CN110078699B - Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light - Google Patents
Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light Download PDFInfo
- Publication number
- CN110078699B CN110078699B CN201910336198.3A CN201910336198A CN110078699B CN 110078699 B CN110078699 B CN 110078699B CN 201910336198 A CN201910336198 A CN 201910336198A CN 110078699 B CN110078699 B CN 110078699B
- Authority
- CN
- China
- Prior art keywords
- thiocyanate
- substituted
- reaction
- coumarin
- visible light
- 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
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of C-3-thiocyanate substituted 4-aminocoumarin derivatives, namely a novel method for constructing C-3-thiocyanate substituted coumarins through reaction of the 4-aminocoumarin derivatives and thiocyanate under the condition of visible light promotion. Firstly, mixing and dissolving C-4 arylamine substituted coumarin compounds and thiocyanate substances in an organic solvent, adding protonic acid, and carrying out magnetic stirring reaction for 10-24 h under the conditions of oxygen and room temperature and under the irradiation of a blue 12W LED light source; after the reaction is finished, removing the solvent from the reaction liquid through a rotary evaporator, and purifying the residue by using a silica gel column to obtain the C-3 thiocyanate substituted 4-aminocoumarin derivative with the general formula (I).
Description
Technical Field
The invention relates to a method for synthesizing a visible light-promoted C-3 thiocyanate-substituted 4-aminocoumarin derivative, belonging to the field of organic chemistry.
Background
The coumarin compound is widely present in drugs, natural products and organic molecules with biological activity. Some researches show that the coumarin derivatives have the effects of resisting tumors, fungi, blood sugar and blood coagulation. Therefore, the method for researching the synthesis and derivatization of the coumarin compound has important practical significance in the field of drug research and development. Recently, it has been reported in literature that arylamino substituted coumarin derivatives at the C-4 position show better activity in anticancer activity (j.med.chem.2016,59,5721). Therefore, the development of a synthesis method based on C-4 arylamine substituted coumarin core skeleton compound is of great significance for developing new anticancer drugs.
Thiocyanate groups are an important group of sulfur-containing functional groups and are widely found in natural products and bioactive molecules. The introduction of thiocyanate radicals into organic molecules may cause the change of the biological activity of the organic molecules, and has important effect on searching effective medicines. The method for introducing thiocyanate groups into aromatic rings mainly comprises the following steps: (1) common oxidants include potassium hydrogen persulfate complex salt, persulfate, DDQ and the like by an oxidant oxidation method; (2) visible light catalysis methods, but the methods are all carried out under the condition of a photocatalyst, and common photocatalysts comprise rose bengal, eosin, silver/titanium dioxide nanotubes and the like. The above two methods have certain limitations, for example, the reaction needs to use a strong oxidant, needs to be performed under a photocatalyst condition, and the like, so that the cost is high and the method is not environment-friendly. It is therefore of particular importance to develop new processes for introducing thiocyanate groups into aromatic rings. On the basis of the research of photocatalysis of our subject group, we propose a simpler, green and efficient method for introducing thiocyanate on aromatic ring.
Disclosure of Invention
The invention provides a C-3-site thiocyanate group substituted 4-amino coumarin derivative and a preparation method thereof, which take the importance of C-4 site arylamine group substituted coumarin and thiocyanate into consideration and aim at the blank of the compound in the field of chemical synthesis. Namely, a novel method for constructing the C-3 thiocyanate-substituted 4-amino coumarin derivative by directly thiocyanizing substituted C-3C-H bonds of coumarin under the condition of visible light promotion.
The technical scheme of the invention is as follows:
a C-3 thiocyanate group substituted 4-amino coumarin derivative is characterized in that the chemical structural general formula (I) is as follows:
wherein:
R1is a substituent group connected on the benzene ring of coumarin, and is selected from linear alkyl of C1-C5; halogen;
R2is a substituent group connected on an amino benzene ring and is selected from linear alkyl of C1-C5;
the synthesis equation of the C-3 thiocyanate group substituted 4-amino coumarin derivative is as follows:
a synthesis method of a C-3 thiocyanate substituted 4-aminocoumarin derivative promoted by visible light is synthesized by the following steps: firstly, mixing and dissolving C-4 arylamine substituted coumarin compounds and thiocyanate substances in an organic solvent, adding protonic acid, and carrying out magnetic stirring reaction for 10-24 h under the conditions of oxygen, room temperature and irradiation of a blue 12W LED light source; after the reaction is finished, removing the solvent from the reaction liquid through a rotary evaporator, and purifying the residue by using a silica gel column to obtain the C-3 thiocyanate substituted 4-aminocoumarin derivative with the general formula (I).
Preferably, the C-4 arylamine group substituted coumarin compound contains arylamine group linked to C-4 of coumarin, and the general formula is shown in formula (II); the thiocyanate compound is one of sodium thiocyanate, potassium thiocyanate and ammonium thiocyanate. The general formula is shown as a formula (III);
substituent R in the compound of formula (II)1、R2Is as defined in formula (I);
in the formula (III), M is Na, K or NH4。
Preferably, the amount of the thiocyanate is 2-5 times of that of the C-4 arylamine group substituted coumarin; the protonic acid accounts for 1.5-3 times of the amount of the C-4 arylamine substituted coumarin.
Preferably, the organic solvent is one of tetrahydrofuran, 1, 4-dioxane, toluene and 1, 2-dichloroethane; the protonic acid is one of trifluoroacetic acid and acetic acid.
Preferably, the reaction is carried out under oxygen condition, and the reaction temperature is room temperature;
or, the reaction is carried out without adding a ligand and a metal catalyst;
or the blue light is emitted by a 12-watt LED lamp, and the C-3-position C-H bond of the reactant coumarin is induced to be directly thiocyanized by using visible light as an accelerator to construct a C-3-position thiocyanate group substituted coumarin compound;
or the silica gel column is preferably silica gel with the specification of 200-300 meshes, and petroleum ether/ethyl acetate with the volume ratio of 5:1-20:1 is used as an eluent during purification.
Preferably, the substituent R1、R 20, 1, or 2.
Preferably, a 25 ml Schlenk tube equipped with a magnetic stirrer is charged with ammonium thiocyanate (0.6 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube is replaced three times with oxygen, and an oxygen-filled balloon is attached to the reaction tube; trifluoroacetic acid (0.4 mmol) and 1, 4-dioxane (2 ml) are added into a reaction tube by an injector, a 12-watt blue LED lamp is placed at a position 3 cm away from the reaction tube, and the reaction is carried out for 12 hours at room temperature; after the reaction was completed, the organic phase was passed through a rotary evaporator to remove the solvent, and the residue was purified by a silica gel column (silica gel size: 200 to 300 mesh; eluent: petroleum ether/ethyl acetate (6:1, v/v)) to obtain 50.5mg of an aimed product,
the nuclear magnetic spectrum data of the obtained product are as follows:
1H NMR:(CDCl3,500MHz,ppm)δ7.60(t,1H,J＝7.2Hz),7.49-7.41(m,2H),7.31(t,2H,J＝8.0Hz),7..22(t,1H,J＝7.6Hz),7.01(t,1H,J＝7.4Hz),6.85(d,2H,J＝8.0Hz),3.57(s,3H)；
13C NMR(CDCl3,125MHz,ppm)δ160.3,158.9,153.7,145.6,133.6,129.8,126.1,124.7,122.0,118.1,117.7,116.3,109.0,108.7,39.6；
the infrared spectrum data of the obtained product are as follows: vmax (KBr)/cm-13460,2894,2167,1721,1633,1509,1375,757；
The high resolution mass spectrum data of the obtained product are as follows: HRMS calcd for C17H12N2O2S[M+H]+309.0692；found 309.0695。
The scheme of the invention also provides application of the C-3 thiocyanate substituted 4-aminocoumarin derivative in the field of drug research and development, wherein the field of drug research and development comprises the aspects of antitumor, antifungal, blood sugar reduction, anticoagulation and the like.
The traditional reaction for introducing thiocyanate groups on aromatic rings needs to use a strong oxidant, needs to be carried out under the condition of a photocatalyst, and the like, so that the cost is high and the environment is not friendly enough. The preparation method of the invention does not need harsh conditions, strong oxidant and photocatalyst, has simple and convenient operation, and can complete the reaction by one step, which is a universal method. The method is suitable for synthesizing various C-3-thiocyanate-substituted coumarin compounds and derivatives, and has high universality on various functional groups on an aromatic ring, so that the number and the types of substituents of the C-3-thiocyanate-substituted coumarin and derivatives are not particularly limited in fact. Accordingly, the number and kind of substituents of the coumarin derivative are not particularly limited.
The invention has the beneficial effects that: according to the preparation method, C-4 arylamine substituted coumarin and thiocyanate are used as raw materials, one of tetrahydrofuran, 1, 4-dioxane, toluene and 1, 2-dichloroethane is used as a solvent, the reaction temperature is room temperature, and the C-3 thiocyanate substituted coumarin compound is efficiently synthesized for the first time under the irradiation of a blue LED light source. Compared with the traditional method for introducing thiocyanate radicals into aromatic rings, the method has the advantages of mild reaction conditions, low cost, small environmental pollution, high yield, good functional group compatibility, convenience in separation and purification and the like.
Drawings
FIG. 1 is a schematic diagram of the synthesis equation of the present invention.
Detailed description of the invention
The invention is further illustrated by the following specific examples, it being understood that the preparation of the examples is illustrative only and is not intended to be limiting; on the premise of the conception of the invention, simple modification of the preparation method of the invention belongs to the protection scope of the invention.
The preparation method, the adding sequence of various materials and the specific reaction steps can be automatically adjusted by a person skilled in the art, and the preparation method is not only suitable for small-scale preparation in a laboratory, but also suitable for industrial large-scale production in a chemical plant. In the case of industrial large-scale production, the specific reaction parameters can be determined experimentally by the person skilled in the art.
It should also be noted that various preferred features of the method of the present invention mentioned above and various specific features in the embodiments specifically described below may be combined, and all combinations of these features, all numerical ranges bounded by upper and lower numerical values specifically disclosed herein, and the like, fall within the scope of the present invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
The materials and reagents used in the following examples are commercially available or synthesized from commercially available starting materials, unless otherwise specified.
Example 1:
a25 mL Schlenk tube containing a magnetic stirrer was charged with ammonium thiocyanate (0.6 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Trifluoroacetic acid (0.4 mmol) and 1,4 dioxane (2 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed 3 cm from the reaction tube and reacted at room temperature for 12 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent. The residue was purified by a silica gel column (specification of silica gel: 200 to 300 mesh, eluent petroleum ether/ethyl acetate (6:1, v/v)) to obtain 50.5mg of the objective product in a yield of 82%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR:(CDCl3,500MHz,ppm)δ7.60(t,1H,J＝7.2Hz),7.49-7.41(m,2H),7.31(t,2H,J＝8.0Hz),7.22(t,1H,J＝7.6Hz),7.01(t,1H,J＝7.4Hz),6.85(d,2H,J＝8.0Hz),3.57(s,3H).13C NMR(CDCl3,125MHz,ppm)δ160.3,158.9,153.7,145.6,133.6,129.8,126.1,124.7,122.0,118.1,117.7,116.3,109.0,108.7,39.6.vmax(KBr)/cm-13460,2894,2167,1721,1633,1509,1375,757.HRMS calcd for C17H12N2O2S[M+H]+309.0692；found 309.0695.
example 2:
a25 mL Schlenk tube containing a magnetic stirrer was charged with potassium thiocyanate (0.5 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Trifluoroacetic acid (0.3 mmol) and tetrahydrofuran (1.5 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed at a distance of 3 cm from the reaction tube and reacted at room temperature for 18 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent, and the residue was purified by a silica gel column (silica gel size: 200 to 300 mesh, eluent petroleum ether/ethyl acetate (5: 1, v/v)) to obtain 39.9mg of the objective product in 62% yield.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR:(CDCl3,500MHz,ppm)δ7.58(t,1H,J＝7.8Hz),7.47(d,1H,J＝8.1Hz),7.41(d,1H,J＝8.1Hz),7.21(t,1H,J＝7.4Hz),7.11(d,2H,J＝8.3Hz),6.80(d,2H,J＝8.5Hz),3.59(s,3H),2.30(s,3H).13C NMR(CDCl3,125MHz,ppm)δ160.4,159.1,153.6,143.3133.4,131.9,130.3,126.5,124.6,118.1,117.6,117.0,109.0,107.4,40.0,20.5.vmax(KBr)/cm-13427,2942,2154,1702,1601,1581,1432,785.HRMS calcd for C18H14N2O2S[M+H]+323.0849；found 323.0849。
example 3:
a25 mL Schlenk tube containing a magnetic stirrer was charged with sodium thiocyanate (0.4 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Acetic acid (0.4 mmol), toluene (2.5 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed 3 cm from the reaction tube and reacted at room temperature for 24 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent, and the residue was purified by a silica gel column (silica gel size: 200 to 300 mesh, eluent petroleum ether/ethyl acetate (10:1, v/v)) to obtain the objective product 34.8mg in 54% yield.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(CDCl3,500MHz,ppm)δ7.31(dd,3H,J＝9.0,8.3Hz),7.22(s,1H),7.04-6.98(m,2H),6.84(d,2H,J＝8.2Hz),3.56(s,3H),2.45(s,3H).13C NMR(CDCl3,125MHz,ppm)δ160.8,159.2,153.8,145.7,145.5,129.7,126.0,125.9,121.8,117.7,116.3,115.7,108.9,107.4,39.6,21.7.vmax(KBr)/cm-13458,2897,2154,1718,1632,1502,1413,827.HRMS calcd for C18H14N2O2S[M+H]+323.0849；found 323.0849
example 4:
a25 mL Schlenk tube containing a magnetic stirrer was charged with ammonium thiocyanate (1.0 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Trifluoroacetic acid (0.5 mmol) and 1, 4-dioxane (2 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed 3 cm from the reaction tube and reacted at room temperature for 19 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent. The residue was purified by silica gel column (specification of silica gel 200 to 300 mesh, eluent petroleum ether/ethyl acetate (15:1, v/v)) to give 49.9mg of the objective product in 73% yield.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(CDCl3,500MHz,ppm)δ7.54(dd,1H,J＝8.8,7.2Hz),7.42(d,1H,J＝2.3Hz),7.38(d,1H,J＝8.8Hz),7.34(t,2H,J＝8.0Hz),7.06(t,1H,J＝7.4Hz),6.87(d,2H,J＝8.0Hz),3.58(s,3H).13C NMR(CDCl3,125MHz,ppm)δ158.8,158.4,152.0,145.1,133.6,130.4,130.0,125.4,122.6,119.3,119.2,116.7,110.2,108.5,39.5.vmax(KBr)/cm-13443,2958,2161,1699,1585,1491,1363,1098,821,692.HRMS calcd for C17H11ClN2O2S[M+H]+343.0303；found 343.0305.
example 5:
a25 mL Schlenk tube containing a magnetic stirrer was charged with ammonium thiocyanate (0.5 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Trifluoroacetic acid (0.6 mmol) and 1, 2-dichloroethane (2 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed at a distance of 3 cm from the reaction tube and reacted at room temperature for 22 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent. The residue was purified by a silica gel column (specification of silica gel: 200 to 300 mesh; eluent: petroleum ether/ethyl acetate (10:1, v/v)) to give 49.8mg of the objective product in 70% yield.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(CDCl3,500MHz,ppm)δ7.52(dd,1H,J＝8.8,6.9Hz),7.42(d,1H,J＝2.3Hz),7.36(d,1H,J＝8.8Hz),7.14(d,2H,J＝8.3Hz),6.80(d,2H,J＝8.4Hz),3.58(s,3H),2.32(s,3H).13C NMR(CDCl3,125MHz,ppm)δ159.0,158.6,151.9,142.8,133.4,132.6,130.5,130.2,125.5,119.4,119.2,117.3,108.8,108.5,40.0,20.6.vmax(KBr)/cm-13411,2909,2152,1719,1588,1525,1511,826.HRMS calcd for C18H13ClN2O2S[M+H]+357.0459；found 357.0459.
example 6:
a25 mL Schlenk tube containing a magnetic stirrer was charged with ammonium thiocyanate (1.0 mmol), C-4 aniline substituted coumarin (0.2 mmol) at room temperature, the reaction tube was replaced three times with oxygen, and an oxygen-filled balloon was attached to the reaction tube. Trifluoroacetic acid (0.4 mmol) and 1,4 dioxane (2 ml) were added to the reaction tube by syringe, and a 12-watt blue LED lamp was placed 3 cm from the reaction tube and reacted at room temperature for 12 hours. After completion of the reaction, the organic phase was passed through a rotary evaporator to remove the solvent. The residue was purified by silica gel column (specification of silica gel 200 to 300 mesh, eluent petroleum ether/ethyl acetate (6:1, v/v)) to give 46.4mg of the objective product in 58% yield.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(CDCl3,500MHz,ppm)δ7.66(dd,1H,J＝8.8,6.6Hz),7.58(d,1H,J＝2.2Hz),7.30(d,1H,J＝8.8Hz),7.14(d,2H,J＝8.4Hz),6.80(d,2H,J＝8.5Hz),3.58(s,3H),2.32(s,3H).13C NMR(CDCl3,125MHz,ppm)δ158.9,158.6,152.4,142.8,136.2,132.7,130.5,128.6,119.8,119.5,117.5,117.4,108.89,108.5,40.0,20.6.vmax(KBr)/cm-13674,3422,2155,1720,1513,1406,1393,1065,621.HRMS calcd for C18H13BrN2O2S[M+H]+400.9954；found 400.9957.
Claims (5)
1. a synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivatives promoted by visible light is characterized by comprising the following steps: synthesized by the following steps: firstly, mixing and dissolving C-4 arylamine substituted coumarin compounds and thiocyanate substances in an organic solvent, adding protonic acid, and carrying out magnetic stirring reaction for 10-24 h under the conditions of oxygen, room temperature and irradiation of a blue 12W LED light source; after the reaction is finished, removing the solvent from the reaction solution by a rotary evaporator, purifying the residue by a silica gel column to obtain the C-3 thiocyanate substituted 4-aminocoumarin derivative shown in the general formula (I),
wherein:
R1is a substituent group connected on the benzene ring of coumarin, and is selected from linear alkyl of C1-C5 and halogen;
R2is a substituent group connected on a benzene ring connected with an amino group, and is selected from linear alkyl of C1-C5;
the C-4 arylamine group substituted coumarin compound contains arylamine group connected to C-4 of coumarin and has a general formula shown in formula (II); the thiocyanate compound is one of sodium thiocyanate, potassium thiocyanate and ammonium thiocyanate, and the general formula is shown as a formula (III);
substituent R in the compound of formula (II)1、R2Is as defined in formula (I); in the formula (III), M is Na, K or NH4(ii) a Substituent R1、R2Is 0, 1 or 2.
2. The method for synthesizing the C-3 thiocyanate substituted 4-aminocoumarin derivative promoted by visible light according to claim 1, wherein the method comprises the following steps: the amount of the thiocyanate is 2-5 times of that of the C-4 arylamine substituted coumarin; the protonic acid accounts for 1.5-3 times of the amount of the C-4 arylamine substituted coumarin.
3. The method for synthesizing the C-3 thiocyanate substituted 4-aminocoumarin derivative promoted by visible light according to claim 1, wherein the method comprises the following steps: the organic solvent is one of tetrahydrofuran, 1, 4-dioxane, toluene and 1, 2-dichloroethane; the protonic acid is one of trifluoroacetic acid and acetic acid.
4. The method for synthesizing the C-3 thiocyanate substituted 4-aminocoumarin derivative promoted by visible light according to claim 1, wherein the method comprises the following steps: the reaction is carried out under the condition of oxygen, and the reaction temperature is room temperature;
or, the reaction is carried out without adding a ligand and a metal catalyst;
or the blue light is emitted by a 12-watt LED lamp, and the C-3-position C-H bond of the reactant coumarin is promoted and induced to be directly thiocyanized through visible light to construct a C-3-position thiocyanate group substituted coumarin compound;
or the silica gel column is preferably silica gel with the specification of 200-300 meshes, and petroleum ether/ethyl acetate with the volume ratio of 5:1-20:1 is used as an eluent during purification.
5. The method for synthesizing the C-3 thiocyanate substituted 4-aminocoumarin derivative promoted by visible light according to claim 1, wherein the method comprises the following steps: at room temperature, a 25 ml Schlenk schlank tube with a magnetic stirrer is filled with 0.6 mmol of ammonium thiocyanate and 0.2 mmol of C-4 aniline substituted coumarin, the reaction tube is replaced by oxygen for three times, and a balloon filled with oxygen is connected to the reaction tube; adding 0.4 mmol of trifluoroacetic acid and 2 ml of 1, 4-dioxane into the reaction tube by using an injector, placing a 12-watt blue LED lamp at a position 3 cm away from the reaction tube, and reacting for 12 hours at room temperature; after the reaction is finished, removing the solvent from the organic phase by a rotary evaporator, purifying the residue by a silica gel column, wherein the specification of the silica gel is 200-300 meshes, the eluent is petroleum ether and ethyl acetate, and the volume ratio is 6:1, obtaining 50.5mg of a target product,
the nuclear magnetic spectrum data of the obtained product are as follows:
1HNMR:(CDCl3,500MHz,ppm)δ7.60(t,1H,J＝7.2Hz),7.49-7.41(m,2H),7.31(t,2H,J＝8.0Hz),7.22(t,1H,J＝7.6Hz),7.01(t,1H,J＝7.4Hz),6.85(d,2H,J＝8.0Hz),3.57(s,3H)；
13CNMR(CDCl3,125MHz,ppm)δ160.3,158.9,153.7,145.6,133.6,129.8,126.1,124.7,122.0,118.1,117.7,116.3,109.0,108.7,39.6；
the infrared spectrum data of the obtained product are as follows: vmax (KBr)/cm-13460,2894,2167,1721,1633,1509,1375,757；
The high resolution mass spectrum data of the obtained product are as follows: HRMScalcdforC17H12N2O2S[M+H]+309.0692；found309.0695。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910336198.3A CN110078699B (en) | 2019-04-24 | 2019-04-24 | Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910336198.3A CN110078699B (en) | 2019-04-24 | 2019-04-24 | Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110078699A CN110078699A (en) | 2019-08-02 |
| CN110078699B true CN110078699B (en) | 2021-04-02 |
Family
ID=67416576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910336198.3A Active CN110078699B (en) | 2019-04-24 | 2019-04-24 | Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110078699B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0229076B2 (en) * | 1982-09-17 | 1990-06-27 | Kowa Co | SHINKINABENZO PIRANJUDOTAI |
| US10544134B2 (en) * | 2015-09-24 | 2020-01-28 | Guizhou Bailing Group Pharmaceutical Co., Ltd. | 4-substituted coumarin derivatives and preparation methods and uses thereof |
| CN109053661B (en) * | 2018-08-28 | 2022-02-25 | 青岛科技大学 | Synthesis method of C-3 arylseleno substituted coumarin promoted by visible light |
-
2019
- 2019-04-24 CN CN201910336198.3A patent/CN110078699B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110078699A (en) | 2019-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109053661B (en) | Synthesis method of C-3 arylseleno substituted coumarin promoted by visible light | |
| CN110845428B (en) | Photocatalytic preparation method of 3-acyl quinoxalinone compound | |
| CN104230942B (en) | Spiro[pyrrolinyl-3,2'-oxoindole] derivatives, and synthesis method and application thereof | |
| CN111072720A (en) | Synthesis method of five-membered cyclic compound substituted by phosphono methylene | |
| CN102977017A (en) | Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component | |
| CN110078699B (en) | Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light | |
| CN110668987B (en) | Synthesis method and application of visible light-promoted dithiocarbamate compound | |
| CN103408525A (en) | Synthetic method and application of flavonoid | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN106831474B (en) | One kind-the α containing alpha-aromatic, β-diamino acid ester derivant and its synthetic method and application | |
| CN111004145B (en) | Chiral optical amide substituted alpha, beta-diamino acid derivative and preparation method and application thereof | |
| CN108276420B (en) | 8, 13-dihydrobenzo [5,6] chromene [2,3-b ] indole compound and synthetic method thereof | |
| CN113004248A (en) | Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt | |
| CN114773245B (en) | Preparation method of trifluoromethyl selenoether | |
| CN111559989A (en) | Synthesis method and application of visible light-promoted 2-aminonaphtho [2,1-d ] thiazole compound | |
| CN108794395B (en) | Preparation method of 2-quinolinone compounds | |
| CN113735873B (en) | Method for preparing Artemisinin G | |
| CN115304557B (en) | Enamine derivative and preparation method thereof | |
| CN113717037B (en) | Green synthesis method of 2, 5-dimethoxy benzaldehyde | |
| CN111410656B (en) | Preparation method of isoquinolone derivative | |
| CN115385835B (en) | Synthesis method of selenate compound | |
| CN110294757B (en) | Synthetic method and application for preparing C-3-thioimidazopyridine derivative by copper catalysis one-pot method | |
| CN117143066A (en) | Synthesis method of selenylbenzoxepin compound | |
| CN114957089A (en) | Method for green synthesis of aza spiro oxime compound driven by visible light | |
| CN106565644A (en) | 3- alkyl-5-hydroxy-4-aryl furanone derivative and preparation method thereof |
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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Yang Daoshan Inventor after: Yan Qiuli Inventor before: Yang Daoshan Inventor before: Yan Qiuli |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |