CN108947900B - Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction - Google Patents
Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction Download PDFInfo
- Publication number
- CN108947900B CN108947900B CN201810885686.5A CN201810885686A CN108947900B CN 108947900 B CN108947900 B CN 108947900B CN 201810885686 A CN201810885686 A CN 201810885686A CN 108947900 B CN108947900 B CN 108947900B
- Authority
- CN
- China
- Prior art keywords
- formula
- reaction
- compound
- formula iii
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing a heterocyclic compound by photoinduced metal-free catalyzed carbon arylation series reaction, which comprises the following steps: taking a compound shown in a formula III and a compound shown in a formula IV as substrates, stirring for 24-48 hours in an organic solvent under the action of a photosensitizer and an alkaline compound under the condition of room temperature and illumination, quenching reaction, extracting, washing, drying, concentrating and purifying to obtain the heterocyclic compound shown in the formula I or the formula II. The method disclosed by the invention has the advantages that the reaction is carried out under the illumination of room temperature, no metal catalysis is carried out, and compared with the traditional Ullmann-Hurtley coupling ring-closing reaction, the method does not need to add a catalyst, only needs to carry out the reaction under the room temperature condition, is low in energy consumption, greatly reduces the occurrence of side reactions, and is green and environment-friendly.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a method for synthesizing a heterocyclic compound by photoinduced metal-free carbon arylation series reaction, in particular to a method for synthesizing isoquinolinone compounds and isocoumarin compounds by photoinduced metal-free carbon arylation series reaction.
Background
The Ullmann reaction is a cross coupling reaction under the copper catalysis condition, and compared with coupling reactions in which a plurality of transition metals participate, the Ullmann reaction has great advantages in the aspects of economy and environmental protection because a copper reagent with low price and low toxicity is used. Researchers find that the Ullmann reaction can be applied to the formation of C-C, C-N, C-O bonds, and can also be popularized to the formation of C-S, C-P and C-Se bonds, so that the application range of the Ullmann reaction in organic synthesis is widened. In the Ullmann reaction, copper is mostly used for catalyzing reaction, a ligand and alkali play important roles, and the ligand can increase the reaction activity and selectivity of a copper catalyst.
Isocoumarin compounds are natural lactone compounds widely existing in nature, and have physiological and biological activities (such as Urolithin A) of resisting bacteria, diminishing inflammation, inhibiting protease, weeding, resisting cancer and the like, and the basic parent nucleus of the isocoumarin compounds is benzo hexa-lactone ring. Because the isocoumarin compound has anticancer activity, the synthetic method is always a hot spot in organic synthesis. The Xi subject group in 2012 catalyzes 2-bromobenzamide compounds or N-substituted-2-bromobenzamide compounds and 1 through CuI3-diketones, DMF as solvent at 120 ℃ and K3PO4As the alkali, the 3-substituted isocoumarin derivative can be obtained. When the asymmetric 1, 3-diketone compound is used as a substrate, the regioselectivity is very good, but the yield is low, and the method is only suitable for the 2-bromobenzamide compound containing an electron-donating group. In 2012, a Yao subject group reports a new synthetic method for rapidly synthesizing isocoumarin derivatives by copper-catalyzed serial C-C/C-O coupling cyclization. The method takes 2-iodine-N-phenyl benzamide and 1, 3-diketone compounds as substrates, CuI as a catalyst, DMSO as a solvent, and Cs2CO3Is alkali, and can obtain the 3-substituted isocoumarin derivative with medium yield after 5-60min at the temperature of 100 ℃. When an asymmetric 1, 3-diketone compound is used as a substrate, an isomer product can be obtained; when a symmetrical 1, 3-diketone compound is taken as a substrate, a single target product can be obtained; when a 2-substituted-1, 3-dione compound or a β -keto acid ester is used as a substrate, a corresponding product is not obtained. Therefore, the method has good universality only for symmetrical 1, 3-diketone compounds.
The isoquinolone compounds are also important chemical intermediates, for example, the tetrahydroisoquinolinone derivatives prepared from the isoquinolone compounds are not only used for preparing efficient pesticides, color films, dyes and the like, but also have important pharmacological effects, such as antihypertensive, antiarrhythmic, antithrombotic activity and the like, and are also important intermediates of gastric ulcer resistant medicaments. In recent years, the reported methods for isoquinolinone and its derivatives have the disadvantages of harsh reaction conditions, low yield, many by-products, difficult purification and expensive catalysts.
The preparation method of the two heterocyclic compounds still needs a Cu catalyst, the reaction temperature is high, the chemical selectivity of each reaction is poor, and only one product can be synthesized. Therefore, it is necessary to develop a new method with mild reaction conditions, environmental protection and high chemical selectivity.
Disclosure of Invention
The invention aims to provide a method for synthesizing a heterocyclic compound by photoinduced metal-catalysis-free carbon arylation series reaction, which has the advantages of reaction under room-temperature illumination, no metal catalysis, low energy consumption, greatly reduced side reaction and environmental protection.
In order to achieve the purpose, the invention adopts the following technical scheme:
the method for synthesizing the heterocyclic compound by the photo-induced metal-free carbon arylation cascade reaction comprises the following steps: taking a compound shown in a formula III and a compound shown in a formula IV as substrates, stirring for 24-48 hours in an organic solvent under the action of a photosensitizer and an alkaline compound under the condition of room temperature and illumination, quenching reaction, extracting, washing, drying, concentrating and purifying to obtain a heterocyclic compound shown in a formula I or a formula II;
wherein R in the formula III1R is any one selected from a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom or a nitro group2Selected from any one of hydrogen atom, alkyl or aryl, X is selected from I, Br or Cl;
in the formula IV, R3And R4Selected from alkyl, R5Any one selected from a hydrogen atom, an alkyl group or an aryl group;
r in formula I and formula II1、R3Is as defined in formula III; in the formula I, R4Is as defined in formula IV; in the formula II R5Is as defined in formula IV.
Further, the molar ratio of the compound shown in the formula III, the compound shown in the formula IV and the alkaline compound is 1: 3: 2.
further, the organic solvent is any one of DMSO, acetonitrile, toluene, 1, 4-dioxane, methanol or DMF.
Further, the photosensitizer is selected from I2、Ru[bpy]3Cl2Eosin Y, fluorescein, methylene blue, tetraphenylporphyrin, tiger red or eosin B, wherein the molar ratio of the photosensitizer to the compound shown in the formula III is 1: (0.05-0.20).
Further, the basic compound is any one of cesium carbonate, tripotassium phosphate, potassium carbonate, lithium tert-butoxide, sodium tert-butoxide or potassium tert-butoxide.
Further, the illumination condition is any one of ultraviolet light with a wavelength of 365nm, ultraviolet light with a wavelength of 310nm, ultraviolet light with a wavelength of 254nm, incandescent light, xenon light, LED green light, LED blue light or LED red light.
Compared with the prior art, the invention has the beneficial effects that:
1. the carbon arylation series reaction adopted by the invention is carried out under the illumination of room temperature, and has no metal catalysis, compared with the traditional Ullmann coupling ring-closing reaction, the carbon arylation series reaction does not need to add a catalyst, only needs to be carried out under the room temperature condition, has low energy consumption, greatly reduces the occurrence of side reaction, and is green and environment-friendly.
2. The carbon arylation series reaction adopted by the invention can be used for controllably synthesizing a series of isoquinolone compounds or isocoumarin compounds with different substituents by using different substrates under the photocatalysis condition, and the good chemical selectivity is embodied; when an unsymmetrical beta-diketone is used as the substrate, and R3The substituent being less than R4When the substituent is used, the isoquinolone compound can be selectively synthesized, and good regioselectivity is embodied; when the alpha position of the substrate beta-diketone has a large steric hindrance group (such as aryl), the reaction can also occur to obtain the isocoumarin compound.
Detailed Description
The following examples are intended to illustrate the invention, but are not intended to limit the scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.
Organic solvents used in the following examples, DMSO (dimethyl sulfoxide), acetonitrile, DMF (dimethylformamide), toluene, 1, 4-dioxane or methanol, were treated with anhydrous oxygen-free treatment before use.
The heterocyclic compound shown in the formula I is an isoquinolone compound, the heterocyclic compound shown in the formula II is an isocoumarin compound, and the reaction equation for synthesizing the two compounds is shown as follows:
EXAMPLE 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin Y (0.025 mmol, 17.3 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 36 h under UV irradiation at room temperature 254nm and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 90mg in 90% yield.
Nuclear magnetic characterization of 4-acetyl-3-methylisoquinolin-1 (2H) -one is as follows:1H NMR (400 MHz, DMSO-d 6) δ 11.50 (s, 1H), 8.30-8.09 (m, 1H), 7.80-7.61 (m, 1H), 7.48 (t, J = 7.8 Hz, 2H), 2.52 (s, 3H), 2.24 (s, 3H). 13C NMR (100 MHz, DMSO) δ 203.3, 162.1, 138.0, 135.1, 133.3, 127.4, 126.6, 124.5, 124.0, 117.20, 33.00, 17.70. ESI-MS [M+H]+ m/z 202.18。
example bis 4-acetyl-3-methyl-7-nitroisoquinolin-1 (2H) -one
5-Nitro-o-bromobenzamide (0.5 mmol, 122.5 mg) (X = Br, R in formula III)1=NO2，R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin B (0.025 mmol, 15.6 mg), DMF (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 36 h under UV irradiation at room temperature of 254nm and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give 117mg of a yellow solid product in 95% yield.
The nuclear magnetic characterization of 4-acetyl-3-methyl-7-nitroisoquinolin-1 (2H) -one is as follows:1H NMR (400 MHz, DMSO-d 6) δ 12.01 (s, 1H), 8.88 (d, J = 2.6 Hz, 1H), 8.44-8.40 (m, 1H), 7.73 (d, J = 9.0 Hz, 1H), 2.57 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, DMSO) δ 202.5, 161.3, 145.1, 143.3, 139.8, 127.1, 125.9, 124.3, 123.2, 116.9, 33.0, 18.3. ESI-MS [M+H]+ m/z 247.13。
example tris 4-acetyl-3-cyclopropylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), 1-cyclopropyl-1, 3-butanedione (1.5 mmol, 172 μ L) (R in formula IV)3=CH3，R4= cyclopropyl, R5=H），t-BuOLi（1mmol，80.1mg），I2(0.1 mmol, 25.4 mg), toluene (2.5 mL) were added to the quartz reaction tube and the mixture was treated with xenon under a nitrogen atmosphere at room temperatureThe lamp was stirred for 36 hours and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give 89mg of a white solid product in 78% yield.
The nuclear magnetic characterization of 4-acetyl-3-cyclopropylisoquinolin-1 (2H) -one is as follows:1H NMR (400 MHz, DMSO-d 6) δ 11.56 (s, 1H), 8.24-8.18 (m, 1H), 7.75-7.68 (m, 1H), 7.56 (d, J = 8.2 Hz, 1H), 7.53-7.45 (m, 1H), 2.40-2.32 (m, 1H), 2.28 (s, 3H), 1.19-1.13 (m, 2H), 1.13-1.07 (m, 2H). 13C NMR (100 MHz, DMSO) δ 204.6, 162.1, 138.6, 135.4, 133.3, 127.4, 126.6, 124.5, 124.1, 117.1, 24.1, 17.9, 13.2. ESI-MS [M+H]+ m/z228.19。
example tetrakis 7-ethyl-8-propionyl-1, 6-naphthyridin-5 (6H) -one
2-Chloropyridinecarboxamide (0.5 mmol, 78 mg) (formula III X = Cl, R)1=R2= H), 3, 5-heptanedione (1.5 mmol, 213.7 μ L) (R in formula IV3=R4= ethyl, R5=H），tBuONa (1 mmol, 96.1 mg), fluorescein (0.025 mmol, 8.3 mg), MeOH (2.5 mL) were added to the quartz reaction tube and the mixture was stirred under nitrogen at room temperature under blue LED illumination for 36 h, and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product 81mg as a white solid in a yield of 70%.
The nuclear magnetic characterization of 7-ethyl-8-propionyl-1, 6-naphthyridin-5 (6H) -one is as follows:1H NMR (400 MHz, DMSO-d 6) δ 11.78 (s, 1H), 8.94-8.87 (m, 1H), 8.53-8.46 (m, 1H), 7.53-7.48 (m, 1H), 2.97-2.90 (m, 2H), 2.50-2.42 (m, 2H), 1.20 (t, J = 7.5 Hz, 3H), 1.09 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, DMSO) δ 206.0, 162.5, 154.8, 152.8, 147.0, 135.7, 122.0, 120.0, 117.9, 38.4, 24.7, 14.8, 8.7. ESI-MS [M+H]+ m/z 231.15。
example five 3-Methylisochromycin
N-propyl-o-bromobenzamide (0.5 mmol, 121 mg) (X = Br, R in formula III)1=H，R2= n-propyl), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin Y (0.025 mmol, 17.3 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 36 h under ambient temperature green LED light irradiation and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 8: 1) to give the product as a white solid 60mg, yield 75%.
The nuclear magnetic characterization of 3-methylisothiavalin is as follows:1H NMR (400 MHz, CDCl3) δ 8.32-8.19 (m, 1H), 7.74-7.60 (m, 1H), 7.51-7.41 (m, 1H), 7.34 (d, J = 7.9 Hz, 1H), 6.26 (t, J = 1.0 Hz, 1H), 2.29 (d, J = 0.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 158.2, 149.8, 132.9, 130.0, 124.8, 122.8, 120.1, 115.2, 98. 8, 14.9. ESI-MS [M+H]+ m/ z 161.20。
example six 3, 4-dimethyl isocoumarin
N-Phenylo-iodobenzamide (0.5 mmol, 161.5 mg) (X = I, R in formula III)1=H，R2Ph), 3-methyl-2, 4-pentanedione (1.5 mmol, 175 μ L) (R in formula IV3=R4=CH3，R5=CH3），Cs2CO3(1 mmol, 326 mg), eosin Y (0.025 mmol, 17.3 mg), 1, 4-dioxane: (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere at room temperature under 310nm uv irradiation for 36 hours and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 8: 1) to give the product 61mg as a white solid in a yield of 70%.
The nuclear magnetic characterization of 3, 4-dimethylisocoumarin was as follows:1H NMR (400 MHz, CDCl3) δ 8.33-8.27 (m, 1H), 7.76-7.71 (m, 1H), 7.52-7.44 (m, 2H), 2.32 (s, 3H), 2.18 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.9, 150.1, 138.7, 134.6, 129. 7, 127.1, 122.4, 120. 5, 107.7, 17.3, 12.2. ESI-MS [M+H]+ m/z 175.19。
example hepta-3-methyl-4-phenylisocoumarin
N-Phenylo-iodobenzamide (0.5 mmol, 161.5 mg) (X = I, R in formula III)1=H，R2Ph), 3-phenyl-2, 4-pentanedione (1.5 mmol, 264.3 mg) (R in formula IV3=R4=CH3，R5=Ph），Cs2CO3(1 mmol, 326 mg), tiger red (0.025 mmol, 25.5 mg), DMSO (2.5 mL) were added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere at room temperature under red LED illumination for 36 h and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 8: 1) to give the product 71mg as a white solid in 60% yield.
EXAMPLE octa 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin B (0.025 mmol, 15.6 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 36 h under 365nm UV light at room temperature and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to obtain the product as a white solid 85mg in 85% yield.
EXAMPLE nine 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3（1mmol，326mg），I2(0.1 mmol, 25.4 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere at room temperature under UV irradiation at 254nm for 36 h, and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give 88mg of a white solid product, yield 88%.
Example Dec 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），tBuOK (1 mmol, 112.2 mg), methylene blue (0.025 mmol, 9.3 mg), DMSO (2.5 mL) were added to a quartz reaction tube and the mixture was placed under a nitrogen atmosphere at room temperature under incandescent lightStirred for 48 hours and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 70mg in 70% yield.
EXAMPLE undec-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), tetraphenylporphyrin (0.025 mmol, 15.4 mg), DMSO (2.5 mL) were added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 24 h under 365nm UV irradiation at room temperature and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give 65mg of a white solid product, yield 65%.
EXAMPLE dodeca4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），K3PO4（1mmol，212mg），Ru[bpy]3Cl2(0.025 mmol, 18.7 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere at room temperature under UV irradiation at 254nm for 24 h, and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine and dried over sodium sulfateFiltered and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 60mg in 60% yield.
EXAMPLE thirteen 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin Y (0.025 mmol, 17.3 mg), DMSO (2.5 mL) was added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 48 h under UV irradiation at room temperature 254nm and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 90mg in 90% yield.
Example tetradecyl 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5=H），Cs2CO3(1 mmol, 326 mg), eosin Y (0.025 mmol, 17.3 mg), MeCN (2.5 mL) were added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere for 24 h under UV irradiation at room temperature 254nm and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 60mg in 60% yield.
Example fifteen 4-acetyl-3-methylisoquinolin-1 (2H) -one
O-bromobenzamide (0.5 mmol, 100 mg) (X = Br, R in formula III)1=R2= H), acetylacetone (1.5 mmol, 154 μ L) (R in formula IV)3=R4=CH3，R5= H), potassium carbonate (1 mmol, 138.2 mg), eosin Y (0.025 mmol, 17.3 mg), DMSO (2.5 mL) were added to a quartz reaction tube and the mixture was stirred under nitrogen atmosphere at room temperature under 254nm UV irradiation for 24H and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2: 1) to give the product as a white solid 70mg in 70% yield.
The above-mentioned embodiments are merely preferred embodiments of the present invention, which are merely illustrative and not restrictive, and it should be understood that other embodiments may be easily made by those skilled in the art by replacing or changing the technical contents disclosed in the specification, and therefore, all changes and modifications that are made on the principle of the present invention should be included in the scope of the claims of the present invention.
Claims (3)
1. The method for synthesizing the heterocyclic compound by the photo-induced metal-free carbon arylation cascade reaction is characterized by comprising the following steps of: taking a compound shown in a formula III and a compound shown in a formula IV as substrates, stirring for 24-48 hours in an organic solvent under the action of a photosensitizer and an alkaline compound under the condition of room temperature and illumination, quenching reaction, extracting, washing, drying, concentrating and purifying to obtain a heterocyclic compound shown in a formula I or a formula II;
wherein R in the formula III1R is any one selected from a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom or a nitro group2Selected from any one of hydrogen atom, alkyl or aryl, X is selected from I, Br or Cl; in the formula IV, R3And R4Selected from alkyl, R5Any one selected from a hydrogen atom, an alkyl group or an aryl group;
when R in the formula III2And R in the formula IV5Are all selected from hydrogen atoms, to obtain heterocyclic compounds represented by the formula I, wherein R in the formula I1Is as defined for formula III, R3、R4Is as defined in formula IV;
when R in the formula III2And R in the formula IV5When both are selected from alkyl or aryl, to give a heterocyclic compound of the formula II in which R is1Is as defined for formula III, R3、R5Is as defined in formula IV;
the organic solvent is any one of DMSO, acetonitrile, toluene, 1, 4-dioxane, methanol or DMF; the photosensitizer is selected from I2、Ru[bpy]3Cl2Any one of eosin Y, fluorescein, methylene blue, tetraphenylporphyrin, tiger red or eosin B; the alkaline compound is any one of cesium carbonate, tripotassium phosphate, potassium carbonate, lithium tert-butoxide, sodium tert-butoxide or potassium tert-butoxide; the illumination condition is any one of 365nm ultraviolet light, 310nm ultraviolet light, 254nm ultraviolet light, incandescent light, xenon light, LED green light, LED blue light or LED red light.
2. The method for synthesizing a heterocyclic compound by a series reaction of photo-induced metal-free carbon arylation according to claim 1, wherein the molar ratio of the compound represented by the formula III to the compound represented by the formula IV to the basic compound is 1: 3: 2.
3. the method for synthesizing a heterocyclic compound by photoinduced metal-free carbon arylation tandem reaction according to claim 1, wherein the molar ratio of the photosensitizer to the compound shown in formula III is (0.05-0.20): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810885686.5A CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810885686.5A CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108947900A CN108947900A (en) | 2018-12-07 |
| CN108947900B true CN108947900B (en) | 2021-07-30 |
Family
ID=64467652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810885686.5A Active CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108947900B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110845404B (en) * | 2019-12-05 | 2022-03-04 | 哈尔滨工业大学 | Preparation method of 2-phenyl substituted pyridine nitrogen oxide compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102382051A (en) * | 2011-09-13 | 2012-03-21 | 清华大学 | Method for preparing isoquinoline ketone and derivatives thereof |
| CN105153030A (en) * | 2015-10-14 | 2015-12-16 | 吉首大学 | Perfluoro group substituted isoquinoline-1,3(2H,4H)-diketone as well as preparation method and application thereof |
| CN107531589A (en) * | 2015-01-23 | 2018-01-02 | Gvk生物科技私人有限公司 | Trka kinase inhibitors |
-
2018
- 2018-08-06 CN CN201810885686.5A patent/CN108947900B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102382051A (en) * | 2011-09-13 | 2012-03-21 | 清华大学 | Method for preparing isoquinoline ketone and derivatives thereof |
| CN107531589A (en) * | 2015-01-23 | 2018-01-02 | Gvk生物科技私人有限公司 | Trka kinase inhibitors |
| CN105153030A (en) * | 2015-10-14 | 2015-12-16 | 吉首大学 | Perfluoro group substituted isoquinoline-1,3(2H,4H)-diketone as well as preparation method and application thereof |
Non-Patent Citations (7)
| Title |
|---|
| An Efficient One-Pot Copper-Catalyzed Approach to Isoquinolin-1(2H)-one Derivatives;Feng Wang et al.;《ORGANIC LETTERS》;20091231;第11卷;第2469-2472页 * |
| One-pot synthesis of 1-oxo-1,2-dihydroisoquinolines (isocarbostyrils) via SRN1 (Ar) reactions;Rene Beugelmans et al.;《Synthesis》;19810930;第9卷;第729-731页 * |
| One-Pot Synthesis of 3-Substituted Isoquinolin-1-(2H)-ones and Fused Isoquinolin-1-(2H)-ones by SRN1 Reactions in DMSO;Javier F. Guastavino et al.;《Eur. J. Org. Chem.》;20060711;第2006卷;第3898-3902页 * |
| ortho-Induced transition-metal-free C-arylation cyclization reaction for the synthesis of polysubstituted isocoumarins;Lei Liu et al.;《Tetrahedron》;20120504;第68卷;第5391-5395页 * |
| SRN1-Based Methodology for Synthesis of Naphthylquinolines and Naphthylisoquinolines;Rene Beugelmans et al.;《J. Org. Chem.》;19911231;第56卷;第2518-2522页 * |
| Synthesis of 3-Substituted Isocoumarin Derivatives via CuI-Catalyzed Reaction of o-Bromobenzamides with 1,3-Diketones;Shangjun Cai, et al.;《SYNTHESIS》;20121005;第44卷;第1892-1897页 * |
| Synthesis of Isocoumarin Derivatives via the Copper-Catalyzed Tandem Sequential Cyclization of 2- Halo-N-phenyl Benzamides and Acyclic 1,3-Diketones;Veerababurao Kavala et al.;《J. Org. Chem.》;20120418;第77卷;第5022-5029页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108947900A (en) | 2018-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yu et al. | Copper-catalyzed radical cascades of para-quinone methides with AIBN and H 2 O via α-cyanoalkylation by C–C bond cleavage: new access to benzofuran-2 (3 H)-ones | |
| CN109988117B (en) | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives | |
| CN114315823B (en) | Intermediate of berberine hydrochloride and analogues thereof and preparation method thereof | |
| CN108947900B (en) | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction | |
| EP1717276B1 (en) | Heteropolycyclic compound and dye | |
| CN108863890B (en) | 4-pyrroline-2-ketone derivative and preparation method thereof | |
| WO2018205299A1 (en) | 4,5-disubstituted-1-hydro-pyrrole(2,3-f)quinolone-2,7,9-tricarboxylate compound and applications | |
| CN102863399B (en) | Synthetic method for isatoic anhydride derivative | |
| CN110590788B (en) | 2-acyl-9H-pyrrolo [1,2-a]Synthesis method of indole compound | |
| CN114716438B (en) | Benzo [7,8] indolizine [1,2-c ] quinoline skeleton derivative and synthetic method thereof | |
| CN108164483A (en) | A kind of five yuan of new heteroaromatics and aromatic ring and five yuan of heteroaromatic arylation synthetic methods | |
| CN113912609B (en) | Preparation method of natural alkaloid tryptanthrin and derivatives thereof | |
| CN111777564B (en) | Method for synthesizing quinazolinone compound by photocatalytic alcohol oxidation in aqueous phase | |
| KR102090719B1 (en) | Tetrahydroquinoline derivatives and their synthesis through Fe-catalyzed intermolecular cycloaddition reaction | |
| CN109836383B (en) | Method for preparing 3, 4-dihydroquinoline-2 (1H) -ketone compound | |
| CN108794396B (en) | Oxidation method of 4-oxo-2, 3-dihydroquinoline compound | |
| CN111875549A (en) | Method for synthesizing quinazolinone compound in aqueous phase through photocatalysis | |
| CN110684003A (en) | Simple and efficient total synthesis method of icaritin and derivatives thereof | |
| KR102628273B1 (en) | Method for synthesizing a tetrahydroquinoline derivative comprising an acetamide functional group and a tetrahydroquinoline derivative synthesized using the same | |
| CN110698483B (en) | Synthesis of 2-sulfonyl-9H-pyrrolo [1,2-a ] indole compound | |
| CN109970643A (en) | A kind of green synthesis method of the Activities of Tetrahydroacridine Derivatives under the promotion of iodine anion | |
| CN113444041B (en) | Method for synthesizing polysubstituted quinoline compound by photocatalysis | |
| CN111100123A (en) | Simple method for preparing ellipticine or substituted ellipticine | |
| CN114736181B (en) | Synthesis method of visible light mediated acylated benzofuran derivative | |
| CN112028841B (en) | Photocatalytic synthesis method of 3-aryl-N-methylquinoxaline-2 (1H) -ketone compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |