CN107188851A - A kind of method for synthesizing astemizole key intermediate and its derivative - Google Patents
A kind of method for synthesizing astemizole key intermediate and its derivative Download PDFInfo
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- CN107188851A CN107188851A CN201710514373.4A CN201710514373A CN107188851A CN 107188851 A CN107188851 A CN 107188851A CN 201710514373 A CN201710514373 A CN 201710514373A CN 107188851 A CN107188851 A CN 107188851A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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Abstract
The present invention is a kind of method for synthesizing astemizole key intermediate and its derivative.Catalyst is made using the nonmetallic organic boron nitrogen Lewis Acids and Bases dual-function compound of fluorescence labeling, the pollution of heavy metal is effectively avoided；Catalyst can recycle and reuse and can the residual quantity of quick detection catalyst in the product；Extensively, the selectivity and yield of target product are close to 100%, and catalyst can be used repeatedly, and reaction condition is simple, it is easy to operate, and cost is low, preparation process environmental protection for raw material sources.
Description
【Technical field】
The invention belongs to be catalyzed organic synthesis field, relate in particular to a kind of synthesis astemizole key intermediate and its
The method of derivative.
【Background technology】
Astemizole is frequently used in our daily lifes as strength and long-acting H1 receptor antagonists.Astemizole
Most important key intermediate is benzimidazoles derivative, and structural formula is as follows：
But, difficult challenge is still suffered from during synthesizing benzimidazole analog derivative.The method of conventional synthesis is
Obtained in strong acid as the ring closure reaction of o-phenylenediamine under catalyst and carboxylic acid, the method uses strong acid, such as dense HCl, dense H2SO4Deng,
So as to which some are not applied to the sensitive substrate of highly basic, while also causing certain environmental pollution to environment.Improved method be
In the presence of catalyst/oxidant, the reaction of o-phenylenediamine and aldehyde is first condensed to yield Schiff base intermediate, then carry out schiff bases
Ring closure reaction, last oxidative dehydrogenation obtains benzimidazoles compound.Wherein catalyst/oxidant is I2、H2O2、H2SO4/SiO2
Deng the deficiency of the method is that catalyst can not be recycled and reused, and the time is long, has not both met power conservation requirement or has not met
The requirement of Atom economy.The use organo-bismuth Louis acid catalysis reported recently synthesizes a series of benzimidazoles derivatives,
This method is simple to operate, and yield is higher, but introduced in reaction it is unavoidable in bismuth metal, product there is metal residual, and
And without effective detection method.
In recent years, fluorescence labeling is chemical because it has the advantages that highly sensitive, low test limit is of great interest.With
This simultaneously, Organic base bifunctional catalyst has good catalytic activity, is widely used in organic synthesis field.It is comprehensive
The deficiency of above synthesizing benzimidazole class compound method is closed, we, which design, has synthesized a fluorescence marked organic boron nitrogen Louis
This difunction catalyst (in patent 201710133198.4 it has been reported that), its general structure is as follows：
Wherein, the R1、R2、R3、R4、R5、R6Group is hydrogen, methyl, methoxyl group, the tert-butyl group, isopropyl, nitro, acetylene
One kind in base, vinyl, pi-allyl, carbonyl, hydroxyl, aldehyde radical, trifluoromethyl, fluorine, chlorine, bromine, iodine, RfFor containing fluoro aryl or alkane
Base group.
This kind of catalyst due to high catalytic activity and fluorescence quantum efficiency, can efficient catalytic organic reaction,
Simultaneously catalyst in reaction system can quick separating come out, and pass through its residual quantity in the product of spectral detection.Secondly,
It has good stability, dissolubility and heavy metal pollution is not present.Therefore, urged by a kind of the nonmetallic of fluorescence labeling
Agent efficiently synthesizes this kind of compound, and can be with quick detection catalyst in the product trace residue, with important
Practical value and meaning.
【The content of the invention】
It is an object of the invention to provide a kind of organic boron nitrogen lewis acid base bifunctional catalyst of use fluorescence labeling
The method for synthesizing astemizole key intermediate and its derivative, to improve the yield of target product and the repeatable profit of catalyst
With property, while the residual quantity for quick detection catalyst in the product provides a kind of new route.
To achieve the above object of the invention, the present invention proposes following technical scheme：
The present invention is using aryl aldehyde compound, o-phenylenediamine as raw material, with the organic boron nitrogen Lewis Acids and Bases of fluorescence labeling
Dual-function compound is catalyst, and reaction dissolvent is made with conventional organic solvent, reacts anti-at a certain temperature, answers a timing
Between, high yield, astemizole key intermediate class compound is obtained with high selectivity.After reaction terminates, it must be produced through chromatographic isolation
Thing and recovery catalyst.
There are the organic boron nitrogen Lewis Acids and Bases of structural formula I fluorescence labeling in above-mentioned synthetic method, during the catalyst
Difunctional complex, wherein, B centers in the complex and a nitrogen-atoms bonding in part, also with it is another in part
Individual nitrogen-atoms formation coordinate bond.
In above-mentioned synthetic method, mole addition of the catalyst is 0.01-0.12mol%.
In above-mentioned synthetic method, the raw material aldehyde is fatty aldehyde or aromatic aldehyde, preferably pentafluorobenzaldehyde, 2,4,6- trifluoro-benzenes
The fluoro- 3- tolyl aldehydes of formaldehyde, 4-, the fluoro- 3- trifluoromethylated benzaldehydes of 4-, the chloro- 4- fluorobenzaldehydes of 3-, the bromo- 4- fluorobenzene first of 3-
Aldehyde, 4,5- difluoros salicylide, the fluoro- 1- naphthaldehydes of 4-, 2- cyano group -4- fluorobenzaldehydes, 2- amino -4- fluorobenzaldehydes, 2- nitros -
4- fluorobenzaldehydes
In above-mentioned synthetic method, the raw material amine is o-phenylenediamine class, preferably adjacent bromine o-phenylenediamine, adjacent chlorine o-phenylenediamine,
Adjacent fluorine o-phenylenediamine, to chlorine o-phenylenediamine, to bromine o-phenylenediamine, to methyl-o-phenylenediamine, to fluorine o-phenylenediamine, to the adjacent benzene of cyano group
Diamines, to nitro-o-phenylenediamine, 4,5- difluorobenzene -1,2- diamines, 4,5- dimethyl -1,2- phenylenediamines
In above-mentioned synthetic method, the solvent is toluene, acetonitrile, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), N, N-
One kind in dimethylformamide (DMF).
In above-mentioned synthetic method, the condition of the catalytic reaction is：Reacted 0.5-12 hours at 0-120 DEG C.
Synthetic method provided by the present invention for the preparation of astemizole key intermediate derivative open it is new it is low into
This " green " approach, the advantage is that：Made using the nonmetallic organic boron nitrogen Lewis Acids and Bases dual-function compound of fluorescence labeling
Catalyst, effectively avoids the pollution of heavy metal；Catalyst can be recycled and reused and energy quick detection catalyst is in production
Residual quantity in thing；Extensively, the selectivity and yield of target product are close to 100%, and catalyst can be weighed repeatedly for raw material sources
Multiple to utilize, reaction condition is simple, it is easy to operate, cost is low, preparation process environmental protection.
【Brief description of the drawings】
It is the synthesis path figure for the astemizole key intermediate derivative that the present invention is provided shown in Fig. 1.
【Embodiment】
The synthesis path of the method provided by the present invention for catalyzing and synthesizing astemizole key intermediate derivative, is referred to
Accompanying drawing 1：The organic boron nitrogen lewis acid base bifunctional catalyst of the aldehyde of starting compound, o-phenylenediamine class, fluorescence labeling is put
Enter in reaction vessel, add solvent toluene, reacted 0.5-12 hours in the environment of 0-120 DEG C, after the completion of reaction, target chemical combination
Look for spectrum isolated.
With reference to specific preparation example, the present invention will be further described：
Preparation example 1
0.01mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11=
H), 15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 85%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 2
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11=
H), 15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 3
0.08mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11=
H), 15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 4
0.12mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11=
H), 15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 5
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=C2F5；
R1、R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 6
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R2
=OMe；R1、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 92%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 7
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=C3F7；
R1、R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 97%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 8
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=(- C (CH3)3)；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 9
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=C6F5；
R1、R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 10
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=
CF3；R1=CH3；R2=OMe；R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), the adjacent benzene two of 0.1mol
Amine (R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Instead
Should result be：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 89%；Catalyst system recycling 10
After secondary, its catalytic performance has no decline.
Preparation example 11
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=
C4F9；R1、R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 12
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2=F；R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 13
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=NO2；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 92%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 14
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=(C2H-)、R2=Me, R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 15
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R2
=Cl；R1、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 16
0.03mol% lewis acid base bifunctional catalyst I (R are added in 100mL single-necked flasksf=CF3；R4=
CH3；R1、R2、R3、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 88%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 17
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=I；R2=Cl；R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 18
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R5
=OCH3；R1、R2、R3、R4、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 19
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 94%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 20
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-CH3-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 94%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 21
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-CF3-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 22
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-OCH3-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 23
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-OH-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 92%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 24
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-COCH3-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 25
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=CF3；R1=Cl；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 26
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=COCH3；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 92%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 27
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=CN；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 28
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=F；R2=CF3；R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 29
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-COH-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 30
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-C2H3-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 31
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=I；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product
II(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its catalytic
Decline can be had no.
Preparation example 32
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=(2-C2H3)-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 33
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=O-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 34
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=((CH3)2CH-)；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 35
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-S-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 94%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 36
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=OCH3；R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 37
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-Se-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 91%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 38
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-Te-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 94%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 39
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=-H2C-CH=CH2；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 40
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1
=CF3；R2=CH3；R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 41
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=C12H8N；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 42
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=p-Cl-Ph；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 90%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 43
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=2-C4H3S；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、
R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 93%；After catalyst system is reused 10 times, its
Catalytic performance has no decline.
Preparation example 44
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=C6F5；
R1、R2、R3、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11
=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 45
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=Cl；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 92%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 46
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=Cl；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 94%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 47
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R3
=Br；R1、R2、R4、R5、R6=H), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、
R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Production
Thing II (R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 95%；After catalyst system is reused 10 times, it is catalyzed
Performance has no decline.
Preparation example 48
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 4-Fluorobenzaldehydes (R7=4-F-C6H4), 0.1mol o-phenylenediamines (R8、R9、R10、R11=
H), 15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II
(R7=4-F-C6H4；R8、R9、R10、R11=H) yield be 100%；After catalyst system is reused 10 times, its catalytic performance
Have no decline.
Preparation example 49
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol pentafluorobenzaldehydes (R7=C6F5), 0.1mol o-phenylenediamines (R8、R8、R10、R11=H),
15mL toluene, reaction is stirred 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result is：Product II (R7=
C6F5；R8、R8、R10、R11=H) yield be 100%；After catalyst system is reused 10 times, its catalytic performance has no decline.
Preparation example 50
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 2,4,6- trifluro benzaldehydes (R7=2,4,6-C6F3H2), bromine o-phenylenediamine between 0.1mol
(R8=Br；R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.
Reaction result is：Product II (R7=2,4,6-C6F3H2；R8=Br；R9、R10、R11=H) yield be 98%；Catalyst system
After recycling 10 times, its catalytic performance has no decline.
Preparation example 51
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- 3- tolyl aldehydes (R of 0.2mol 4-7=4-F-3-Me-C6H3), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-3-Me-C6H3；R8、R9、R10、R11=H) yield be 97%；Catalyst system repeats profit
After 10 times, its catalytic performance has no decline.
Preparation example 52
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- 3- trifluoromethylated benzaldehydes (R of 0.2mol 4-7=4-F-3-CF3-C6H3), 0.1mol m-chloros it is adjacent
Phenylenediamine (R8=Cl；R9、 R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking is reacted to anti-
Should be complete.Reaction result is：Product II (R7=4-F-3-CF3-C6H3；R8=Cl； R9、R10、R11=H) yield be 97%；
After catalyst system is reused 10 times, its catalytic performance has no decline.
Preparation example 53
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the chloro- 4- fluorobenzaldehydes (R of 0.2mol 3-7=4-F-3-Cl-C6H3), 0.1mol o-phenylenediamines (R8、
R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-3-Cl-C6H3；R8、R9、R10、R11=H) yield be 93%；Catalyst system recycling 10
After secondary, its catalytic performance has no decline.
Preparation example 54
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the bromo- 4- fluorobenzaldehydes (R of 0.2mol 3-7=4-F-3-Br-C6H3), 0.1mol is to fluorine o-phenylenediamine
(R8=F；R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.
Reaction result is：Product II (R7=4-F-3-Br-C6H3；R8=F；R9、R10、R11=H) yield be 99%；Catalyst system
After recycling 10 times, its catalytic performance has no decline.
Preparation example 55
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 4,5- difluoro salicylides (R7=4,5-2F-2-OH-C6H2), 0.1mol is to the adjacent benzene two of fluorine
Amine (R9=F；R8、R10、 R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reactions are to having reacted
Entirely.Reaction result is：Product II (R7=4,5-2F-2-OH-C6H2；R9=F；R8、 R10、R11=H) yield be 93%；Catalysis
After agent system is reused 10 times, its catalytic performance has no decline.
Preparation example 56
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 2- cyano group -4- fluorobenzaldehydes (R7=4-F-2-CN-C6H3), 0.1mol is to the adjacent benzene of nitro
Diamines (R9=NO2；R8、 R10、R11=H), 15mL toluene stirs reaction 4 hours at 25 DEG C, and TLC tracking reactions are extremely reacted
Completely.Reaction result is：Product II (R1=4-F-2-CN-C6H3；R9=NO2； R8、R10、R11=H) yield be 99%；Urge
After agent system is reused 10 times, its catalytic performance has no decline.
Preparation example 57
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 2- amino -4- fluorobenzaldehydes (R7=4-F-2-NH2-C6H3), 0.1mol o-phenylenediamines
(R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction
As a result it is：Product II (R7=4-F-2-NH2-C6H3；R8、R9、R10、R11=H) yield be 98%；Catalyst system repeats profit
After 10 times, its catalytic performance has no decline.
Preparation example 58
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- 1- naphthaldehydes (R of 0.2mol 4-7=4-F-C11H6), 0.1mol 4,5- difluorobenzene -1,2- benzene
Diamines (R9、R10=F；R8、 R11=H), 15mL toluene stirs reaction 5 hours at 25 DEG C, and TLC tracking reactions are to having reacted
Entirely.Reaction result is：Product II (R7=4-F-C11H6；R9、R10=F；R8、 R11=H) yield be 100%；Catalyst system
After recycling 10 times, its catalytic performance has no decline.
Preparation example 59
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- 3- tolyl aldehydes (R of 0.2mol4-7=4-F-3-Me-C6H3), bromine o-phenylenediamine between 0.1mol
(R8=Br；R9、R10、 R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.
Reaction result is：Product II (R7=4-F-3-Me-C6H3；R8=Br；R9、 R10、R11=H) yield be 99%；Caltalyst
After system's recycling 10 times, its catalytic performance has no decline.
Preparation example 60
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- benzaldehyde (R of 0.2mol 4-7=4-F-C6H4), 0.1mol m-chloro o-phenylenediamines (R8=Cl；
R9、R10、R11=H), 15 mL toluene stir reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R8=Cl；R9、R10、R11=H) yield be 95%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 61
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the chloro- 4- fluorobenzaldehydes (R of 0.2mol 3-7=4-F-3-Cl-C6H3), fluorine o-phenylenediamine between 0.1mol
(R8=F；R9、R10、 R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.
Reaction result is：Product II (R7=4-F-3-Cl-C6H3；R8=F；R9、R10、 R11=H) yield be 100%；Caltalyst
After system's recycling 10 times, its catalytic performance has no decline.
Preparation example 62
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the bromo- 4- fluorobenzaldehydes (R of 0.2mol 3-7=4-F-3-Br-C6H3), 0.1mol is to chlorine o-phenylenediamine
(R9=Cl；R10、R11、 R12=H), 15mL toluene stirs reaction 6 hours at 25 DEG C, and TLC tracking reactions are to having reacted
Entirely.Reaction result is：Product II (R7=4-F-3-Br-C6H3；R9=Cl；R10、 R11、R12=H) yield be 99%；Catalysis
After agent system is reused 10 times, its catalytic performance has no decline.
Preparation example 63
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- benzaldehyde (R of 0.2mol 4-7=4-F-C6H4), 0.1mol is to bromine o-phenylenediamine (R9=Br；
R8、R10、R11=H), 15 mL toluene stir reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R9=Br；R8、R10、R11=H) yield be 94%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 64
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 4,5- difluoro salicylides (R7=4,5-2F-2-OH-C6H2), 0.1mol is to the adjacent benzene of methyl
Diamines (R9=Me；R8、 R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reactions are extremely reacted
Completely.Reaction result is：Product II (R7=4,5-2F-2-OH-C6H2； R9=Me；R8、R10、R11=H) yield be 96%；
After catalyst system is reused 10 times, its catalytic performance has no decline.
Preparation example 65
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 2- cyano group -4- fluorobenzaldehydes (R7=4-F-2-CN-C6H3), 0.1mol is to the adjacent benzene two of fluorine
Amine (R9=F；R8、R10、 R11=H), 15mL toluene stirs reaction 8 hours at 25 DEG C, and TLC tracking reactions are to having reacted
Entirely.Reaction result is：Product II (R7=4-F-2-CN-C6H3；R9=F；R8、 R10、R11=H) yield be 99%；Catalyst
After system is reused 10 times, its catalytic performance has no decline.
Preparation example 66
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- benzaldehyde (R of 0.2mol 4-7=4-F-C6H4), 0.1mol is to cyano group o-phenylenediamine (R9=CN；
R8、R10、R11=H), 15mL toluene stirs reaction 5 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=4-F-C6H4；R9=CN；R8、R10、R11=H) yield be 94%；Catalyst system is reused 10 times
Afterwards, its catalytic performance has no decline.
Preparation example 67
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol 2- amino -4- fluorobenzaldehydes (R7=4-F-2-NH2-C6H3), 0.1mol is to the adjacent benzene of nitro
Diamines (R9=NO2；R8、 R10、R11=H), 15mL toluene stirs reaction 1 hour at 25 DEG C, and TLC tracking reactions are extremely reacted
Completely.Reaction result is：Product II (R7=4-F-2-NH2-C6H3；R9=NO2； R8、R10、R11=H) yield be 99%；Urge
After agent system is reused 10 times, its catalytic performance has no decline.
Preparation example 68
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- benzaldehyde (R of 0.2mol 4-7=4-F-C6H4), 0.1mol is to nitro-o-phenylenediamine (R9=
NO2；R8、R10、R11=H), 15mL toluene stirs reaction 2.5 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Instead
Should result be：Product II (R7=4-F-C6H4；R9=CN；R8、R10、R11=H) yield be 99%；Catalyst system repeats profit
After 10 times, its catalytic performance has no decline.
Preparation example 69
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), 0.2mol pentafluorobenzaldehydes (R7=C6F5), 0.1mol 4,5- difluorobenzene -1,2- phenylenediamines (R9、R10
=F；R8、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, and TLC tracking reaction extremely reacts complete.Reaction result
For：Product II (R7=C6F5；R9、R10=F；R8、R11=H) yield be 100%；After catalyst system is reused 10 times,
Its catalytic performance has no decline.
Preparation example 70
0.03mol% lewis acid base bifunctional catalyst I (wherein R are added in 100mL single-necked flasksf=CF3；R1、
R2、R3、R4、R5、R6=F), the fluoro- 1- naphthaldehydes (R of 0.2mol4-7=4-F-C11H6), 0.1mol 4,5- dimethyl -1,2- benzene two
Amine (R9、R10=Me；R8、 R11=H), 15mL toluene stirs reaction 5 hours at 25 DEG C, and TLC tracking reactions are to having reacted
Entirely.Reaction result is：Product II (R7=4-F-C11H6；R9、R10=Me；R8、 R11=H) yield be 100%；Caltalyst
After system's recycling 10 times, its catalytic performance has no decline.
In order to further illustrate the superiority of the inventive method, from following catalyst system and catalyzing as a comparison case.
Comparative example 1
The 0.03mol% concentrated sulfuric acids (H is added in 100mL single-necked flasks2SO4), 0.2mol 4-Fluorobenzaldehydes (R7=4-
C6H5), 0.1mol o-phenylenediamines (R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, reaction knot
It is really：Product II (R7=4-C6H5； R8、R9、R10、R11=H) yield be 55%；Catalyst reclaims difficult.
Comparative example 2
0.03mol% iodine (I is added in 100mL single-necked flasks2), 0.2mol 4-Fluorobenzaldehydes (R7=4-C6H5)、
0.1mol o-phenylenediamines (R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours, reaction result is at 25 DEG C：Production
Thing II (R7=4-C6H5；R8、 R9、R10、R11=H) yield be 67%；Catalyst reclaims difficult.
Comparative example 3
0.03mol% antimony chlorides (SbCl is added in 100mL single-necked flasks3), 0.2mol 4-Fluorobenzaldehydes (R7=4-
C6H5), 0.1mol o-phenylenediamines (R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, reaction knot
It is really：Product II (R7=4-C6H5； R8、R9、R10、R11=H) yield be 45%；Catalyst hydrolysis is very serious, it is impossible to reclaim.
Comparative example 4
0.03mol%AlCl is added in 100mL single-necked flasks3(SbCl3), 0.2mol 4-Fluorobenzaldehydes (R7=4-
C6H5), 0.1mol o-phenylenediamines (R8、R9、R10、R11=H), 15mL toluene stirs reaction 3 hours at 25 DEG C, reaction knot
It is really：Product II (R7=4-C6H5； R8、R9、R10、R11=H) yield be 73%；Catalyst hydrolysis is very serious, it is impossible to reclaim.
Embodiment described above only expresses the several embodiments of the present invention, and it describes more specific and detailed, but simultaneously
Therefore it can not be interpreted as should be pointed out that for one of ordinary skill in the art the limitation of the scope of the claims of the present invention
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (7)
1. the present invention is a kind of method for synthesizing astemizole key intermediate and its derivative, it is characterised in that with aryl aldehyde
Class compound, o-phenylenediamine are raw material, using the organic boron nitrogen lewis acid alkali bifunctional complex of fluorescence labeling as catalyst, with
Toluene is solvent, after reaction terminates, and obtains product through chromatographic isolation and reclaims catalyst.
2. synthetic method according to claim 1, it is characterised in that there is structural formula I fluorescence mark during the catalyst
The organic boron nitrogen lewis acid alkali bifunctional complex of note, wherein, the B centers in the complex and a nitrogen-atoms in part
Bonding, also with another nitrogen-atoms formation coordinate bond in part；Its described structural formula I is as follows：
Wherein, the R in the structural formula I1、R2、R3、R4、R5、R6Group is hydrogen, methyl, methoxyl group, the tert-butyl group, isopropyl, nitre
One kind in base, acetenyl, vinyl, pi-allyl, carbonyl, hydroxyl, aldehyde radical, trifluoromethyl, fluorine, chlorine, bromine, iodine, RfTo be fluorine-containing
Aryl or alkyl group.
3. synthetic method according to claim 1 or 2, it is characterised in that mole addition of the catalyst is 0.01-
0.12mol%.
4. synthetic method according to claim 1, it is characterised in that the raw material aldehyde is aromatic aldehyde, preferably phenyl-pentafluoride first
The fluoro- 3- tolyl aldehydes of aldehyde, 2,4,6- trifluro benzaldehydes, 4-, the fluoro- 3- trifluoromethylated benzaldehydes of 4-, the chloro- 4- fluorobenzaldehydes of 3-,
The bromo- 4- fluorobenzaldehydes of 3-, 4,5- difluoros salicylide, the fluoro- 1- naphthaldehydes of 4-, 2- cyano group -4- fluorobenzaldehydes, 2- amino -4- fluorobenzene
Formaldehyde, 2- nitro -4- fluorobenzaldehydes.
5. synthetic method according to claim 1, it is characterised in that the raw material o-phenylenediamine class, preferably bromine neighbour's benzene two
Amine, adjacent chlorine o-phenylenediamine, adjacent fluorine o-phenylenediamine, to chlorine o-phenylenediamine, to bromine o-phenylenediamine, to methyl-o-phenylenediamine, it is adjacent to fluorine
Phenylenediamine, to cyano group o-phenylenediamine, to nitro-o-phenylenediamine, 4,5- difluorobenzene -1,2- diamines, 4,5- dimethyl -1,2- benzene two
Amine.
6. synthetic method according to claim 1, it is characterised in that the solvent is toluene, acetonitrile, tetrahydrofuran
(THF), one kind in dimethyl sulfoxide (DMSO), DMF (DMF).
7. synthetic method according to claim 1, it is characterised in that the condition of the catalytic reaction is：At 0-120 DEG C
Reaction 0.5-12 hours.
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| CN111620896A (en) * | 2020-06-11 | 2020-09-04 | 石河子大学 | Preparation method of tetra-coordinated N, N-chelated diaryl borate compound with 8-aminoquinoline derivative as bidentate ligand |
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|---|---|---|---|---|
| CN101481355A (en) * | 2009-02-20 | 2009-07-15 | 中山大学 | Preparation of 2-substituted benzimidazole |
| CN106861757A (en) * | 2017-03-08 | 2017-06-20 | 湖南大学 | The organic boron of a kind of fluorescence labeling/nitrogen lewis acid base bifunctional catalyst and preparation method thereof |
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| CN101481355A (en) * | 2009-02-20 | 2009-07-15 | 中山大学 | Preparation of 2-substituted benzimidazole |
| CN106861757A (en) * | 2017-03-08 | 2017-06-20 | 湖南大学 | The organic boron of a kind of fluorescence labeling/nitrogen lewis acid base bifunctional catalyst and preparation method thereof |
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| CN111620896A (en) * | 2020-06-11 | 2020-09-04 | 石河子大学 | Preparation method of tetra-coordinated N, N-chelated diaryl borate compound with 8-aminoquinoline derivative as bidentate ligand |
| CN111620896B (en) * | 2020-06-11 | 2023-04-07 | 石河子大学 | Preparation method of tetra-coordinated N, N-chelated diaryl borate compound with 8-aminoquinoline derivative as bidentate ligand |
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