CN112501643B - Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound - Google Patents
Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound Download PDFInfo
- Publication number
- CN112501643B CN112501643B CN202011269357.1A CN202011269357A CN112501643B CN 112501643 B CN112501643 B CN 112501643B CN 202011269357 A CN202011269357 A CN 202011269357A CN 112501643 B CN112501643 B CN 112501643B
- Authority
- CN
- China
- Prior art keywords
- anilino
- alkylthio
- coumarin
- compound
- reaction
- 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
- 238000001308 synthesis method Methods 0.000 title claims abstract description 13
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 38
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 28
- BOHONKNXXMHSHO-UHFFFAOYSA-N 4-anilinochromen-2-one Chemical compound C12=CC=CC=C2OC(=O)C=C1NC1=CC=CC=C1 BOHONKNXXMHSHO-UHFFFAOYSA-N 0.000 claims abstract description 22
- -1 thiol compounds Chemical class 0.000 claims abstract description 20
- 229910052759 nickel Inorganic materials 0.000 claims abstract description 19
- 229910052742 iron Inorganic materials 0.000 claims abstract description 18
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 13
- 239000003792 electrolyte Substances 0.000 claims abstract description 11
- 238000003487 electrochemical reaction Methods 0.000 claims abstract description 9
- 239000006260 foam Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 41
- 238000000034 method Methods 0.000 abstract description 8
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 26
- 229940107816 ammonium iodide Drugs 0.000 description 18
- 125000001453 quaternary ammonium group Chemical group 0.000 description 16
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 12
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
- 229910052802 copper Inorganic materials 0.000 description 7
- 239000010949 copper Substances 0.000 description 7
- 229910002804 graphite Inorganic materials 0.000 description 7
- 239000010439 graphite Substances 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- JOZPPMPSGRVNEY-UHFFFAOYSA-N N(C1=CC=CC=C1)C1=C(C(OC2=CC=CC=C12)=S)C Chemical compound N(C1=CC=CC=C1)C1=C(C(OC2=CC=CC=C12)=S)C JOZPPMPSGRVNEY-UHFFFAOYSA-N 0.000 description 2
- UDUXBOIWNXOBPO-UHFFFAOYSA-N N(C1=CC=CC=C1)C1=C(C(OC2=CC=CC=C12)=S)CC1=CC=CC=C1 Chemical compound N(C1=CC=CC=C1)C1=C(C(OC2=CC=CC=C12)=S)CC1=CC=CC=C1 UDUXBOIWNXOBPO-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000007772 electrode material Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000005732 thioetherification reaction Methods 0.000 description 2
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000001356 alkyl thiols Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an electrochemical synthesis method of a 3-alkylthio-4-anilino coumarin compound. The method comprises the steps of taking an N, N-dimethylformamide solution containing 4-anilino coumarin, thiol compounds and iodinated organic quaternary ammonium salts as electrolyte, placing an iron anode and a nickel cathode in the electrolyte, and introducing direct current to carry out electrochemical reaction to obtain a 3-alkylthio-4-anilino coumarin compound; the method has the advantages of mild reaction conditions, simple and convenient operation, environmental protection, easily obtained raw materials, excellent substrate functional group compatibility, high reaction yield and the like.
Description
Technical Field
The invention relates to an electrochemical synthesis method of a 3-alkylthio-4-anilino coumarin compound. In particular to a method for synthesizing a 3-alkylthio-4-anilino coumarin compound by catalyzing an electrochemical reaction between a 4-anilino coumarin compound and a thiol compound by an iodinated organic quaternary ammonium salt under the action of direct current without an external oxidant and an electrolyte, belonging to the technical field of organic intermediate synthesis.
Background
The 3-alkylthio-4-anilino coumarin compound has wide biological activity and plays an important role in the field of drug research and development. The alkyl mercaptan is a very easily obtained raw material, and the C-H bond thioetherification reaction of the 4-anilino coumarin by using the alkyl mercaptan as a thioetherification reagent is one of ideal methods for preparing the 3-alkylthio-4-anilino coumarin derivative.
In 2018, Yangtze mountain et al, Qingdao science and technology university, reported a method for preparing a 3-alkylthio-4-anilino coumarin compound by using an iodonium salt to catalyze the reaction of 4-anilino coumarin and Bunte salt, Org.Biomol.chem.,2018,16, 8015-one 8019. However, the method needs 1.5 times of chemical equivalent of expensive Bunte salt with limited source as a sulfur source, has low atomic efficiency and long reaction time, increases the reaction cost and increases the difficulty of separation and purification of the product.
Disclosure of Invention
Aiming at the defects of the synthesis method of the 3-alkylthio-4-anilino coumarin compound in the prior art, the invention aims to provide the electrochemical synthesis method of the 3-alkylthio-4-anilino coumarin compound, the 3-alkylthio-4-anilino coumarin compound is obtained under mild conditions with high selectivity and high yield without adding an oxidant and electrolyte, the reaction atom efficiency is high, the cost is low, the environment is friendly, the separation is simple, the chromatographic purification is not needed, and the industrial production and application are facilitated.
In order to realize the technical purpose, the invention provides an electrochemical synthesis method of a 3-alkylthio-4-anilino coumarin compound, which takes N, N-dimethylformamide solution containing 4-anilino coumarin, thiol compounds and iodinated organic quaternary ammonium salt as electrolyte, an iron anode and a nickel cathode are placed in the electrolyte, direct current is introduced, and electrochemical reaction is carried out, thus obtaining the compound;
the 4-anilino coumarin has a structure shown in a formula 1:
the thiol compound has a structure of formula 2:
R-SH
The 3-alkylthio-4-anilino coumarin compound has a structure shown in a formula 3:
wherein,
r is C1~C5Or containing phenyl substituents C1~C5Alkyl group of (1).
R in the 3-alkylthio-4-anilino coumarin compound is introduced by thiol compounds, and the common thiol compounds in the prior art are all suitable for synthesis of the 3-alkylthio-4-anilino coumarin compound. R may be C1~C5The alkyl group (C) is specifically methyl, ethyl, propyl, etc., and the alkyl group having 3 or more carbon atoms includes isomers such as branched alkylExamples of the group include isopropyl group and the like. R may be C containing a phenyl substituent1~C5Such as benzyl, phenethyl, 3-phenylpropyl, and the like, are common.
As a preferred embodiment, the iodinated organic quaternary ammonium salt has a general structural formula: NR (nitrogen to noise ratio)1 4I, wherein R1Is C1~C4Is preferably C1~C4Linear alkyl group of (1). The organic quaternary ammonium iodide salt is usually tetramethyl quaternary ammonium iodide salt, tetraethyl quaternary ammonium iodide salt, tetrabutyl quaternary ammonium iodide salt and the like, and the most preferable quaternary ammonium iodide salt can improve the yield of the target product to over 95 percent, while other organic quaternary ammonium iodide salts such as tetrabutyl quaternary ammonium iodide salt can ensure that the yield of the target product is over 85 percent, if the quaternary ammonium iodide is replaced by inorganic ammonium iodide, the yield of the target product is under 70 percent, and if the quaternary ammonium iodide is replaced by potassium iodide, the yield of the target product is under 60 percent.
Preferably, the dosage of the iodinated organic quaternary ammonium salt is 8-15% of the molar weight of the 4-anilino coumarin. When the using amount of the organic quaternary ammonium iodide salt is 10% of the molar amount of the 4-anilinocoumarol, the optimal reaction effect is achieved, the yield of the target product is highest, the relative using amount of the organic quaternary ammonium iodide salt exceeds 10%, the reaction effect is not obviously increased, and when the relative using amount of the organic quaternary ammonium iodide salt is less than 10%, the yield of the target product is obviously reduced, particularly when the relative using amount of the organic quaternary ammonium iodide salt is less than 5%, the yield of the target product is reduced to be less than 60%.
As a preferred scheme, the iron anode is a foam iron electrode; the nickel cathode is a foam nickel electrode. A large number of experiments show that the reaction can be carried out when materials such as iron, nickel, copper, graphite, platinum and the like are adopted as electrodes, but the selection of electrode materials and the selection of electrode pairs have great influence on the yield of target products, for example, when the nickel electrode is adopted as a cathode, the effect of adopting the iron electrode as the anode is better than that of adopting the nickel electrode, the copper electrode, the platinum electrode and the graphite electrode in sequence, and for example, when the iron electrode is adopted as the anode, the effect of adopting the nickel electrode as the cathode is better than that of adopting the iron electrode, the copper electrode, the platinum electrode and the graphite electrode in sequence, so that the electrode pair with the iron anode and the nickel cathode as the best electrodes is preferred. Further preferably, the foam electrode has higher current efficiency and catalytic effect than a general metal sheet or rod electrode.
In a preferable embodiment, the molar ratio of the 4-anilino coumarin to the thiol compound is 1: 0.8-1.2. In the technical scheme of the invention, the dosage ratio of the alkyl mercaptan to the 4-anilino coumarin is low, high yield can still be obtained, and the utilization rate of the mercaptan compound is greatly improved.
As a preferred scheme, the conditions of the electrochemical reaction are as follows: under the condition of room temperature, the direct current is introduced to 12-20 mA for 3-5 hours. The yield of the 3-alkylthio-4-anilino coumarin compound can be ensured to reach over 74 percent under the optimized reaction conditions. Further preferably, the direct current is 14-16 mA, and the yield of the 3-alkylthio-4-anilino coumarin compound can be ensured to be more than 95%.
As a preferable scheme, after the electrochemical reaction is finished, adding excessive water into electrolyte to precipitate a 3-alkylthio-4-anilino coumarin compound, filtering and separating to obtain a 3-alkylthio-4-anilino coumarin compound crystal, and performing reduced pressure distillation on the filtrate to remove water to obtain a DMF solution containing the iodinated organic quaternary ammonium salt for direct recycling. The method has the characteristic of easy separation of target products. The excessive water means that the volume of the added water is larger than that of the electrolyte.
As a preferable scheme, the electrochemical reaction is carried out in an air atmosphere, and the reaction is carried out without the protection of nitrogen.
The route of the coupling reaction between the 4-anilino coumarin compound and the thiol compound is as follows:
the invention also provides a reaction mechanism for synthesizing the 3-alkylthio-4-anilino coumarin compound, and the reaction between the 4-anilino coumarin and benzyl mercaptan is taken as an example for specific explanation. The iodine negative ions lose 2 electrons on the surface of the foam iron anode and are oxidized to generate iodine positive ions, and the iodine positive ions react with the 4-anilino coumarin (1) to generate an active 3-iodine-4-anilino coumarin intermediate (2). And (3) reacting the intermediate 2 with benzylmercaptan (3) to generate 3-benzylthio-4-anilinocoumarol (4) and release molecular iodine. Molecular iodine obtains 1 electron on the surface of the foamed nickel cathode to generate iodine negative ions to complete catalytic circulation, and hydrogen ions obtain electrons on the surface of the foamed nickel cathode to be reduced to generate hydrogen.
Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:
1) the invention adopts electrons as traceless oxidant, is safe, cheap and easy to obtain;
2) the invention has wide selectivity to thiol compounds and good functional group compatibility;
3) the invention does not use transition metal catalyst and oxidant, has high reaction selectivity, easy separation and purification of the product and high yield.
4) The method has mild reaction conditions, can be carried out at room temperature, is easy to separate and purify the product, is simple to operate, and is beneficial to large-scale production.
5) The catalyst and the solvent can be recycled, so that the recovery steps of the catalyst and the solvent are reduced, and the cost is reduced.
Drawings
FIG. 1 shows 4-anilino-3-benzylthiocoumarin1H NMR;
FIG. 2 shows 4-anilino-3-benzylthiocoumarin13C NMR;
FIG. 3 shows 4-anilino-3-methylthiocoumarin1H NMR;
FIG. 4 shows 4-anilino-3-methylthiocoumarin13C NMR。
Detailed Description
The following specific examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.
The invention takes the reaction of 4-anilino coumarin and benzyl mercaptan as an example for specific explanation, takes the screened optimal reaction condition as the standard reaction condition, and has the following specific reaction formula:
the specific operation steps are as follows: 4-anilino coumarin (0.6mmol), benzyl mercaptan (0.6mmol), an iodine reagent (0.06mmol), N, N-dimethylformamide (8mL), an anode and a cathode are sequentially added into a 25mL three-neck round-bottom flask, the obtained mixed solution is stirred and reacted for 4 hours at room temperature in 15mA direct current, a thin layer chromatography plate tracks the reaction progress, after the reaction is finished, the solvent is removed under reduced pressure, and the yield is analyzed by nuclear magnetic crude spectroscopy.
The following control experiment groups 1 to 22 are described by comparison with reference to standard reaction conditions:
foam iron, foam nickel, foam copper, graphite sheet electrode: 10mm × 10mm × 3 mm; metal platinum sheet electrode: 10mm × 10mm × 0.3 mm;
in the table, experiment groups 1-9 investigate the influence of electrode pairs made of different materials on the coupling reaction of 4-anilino coumarin and benzyl mercaptan, experiments show that the electrodes made of foamed iron, foamed nickel, foamed copper, graphite flakes and platinum flakes can be used as anodes or cathodes for reaction, but the selection of electrode materials and electrode pairs has a large influence on the yield of target products, the selection of the anodes is better than that of nickel electrodes, copper electrodes, platinum electrodes and graphite electrodes in sequence, and the selection of the cathodes is better than that of the iron electrodes, copper electrodes, platinum electrodes and graphite electrodes in sequence. Thus, it can be seen that the use of both a foamed iron electrode as the anode and a foamed nickel electrode as the cathode is the best electrode pair for this reaction.
In the table, experiment groups 1 and 10-12 investigate the influence of an iodide salt catalyst on the coupling reaction of 4-anilino coumarin and benzyl mercaptan, and experiments show that the yield of a target product can be obviously improved by adopting an organic quaternary ammonium iodide compared with an inorganic quaternary ammonium salt, if the organic quaternary ammonium iodide is used for ensuring that the yield of the target product is over 85 percent, if the inorganic quaternary ammonium iodide is replaced, the yield of the target product is below 70 percent, and if the inorganic quaternary ammonium iodide is used for replacing the potassium iodide, the yield of the target product is below 60 percent. Most preferably tetramethyl ammonium iodide, and can improve the yield of the target product to more than 95%.
In the table, experimental groups 1 and 13-14 investigate the influence of the usage amount of tetramethylammonium iodide on the coupling reaction of 4-anilinocoumarol and benzyl mercaptan, and experiments show that 0.1 equivalent of tetramethylammonium iodide is used as the catalyst usage amount of the reaction. When the relative amount of tetramethylammonium iodide is less than 0.1 equivalent, the yield of the target product is remarkably reduced, and particularly, when the relative amount of tetramethylammonium iodide is less than 0.05 equivalent, the yield of the target product is reduced to less than 60%.
In the table, experiment groups 1 and 15-17 investigate the influence of a reaction medium on the coupling reaction of the 4-anilino coumarin and the benzyl mercaptan, and experiments show that the reaction can be carried out by adopting dimethyl sulfoxide, ethanol, acetonitrile and N, N-dimethylformamide as reaction solvents. Wherein acetonitrile and ethanol are used as reaction media, the yield of the target product is lower than 30 percent, and N, N-dimethylformamide is the optimal reaction solvent for the reaction.
In the table, experimental groups 1 and 18-20 investigate the influence of direct current intensity on the coupling reaction of 4-anilino coumarin and benzyl mercaptan, and when the current is lower than 12mA, the yield of the product is obviously and greatly reduced; when the current is lower than 8mA, the reaction can not be carried out; the current is higher than 20mA, side reactions are increased, and the yield is reduced; experiments have shown that a direct current of 15mA is the optimum current intensity for the reaction.
The experimental group 21 in the table above investigates the influence of iodide on the coupling reaction of 4-anilinocoumarin and benzyl mercaptan, and experiments show that the reaction cannot occur under the condition without iodide, which indicates that an iodonium salt catalyst is a necessary condition for the reaction.
The effect of current on the coupling reaction of 4-anilinocoumarol and benzylthiol was examined by experimental group 22 in the above table, which showed that the reaction did not occur in the absence of current.
Examples 1 to 3
The following examples 1-2 all react according to the following reaction equation, mainly examining the yield conditions of different substrates reacting under the optimal conditions:
the specific operation steps are as follows: in a 25mL three-necked round-bottomed flask, 4-anilinocoumarin (0.6mmol), an alkylthiol (0.6mmol), tetramethylammonium iodide (0.06mmol), DMF (8mL), a 10 mm. times.10 mm. times.3 mm foamed iron electrode as an anode, and a 10 mm. times.10 mm. times.3 mm foamed nickel electrode as a cathode were added in this order. The resulting mixture was reacted at room temperature with 15mA of direct current under stirring. The reaction progress was followed by a thin layer chromatography plate for 4 hours. After the reaction is finished, 8mL of water product is added for precipitation, and a pure product can be obtained after filtration and drying.
Example 1
Yield 97% 3- (benzylthio) -4- (phenylaminono) -2H-chromen-2-one
1H NMR(CDCl3,500MHz)δ7.74(s,1H),7.42-7.38(m,1H),7.32-7.29(m,1H),7.25-7.10(m,8H),6.99(d,1H,J=5.0Hz),6.85(t,1H,J=15.0Hz),6.632(d,2H,J=10.0Hz),4.05(s,2H).
13C NMR(CDCl3,125MHz)δ161.03,156.30,153.75,140.73,138.24,132.10,129.50,129.29,128.85,128.56,127.17,126.65,125.81,124.02,122.79,113.66,97.58,37.76。
Example 2
Yield 95%, 3- (Methylthioo) -4- (phenylaminono) -2H-chromen-2-one
1H NMR(CDCl3,500MHz)δ8.00(s,1H),7.45-7.42(m,1H),7.37-7.32(m,3H),7.25-7.19(m,2H),7.09(d,2H,J=5.0Hz),6.96-6.93(m,1H),2.40(s,3H).
13C NMR(CDCl3,125MHz)δ160.69,154.92,153.66,141.36,132.07,129.65,126.61,125.72,123.59,122.92,117.64,113.89,101.83,17.37。
Example 3
Experimental procedure according to example 1, after removing water from the filtrate of the final separation product in the example by simple vacuum distillation, the dimethyl sulfoxide solution containing the iodinated organic quaternary ammonium salt is directly circulated to a new reaction, and the number of the circulating reactions and the nuclear magnetic yield of the target product are shown in the following table, which shows that the iodinated organic quaternary ammonium salt and the DMF solvent can be recycled.
|
|
|
|
|
98% | 96% | 95% | 93% | 90% |
Claims (6)
1. An electrochemical synthesis method of a 3-alkylthio-4-anilino coumarin compound is characterized in that: taking N, N-dimethylformamide solution containing 4-anilino coumarin, thiol compounds and iodinated organic quaternary ammonium salt as electrolyte, placing an iron anode and a nickel cathode in the electrolyte, and introducing direct current to carry out electrochemical reaction to obtain the catalyst; the conditions of the electrochemical reaction are as follows: under the condition of room temperature, introducing a direct current of 12-20 mA for 3-5 hours;
the 4-anilino coumarin has a structure shown in a formula 1:
the thiol compound has a structure of formula 2:
R-SH
formula 2
The 3-alkylthio-4-anilino coumarin compound has a structure shown in a formula 3:
wherein,
r is C1~C5Or containing phenyl substituents C1~C5Alkyl group of (1).
2. The electrochemical synthesis method of 3-alkylthio-4-anilinocoumarin compound according to claim 1, characterized in that: the structural general formula of the iodinated organic quaternary ammonium salt is as follows: NR (nitrogen to noise ratio)1 4I, wherein R1Is C1~C4Alkyl group of (1).
3. The electrochemical synthesis method of 3-alkylthio-4-anilinocoumarin compound according to claim 1 or 2, characterized in that: the dosage of the iodinated organic quaternary ammonium salt is 8-15% of the molar weight of the 4-anilino coumarin.
4. The electrochemical synthesis method of 3-alkylthio-4-anilinocoumarin compound according to claim 1, characterized in that: the iron anode is a foam iron electrode; the nickel cathode is a foam nickel electrode.
5. The electrochemical synthesis method of 3-alkylthio-4-anilinocoumarin compound according to claim 1, characterized in that: the molar ratio of the 4-anilino coumarin to the thiol compound is 1: 0.8-1.2.
6. The electrochemical synthesis method of 3-alkylthio-4-anilinocoumarin compound according to claim 1, characterized in that: after the electrochemical reaction is finished, adding excessive water into electrolyte to precipitate a 3-alkylthio-4-anilino coumarin compound, filtering and separating to obtain a 3-alkylthio-4-anilino coumarin compound crystal, and removing water from the filtrate through reduced pressure distillation to obtain a DMF solution containing the iodinated organic quaternary ammonium salt, wherein the DMF solution is directly recycled.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011269357.1A CN112501643B (en) | 2020-11-13 | 2020-11-13 | Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011269357.1A CN112501643B (en) | 2020-11-13 | 2020-11-13 | Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112501643A CN112501643A (en) | 2021-03-16 |
CN112501643B true CN112501643B (en) | 2021-12-10 |
Family
ID=74957533
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011269357.1A Active CN112501643B (en) | 2020-11-13 | 2020-11-13 | Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112501643B (en) |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999064379A2 (en) * | 1998-06-11 | 1999-12-16 | President And Fellows Of Harvard College | Biomimetic combinatorial synthesis |
WO2010052734A1 (en) * | 2008-11-06 | 2010-05-14 | Council Of Scientific & Industrial Research | Substituted benzfurochromenes and related compounds for the prevention and treatment of bone related disorders |
CN111705329B (en) * | 2020-07-31 | 2021-07-02 | 湖南科技学院 | Electrochemical synthesis method of 5-arylthio uracil compound |
CN111910208B (en) * | 2020-08-14 | 2021-07-20 | 怀化学院 | Electrochemical synthesis method of 3-thiophenyl quinolinone |
-
2020
- 2020-11-13 CN CN202011269357.1A patent/CN112501643B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN112501643A (en) | 2021-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111910209B (en) | Electrochemical synthesis method of 3-arylseleno quinolinone compound | |
JP6523335B2 (en) | Porphyrin molecular catalysts for selective electrochemical reduction of CO2 to CO | |
CN111705329B (en) | Electrochemical synthesis method of 5-arylthio uracil compound | |
CN112126942B (en) | Method for realizing secondary arylamine N-N coupling by using electrochemical reaction | |
CN111534832A (en) | Preparation method of sulfoxide compound under electrocatalysis | |
CN111910208B (en) | Electrochemical synthesis method of 3-thiophenyl quinolinone | |
CN112501642B (en) | Electrochemical synthesis method of 3-arylseleno-4-aminocoumarin compound | |
CN112301370B (en) | Electrochemical synthesis method of 1, 3-dimethyl-3-difluoroethyl-2-oxindole compound | |
CN112501643B (en) | Electrochemical synthesis method of 3-alkylthio-4-anilino coumarin compound | |
CN110724107B (en) | Preparation method and application of diallyl ionic liquid | |
CN108276356B (en) | Preparation method of 3, 5-disubstituted thiazolidine-2-thioketone compound | |
CN111362952A (en) | Preparation and application of mono-substituted metal phthalocyanine derivative | |
CN112359375B (en) | Method for electrochemically synthesizing 3-alkylseleno-4-aminocoumarin compound | |
CN111945181B (en) | Electrochemical synthesis method of 3-alkylselenoquinolinone compound | |
CN112195480B (en) | Method for synthesizing aromatic nitrile by electrocatalysis with aromatic methyl compound as raw material | |
Khrizanforov et al. | Fe and Ni-catalyzed electrochemical perfluoroalkylation of C—H bonds of coumarins | |
CN114409609B (en) | Preparation method of sulfonyl substituted 4,5,6, 7-tetrahydro-1, 3-oxazepan | |
CN114395770B (en) | Method for electrochemically synthesizing 5-trifluoromethyl uracil compound | |
US6419814B1 (en) | Methods for electrochemical synthesis of organoiodonium salts and derivatives | |
CN114381748B (en) | Hydroboration reaction method for electrochemically catalyzing aldehyde ketone | |
CN116284154B (en) | Monophosphine ligand-containing [ iron-iron ] hydrogenase mimic, and synthetic method and application thereof | |
CN115896823B (en) | D2Method for preparing alpha, beta-deuterated amine medicaments and prodrugs by using O as deuterium source to electrically catalyze nitrile | |
CN114892191A (en) | Electrochemical preparation method and application of 4,4' -dibromodiphenyl ether | |
CN118547299A (en) | Method for electrochemical reduction of diaryl ketone | |
CN115786942A (en) | Electrochemical method for preparing N-aryl sulfimide 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 | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240428 Address after: 214142 Tian'an Smart City 3-505, No. 228 Linghu Avenue, Xinwu District, Wuxi City, Jiangsu Province Patentee after: Wuxi all things Ecological Technology Co.,Ltd. Country or region after: China Address before: No. 130, yangzitang Road, Lingling District, Yongzhou City, Hunan Province Patentee before: HUNAN University OF SCIENCE AND ENGINEERING Country or region before: China |
|
TR01 | Transfer of patent right |