CN115074760A - Electrochemical synthesis method of 5-aminopyrazole-4-thiocyanic acid ester compound - Google Patents
Electrochemical synthesis method of 5-aminopyrazole-4-thiocyanic acid ester compound Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- -1 5-aminopyrazole compound Chemical class 0.000 claims abstract description 25
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims abstract description 11
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000000746 purification Methods 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- 230000003197 catalytic effect Effects 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 10
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 8
- 229940116357 potassium thiocyanate Drugs 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 239000007772 electrode material Substances 0.000 claims description 2
- 238000004811 liquid chromatography Methods 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000012822 chemical development Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- 239000000047 product Substances 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 11
- 239000003480 eluent Substances 0.000 description 9
- 238000010586 diagram Methods 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- XKCAWOAQPYMJEN-UHFFFAOYSA-N (5-amino-1,3-diphenylpyrazol-4-yl) thiocyanate Chemical compound NC1=C(SC#N)C(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 XKCAWOAQPYMJEN-UHFFFAOYSA-N 0.000 description 3
- LRJWBZOWAHNTSL-UHFFFAOYSA-N (5-amino-3-methyl-1-phenylpyrazol-4-yl) thiocyanate Chemical compound NC1=C(SC#N)C(C)=NN1C1=CC=CC=C1 LRJWBZOWAHNTSL-UHFFFAOYSA-N 0.000 description 3
- XTZOZXRBDUYZEY-UHFFFAOYSA-N Nc1c(SC#N)cnn1-c1ccccc1 Chemical compound Nc1c(SC#N)cnn1-c1ccccc1 XTZOZXRBDUYZEY-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- SXOFMEWDEKEVJU-UHFFFAOYSA-N 2,5-diphenylpyrazol-3-amine Chemical compound NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 SXOFMEWDEKEVJU-UHFFFAOYSA-N 0.000 description 1
- ZVNYYNAAEVZNDW-UHFFFAOYSA-N 2-phenylpyrazol-3-amine Chemical compound NC1=CC=NN1C1=CC=CC=C1 ZVNYYNAAEVZNDW-UHFFFAOYSA-N 0.000 description 1
- FMKMKBLHMONXJM-UHFFFAOYSA-N 5-methyl-2-phenylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1=CC=CC=C1 FMKMKBLHMONXJM-UHFFFAOYSA-N 0.000 description 1
- GFWSTBBSSBVVQP-UHFFFAOYSA-N 5-tert-butyl-2-phenylpyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC=C1 GFWSTBBSSBVVQP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000662429 Fenerbahce Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- 241000223229 Trichophyton rubrum Species 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- XMDRIBPTIGVLOD-UHFFFAOYSA-N tert-butyl 5-amino-3-methylpyrazole-1-carboxylate Chemical compound CC=1C=C(N)N(C(=O)OC(C)(C)C)N=1 XMDRIBPTIGVLOD-UHFFFAOYSA-N 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
- C25B3/23—Oxidation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention discloses an electrochemical synthesis method of a 5-aminopyrazole-4-thiocyanate compound, which relates to the technical field of organic electrochemical synthesis and comprises the following steps: (1) electrocatalytic reaction: adding thiocyanate, a 5-aminopyrazole compound, acid and a solvent into a reaction tank respectively, installing a catalytic electrode, and electrifying, stirring and reacting; (2) separation and purification: and (3) separating and purifying the solution after the electrocatalysis reaction is finished to obtain the 5-aminopyrazole-4-thiocyanate compound. The method adopts thiocyanate and 5-aminopyrazole compounds as reaction raw materials, synthesizes the 5-aminopyrazole-4-thiocyanate compound by a one-pot method under electrochemical conditions, does not need the use of metal and chemical oxidant, has high reaction atom economy, and meets the requirement of green chemical development.
Description
The technical field is as follows:
the invention relates to the technical field of organic electrochemical synthesis, in particular to an electrochemical synthesis method of a 5-aminopyrazole-4-thiocyanate compound.
Background art:
pyrazole is a five-membered heterocyclic compound containing two linked nitrogen atoms, and its derivatives are widely found in synthetic chemicals. Because of its high-efficiency broad-spectrum biological activity and wide application in the fields of medicine and agricultural chemicals, it has been widely noticed by workers in the fields of organic chemistry, pharmaceutical chemistry and biology for many years, especially the N-aryl-5-aminopyrazole-4-thiocyanate compound with antifungal activity has the efficacy of resisting Trichophyton floccosum and Trichophyton rubrum. The research finds that the inhibitory effect of the molecule on the two types of fungi is not inferior to that of the clinical standard drug ketoconazole. Therefore, the research on the synthesis method thereof has been the focus of research of organic chemists. However, due to the existence of amino group in the reaction substrate, the compatibility in the oxidation system is difficult, and the synthesis research on the 5-aminopyrazole-4-thiocyanate compound is less.
In 2020, the Choudhury topic group reported a hydrogen peroxide promoted thiocyanization of the C (sp2) -H bond of N-aryl-5-aminopyrazole compounds, synthesizing a series of compounds of N-aryl-5-aminopyrazole-4-thiocyanate (D.Ali, A.K.Panday, L.H.Choudhury.J.Org.Chem.2020,85,13610). This method, although it achieves its synthesis well, requires a large amount of hydrogen peroxide (8 equivalents). The use of a large amount of chemical oxidant leads to a complex reaction system and low atom economy, and a large amount of waste liquid is discharged in the industrial production process.
The invention content is as follows:
the technical problem to be solved by the invention is to provide an electrochemical synthesis method of 5-aminopyrazole-4-thiocyanate compounds, which adopts a green organic electrochemical synthesis method to prepare the 5-aminopyrazole-4-thiocyanate compounds in a reaction environment without adding metals and chemical oxidants, so as to overcome the defects of the prior art.
The invention aims to provide an electrochemical synthesis method of a 5-aminopyrazole-4-thiocyanate compound, which comprises the following steps:
(1) electrocatalytic reaction: adding thiocyanate, a 5-aminopyrazole compound, acid and a solvent into a reaction tank respectively, installing a catalytic electrode, and electrifying, stirring and reacting;
(2) separation and purification: and (3) separating and purifying the solution after the electrocatalysis reaction is finished to obtain the 5-aminopyrazole-4-thiocyanate compound.
The 5-aminopyrazole-4-thiocyanate compound has the following structure:
wherein R is 1 Is hydrogen, C 1 ～C 5 Alkyl, aryl; r 2 Aryl and ester groups.
The invention has the beneficial effects that: the invention provides an electrochemical synthesis method of a 5-aminopyrazole-4-thiocyanate compound, which adopts thiocyanate and a 5-aminopyrazole compound as reaction raw materials to synthesize the 5-aminopyrazole-4-thiocyanate compound by a one-pot method under electrochemical conditions.
Description of the drawings:
FIG. 1 shows the product obtained in example 1 of the present invention 1 H NMR；
FIG. 2 shows the product obtained in example 1 of the present invention 13 C NMR；
FIG. 3 shows the product obtained in example 2 of the present invention 1 H NMR；
FIG. 4 shows the product obtained in example 2 of the present invention 13 C NMR；
FIG. 5 shows the product obtained in example 3 of the present invention 1 H NMR；
FIG. 6 shows the product obtained in example 3 of the present invention 13 C NMR；
FIG. 7 shows the product obtained in example 4 of the present invention 1 H NMR；
FIG. 8 shows the product obtained in example 4 of the present invention 13 C NMR；
FIG. 9 shows the results of example 5 of the present invention 1 H NMR；
FIG. 10 shows the results of example 5 of the present invention 13 C NMR；
FIG. 11 shows the results of example 6 of the present invention 1 H NMR；
FIG. 12 shows the results of example 6 of the present invention 13 C NMR。
The specific implementation mode is as follows:
in order to make the technical means, the original characteristics, the achieved purposes and the effects of the invention easy to understand, the invention is further explained by combining the specific embodiments and the drawings.
The invention provides an electrochemical synthesis method of a 5-aminopyrazole-4-thiocyanate compound, which comprises the following steps:
(1) electrocatalytic reaction: adding thiocyanate, a 5-aminopyrazole compound, acid and a solvent into a reaction tank respectively, installing a catalytic electrode, and electrifying, stirring and reacting;
(2) separation and purification: and (3) separating and purifying the solution after the electrocatalysis reaction is finished to obtain the 5-aminopyrazole-4-thiocyanate compound.
The 5-aminopyrazole-4-thiocyanate compound has the following structure:
wherein R is 1 Is hydrogen, C 1 ～C 5 Alkyl, aryl; r 2 Aryl and ester groups.
Preferably, the thiocyanate is one of potassium thiocyanate, ammonium thiocyanate and sodium thiocyanate.
Preferably, the 5-amino pyrazole compound has a structure shown as follows:
wherein R is 1 Is hydrogen, C 1 ～C 5 Alkyl, aryl; r 2 Aryl and ester groups.
Preferably, the mass ratio of the 5-amino pyrazole compound to the thiocyanate is 1: 1-1: 4.
Preferably, the initial concentration of the 5-amino pyrazole compound is 0.05-0.2 mol/L.
Preferably, the acid is one of acetic acid (acetic acid), benzoic acid, hydrochloric acid, sulfuric acid and diphenyl phosphoric acid, and the amount of the substance is 30-120% of that of the 5-aminopyrazole compound.
Preferably, the temperature of the stirring reaction is 0-80 ℃.
Preferably, the solvent is one or more of dimethyl sulfoxide, N-dimethylformamide, methanol, ethanol, N-methylpyrrolidone, N-dimethylacetamide, acetonitrile, water and 1, 2-dichloroethane.
Preferably, the electrode is a conventional commercially available electrode material, such as a platinum electrode, a carbon electrode, a nickel electrode, a copper electrode, and the like.
Preferably, the separation and purification method is one of column chromatography, liquid chromatography, distillation and recrystallization. Further preferably, the separation and purification method is column chromatography. The solution after completion of the reaction was spin-dried under reduced pressure, and the residue was separated by silica gel column chromatography.
The eluent for the column chromatography is petroleum ether/ethyl acetate, which is not to say that other eluent systems cannot be used, as long as the reagent for the purpose of elution is used.
The chemical reaction formula of the 5-aminopyrazole-4-thiocyanate compound is as follows:
the invention realizes the reaction of the 5-aminopyrazole compound and the thiocyanate for the first time under the electrochemical condition, and obtains the 5-aminopyrazole-4-thiocyanate compound with high selectivity. The method belongs to a method for synthesizing the 5-aminopyrazole-4-thiocyanate compound in a green and high-efficiency manner.
The 5-aminopyrazole compounds and thiocyanates used in the examples were all analytical reagents purchased directly from Annigi chemistry, Jiuding chemistry, Aladdin and Adamas, without further treatment before use, and the solvents or eluents used were purchased from Chinese medicine.
Example 1
In a 10mL undivided electrolytic cell, 3-methyl-1-phenyl-1H-pyrazol-5-amine (0.3mmoL,52.0mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL), and water (0.5mL) were placed, and the reaction was stirred with a platinum sheet electrode as both an anode and a cathode, and energized at room temperature (I ═ 5mA), followed by TLC. After the reaction was complete, the residue obtained was spin-dried over a chromatographic column using ethyl acetate/petroleum ether system as eluent to give the product 3-methyl-1-phenyl-4-thiocyano-1H-pyrazole-5-amine compound in 94% yield.
The structure of the obtained product 3-methyl-1-phenyl-4-thiocyano-1H-pyrazole-5-amine is analyzed by a nuclear magnetic resonance spectrometer, and the result is shown in the figure 1-2. FIG. 1 is a diagram of the 3-methyl-1-phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 1 of the invention 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 2 is a diagram of the 3-methyl-1-phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 1 of the invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrum. 1 H NMR(DMSO-d 6 ,400MHz,ppm):δ＝7.53-7.49(m,4H),7.41-7.36(m,1H),6.34(br,2H),2.19(s,3H)； 13 C NMR(DMSO-d 6 ,100MHz,ppm):δ＝150.6,150.3,138.3,129.4,127.2,123.4,112.4,75.1,12.0。
Example 2
In a 10mL undivided electrolytic cell, 3-tert-butyl-1-phenyl-1H-pyrazol-5-amine (0.3mmoL,64.6mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL), and water (0.5mL) were placed, and the reaction was stirred with a platinum sheet electrode as both an anode and a cathode, and energized at room temperature (I ═ 5mA), followed by TLC. After the reaction was complete, the residue obtained was spin-dried over a chromatographic column using ethyl acetate/petroleum ether system as eluent to give the product 3-tert-butyl-1-phenyl-4-thiocyano-1H-pyrazole-5-amine compound in 91% yield.
The structure of the obtained product 3-tert-butyl-1-phenyl-4-thiocyano-1H-pyrazole-5-amine is analyzed by a nuclear magnetic resonance spectrometer, and the result is shown in figures 3-4. FIG. 3 is a diagram of the 3-tert-butyl-1-phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 2 of the invention 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 4 is a diagram of the 3-tert-butyl-1-phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 2 of the invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrum. 1 H NMR(CDCl 3 ,400MHz,ppm):δ＝7.53-7.47(m,4H),7.40-7.36(m,1H),4.44(br,2H),1.48(s,9H)； 13 C NMR(CDCl 3 ,100MHz,ppm):δ＝161.0,149.5,137.9,129.7,128.0,123.8,111.5,74.8,33.4,29.2。
Example 3
In a 10mL undivided electrolytic cell, 1, 3-diphenyl-1H-pyrazol-5-amine (0.3mmoL,70.5mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL), and water (0.5mL) were placed, and a platinum sheet electrode was used as both an anode and a cathode, and the reaction was stirred at room temperature with energization (I ═ 5mA), followed by TLC. After the reaction was complete, the residue obtained was spin-dried and passed through a chromatographic column using ethyl acetate/petroleum ether system as eluent to give the product 1, 3-diphenyl-4-thiocyano-1H-pyrazole-5-amine compound in 80% yield.
The structure of the obtained 1, 3-diphenyl-4-thiocyano-1H-pyrazole-5-amine product was analyzed by NMR spectroscopy, and the results are shown in FIGS. 5 to 6, and FIG. 5 shows the structure of the 1, 3-diphenyl-4-thiocyano-1H-pyrazole-5-amine product prepared in example 3 of the present invention 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 6 is a diagram of the production of 1, 3-diphenyl-4-thiocyano-1H-pyrazol-5-amine prepared in example 3 of the invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrumFigure (a). 1 H NMR(CDCl 3 ,400MHz,ppm):δ＝7.92-7.89(m,2H),7.59-7.42(m,8H),4.58(br,2H)； 13 C NMR(CDCl 3 ,100MHz,ppm):δ＝152.7,149.4,137.6,131.3,129.8,128.9,128.5,128.5,127.9,124.0,111.2,76.0。
Example 4
In a 10mL undivided electrolytic cell, 1-phenyl-1H-pyrazol-5-amine (0.3mmoL,47.7mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL), and water (0.5mL) were placed, and the reaction was stirred with a platinum sheet electrode as both an anode and a cathode, and energized at room temperature (I ═ 5mA), followed by TLC. After the reaction was complete, the residue obtained was spin-dried and chromatographed using ethyl acetate/petroleum ether system as eluent to give the product 1-phenyl-4-thiocyano-1H-pyrazol-5-amine compound in 77% yield.
The structure of the obtained product 1-phenyl-4-thiocyano-1H-pyrazole-5-amine is analyzed by a nuclear magnetic resonance spectrometer, and the result is shown in figures 7-8. FIG. 7 is a diagram of the production of 1-phenyl-4-thiocyano-1H-pyrazol-5-amine prepared in example 4 of the present invention 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 8 is a diagram of the production of 1-phenyl-4-thiocyano-1H-pyrazol-5-amine prepared in example 4 of the invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrum. 1 HNMR(CDCl 3 ,400MHz,ppm):δ＝7.59(s,1H),7.55-7.50(m,4H),7.46-7.42(m,1H),4.50(br,2H)； 13 C NMR(CDCl 3 ,100MHz,ppm):δ＝148.1,143.5,137.7,129.8,128.6,123.9,111.0,77.7。
Example 5
In a 10mL undivided electrolytic cell, 3-methyl-1- (p-methyl) phenyl-1H-pyrazol-5-amine (0.3mmoL,56.1mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL), and water (0.5mL) were placed, and the reaction was stirred with energization (I ═ 5mA) at room temperature with a platinum sheet electrode serving as both an anode and a cathode, followed by TLC. After the reaction was completed, the residue obtained by spin-drying was passed through a column chromatography using ethyl acetate/petroleum ether system as an eluent to give the product 3-methyl-1- (p-methyl) phenyl-4-thiocyano-1H-pyrazol-5-amine compound in a yield of 85%.
The structure of the obtained product 3-methyl-1- (p-methyl) phenyl-4-thiocyano-1H-pyrazole-5-amine is analyzed by a nuclear magnetic resonance spectrometer, and the result is shown in figures 9-10. FIG. 9 is a 3-methyl-1- (p-methyl) phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 5 of the invention 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 10 is a drawing of the 3-methyl-1- (p-methyl) phenyl-4-thiocyano-1H-pyrazol-5-amine product prepared in example 5 of the invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrum. 1 H NMR(CDCl 3 ,400MHz,ppm):δ＝7.35-7.32(m,2H),7.28(d,J＝8.0Hz,2H),4.43(br,2H),2.40(s,3H),2.32(s,3H)； 13 C NMR(CDCl 3 ,100MHz,ppm):δ＝151.4,148.4,138.3,135.1,130.2,123.8,111.0,76.8,21.1,12.1。
Example 6
In a 10mL undivided electrolytic cell, tert-butyl-5-amino-3-methyl-1H-pyrazole-1-carboxylate (0.3mmoL,59.1mg), potassium thiocyanate (0.6mmoL,58.3mg), acetic acid (0.3mmoL,18.2mg), acetonitrile (2.5mL) and water (0.5mL) were placed, and the reaction was stirred with a platinum plate electrode as both anode and cathode and energized at room temperature (I ═ 5mA), followed by TLC. After the reaction is completed, the residue obtained by spin-drying is passed through a chromatographic column using an ethyl acetate/petroleum ether system as an eluent to obtain a product tert-butyl-5-amino-3-methyl-4-thiocyano-1H-pyrazole-1-formate compound with a yield of 54%.
The obtained product tert-butyl-5-amino-3-methyl-4-thiocyano-1H-pyrazole-1-formate is subjected to structural analysis by a nuclear magnetic resonance spectrometer, and the result is shown in FIGS. 9-10. FIG. 9 shows tert-butyl-5-amine prepared in example 5 of the present inventionProcess for preparing 3-methyl-4-thiocyano-1H-pyrazole-1-carboxylic acid ester products 1 H nuclear magnetic resonance ( 1 H-NMR) spectrum; FIG. 10 is a representation of the tert-butyl-5-amino-3-methyl-4-thiocyano-1H-pyrazole-1-carboxylate product prepared in example 5 of the present invention 13 C nuclear magnetic resonance ( 13 C-NMR) spectrum. 1 H NMR(CDCl 3 ,400MHz,ppm):δ＝6.05(br,2H),2.30(s,3H),1.65(s,9H)； 13 C NMR(CDCl 3 ,100MHz,ppm):δ＝154.0,153.3,149.8,110.1,86.6,76.5,27.9,12.5。
The reaction time of the electrification and stirring in the embodiment of the invention can be any, 5-aminopyrazole-4-thiocyanate compounds can be prepared as long as the electrification is carried out, the optimal electrification time is about 5 hours, and the yield of the obtained product is highest. 5-aminopyrazole-4-thiocyanic acid ester compounds can be prepared at any other time, except that the yield is changed, the yield is gradually increased from the start of electrification to 5 hours, and when the yield is reduced after 5 hours, the generated products are converted into other by-products possibly due to overlong electrification catalysis time.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1. An electrochemical synthesis method of 5-aminopyrazole-4-thiocyanate compounds is characterized by comprising the following steps:
(1) electrocatalytic reaction: adding thiocyanate, a 5-aminopyrazole compound, acid and a solvent into a reaction tank respectively, installing a catalytic electrode, and electrifying, stirring and reacting;
(2) separation and purification: separating and purifying the solution after the electrocatalysis reaction is finished to obtain a 5-aminopyrazole-4-thiocyanate compound;
the 5-aminopyrazole-4-thiocyanate compound has the following structure:
wherein R is 1 Is hydrogen, C 1 ～C 5 Alkyl, aryl; r 2 Aryl and ester groups.
2. The electrochemical synthesis method of claim 1, wherein: the thiocyanate is one of potassium thiocyanate, ammonium thiocyanate and sodium thiocyanate.
3. The electrochemical synthesis method of claim 1, wherein: the 5-amino pyrazole compound has the following structure:
wherein R is 1 Is hydrogen, C 1 ～C 5 Alkyl, aryl; r 2 Aryl and ester groups.
4. The electrochemical synthesis method according to claim 1, characterized in that: the mass ratio of the 5-amino pyrazole compound to the thiocyanate is 1: 1-1: 4.
5. The electrochemical synthesis method of claim 1, wherein: the initial concentration of the 5-aminopyrazole compound is 0.05-0.2 mol/L.
6. The electrochemical synthesis method of claim 1, wherein: the acid is one of acetic acid, benzoic acid, hydrochloric acid, sulfuric acid and diphenyl phosphoric acid, and the amount of the substance is 30-120% of that of the 5-aminopyrazole compound.
7. The electrochemical synthesis method of claim 1, wherein: the temperature of the stirring reaction is 0-80 ℃.
8. The electrochemical synthesis method of claim 1, wherein: the solvent is one or more of dimethyl sulfoxide, N-dimethylformamide, methanol, ethanol, N-methylpyrrolidone, N-dimethylacetamide, acetonitrile, water and 1, 2-dichloroethane.
9. The electrochemical synthesis method of claim 1, wherein: the electrodes are conventional commercially available electrode materials.
10. The electrochemical synthesis method of claim 1, wherein: the separation and purification method is one of column chromatography, liquid chromatography, distillation and recrystallization.
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| US20160217936A1 (en) * | 2012-12-14 | 2016-07-28 | Sharp Kabushiki Kaisha | Photoelectric conversion element |
| CN107382867A (en) * | 2017-07-03 | 2017-11-24 | 大连理工大学 | 4 isothiocyanate group pyrazoline ketone compounds |
| CN108002969A (en) * | 2017-12-01 | 2018-05-08 | 赣南师范大学 | A kind of preparation method of thiocyanate ester compound |
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| US20160217936A1 (en) * | 2012-12-14 | 2016-07-28 | Sharp Kabushiki Kaisha | Photoelectric conversion element |
| CN107382867A (en) * | 2017-07-03 | 2017-11-24 | 大连理工大学 | 4 isothiocyanate group pyrazoline ketone compounds |
| CN108002969A (en) * | 2017-12-01 | 2018-05-08 | 赣南师范大学 | A kind of preparation method of thiocyanate ester compound |
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| Title |
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| OLEG V. BITYUKOV ET AL.: "Electrochemical thiocyanation of barbituric acids", 《ORG. BIOMOL. CHEM.》, vol. 20, pages 3629 * |
| PENG QIAN ET AL.: "Electrosynthesis of Thiocyanated/Iodinated/Brominated Pyrazol- 5-amines and Thiocyanated Enamines via C(sp2)-H Functionalization", 《ADV. SYNTH. CATAL.》, vol. 365, pages 1782 * |
| VLADIMIR A. KOKOREKIN ET AL.: "New data on heteroarene thiocyanation by anodic oxidation of NH 4 SCN. The processes of electroinduced nucleophilic aromatic substitution of hydrogen", 《TETRAHEDRON LETTERS 》, vol. 55, pages 4306, XP028876452, DOI: 10.1016/j.tetlet.2014.06.028 * |
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