CN110105285A - Three substituted pyrazole derivatives and preparation method thereof - Google Patents
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- CN110105285A CN110105285A CN201910258110.0A CN201910258110A CN110105285A CN 110105285 A CN110105285 A CN 110105285A CN 201910258110 A CN201910258110 A CN 201910258110A CN 110105285 A CN110105285 A CN 110105285A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical class C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 title claims abstract description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 30
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 229940102001 zinc bromide Drugs 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- -1 substituted-phenyl Chemical group 0.000 claims description 5
- 239000002841 Lewis acid Substances 0.000 claims description 4
- 230000031709 bromination Effects 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 239000000376 reactant Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000005864 Sulphur Substances 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- 239000011968 lewis acid catalyst Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 6
- 150000003217 pyrazoles Chemical class 0.000 description 5
- OWQUYBAASOSGNO-CDNKMLFNSA-N 2-[[(Z)-N-(2-hydroxy-5-sulfoanilino)-C-phenylcarbonimidoyl]diazenyl]benzoic acid Chemical compound C1=CC=C(C=C1)/C(=N/NC2=C(C=CC(=C2)S(=O)(=O)O)O)/N=NC3=CC=CC=C3C(=O)O OWQUYBAASOSGNO-CDNKMLFNSA-N 0.000 description 3
- 230000005311 nuclear magnetism Effects 0.000 description 3
- 229940043798 zincon Drugs 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- MILPTZJEXYXOLP-UHFFFAOYSA-N (4-aminobenzoyl)oxymethyl 4-aminobenzoate Chemical compound C1=CC(N)=CC=C1C(=O)OCOC(=O)C1=CC=C(N)C=C1 MILPTZJEXYXOLP-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- YYPKLNBXHOZIGN-UHFFFAOYSA-N 4,7-dimethoxy-5-[5-(trifluoromethyl)-1H-pyrazol-3-yl]-1-benzofuran-6-ol Chemical compound COc1c(O)c(-c2cc(n[nH]2)C(F)(F)F)c(OC)c2ccoc12 YYPKLNBXHOZIGN-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The main purpose of the present invention is to provide a kind of completely new three substituted pyrazole derivatives and preparation method thereof.The method achieve by 2,5- dihydro-Isosorbide-5-Nitrae, 5- sulphur phenodiazine Zhuo oxide makees lewis acid catalyst as starting material, with zinc bromide, and methylene chloride does reaction dissolvent, under room temperature, can three substituted pyrazole derivatives of synthesis that are simple and efficient of a step.
Description
Technical field
The present invention relates to synthetic organic chemical arts, are specifically related to a kind of three substituted pyrazole derivatives and its preparation side
Method.
Background technique
Pyrazoles is a kind of containing there are two the five-ring heterocycles skeleton of continuous nitrogen-atoms, and pyrazole derivatives are because of its special activity
Fabulous application value is had been demonstrated in agriculture field and drug field.In addition to this, pyrazole derivatives are also applied to
Supramolecular chemistry, polymer chemistry field, even foods and cosmetics field.Currently, the synthesis of pyrazole derivatives also has
It is reported, though synthetic method is each advantageous, all in all, still remains and need using metallic catalyst, synthesis step is numerous
It is trivial, the disadvantages of substrate applicability is low, and the reaction time is long.Therefore, how succinct, efficient synthesizing pyrazole analog derivative is studied still
It has a very important significance.
Summary of the invention
The main purpose of the present invention is to provide a kind of completely new three substituted pyrazole derivatives and preparation method thereof.It should
Method is realized by 2,5- dihydro-Isosorbide-5-Nitrae, and 5- sulphur phenodiazine Zhuo oxide makees lewis acid, dichloro as starting material, with zinc bromide
Methane does reaction dissolvent, reacts 8 hours under room temperature, can three substituted pyrazole derivatives of synthesis that are simple and efficient of a step,
The preparation method of this kind of compound is provided simultaneously.
Compound of the present invention is such as the substituted pyrazole derivatives of I compound represented-tri-.
Wherein: R1It is miscellaneous for phenyl or substituted-phenyl (substituent group includes 4- methoxyl group, 4- methyl, 4- trifluoromethyl, 4- fluorine)
Ring substituents, alkyl substituent, alkenyl group；R2For methyl substituents or ethyl substituent.
The preparation method of three substituted pyrazole derivatives of the invention is as follows:
The preparation method of target compound I: i.e. at room temperature by compound shown in general formula II, Zinc Bromide Anhydrous powder
It is dissolved in dichloromethane solvent, reactant II disappears completely, and organic solvent, column layer will be removed under reaction mixture reduced pressure
It analyses and affords target compound I, in reactant II: R1It (include 4- methoxyl group, 4- first for phenyl or substituted-phenyl substituent group
Base, 4- trifluoromethyl, 4- fluorine), heterocyclic substituent, alkyl substituent, alkenyl group；R2Replace for methyl substituents or ethyl
Base.
The preparation method of currently preferred three substituted pyrazole derivatives is to make lewis acid, dichloro using zinc bromide
Methane is as solvent.
Further, currently preferred preparation method is: compound ii when reaction, bromination zincon molar ratio (work as
Measure ratio) be II: zinc bromide=1.0:1.0, dichloromethane solution concentration be 0.1M, i.e., 0.1 mole every liter.
Further, for currently preferred preparation method in silica gel column chromatography, eluent used is petroleum ether and second
The mixed solvent of acetoacetic ester, and volume ratio VPetroleum ether:VEthyl acetate=6:1~3:1.
Method of the present invention is very novel, is by Louis acid catalysis contracting ring construction of strategy pyrazole ring, this is in text
It is rarely found in offering.Obtained pyrazole ring is three substituted pyrazole derivatives of highly functionalized, and does not use in reaction
Precious metal catalyst, operation is simple, convenient post-treatment, and yield is generally very high, and is not necessarily to indifferent gas during the preparation process
Body protection.
Detailed description of the invention
Fig. 1-2 is the nuclear-magnetism spectrum (hydrogen spectrum and carbon spectrum) of products therefrom I -1:
Specific embodiment
The present invention is explained below in conjunction with specific embodiment.
The preparation method is that compound ii and bromination zincon to be dissolved in organic solvent and react, react
At rear removing solvent, target compound then is obtained with column chromatography method.Experiment shows that currently preferred lewis acid is bromine
Change zinc, preferred organic solvent is methylene chloride, and reaction product yield is generally higher, and best material molar ratio is compound
II: bromination zincon=1.0:1.0, the optimal concentration of solution are 0.1M.It is that a prepare compound of the invention is best below
Embodiment.In following all examples, nuclear-magnetism spectrum detection passes through Varian 300, Bruker 400, JEOL 400and
Varian 600MHz instrument is in CDCl3、(CD3)2It is obtained in CO.δ value is internal standard relative value (CDCl3Calibrate δ 7.261H NMR and
77.00 13C NMR).High resolution mass spectrum (HRMS) passes through 4G quadrupole time-of-flight (QTof) mass spectrometer
It obtains.
Embodiment 1
The reaction equation of embodiment 1, specifically used compound ii -1 and I -1 structure of product are as follows
Specific experiment step is: the compound ii -1 of 127mg (0.300mmol, 1.0 equivalents) is dissolved in the dichloromethane of 3mL
In alkane, the zinc bromide of 68mg (0.30mmol, 1.0 equivalents) is added, is reacted in 25 DEG C.After reaction, reaction mixture is existed
Water pump decompression is lower to rotate evaporation of solvent methylene chloride.Residue is with 200-300 mesh silica gel, eluent (volume ratio VPetroleum ether:
VEthyl acetate=6:1~3:1) column chromatographs to obtain compound shown in I -1, and product is by nuclear-magnetism (hydrogen spectrum, carbon spectrum), high resolution mass spectrum
Identification.
Product I -1 is yellow oily liquid, yield 92%.1H NMR(600MHz,CDCl3)δ7.60–7.53(m,2H),
7.42–7.38(m,3H),3.83(s,3H),3.78(s,3H)；13C NMR(100MHz,CDCl3)δ164.2,161.1,146.6,
141.0,129.6,128.7,128.3,128.0,113.1,52.4,52.4；ESI-HRMS m/z calcd for C13H12N2O4
+Na+283.0689,found 283.0688.
Prepare method and implementation used in the embodiment of other compounds of the invention (chemical compounds I -2 to chemical compounds I -9)
Example 1 is identical, and reaction condition is as follows: compound ii (0.3mmol, 1.0 equivalents) is dissolved in the methylene chloride of 3mL, and zinc bromide is added
68mg (0.3mmol, 1.0 equivalents), 25 DEG C of room temperature are reacted 8 hours.
Each product structure of gained and data are characterized as below:
Product I -2 is yellow oily liquid, yield 85%.1H NMR(400MHz,CDCl3) δ 7.50 (d, J=7.6Hz,
2H), 6.90 (d, J=7.6Hz, 2H), 3.81 (s, 6H), 3.78 (s, 3H)；13C NMR(100MHz,CDCl3)δ164.1,
161.4,160.7,146.2,141.6,129.5,120.1,114.1,112.4,55.3,52.4,52.3；ESI-HRMS m/z
calcd for C14H14N2O5+H+291.0975,found 291.0973.
Product I -3 is yellow oily liquid, yield 92%.1H NMR(400MHz,CDCl3) δ 7.43 (d, J=8.0Hz,
2H), 7.17 (d, J=7.6Hz, 2H), 3.81 (s, 3H), 3.74 (s, 3H), 2.35 (s, 3H)；13C NMR(100MHz,CDCl3)
δ164.3,161.3,146.2,141.4,139.6,129.3,127.8,125.1,112.6,52.3,52.2,21.2；ESI-
HRMS m/z calcd for C14H14N2O4+H+275.1026,found 275.1027.
Product I -4 is yellow oily liquid, yield 81%.1H NMR(400MHz,CDCl3) δ, 7.70 (d, J=
8.4Hz, 2H), 7.63 (d, J=8.4Hz, 2H), 3.84 (s, 3H), 3.80 (s, 3H)；13C NMR(100MHz,CDCl3)δ
(164.0,160.4,146.1,139.6,132.3,131.3 q, J=32.5Hz), 128.3,125.6 (q, J=3.7Hz),
123.8 (q, J=270.6Hz), 113.8,52.6, (1C missing)；ESI-HRMS m/z calcd for C14H11F3N2O4
+Na+351.0563,found 351.0562.
Product I -5 is yellow oily liquid, yield 76%.1H NMR(400MHz,CDCl3)δ7.58–7.52(m,2H),
7.06 (t, J=8.8Hz, 2H), 3.82 (s, 3H), 3.74 (s, 3H)；13C NMR(100MHz,CDCl3)δ164.1,163.4(d,
), J=248.6Hz 161.0,145.7,140.8,130.1 (d, J=8.4Hz), 124.4 (d, J=3.1Hz), 115.8 (d, J=
21.7Hz),112.8,52.4(2C)；ESI-HRMS m/z calcd for C13H11FN2O4+Na+301.0595,found
301.0593.
Product I -6 is yellow oily liquid, yield 37%.1H NMR(400MHz,CDCl3) δ 7.50 (d, J=1.2Hz,
1H), 7.24 (d, J=3.2Hz, 1H), 6.53 (dd, J=3.2,1.6Hz, 1H), 3.93 (s, 3H), 3.93 (s, 3H)；13C NMR
(100MHz,CDCl3)δ163.2,161.6,143.5,142.9,142.6,137.7,112.6,112.2,110.1,52.6,
52.2；ESI-HRMS m/z calcd for C11H10N2O5+Na+273.0482,found 273.0481.
Product I -7 is white solid, yield 77%, fusing point: 117-118 DEG C of1H NMR(400MHz,CDCl3)δ3.90
(s,3H),3.88(s,3H),1.40(s,9H)；13C NMR(100MHz,CDCl3)δ165.6,161.7,153.3,141.5,
112.7,52.3,52.1,32.4,29.0；ESI-HRMS m/z calcd for C11H16N2O4+Na+263.1002,found
263.1001.
Product I -8 is white solid, yield 63%, fusing point: 117.5-118.3 DEG C of1H NMR(400MHz,CDCl3)δ
7.48 (d, J=7.2Hz, 2H), 7.40-7.28 (m, 5H), 3.93 (s, 3H), 3.70 (s, 3H)；13C NMR(100MHz,
CDCl3)δ163.2,161.7,145.1,142.8,135.6,134.3,129.0,128.7,127.1,113.7,111.5,
52.4,52.0；ESI-HRMS m/z calcd for C15H14N2O4+Na+309.0846,found 309.0845.
Product I -9 is yellow oily liquid, yield 91%.1H NMR(400MHz,CDCl3)δ7.60–7.52(m,2H),
7.39-7.33 (m, 3H), 4.29 (q, J=7.2Hz, 2H), 4.18 (q, J=7.2Hz, 2H), 1.26 (t, J=7.2Hz, 3H),
1.18 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ163.8,160.7,146.1,141.0,129.3,128.5,
128.4,127.9,113.3,61.4,61.3,13.9,13.9；ESI-HRMS m/z calcd for C15H16N2O4+Na+
311.1002,found 311.1002。
Finally, it should be noted that the foregoing is only a preferred embodiment of the present invention, it is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
To modify the technical solutions described in the foregoing embodiments or equivalent replacement of some of the technical features.
It is all within the contents of the present invention and principle, any modification, equivalent replacement, improvement and so on should be included in of the invention
Within protection scope.
Claims (5)
1. three substituted pyrazole derivatives, which is characterized in that as shown in I, pyrazol framework structure contains there are three substituent group structural formula,
It is unsubstituted structure on nitrogen；
Wherein: R1For phenyl or substituted-phenyl (substituent group includes: 4- methoxyl group, 4- methyl, 4- trifluoromethyl, 4- fluorine), heterocycle is taken
Dai Ji, alkyl substituent, one of alkenyl group；R2For methyl substituents or ethyl substituent.
2. three substituted pyrazole derivatives according to claim 1, which is characterized in that preparation method is as follows:
The preparation method of target compound I: compound shown in general formula II, Zinc Bromide Anhydrous powder are dissolved at room temperature
In dichloromethane solvent, reactant II disappears completely, and organic solvent will be removed under reaction mixture reduced pressure, and column chromatography is washed
It is de- to obtain target compound I.
3. the preparation method of three substituted pyrazole derivatives according to claim 2, it is characterised in that made using zinc bromide
For lewis acid reagent, using methylene chloride as reaction dissolvent, target compound I is can be obtained in reaction under room temperature.
4. the preparation method of three substituted pyrazole derivatives according to claim 3, it is characterised in that compound ii, bromination
The molar ratio of zinc is II: zinc bromide=1.0:1.0, dichloromethane solution concentration are 0.1M, i.e., 0.1 mole every liter can be obtained mesh
Mark chemical compounds I.
5. the preparation method of three substituted pyrazole derivatives according to claim 2 to 6, it is characterised in that silica gel column chromatography
Eluent used is the mixed solvent of petroleum ether and ethyl acetate, and volume ratio VPetroleum ether:VEthyl acetate=6:1~3:1 can be obtained
Target compound I.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114560811A (en) * | 2022-03-11 | 2022-05-31 | 中国药科大学 | 1,3, 5-trisubstituted-pyrazole-4 carboxylic acid derivative and preparation method and application thereof |
| CN115677584A (en) * | 2022-11-10 | 2023-02-03 | 南京林业大学 | Preparation method and application of 4, 5-dihydropyrazole derivative |
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| CN103936673A (en) * | 2014-03-27 | 2014-07-23 | 华东师范大学 | 1,4,5-trisubstituted pyrazoles compound and preparation method thereof |
| CN108129389A (en) * | 2018-01-15 | 2018-06-08 | 西华师范大学 | A kind of N- benzyl pyrazoles class compound and preparation method thereof |
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Cited By (3)
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| CN114560811A (en) * | 2022-03-11 | 2022-05-31 | 中国药科大学 | 1,3, 5-trisubstituted-pyrazole-4 carboxylic acid derivative and preparation method and application thereof |
| CN114560811B (en) * | 2022-03-11 | 2023-09-01 | 上海立森印迹医药技术有限公司 | 1,3, 5-trisubstituted-pyrazole-4 carboxylic acid derivative, preparation method and application thereof |
| CN115677584A (en) * | 2022-11-10 | 2023-02-03 | 南京林业大学 | Preparation method and application of 4, 5-dihydropyrazole derivative |
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