CN115504932B - 一种3-取代喹啉类化合物的合成方法 - Google Patents
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- -1 3-substituted quinoline compound Chemical class 0.000 title claims abstract description 25
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 52
- OBAJXDYVZBHCGT-UHFFFAOYSA-N tris(pentafluorophenyl)borane Chemical group FC1=C(F)C(F)=C(F)C(F)=C1B(C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F OBAJXDYVZBHCGT-UHFFFAOYSA-N 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 claims description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 abstract description 13
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 150000008316 benzisoxazoles Chemical class 0.000 abstract description 2
- 238000011065 in-situ storage Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- 238000003756 stirring Methods 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 16
- 238000012512 characterization method Methods 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 16
- 239000007788 liquid Substances 0.000 description 9
- 239000012263 liquid product Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 5
- 239000012265 solid product Substances 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
本发明公开了一种3‑取代喹啉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:将饱和胺类化合物和苯并异噁唑类化合物溶于溶剂中,再向反应体系加入催化剂,在空气气氛下于120‑160℃反应制得目标产物3‑取代喹啉类化合物。本发明通过饱和胺类化合物与苯并异噁唑类化合物之间的串联反应直接合成3‑取代喹啉类化合物,该反应不仅直接构建出喹啉结构单元,而且同时将仲胺基团引入到原位生成喹啉的3位,整个过程操作简单,无需任何金属催化剂或氧化剂且反应原子经济性高;原料简单易得;底物的适用范围广,适合于工业化生产。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种3-取代喹啉类化合物的合成方法。
背景技术
取代喹啉类化合物是许多天然产物以及抗肿瘤药物的重要结构单元,在化学生物学和药物合成等领域具有重要的研究价值。目前,3-取代喹啉类化合物的合成通常是以喹啉为原料、经后期进一步官能团化来完成。这一方法尽管比较可靠,但仍存在反应条件苛刻、添加剂用量高、化学区域选择性低、反应步骤繁琐等问题。需要指出的是,从易得的简单饱和胺类原料出发完成3-取代喹啉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简单原料出发合成3-取代喹啉类化合物的简捷、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3-取代喹啉类化合物的合成方法,该合成方法通过简便易得饱和胺类化合物与苯并异噁唑类化合物之间的一锅多步串联反应合成3-取代喹啉类化合物,具有操作简便、条件温和、无需等量或过量添加剂、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3-取代喹啉类化合物的合成方法,其特征在于具体过程为:将饱和胺类化合物1和苯并异噁唑类化合物2溶于溶剂中,再向反应体系加入催化剂,在空气气氛下于120-160℃反应制得目标产物3-取代喹啉类化合物3,该合成方法中的反应方程式为:
其中R为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、碘、氰基、硝基、三氟甲基、C1-4烷基、烷氧基或烷硫基,R1为氢、C1-4烷基或苯基,R2为氟、氯、溴、碘、氰基、硝基、三氟甲基、C1-4烷基或烷氧基,催化剂为三(五氟苯基)硼烷、三氟乙酸或三溴化铟,溶剂为甲苯、1,2-二氟苯、三氟甲基苯、二氯乙烷或氯仿。
进一步优选,所述饱和胺类化合物1、苯并异噁唑类化合物2与催化剂的投料物质的量之比为1:1.5-4:0.1-0.3。
本发明与现有技术相比具有以下优点:(1)本发明通过饱和胺类化合物与苯并异噁唑类化合物之间的串联反应直接合成目标产物3-取代喹啉类化合物,该反应不仅直接构建出喹啉结构单元,而且同时将仲胺基团引入到原位生成喹啉的3位,整个过程操作简单,无需任何金属催化剂或氧化剂且反应原子经济性高;(2)原料简单易得;(3)底物的适用范围广。因此,本发明为3-取代喹啉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,32mg),氯仿(CHCl3,1mL),2a(0.6mmol,71mg),和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(35mg,66%)。该化合物的表征数据如下:1H NMR(400MHz,DMSO-d6):δ8.84(d,J=2.0Hz,1H),8.15(s,1H),8.01(d,J=8.4Hz,1H),7.91(d,J=8.4Hz,1H),7.72-7.68(m,1H),7.60-7.56(m,1H),7.07(t,J=8.0Hz,2H),6.58(d,J=8.4Hz,1H),6.53(t,J=7.2Hz,2H),5.64(br s,1H),3.07(t,J=6.8Hz,2H),2.90(t,J=7.6Hz,2H),2.01-1.94(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.8,148.2,146.9,134.4,134.3,129.3,129.1,128.8,128.2,127.4,126.8,117.5,112.8,43.3,30.8,30.7.MS:m/z 263[M+H]+。
实施例2
在反应管中依次加入1a(0.2mmol,32mg),1,2-二氟苯(1mL),2a(0.6mmol,71mg),和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(34mg,64%)。
实施例3
在反应管中依次加入1a(0.2mmol,32mg),二氯乙烷(1mL),2a(0.6mmol,71mg),和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(32mg,62%)。
实施例4
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.3mmol,36mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(28mg,53%)。
实施例5
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.8mmol,95mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(30mg,57%)。
实施例6
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.02mmol,10mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(21mg,41%)。
实施例7
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.06mmol,31mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(31mg,60%)。
实施例8
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三氟乙酸(0.04mmol,3μL),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(21mg,41%)。
实施例9
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三溴化铟(0.04mmol,14mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(27mg,52%)。
实施例10
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于100℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(21mg,41%)。
实施例11
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于160℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3a(30mg,57%)。
实施例12
在反应管中依次加入1b(0.2mmol,36mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3b(40mg,71%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.80(d,J=2.0Hz,1H),8.09(d,J=8.4Hz,1H),7.93(d,J=1.2Hz,1H),7.76(d,J=8.4Hz,1H),7.69-7.65(m,1H),7.53(t,J=8.0Hz,1H),6.90-6.85(m,2H),6.54-6.51(m,2H),3.74(br s,1H),3.17(t,J=7.2Hz,2H),2.93(t,J=7.6Hz,2H),2.09-2.01(m,2H).13C{1H}NMR(150MHz,CDCl3):δ155.1(d,1JC-F=234.2Hz),151.8,146.9,144.5,134.3,134.2,129.2,128.8,128.1,127.3,126.8,115.7(d,2JC-F=23.0Hz),113.6(d,3JC-F=7.5Hz),43.9,30.8,30.6.19F{1H}NMR(CDCl3,376MHz):δ-128.0.MS:m/z 281[M+H]+。
实施例13
在反应管中依次加入1c(0.2mmol,39mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3c(40mg,68%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.80(s,1H),8.09(d,J=8.4Hz,1H),7.93(d,J=1.2Hz,1H),7.76(d,J=8.4Hz,1H),7.69-7.65(m,1H),7.55-7.51(m,1H),7.10(dd,J1=6.8Hz,J2=2.0Hz,2H),6.50(dd,J1=6.8Hz,J2=2.4Hz,2H),3.18(t,J=6.8Hz,2H),2.92(t,J=7.6Hz,2H),2.07-2.03(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.8,146.9,146.7,134.4,134.1,129.2,129.1,128.9,128.1,127.3,126.8,122.0,113.8,43.3,30.7,30.6.MS:m/z 297[M+H]+。
实施例14
在反应管中依次加入1d(0.2mmol,48mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3d(43mg,63%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.80(d,J=2.4Hz,1H),8.09(d,J=8.4Hz,1H),7.92(d,J=1.6Hz,1H),7.75(d,J=8.0Hz,1H),7.69-7.65(m,1H),7.55-7.51(m,1H),7.26-7.21(m,2H),6.47-6.44(m,2H),3.74(br s,1H),3.17(t,J=6.8Hz,2H),2.91(t,J=7.2Hz,2H),2.08-2.00(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.8,147.1,146.9,134.3,134.1,132.0,129.2,128.9,128.1,127.3,126.8,114.3,109.0,43.2,30.64,30.60.MS:m/z 341[M+H]+。
实施例15
在反应管中依次加入1e(0.2mmol,57mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3e(47mg,60%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.78(d,J=2.0Hz,1H),8.08(d,J=8.8Hz,1H),7.91(d,J=1.2Hz,1H),7.75(d,J=8.0Hz,1H),7.69-7.65(m,1H),7.55(t,J=8.0Hz,1H),7.41(dd,J1=6.8Hz,J2=2.0Hz,2H),6.36(dd,J1=6.8Hz,J2=2.0Hz,2H),3.67(br s,1H),3.17(t,J=6.8Hz,2H),2.91(t,J=7.6Hz,2H),2.05-2.02(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.8,147.7,147.0,137.8,134.3,134.0,129.2,128.9,128.1,127.4,126.8,115.0,43.0,30.61,30.60.MS:m/z 389[M+H]+。
实施例16
在反应管中依次加入1f(0.2mmol,43mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3f(38mg,60%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.80(d,J=2.0Hz,1H),8.09(d,J=8.4Hz,1H),7.93(d,J=1.6Hz,1H),7.75(d,J=8.4Hz,1H),7.68-7.64(m,1H),7.54-7.50(m,1H),7.20(dd,J1=6.8Hz,J2=2.0Hz,2H),6.56(dd,J1=6.8Hz,J2=2.0Hz,2H),3.20(t,J=6.8Hz,2H),2.92(t,J=7.6Hz,2H),2.06-2.03(m,2H),1.28(s,9H).13C{1H}NMR(150MHz,CDCl3):δ151.9,146.8,145.9,140.3,134.38,134.37,129.1,128.8,128.2,127.4,126.7,126.1,112.6,43.5,33.9,31.6,31.0,30.7.MS:m/z 319[M+H]+。
实施例17
在反应管中依次加入1g(0.2mmol,37mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3g(32mg,55%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.79(d,J=2.0Hz,1H),8.09(d,J=8.0Hz,1H),7.93(s,1H),7.76(d,J=8.0Hz,1H),7.70-7.66(m,1H),7.56-7.52(m,1H),7.41-7.39(m,2H),6.53(d,J=8.8Hz,2H),4.28(br s,1H),3.25(br s,2H),2.93(t,J=7.2Hz,2H),2.11-2.04(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.6,151.2,147.0,134.4,133.8,133.7,129.2,129.0,128.1,127.3,126.9,120.4,112.2,98.9,42.5,30.5,30.4.MS:m/z 288[M+H]+。
实施例18
在反应管中依次加入1h(0.2mmol,46mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3h(43mg,65%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.80(d,J=2.4Hz,1H),8.09(d,J=8.4Hz,1H),7.93(d,J=1.6Hz,1H),7.76(d,J=8.0Hz,1H),7.70-7.66(m,1H),7.56-7.52(m,1H),7.39(d,J=8.0Hz,2H),6.58(d,J=8.8Hz,2H),3.98(br s,1H),3.25(t,J=7.2Hz,2H),2.94(t,J=7.6Hz,2H),2.11-2.04(m,2H).13C{1H}NMR(100MHz,CDCl3):δ151.7,150.5,147.0,134.3,133.9,129.2,128.9,128.1,127.7,127.3,126.7(q,4JC-F=2.2Hz),126.6(q,1JC-F=256.7Hz),118.9(q,2JC-F=21.2Hz),111.8,42.8,30.57,30.55.19F{1H}NMR(CDCl3,376MHz):δ-61.0.MS:m/z 331[M+H]+。
实施例19
在反应管中依次加入1i(0.2mmol,41mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3i(35mg,57%)。该化合物的表征数据如下:1H NMR(600MHz,CDCl3):δ8.81(d,J=2.4Hz,1H),8.09(d,J=8.4Hz,1H),7.95(d,J=1.2Hz,1H),7.77(d,J=7.8Hz,1H),7.70-7.67(m,1H),7.56-7.51(m,2H),7.38-7.26(t,J=1.8Hz,1H),7.27-7.25(m,1H),6.84(dd,J1=7.8Hz,J2=1.8Hz,1H),4.06(br s,1H),3.29-3.26(m,2H),2.95(t,J=7.8Hz,2H),2.12-2.07(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.7,149.5,148.9,147.0,134.4,133.8,129.8,129.2,129.0,128.1,127.4,126.9,118.7,112.0,106.3,53.4,43.0,30.6,30.4.MS:m/z 308[M+H]+。
实施例20
在反应管中依次加入1j(0.2mmol,41mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色固体产物3j(25mg,41%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.79(d,J=2.4Hz,1H),8.09(d,J=8.8Hz,1H),7.92(d,J=1.6Hz,1H),7.75(d,J=8.0Hz,1H),7.69-7.64(m,1H),7.54-7.50(m,1H),7.21(dd,J1=6.4Hz,J2=2.0Hz,2H),6.54(dd,J1=6.8Hz,J2=2.0Hz,2H),3.71(br s,1H),3.19(t,J=7.2Hz,2H),2.91(t,J=7.6Hz,2H),2.40(s,3H),2.06-2.02(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.8,147.0,146.9,134.3,134.1,131.6,129.1,128.8,128.1,127.3,126.8,124.3,113.4,43.2,30.6,19.2.MS:m/z 309[M+H]+。
实施例21
在反应管中依次加入1k(0.2mmol,35mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3k(31mg,56%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.76(d,J=2.0Hz,1H),8.09(d,J=8.4Hz,1H),7.90(d,J=1.6Hz,1H),7.75(d,J=8.4Hz,1H),7.66(td,J1=6.8Hz,J2=1.6Hz,1H),7.54-7.50(m,1H),7.18-7.13(m,2H),6.69(t,J=7.2Hz,1H),6.57(dd,J1=8.4Hz,J2=0.8Hz,2H),3.75(br s,1H),3.16-3.11(m,1H),3.04-2.97(m,2H),2.68-2.62(m,1H),2.21-2.16(m,1H),1.00(d,J=7.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ152.2,148.3,146.8,135.3,133.2,129.3,129.1,128.9,128.1,127.4,126.8,117.4,112.8,49.7,38.3,35.0,17.8.MS:m/z 277[M+H]+。
实施例22
在反应管中依次加入1l(0.2mmol,29mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3l(25mg,50%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):δ8.81(d,J=2.4Hz,1H),8.10(d,J=8.4Hz,1H),7.96(d,J=1.6Hz,1H),7.78(d,J=8.0Hz,1H),7.70-7.66(m,1H),7.56-7.52(m,1H),7.19(td,J1=7.2Hz,J2=2.0Hz,2H),6.75-6.71(m,1H),6.64(dd,J1=8.4Hz,J2=1.2Hz,2H),3.72(br s,1H),3.53(t,J=7.2Hz,2H),3.11(t,J=6.8Hz,2H).13C{1H}NMR(150MHz,CDCl3):δ151.9,147.6,147.1,135.0,132.1,129.4,129.2,129.0,128.1,127.4,126.8,117.8,113.1,44.7,32.9.MS:m/z 249[M+H]+。
实施例23
在反应管中依次加入1m(0.2mmol,35mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3m(29mg,52%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):8.78(d,J=2.0Hz,1H),8.08(d,J=8.4Hz,1H),7.91(s,1H),7.76(d,J=8.0Hz,1H),7.68-7.63(m,1H),7.54-7.50(m,1H),7.18-7.14(m,2H),6.69(t,J=7.2Hz,1H),6.60-6.58(m,2H),3.57(s,1H),3.17(t,J=7.2Hz,2H),2.85(t,J=7.6Hz,2H),1.87-1.81(m,2H),1.75-1.69(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.4,148.3,146.2,134.9,134.8,129.3,129.0,128.5,128.2,127.4,126.9,117.4,112.8,43.7,32.9,29.1,28.6.MS:m/z 277[M+H]+。
实施例24
在反应管中依次加入1n(0.2mmol,35mg),氯仿(1mL),2a(0.6mmol,71mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3n(9mg,31%)。该化合物的表征数据如下:1H NMR(400MHz,DMSO-d6):8.77(d,J=2.0Hz,1H),8.12(s,1H),7.98(d,J=7.6Hz,1H),7.98(d,J=7.6Hz,1H),7.69(t,J=7.6Hz,1H),7.57(t,J=7.6Hz,1H),2.49(s,3H).13C{1H}NMR(150MHz,CDCl3):δ152.4,146.6,134.7,130.5,129.2,128.4,128.2,127.1,126.6,18.7.MS:m/z 144[M+H]+。
实施例25
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2b(0.6mmol,165mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3o(33mg,40%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):8.89(d,J=2.0Hz,1H),8.09(d,J=2.0Hz,1H),7.87(d,J=2.0Hz,1H),7.82(d,J=2.0Hz,1H),7.17(td,J1=7.6Hz,J2=2.0Hz,2H),6.71(t,J=7.2Hz,1H),6.60-6.58(m,2H),3.35(br s,1H),3.21(t,J=7.2Hz,2H),2.95(t,J=7.6Hz,2H),2.06-2.00(m,2H).13C{1H}NMR(100MHz,CDCl3):δ152.9,148.0,142.8,136.4,135.2,133.8,130.0,129.34,129.30,125.7,120.0,117.7,112.9,43.2,30.6,30.4.MS:m/z 419[M+H]+。
实施例26
在反应管中依次加入1a(0.2mmol,32mg),氯仿(1mL),2c(0.6mmol,80mg)和三(五氟苯基)硼烷(0.04mmol,20mg),在空气气氛下于140℃搅拌反应3h,然后旋干,过硅胶柱分离(石油醚/乙酸乙酯=2/1,v/v)得黄色液体产物3p(19mg,34%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3):8.75(d,J=2.4Hz,1H),7.89(d,J=1.6Hz,1H),7.86(s,1H),7.65(d,J=8.4Hz,1H),7.36(dd,J1=8.4Hz,J2=1.6Hz,1H),7.17(td,J1=7.6Hz,J2=2.0Hz,2H),6.70(t,J=7.2Hz,1H),6.59(dd,J1=8.4Hz,J2=1.2Hz,2H),3.21(t,J=7.2Hz,2H),2.91(t,J=7.2Hz,2H),2.56(s,3H),2.07-2.03(m,2H).13C{1H}NMR(150MHz,CDCl3):δ151.7,148.2,147.1,139.1,134.2,133.4,129.3,129.0,128.1,127.0,126.2,117.5,112.8,43.3,30.9,30.6,21.8.MS:m/z 277[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3-取代喹啉类化合物的合成方法,其特征在于具体过程为:将饱和胺类化合物1和苯并异噁唑类化合物2溶于溶剂中,再向反应体系加入催化剂,在空气气氛下于120-160℃反应制得目标产物3-取代喹啉类化合物3,该合成方法中的反应方程式为:
其中R为苯基或取代苯基,该取代苯基苯环上的取代基为氟、氯、溴、碘、氰基、硝基、三氟甲基、C1-4烷基、烷氧基或烷硫基,R1为氢、C1-4烷基或苯基,R2为氟、氯、溴、碘、氰基、硝基、三氟甲基、C1-4烷基或烷氧基,催化剂为三(五氟苯基)硼烷、三氟乙酸或三溴化铟,溶剂为甲苯、1,2-二氟苯、三氟甲基苯、二氯乙烷或氯仿。
2.根据权利要求1所述的3-取代喹啉类化合物的合成方法,其特征在于:所述饱和胺类化合物1、苯并异噁唑类化合物2与催化剂的投料物质的量之比为1:1.5-4:0.1-0.3。
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