CN107474001A - 一种α‑二乙酰氧甲基取代含氮杂环类化合物的合成方法 - Google Patents
一种α‑二乙酰氧甲基取代含氮杂环类化合物的合成方法 Download PDFInfo
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 18
- 238000010189 synthetic method Methods 0.000 title claims abstract description 15
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims abstract description 28
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims abstract description 28
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229940125904 compound 1 Drugs 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 63
- 238000006243 chemical reaction Methods 0.000 claims description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- -1 substituted-phenyl Chemical group 0.000 claims description 8
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract description 9
- 230000032050 esterification Effects 0.000 abstract description 3
- 238000005886 esterification reaction Methods 0.000 abstract description 3
- 235000006408 oxalic acid Nutrition 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000010523 cascade reaction Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- 229920006395 saturated elastomer Polymers 0.000 description 23
- 238000000926 separation method Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 235000002639 sodium chloride Nutrition 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 238000001035 drying Methods 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 239000011734 sodium Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- BPGDAMSIGCZZLK-UHFFFAOYSA-N acetyloxymethyl acetate Chemical class CC(=O)OCOC(C)=O BPGDAMSIGCZZLK-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Abstract
本发明公开了一种α‑二乙酰氧甲基取代含氮杂环类化合物的合成方法,属于有机化学技术领域。将N‑芳基取代含氮杂环类化合物1溶于溶剂中,加入醋酸铜和碘苯二乙酸,在氧气中加热升温反应,经历氧化、缩环和二乙酸酯化等串联反应后制得α‑二乙酰氧甲基取代含氮杂环类化合物2。该合成方法,具有操作简便、条件温和、底物适用范围广等优点,适合于工业化生产。
Description
技术领域
本发明属于有机化学中有机合成技术领域,具体涉及一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法。
背景技术
吡咯烷和哌啶均为非常重要的含氮杂环,它们不仅是多种天然产物及临床药物中的核心结构单元,而且也是合成香料、染料、生物探针等多种有机功能分子的重要原料。另一方面,亚甲基二乙酸酯是醛羰基的主要保护形式之一,具有生成效率高、在多种反应条件下相对稳定、易去除等优点。同时,亚甲基二乙酸酯类化合物也是常用的有机合成中间体。作为含氮杂环和亚甲基二乙酸酯的杂化体,α-二乙酰氧甲基取代含氮杂环类化合物在有机合成化学、药物化学、材料化学等领域均具有潜在的应用价值。需要指出的是,尽管这两类化合物具有重要的研究意义,但它们的合成目前却鲜有报道。因此,研究并开发以简单易得的试剂为原料、经由简便的操作步骤、在温和的反应条件下合成α-二乙酰氧甲基取代含氮杂环类化合物的有效方法,不仅具有重要的理论意义,而且具有潜在的应用价值。
发明内容
本发明解决的技术问题是提供了一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,该合成方法通过N-芳基取代含氮杂环类化合物的氧化、缩环和二乙酸酯化等串联反应合成α-二乙酰氧甲基取代含氮杂环类化合物,具有操作简便、条件温和、底物适用范围广等优点,适合于工业化生产。
本发明为解决上述技术问题采用如下技术方案,一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于,合成过程包括以下步骤:将N-芳基取代含氮杂环类化合物1溶于溶剂中,然后加入醋酸铜和碘苯二乙酸,在氧气中加热升温反应制得α-二乙酰氧甲基取代含氮杂环类化合物2,该合成方法的反应方程式为:
其中R为苯基或取代苯基,取代苯基苯环上的取代基为氟、氯、溴、硝基、C1-4烷基或甲氧基中的一个或多个,n为1或2。
进一步地,所述反应溶剂为起到溶解原料的作用,优选乙腈、二氯乙烷、1,4-二氧六环、N,N-二甲基甲酰胺或二甲基亚砜。
进一步地,所述反应温度为50-100℃,所述反应在1-2atm氧气氛围下进行。
进一步地,所述N-芳基取代含氮杂环类化合物1、醋酸铜和碘苯二乙酸的摩尔比为1:0.5-2:0.5-2。
本发明与现有技术相比具有以下优点:(1)合成过程简单、高效,通过N-芳基取代含氮杂环类化合物的氧化、缩环和二乙酸酯化等串联反应,在一锅中直接得到α-二乙酰氧甲基取代含氮杂环类化合物;(2)原料价廉易得;(3)反应条件温和,操作简便;(4)底物的适用范围广。因此,本发明为α-二乙酰氧甲基取代含氮杂环类化合物的合成提供了一种经济实用且绿色环保的新方法。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明,但不应该将此理解为本发明上述主题的范围仅限于以下的实施例,凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(89mg,64%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.83-2.15(m,10H),3.09(dd,J1=16.8Hz,J2=9.2Hz,1H),3.43(t,J=8.8Hz,1H),3.96(dd,J1=8.0Hz,J2=4.8Hz,1H),6.64(t,J=7.2Hz,1H),6.72(d,J=8.4Hz,2H),6.81(d,J=4.8Hz,1H),7.16(t,J=8.4Hz,2H).13C NMR(150MHz,CDCl3):20.7,20.9,23.8,26.6,49.1,59.6,89.4,112.6,116.8,129.1,147.5,169.0.HRMS calcd forC15H20NO4:278.1387[M+H]+,found:278.1395。
实施例2
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.25mmol,45mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(49mg,35%)。
实施例3
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(1.0mmol,180mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(67mg,48%)。
实施例4
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、二氯乙烷(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(55mg,40%)。
实施例5
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、1,4-二氧六环(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(57mg,41%)。
实施例6
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、二甲基亚砜(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(54mg,39%)。
实施例7
向10mL史莱克管中依次加入1a(0.5mmol,81mg)、N,N-二甲基甲酰胺(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氮气之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(61mg,44%)。
实施例8
将1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg)加入到10mL史莱克管中,在氧气(1atm)气氛下于50℃搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(28mg,20%)。
实施例9
将1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg)加入到10mL耐压管中,在氧气(1atm)气氛下于100℃搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(19mg,14%)。
实施例10
将1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.25mmol,81mg)加入到10mL史莱克管中,在氧气(1atm)气氛下于80℃搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(19mg,10%)。
实施例11
将1a(0.5mmol,81mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(1.0mmol,322mg)加入到10mL史莱克管中,在氧气(1atm)气氛下于80℃搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2a(83mg,60%)。
实施例12
向10mL史莱克管中依次加入1b(0.5mmol,98mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2b(86mg,55%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.76-2.18(m,10H),3.00-3.05(m,1H),3.70-3.76(m,1H),4.38-4.42(m,1H),6.72(d,J=5.6Hz,1H),6.89(t,J=7.6Hz,1H),7.09(d,J=7.6Hz,1H),7.16(t,J=7.6Hz,1H),7.31(d,J=8.0Hz,1H).13C NMR(150MHz,CDCl3):20.4,20.8,24.1,26.4,52.9,59.5,89.3,121.7,122.7,127.2,127.9,130.8,145.9,168.69,168.73.HRMS calcd forC15H19ClNO4:312.0997[M+H]+,found:312.0982。
实施例13
向10mL史莱克管中依次加入1c(0.5mmol,90mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2c(77mg,52%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.93-2.22(m,10H),3.15(dd,J1=16.8Hz,J2=8.8Hz,1H),3.46(t,J=8.8Hz,1H),4.00(dd,J1=8.0Hz,J2=5.2Hz,1H),6.39-6.43(m,1H),6.48(d,J=12.8Hz,1H),6.55(dd,J1=8.4Hz,J2=1.6Hz,1H),6.85(d,J=5.2Hz,1H),7.14(dd,J1=15.6Hz,J2=7.6Hz,1H).13C NMR(150MHz,CDCl3):20.7,20.9,23.7,26.6,49.1,59.8,89.2,99.8(d,2JC-F=26.3Hz),103.3(d,2JC-F=21.9Hz),108.3(d,4JC-F=2.3Hz),130.1(d,3JC-F=11.0Hz),149.2(d,3JC-F=9.9Hz),163.9(d,1JC-F=240.6Hz),168.92,168.95.HRMS calcd forC15H18FNNaO4:318.1112[M+Na]+,found:318.1105。
实施例14
向10mL史莱克管中依次加入1d(0.5mmol,120mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2d(91mg,51%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.94-2.21(m,10H),3.14(dd,J1=16.8Hz,J2=9.2Hz,1H),3.46(t,J=8.4Hz,1H),4.02(dd,J1=7.6Hz,J2=5.2Hz,1H),6.71(dd,J1=8.4Hz,J2=1.6Hz,1H),6.82(d,J=5.6Hz,2H),6.93(s,1H),7.07(t,J=8.0Hz,1H).13C NMR(100MHz,CDCl3):20.7,20.9,23.6,26.7,49.1,59.6,89.2,111.3,115.5,119.6,123.2,130.3,148.6,168.90,168.94.HRMS calcd for C15H18BrNNaO4:378.0311[M+Na]+,found:378.0341。
实施例15
向10mL史莱克管中依次加入1e(0.5mmol,95mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2e(102mg,67%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.19(t,J=7.6Hz,3H),1.90-2.20(m,10H),2.55(q,J=7.6Hz,2H),3.10-3.14(m,1H),3.49(t,J=8.4Hz,1H),3.98(dd,J1=8.0Hz,J2=4.4Hz,1H),6.74(d,J=8.4Hz,2H),6.87(d,J=4.4Hz,1H),7.07(d,J=8.4Hz,2H).13C NMR(150MHz,CDCl3):16.1,20.8,20.9,24.0,26.5,27.8,49.3,59.8,89.4,112.6,128.5,132.6,145.7,169.0.HRMS calcd forC17H23NNaO4:328.1519[M+Na]+,found:328.1520。
实施例16
向10mL史莱克管中依次加入1f(0.5mmol,95mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=10/1)得油状产物2f(101mg,66%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.89-2.17(m,10H),2.28(s,6H),3.11-3.18(m,1H),3.49(t,J=8.4Hz,1H),4.00(dd,J1=8.0Hz,J2=4.4Hz,1H),6.40(s,1H),6.45(s,2H),6.87(d,J=4.4Hz,1H).13C NMR(100MHz,CDCl3):20.8,20.9,21.7,23.9,26.5,49.2,59.6,89.5,110.6,118.8,138.7,147.7,168.99,169.01.HRMScalcd for C17H23NNaO4:328.1519[M+Na]+,found:328.1538。
实施例17
向10mL史莱克管中依次加入1g(0.5mmol,88mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2g(87mg,60%)。该化合物的表征数据如下:1H NMR(600MHz,CDCl3):1.53(s,3H),1.58-1.85(m,6H),2.08(s,3H),3.21(t,J=11.4Hz,1H),3.42(d,J=12.0Hz,1H),4.19(s,1H),6.72(t,J=6.6Hz,1H),6.86(d,J=7.2Hz,2H),7.19(t,J=6.6Hz,2H),7.26(d,J=7.2Hz,1H).13C NMR(150MHz,CDCl3):19.5,20.3,20.8,25.0,25.0,43.5,56.8,86.6,115.8,118.1,129.0,151.2,168.8,168.9.HRMS calcd forC16H22NO4:292.1543[M+H]+,found:292.1540。
实施例18
向10mL史莱克管中依次加入1h(0.5mmol,103mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2h(109mg,68%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.60(s,3H),1.62-1.82(m,6H),2.07(s,3H),3.16-3.25(m,2H),3.74(s,3H),3.94-3.97(m,1H),6.79(d,J=8.8Hz,2H),6.84(d,J=8.8Hz,2H),7.17(d,J=8.0Hz,1H).13C NMR(100MHz,CDCl3):19.9,20.5,20.9,25.08,25.12,45.5,55.7,57.9,86.8,114.4,118.3,145.5,152.8,168.8,168.9.HRMScalcd for C17H23NNaO5:344.1468[M+Na]+,found:344.1476。
实施例19
向10mL史莱克管中依次加入1i(0.5mmol,97mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2i(74mg,48%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.59(s,3H),1.61-1.86(m,6H),2.10(s,3H),3.16-3.22(m,1H),3.42(d,J=12.8Hz,1H),4.10-4.17(m,1H),6.39-6.43(m,1H),6.54(d,J=12.8Hz,1H),6.61(d,J=8.0Hz,1H),7.12(dd,J1=16.0Hz,J2=7.6Hz,1H),7.24(s,1H).13C NMR(100MHz,CDCl3):19.3,20.3,20.8,24.7,24.9,43.4,56.6,86.5,102.5(d,2JC-F=24.7Hz),104.3(d,2JC-F=21.1Hz),110.9(d,4JC-F=2.9Hz),129.9(d,3JC-F=9.5Hz),152.9(d,3JC-F=10.2Hz),163.9(d,1JC-F=240.7Hz),168.7,168.8.HRMS calcd forC16H20FNNaO4:332.1269[M+Na]+,found:332.1276。
实施例20
向10mL史莱克管中依次加入1j(0.5mmol,127mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2j(91mg,49%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.53(s,3H),1.57-1.78(m,6H),2.03(s,3H),3.09-3.15(m,1H),3.33(d,J=13.2Hz,1H),4.06-4.08(m,1H),6.70(dd,J1=8.4Hz,J2=1.6Hz,1H),6.76(d,J=7.6Hz,1H),6.91(s,1H),6.97(t,J=8.4Hz,1H),7.18(d,J=9.2Hz,1H).13C NMR(100MHz,CDCl3):19.3,20.3,20.8,24.8,24.9,43.4,56.7,86.5,114.2,118.5,120.8,123.1,130.1,152.5,168.7,168.8.HRMS calcd for C16H20BrNNaO4:392.0468[M+Na]+,found:392.0499。
实施例21
向10mL史莱克管中依次加入1k(0.5mmol,95mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2k(101mg,66%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):1.57(s,3H),1.62-1.80(m,6H),2.08(s,3H),2.23(s,3H),3.16-3.22(m,1H),3.34-3.37(m,1H),4.07-4.11(m,1H),6.77(d,J=8.4Hz,2H),7.01(d,J=8.0Hz,2H),7.23(d,J=8.4Hz,1H).13C NMR(150MHz,CDCl3):19.7,20.3,20.4,20.9,24.9,25.0,44.11,57.2,86.7,116.2,127.5,129.4,149.0,168.8,168.9.HRMS calcd forC17H23NNaO4:328.1519[M+Na]+,found:328.1520。
实施例22
向10mL史莱克管中依次加入1l(0.5mmol,105mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得油状产物2l(88mg,54%)。该化合物的表征数据如下:1H NMR(600MHz,CDCl3):1.58(s,3H),1.60-1.85(m,6H),2.09(s,3H),3.17-3.21(m,1H),3.36(d,J=12.6Hz,1H),4.12(s,1H),6.78(d,J=8.4Hz,2H),7.14(d,J=8.4Hz,2H),7.23(d,J=8.4Hz,1H).13C NMR(150MHz,CDCl3):19.3,20.4,20.8,24.8,25.0,43.6,56.8,86.6,116.9,122.7,128.7,149.8,168.7,168.8.HRMS calcdforC16H21ClNO4:326.1154[M+H]+,found:326.1172。
实施例23
向10mL史莱克管中依次加入1m(0.5mmol,110mg)、乙腈(5mL)、醋酸铜(0.5mmol,90mg)和碘苯二乙酸(0.5mmol,161mg),抽真空充氧气(1atm)之后将其置于80℃油浴中搅拌反应12h。然后,加入10mL饱和食盐水淬灭反应,用乙酸乙酯萃取(10mL×3),合并有机相,用无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=5/1)得目标产物2m。
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明原理的范围下,本发明还会有各种变化和改进,这些变化和改进均落入本发明保护的范围内。
Claims (5)
1.一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于,包括以下步骤:将N-芳基取代含氮杂环类化合物1溶于溶剂中,加入醋酸铜和碘苯二乙酸,在氧气中加热升温反应制得α-二乙酰氧甲基取代含氮杂环类化合物2,该合成方法的反应方程式为:
其中R为苯基或取代苯基,取代苯基苯环上的取代基为氟、氯、溴、硝基、C1-4烷基或甲氧基中的一个或多个,n为1或2。
2.根据权利要求1中一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于:所述反应溶剂选自乙腈、二氯乙烷、1,4-二氧六环、N,N-二甲基甲酰胺或二甲基亚砜。
3.根据权利要求1中一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于:所述反应温度为50-100℃。
4.根据权利要求1中一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于:所述化合物1、醋酸铜和碘苯二乙酸的摩尔比为1:0.5-2:0.5-2。
5.根据权利要求1中一种α-二乙酰氧甲基取代含氮杂环类化合物的合成方法,其特征在于:所述氧气在1-2atm氛围下进行。
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Title |
---|
HE, YAN, ET AL.: ""C (sp 3)–H dehydrogenation and C (sp 2)–H alkoxy carbonylation of inactivated cyclic amines towards functionalized N-heterocycles"", 《CHEMICAL COMMUNICATIONS》 * |
TIAN, JIE‐SHENG, ET AL.: ""Copper‐Catalyzed Rearrangement of Tertiary Amines through Oxidation of Aliphatic C-H Bonds in Air or Oxygen: Direct Synthesis of α‐Amino Acetals."", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION》 * |
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