CN102250021B - Method for preparing quinoxaline compounds and benzimidazole compounds - Google Patents
Method for preparing quinoxaline compounds and benzimidazole compounds Download PDFInfo
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- CN102250021B CN102250021B CN 201110106702 CN201110106702A CN102250021B CN 102250021 B CN102250021 B CN 102250021B CN 201110106702 CN201110106702 CN 201110106702 CN 201110106702 A CN201110106702 A CN 201110106702A CN 102250021 B CN102250021 B CN 102250021B
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- LHZACPVONBOQEW-UHFFFAOYSA-N Cc1nc(cccc2)c2nc1-c1cccc(F)c1 Chemical compound Cc1nc(cccc2)c2nc1-c1cccc(F)c1 LHZACPVONBOQEW-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a method for preparing quinoxaline compounds shown in formula (I) and benzimidazole compounds shown in formula (II), which comprises the following steps: reacting allenic compounds shown in formula (III) in an inert organic solvent at 25-90 DEG C for 1-48 hours under the action of a catalyst, protonic acid and water; then adding oxalic acid and o-phenylenediamine, and reacting at 50-120 DEG C for 1-24 hours; and after the reaction, carrying out post treatment on the reaction liquid to obtain the quinoxaline compounds shown in formula (I) and the benzimidazole compounds shown in formula (II), wherein the catalyst is triphenyl gold chloride and silver tetrafluoroborate; the protonic acid is concentrated sulfuric acid, and methanesulfonic acid or p-toluenesulfonic acid or trifluoroacetic acid; and the inert organic solvent is an organic solvent which can not react with the allenic compounds. By using the one-pot method to prepare the quinoxaline compounds, the invention has the advantages of mild reaction conditions, convenient operation process and high product purity.
Description
(1) technical field
The present invention relates to a kind of preparation method of pharmaceutical intermediate, particularly a kind of quinoline the preparation method of cilin analog compound and benzimidazoles compound.
(2) background technology
Quinoline Nuo Xilin is a kind of important nitrogen-containing heterocycle compound, and many pharmacologically actives are arranged, as protozoacide, antibiotic, antimycotic and anticancer pharmacologically active.Synthetic quinoline the method in XiLin be mainly that condensation reaction by 1,2-diketone and O-Phenylene Diamine obtains (Alireza Hasaninejad, AbdolkarimZare, Mohammad Reza Mohammadizadeh, ARKIVOC (2008), xiii, 28-35).
Benzoglyoxaline is a kind of important nitrogen-containing heterocycle compound, and imidazole group, as the part of group amino side-chain, plays the bioactive Main Function of peptide and protein.The imidazole group of functionalization also has many pharmacologically actives, as anti-HIV, anti-faint, calcium antagonist and inhibitor, antihistamine, effect (Synthetic Communications, 39 (18), the 3232-3242 such as calm; 2009, E-Journal ofChemisrty, 5 (3), 447-452; 2008).Although the synthetic method of relevant quinoline Nuo Xilin and benzoglyoxaline has some reports, but still have a lot of defects: as raw materials used, be difficult to obtain, the scope of application is not wide, limitation is larger, complex operation step, and the condition harshness, therefore limited its applicability.
(3) summary of the invention
The object of the invention be to provide a kind of quinoline the preparation method of cilin analog compound and benzimidazoles compound, the method processing condition gentleness, use range is extensive, pass through one pot reaction, one-step synthesis quinoline cilin analog compound and benzimidazoles compound, the raw material that has overcome prior art is not easy to obtain, the shortcomings such as complex operation.
The technical solution used in the present invention is:
Quinoline shown in a kind of formula (I) the preparation method of the benzimidazoles compound shown in cilin analog compound and formula (II), described method is: the connection vinyl compound shown in formula (III) is under the effect of catalyzer, protonic acid and water, in inert organic solvents, 25～90 ℃ of reaction 1～48h, add again oxalic acid and O-Phenylene Diamine to react 1～24h under 50～120 ℃, reaction finish by the reaction solution aftertreatment make the quinoline shown in formula (I) the benzimidazoles compound shown in cilin analog compound and formula (II); Described catalyzer is triphenyl gold trichloride and silver tetrafluoroborate; Described protonic acid is the vitriol oil, methylsulfonic acid, tosic acid or trifluoroacetic acid; Described inert organic solvents for not with the aitiogenic organic solvent of described vinyl compound, the feed intake ratio of amount of substance of connection vinyl compound shown in described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.001～0.2: 0.001～0.2, connection vinyl compound shown in described formula (III) is 1: 0.001～0.05: 0.05～40.0 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in described formula (III) is 1: 0.01～0.4: 0.03～1.5 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine;
Formula (I), (II) and (III) in R be phenyl, to butyl phenyl, to bromophenyl or a fluorophenyl.
The cyclic ether compounds of the alkyl substituted benzene compounds of the halogenated hydrocarbon compound that described inert organic solvents is C1～C4, C7～C10, the aliphatic ether compounds of C2～C4 or C4～C8, be preferably one of following: methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane, more preferably dioxane.
Described protonic acid is preferably 95～98% vitriol oils.
Further, the feed intake ratio of amount of substance of connection vinyl compound shown in described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound shown in described formula (III) is 1: 0.005～0.02: 8.3～33.4 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in described formula (III) is 1: 0.2: 0.7 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine.
The volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in formula (III).
Described quinoline the aftertreatment described in the preparation method of cilin analog compound and benzimidazoles compound be: after reaction finishes, add water in reaction solution, be extracted with ethyl acetate, get organic layer with filtering after anhydrous sodium sulfate drying, the filtrate distillation is carried out column chromatography as follows except the chromatography column of packing into after desolventizing:
(1) chromatography column first using sherwood oil, within 5: 1, as developping agent, TLC follows the tracks of and collects R the ethyl acetate volume ratio
fthe elutriant that value is 0.6～0.7, elutriant removes eluent under reduced pressure, obtain the quinoline shown in formula (I) cilin analog compound; Described TLC developping agent is the volume ratio sherwood oil of 5: 1, ethyl acetate mixture;
(2) chromatography column is usingd sherwood oil, ethyl acetate volume ratio 3: 1 again as developping agent, and TLC follows the tracks of and collects R
fthe elutriant that value is 0.25～0.4, elutriant removes eluent under reduced pressure, obtains the benzimidazoles compound shown in formula (II); Described TLC developping agent is the volume ratio sherwood oil of 3: 1, ethyl acetate mixture.
Further, preferred R in described step (1)
fbe worth the elutriant of collecting at 0.6～0.65 o'clock, remove eluent under reduced pressure, obtain the quinoline shown in formula (I) cilin analog compound; In described step (2), get R
fvalue is 0.3～0.35 o'clock elutriant of collecting, and removes eluent under reduced pressure, obtains the benzimidazoles compound shown in formula (II).
Further, described quinoline cilin analog compound, the preparation method of benzimidazoles compound, described method recommends to carry out according to following steps: by connection vinyl compound and the triphenyl gold trichloride shown in formula (III), silver tetrafluoroborate, the vitriol oil and water mix, in inert organic solvents, 50～80 ℃ of reaction 2～20h, add again oxalic acid and O-Phenylene Diamine to react 2～20h under 60～90 ℃, TLC follows the tracks of reaction, reaction finishes reaction solution is added to water, be extracted with ethyl acetate, get organic layer with filtering after anhydrous sodium sulfate drying, the filtrate distillation is carried out column chromatography except the chromatography column of packing into after desolventizing, (1) chromatography column is first with sherwood oil, the ethyl acetate volume ratio as eluent is carried out column chromatography at 5: 1, TLC follows the tracks of and collects R
fthe elutriant that value is 0.6～0.65, described step (1) TLC developping agent is the volume ratio sherwood oil of 5: 1, ethyl acetate mixture, elutriant removes eluting solvent under reduced pressure, the quinoline shown in acquisition formula (I) cilin analog compound, (2) chromatography column is usingd sherwood oil, ethyl acetate volume ratio again and as eluent is carried out column chromatography at 3: 1, and TLC follows the tracks of and collects R
fthe elutriant that value is 0.3～0.35, described step (2) TLC developping agent is the volume ratio sherwood oil of 3: 1, ethyl acetate mixture, elutriant removes eluting solvent under reduced pressure, the benzimidazoles compound shown in acquisition formula (II), described inert organic solvents is methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane, connection vinyl compound shown in described formula (III) and triphenyl gold trichloride, the feed intake ratio of amount of substance of silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound and protonic acid shown in described formula (III), the ratio of the amount of substance that feeds intake of water is 1: 0.005～0.02: 8.3～33.4, connection vinyl compound and oxalic acid shown in described formula (III), the ratio of the amount of substance that feeds intake of O-Phenylene Diamine is 1: 0.2: 0.7, the volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in formula (III).
Compared with prior art, beneficial effect of the present invention is mainly reflected in: the present invention adopt one kettle way, a step prepare quinoline cilin analog compound and benzimidazoles compound, reaction conditions is gentle, easy to operate, product purity is high, has prospects for commercial application is widely arranged.
(4) embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Embodiment 1 quinoline cilin analog compound I-a, benzimidazoles compound II-a
By 58mg (0.5mmol) phenylpropyl alcohol diene, 4.94mg (0.01mmol) triphenylphosphine gold trichloride ((PPh)
3auCl), 7.8mg (0.04mmol) silver tetrafluoroborate, 98% vitriol oil 2uL (0.005mmol) and 150uL (8.3mmol) water mix in the 1mL dioxane, under 60 ℃, reaction is 24 hours, add again 37.8mg (0.35mmol) O-Phenylene Diamine, 9.0mg (0.1mmol) oxalic acid, 80 ℃ of lower back flow reaction 4 hours, TLC follows the tracks of detection, reaction finishes with ethyl acetate (50mL * 3) extraction, anhydrous sodium sulfate drying, filter, concentrated, with the silica gel column chromatography separation, (the chromatography column height is 20cm, and diameter is 1cm; Elution flow rate is 1mL/min) (eluent: V
sherwood oil: V
ethyl acetate=5: 1), TLC (developping agent: V
sherwood oil: V
ethyl acetate=5: 1) follow the tracks of and detect collection R
fvalue 0.6～0.65 elutriant, remove eluent by the elutriant underpressure distillation, drying, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 31.2mg, yield is 28.4%, orange solids; Then, column chromatography (eluent: V
sherwood oil: V
ethyl acetate=3: 1), TLC (developping agent: V
sherwood oil: V
ethyl acetate=3: 1) follow the tracks of and detect collection R
fthe elutriant of value 0.3～0.35, remove eluent by the elutriant underpressure distillation, and drying, obtain 1-benzyl-2-Phenylbenzimidazole (II-a) 25.8mg, and yield is 36.4%, white solid.
1H?NMR(500MHz，CDCl
3)：
(I-a)：δ8.13-8.06(m，2H)，7.75-7.64(m，4H)，7.51-7.45-(m，3H)，2.78(s，3H)
(II-a)：δ7.88-7.86(m，1H)，7.70-7.68(m，2H)，7.48-7.43(m，3H)，7.35-7.20(m，6H)，7.11-7.10(m，2H)，5.46(s，2H).
Embodiment 2 quinolines cilin analog compound I-a, benzimidazoles compound II-a
Change dioxane into tetrahydrofuran (THF), other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 9.53mg, yield is 8.7%; 1-benzyl-2-Phenylbenzimidazole (II-a) 6.58mg, yield is 9.3%.
Embodiment 3
Change dioxane into toluene, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 20.0mg, yield is 18.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.5mg, yield is 27.5%.
Embodiment 4
Change dioxane into 1,2-ethylene dichloride, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.0mg, yield is 24.5%, 1-benzyl-2-Phenylbenzimidazole (II-a) 22.3mg, yield is 31.5%.
Embodiment 5
Change dioxane into ether, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 13.9mg, yield is 12.6%, 1-benzyl-2-Phenylbenzimidazole (II-a) 15.5mg, yield is 21.8%.
Embodiment 6
Change 98% vitriol oil into trifluoroacetic acid, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 26.1mg, yield is 23.7%, 1-benzyl-2-Phenylbenzimidazole (II-a) 21.6mg, yield is 30.4%.
Embodiment 7
Change 98% vitriol oil into methylsulfonic acid, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.7mg, yield is 25.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 27.1mg, yield is 38.2%.
Embodiment 8
Change 98% vitriol oil into tosic acid, other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 18.6mg, yield is 16.9%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.7mg, yield is 27.8%.
Embodiment 9
Change the amount of 98% vitriol oil into 5.2uL (0.01mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 21.6mg, yield is 19.7%, 1-benzyl-2-Phenylbenzimidazole (II-a) 15.9mg, yield is 22.3%.
Embodiment 10
Change the amount of 98% vitriol oil into 0.65uL (0.0025mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 31.4mg, yield is 28.6%, 1-benzyl-2-Phenylbenzimidazole (II-a) 22.2mg, yield is 31.2%.
Embodiment 11
Change the amount of water into 0.075mL (4.17mmol), other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 13.0mg, yield is 9.4%, 1-benzyl-2-Phenylbenzimidazole (II-a) 20.3mg, yield is 20.5%
Embodiment 12
Change the amount of water into 0.3mL (16.7mmol), other operate with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 26.2mg, yield is 19.0%, 1-benzyl-2-Phenylbenzimidazole (II-a) 17.2mg, yield is 17.4%
Embodiment 13
Change the amount of triphenylphosphine gold trichloride into 2.47mg (0.005mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 24.0mg, yield is 17.3%, 1-benzyl-2-Phenylbenzimidazole (II-a) 21.1mg, yield is 22.0%.
Embodiment 14
Change the amount of triphenylphosphine gold trichloride into 9.88mg (0.02mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.9mg, yield is 20.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 27.4mg, yield is 27.7%.
Embodiment 15
Change the amount of silver tetrafluoroborate into 3.9mg (0.02mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 20.9mg, yield is 15.1%, 1-benzyl-2-Phenylbenzimidazole (II-a) 18.4mg, yield is 18.4%.
Embodiment 16
Change the amount of silver tetrafluoroborate into 15.6mg (0.08mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 16.4mg, yield is 11.9%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.8mg, yield is 20.0%.
Embodiment 17 quinolines cilin analog compound (I-b), benzimidazoles compound (II-b)
With the butylbenzene propadiene is replaced to the phenylpropyl alcohol diene, other operate with embodiment 1, obtain target product formula (I-b) 45.0mg, and yield is 32.6%, orange solids, and target product formula (II-b) 33.8mg, yield is 34.2%, white solid.
1H?NMR(500MHz，CDCl
3)：
(I-b)：δ8.13-8.05(m，2H)，7.76-7.70(m，2H)，7.60-7.58(m，2H)，7.36-7.34(m，2H)，2.81(s，3H)，2.73-2.70(m，2H)，1.70-1.64(m，2H)，1.45-1.37(m，2H)，0.98-0.95(m，3H)；
(II-b)：δ7.86-7.84(m，1H)，7.62-7.61(m，2H)，7.30-7.20(m，5H)，7.13-7.12(m，2H)，7.02-7.00(m，2H)，5.42(s，2H)，2.67-2.57(m，4H)，1.63-1.56(m，4H)，1.38-1.24(m，4H)，0.94-0.91(m，6H).
Embodiment 18 quinolines cilin analog compound I-c
Replace the phenylpropyl alcohol diene with a fluorobenzene propadiene, other operate with embodiment 1, obtain target product formula (I-c) 33.2mg, and yield is 27.9%, orange solids.
1H?NMR(500MHz，CDCl
3)：
(I-c)：δ8.13-8.06(m，2H)，7.79-7.73(m，2H)，7.54-7.38(m，3H)，7.23-7.19(m，1H)，2.80(s，3H).
Embodiment 19 quinolines cilin analog compound I-d, benzimidazoles compound II-d
With the bromobenzene propadiene is replaced to the phenylpropyl alcohol diene, other operate with embodiment 1, obtain target product formula (I-d) 48.9mg, and yield is 32.8%, orange solids, and target product formula (II-d) 31.6mg, yield is 28.7%, faint yellow solid.
1H?NMR(500MHz，CDCl
3)：
(I-d)：δ8.12-8.05(m，2H)，7.79-7.72(m，2H)，7.72-7.66(m，2H)，7.58-7.55(m，2H)，2.79(s，3H)；
(II-d)：δ7.88-7.87(m，1H)，7.70-7.68(m，2H)，7.50-7.43(m，3H)，7.35-7.21(m，4H)，7.10-7.11(m，2H)，5.46(s，1H).
Claims (9)
- Quinoline shown in a formula I the preparation method of the benzimidazoles compound shown in cilin analog compound and formula II, it is characterized in that described method is: the connection vinyl compound shown in formula III is under the effect of catalyzer, protonic acid and water, in inert organic solvents, 25 ~ 90 ℃ of reaction 1 ~ 48h, add again oxalic acid and O-Phenylene Diamine to react 1 ~ 24h under 50 ~ 120 ℃, reaction finish by the reaction solution aftertreatment make the quinoline shown in formula I the benzimidazoles compound shown in cilin analog compound and formula II, described catalyzer is triphenyl gold trichloride and silver tetrafluoroborate, described protonic acid is the vitriol oil, methylsulfonic acid, tosic acid or trifluoroacetic acid, the halogenated hydrocarbon compound that described inert organic solvents is C1 ~ C4, the alkyl substituted benzene compounds of C7 ~ C10, the aliphatic ether compounds of C2 ~ C4 or the cyclic ether compounds of C4 ~ C8, connection vinyl compound shown in described formula III and triphenyl gold trichloride, the feed intake ratio of amount of substance of silver tetrafluoroborate is 1:0.001 ~ 0.2:0.001 ~ 0.2, connection vinyl compound and protonic acid shown in described formula III, the ratio of the amount of substance that feeds intake of water is 1:0.001 ~ 0.05:0.05 ~ 40.0, connection vinyl compound and oxalic acid shown in described formula III, the ratio of the amount of substance that feeds intake of O-Phenylene Diamine is 1:0.01 ~ 0.4:0.03 ~ 1.5,
In formula I, (II) and (III) R be phenyl, to butyl phenyl, to bromophenyl or a fluorophenyl. - Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described inert organic solvents is one of following: methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane.
- Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described inert organic solvents is dioxane.
- Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described protonic acid is 95 ~ 98% vitriol oils.
- Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that the feed intake ratio of amount of substance of the connection vinyl compound shown in described formula III and triphenyl gold trichloride, silver tetrafluoroborate is 1:0.01 ~ 0.04:0.04 ~ 0.16, connection vinyl compound shown in described formula III is 1:0.005 ~ 0.02:8.3 ~ 33.4 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in described formula III is 1:0.2:0.7 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine.
- Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that the volumetric usage of described inert organic solvents is counted 0.5 ~ 5mL/mmol with the connection vinyl compound amount of substance shown in formula III.
- Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described aftertreatment is: after reaction finishes, add water in reaction solution, be extracted with ethyl acetate, get organic layer with filtering after anhydrous sodium sulfate drying, the filtrate distillation is carried out column chromatography as follows except the chromatography column of packing into after desolventizing:(1) chromatography column is usingd sherwood oil, ethyl acetate volume ratio 5:1 and is carried out column chromatography as eluent, and TLC follows the tracks of and collects R fthe elutriant that value is 0.6 ~ 0.7, elutriant removes eluent under reduced pressure, obtain the quinoline shown in formula I cilin analog compound; Sherwood oil, ethyl acetate mixture that the developping agent of described step (1) TLC is volume ratio 5:1;(2) chromatography column is usingd sherwood oil, ethyl acetate volume ratio 3:1 again as eluent, and TLC follows the tracks of and collects R fthe elutriant that value is 0.25 ~ 0.4, elutriant removes eluent under reduced pressure, obtains the benzimidazoles compound shown in formula II; Sherwood oil, ethyl acetate mixture that the developping agent of described step (2) TLC is volume ratio 3:1.
- Quinoline as claimed in claim 7 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that getting R in described step (1) fbe worth the elutriant of collecting at 0.6 ~ 0.65 o'clock, remove eluent under reduced pressure, obtain the quinoline shown in formula I cilin analog compound; In described step (2), get R fvalue is 0.3 ~ 0.35 o'clock elutriant of collecting, and removes eluent under reduced pressure, obtains the benzimidazoles compound shown in formula II.
- Quinoline as claimed in claim 1 cilin analog compound, the preparation method of benzimidazoles compound, it is characterized in that described method carries out according to following steps: by the connection vinyl compound shown in formula III and triphenyl gold trichloride, silver tetrafluoroborate, the vitriol oil and water mix, in inert organic solvents, 50 ~ 80 ℃ of reaction 2 ~ 20h, add again oxalic acid and O-Phenylene Diamine to react 2 ~ 20h under 60 ~ 90 ℃, TLC follows the tracks of reaction, reaction finishes reaction solution is added to water, be extracted with ethyl acetate, get organic layer with filtering after anhydrous sodium sulfate drying, the filtrate distillation is carried out column chromatography except the chromatography column of packing into after desolventizing, (1) chromatography column is first with sherwood oil, 5:1 is as eluent for the ethyl acetate volume ratio, TLC follows the tracks of and collects R fthe elutriant that value is 0.6 ~ 0.65, elutriant removes eluent under reduced pressure, obtain the quinoline shown in formula I cilin analog compound, (2) chromatography column is usingd sherwood oil, ethyl acetate volume ratio 3:1 again as eluent, and TLC follows the tracks of and collects R fthe elutriant that value is 0.3 ~ 0.35, elutriant removes eluent under reduced pressure, obtains the benzimidazoles compound shown in formula II, described inert organic solvents is methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane, the feed intake ratio of amount of substance of connection vinyl compound shown in described formula III and triphenyl gold trichloride, silver tetrafluoroborate is 1:0.01 ~ 0.04:0.04 ~ 0.16, connection vinyl compound shown in described formula III is 1:0.005 ~ 0.02:8.3 ~ 33.4 with the ratio of the amount of substance that feeds intake of protonic acid, water, connection vinyl compound shown in described formula III is 1:0.2:0.7 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine, and the volumetric usage of described inert organic solvents is counted 0.5 ~ 5mL/mmol with the connection vinyl compound amount of substance shown in formula III.
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