7Hz,2H),6.5(d,J=7.7Hz,2H),3.9(s,2H),2.2(s,3H);13C NMR(101MHz,CDCl3)δ146.7,135.4,135.3,131.0,129.8,128.0,127.5,125.9,58.4,45.9,20.9。
实施例3
称取(56.9mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到23.0mg产物(石油醚:乙酸乙酯=50:1),产率55%,1H NMR(400MHz,CDCl3)δ7.3–7.2(m,12H),7.2–7.1(m,3H),6.8(d,J=7.5Hz,2H),6.6(d,J=8.6Hz,2H),3.9(s,2H);13CNMR(101MHz,CDCl3)δ147.6(q,J=2.02Hz),146.3,137.3,132.2,129.7,127.7,126.1,119.7,118.2(q,J=216.1Hz),58.5,45.5。
实施例4
称取(59.9mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到20.2mg产物(石油醚:乙酸乙酯=50:1),产率58%,1H NMR(400MHz,CDCl3)δ7.2–7.1(m,15H),7.0(t,J=7.3Hz,1H),6.9(d,J=7.4Hz,1H),6.9(d,J=6.4Hz,1H),6.8(t,J=6.7Hz,1H),3.9(s,2H),1.5(s,3H);13C NMR(101MHz,CDCl3)δ146.5,138.8,137.1,130.2,129.9,129.7,127.5,126.0,125.9,125.0,58.2,41.6,19.2。
实施例5
称取(55.3mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到22.5mg产物(石油醚:乙酸乙酯=50:1),产率56%,1H NMR(400MHz,CDCl3)δ7.5(d,J=7.8Hz,1H),7.3–7.1(m,15H),7.1(d,J=7.6Hz,1H),7.0(q,J=8.0Hz,2H),4.3(s,2H);13CNMR(101MHz,CDCl3)δ146.7,137.9(q,J=1.01Hz),131.2(d,J=134.3Hz),130.5,129.7,127.8,126.3(q,J=3.03Hz),126.1,125.8(q,J=3.03Hz),125.6,122.0(q,J=216.1Hz),57.4,41.2(d,J=2.02Hz)。
实施例6
称取(51.9mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到25.0mg产物(石油醚:乙酸乙酯=50:1),产率68%,1H NMR(400MHz,CDCl3)δ7.3–7.2(m,12H),7.2(m,3H),7.0(d,J=8.7Hz,1H),6.9(t,J=7.8Hz,1H),6.5(d,J=9.9Hz,2H),3.9(s,2H);13C NMR(101MHz,CDCl3)δ146.2,140.5,133.0,131.2,129.7,129.2,128.4,127.7,126.1,126.1,58.5,45.9。
实施例7
称取(54.5mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到25.2mg产物(石油醚:乙酸乙酯=50:
1),产率64%,1H NMR(400MHz,CDCl3)δ7.2(d,J=4.1Hz,12H),7.2(h,J=4.1Hz,3H),6.2(s,1H),5.8(s,2H),3.9(s,2H),3.5(s,6H);13C NMR(101MHz,CDCl3)δ159.6,146.6,140.7,129.8,127.6,125.9,108.9,99.0,58.4,55.0,46.7。
实施例8
称取(53.7mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到22.0mg产物(石油醚:乙酸乙酯=50:1),产率57%,1H NMR(400MHz,CDCl3)δ7.3–7.1(m,15H),6.7(t,J=8.7Hz,1H),6.6–6.5(m,2H),3.8(s,2H);13C NMR(101MHz,CDCl3)δ156.6,(d,J=46.5Hz),146.1,135.4(d,J=4.0Hz),133.0,130.5(d,J=7.07Hz),129.6,128.8(d,J=10.1Hz),127.7,126.2,119.5(d,J=17.2Hz),115.2(d,J=21.2Hz),58.5,45.2。
实施例9
称取(49.1mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到23.5mg产物(石油醚:乙酸乙酯=40:1),产率69%,1H NMR(400MHz,CDCl3)δ7.2(m,J=7.7,7.0Hz,15H),6.9(d,J=5.1Hz,1H),6.7(t,J=4.1Hz,1H),6.3(d,J=3.4Hz,1H),4.1(s,2H);13C NMR(101MHz,CDCl3)δ146.5,140.7,129.6,127.9,127.7,126.2,125.7,124.3,58.1,41.8。
实施例10
称取(48.6mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到24.5mg产物(石油醚:乙酸乙酯=50:1),产率73%,1H NMR(400MHz,CDCl3)δ8.3(d,J=3.6Hz,1H),7.3(d,J=7.7Hz,6H),7.3–7.1(m,10H),6.9(dd,J=7.5,5.0Hz,1H),6.3(d,J=7.9Hz,1H),4.2(s,2H);13C NMR(101MHz,CDCl3)δ158.9,148.3,146.7,135.0,129.7,127.7,126.0,125.0,121.0,58.2,49.0。
实施例11
称取(50.0mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到26.5mg产物(石油醚:乙酸乙酯=10:1),产率76%,1H NMR(400MHz,CDCl3)δ7.3(d,J=7.8Hz,6H),7.2(dd,J=7.5Hz,6H),7.2(t,J=7.3Hz,3H),7.1(t,J=7.8Hz,1H),6.8(d,J=7.6Hz,1H),6.1(d,J=7.9Hz,1H),4.2(s,2H),2.4(s,3H);13C NMR(101MHz,CDCl3)δ158.1,156.7,146.8,135.3,129.8,127.6,125.9,121.7,120.3,58.1,49.0,24.3。
实施例12
称取(48.7mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到13.8mg产物/>(石油醚:乙酸乙酯=10:1),产率41%,1H NMR(400MHz,CDCl3)δ8.3(d,J=4.9Hz,2H),7.3(d,J=8.0Hz,6H),7.2(t,J=7.4Hz,6H),7.1(t,J=7.2Hz,3H),6.9(t,J=4.9Hz,1H),4.4(s,2H);13C NMR(101MHz,CDCl3)δ168.8,155.9,147.0,129.6,128.2,127.4,125.8,118.0,58.2,49.9。
实施例13
称取(48.7mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到19.8mg产物/>(石油醚:乙酸乙酯=10:1),产率59%,1H NMR(400MHz,CDCl3)δ8.3–8.3(m,1H),8.2(d,J=2.6Hz,1H),7.5(d,J=1.6Hz,1H),7.4–7.3(m,6H),7.3–7.2(m,6H),7.2–7.1(m,3H),4.2(s,2H);13CNMR(101MHz,CDCl3)δ154.9,146.4,146.2,143.0,141.6,129.5,127.8,126.2,58.4,46.3。
实施例14
称取(52.7mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到11.3mg产物(石油醚:乙酸乙酯=50:1),产率30%,1H NMR(400MHz,CDCl3)δ7.3(t,J=7.4Hz,5H),7.2(t,J=6.4Hz,7H),7.1(d,J=7.8Hz,6H),7.1–6.9(m,2H),3.3(dt,J=12.8,6.5Hz,1H),2.8(ddd,J=14.0,9.4,4.9Hz,1H),2.7–2.6(m,1H),2.1–1.9(m,1H),1.0(d,J=6.4Hz,3H),0.8(dtd,J=13.8,9.3,4.8Hz,1H);13C NMR(101MHz,CDCl3)δ142.3,129.4,129.4,128.7,128.3,126.9,126.2,125.8,61.9,35.3,35.1,34.2,16.1。
实施例15
称取(44.9mg,0.1mmol),2,2,2-三苯乙酸(28.8mg,0.1mmol),KHCO3(10.0mg,0.1mmol),加入反应管,通过真空管线抽换气三次,在氮气氛围下、DMSO(0.5mL)、室温反应6h。干法上样,柱层析(300-400目层析硅胶)得到29.1mg产物/>(石油醚:乙酸乙酯=50:1),产率98%,1H NMR(400MHz,CDCl3)δ7.2(dd,J=13.7,6.6Hz,12H),7.2–7.1(m,3H),4.7(s,1H),4.3(s,1H),3.4(s,2H),1.4(s,3H)。
以上所描述的实施例仅表达了本发明的几种优选实施例,其描述较为具体和详细,但并不用于限制本发明。应当指出,对于本领域的技术人员来说,本发明还可以有各种变化和更改,凡在本发明的构思和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (7)
1.一种构建季碳中心的方法,其特征在于,包括如下步骤:
步骤一、取Katritzky盐与2,2,2-三苯乙酸混合,再加入碳酸氢钾,混合物在氮气氛围下加至溶剂中;
步骤二、步骤一体系在室温下搅拌反应,反应结束加水淬灭,用乙酸乙酯萃取,有机层浓缩层析得到产物;
反应合成路线如下:
2.根据权利要求1所述的构建季碳中心的方法,其特征在于,Katritzky盐中的R1、R2基团分别为各种取代的芳基、烷基、氢。
3.根据权利要求1所述的构建季碳中心的方法,其特征在于,Katritzky盐中的R1基团是各种取代的芳基时,R2为氢。
4.根据权利要求1所述的构建季碳中心的方法,其特征在于,Katritzky盐中的R1基团是-C10H13时,R2为甲基。
5.根据权利要求1所述的构建季碳中心的方法,其特征在于,步骤一所述Katritzky盐、2,2,2-三苯乙酸和碳酸氢钾的物质的量之比为1:1:1。
6.根据权利要求1所述的构建季碳中心的方法,其特征在于,步骤一所述溶剂为0.2M的二甲基亚砜。
7.根据权利要求1所述的构建季碳中心的方法,其特征在于,步骤二搅拌反应时间为6h。
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