CN108707116A - A kind of 2- alkyl substituted benzenes benzimidazole derivative and preparation method thereof - Google Patents
A kind of 2- alkyl substituted benzenes benzimidazole derivative and preparation method thereof Download PDFInfo
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- CN108707116A CN108707116A CN201810733408.8A CN201810733408A CN108707116A CN 108707116 A CN108707116 A CN 108707116A CN 201810733408 A CN201810733408 A CN 201810733408A CN 108707116 A CN108707116 A CN 108707116A
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- BXPUDHZQKRBSLM-UHFFFAOYSA-N CC(C)Cc1nc(cccc2)c2[n]1C(OCc1ccccc1)=O Chemical compound CC(C)Cc1nc(cccc2)c2[n]1C(OCc1ccccc1)=O BXPUDHZQKRBSLM-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
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
A kind of 2- alkyl substituted benzenes benzimidazole derivative and preparation method thereof.The invention discloses a kind of 2- alkyl benzimidazoles derivatives and preparation method thereof, and structural formula is：Wherein, R1For formate ester blocking group, R2For alkyl.The present invention has synthesized 2- alkyl benzimidazole derivatives, all has profound significance from organic synthesis and pharmaceutical chemical angle, and the present invention method it is raw materials used be easy to get, high income, reaction condition is mild, and substrate spectrum is wide, and post-processing is easy.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of 2- alkyl substituted benzenes benzimidazole derivative and its system
Preparation Method.
Background technology
Simultaneously imidazoles has a variety of important bioactivity such as sterilization, anti-inflammatory, antiviral, anticancer to 2- alkyl substituted benzenes, extensively
Applied to fields such as natural products, medicine, pesticides.Therefore, the new conjunction of 2- alkyl substituted benzenes benzimidazole compounds and the like
There is important applying value at technique study, paid close attention to by related field researcher.
Traditional 2- alkyl substituted benzenes and imidazoles synthetic method are mainly o-phenylenediamine class compound and containing there are one the synthesis of C
The condensation reaction that is carried out under severe conditions between son, such as reacted with carboxylic acid, aldehyde ketone.In recent years, transition metal-catalyzed
Neighbour's halogenated amino benzenes compounds 2- alkyl substituted benzene benzimidazole compounds synthesized by cascade reaction cause organic synthesis
The concern of scholars.But often there is more reaction step, severe reaction conditions, raw material and need pre-activate, area in said synthesis route
The problems such as field selectivity is poor.Structure diversity based on 2- alkyl substituted benzenes and glyoxaline compound and its in medicine, pesticide, work
Extensive use in industry, developing new Study of synthesis method has far-reaching significance.
Invention content
The purpose of the present invention is to provide a kind of 2- alkyl substituted benzenes benzimidazole derivatives.
Another object of the present invention is to provide the preparation methods of above-mentioned 2- alkyl substituted benzenes benzimidazole derivative.
The specific technical solution of the present invention is as follows：
A kind of 2- alkyl substituted benzenes benzimidazole derivative, structural formula are as follows：
Wherein, R1For formate ester blocking group, R2For alkyl.
In a preferred embodiment of the invention, the R1For Boc or Cbz.
The preparation method of above-mentioned 2- alkyl substituted benzenes benzimidazole derivative, reaction equation are：
In a preferred embodiment of the invention, include the following steps：Under air atmosphere, by the N- phenyl spy penta
Azanol, rhodium catalyst, oxidant, Organic Acid and Base and the chloro-carbon solvent that base amidine, formic acid esters are protected are placed in reaction vessel,
Chloro-carbon solvent is removed after the completion of 50~120 DEG C of reactions, reaction and is derived after purification to get the 2- alkyl benzimidazoles
Object；
Above-mentioned rhodium catalyst is the rhodium salt of trivalent, and above-mentioned oxidant includes the peroxide of silver salt and silver, and above-mentioned alkali includes
Potassium tert-butoxide, potassium carbonate, sodium bicarbonate, sodium hydroxide, triethylamine and diethylamine；
Above-mentioned N- phenylalkyls amidine, formic acid esters protection azanol, rhodium catalyst, oxidant, organic bronsted lowry acids and bases bronsted lowry molar ratio
It is 1: 1~4.0: 0.01~0.1: 0~2.0: 0~6: 0~1.
It is further preferred that the rhodium catalyst, which includes dichloro (pentamethylcyclopentadiene base), closes rhodium (III) dimer.
It is further preferred that the oxidant is to include silver oxide and silver carbonate.
It is further preferred that the organic acid includes benzoic acid, phenylacetic acid, acetic acid and pivalic acid.
It is further preferred that the chloro-carbon solvent includes dichloroethanes, dichloromethane, chloroform and chlorobenzene.More into one
Step is preferred, and the chloro-carbon solvent is dichloroethanes.
It is further preferred that the reaction temperature is 100 DEG C, azanol, the rhodium that the N- phenylalkyls amidine, formic acid esters are protected
Catalyst, oxidant, organic bronsted lowry acids and bases bronsted lowry molar ratio be 1: 3: 0.025: 1: 2: 0.5.
The beneficial effects of the invention are as follows：
1, synthesis of the invention has 2- alkyl benzimidazole derivatives, has from pharmaceutical chemical angle far-reaching
Meaning；
2, method of the invention is raw materials used is easy to get, and high income, reaction condition is mild, and substrate spectrum is wide, and post-processing is easy.
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 target product 1
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4 dryings, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains 56.1mg target products 1,91% yield.The characterize data of the compound
It is as follows：1H NMR (400MHz, CDCl3) δ 7.72 (dd, J=9.9,8.4Hz, 2H), 7.51 (dd, J=7.6,1.6Hz, 2H),
7.46-7.37 (m, 3H), 7.30-7.20 (m, 2H), 5.51 (s, 2H), 1.57 (s, 9H)；13CNMR (101MHz, CDCl3)δ
162.60,150.78,141.26,134.13,134.00,129.08,128.92,128.87,124.41,124.03,119.84,
114.69,69.85,36.08,28.99.HRMS m/z (ESI) calcd for C19H21N2O2(M+H)+309.1598, found
309.1598.
Embodiment 2
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver acetate 0.2mmol,
Pivalic acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains 27.7mg target products 1, yield 45%.
Embodiment 3
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver oxide 0.2mmol,
Pivalic acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains 48.0mg target products 1, yield 78%.
Embodiment 4
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, sodium alkoxide 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in air
In, at 100 DEG C, react 36h.Stop reaction, the mixture of reaction is cooled to room temperature, it is full that 30mL is added in ethyl acetate dilution
It is washed with salt, ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation concentration,
By silica gel column chromatogram separating purification, 41.2mg target products 1, yield 67% are obtained.
Embodiment 5
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, sodium hydroxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains 32.0mg target products 1, yield 52%.
Embodiment 6
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, triethylamine 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in sky
In gas, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, 30mL is added in ethyl acetate dilution
Saturated common salt is washed, and ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, it filters, rotary evaporation is dense
Contracting, by silica gel column chromatogram separating purification, obtains 28.9mg target products 1, yield 47%.
Embodiment 7
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, potassium carbonate 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in sky
In gas, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, 30mL is added in ethyl acetate dilution
Saturated common salt is washed, and ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, it filters, rotary evaporation is dense
Contracting, by silica gel column chromatogram separating purification, obtains 43.1mg target products 1, yield 70%.
Embodiment 8
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Benzoic acid 0.4mmol, potassium carbonate 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in sky
In gas, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, 30mL is added in ethyl acetate dilution
Saturated common salt is washed, and ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, it filters, rotary evaporation is dense
Contracting, by silica gel column chromatogram separating purification, obtains 34.1mg target products 1, yield 51%.
Embodiment 9
By N- phenyl tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Acetic acid 0.4mmol, potassium carbonate 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in air
In, at 100 DEG C, react 36h.Stop reaction, the mixture of reaction is cooled to room temperature, it is full that 30mL is added in ethyl acetate dilution
It is washed with salt, ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation concentration,
By silica gel column chromatogram separating purification, 19.1mg target products 1, yield 31% are obtained.
Embodiment 10
The preparation of target product 2
By N- (p-methylphenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 2 of 59.9mg, 93% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.91-7.86 (m, 1H), 7.77-7.69 (m, 1H), 7.42-
7.36 (m, 5H), 7.35-7.28 (m, 2H), 7.25 (d, J=4.8Hz, 2H), 7.21 (t, J=5.4Hz, 3H), 5.39 (s,
2H), 4.59 (s, 2H)；13C NMR (101MHz, CDCl3) δ 154.34,150.03,142.17,136.45,134.07,
133.00,129.04,128.84,128.79,128.70,128.44,126.64,124.76,124.46,119.86,115.05,
69.59,36.88.HRMS m/z (ESI) calcd for C20H22N2O2(M+H)+323.1754, found 322.323.1752
Embodiment 11
The preparation of target product 3
By N- (p-fluorophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 3 of 43.1mg, 66% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.61 (dd, J=8.7,5.1Hz, 0H), 7.54-7.49 (m,
0H), 7.48-7.40 (m, 0H), 7.01 (td, J=9.0,2.5Hz, 0H), 5.51 (s, 0H), 1.55 (s, 1H)；13CNMR
(101MHz, CDCl3) δ 163.07 (d, J=3.4Hz), 160.34 (d, J=240.5Hz), 159.15,150.36,137.57,
134.24 (d, J=13.6Hz), 133.88,129.25,129.02,128.95,120.38 (d, J=10.0Hz, 4H), 111.99
(d, J=24.7Hz, 5H), 102.35 (d, J=30.1Hz, 4H), 70.09,36.18,28.95.HRMS m/z (ESI) calcd
for C19H20FN2O2(M+H)+327.1503, found 327.1502.
Embodiment 12
The preparation of target product 4
By N- (rubigan) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 4 of 40.4mg, 59% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.75 (d, J=1.9Hz, 1H), 7.59 (d, J=8.5Hz,
1H), 7.52 (dd, J=7.7,1.6Hz, 2H), 7.49-7.38 (m, 3H), 7.25 (dd, J=8.4,2.0Hz, 1H), 5.52 (s,
2H), 1.55 (s, 9H)；13C NMR (101MHz, CDCl3) δ 163.29,150.30,139.87,134.60,133.85,
130.14,129.27,129.03,128.95,124.59,120.51,115.11,70.19,36.17,28.93.HRMS m/z
(ESI)calcd for C19H20ClN2O2(M+H)+343.1208, found 343.1211.
Embodiment 13
The preparation of target product 5
By N- (p-bromophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 5 of 63.5mg, 82% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.91 (d, J=1.4Hz, 1H), 7.58-7.48 (m, 3H),
7.48-7.36 (m, 4H), 5.51 (s, 2H), 1.55 (d, J=1.3Hz, 9H)；13C NMR (101MHz, CDCl3) δ 163.16,
150.25,140.23,134.97,133.81,129.26,129.03,128.94,127.30,120.92,117.97,117.74,
70.21,36.14,28.91.HRMS m/z (ESI) calcd for C19H20BrN2O2(M+H)+387.0703, found
387.0704.
Embodiment 14
The preparation of target product 6
By N- (to iodophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 6 of 53.8mg, 62% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 8.10 (d, J=1.5Hz, 1H), 7.56 (dd, J=8.4,
1.6Hz, 1H), 7.52 (dd, J=7.8,1.4Hz, 2H), 7.49-7.39 (m, 4H), 5.51 (s, 2H), 1.54 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 162.94,150.26,140.83,135.32,133.77,133.02,129.28,129.04,
128.98,123.80,121.39,88.28,70.24,36.07,28.90.HRMS m/z (ESI) calcd for C19H20IN2O2
(M+H)+435.0564, found 435.0564.
Embodiment 15
The preparation of target product 7
By N- (p-isopropyl phenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol,;RhCp*Cl2]22.5mol%, carbonic acid
Silver-colored 0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2-, bis- chloroethenes
Alkane 1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 7 of 47.6mg, 68% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.60 (d, J=8.2Hz, 1H), 7.54 (dd, J=7.0,
5.3Hz, 3H), 7.48-7.39 (m, 3H), 7.14 (d, J=8.2Hz, 1H), 5.50 (s, 2H), 2.91 (hept, J=6.8Hz,
1H), 1.56 (s, 9H), 1.16 (d, J=6.9Hz, 6H)；13C NMR (101MHz, CDCl3) δ 162.23,150.83,145.64,
139.59,134.16,134.10,129.12,129.11,128.90,123.14,119.36,112.19,69.88,36.02,
34.45,29.01,24.28.HRMS m/z (ESI) calcd for C22H27N2O2(M+H)+351.2067, found
351.2067.
Embodiment 16
The preparation of target product 8
By N- (to methyl mercapto phenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol,;RhCp*Cl2]22.5mol%, carbonic acid
Silver-colored 0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2-, bis- chloroethenes
Alkane 1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 8 of 40.4mg, 57% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.58 (dd, J=5.0,3.2Hz, 2H), 7.55-7.50 (m,
2H), 7.49-7.38 (m, 3H), 7.20 (dd, J=8.4,1.7Hz, 1H), 5.49 (s, 2H), 2.25 (s, 3H), 1.56 (s,
9H)；13C NMR (101MHz, CDCl3) 6162.37,150.53,139.37,134.60,133.93,129.25,129.23,
128.97,123.89,119.86,113.01,70.09,36.10,28.96,16.58.HRMS m/z (ESI) calcd for
C20H23N2O2S (M+H)+355.1475, found 355.1478.
Embodiment 17
The preparation of target product 9
By N- (p-methoxyphenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, carbonic acid
Silver-colored 0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2-, bis- chloroethenes
Alkane 1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 9 of 48.0mg, 71% yield.The change
The characterize data for closing object is as follows：1H NMR (400MHz, CDCl3) δ 7.56 (d, J=8.7Hz, 1H), 7.54-7.50 (m, 2H),
7.46-7.39 (m, 3H), 7.21 (d, J=2.4Hz, 1H), 6.87 (dd, J=8.7,2.5Hz, 1H), 5.49 (s, 2H), 3.60
(s, 3H), 1.56 (s, 9H)；13C NMR (101MHz, CDCl3) δ 161.47,157.42,150.67,135.44,134.67,
134.06,129.15,129.14,128.90,120.09,112.75,99.14,69.90,55.47,36.03,29.01.HRMS
m/z(ESI)calcd for C20H23N2O3(M+H)+339.1703, found 339.1704.
Embodiment 18
The preparation of target product 10
By N- (aminomethyl phenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 10 of 59.9mg, 93% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.64-7.56 (m, 1H), 7.49 (d, J=5.4Hz, 3H),
7.46-7.36 (m, 3H), 7.04 (d, J=8.4Hz, 1H), 5.49 (s, 2H), 2.41 (s, 3H), 1.57 (d, J=1.9Hz,
9H)；13CNMR (101MHz, CDCl3) δ 162.64,150.71,141.50,134.22,133.77,131.95,128.98,
128.83,128.82,125.63,119.80,114.33,69.66,36.06,28.94,21.20.HRMS m/z (ESI) calcd
for C20H23N2O2(M+H)+323.1754, found 323.1754.
Embodiment 19
The preparation of target product 11
By N- (chlorphenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol,;RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 11 of 58.1mg, 85% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.65 (dd, J=17.5,5.3Hz, 2H), 7.49 (d, J=
5.7Hz, 2H), 7.42 (d, J=6.5Hz, 3H), 7.18 (d, J=8.7Hz, 1H), 5.50 (s, 2H), 1.55 (s, 9H)；13C
NMR (101MHz, CDCl3) δ 163.92,150.33,142.19,133.87,132.62,129.51,129.22,128.98,
128.92,124.62,119.70,115.56,70.10,36.21,28.89.HRMS m/z (ESI) calcd for
C19H20ClN2O2(M+H)+343.1208, found 343.1204.
Embodiment 20
The preparation of target product 12
By N- (m-bromophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 12 of 58.1mg, 85% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.74 (d, J=1.8Hz, 1H), 7.49 (d, J=8.8Hz,
1H), 7.40 (dd, J=7.5,1.9Hz, 2H), 7.37-7.30 (m, 3H), 7.23 (dd, J=8.8,1.9Hz, 1H), 5.41 (s,
2H), 1.46 (s, 9H)；13C NMR (101MHz, CDCl3) δ 163.74,150.31,142.59,133.84,133.04,
129.21,128.97,128.91,127.31,122.76,116.93,115.96,70.11,36.19,28.89.HRMS m/z
(ESI)calcd for C19H20BrN2O2(M+H)+387.0703, found 387.0703.
Embodiment 21
The preparation of target product 13
By N- (iodophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 13 of 68.6mg, 79% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 8.03 (d, J=1.0Hz, 1H), 7.52-7.39 (m, 7H),
5.50 (s, 2H), 1.55 (s, 9H)；13C NMR (101MHz, CDCl3) δ 163.36,150.33,142.84,133.83,
133.70,132.98,129.21,128.96,128.91,128.89,116.43,87.28,70.11,36.13,28.89.HRMS
m/z(ESI)calcd for C19H20IN2O2(M+H)+435.0564, found 435.0565.
Embodiment 22
The preparation of target product 14
By N- (o-methyl-phenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 14 of 62.5mg, 97% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.55 (d, J=7.9Hz, 1H), 7.49 (d, J=7.5Hz,
2H), 7.44-7.36 (m, 3H), 7.09 (dt, J=12.7,7.4Hz, 2H), 5.49 (s, 2H), 2.61 (s, 3H), 1.61-1.52
(m, 9H)；13C NMR (101MHz, CDCl3) δ 161.46,150.98,140.51,134.29,133.81,129.94,128.97,
128.85,128.83,124.48,124.09,112.08,69.64,36.14,29.04,16.31.HRMS m/z (ESI) calcd
for C20H23N2O2(M+H)+323.1754, found 323.1754.
Embodiment 23
The preparation of target product 15
By N- (Chloro-O-Phenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, and anhydrous MgSO4 is dried, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 15 of 56.8mg, 83% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.62 (d, J=8.3Hz, 1H), 7.54-7.48 (m, 2H),
7.46-7.38 (m, 3H), 7.28 (d, J=7.8Hz, 1H), 7.13 (t, J=8.1Hz, 1H), 5.51 (s, 2H), 1.57 (s,
9H)；13C NMR (101MHz, CDCl3) δ 163.19,150.48,138.64,135.18,133.85,129.21,129.02,
128.91,124.82,124.74,124.03,113.20,70.17,36.30,28.96.HRMS m/z (ESI) calcd for
C19H20ClN2O2(M+H)+343.1208, found 343.1208.
Embodiment 24
The preparation of target product 16
By N- (o-bromophenyl) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2 one two chloroethenes
Alkane 1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 16 of 58.8mg, 76% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 7.66 (d, J=8.2Hz, 1H), 7.54-7.47 (m, 2H),
7.47-7.40 (m, 4H), 7.07 (t, J=8.1Hz, 1H), 5.51 (s, 2H), 1.57 (s, 9H)；13CNMR (101MHz, CDCl3)
δ 163.08,150.52,140.05,134.71,133.86,129.21,129.01,128.92,127.09,125.12,
113.82,113.59,70.16,36.32,28.94.HRMS m/z (ESI) calcd for C19H20BrN2O2(M+H)+
387.0703 found 387.0703.
Embodiment 25
The preparation of target product 17
By N- (1- naphthalenes) tertiary amyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate
0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, are eventually adding 1,2- dichloroethanes
1.5mL at 100 DEG C, reacts 36h in air.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate is dilute
It releases, the washing of 30mL saturated common salts is added, ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, filtering,
Rotary evaporation concentrates, and by silica gel column chromatogram separating purification, obtains the corresponding target products 17 of 48.7mg, 68% yield.It should
The characterize data of compound is as follows：1H NMR (400MHz, CDCl3) δ 8.63 (d, J=8.2Hz, 1H), 7.85 (t, J=8.4Hz,
2H), 7.67-7.56 (m, 2H), 7.56-7.37 (m, 6H), 5.54 (s, 2H), 1.62 (s, 9H)；13C NMR (101MHz,
CDCl3) δ 160.89,150.96,136.76,134.12,130.76,130.41,129.13,129.00,128.91,127.84,
126.47,125.13,124.68,122.42,114.33,70.00,36.22,29.19.HRMS m/z (ESI) calcd for
C23H23N2O2(M+H)+359.1754, found 359.1756.
Embodiment 26
The preparation of target product 18
By N- phenyl isobutyl base amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains the corresponding target products 18 of 46.3mg, 75% yield.The compound
Characterize data is as follows：1H NMR (400MHz, CDCl3) δ 7.91-7.87 (m, 1H), 7.73-7.68 (m, 1H), 7.50 (dd, J=
7.4,1.4Hz, 2H), 7.47-7.39 (m, 3H), 7.33-7.24 (m, 2H), 5.49 (s, 2H), 3.08 (d, J=7.1Hz, 2H),
2.29-2.14 (m, 1H), 0.97 (d, J=6.6Hz, 6H)；13C NMR (101MHz, CDCl3) δ 155.93,150.38,
142.09,134.14,132.83,129.13,128.91,128.89,124.42,124.36,119.54,114.97,69.65,
39.55,27.51,22.45.HRMS m/z (ESI) calcd for C19H21N2O2(M+H)+309.1598, found
309.1598.
Embodiment 27
The preparation of target product 19
By N- phenycyclopropyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol,
Pivalic acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, is eventually adding 1,2- dichloroethanes 1.5mL,
In air, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, ethyl acetate dilution is added
30mL saturated common salts are washed, and ethyl acetate extracts (10mL × 3), merge organic phase, anhydrous MgSO4It is dry, filtering, rotary evaporation
Concentration, by silica gel column chromatogram separating purification, obtains the corresponding target products 19 of 52.6mg, 90% yield.The compound
Characterize data is as follows：1H NMR (400MHz, CDCl3) δ 7.88-7.84 (m, 1H), 7.63-7.58 (m, 1H), 7.51 (dd, J=
7.8,1.6Hz, 2H), 7.46-7.37 (m, 3H), 7.29-7.21 (m, 2H), 5.52 (s, 2H), 2.83 (tt, J=8.3,
5.1Hz, 1H), 1.31-1.21 (m, 2H), 1.14-1.03 (m, 2H)；13C NMR (101MHz, CDCl3) δ 158.33,150.74,
142.12,134.33,133.05,129.02,128.87,128.70,124.36,124.03,119.23,114.78,69.50,
10.52,9.47.HRMS m/z (ESI) calcd for C18H17N2O2(M+H)+293.1285, found293.1282.
Embodiment 28
The preparation of target product 20
By N- phenylbenzyl amidine 0.2mmol, azanol 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol, it is special
Valeric acid 0.4mmol, potassium tert-butoxide 50mol%, is added sequentially in reaction tube, 1,2- dichloroethanes 1.5mL is eventually adding, in sky
In gas, at 100 DEG C, 36h is reacted.Stop reaction, the mixture of reaction is cooled to room temperature, 30mL is added in ethyl acetate dilution
Saturated common salt is washed, and ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous MgSO4It is dry, it filters, rotary evaporation is dense
Contracting, by silica gel column chromatogram separating purification, obtains the corresponding target products 20 of 38.3mg, 56% yield.The table of the compound
It is as follows to levy data：1H NMR (400MHz, CDCl3) δ 7.91-7.86 (m, 1H), 7.77-7.69 (m, 1H), 7.42-7.36 (m,
5H), 7.35-7.28 (m, 2H), 7.25 (d, J=4.8Hz, 2H), 7.21 (t, J=5.4Hz, 3H), 5.39 (s, 2H), 4.59
(s, 2H)；13C NMR (101MHz, CDCl3) δ 154.34,150.03,142.17,136.45,134.07,133.00,129.04,
128.84,128.79,128.70,128.44,126.64,124.76,124.46,119.86,115.05,69.59,
36.88.HRMS m/z(ESI)calcd for C22H19N2O2(M+H)+343.1441, found 343.1441.
Embodiment 29
The preparation of target product 21
By N- phenyl tertiary amyl amidine 0.2mmol, tert-butyl hydroxy carbamate 0.6mmol ,s [RhCp*Cl2]22.5mol%, silver carbonate 0.2mmol, pivalic acid 0.4mmol, potassium tert-butoxide 50mol% are added sequentially in reaction tube, finally
1,2- dichloroethanes 1.5mL are added, in air, at 100 DEG C, react 36h.Stop reaction, the mixture of reaction is cooled to
The washing of 30mL saturated common salts is added in room temperature, ethyl acetate dilution, and ethyl acetate extracts (10mL × 3), merges organic phase, anhydrous
MgSO4Dry, filtering, rotary evaporation concentration by silica gel column chromatogram separating purification, obtains the corresponding target products of 53.8mg
21,62% yield.The characterize data of the compound is as follows：1H NMR (400MHz, CDCl3) δ 7.77-7.68 (m, 2H), 7.28
(dt, J=7.8,4.2Hz, 2H), 1.72 (s, 9H), 1.59 (s, 9H)；13C NMR (101MHz, CDCl3) δ 162.50,
149.51,141.24,134.20,124.01,123.63,119.76,114.06,85.33,35.89,29.11,28.02.HRMS
m/z(ESI)calcd for C16H23N2O2(M+H)+275.1754, found 275.1753.
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 2- alkyl substituted benzenes benzimidazole derivative, structural formula are as follows：
Wherein, R1For formate ester blocking group, R2For alkyl.It is preferred that the R1For Boc or Cbz.
The preparation method of above-mentioned 2- alkyl substituted benzenes benzimidazole derivative, it is characterised in that：Its reaction equation is：
Specifically comprise the following steps：Under air atmosphere, azanol, rhodium that the N- phenyl tertiary amyl amidine, formic acid esters are protected
Catalyst, oxidant, Organic Acid and Base and chloro-carbon solvent are placed in reaction vessel, and in 50~120 DEG C of reactions, reaction is completed
Chloro-carbon solvent is removed afterwards and after purification to get the 2- alkyl benzimidazoles derivative；
Above-mentioned rhodium catalyst is the rhodium salt of trivalent, and above-mentioned oxidant includes the peroxide of silver salt and silver, and above-mentioned alkali includes
Potassium tert-butoxide, potassium carbonate, sodium bicarbonate, sodium hydroxide, triethylamine and diethylamine；
Above-mentioned N- phenylalkyls amidine, formic acid esters protection azanol, rhodium catalyst, oxidant, organic bronsted lowry acids and bases bronsted lowry molar ratio
It is 1: 1~4.0: 0.01~0.1: 0~2.0: 0~6: 0~1.
Preferably, the rhodium catalyst includes that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer.Described
Oxidant be include silver oxide and silver carbonate.The organic acid includes benzoic acid, phenylacetic acid, acetic acid and pivalic acid.It is described to contain chlorine
Organic solvent includes dichloroethanes, dichloromethane, chloroform and chlorobenzene.
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 (10)
1. a kind of 2- alkyl substituted benzenes benzimidazole derivative, it is characterised in that：Its structural formula is as follows：
Wherein, R1For formate ester blocking group, R2For alkyl.
2. a kind of 2- alkyl substituted benzenes benzimidazole derivative as described in claim 1, it is characterised in that：The R1For Boc or
Cbz。
3. a kind of preparation method of 2- alkyl substituted benzenes benzimidazole derivative as claimed in claim 1 or 2, it is characterised in that：Its
Reaction equation is：
4. preparation method as claimed in claim 3, it is characterised in that：Include the following steps：Under air atmosphere, by the N- benzene
Azanol, rhodium catalyst, oxidant, Organic Acid and Base and the chloro-carbon solvent that base tertiary amyl amidine, formic acid esters are protected, which are placed in reaction, to be held
In device, chloro-carbon solvent is removed after the completion of 50~120 DEG C of reactions, reaction and after purification to get the 2- alkyl benzo miaow
Zole derivatives；
Above-mentioned rhodium catalyst is the rhodium salt of trivalent, and above-mentioned oxidant includes the peroxide of silver salt and silver, and above-mentioned alkali includes tertiary fourth
Potassium alcoholate, potassium carbonate, sodium bicarbonate, sodium hydroxide, triethylamine and diethylamine；
Above-mentioned N- phenylalkyls amidine, formic acid esters protection azanol, rhodium catalyst, oxidant, organic bronsted lowry acids and bases bronsted lowry molar ratio be 1: 1
~4.0: 0.01~0.1: 0~2.0: 0~6: 0~1.
5. preparation method as described in claim 3 or 4, it is characterised in that：The rhodium catalyst includes dichloro (pentamethyl ring
Pentadienyl) close rhodium (III) dimer.
6. preparation method as described in claim 3 or 4, it is characterised in that：The oxidant be include silver oxide and carbonic acid
Silver.
7. preparation method as described in claim 3 or 4, it is characterised in that：The organic acid includes benzoic acid, phenylacetic acid, vinegar
Acid and pivalic acid.
8. preparation method as described in claim 3 or 4, it is characterised in that：The chloro-carbon solvent includes dichloroethanes, two
Chloromethanes, chloroform and chlorobenzene.
9. preparation method as claimed in claim 8, it is characterised in that：The chloro-carbon solvent is dichloroethanes.
10. preparation method as described in claim 3 or 4, it is characterised in that：The reaction temperature is 100 DEG C, the N- phenyl
Acid amidine, formic acid esters protection azanol, rhodium catalyst, oxidant, organic bronsted lowry acids and bases bronsted lowry molar ratio be 1: 3: 0.025: 1: 2:
0.5。
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| CN111253293A (en) * | 2018-11-30 | 2020-06-09 | 中国科学院大连化学物理研究所 | Cyanoalkyl substituted tetra-substituted olefin derivatives and synthesis thereof |
| CN111747875A (en) * | 2019-03-29 | 2020-10-09 | 中国科学院大连化学物理研究所 | Cyanoalkoxy-substituted tetrasubstituted olefin derivatives and synthesis thereof |
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| CN111253293A (en) * | 2018-11-30 | 2020-06-09 | 中国科学院大连化学物理研究所 | Cyanoalkyl substituted tetra-substituted olefin derivatives and synthesis thereof |
| CN111747875A (en) * | 2019-03-29 | 2020-10-09 | 中国科学院大连化学物理研究所 | Cyanoalkoxy-substituted tetrasubstituted olefin derivatives and synthesis thereof |
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