CN109369645B - Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound - Google Patents
Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound Download PDFInfo
- Publication number
- CN109369645B CN109369645B CN201811291079.2A CN201811291079A CN109369645B CN 109369645 B CN109369645 B CN 109369645B CN 201811291079 A CN201811291079 A CN 201811291079A CN 109369645 B CN109369645 B CN 109369645B
- Authority
- CN
- China
- Prior art keywords
- azaindole
- arylthio
- thiophenol
- base
- compound
- 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
- 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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A green synthesis method of a base-catalyzed 3-arylthio-7-azaindole compound comprises the steps of adding 7-azaindole and an arylthio reagent into a solvent, then adding a catalyst, and reacting at 60-120 ℃ for 2-14 h to obtain a 3-arylthio-7-azaindole compound; wherein the aryl thioreagent is aryl thiophenol. The method has the advantages of simple operation, high conversion rate and good selectivity, does not need to use a transition metal catalyst or stoichiometric elemental iodine, does not need an anhydrous oxygen-free system, can be smoothly carried out by only adding catalytic metered alkali, and is a clean and green synthesis way.
Description
Technical Field
The invention relates to the field of organic synthesis and natural product chemistry, in particular to a base-catalyzed green synthesis method of 3-arylthio-7-azaindole.
Background
Azaindole (1H-pyrrolo [2,3-b ] pyridine) is an aromatic organic compound, widely exists in natural products, and the derivatives thereof are widely applied in the fields of material science and pharmaceutical chemistry. As derivatives thereof, 3-arylthio-7-azaindoles have high utility values in the control and treatment of diseases, particularly heart diseases, allergies, cancers, HIV and obesity (P.C. Unangst, et. al. journal of Medicinal Chemistry,1989,32, 1360; C.D. funk, Nature Reviews Drug discovery,2005,4, 664; R.Ragno, et. al. journal of Medicinal Chemistry,2006,49, 3172; G.La Regina, et. al. journal of Medicinal Chemistry,2007,50, 2865).
The synthesis of 3-arylthio-7-azaindoles generally starts with a 7-azaindole skeleton and is effected by regioselective thionation (nucleophilic substitution) under certain conditions. In review of the literature, the reported processes for preparing 3-arylthio-7-azaindole compounds starting from 7-azaindoles by sulfurization of the carbon atom at the 3-position generally require the transition metal copper, a stoichiometric/excess of a strong base, elemental iodine or trifluoroacetic anhydride, or the like, as a promoter or catalyst for the reaction.
In these methods, a variety of arylthioic reagents are included, each of which can undergo electrophilic substitution with 7-azaindole to yield the desired product, including: diphenyl sulfide (relating to transition metal copper catalysis, see: A. Coluccia, et. al. journal of Medicinal Chemistry,2016,59, 9760; H.Liao, et. al. Current Organic Chemistry,2017,21, 2509; relating to stoichiometric alkali-promoted reactions, see: J.Porter, et. al. bioorganic & Medicinal Chemistry Letters,2009,19, 2780; G.C.visor, et. PCT. Int. Appl. WO 5634A 1, Nov 11, 2010; P.Sangg, I.Green Chemistry,2013,15, 2096; J.Zhang, et. al. Int. WOl. WOOL 1, Sep 18,2014; I.T.Bharanthan, Int. Bharanthan, WO 3,15, 20152096; J.Zhang, et. PCT. Appl. WO 145a. WO 26, WO 3, RSC. WO 26, WO 25, WO 53, WO 25, WO 53, WO 25, WO 53, 103,26, 103, WO 53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,103,103,53,53,53,53,53,53,53,103,53,53,53,103,103,53,53,103,103,103,103,53,53,53,53,53,103,53,53,53,103,53,53,103,103,103,103,103,103,103,103,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,53,103,103,103,53,103,103,103,103,103,103,103,53,53,55,103,53,53,53,103,103,103,103,103,103,103,103,103,103,103,103,103,103,103,103,55,55,55,103,53,53,55,55,55,103,103,53,103,103,103,103,103,53,55,103,103,55,55,103,103,103,55,55,103,103,103,55,55,103,103,103,55,55,55,103,55,55,55,55,55,55,55,55,55,103,103,55,103,103,55,55,103,103,103,103,103,103,103,103,55,55,55,55,55,55,55,55,55,55,55,103,55,55,55,55,55,55,55,55,55,55,55,55,103,55,55,55,55,55,55,55,55,55,55,55,55,55,55,55,55,103,103,103,103,103,103,103,103,103,103,103,103,103,103,103,103,103,55,103,103,103,103,103,103,55,103,103,103,55,55,55,103,103,55,55,103,103,55,103,103,55,55,103,103,103,103,103,103,103,103,55,103,103,55,55,103,103,55,55,55,103,103,55,55,55,55,55,55,55,55,55 to a, preferably, see: liu, et al, chinese Journal of Chemistry,2018,36, 819), benzenesulfonyl chloride (involving transition metal copper catalysis, see: z.wu.et.al.asian Journal of Organic Chemistry,2016,5,625.), benzenesulfonyl hydrazide (relating to high temperature reactions in aqueous media, see: y.yang, et.al.green Chemistry,2016,18,2609.), benzenesulfonyl hydroxamic acid (involving elemental iodine catalysis, see: F. wang, et al, organic & Biomolecular Chemistry,2017,15,5284.) and bangtel sodium salt (relating to iodine catalysis, see: qi, et al, journal of Organic Chemistry,2016,81, 4262; m.luo, et.al.family Zhuanli Shenqing, CN 105418481 a, Mar 23,2016.).
In addition, in the conversion process, 7-azaindole can be firstly reacted with iodine simple substance at the 3-position to perform iodination, and then reacted with aryl thiophenol to obtain the corresponding product (step one: iodination with iodine simple substance; step two: arylthio under the catalysis of transition metal copper, see: R.C. Bernoutas, et.al.PCT Int.appl.WO 2003101990A 1, Dec 112003; H.Tian, et.al.Faming Zhuanli Shenqing, CN 103613591A, Mar 05,2014; W.McCoull, et.al.al.MedChemcomm, 2014,5, 1533; N.Liu, et.al.Bioorganic Chemistry,2016,65, 146.).
As described above, in the conventional reports, a relatively complex compound is generally used as the arylthioic reagent; in the reaction process, transition metal, iodine or excessive strong alkali is usually required to be added to promote the nucleophilic substitution reaction, and some reactions are even required to be carried out under anhydrous and oxygen-free conditions, so that the development of a clean and green method for synthesizing the 3-arylthio-7-azaindole compound is urgent.
Disclosure of Invention
In order to obtain a target product more efficiently and overcome the limitation of conditions such as transition metal, iodine simple substance and even no water or oxygen, the invention aims to provide a base-catalyzed green synthesis method of 3-arylthio-7-azaindole, the whole synthesis process is simple and efficient, the operation is convenient, and the efficient synthesis of the 3-arylthio-7-azaindole compound is realized by a one-pot method.
In order to achieve the purpose, the invention adopts the following technical scheme:
a green synthesis method of a base-catalyzed 3-arylthio-7-azaindole compound comprises the steps of adding 7-azaindole and an arylthio reagent into a solvent, then adding a base catalyst, and reacting at 60-120 ℃ for 2-14 h to obtain a 3-arylthio-7-azaindole compound; wherein the aryl thioreagent is aryl thiophenol.
The invention is further improved in that the solvent is one of dichloroethane, N-dimethylformamide, dimethyl sulfoxide and acetonitrile.
The invention is further improved in that the alkali catalyst is one or more of potassium carbonate, cesium hydroxide, cesium acetate and sodium acetate.
The invention is further improved in that the aryl thiophenol is thiophenol, 4-methyl thiophenol, 4-chlorobenzenethiol, 4-fluorobenzenethiol, 2, 4-dimethyl thiophenol or 3-methyl thiophenol.
The invention further improves the technical scheme that after the 7-azaindole and the aryl thio reagent are added into the solvent, the molar concentration of the 7-azaindole in the solvent is 0.05-0.5 mol/L.
In a further development of the invention, the mass ratio of 7-azaindole to arylthiophenol is 1: (1.1-1.5).
In a further development of the invention, the mass ratio of 7-azaindole to base catalyst is 1: (0.1-0.5).
A further improvement of the invention is that the pressure of the reaction is 0.1 MPa.
Compared with the prior art, the invention has the following beneficial effects: the synthesis process is simple and efficient, no transition metal catalyst is required to be added in the reaction, no iodine simple substance is required to be used, and the smoothness of the reaction can be ensured only by adding alkali in a catalytic measurement manner; research on a reaction transition state shows that in the reaction process, alkali can catalyze aryl thiophenol to perform a coupling reaction to generate a diaryl thioether intermediate, and then the intermediate and a 7-azaindole derivative perform an electrophilic substitution reaction to obtain a corresponding target product; the synthetic route has strong selectivity, cleanness and greenness and high synthetic efficiency; the reaction raw materials are cheap and easy to obtain; has wide potential application prospect.
Detailed Description
In order to further understand the present invention, the following examples are further illustrated, which are only used for explaining the present invention and are not to be construed as limiting the scope of the present invention.
In the invention, 7-azaindole and derivatives thereof and an aryl thio reagent are used as raw materials, alkali is used as a catalyst, an alkaline environment is provided for the reaction, and a corresponding 3-aryl thio compound is prepared in a solvent at a certain temperature.
The reaction equation of a base-catalyzed green synthesis method of a 3-arylthio-7-azaindole compound is as follows:
adding 7-azaindole and an arylthio reagent into a solvent, then adding a catalyst, and reacting at 60-120 ℃ for 2-14 h to obtain a 3-arylthio-7-azaindole compound;
wherein the aryl thio reagent is aryl thiophenol; the method specifically comprises the following steps: thiophenol, 4-methylthiophenol, 4-chlorothiophenol, 4-fluorothiophenol, 2, 4-dimethylthiophenol or 3-methylthiophenol.
The catalyst is alkali, specifically one or more of potassium carbonate, cesium hydroxide, cesium acetate and sodium acetate;
the solvent is one of dichloroethane, N-dimethylformamide, dimethyl sulfoxide and acetonitrile.
The molar concentration of the 7-azaindole in the solvent is 0.05-0.5 mol/L.
The mass ratio of 7-azaindole to arylthioic reagent is 1: (1.1-1.5).
The mass ratio of 7-azaindole to catalyst base is 1: (0.1-0.5).
The pressure of the reaction was 0.1 MPa.
Example 1
Synthesis of 3- (Phenylthio) 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.165g (1.5mmol) of thiophenol and cesium acetate are weighed respectively; the mass ratio of the 7-azaindole to the cesium acetate is 1: 0.1; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 120 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 2h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. And washing the organic phase by using a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by using column chromatography, purifying the product by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 86%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,CDCl3)δ/ppm＝12.26(br s,1H),7.66(d,J＝7.6Hz,1H),7.50(d,J＝2.8Hz,1H),7.46(d,J＝8.4Hz,1H),7.33–7.28(m,1H),7.23–7.08(m,6H)；13CNMR(101MHz,CDCl3)δ/ppm＝139.9,137.0,131.4,129.4,126.5,125.2,123.8,121.6,120.3,118.2,103.5.
example 2
Synthesis of 3- [ (4-methylbenzene) thio ] 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.186g (1.5mmol) of 4-toluene thiophenol and cesium acetate are weighed respectively; the mass ratio of the 7-azaindole to the cesium acetate is 1: 0.1; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 120 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 3h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. And washing the organic phase by using a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by using column chromatography, purifying the product by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 82%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,DMSO-d6)δ/ppm＝12.23(s,1H),8.29(s,1H),7.90(d,J＝2.3Hz,1H),7.76(dd,J＝7.8Hz,J＝1.3Hz,1H),7.11(dd,J＝7.8Hz,J＝4.7Hz,1H),7.02(d,J＝8.2Hz,2H),6.96(d,J＝8.3Hz,2H),2.19(s,3H)；13C NMR(101MHz,DMSO)δ/ppm＝148.9,143.6,134.8,134.5,132.7,129.6,126.7,126.1,122.2,116.5,99.4,20.4。
example 3
Synthesis of 3- [ (4-fluorobenzene) thio ] 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.192g (1.5mmol) of 4-fluorobenzothiophenol and cesium acetate are weighed respectively; the mass ratio of the 7-azaindole to the cesium acetate is 1: 0.1; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 120 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 6h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. Washing the organic phase with a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by column chromatography, and purifying the product by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 79%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,CDCl3)δ/ppm＝12.30(s,1H),8.32(s,1H),7.94(s,1H),7.80(d,J＝7.7Hz,1H),7.16–7.03(m,5H)；13C NMR(101MHz,CDCl3)δ/ppm＝148.8,142.8,133.6,130.2(d,J＝248.2Hz),127.9,127.6(d,J＝7.8Hz),124.9,117.2,115.5(d,J＝22.0Hz),115.3,100.3。
example 4
Synthesis of 3- [ (4-chlorophenyl) thio ] 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.219g (1.5mmol) of 4-chlorothiophenol and cesium hydroxide are weighed respectively; the mass ratio of 7-azaindole to cesium hydroxide is 1: 0.2; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 100 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 6h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. Washing the organic phase with a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by column chromatography, and purifying the product by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 77%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,DMSO-d6)δ/ppm＝12.33(s,1H),8.32(dd,J＝4.7Hz,J＝1.5Hz,1H),7.96(d,J＝2.3Hz,1H),7.79(dd,J＝7.8Hz,J＝1.3Hz,1H),7.27(d,J＝8.6Hz,2H),7.14(dd,J＝7.9Hz,J＝4.7Hz,1H),7.04(d,J＝8.6Hz,2H)；13C NMR(101MHz,DMSO)δ/ppm＝148.9,143.8,137.8,133.5,129.6,128.9,127.1,126.7,120.8,116.8,98.0。
example 5
Synthesis of 3- [ (2, 4-dimethylbenzene) thio ] 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.207g (1.5mmol) of 2, 4-dimethylthiophenol and cesium acetate are weighed respectively; the mass ratio of the 7-azaindole to the cesium acetate is 1: 0.2; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 120 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 6h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. And washing the organic phase by using a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by using column chromatography, purifying the product by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 72%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,CDCl3)δ/ppm＝12.34(s,1H),8.44(d,J＝5.9Hz,1H),7.96(d,J＝9.2Hz,1H),7.71(s,1H),7.20–7.15(m,1H),7.01(s,1H),6.78(d,J＝8.8Hz,1H),6.70(d,J＝9.4Hz,1H),2.50(s,3H),2.26(s,3H)；13C NMR(101MHz,CDCl3)δ/ppm＝148.4,142.5,134.3,134.2,133.7,131.5,130.4,128.1,126.6,125.5,121.9,116.2,100.4,20.3,19.5。
example 6
Synthesis of 3- [ (3-methylbenzene) thio ] 1H-pyrrolo [2,3-b ] pyridine: 0.118g (1mmol) of 7-azaindole, 0.187g (1.5mmol) of 3-methylthiophenol and cesium acetate are weighed respectively, and the mass ratio of the 7-azaindole to the cesium acetate is 1: 0.2; weighing 5mL of dimethyl sulfoxide, sequentially adding weighed reactants into a 25mL reaction tube with magnetons, stirring on a magnetic stirrer at room temperature until the system is a homogeneous solution, slowly heating to 120 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 6h at 0.1MPa and cooled to room temperature. The mixture was diluted with 0.1mol/L hydrochloric acid (5mL) and extracted with ethyl acetate (3X 10mL), and the organic phases were combined. Washing the organic phase with a saturated saline solution (5mL), adding anhydrous sodium sulfate, drying, filtering, concentrating, separating by column chromatography, and purifying the product with silica gel of 300-400 meshes as a stationary phase and a mixed solvent of ethyl acetate and petroleum ether in different proportions as an eluent, wherein the yield is 65%.
The obtained compound is a known compound, and the physical properties and the characterization data thereof are as follows:
a yellow solid;1H NMR(400MHz,CDCl3)δ/ppm＝11.88(s,1H),8.41(d,J＝4.7Hz,1H),7.97(dd,J＝7.9Hz,J＝1.4Hz,1H),7.71(s,1H),7.16(dd,J＝7.9Hz,J＝4.8Hz,1H),7.05(d,J＝7.6Hz,1H),6.96(s,1H),6.89(d,J＝7.7Hz,2H),2.23(s,3H)；13C NMR(101MHz,CDCl3)δ/ppm＝149.4,143.5,138.8,138.7,132.0,128.8,128.7,126.7,126.2,123.3,122.4,116.9,101.8,21.5。
example 7
Adding 7-azaindole and an arylthio reagent into a solvent, wherein the molar concentration of the 7-azaindole is 0.05 mol/L; then adding a catalyst, and reacting for 14h at 0.1MPa and 60 ℃ to obtain a 3-arylthio-7-azaindole compound;
wherein the solvent is dichloroethane.
The catalyst is potassium carbonate.
The mass ratio of 7-azaindole to catalyst is 1: 0.5.
the arylthioic reagent is thiophenol.
The mass ratio of the 7-azaindole to the arylthiophenol is 1: 1.1.
example 8
Adding 7-azaindole and an arylthio reagent into a solvent, wherein the molar concentration of the 7-azaindole is 0.5 mol/L; then adding a catalyst, and reacting for 12h at the temperature of 120 ℃ under the pressure of 0.1MPa to obtain a 3-arylthio-7-azaindole compound;
wherein the solvent is N, N-dimethylformamide.
The catalyst is cesium carbonate.
The mass ratio of 7-azaindole to catalyst is 1: 0.2.
the arylthioic reagent is 4-methylthiophenol.
The mass ratio of the 7-azaindole to the arylthiophenol is 1: 1.3.
example 9
Adding 7-azaindole and an arylthio reagent into a solvent, wherein the molar concentration of the 7-azaindole is 0.3 mol/L; then adding a catalyst, and reacting for 10 hours at the temperature of 80 ℃ under the pressure of 0.1MPa to obtain a 3-arylthio-7-azaindole compound;
wherein the solvent is acetonitrile.
The catalyst is sodium acetate.
The mass ratio of 7-azaindole to catalyst is 1: 0.3.
the aryl thio reagent is 4-chlorobenzenethiol.
The mass ratio of the 7-azaindole to the arylthiophenol is 1: 1.5.
example 10
Adding 7-azaindole and an arylthio reagent into a solvent, wherein the molar concentration of the 7-azaindole is 0.1 mol/L; then adding a catalyst, and reacting for 10 hours at 100 ℃ under 0.1MPa to obtain a 3-arylthio-7-azaindole compound;
wherein the solvent is N, N-dimethylformamide.
The catalyst is potassium carbonate.
The mass ratio of 7-azaindole to catalyst is 1: 0.1.
the arylthioic reagent is 2, 4-dimethylthiophenol.
The mass ratio of the 7-azaindole to the arylthiophenol is 1: 1.2.
materials, reagents and experimental equipment related to the embodiment of the invention are all commercial products conforming to the field of organic compound synthesis unless otherwise specified.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, modifications and decorations can be made without departing from the core technology of the present invention, and the modifications and decorations shall also fall within the scope of the patent protection of the present invention. Any changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
Claims (3)
1. A green synthesis method of a base-catalyzed 3-arylthio-7-azaindole compound is characterized by comprising the steps of adding 7-azaindole and an arylthio reagent into a solvent, adding a base catalyst, and reacting at 60-120 ℃ for 2-14 h to obtain a 3-arylthio-7-azaindole compound; wherein the aryl thio reagent is aryl thiophenol; the alkali catalyst is one or more of potassium carbonate, cesium hydroxide, cesium acetate and sodium acetate; the mass ratio of the 7-azaindole to the base catalyst is 1: (0.1 to 0.5); the aryl thiophenol is thiophenol, 4-methyl thiophenol, 4-chlorothiophenol, 4-fluorobenzothiophenol, 2, 4-dimethyl thiophenol or 3-methyl thiophenol; the mass ratio of the 7-azaindole to the arylthiophenol is 1: (1.1-1.5) and the reaction pressure is 0.1 MPa.
2. The base-catalyzed green synthesis process of a 3-arylthio-7-azaindole compound of claim 1, wherein the solvent is one of dichloroethane, N-dimethylformamide, dimethylsulfoxide, and acetonitrile.
3. The base-catalyzed green synthesis method of the 3-arylthio-7-azaindole compound as claimed in claim 1, wherein the molar concentration of the 7-azaindole in the solvent is 0.05-0.5 mol/L after the 7-azaindole and the arylthio reagent are added into the solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811291079.2A CN109369645B (en) | 2018-10-31 | 2018-10-31 | Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811291079.2A CN109369645B (en) | 2018-10-31 | 2018-10-31 | Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109369645A CN109369645A (en) | 2019-02-22 |
| CN109369645B true CN109369645B (en) | 2021-08-24 |
Family
ID=65397190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811291079.2A Active CN109369645B (en) | 2018-10-31 | 2018-10-31 | Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109369645B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110759907A (en) * | 2019-10-29 | 2020-02-07 | 陕西科技大学 | Selective deoxythionation of 7-azaindole-nitrogen oxide region |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382819A (en) * | 2017-08-11 | 2017-11-24 | 赣南师范大学 | A kind of preparation method of 3 thioindole class compound |
| CN108530339A (en) * | 2018-05-07 | 2018-09-14 | 青岛农业大学 | A kind of synthetic method of the compound of class containing Benzenesulfonylindole |
-
2018
- 2018-10-31 CN CN201811291079.2A patent/CN109369645B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382819A (en) * | 2017-08-11 | 2017-11-24 | 赣南师范大学 | A kind of preparation method of 3 thioindole class compound |
| CN108530339A (en) * | 2018-05-07 | 2018-09-14 | 青岛农业大学 | A kind of synthetic method of the compound of class containing Benzenesulfonylindole |
Non-Patent Citations (4)
| Title |
|---|
| An efficient t-BuOK promoted C3-chalcogenylation of indoles with dichalcogenides;Yuanzu Yu 等;《Org. Biomol. Chem.》;20180626(第16期);第4958-4962页 * |
| Cs2CO3-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Coupling of Thiols with Phosphonates and Arenes;Song Song 等;《Angew. Chem. Int. Ed.》;20171230;第56卷;第1-6页，尤其是第4页流程6 * |
| K2CO3 promoted direct sulfenylation of indoles: a facile approach towards 3-sulfenylindoles;Peng Sang 等;《Green Chem.》;20130604;第15卷;第2096-2100页 * |
| Synthesis of 3-sulfenylated indoles by simple NaOH promoted sulfenylation reaction;Yunyun Liu 等;《RSC Advances》;20140806;第4卷(第67期);第35528-35530页，尤其是第35529页表2中化合物3k的制备过程 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109369645A (en) | 2019-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2013293200B2 (en) | Process for the preparation of 4-amino-5-fluoro-3-halo-6-(substituted)picolinates | |
| CN104876995A (en) | A preparing method of a chenodeoxycholic acid derivative | |
| CN109134326B (en) | Synthetic method of S-aryl thiosulfone compound | |
| CN110862354B (en) | Bifunctional 1,2, 3-triazole derivative intermediate, preparation method and application | |
| CN109369645B (en) | Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound | |
| CN107445795B (en) | Synthesis method of 2-bromo-1, 1, 2, 2-tetrafluoroethyl substituted aryl building block | |
| CN113717038B (en) | Method for synthesizing diaryl ether by nickel/ketone double-catalysis reaction of halogenated aromatic hydrocarbon and aryl phenol | |
| CN102884043A (en) | Method of synthesis | |
| CN112321553B (en) | Method for synthesizing 3-position difluoromethyl substituted coumarin derivative from aryl alkyne acid ester | |
| CN102775315A (en) | Preparation method of 3-aminophenylacetylene | |
| CN104447336B (en) | A kind of three dish ene derivatives and preparation method thereof | |
| JP5371993B2 (en) | Method for producing sulfide compound using sulfide compound and organic sulfur-indium complex | |
| CN111848464B (en) | Method for preparing 2- (methylsulfinyl) benzoic acid | |
| CN110590621B (en) | Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne | |
| CN112694427B (en) | Method for preparing 2, 3-dimethyl sulfide | |
| CN107501171B (en) | Synthetic method of 2-chloro-3-pyridylaldehyde | |
| CN109232564B (en) | Method for synthesizing 3-sulfenyl substituted imidazo [1,2-a ] pyridine compound by molecular iodine promoted one-pot method | |
| CN111574427A (en) | Synthesis method of 2-indole-3-oxoindoline compound | |
| CN112142656A (en) | Sulfonyl pyridine amide derivatives and preparation method thereof | |
| CN106117203B (en) | A kind of synthetic method of 3 arylthio Imidazoheterocyclic compounds | |
| EP3162795B1 (en) | Method for manufacturing 3-(alkyl sulfonyl)pyridine-2-carboxylic acid | |
| CN111320592A (en) | Preparation method of 1- [2- (2, 4-dimethylphenylsulfanyl) -phenyl ] piperazine | |
| CN111004176A (en) | Synthesis method of 2-aryloxy ethanol compound | |
| CN115109009B (en) | Synthesis method of 2-sulfonyl benzothiazole compound | |
| CN104418805B (en) | Dabigatran etexilate intermediate as well as preparation method and application 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |