CN108947906A - A method of preparing tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- - Google Patents
A method of preparing tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- Download PDFInfo
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- CN108947906A CN108947906A CN201810922123.9A CN201810922123A CN108947906A CN 108947906 A CN108947906 A CN 108947906A CN 201810922123 A CN201810922123 A CN 201810922123A CN 108947906 A CN108947906 A CN 108947906A
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- 238000000034 method Methods 0.000 title claims abstract description 25
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- -1 methylhydrazine acyl chlorides Chemical class 0.000 claims abstract description 22
- 125000005605 benzo group Chemical group 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 238000007259 addition reaction Methods 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Chemical class 0.000 claims description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical class [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 13
- 239000000758 substrate Substances 0.000 abstract description 7
- 150000003217 pyrazoles Chemical class 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 2
- 230000003993 interaction Effects 0.000 abstract description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 abstract description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- ISRXMEYARGEVIU-UHFFFAOYSA-N n-methyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C)C(C)C ISRXMEYARGEVIU-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- MREIFUWKYMNYTK-UHFFFAOYSA-N 1H-pyrrole Chemical class C=1C=CNC=1.C=1C=CNC=1 MREIFUWKYMNYTK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- RUKDVLFJSMVBLV-UHFFFAOYSA-N 5-iodo-1h-pyrazole Chemical class IC1=CC=NN1 RUKDVLFJSMVBLV-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- WHJQJCCPKCLSOD-UHFFFAOYSA-N BBCBC Chemical compound BBCBC WHJQJCCPKCLSOD-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005406 washing Methods 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
- C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a kind of methods for preparing tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5-.This method is under basic catalyst effect, and addition reaction occurs for benzo sultam and N- aryl virtue methylhydrazine acyl chlorides, is connected using dipole-diople interaction and takes off SO2Single step reaction prepares tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5-.Reactions steps of this method is short, and reaction condition is mild；Reaction substrate feed ratio is low, will not generate a large amount of wastes；Conversion zone selectivity is high, will not generate other by-products, therefore reaction yield is high, is connected with methylamino on 5 aromatic rings in product structure, can be utilized and prepare further types of pyrazole derivatives.
Description
Technical field
The present invention relates to a kind of methods for preparing tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5-.
Background technique
Polyaryl substituted pyrazolecarboxylic is a kind of important nitrogenous five member ring heterocyclic compound, be successfully applied to field of medicaments,
Agricultural chemicals, ligands for transition metal catalysts and good fluorescent material potentiality to be exploited；But related polyaryl takes so far
It is seldom for the synthetic method report of pyrazole compound, and generally existing product yield is low, the substrate scope of application is small, and substrate synthesis is tired
The disadvantages of difficult, greatly limits the molecular diversity of such compound.
Currently, the conventional method of synthesis polyaryl substituted pyrazolecarboxylic mainly utilizes hydrazine class compound and 1,3- dicarbapentaborane chemical combination
Condensation reaction (Murray, W.V. between object or alpha, beta-unsaturated carbonyl compound；Wachter,
M.P.J.Heterocycl.Chem.1989,26,1389), reaction equation is as follows:
This method it is small there are the substrate scope of application and reaction regioselectivity it is poor, usually there will be N1 replace and N2
Substituted mixture.
2015, T.Morita et al. was using 3- iodo -1H- pyrazoles as substrate, by SNAr reaction, coupling reaction and C-H
Arylation reaction, altogether four-step reaction synthesized tool there are four different aryl replace pyrazole compound (T.Morita,
D.Kobayashi,K.Matsumura,K.Johmoto,H.Uekusa,S.Fuse,T.Takahashi,Chem.Asian
J.2015,10,1626), reaction equation is as follows:
But the economy that reaction is affected using precious metals palladium catalyst is needed in this method, while this method route compared with
It is long, cause product yield lower.
In conclusion providing, a kind of reaction condition is mild, regioselectivity is high, product yield is high and synthetic route is simple
The preparation method of 1,3,4,5- tetra- aryl substituted pyrazolecarboxylic, is of great significance.
Summary of the invention
It needs to heat to solve the preparation method of tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- in the prior art, regional choice
The problem that property is low, product yield is low and synthetic route is more complicated, the present invention provides a kind of methods.
In order to solve the above-mentioned technical problem, the invention adopts the following technical scheme:
A kind of method preparing 1,3,4,5- tetra- aryl substituted pyrazolecarboxylics has formula (I) structure under basic catalyst effect
Benzo sultam and with formula (II) structure N- aryl virtue methylhydrazine acyl chlorides occur addition reaction, generate have formula (III) knot
The tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- of structure；Specific reaction route is as follows:
Wherein, Ar be 2- pyridyl group, 3- pyridyl group, 4 pyridyl groups, 2- furyl, phenyl or C1-C4 alkyl-substituted phenyl,
Fluorine substituted-phenyl, chlorine substituted-phenyl, bromine substituted-phenyl or methoxy substitution phenyl；R1 be hydrogen, C1-C4 alkyl, fluorine-based, chloro,
Bromo, methoxyl group, nitro or cyano；R2 is hydrogen, C1-C4 alkyl, fluorine-based, chloro, bromo, methoxyl group, nitro or cyano.
Preferably, the basic catalyst is selected from trimethylamine, triethylamine, diisopropyl methylamine, diisopropylethylamine, pyrrole
Pyridine, triethylenediamine or diazabicylo one or more.
Preferably, the addition reaction carries out in aprotic organic solvent, the aprotic organic solvent be selected from benzene,
Toluene, ortho-xylene, meta-xylene, paraxylene, methylene chloride, 1,2- dichloroethanes or tetrahydrofuran are one or more of.
Preferably, the molar ratio between the benzo sultam, N- aryl virtue methylhydrazine acyl chlorides and basic catalyst is
1:1:1~1:1.5:5.
Preferably, the reaction condition of the addition reaction is, reaction temperature is anti-0-40 DEG C, reaction time 1.0-
12.0。
Another goal of the invention of the invention, the present invention also provides a kind of 1,3,4,5- tetra- aryl of above method preparation
Substituted pyrazole compounds.
Compared to the method for 1,3,4,5- tetra- aryl substituted pyrazolecarboxylics of preparation in the prior art, there are following excellent by the present invention
Point: (one) reaction step is brief, is connected using dipole-diople interaction and takes off SO2Single step reaction prepares four aryl substituted pyrazole compounds；
(2) reaction condition is mild, can be completed in the short period at room temperature, and without heating, two substrates of simultaneous reactions feed intake
Than low, a large amount of wastes will not be generated；(3) substrate stability is strong, and autoreactivity, simultaneous reactions will not occur in reaction process
Regioselectivity is high, will not generate other by-products, therefore reaction yield is high, and generation product is single-minded, so that convenient product separation；
(4) it is connected with methylamino on 5 aromatic rings in product structure, can be utilized and prepares further types of pyrazole derivatives.
Specific embodiment
The invention discloses a kind of method for preparing 1,3,4,5- tetra- aryl substituted pyrazolecarboxylics, those skilled in the art can be borrowed
Reflect present disclosure, is suitably modified realization of process parameters.In particular, it should be pointed out that all similar substitutions and modifications are to this field
It is it will be apparent that they are considered as including in the present invention for technical staff.Method and application of the invention is
Be described by preferred embodiment, related personnel obviously can not depart from the content of present invention, in spirit and scope to herein
The methods and applications are modified or appropriate changes and combinations, carry out implementation and application the technology of the present invention.
In preparation method provided by the invention, further include the steps that purifying product.Specifically, including to product into
Row liquid separation, washing or drying steps.
Below with reference to embodiment, the present invention is further explained:
Embodiment 1
0.25 mM of benzo sultam, 0.25 mM of N- aryl virtue methylhydrazine acyl chlorides and 1 milli are put into reaction flask
Methylene chloride is risen, 10 DEG C are stirred five minutes, and then by the benzene 1 of 0.25 mM of triethylamine, 2- dichloroethane solution is in 1 hour
It is added dropwise in reaction solution, is reacted 6.5 hours at 25 DEG C after being added dropwise, directly column chromatography for separation obtains pure production after removing solvent
Tetra- aryl substituted pyrazolecarboxylic of object 1,3,4,5-.
Embodiment 2
1 mM of benzo sultam, 1.5 mMs of N- aryl virtue methylhydrazine acyl chlorides and 1 milliliter of neighbour are put into reaction flask
Dimethylbenzene and meta-xylene, 10 DEG C are stirred five minutes, then drip the dichloromethane solution of 5 mMs of triethylamines in 1 hour
It is added in reaction solution, is reacted 1 hour at 40 DEG C after being added dropwise, be added saturated ammonium chloride solution into reaction solution, split-phase,
Organic phase is washed through saturated sodium chloride solution, and anhydrous sodium sulfate is dry, and column, which chromatographs, is made the substitution of 1,3,4,5- tetra- aryl of pure products
Pyrazoles.
Embodiment 3
1 mM of benzo sultam, 1.25 mMs of N- aryl virtue methylhydrazine acyl chlorides and 1 milliliter four are put into reaction flask
Hydrogen furans, 10 DEG C are stirred five minutes, are then added dropwise to the dichloromethane solution of 3 mMs of diisopropyl methylamines in 1 hour
In reaction solution, is reacted 12 hours at 10 DEG C after being added dropwise, saturated ammonium chloride solution is added into reaction solution, split-phase has
Machine is mutually washed through saturated sodium chloride solution, and anhydrous sodium sulfate is dry, and column, which chromatographs, is made 1,3,4,5- tetra- aryl of pure products substitution pyrrole
Azoles.
Embodiment 4
1 mM of benzo sultam, 1.5 mMs of N- aryl virtue methylhydrazine acyl chlorides and 1 milliliter two are put into reaction flask
Chloromethanes, 10 DEG C are stirred five minutes, then by the dichloromethane solution of 5 mMs of diisopropylethylamine and pyridine in 1 hour
It is added dropwise in reaction solution, is reacted 1 hour at 40 DEG C after being added dropwise, saturated ammonium chloride solution is added into reaction solution, point
Phase, organic phase are washed through saturated sodium chloride solution, and anhydrous sodium sulfate is dry, and column chromatographs obtained 1,3,4,5- tetra- aryl of pure products and takes
For pyrazoles.Part has the tetra- aryl substituted pyrazolecarboxylic structure of 1,3,4,5- and its corresponding yield such as table 1 of formula (III) structure
It is shown:
The structure and its yield of 1 part 1,3,4,5- of table, tetra- aryl substituted pyrazole compounds
| Serial number | 1 Ar | 2 R1 | 2 R2 | Yield (%) |
| 1 | 4- pyridyl group | Hydrogen | Hydrogen | 74 |
| 2 | 2- furyl | Hydrogen | Hydrogen | 72 |
| 3 | 4- fluorophenyl | Hydrogen | Hydrogen | 82 |
| 4 | 4- chlorphenyl | Hydrogen | Hydrogen | 85 |
| 5 | 4- bromophenyl | Hydrogen | Hydrogen | 90 |
| 6 | 4- aminomethyl phenyl | Hydrogen | Hydrogen | 82 |
| 7 | 4- methoxyphenyl | Hydrogen | Hydrogen | 81 |
| 8 | 2- aminomethyl phenyl | Hydrogen | Hydrogen | 76 |
| 9 | 3- aminomethyl phenyl | Hydrogen | Hydrogen | 79 |
| 10 | Phenyl | Hydrogen | 4- chlorine | 71 |
| 11 | Phenyl | 4- methyl | 4- chlorine | 85 |
| 12 | Phenyl | Hydrogen | 4- nitro | 74 |
| 13 | Phenyl | 4- methyl | 4- nitro | 88 |
| 14 | Phenyl | 2- fluorine | Hydrogen | 80 |
| 15 | Phenyl | 2- fluorine | 4- chlorine | 86 |
| 16 | Phenyl | 2- methyl | Hydrogen | 83 |
| 17 | Phenyl | 2- methyl | 4- chlorine | 87 |
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (6)
1. a kind of method for preparing 1,3,4,5- tetra- aryl substituted pyrazolecarboxylics, which is characterized in that under basic catalyst effect, have
The benzo sultam of formula (I) structure and the N- aryl virtue methylhydrazine acyl chlorides generation addition reaction with formula (II) structure, generate tool
There is the tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- of formula (III) structure；
Wherein, Ar is that 2- pyridyl group, 3- pyridyl group, 4 pyridyl groups, 2- furyl, phenyl or C1-C4 alkyl-substituted phenyl, fluorine take
For phenyl, chlorine substituted-phenyl, bromine substituted-phenyl or methoxy substitution phenyl；R1 be hydrogen, C1-C4 alkyl, fluorine-based, chloro, bromo,
Methoxyl group, nitro or cyano；R2 is hydrogen, C1-C4 alkyl, fluorine-based, chloro, bromo, methoxyl group, nitro or cyano.
2. the method as described in claim 1, which is characterized in that the basic catalyst is selected from trimethylamine, triethylamine, diisopropyl
The one or more of base methylamine, diisopropylethylamine, pyridine, triethylenediamine or diazabicylo.
3. the method as described in claim 1, which is characterized in that the addition reaction carries out in aprotic organic solvent, institute
It states aprotic organic solvent and is selected from benzene, toluene, ortho-xylene, meta-xylene, paraxylene, methylene chloride, 1,2- dichloroethanes
Or tetrahydrofuran is one or more of.
4. the method as described in claim 1, which is characterized in that the benzo sultam, N- aryl virtue methylhydrazine acyl chlorides and alkali
Property catalyst between molar ratio be 1:1:1~1:1.5:5.
5. the method as described in claim 1, which is characterized in that the reaction condition of the addition reaction is that reaction temperature is anti-
0-40 DEG C, reaction time 1.0-12.0.
6. using the tetra- aryl substituted pyrazolecarboxylic of 1,3,4,5- of method a method as claimed in any one of claims 1 to 5 preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922123.9A CN108947906B (en) | 2018-08-14 | 2018-08-14 | Method for preparing 1,3,4, 5-tetraaryl substituted pyrazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922123.9A CN108947906B (en) | 2018-08-14 | 2018-08-14 | Method for preparing 1,3,4, 5-tetraaryl substituted pyrazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108947906A true CN108947906A (en) | 2018-12-07 |
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| CN110885313A (en) * | 2019-12-16 | 2020-03-17 | 扬州工业职业技术学院 | Antibacterial active tetraphenylpyrazole compound and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108299303A (en) * | 2018-02-09 | 2018-07-20 | 中山大学 | A kind of new synthetic method of four arylpyrazoles compound |
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Non-Patent Citations (6)
| Title |
|---|
| H. M. HASSANEEN ET AL.: "A New Synthesis of Oxadiazole, Thiazolidinone, N-Phthalimidoamino Carbonyl and Arylidene Derivatives with Potential Antimicrobial Activity", 《ARCH. PHARM. PHARM. MED. CHEM.》 * |
| HELENA MODRZEJEWSKA ET AL.: "Synthesis and reactions of 3-alkylsulfanyl-1,3-dihydro-2,1-benzisothiazole 2,2-dioxides", 《TETRAHEDRON》 * |
| ISSA YAVARI ET AL.: "A Convenient Synthesis of Tetrasubstituted Pyrazoles from Nitrile Imines and 2-(Thioxothiazolidin-5-ylidene)acetates", 《SYNLETT》 * |
| KRZYSZTOF WOJCIECHOWSKI ET AL.: "New Synthesis of 2-Phenylindene Derivatives", 《SYNTHETIC COMMUNICATIONS》 * |
| SZYMON KOSIN´SKI ET AL.: "Reactions of Pyridine Analogues of Aza-ortho-xylylenes Generated from 1,3-Dialkylpyridosultams", 《EUR.J.ORG.CHEM.》 * |
| YAO LI ET AL.: "Synthesis of pyrazoles from 2-azidoacrylates and hydrazonyl chlorides", 《TETRAHEDRON LETTERS》 * |
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| CN110885313A (en) * | 2019-12-16 | 2020-03-17 | 扬州工业职业技术学院 | Antibacterial active tetraphenylpyrazole compound and preparation method and application thereof |
| CN110885313B (en) * | 2019-12-16 | 2021-09-17 | 扬州工业职业技术学院 | Antibacterial active tetraphenylpyrazole compound and preparation method and application thereof |
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