CN108640876A - A kind of Multi substituted benzenes benzimidazole derivative and preparation method thereof - Google Patents
A kind of Multi substituted benzenes benzimidazole derivative and preparation method thereof Download PDFInfo
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- CN108640876A CN108640876A CN201810870509.XA CN201810870509A CN108640876A CN 108640876 A CN108640876 A CN 108640876A CN 201810870509 A CN201810870509 A CN 201810870509A CN 108640876 A CN108640876 A CN 108640876A
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- QCWQQNUVRZVJID-UHFFFAOYSA-N CC(C)(C)c1nc(c(Nc(cccc2)c2C(c2ccc(C)cc2)=O)ccc2)c2[n]1-c(cccc1)c1C(c1ccc(C)cc1)=O Chemical compound CC(C)(C)c1nc(c(Nc(cccc2)c2C(c2ccc(C)cc2)=O)ccc2)c2[n]1-c(cccc1)c1C(c1ccc(C)cc1)=O QCWQQNUVRZVJID-UHFFFAOYSA-N 0.000 description 1
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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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- 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
- C07D405/14—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 three or more hetero rings
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Abstract
The invention discloses a kind of Multi substituted benzenes benzimidazole derivatives and preparation method thereof, and structural formula is as follows：
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of Multi substituted benzenes benzimidazole derivative and its preparation side
Method.
Background technology
Polysubstituted benzimidazole, which has, adjusts immune system, decompression, anti-glycosuria, a variety of important lifes such as anti-inflammatory, anticancer is sick
Object activity, is widely used in the fields such as natural products, medicine, pesticide.Therefore, Multi substituted benzenes benzimidazole compounds and the like
Novel synthesis research have important applying value, paid close attention to by related field researcher.
The polysubstituted method for synthesizing benzoimidazole of tradition is mainly the o-phenylenediamine class compound of benzene and containing there are two the synthesis of C
Condensation reaction between son, such as o-phenylenediamine class compound and aldehyde, carboxylic acid or their derivatives reaction.In recent years, transition gold
The cascade reaction synthesizing benzimidazole compound for belonging to catalysis causes the concern of synthetic organic chemists.But conventional synthesis route
Often there is the problems such as more reaction step, severe reaction conditions, raw material are not easy to obtain, regioselectivity is poor.Transition metal-catalyzed
Synthetic route solves the problems, such as that conventional synthesis route reaction step is more, regioselectivity is poor to a certain extent, however due to
Many transition-metal catalysis need to add oxidant, cause to waste.And anthranil is as a kind of novel amination reagent, instead
It should be not necessarily to additionally add oxidant in the process, it is generally possible to obtain amino, carbonyl difunctionals in simultaneous reactions product, subsequent
There are huge potentiality during organic synthesis.Structure diversity based on benzimidazoles compound and its medicine, pesticide,
Industrial extensive use, developing new Study of synthesis method has far-reaching significance.
Invention content
The purpose of the present invention is to provide a kind of Multi substituted benzenes benzimidazole derivatives.
Another object of the present invention is to provide the preparation methods of above-mentioned Multi substituted benzenes benzimidazole derivative.
Technical scheme is as follows：
A kind of Multi substituted benzenes benzimidazole derivative, structural formula are as follows：
Wherein, R1For H, alkyl, halogen group, alkoxy or alkylthio group, R2For H, alkyl, halogen group or alkoxy, R3
For H, alkyl or aryl.
The preparation method of above-mentioned Multi substituted benzenes benzimidazole derivative, reaction equation are：
N- phenyl benzamidine derivative anthranil derivative Multi substituted benzenes benzimidazole derivatives
Above-mentioned catalyst is that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer, bis- (the 4- isopropyl methyls of dichloro
Phenyl) ruthenium (II) or dichloro (pentamethylcyclopentadiene base) close iridium (III) dimer；Above-mentioned silver salt is silver hexafluoroantimonate, bis- (three
Fluoromethane sulfonyl) acid imide silver or silver trifluoromethanesulfonate；Above-mentioned organic solvent is 1,2- dichloroethanes, 1,2- dichloro-benzenes, chlorine
Benzene, benzotrifluoride, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, n,N-Dimethylformamide, acetonitrile or toluene.
In a preferred embodiment of the invention, including：N- phenyl benzamidine derivative, anthranil are derived
Object, catalyst, silver salt, metal acetate salt and organic solvent are placed in reaction vessel, in 100~110 DEG C of reactions, after the completion of reaction
Organic solvent is evaporated off, is then detached to get the Multi substituted benzenes benzimidazole derivative by column chromatography chromatogram；Above-mentioned N- phenyl benzene
Carboxamidine derivatives, anthranil derivative, catalyst, silver salt and metal acetate salt molar ratio be 0.8~1.2: 2.5~3.5
: 0.02~0.03: 0.08~0.12: 0.25~0.35.
It is further preferred that the catalyst, which is dichloro (pentamethylcyclopentadiene base), closes rhodium (III) dimer.
It is further preferred that the silver salt is bis- (trifluoromethane sulfonyl group) acid imides silver.
It is further preferred that the metal acetate salt is lithium acetate, sodium acetate, zinc acetate, copper acetate or silver acetate.More into
One step is preferred, and the metal acetate salt is lithium acetate.
It is further preferred that the organic solvent is benzotrifluoride, 1,2- dichloro-benzenes or Isosorbide-5-Nitrae-dioxane.
It is further preferred that the N- phenyl benzamidine derivative, anthranil derivative, catalyst, silver salt and metal
The molar ratio of acetate is 1: 3: 0.025: 0.1: 0.3.
The beneficial effects of the invention are as follows：
1, synthesis of the invention has a variety of substituent group benzimidizole derivatives, has from pharmaceutical chemical angle deep
Remote meaning；
2, method of the invention is raw materials used is easy to get, and yield is higher, and reaction condition is mild, good functional group compatibility,
Without oxidant applying, air is as reaction atmosphere.
Specific implementation mode
Technical scheme of the present invention is further detailed and is described below by way of specific implementation mode.
Embodiment 1
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, 1,2- dichloroethanes 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.1,2-, bis- chloroethenes are evaporated off
After alkane, column chromatography for separation obtains 92mg products 1, yield 74%.
Embodiment 2
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, 1,2- dichloro-benzenes 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Column chromatography for separation obtains
96mg products 1, yield 78%.
Embodiment 3
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, chlorobenzene 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After chlorobenzene is evaporated off, column chromatography for separation obtains
To 84mg products 1, yield 68%.
Embodiment 4
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, toluene 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After toluene is evaporated off, column chromatography for separation obtains
To 87mg products 1, yield 70%.
Embodiment 5
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour sodium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column layer
Analyse isolated 93mg products 1, yield 75%.
Embodiment 6
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour silver 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column layer
Analyse isolated 58mg products 1, yield 47%.
Embodiment 7
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour zinc 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column layer
Analyse isolated 69mg products 1, yield 56%.
Embodiment 8
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, extract air, pour nitrogen, are reacted for 24 hours at 110 DEG C.
After benzotrifluoride is evaporated off, column chromatography for separation obtains 104mg products 1, yield 84%.
Embodiment 9
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, extract air, pour oxygen, are reacted for 24 hours at 110 DEG C.
After benzotrifluoride is evaporated off, column chromatography for separation obtains 107mg products 1, yield 87%.
Embodiment 10
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, silver hexafluoroantimonate 0.02mmol, lithium acetate 0.06mmol, three
Toluene fluoride 2mL is added into 25mL reaction tubes, is reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column chromatography purifies to obtain 99mg
Product 1, yield 80%.
Embodiment 11
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.After benzotrifluoride is evaporated off, column layer
Analysis purifying obtains 101mg products 1, yield 82%.
Embodiment 12
The preparation of product 1
By N- phenyl pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, tube sealing, are reacted for 24 hours at 110 DEG C.Benzotrifluoride is evaporated off
Afterwards, column chromatography for separation obtains 106mg products 1, yield 86%.
Embodiment 13
The preparation of product 2
By chloro- 3- phenyl benzo [c] isoxazole of N- (4- isopropyl phenyls) pivaloyl imines amide 0.2mmol, 5-
0.6mmol, dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer 0.005mmol, and bis- (trifluoromethane sulfonyl group) acyls are sub-
Amine silver 0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.It is evaporated off
After benzotrifluoride, column chromatography for separation obtains 111mg products 2, yield 84%.
Embodiment 14
The preparation of product 3
By chloro- 3- phenyl benzo [c] isoxazole of N- (4- aminomethyl phenyls) pivaloyl imines amide 0.2mmol, 5-
0.6mmol, dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer 0.005mmol, and bis- (trifluoromethane sulfonyl group) acyls are sub-
Amine silver 0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.It is evaporated off
After benzotrifluoride, column chromatography for separation obtains 109mg products 3, yield 87%.
Embodiment 15
The preparation of product 4
By N- (4- fluorophenyls) pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-,
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 76mg products 4, yield 60%.
Embodiment 16
The preparation of product 5
By N- (4- chlorphenyls) pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-,
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 58mg products 5, yield 45%.
Embodiment 17
The preparation of product 6
By N- (4- bromophenyls) pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-,
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 103mg products 6, yield 74%.
Embodiment 18
The preparation of product 7
By N- (4- iodophenyls) pivaloyl imines amide chloro- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-,
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 102mg products 7, yield 68%.
Embodiment 19
The preparation of product 8
By chloro- 3- phenyl benzo [c] isoxazoles of N- (4- sulfidomethyls phenyl) pivaloyl imines amide 0.2mmol, 5-
0.6mmol, dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer 0.005mmol, and bis- (trifluoromethane sulfonyl group) acyls are sub-
Amine silver 0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.It is evaporated off
After benzotrifluoride, column chromatography for separation obtains 64mg products 8, yield 49%.
Embodiment 20
The preparation of product 9
By chloro- 3- phenyl benzo [c] isoxazole of N- (4- methoxyphenyls) pivaloyl imines amide 0.2mmol, 5-
0.6mmol, dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer 0.005mmol, and bis- (trifluoromethane sulfonyl group) acyls are sub-
Amine silver 0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.It is evaporated off
After benzotrifluoride, column chromatography for separation obtains 54mg products 9, yield 42%.
Embodiment 21
The preparation of product 10
By N- phenyl pivaloyl imines amide 0.2mmol, 3- phenyl benzo [c] isoxazole 0.6mmol, dichloro (pentamethyl
Cyclopentadienyl group) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, lithium acetate
0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column chromatography point
From obtaining 73mg products 10, yield 67%.
Embodiment 22
The preparation of product 11
By N- phenyl pivaloyl imines amide 0.2mmol, 5- methyl -3- phenyl benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 90mg products 11, yield 78%.
Embodiment 23
The preparation of product 12
By N- phenyl pivaloyl imines amide bromo- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column layer
Analyse isolated 105mg products 12, yield 75%.
Embodiment 24
The preparation of product 13
By N- phenyl pivaloyl imines amide iodo- 3- phenyl benzo [c] the isoxazole 0.6mmol of 0.2mmol, 5-, dichloro (five
Methyl cyclopentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, vinegar
Sour lithium 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.After benzotrifluoride is evaporated off, column layer
Analyse isolated 64mg products 13, yield 40%.
Embodiment 25
The preparation of product 14
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (4- fluorophenyls) benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02
Mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Benzotrifluoride is evaporated off
Afterwards, column chromatography for separation obtains 96mg products 14, yield 82%.
Embodiment 26
The preparation of product 15
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (4- chlorphenyls) benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02
Mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Benzotrifluoride is evaporated off
Afterwards, column chromatography for separation obtains 92mg products 15, yield 75%.
Embodiment 27
The preparation of product 16
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (4- bromophenyls) benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02
Mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Benzotrifluoride is evaporated off
Afterwards, column chromatography for separation obtains 106mg products 16, yield 75%.
Embodiment 28
The preparation of product 17
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (4- trifluoromethyls) benzo [c] isoxazole 0.6mmol,
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 114mg products 17, yield 83%.
Embodiment 29
The preparation of product 18
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (4- aminomethyl phenyls) benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver
0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Trifluoro is evaporated off
After toluene, column chromatography for separation obtains 81mg products 18, yield 70%.
Embodiment 30
The preparation of product 19
By N- phenyl pivaloyl imines amide 0.2mmol, 3- (3- fluorophenyls) benzo [c] isoxazole 0.6mmol, dichloro
(pentamethylcyclopentadiene base) closes rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02
Mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.Benzotrifluoride is evaporated off
Afterwards, column chromatography for separation obtains 87mg products 19, yield 75%.
Embodiment 31
The preparation of product 20
By N- phenyl pivaloyl imines amide 0.2mmol, 5- chloro- 3- (4- methoxyphenyls) benzo [c] isoxazole
0.6mmol, dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer 0.005mmol, and bis- (trifluoromethane sulfonyl group) acyls are sub-
Amine silver 0.02mmol, lithium acetate 0.06mmol, benzotrifluoride 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 110 DEG C.It is evaporated off
After benzotrifluoride, column chromatography for separation obtains 121mg products 20, yield 89%.
Embodiment 32
The preparation of product 21
By N- phenyl pivaloyl imines amide 0.2mmol, 3- methyl benzo [c] isoxazole 0.6mmol, dichloro (pentamethyl
Cyclopentadienyl group) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, lithium acetate
0.06mmol, six alkane 2mL of Isosorbide-5-Nitrae-dioxy are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.Six alkane of Isosorbide-5-Nitrae-dioxy is evaporated off
Afterwards, column chromatography for separation obtains 64mg products 21, yield 76%.
Embodiment 33
The preparation of product 22
By N- phenyl pivaloyls imines amide 0.2mmol, benzo [c] isoxazole 0.6mmol, dichloro (pentamethyl ring penta 2
Alkenyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, lithium acetate
0.06mmol, 1,2- dichloroethanes 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.1,2- dichloroethanes is evaporated off
Afterwards, column chromatography for separation obtains 57mg products 22, yield 72%.
Embodiment 34
The preparation of product 23
By N- phenyl pivaloyl imines amide 0.2mmol, [1,3] dioxole simultaneously [4 ', 5 '：4,5] benzo [1,2-
C] isoxazole 0.6mmol, dichloro (pentamethylcyclopentadiene base) conjunction rhodium (III) dimer 0.005mmol, bis- (fluoroform sulphurs
Acyl group) acid imide silver 0.02mmol, lithium acetate 0.06mmol, 1,2- dichloroethanes 2mL be added into 25mL reaction tubes, 120 DEG C
Lower reaction is for 24 hours.After 1,2- dichloroethanes is evaporated off, column chromatography for separation obtains 75mg products 23, yield 78%.
Embodiment 35
The preparation of product 24
By N- phenyl pivaloyl imines amide 0.2mmol, 5- chlorobenzene simultaneously [c] isoxazole 0.6mmol, dichloro (pentamethyl ring
Pentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, lithium acetate
0.06mmol, six alkane 2mL of Isosorbide-5-Nitrae-dioxy are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.Six alkane of Isosorbide-5-Nitrae-dioxy is evaporated off
Afterwards, column chromatography for separation obtains 72mg products 24, yield 77%.
Embodiment 36
The preparation of product 25
By N- phenyl pivaloyl imines amide 0.2mmol, 5- bromobenzene simultaneously [c] isoxazole 0.6mmol, dichloro (pentamethyl ring
Pentadienyl) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, lithium acetate
0.06mmol, 1,2- dichloroethanes 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.1,2- dichloroethanes is evaporated off
Afterwards, column chromatography for separation obtains 44mg products 25, yield 40%.
Embodiment 37
The preparation of product 26
By N- phenyl pivaloyl imines amide 0.2mmol, 5- methoxyl group benzo [c] isoxazole 0.6mmol, dichloro (five first
Cyclopentadienyl group) close rhodium (III) dimer 0.005mmol, bis- (trifluoromethane sulfonyl group) acid imide silver 0.02mmol, acetic acid
Lithium 0.06mmol, 1,2- dichloroethanes 2mL are added into 25mL reaction tubes, are reacted for 24 hours at 120 DEG C.1,2- dichloroethanes is evaporated off
Afterwards, column chromatography for separation obtains 40mg products 26, yield 44%.
Those of ordinary skill in the art still are able to it is found that when the parameter and group of the present invention change in following ranges
To same as the previously described embodiments or similar technique effect, protection scope of the present invention is still fallen within：
A kind of Multi substituted benzenes benzimidazole derivative, structural formula are as follows：
Wherein, R1For H, alkyl, halogen group, alkoxy or alkylthio group, R2For H, alkyl, halogen group or alkoxy, R3
For H, alkyl or aryl.
The preparation method of above-mentioned Multi substituted benzenes benzimidazole derivative, reaction equation are：
N- phenyl benzamidine derivative anthranil derivative Multi substituted benzenes benzimidazole derivatives
Above-mentioned catalyst is that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer, bis- (the 4- isopropyl methyls of dichloro
Phenyl) ruthenium (II) or dichloro (pentamethylcyclopentadiene base) close iridium (III) dimer；Above-mentioned silver salt is silver hexafluoroantimonate, bis- (three
Fluoromethane sulfonyl) acid imide silver or silver trifluoromethanesulfonate；Above-mentioned organic solvent is 1,2- dichloroethanes, 1,2- dichloro-benzenes, chlorine
Benzene, benzotrifluoride, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, n,N-Dimethylformamide, acetonitrile or toluene；Above-mentioned metal acetate salt
For lithium acetate, sodium acetate, zinc acetate, copper acetate or silver acetate.Still more preferably, the metal acetate salt is lithium acetate.
In a preferred embodiment of the invention, including：N- phenyl benzamidine derivative, anthranil are derived
Object, catalyst, silver salt, metal acetate salt and organic solvent are placed in reaction vessel, in 100~110 DEG C of tube sealing reactions, have been reacted
Organic solvent is evaporated off after, is then detached to get the Multi substituted benzenes benzimidazole derivative by column chromatography chromatogram；Above-mentioned N-
Phenyl benzamidine derivative, anthranil derivative, catalyst, silver salt and metal acetate salt molar ratio be 0.8~1.2: 2.5
~3.5: 0.02~0.03: 0.08~0.12: 0.25~0.35.
The foregoing is only a preferred embodiment of the present invention, therefore cannot limit the scope of implementation of the present invention according to this, i.e.,
According to equivalent changes and modifications made by the scope of the claims of the present invention and description, all should still belong in the range of the present invention covers.
Claims (9)
1. a kind of Multi substituted benzenes benzimidazole derivative, it is characterised in that：Its structural formula is as follows：
Wherein, R1For H, alkyl, halogen group, alkoxy or alkylthio group, R2For H, alkyl, halogen group or alkoxy, R3For H,
Alkyl or aryl.
2. the preparation method of Multi substituted benzenes benzimidazole derivative described in claim 1, it is characterised in that：Its reaction equation
For：
N- phenyl benzamidine derivative anthranil derivative Multi substituted benzenes benzimidazole derivatives
Above-mentioned catalyst is that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer, bis- (the 4- cymols of dichloro
Base) ruthenium (II) or dichloro (pentamethylcyclopentadiene base) close iridium (III) dimer；Above-mentioned silver salt is silver hexafluoroantimonate, bis- (trifluoros
Methane sulfonyl) acid imide silver or silver trifluoromethanesulfonate；Above-mentioned organic solvent be 1,2- dichloroethanes, 1,2- dichloro-benzenes, chlorobenzene,
Benzotrifluoride, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, n,N-Dimethylformamide, acetonitrile or toluene.
3. preparation method as claimed in claim 2, it is characterised in that：Including：By N- phenyl benzamidine derivative, anthranil
Derivative, catalyst, silver salt, metal acetate salt and organic solvent are placed in reaction vessel, in 100~110 DEG C of tube sealing reactions, instead
Should organic solvent be evaporated off after the completion, then be detached to get the Multi substituted benzenes benzimidazole derivative by column chromatography chromatogram；It is above-mentioned
N- phenyl benzamidine derivative, anthranil derivative, catalyst, silver salt and metal acetate salt molar ratio be 0.8~1.2:
2.5~3.5: 0.02~0.03: 0.08~0.12: 0.25~0.35.
4. preparation method as claimed in claim 2 or claim 3, it is characterised in that：The catalyst is dichloro (pentamethylcyclopentadiene
Base) close rhodium (III) dimer.
5. preparation method as claimed in claim 2 or claim 3, it is characterised in that：The silver salt is bis- (trifluoromethane sulfonyl group) acyls
Imines silver.
6. preparation method as claimed in claim 2 or claim 3, it is characterised in that：The metal acetate salt be lithium acetate, sodium acetate,
Zinc acetate, copper acetate or silver acetate.
7. preparation method as claimed in claim 6, it is characterised in that：The metal acetate salt is lithium acetate.
8. preparation method as claimed in claim 2 or claim 3, it is characterised in that：The organic solvent is benzotrifluoride, 1,2- dichloros
Benzene or Isosorbide-5-Nitrae-dioxane.
9. preparation method as claimed in claim 2 or claim 3, it is characterised in that：The N- phenyl benzamidine derivative, anthranil
Derivative, catalyst, silver salt and metal acetate salt molar ratio be 1: 3: 0.025: 0.1: 0.3.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946790A (en) * | 2017-04-26 | 2017-07-14 | 华侨大学 | A kind of preparation method of 1,2 substituted benzimidazole analog derivative |
| CN106946877A (en) * | 2017-02-22 | 2017-07-14 | 沈阳师范大学 | The preparation method and the compound of a kind of nitrogenous fused heterocyclic compound |
| CN107445899A (en) * | 2017-07-19 | 2017-12-08 | 枣庄学院 | A kind of benzimidazoles compound and preparation method thereof |
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2018
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|---|---|---|---|---|
| CN106946877A (en) * | 2017-02-22 | 2017-07-14 | 沈阳师范大学 | The preparation method and the compound of a kind of nitrogenous fused heterocyclic compound |
| CN106946790A (en) * | 2017-04-26 | 2017-07-14 | 华侨大学 | A kind of preparation method of 1,2 substituted benzimidazole analog derivative |
| CN107445899A (en) * | 2017-07-19 | 2017-12-08 | 枣庄学院 | A kind of benzimidazoles compound and preparation method thereof |
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