WO2022226855A1 - Method for preparing pyrano[2,3-b]-indole-2-one without catalyst - Google Patents

Method for preparing pyrano[2,3-b]-indole-2-one without catalyst Download PDF

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WO2022226855A1
WO2022226855A1 PCT/CN2021/090786 CN2021090786W WO2022226855A1 WO 2022226855 A1 WO2022226855 A1 WO 2022226855A1 CN 2021090786 W CN2021090786 W CN 2021090786W WO 2022226855 A1 WO2022226855 A1 WO 2022226855A1
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compound
pyrano
indol
preparing
isatin
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PCT/CN2021/090786
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French (fr)
Chinese (zh)
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徐凡
陈启发
姚志刚
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苏州大学
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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
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered

Definitions

  • the invention belongs to organic synthesis, in particular to a method for preparing pyrano[2,3- b ]-indol-2-one without catalyst.
  • the invention discloses a method for preparing pyrano[2,3-b]-indol-2-one without catalyst, which is the first time in the preparation of pyrano[2,3-b]-indol-2-one compound
  • the catalyst is avoided in the process, and the product is obtained efficiently and simply.
  • the present invention adopts the following technical solutions.
  • DBU 1,8-diazabicycloundec-7-ene
  • the red compound and the cyclopropenone compound are used as raw materials to react in a solvent to obtain pyrano[2,3- b ]indol-2-one.
  • DBU (1,8-diazabicycloundec-7-ene) is prepared by reacting an isatin compound and a cyclopropenone compound as raw materials in a solvent to prepare pyrano[2,3- b ] Indol-2-one application.
  • the general chemical structure of the isatin compound is as follows.
  • R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl;
  • R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl One of the base and trifluoromethoxy.
  • Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
  • R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl
  • R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, three One of fluoromethyl and trifluoromethoxy
  • Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
  • the reaction is carried out in an organic solvent, and the organic solvent is tetrahydrofuran, ethanol, acetonitrile, 1,4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1,2-dichloroethane, A kind of chlorobenzene; preferably tetrahydrofuran.
  • the organic solvent is tetrahydrofuran, ethanol, acetonitrile, 1,4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1,2-dichloroethane, A kind of chlorobenzene; preferably tetrahydrofuran.
  • the consumption of DBU is 0.8 to 1.5 times the molar weight of the isatin compound, and the consumption of the cyclopropenone compound is 1.8 to 2.5 times the molar weight of the isatin compound; preferably, the consumption of DBU is the molar weight of the isatin compound. 1 times, the amount of cyclopropenone compound is 2 times the molar amount of isatin compound.
  • the reaction temperature is 20-60°C
  • the reaction time is 0.5-3 hours; preferably, the reaction is performed at 50°C for 1.5 hours.
  • the invention discloses for the first time that in the presence of DBU (1,8-diazabicycloundec-7-ene), using isatin compound and cyclopropenone compound as raw materials, reacting in a solvent to obtain pyrano[ 2,3- b ]indol-2-one, which does not require the participation of metal catalysts, has mild reaction conditions, and has excellent atom economy, has certain value.
  • the raw materials used in the present invention are all commercially available products or compounds reported in existing literature.
  • the inventiveness of the present invention lies in that only DBU (1,8-diazabicycloundec-7-ene), isatin compound and cyclopropenone compound are used as raw materials to react in a solvent to obtain pyrano[2 ,3- b ]indol-2-one; no metal catalyst, phosphite and other reagents are needed; unless otherwise specified, the reaction of the present invention is carried out in a conventional environment.
  • Reaction conditions 0.24 mmol compound 1 , 0.48 mmol compound 2 , 1.0 eq DBU (relative to compound 1 ), 0.5 mL THF, reaction time 1.5 h, temperature 50 °C; isolated yield.
  • the amount of the base was replaced, the solvent was tetrahydrofuran THF, the base was DBU, the reaction temperature was 50°C, and the yield of the obtained product was as follows. .
  • the reaction conditions of the preferred embodiment of the present invention are: 0.24 mmol N -ethylisatin, 0.48 mmol diphenylcyclopropenone, 1.0 eq DBU (relative to N -ethylisatin), in 0.5 mL THF, 50 The reaction was carried out for 1.5 h at °C.
  • DBU was used for the first time to promote the synthesis of pyrano-[2,3- b ]indol-2-one compounds from isatin and cyclopropenone.
  • the method does not require metal catalysis, has mild reaction conditions, has high atom economy, and has high substrate tolerance, which provides a more convenient and simple post-processing method for the synthesis of this type of framework compound.

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  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Disclosed in the present invention is a method for preparing pyrano[2,3-b]-indole-2-one without a catalyst, the method comprising: in the presence of DBU (1,8-diazabicyclo undec-7-ene), using an isatin compound and a cyclopropenone compound as raw materials, and reacting same in a solvent to obtain pyrano[2,3-b]-indole-2-one. According to the present invention, a catalyst is avoided in the process of preparing a pyrano[2,3-b]-indole-2-one compound for the first time, and the product is obtained in an efficient and simple way.

Description

一种无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法A kind of method for preparing pyrano[2,3-b]-indol-2-one without catalyst 技术领域technical field
本发明属于有机合成，具体涉及一种无催化剂制备吡喃并[2,3- b]-吲哚-2-酮的方法。 The invention belongs to organic synthesis, in particular to a method for preparing pyrano[2,3- b ]-indol-2-one without catalyst.
背景技术Background technique
在之前的工作中，本课题组开发了一种低催化量下进行靛红化合物和环丙烯酮化合物反应的方法；在胺化合物、亚磷酸酯存在下，以硅氨基稀土化合物为催化剂，在有机溶剂中将靛红化合物和环丙烯酮进行反应，合成吡喃并[2,3- b]吲哚-2-酮化合物。虽然催化剂用量少，是一种高效、简易制备吡喃并[2,3- b]吲哚-2-酮骨架化合物的方法，但是依然需要10mol%的催化剂，因此，需要研发新的技术方案，无催化剂制备吡喃并[2,3- b]吲哚-2-酮。 In the previous work, our research group developed a method for the reaction of isatin compounds and cyclopropenone compounds under low catalytic amount; The isatin compound and cyclopropenone are reacted in a solvent to synthesize the pyrano[2,3- b ]indol-2-one compound. Although the amount of catalyst is small, it is an efficient and simple method for preparing pyrano[2,3- b ]indol-2-one skeleton compounds, but it still needs 10 mol% of the catalyst. Therefore, it is necessary to develop new technical solutions. , catalyst-free preparation of pyrano[2,3- b ]indol-2-ones.
技术问题technical problem
本发明公开了一种无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，首次在制备吡喃并[2,3-b]-吲哚-2-酮化合物的工艺中避免了催化剂，且高效、简单的得到了产物。The invention discloses a method for preparing pyrano[2,3-b]-indol-2-one without catalyst, which is the first time in the preparation of pyrano[2,3-b]-indol-2-one compound The catalyst is avoided in the process, and the product is obtained efficiently and simply.
技术解决方案technical solutions
本发明采用如下技术方案。The present invention adopts the following technical solutions.
一种无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，在DBU（1,8-二氮杂二环十一碳-7-烯）存在下，以靛红化合物与环丙烯酮化合物为原料，在溶剂中反应，得到吡喃并[2,3- b]吲哚-2-酮。 A catalyst-free method for the preparation of pyrano[2,3-b]-indol-2-ones from indigo in the presence of DBU (1,8-diazabicycloundec-7-ene) The red compound and the cyclopropenone compound are used as raw materials to react in a solvent to obtain pyrano[2,3- b ]indol-2-one.
本发明公开了DBU（1,8-二氮杂二环十一碳-7-烯）在以靛红化合物与环丙烯酮化合物为原料，在溶剂中反应制备吡喃并[2,3- b]吲哚-2-酮中的应用。 The invention discloses that DBU (1,8-diazabicycloundec-7-ene) is prepared by reacting an isatin compound and a cyclopropenone compound as raw materials in a solvent to prepare pyrano[2,3- b ] Indol-2-one application.
本发明中，所述靛红化合物的化学结构通式如下。In the present invention, the general chemical structure of the isatin compound is as follows.
Figure 679480dest_path_image001
 。
Figure 679480dest_path_image001
.
其中，R 1选自烯丙基、苄基、乙基、甲基、炔丙基中的一种；R 2选自氟、氯、溴、甲基、甲氧基、硝基、三氟甲基、三氟甲氧基中的一种。 Wherein, R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl; R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl One of the base and trifluoromethoxy.
所述环丙烯酮化合物的化学结构通式如下。The general chemical structure of the cyclopropenone compound is as follows.
Figure 494989dest_path_image002
。
Figure 494989dest_path_image002
.
其中，Ar选自苯基、4-甲基苯基、4-氟苯基、4-氯苯基中的一种。Wherein, Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
所述吡喃并[2,3- b]-吲哚-2-酮的化学结构式如下所示。 The chemical structural formula of the pyrano[2,3- b ]-indol-2-one is shown below.
Figure 907516dest_path_image003
。
Figure 907516dest_path_image003
.
上述结构式中，R 1选自烯丙基、苄基、乙基、甲基、炔丙基中的一种；R 2选自氟、氯、溴、甲基、甲氧基、硝基、三氟甲基、三氟甲氧基中的一种；Ar选自苯基、4-甲基苯基、4-氟苯基、4-氯苯基中的一种。 In the above structural formula, R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl; R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, three One of fluoromethyl and trifluoromethoxy; Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
本发明中，反应在有机溶剂中进行，有机溶剂为四氢呋喃、乙醇、乙腈、1,4-二氧六环、甲苯、正己烷、乙二醇二甲醚、1,2-二氯乙烷、氯苯中的一种；优选为四氢呋喃。In the present invention, the reaction is carried out in an organic solvent, and the organic solvent is tetrahydrofuran, ethanol, acetonitrile, 1,4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1,2-dichloroethane, A kind of chlorobenzene; preferably tetrahydrofuran.
本发明中，DBU的用量为靛红化合物摩尔量的0.8～1.5倍，环丙烯酮化合物的用量为靛红化合物摩尔量的1.8～2.5倍；优选的，DBU的用量为靛红化合物摩尔量的1倍，环丙烯酮化合物的用量为靛红化合物摩尔量的2倍。In the present invention, the consumption of DBU is 0.8 to 1.5 times the molar weight of the isatin compound, and the consumption of the cyclopropenone compound is 1.8 to 2.5 times the molar weight of the isatin compound; preferably, the consumption of DBU is the molar weight of the isatin compound. 1 times, the amount of cyclopropenone compound is 2 times the molar amount of isatin compound.
本发明中，反应的温度为20～60℃，时间为0.5～3小时；优选的，50 ℃下反应1.5 h。In the present invention, the reaction temperature is 20-60°C, and the reaction time is 0.5-3 hours; preferably, the reaction is performed at 50°C for 1.5 hours.
有益效果beneficial effect
本发明首次公开了在DBU（1,8-二氮杂二环十一碳-7-烯）存在下，以靛红化合物与环丙烯酮化合物为原料，在溶剂中反应，得到吡喃并[2,3- b]吲哚-2-酮，无需金属催化剂参与、反应条件温和，且具有极好的原子经济性，有一定的价值。 The invention discloses for the first time that in the presence of DBU (1,8-diazabicycloundec-7-ene), using isatin compound and cyclopropenone compound as raw materials, reacting in a solvent to obtain pyrano[ 2,3- b ]indol-2-one, which does not require the participation of metal catalysts, has mild reaction conditions, and has excellent atom economy, has certain value.
本发明的实施方式Embodiments of the present invention
本发明所用原料都是市售产品或者现有文献报道的化合物。本发明的创造性在于，仅采用DBU（1,8-二氮杂二环十一碳-7-烯）、靛红化合物与环丙烯酮化合物为原料，在溶剂中反应，得到吡喃并[2,3- b]吲哚-2-酮；无需金属催化剂、亚磷酸酯等其他试剂；除有特殊说明，本发明的反应在常规环境下进行。 The raw materials used in the present invention are all commercially available products or compounds reported in existing literature. The inventiveness of the present invention lies in that only DBU (1,8-diazabicycloundec-7-ene), isatin compound and cyclopropenone compound are used as raw materials to react in a solvent to obtain pyrano[2 ,3- b ]indol-2-one; no metal catalyst, phosphite and other reagents are needed; unless otherwise specified, the reaction of the present invention is carried out in a conventional environment.
实施例一。Example 1.
Figure 201094dest_path_image004
。
Figure 201094dest_path_image004
.
反应条件：0.24 mmol 化合物 1，0.48 mmol 化合物 2，1.0 eq DBU（相对于化合物 1），0.5 mL THF，反应时间1.5 h，温度为50℃；分离产率。 Reaction conditions: 0.24 mmol compound 1 , 0.48 mmol compound 2 , 1.0 eq DBU (relative to compound 1 ), 0.5 mL THF, reaction time 1.5 h, temperature 50 °C; isolated yield.
在反应瓶中依次加入化合物 1、DBU、化合物 2和四氢呋喃（0.5mL），在50℃下常规搅拌1.5小时。反应结束后抽干溶剂，粗产品经硅胶柱快速柱层析（洗脱剂：乙酸乙酯:石油醚＝1:10）得到黄色固体产物，底物、产物结构以及产率如下。 Compound 1 , DBU, compound 2 and tetrahydrofuran (0.5 mL) were sequentially added to the reaction flask, and the mixture was stirred conventionally for 1.5 hours at 50°C. After the reaction, the solvent was drained, and the crude product was subjected to silica gel flash column chromatography (eluent: ethyl acetate: petroleum ether=1:10) to obtain a yellow solid product. The substrate, product structure and yield are as follows.
Figure 897523dest_path_image005
。
Figure 897523dest_path_image005
.
Figure 352775dest_path_image006
Figure 252598dest_path_image007
Figure 84288dest_path_image008
Figure 651536dest_path_image009
Figure 277689dest_path_image010
Figure 930387dest_path_image011
Figure 300189dest_path_image012
Figure 456364dest_path_image013
。
Figure 352775dest_path_image006
Figure 252598dest_path_image007
Figure 84288dest_path_image008
Figure 651536dest_path_image009
Figure 277689dest_path_image010
Figure 930387dest_path_image011
Figure 300189dest_path_image012
Figure 456364dest_path_image013
.
所制得产物的理论分子式以及主要核磁测试数据如下，通过分析可知，实际合成产物与理论分析一致。The theoretical molecular formula and the main nuclear magnetic test data of the obtained product are as follows. The analysis shows that the actual synthetic product is consistent with the theoretical analysis.
Figure 518998dest_path_image014
3aa。
Figure 518998dest_path_image014
3aa .
1H NMR (400 MHz, CDCl 3) δ7.36−7.31 (m, 4H), 7.25−7.21 (m, 3H), 7.19−7.10 (m, 5H), 7.00−6.96 (m, 1H), 6.78 (d, J = 8.0 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.36−7.31 (m, 4H), 7.25−7.21 (m, 3H), 7.19−7.10 (m, 5H), 7.00−6.96 (m, 1H), 6.78 (d , J = 8.0 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H).
Figure 144145dest_path_image015
3ia。
Figure 144145dest_path_image015
3ia .
1H NMR (400 MHz, CDCl 3) δ 8.16−8.13 (m, 1H), 7.72−7.71 (m, 1H), 7.44−7.39 (m, 4H), 7.26−7.24 (m, 2H), 7.22−7.15 (m, 5H), 4.43 (q, J = 7.2 Hz, 2H), 1.56 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 8.16−8.13 (m, 1H), 7.72−7.71 (m, 1H), 7.44−7.39 (m, 4H), 7.26−7.24 (m, 2H), 7.22−7.15 (m, 5H), 4.43 (q, J = 7.2 Hz, 2H), 1.56 (t, J = 7.2 Hz, 3H).
Figure 317637dest_path_image016
3ja。
Figure 317637dest_path_image016
3ja .
1H NMR (400 MHz, CDCl 3) δ 7.35−7.32 (m, 4H), 7.24−7.20 (m, 2H), 7.18−7.14 (m, 5H), 7.10−7.08 (m, 1H), 6.61 (s, 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.35−7.32 (m, 4H), 7.24−7.20 (m, 2H), 7.18−7.14 (m, 5H), 7.10−7.08 (m, 1H), 6.61 (s , 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H).
Figure 593898dest_path_image017
3na。
Figure 593898dest_path_image017
3na .
1H NMR (400 MHz, CDCl 3) δ 7.34−7.28 (m, 2H), 7.17−7.14 (m, 4H), 7.13−7.09 (m, 4H), 7.07−7.01 (m, 3H), 4.36 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.34−7.28 (m, 2H), 7.17−7.14 (m, 4H), 7.13−7.09 (m, 4H), 7.07−7.01 (m, 3H), 4.36 (q , J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H).
Figure 827433dest_path_image018
3qa。
Figure 827433dest_path_image018
3qa .
1H NMR (400 MHz, CDCl 3) δ 7.49 (s, 1H), 7.33−7.29 (m, 3H), 7.21−7.12 (m, 7H), 7.08 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 8.4 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (s, 1H), 7.33−7.29 (m, 3H), 7.21−7.12 (m, 7H), 7.08 (d, J = 8.4 Hz, 1H), 6.61 ( d, J = 8.4 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H).
Figure 189144dest_path_image019
3ra。
Figure 189144dest_path_image019
3ra .
1H NMR (400 MHz, CDCl 3) δ 7.32−7.30 (m, 3H), 7.22−7.11 (m, 7H), 6.95 (d, J = 7.6 Hz, 1H), 6.86−6.82 (m, 1H), 6.57 (d, J = 8.0 Hz, 1H), 4.55 (q, J = 7.2 Hz, 2H), 2.72 (s, 3H), 1.50 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.32−7.30 (m, 3H), 7.22−7.11 (m, 7H), 6.95 (d, J = 7.6 Hz, 1H), 6.86−6.82 (m, 1H), 6.57 (d, J = 8.0 Hz, 1H), 4.55 (q, J = 7.2 Hz, 2H), 2.72 (s, 3H), 1.50 (t, J = 7.2 Hz, 3H).
Figure 166328dest_path_image020
3sa。
Figure 166328dest_path_image020
3sa .
1H NMR (400 MHz, CDCl 3) δ 7.34−7.32 (m, 3H), 7.24−7.13 (m, 7H), 6.94−6.83 (m, 2H), 6.49 (d, J = 8.0 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 1.53 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.34−7.32 (m, 3H), 7.24−7.13 (m, 7H), 6.94−6.83 (m, 2H), 6.49 (d, J = 8.0 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 1.53 (t, J = 7.2 Hz, 3H).
Figure 31516dest_path_image021
3ua。
Figure 31516dest_path_image021
3ua .
1H NMR (400 MHz, CDCl 3) δ 7.33−7.29 (m, 4H), 7.21−7.10 (m, 7H), 6.78−6.74 (m, 1H), 6.64 (d, J = 8.0 Hz, 1H), 4.74 (q, J = 7.2 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.33−7.29 (m, 4H), 7.21−7.10 (m, 7H), 6.78−6.74 (m, 1H), 6.64 (d, J = 8.0 Hz, 1H), 4.74 (q, J = 7.2 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H).
Figure 435952dest_path_image022
3wa。
Figure 435952dest_path_image022
3wa .
1H NMR (400 MHz, CDCl 3) δ 7.26−7.20 (m, 3H), 7.18−7.08 (m, 7H), 6.90−6.88 (m, 1H), 6.53−6.47 (m, 1H), 4.31 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.26−7.20 (m, 3H), 7.18−7.08 (m, 7H), 6.90−6.88 (m, 1H), 6.53−6.47 (m, 1H), 4.31 (q , J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H).
Figure 284959dest_path_image023
3xa。
Figure 284959dest_path_image023
3xa .
1H NMR (400 MHz, CDCl 3) δ 7.17−7.12 (m, 6H), 7.11−7.06 (m, 3H), 7.05−7.03 (m, 2H), 6.94 (d, J = 8.4 Hz, 1H), 4.80 (q, J = 7.2 Hz, 2H), 1.55 (t, J = 7.2 Hz, 3H)。 1 H NMR (400 MHz, CDCl 3 ) δ 7.17−7.12 (m, 6H), 7.11−7.06 (m, 3H), 7.05−7.03 (m, 2H), 6.94 (d, J = 8.4 Hz, 1H), 4.80 (q, J = 7.2 Hz, 2H), 1.55 (t, J = 7.2 Hz, 3H).
Figure 800254dest_path_image024
3ad。
Figure 800254dest_path_image024
3ad .
1H NMR (400 MHz, CDCl 3) δ 7.39−7.34 (m, 3H), 7.30−7.26 (m, 1H), 7.19−7.17 (m, 4H), 7.08–7.03 (m, 3H), 6.82 (d, J = 8.0 Hz, 1H), 4.37 (q, J = 7.2 Hz, 2H), 1.52 (t, J = 7.2 Hz, 3H) 。 [0045] 实施例二。 1 H NMR (400 MHz, CDCl 3 ) δ 7.39−7.34 (m, 3H), 7.30−7.26 (m, 1H), 7.19−7.17 (m, 4H), 7.08–7.03 (m, 3H), 6.82 (d , J = 8.0 Hz, 1H), 4.37 (q, J = 7.2 Hz, 2H), 1.52 (t, J = 7.2 Hz, 3H). Embodiment two.
Figure 785528dest_path_image025
。
Figure 785528dest_path_image025
.
反应条件：0.24 mmol N-乙基靛红，0.36 mmol二苯基环丙烯酮，1.5当量Lewis碱（相对于 N-乙基靛红），1.0 mL THF，室温，1.5 h，分离收率。 Reaction conditions: 0.24 mmol N -ethylisatin, 0.36 mmol diphenylcyclopropenone, 1.5 equivalents of Lewis base (relative to N -ethylisatin), 1.0 mL THF, room temperature, 1.5 h, isolated yield.
在反应瓶中依次加入化合物 1a、Lewis碱、化合物 2a和四氢呋喃（1.0mL），在室温下常规搅拌1.5小时。反应结束后抽干溶剂，粗产品经硅胶柱快速柱层析（洗脱剂：乙酸乙酯:石油醚＝1:10）得到黄色固体产物。不同Lewis碱的产率为。
Figure 613063dest_path_image026
。 Compound 1a , Lewis base, compound 2a and tetrahydrofuran (1.0 mL) were sequentially added to the reaction flask, and the mixture was stirred conventionally for 1.5 hours at room temperature. After the reaction, the solvent was drained, and the crude product was subjected to flash column chromatography on silica gel (eluent: ethyl acetate: petroleum ether=1:10) to obtain a yellow solid product. The yields of different Lewis bases are .
Figure 613063dest_path_image026
.
在上述反应条件下，仅更换溶剂，碱为DBU，得到的产物产率如下。
Figure 949366dest_path_image027
。 Under the above reaction conditions, only the solvent was replaced, the base was DBU, and the yield of the product obtained was as follows.
Figure 949366dest_path_image027
.
在上述反应条件下，仅更换反应温度，溶剂为四氢呋喃THF，碱为DBU，得到的产物产率如下。
Figure 268352dest_path_image028
。 Under the above reaction conditions, only the reaction temperature was changed, the solvent was tetrahydrofuran, THF, and the base was DBU, and the yield of the obtained product was as follows.
Figure 268352dest_path_image028
.
在上述反应条件下，更换碱的用量，溶剂为四氢呋喃THF，碱为DBU，反应温度为50℃，得到的产物产率如下。
Figure 373712dest_path_image029
。 Under the above reaction conditions, the amount of the base was replaced, the solvent was tetrahydrofuran THF, the base was DBU, the reaction temperature was 50°C, and the yield of the obtained product was as follows.
Figure 373712dest_path_image029
.
实施例三。Example three.
Figure 854371dest_path_image030
。
Figure 854371dest_path_image030
.
反应条件：0.24 mmol N-乙基靛红，1.0 eq DBU（相对于 N-乙基靛红），温度为50℃；分离产率。 Reaction conditions: 0.24 mmol N -ethylisatin, 1.0 eq DBU (relative to N -ethylisatin), temperature 50°C; isolated yield.
在反应瓶中依次加入化合物 1a、DBU、化合物 2a和四氢呋喃，在50℃下常规搅拌一定时间。反应结束后抽干溶剂，粗产品经硅胶柱快速柱层析（洗脱剂：乙酸乙酯:石油醚＝1:10）得到黄色固体产物。反应条件与产率如下。
Figure 412392dest_path_image031
。 Compound 1a , DBU, compound 2a and tetrahydrofuran were sequentially added to the reaction flask, and the mixture was stirred at 50° C. for a certain period of time. After the reaction, the solvent was drained, and the crude product was subjected to flash column chromatography on silica gel (eluent: ethyl acetate: petroleum ether=1:10) to obtain a yellow solid product. The reaction conditions and yields are as follows.
Figure 412392dest_path_image031
.
本发明最佳实施例的反应条件为：0.24 mmol N-乙基靛红，0.48 mmol二苯基环丙烯酮，1.0 eq DBU（相对于 N-乙基靛红），在0.5 mL THF中、50 ℃下反应1.5 h。 The reaction conditions of the preferred embodiment of the present invention are: 0.24 mmol N -ethylisatin, 0.48 mmol diphenylcyclopropenone, 1.0 eq DBU (relative to N -ethylisatin), in 0.5 mL THF, 50 The reaction was carried out for 1.5 h at ℃.
对比例。Comparative ratio.
Figure 535069dest_path_image032
。
Figure 535069dest_path_image032
.
0.24 mmol N-乙基靛红，0.48 mmol二苯基环丙烯酮，在0.5 mL THF中、50 ℃下反应1.5 h，无产物。在没有DBU、标准条件下反应时，没有监测到目标产物的生成。 0.24 mmol N -ethylisatin, 0.48 mmol diphenylcyclopropenone, react in 0.5 mL THF at 50 °C for 1.5 h, no product. In the absence of DBU, standard conditions, the formation of the desired product was not monitored.
在本发明中，首次用DBU促进靛红和环丙烯酮合成吡喃并-[2,3- b]吲哚-2-酮化合物。该方法无需金属催化，反应条件温和，具有高的原子经济性，底物的容忍性高，为合成这一类骨架化合物提供了一种更为便利、后处理简单的方法。 In the present invention, DBU was used for the first time to promote the synthesis of pyrano-[2,3- b ]indol-2-one compounds from isatin and cyclopropenone. The method does not require metal catalysis, has mild reaction conditions, has high atom economy, and has high substrate tolerance, which provides a more convenient and simple post-processing method for the synthesis of this type of framework compound.

Claims (10)

  1. 一种无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，在DBU存在下，以靛红化合物与环丙烯酮化合物为原料，在溶剂中反应，得到吡喃并[2,3- b]吲哚-2-酮； A method for preparing pyrano[2,3-b]-indol-2-one without catalyst, characterized in that, in the presence of DBU, using isatin compound and cyclopropenone compound as raw materials, reacting in a solvent , to obtain pyrano[2,3- b ]indol-2-one;
    所述靛红化合物的化学结构通式如下：The general chemical structure of the isatin compound is as follows:
    Figure 886925dest_path_image001
     
    Figure 886925dest_path_image001
    所述环丙烯酮化合物的化学结构通式如下：The general chemical structure of the cyclopropenone compound is as follows:
    Figure 990010dest_path_image002
    Figure 990010dest_path_image002
    所述吡喃并[2,3- b]-吲哚-2-酮的化学结构式如下所示： The chemical structural formula of the pyrano[2,3- b ]-indol-2-one is shown below:
    Figure 821700dest_path_image003
    Figure 821700dest_path_image003
    上述结构式中，R 1选自烯丙基、苄基、乙基、甲基、炔丙基中的一种；R 2选自氟、氯、溴、甲基、甲氧基、硝基、三氟甲基、三氟甲氧基中的一种；Ar选自苯基、4-甲基苯基、4-氟苯基、4-氯苯基中的一种。 In the above structural formula, R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl; R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, tri One of fluoromethyl and trifluoromethoxy; Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
  2. 根据权利要求1所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，所述反应无需金属催化剂。The method for preparing pyrano[2,3-b]-indol-2-one without a catalyst according to claim 1, wherein the reaction does not require a metal catalyst.
  3. 根据权利要求1所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，所述溶剂为四氢呋喃、乙醇、乙腈、1,4-二氧六环、甲苯、正己烷、乙二醇二甲醚、1,2-二氯乙烷、氯苯中的一种。The method for preparing pyrano[2,3-b]-indol-2-one without catalyst according to claim 1, wherein the solvent is tetrahydrofuran, ethanol, acetonitrile, 1,4-dioxane One of ring, toluene, n-hexane, ethylene glycol dimethyl ether, 1,2-dichloroethane, chlorobenzene.
  4. 根据权利要求1所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，DBU的用量为靛红化合物摩尔量的0.8～1.5倍，环丙烯酮化合物的用量为靛红化合物摩尔量的1.8～2.5倍。The method for preparing pyrano[2,3-b]-indol-2-one without catalyst according to claim 1, wherein the consumption of DBU is 0.8 to 1.5 times the molar weight of the isatin compound, and the cyclopropene The dosage of the ketone compound is 1.8 to 2.5 times the molar amount of the isatin compound.
  5. 根据权利要求4所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，DBU的用量为靛红化合物摩尔量的0.9～1.2倍，环丙烯酮化合物的用量为靛红化合物摩尔量的1.9～2.2倍。The method for preparing pyrano[2,3-b]-indol-2-one without catalyst according to claim 4, wherein the consumption of DBU is 0.9 to 1.2 times the molar weight of the isatin compound, and the cyclopropene The dosage of the ketone compound is 1.9 to 2.2 times the molar amount of the isatin compound.
  6. 根据权利要求1所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，反应的温度为20～60℃，时间为0.5～3小时。The method for preparing pyrano[2,3-b]-indol-2-one without a catalyst according to claim 1, wherein the reaction temperature is 20-60° C. and the reaction time is 0.5-3 hours.
  7. 根据权利要求6所述无催化剂制备吡喃并[2,3-b]-吲哚-2-酮的方法，其特征在于，反应的温度为40～55℃，时间为1～2小时。The method for preparing pyrano[2,3-b]-indol-2-one without a catalyst according to claim 6, wherein the reaction temperature is 40-55° C. and the reaction time is 1-2 hours.
  8. DBU在以靛红化合物与环丙烯酮化合物为原料，在溶剂中反应制备吡喃并[2,3- b]吲哚-2-酮中的应用； The application of DBU in preparing pyrano[2,3- b ]indol-2-one by reaction in solvent with isatin compound and cyclopropenone compound as raw material;
    所述靛红化合物的化学结构通式如下：The general chemical structure of the isatin compound is as follows:
    Figure 326630dest_path_image004
     
    Figure 326630dest_path_image004
    所述环丙烯酮化合物的化学结构通式如下：The general chemical structure of the cyclopropenone compound is as follows:
    Figure 687204dest_path_image005
    Figure 687204dest_path_image005
    所述吡喃并[2,3- b]-吲哚-2-酮的化学结构式如下所示： The chemical structural formula of the pyrano[2,3- b ]-indol-2-one is shown below:
    Figure 339903dest_path_image003
    Figure 339903dest_path_image003
    上述结构式中，R 1选自烯丙基、苄基、乙基、甲基、炔丙基中的一种；R 2选自氟、氯、溴、甲基、甲氧基、硝基、三氟甲基、三氟甲氧基中的一种；Ar选自苯基、4-甲基苯基、4-氟苯基、4-氯苯基中的一种。 In the above structural formula, R 1 is selected from one of allyl, benzyl, ethyl, methyl, and propargyl; R 2 is selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, tri One of fluoromethyl and trifluoromethoxy; Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorophenyl.
  9. 根据权利要求8所述的应用，其特征在于，所述溶剂为四氢呋喃、乙醇、乙腈、1,4-二氧六环、甲苯、正己烷、乙二醇二甲醚、1,2-二氯乙烷、氯苯中的一种；DBU的用量为靛红化合物摩尔量的0.8～1.5倍，环丙烯酮化合物的用量为靛红化合物摩尔量的1.8～2.5倍。The application according to claim 8, wherein the solvent is tetrahydrofuran, ethanol, acetonitrile, 1,4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1,2-dichloromethane One of ethane and chlorobenzene; the dosage of DBU is 0.8-1.5 times the molar amount of the isatin compound, and the dosage of the cyclopropenone compound is 1.8-2.5 times the molar amount of the isatin compound.
  10. 根据权利要求8所述的应用，其特征在于，反应的温度为20～60℃，时间为0.5～3小时。The application according to claim 8, wherein the reaction temperature is 20-60°C, and the reaction time is 0.5-3 hours.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102351777A (en) * 2011-08-16 2012-02-15 苏州大学 Preparation method for chiral 3-hydroxyl-3-methylene nitro indole-2-ketone derivative
CN113651827A (en) * 2021-04-28 2021-11-16 苏州大学 Preparation of pyrano [2,3-b]Process for preparing indol-2-ones

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102351777A (en) * 2011-08-16 2012-02-15 苏州大学 Preparation method for chiral 3-hydroxyl-3-methylene nitro indole-2-ketone derivative
CN113651827A (en) * 2021-04-28 2021-11-16 苏州大学 Preparation of pyrano [2,3-b]Process for preparing indol-2-ones

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KUMAR AREPALLI, NAGARAJAN RAJAGOPAL: "Cyclization Routes for the Synthesis of Functionalized Pyrano[2,3-b]indolones, Pyrazolo[3,4-b]indoles, and Furo[2,3-b]indoles", SYNTHESIS, vol. 45, no. 09, 31 December 2013 (2013-12-31), STUTTGART, DE, pages 1235 - 1246, XP055982649, ISSN: 0039-7881, DOI: 10.1055/s-0032-1316870 *

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