CN112142664A - 一种多取代萘并氮杂环类化合物的合成方法 - Google Patents
一种多取代萘并氮杂环类化合物的合成方法 Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 72
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- 238000000034 method Methods 0.000 claims abstract description 11
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- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
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- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 58
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical group CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- XMNIXWIUMCBBBL-UHFFFAOYSA-N 2-(2-phenylpropan-2-ylperoxy)propan-2-ylbenzene Chemical compound C=1C=CC=CC=1C(C)(C)OOC(C)(C)C1=CC=CC=C1 XMNIXWIUMCBBBL-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
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- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical group Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 3
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
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- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 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 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000012512 characterization method Methods 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 9
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- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002790 naphthalenes Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/08—Aza-anthracenes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
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Abstract
本发明公开了一种多取代萘并氮杂环类化合物的合成方法,属于有机合成技术领域。本发明的技术方案要点为:将邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物和饱和环胺类化合物溶于溶剂中,再向反应体系中加入催化剂或者催化剂和氧化剂,在空气或氧气气氛下于60‑120℃反应制得目标产物多取代萘并氮杂环类化合物。本发明通过邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物与简便易得饱和环胺类化合物之间的一锅多步串联反应合成目标产物多取代萘并氮杂环类化合物,具有操作简便、条件温和、底物适用范围广等优点,适用于工业化生产。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种多取代萘并氮杂环类化合物的合成方法。
背景技术
多取代萘并氮杂环类化合物是许多天然产物、抗肿瘤药物及发光、半导体材料的重要结构单元,在化学生物学和材料化学等领域具有重要的研究价值。目前,多取代萘并氮杂环类化合物的合成通常是以萘并氮杂环为原料、经后期进一步官能团化来完成。这一方法尽管比较可靠,但仍存在原料难以制备、反应步骤繁琐、总收率低等问题。需要指出的是,从易得的原料出发直接完成萘并氮杂环结构单元的一锅法高效构建,目前尚未见相关文献报道。有鉴于此,进一步研究并开发从易得的原料出发合成多取代萘并氮杂环类化合物的简捷、高效新方法具有重要的意义。
发明内容
本发明解决的技术问题是提供了一种多取代萘并氮杂环类化合物的合成方法,该合成方法通过邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物与简便易得饱和环胺类化合物之间的一锅多步串联反应合成目标产物多取代萘并氮杂环类化合物,具有操作简便、条件温和、底物适用范围广等优点,适用于工业化生产。
本发明为解决上述技术问题采用如下技术方案,一种多取代萘并氮杂环类化合物的合成方法,其特征在于具体过程为:将邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物1和饱和环胺类化合物2溶于溶剂中,再向反应体系中加入催化剂或者催化剂和氧化剂,在空气或氧气气氛下于60-120℃反应制得目标产物多取代萘并氮杂环类化合物3,该合成方法中的反应方程式为:
其中R1为氢、氟、氯、溴、苯基、取代苯基、C1-4烷基、C1-4烷氧基或亚甲二氧基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,R2为苯基、取代苯基或C1-4烷基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,R3为氢或C1-5烷基,R4为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,X=C或N-R5,R5为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,n=0或1,催化剂为溴化铜、氯化钯或三氟甲磺酸钯,氧化剂为叔丁基过氧化氢(TBHP)、二叔丁基过氧化物(TBP)或过氧化二异丙苯(DCP),溶剂为甲苯、乙腈、四氢呋喃或1,4-二氧六环。
进一步优选,所述邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物1与饱和环胺类化合物2、催化剂以及氧化剂的投料物质的量之比为1:1-4:0.05-0.2:1-4。
本发明与现有技术相比具有以下优点:(1)本发明通过邻炔基取代芳基醛或邻炔基取代芳基酮类化合物与饱和环胺类化合物之间的一锅多步串联反应直接合成目标产物多取代萘并氮杂环类化合物,该反应不仅直接构建出萘并氮杂环的结构单元,而且同时将酰基引入到分子中,整个过程操作简单、效率较高;(2)本发明的反应原料简单易得;(3)本发明的反应底物适用范围广。因此,本发明为多取代萘并氮杂环类化合物的合成提供了一种经济实用的新方法。
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
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(46mg,63%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:2.04(br s,2H),2.93(t,J=6.4Hz,2H),3.34(t,J=6.4Hz,2H),6.45(d,J=8.0Hz,2H),6.82(t,J=7.6Hz,1H),7.02(t,J=7.6Hz,2H),7.25-7.29(m,2H),7.33-7.37(m,4H),7.45(t,J=6.8Hz,1H),7.73(s,1H),7.77(dd,J1=6.0Hz,J2=3.6Hz,1H),7.84-7.86(m,1H).13C NMR(150MHz,CDCl3)δ:24.3,28.4,50.5,120.9,121.5,124.1,124.4,125.0,126.6,127.4,127.8,128.5,128.8,129.0,129.8,131.4,132.4,133.0,139.4,142.1,149.2,197.1.MS:m/z 364[M+H]+。
实施例2
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.04mmol,7mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(43mg,59%)。
实施例3
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.8mmol,160μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(39mg,53%)。
实施例4
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg)和氯化钯(0.01mmol,2mg),在氧气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(31mg,42%)。
实施例5
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),溴化铜(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(23mg,31%)。
实施例6
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBP(0.2mmol,37μL),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(39mg,54%)。
实施例7
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和DCP(0.2mmol,50μL),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(31mg,42%)。
实施例8
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于120℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(38mg,52%)。
实施例9
在反应管中依次加入1a(0.2mmol,41mg),乙腈(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(44mg,60%)。
实施例10
在反应管中依次加入1a(0.2mmol,41mg),四氢呋喃(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(30mg,41%)。
实施例11
在反应管中依次加入1a(0.2mmol,41mg),1,4-二氧六环(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3a(27mg,37%)。
实施例12
在反应管中依次加入1b(0.2mmol,45mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3b(53mg,70%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:2.03(br s,2H),2.92(t,J=6.0Hz,2H),3.33(t,J=6.4Hz,2H),6.43(d,J=8.0Hz,2H),6.82(t,J=7.2Hz,1H),7.02(t,J=7.6Hz,2H),7.10-7.15(m,1H),7.25-7.40(m,5H),7.44-7.48(m,1H),7.66(s,1H),7.84(dd,J1=9.2Hz,J2=5.6Hz,1H).13C NMR(150MHz,CDCl3)δ:24.2,28.4,50.4,110.5(d,2JC-F=19.8Hz),116.6(d,2JC-F=25.2Hz),120.8,121.6,125.2,126.6(d,3JC-F=8.7Hz),127.8,128.0(d,4JC-F=4.4Hz),128.3,128.5,129.0,130.6(d,3JC-F=8.7Hz),132.6,134.5,139.2,141.5(d,4JC-F=2.3Hz),149.1,159.9(d,1JC-F=243.9Hz),197.0.19FNMR(565MHz,CDCl3)δ:-117.5.MS:m/z 404[M+Na]+。
实施例13
在反应管中依次加入1c(0.2mmol,44mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3c(45mg,60%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:2.02(br s,2H),2.38(s,3H),2.90(t,J=6.4Hz,2H),3.31(t,J=6.4Hz,2H),6.43(d,J=8.0Hz,2H),6.82(t,J=7.6Hz,1H),7.02(t,J=8.0Hz,2H),7.20(d,J=8.4Hz,1H),7.27(t,J=7.6Hz,2H),7.34(d,J=8.0Hz,2H),7.46(t,J=6.8Hz,1H),7.66-7.69(m,3H).13C NMR(150MHz,CDCl3)δ:22.0,24.4,28.3,50.4,120.7,121.3,123.0 124.6,126.7,127.3,127.8,128.2,128.5,128.7,129.0,131.5,132.0,132.4,136.5,139.5,142.2,149.3,197.4.MS:m/z 378[M+H]+。
实施例14
在反应管中依次加入1d(0.2mmol,50mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色固体产物3d(40mg,49%)。该化合物的表征数据如下:m.p.:197-198℃.1H NMR(400MHz,CDCl3)δ:1.98(br s,2H),2.86(t,J=6.4Hz,2H),3.28(t,J=6.4Hz,2H),5.95(s,2H),6.41(d,J=7.6Hz,2H),6.80(t,J=7.6Hz,1H),7.00-7.06(m,3H),7.23-7.34(m,5H),7.43-7.47(m,1H),7.55(s,1H).13C NMR(150MHz,CDCl3)δ:24.1,28.0,50.4,101.0,101.1,103.6,120.6,121.1,125.7,126.9,127.8,128.2,128.5,128.9,131.1,132.4,139.4,140.8,146.5,148.6,149.5,197.5.MS:m/z 408[M+H]+。
实施例15
在反应管中依次加入1e(0.2mmol,44mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色固体产物3e(56mg,74%)。该化合物的表征数据如下:m.p.:166-167℃.1H NMR(400MHz,CDCl3)δ:2.04(br s,2H),2.28(s,3H),2.92(t,J=6.0Hz,2H),3.33(t,J=6.4Hz,2H),6.45(d,J=8.0Hz,2H),6.82(t,J=7.2Hz,1H),7.02(t,J=7.6Hz,2H),7.11-7.17(m,3H),7.25(s,1H),7.34-7.38(m,2H),7.73(s,1H),7.77(dd,J1=6.0Hz,J2=3.2Hz,1H),7.86(dd,J1=6.4Hz,J2=3.6Hz,1H).13C NMR(150MHz,CDCl3)δ:21.2,24.5,28.4,50.3,120.6,121.4,124.1,124.4,125.2,126.2,126.6,127.4,127.6,128.4,128.7,129.5,129.9,131.4,133.16,133.23,137.5,139.4,142.1,149.1,197.4.MS:m/z 378[M+H]+。
实施例16
在反应管中依次加入1f(0.2mmol,34mg),甲苯(1mL),2a(0.6mmol,97mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色固体产物3f(35mg,54%)。该化合物的表征数据如下:m.p.:181-182℃.1H NMR(400MHz,CDCl3)δ:0.69-0.72(m,2H),0.75-0.78(m,2H),2.06-2.09(m,2H),2.21-2.24(m,1H),2.97(t,J=6.0Hz,2H),3.80(t,J=6.4Hz,2H),6.87-6.93(m,3H),7.15-7.18(m,2H),7.33-7.37(m,2H),7.67(s,1H),7.72(dd,J1=7.6Hz,J2=2.0Hz,1H),7.79(dd,J1=7.6Hz,J2=1.6Hz,1H).13C NMR(150MHz,CDCl3)δ:11.9,23.6,23.7,28.5,51.4,121.1,121.6,124.1,124.3,126.5,127.3,128.6,128.7,129.3,129.65,129.67,132.8,140.8,150.0,206.1.MS:m/z328[M+H]+。
实施例17
在反应管中依次加入1a(0.2mmol,41mg),甲苯(1mL),2b(0.6mmol,107mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3g(21mg,28%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:2.03-2.06(m,2H),3.07(t,J=6.4Hz,2H),3.46(t,J=6.0Hz,2H),6.67-6.74(m,2H),6.79-6.88(m,2H),7.27-7.31(m,4H),7.45-7.48(m,3H),7.54(d,J=8.0Hz,1H),7.69-7.74(m,2H).13C NMR(100MHz,CDCl3)δ:22.6,28.6,51.8(d,4JC-F=3.6Hz),116.2(d,2JC-F=19.5Hz),123.8(d,2JC-F=28.8Hz),124.09,124.12,125.1,125.2,126.4,127.3,127.9,128.1(d,4JC-F=2.1Hz),129.1(d,3JC-F=10.1Hz),129.3,130.1,131.3,132.8,137.0(d,3JC-F=10.1Hz),138.0,142.1,157.3(d,1JC-F=247.7Hz),197.4.19F NMR(376MHz,CDCl3)δ:-120.9.MS:m/z 404[M+Na]+。
实施例18
在反应管中依次加入1g(0.2mmol,47mg),甲苯(1mL),2c(0.6mmol,143mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3h(59mg,63%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:2.06(br s,2H),2.92(br s,2H),3.36(t,J=6.4Hz,2H),3.85(d,J=3.6Hz,3H),6.38(d,J=8.8Hz,2H),6.77(d,J=8.8Hz,2H),7.09(d,J=8.8Hz,2H),7.34-7.38(m,4H),7.72(s,1H),7.75-7.80(m,2H).13C NMR(150MHz,CDCl3)δ:24.2,28.2,50.6,55.5,113.2,113.8,122.5,124.2,124.6,125.8,126.6,127.4,128.6,130.0,131.29,131.31,131.3,132.0,132.9,141.0,148.2,163.3,195.8.MS:m/z 472[M+H]+。
实施例19
在反应管中依次加入1g(0.2mmol,47mg),甲苯(1mL),2d(0.6mmol,109mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色固体产物3i(28mg,34%)。该化合物的表征数据如下:m.p.:138-139℃.1H NMR(400MHz,CDCl3)δ:3.30(t,J=8.0Hz,2H),3.83(s,3H),3.89(t,J=7.6Hz,2H),6.58(s,1H),6.71(d,J=8.4Hz,2H),6.78(d,J=8.0Hz,1H),6.88(d,J=8.0Hz,1H),6.99(t,J=8.0Hz,1H),7.27-7.32(m,4H),7.67-7.70(m,2H),7.79(d,J=8.4Hz,1H).13C NMR(150MHz,CDCl3)δ:28.1,55.5,55.8,113.1,113.4,121.1,123.28,123.31,123.8,123.9,125.7,126.8,127.6,129.3,129.7,131.36,131.44,132.1,133.7,134.4,145.2,146.4,163.4,195.6.MS:m/z414[M+H]+。
实施例20
在反应管中依次加入1g(0.2mmol,47mg),甲苯(1mL),2e(0.6mmol,134mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3j(42mg,46%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:3.33(t,J=7.6Hz,2H),3.78(s,3H),3.95(t,J=7.6Hz,2H),6.64(d,J=8.8Hz,2H),6.84(d,J=8.4Hz,2H),7.23-7.34(m,7H),7.43(t,J=7.2Hz,2H),7.50(d,J=7.6Hz,2H),7.67-7.70(m,2H),7.75(d,J=8.4Hz,1H).13C NMR(150MHz,CDCl3)δ:28.1,55.4,56.1,112.8,113.1,123.0,123.6,123.8,125.5,126.7,126.8,127.0,127.3,127.6,128.8,129.1,131.4,131.8,132.3,133.9,136.8,140.8,144.5,145.9,163.2,195.9.MS:m/z 456[M+H]+。
实施例21
在反应管中依次加入1g(0.2mmol,47mg),甲苯(1mL),2f(0.6mmol,143mg),氯化钯(0.01mmol,2mg)和TBHP(0.2mmol,40μL,5-6mol/L in decane),在空气气氛下于80℃搅拌反应8h,然后加入10mL饱和氯化钠溶液淬灭反应,用二氯甲烷萃取(10mL×3),合并有机相,无水硫酸钠干燥。过滤,旋干,过硅胶柱分离(石油醚/乙酸乙酯=40/1,v/v)得黄色液体产物3k(24mg,26%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ:3.67(br s,4H),3.85(s,3H),6.50(d,J=80Hz,2H),6.80(d,J=8.4Hz,2H),6.87(t,J=7.6Hz,1H),7.07-7.15(m,3H),7.21-7.25(m,3H),7.38(d,J=8.0Hz,2H),7.44-7.49(m,3H),7.55(t,J=7.6Hz,3H).13C NMR(150MHz,CDCl3)δ:47.6,49.9,55.4,111.5,113.2,122.1,122.4,123.7,124.2,125.0,125.1,125.4,126.2,128.8,129.9,131.4,131.5,131.8,132.2,138.5,147.0,149.3,163.3,195.7.MS:m/z 471[M+H]+。
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 (2)
1.一种多取代萘并氮杂环类化合物的合成方法,其特征在于具体过程为:将邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物1和饱和环胺类化合物2溶于溶剂中,再向反应体系中加入催化剂或者催化剂和氧化剂,在空气或氧气气氛下于60-120℃反应制得目标产物多取代萘并氮杂环类化合物3,该合成方法中的反应方程式为:
其中R1为氢、氟、氯、溴、苯基、取代苯基、C1-4烷基、C1-4烷氧基或亚甲二氧基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,R2为苯基、取代苯基或C1-4烷基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,R3为氢或C1-5烷基,R4为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,X=C或N-R5,R5为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、C1-4烷基或C1-4烷氧基,n=0或1,催化剂为溴化铜、氯化钯或三氟甲磺酸钯,氧化剂为叔丁基过氧化氢(TBHP)、二叔丁基过氧化物(TBP)或过氧化二异丙苯(DCP),溶剂为甲苯、乙腈、四氢呋喃或1,4-二氧六环。
2.根据权利要求1所述的多取代萘并氮杂环类化合物的合成方法,其特征在于:所述邻炔基取代芳基醛类化合物或邻炔基取代芳基酮类化合物1与饱和环胺类化合物2、催化剂以及氧化剂的投料物质的量之比为1:1-4:0.05-0.2:1-4。
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CN108516952A (zh) * | 2018-03-30 | 2018-09-11 | 河南师范大学 | 一种3-酰基六元含氮杂环类化合物的合成方法 |
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CN107501277A (zh) * | 2017-09-18 | 2017-12-22 | 河南师范大学 | 一种呋喃酮并氢化吖庚因类化合物的合成方法 |
CN108516952A (zh) * | 2018-03-30 | 2018-09-11 | 河南师范大学 | 一种3-酰基六元含氮杂环类化合物的合成方法 |
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