Preparation of pyrano [2,3-b]Process for preparing indol-2-ones
阅读说明：本技术 一种无催化剂制备吡喃并[2,3-b]吲哚-2-酮的方法 (Preparation of pyrano [2,3-b]Process for preparing indol-2-ones ) 是由 徐凡 陈启发 姚志刚 于 2021-04-28 设计创作，主要内容包括：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,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。本发明首次在制备吡喃并[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 ]The indole-2-ketone process includes the reaction of isatin compound and cyclopropenone compound in solvent in the presence of DBU (1, 8-diazabicycloundec-7-ene) to obtain pyrano [2,3- b ]Indol-2-ones. The invention is used for preparing pyrano [2,3- b ]The process of the indol-2-one compound avoids catalysts, and the product is obtained efficiently and simply.)
1. Preparation of pyrano [2,3-b]The method of indole-2-ketone is characterized in that an isatin compound and a cyclopropenone compound are taken as raw materials to react in a solvent in the presence of DBU to obtain pyrano [2,3-b]Indol-2-ones;
the chemical structure general formula of the isatin compound is as follows:
the chemical structural general formula of the cyclopropenone compound is as follows:
said pyrano [2,3-b]Chemistry of indol-2-onesThe structural formula is as follows:
in the above structural formula, R1One selected from allyl, benzyl, ethyl, methyl and propargyl; r2One selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl and trifluoromethoxy; ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorphenyl.
2. The catalyst-free preparation of pyrano [2,3-b]A process for the preparation of indol-2-ones, characterized in that no metal catalyst is required for the reaction.
3. The catalyst-free preparation of pyrano [2,3-b]The method for preparing the indol-2-one is characterized in that the solvent is one of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1, 2-dichloroethane and chlorobenzene.
4. The catalyst-free preparation of pyrano [2,3-b]The method for preparing the indole-2-ketone is characterized in that the dosage of DBU is 0.8-1.5 times of the molar weight of an isatin compound, and the dosage of a cyclopropenone compound is 1.8-2.5 times of the molar weight of the isatin compound.
5. The catalyst-free preparation of pyrano [2,3-b]The method for preparing the indole-2-ketone is characterized in that the dosage of DBU is 0.9-1.2 times of the molar weight of an isatin compound, and the dosage of a cyclopropenone compound is 1.9-2.2 times of the molar weight of the isatin compound.
6. The catalyst-free preparation of pyrano [2,3-b]The method for preparing the indole-2-ketone is characterized in that the reaction temperature is 20-60 ℃ and the reaction time is 0.5-3 hours.
7. The catalyst-free preparation of pyrano [2,3-b]The method for preparing the indole-2-ketone is characterized in that the reaction temperature is 40-55 ℃ and the reaction time is 1-2 hours.
DBU is reacted in solvent with isatin compound and cyclopropenone compound as material to prepare pyrano [2,3-b]The application of the indole-2-ketone;
the chemical structure general formula of the isatin compound is as follows:
the chemical structural general formula of the cyclopropenone compound is as follows:
said pyrano [2,3-b]The chemical structural formula of the indol-2-one is shown as follows:
in the above structural formula, R1One selected from allyl, benzyl, ethyl, methyl and propargyl; r2One selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl and trifluoromethoxy; ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorphenyl.
9. The use according to claim 8, wherein the solvent is one of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1, 2-dichloroethane, chlorobenzene; the dosage of DBU is 0.8-1.5 times of the molar weight of the isatin compound, and the dosage of the cyclopropenone compound is 1.8-2.5 times of the molar weight of the isatin compound.
10. The use according to claim 8, wherein the reaction is carried out at a temperature of 20 to 60 ℃ for 0.5 to 3 hours.
Technical Field
The invention belongs to organic synthesis, and particularly relates to a method for preparing pyrano [2,3-b]Methods for preparing indol-2-ones.
Background
In previous work, the present group developed a method for reacting isatin compounds with cyclopropenone compounds in low catalytic amounts; in the presence of amine compound and phosphite ester, taking silicon amino rare earth compound as catalyst, in organic solvent, making isatin compound and cyclopropenone react to synthesize pyrano [2,3-b]Indol-2-one compounds. Although the catalyst dosage is small, the method is a high-efficiency and simple method for preparing pyrano [2,3-b]Method for preparing indole-2-ketone framework compound, but still needs 10mol% of catalyst, therefore, a new technical scheme needs to be developed, and pyrano [2,3-b]Indol-2-ones.
Disclosure of Invention
The invention discloses a method for preparing pyrano [2,3-b]Process for the preparation of pyrano [2,3-b]The process of the indol-2-one compound avoids catalysts, and the product is obtained efficiently and simply.
The invention adopts the following technical scheme:
preparation of pyrano [2,3-b]The indole-2-ketone process includes the reaction of isatin compound and cyclopropenone compound in solvent in the presence of DBU (1, 8-diazabicycloundec-7-ene) to obtain pyrano [2,3-b]Indol-2-ones.
The invention discloses a preparation method of pyrano [2,3-b]Application of indole-2-ketone.
In the invention, the chemical structure general formula of the isatin compound is as follows:
wherein R is1One selected from allyl, benzyl, ethyl, methyl and propargyl; r2One selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl and trifluoromethoxy;
the chemical structural general formula of the cyclopropenone compound is as follows:
wherein Ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorphenyl.
Said pyrano [2,3-b]The chemical structural formula of the indol-2-one is shown as follows:
in the above structural formula, R1One selected from allyl, benzyl, ethyl, methyl and propargyl; r2One selected from fluorine, chlorine, bromine, methyl, methoxy, nitro, trifluoromethyl and trifluoromethoxy; ar is selected from one of phenyl, 4-methylphenyl, 4-fluorophenyl and 4-chlorphenyl.
In the invention, the reaction is carried out in an organic solvent, wherein the organic solvent is one of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, toluene, n-hexane, ethylene glycol dimethyl ether, 1, 2-dichloroethane and chlorobenzene; tetrahydrofuran is preferred.
In the invention, the dosage of DBU is 0.8-1.5 times of the molar weight of the isatin compound, and the dosage of the cyclopropenone compound is 1.8-2.5 times of the molar weight of the isatin compound; preferably, DBU is used in an amount of 1 time the molar amount of the isatin compound, and the cyclopropenone compound is used in an amount of 2 times the molar amount of the isatin compound.
In the invention, the reaction temperature is 20-60 ℃ and the reaction time is 0.5-3 hours; preferably, the reaction is carried out at 50 ℃ for 1.5 h.
The invention discloses a method for preparing pyrano [2,3-b]The indole-2-ketone does not need a metal catalyst, has mild reaction conditions, has excellent atom economy and has certain value.
Detailed Description
The raw materials used in the invention are all commercial products or compounds reported in the prior literature. The creativity of the invention is that only DBU (1, 8-diazabicycloundec-7-ene), isatin compound and cyclopropenone compound are used as raw materials to react in solvent to obtain pyrano [2,3-b]Indol-2-ones; no other reagents such as metal catalysts, phosphite esters and the like are needed; unless otherwise specified, the reactions of the present invention are carried out in conventional environments.
Example one
Reaction conditions are as follows: 0.24 mmol of compound 1, 0.48 mmol of compound 2, 1.0 eq DBU (relative to compound 1), 0.5mL of THF, reaction time 1.5 h, temperature 50 ℃; isolated yield.
Compound 1, DBU, compound 2 and tetrahydrofuran (0.5 mL) were added sequentially to the reaction flask and stirred at 50 ℃ for 1.5 hours conventionally. After the reaction is finished, the solvent is drained, and the crude product is subjected to silica gel column flash column chromatography (eluent: ethyl acetate: petroleum ether ═ 1: 10) to obtain a yellow solid product, wherein the substrate, the product structure and the yield are as follows:
the theoretical molecular formula and the main nuclear magnetic test data of the prepared product are as follows, and the analysis shows that the actual synthesized product is consistent with the theoretical analysis.
3aa
1H NMR (400 MHz, CDCl3) 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).
3ia
1H NMR (400 MHz, CDCl3) 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).
3ja
1H NMR (400 MHz, CDCl3) 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).
3na
1H NMR (400 MHz, CDCl3) 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).
3qa
1H NMR (400 MHz, CDCl3) 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).
3ra
1H NMR (400 MHz, CDCl3) 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).
3sa
1H NMR (400 MHz, CDCl3) 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).
3ua
1H NMR (400 MHz, CDCl3) 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).
3wa
1H NMR (400 MHz, CDCl3) 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).
3xa
1H NMR (400 MHz, CDCl3) 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).
3ad
1H NMR (400 MHz, CDCl3) 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).
Example two
Reaction conditions are as follows: 0.24 mmolN-ethyl isatin, 0.36 mmol of diphenylcyclopropenone, 1.5 equivalents of Lewis base (relative toN-ethyl isatin), 1.0mL THF, room temperature, 1.5 h, isolated yield.
Compound 1a, Lewis base, compound 2a and tetrahydrofuran (1.0 mL) were added in this order to a reaction flask and stirred at room temperature for 1.5 hours conventionally. After the reaction is finished, the solvent is drained, and the crude product is subjected to silica gel column flash column chromatography (eluent: ethyl acetate: petroleum ether: 1: 10) to obtain a yellow solid product. The yields of the different Lewis bases were:
under the above reaction conditions, only solvent change, base DBU, gave the following product yields:
under the above reaction conditions, only changing the reaction temperature, the solvent was tetrahydrofuran THF, and the base was DBU, the following product yields were obtained:
under the above reaction conditions, the amount of the base was changed, the solvent was THF, the base was DBU, and the reaction temperature was 50 ℃, and the product yield was obtained as follows:
EXAMPLE III
Reaction conditions are as follows: 0.24 mmolN-ethyl isatin, 1.0 eq DBU (relative toN-ethyl isatin) at a temperature of 50 ℃; isolated yield.
The compound 1a, DBU, the compound 2a and tetrahydrofuran were sequentially added to a reaction flask and stirred at 50 ℃ for a certain period of time conventionally. After the reaction is finished, the solvent is drained, and the crude product is subjected to silica gel column flash column chromatography (eluent: ethyl acetate: petroleum ether: 1: 10) to obtain a yellow solid product. The reaction conditions and yields were as follows:
the reaction conditions of the best embodiment of the invention are as follows: 0.24 mmolN-ethyl isatin, 0.48 mmol diphenylcyclopropenone, 1.0 eq DBU (relative toN-ethyl isatin) in 0.5mL THF at 50 ℃ for 1.5 h.
Comparative example
0.24 mmol N-ethyl isatin, 0.48 mmol diphenyl cyclopropenone, in 0.5mL THF at 50 ℃ for 1.5 h, no product. In the absence of DBU, the formation of the target product was not monitored when the reaction was carried out under standard conditions.
In the invention, DBU is used for promoting the synthesis of pyrano [2,3-b]Indol-2-one compounds. The method has the advantages of no need of metal catalysis, mild reaction conditions, high atom economy and high substrate tolerance, and provides a more convenient and simple post-treatment method for synthesizing the skeleton compounds.