CN101643378A - Method for synthesizing aryl-linking compound - Google Patents
Method for synthesizing aryl-linking compound Download PDFInfo
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- CN101643378A CN101643378A CN200910090644A CN200910090644A CN101643378A CN 101643378 A CN101643378 A CN 101643378A CN 200910090644 A CN200910090644 A CN 200910090644A CN 200910090644 A CN200910090644 A CN 200910090644A CN 101643378 A CN101643378 A CN 101643378A
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Abstract
The invention discloses a method for synthesizing an aryl-linking compound, belonging to the technical field of organic synthesis. The aryl-linking compound is obtained by subjecting an organic quinquevalent antimony compound and an aryl-boronic acid compound to the Suzuki-Miyaura reaction in the presence of a Pd/C (palladium/carbon) catalyst. The organic quinquevalent antimony compound adopted bythe invention constitutes a good substitute for aryl halides, for the organic quinquevalent antimony compound, as an electrophilic reagent has higher activity than the aryl halide does; Pd/C, as a heterogeneous catalyst, is low-cost and recyclable, thereby reducing the reaction cost and ensuring high yield at the same time, particularly, the yield is higher either at the inert gas atmosphere or directly at the normal atmosphere in the absence of protective inert gas; and the method dispenses with the addition of alkalis, thereby not only preventing the salt as the by-product from being generated, but also allowing compounds sensitive to alkalis to conduct the Suzuki-Miyaura reaction.
Description
Technical field
The invention belongs to technical field of organic synthesis, particularly a kind of synthetic method of aryl-linking compound.
Background technology
At present, the Suzuki-Miyaura cross-coupling reaction becomes in the modern organic synthesis one of the effective means the most about the generation of C-C gradually.This reaction is used in synthetic a large amount of useful organic intermediate in prepared in laboratory medicine and the fine chemistry industry in a large number, especially is applied in the synthetic aspect of aryl-linking compound.The electrophile middle aryl bromo-derivative or the common reaction result of iodo thing that are used in the Suzuki-Miyaura cross-coupling reaction at present are better, and aryl chloride complex or fluoro thing are relatively poor, not even reaction, but, in experiment or industrial production, the bromo-derivative of some compound, iodo thing are not that to be difficult to preparation be exactly that cost is very high, and this has just seriously limited the practical application of this class reaction.Therefore, just press for the new cationoid reaction system of seeking, secondly existing Suzuki-Miyaura cross-coupling reaction all needs to use expensive homogeneous catalyst zeroth order palladium, as four (triphenyl phosphorus) palladium, two (two subunit acetone) palladium etc., the reaction cost height, and cannot reclaim catalyzer.Once more, the Suzuki-Miyaura cross-coupling reaction that uses all need carry out in inert atmosphere at present, prevents catalyst deactivation, and instrument requires and the cost height.At last, use the aryl halides to carry out the Suzuki-Miyaura cross-coupling reaction and also will add a certain amount of alkali acceleration catalysis, therefore product can be supervened unwanted salt, the more important thing is for those alkali-sensitive compounds and has no idea to be used in the Suzuki-Miyaura cross-coupling reaction.
The Jyoji Kurita of Japan has reported a kind of synthetic method of Suzuki-Miyaura cross-coupling reaction, Tetrahedron Letters, 2007,48,721-724.Though this method has been used the electrophilic reagent of organo-antimony compound as the Suzuki-Miyaura reaction; but reaction still needs to use the palladium catalyst that has part, and it costs an arm and a leg, and needs the protection of argon gas atmosphere; to the requirement height of equipment, industrialization cost height.
Summary of the invention
The synthetic method that the purpose of this invention is to provide a kind of aryl-linking compound.
A kind of synthetic method of aryl-linking compound, it is characterized in that this method steps is as follows: the aryl boric acid compounds shown in organic pentavalent antimony compounds shown in the formula (IV) and the formula (VI) obtains the aryl-linking compound shown in the formula V through the Suzuki-Miyaura reaction under the catalysis of palladium carbon, concrete operations are as follows: at nitrogen, under argon gas or the air atmosphere, with organic pentavalent antimony compounds (IV), aryl boric acid compounds (VI), palladium carbon drops among the solvent c, the mol ratio of material of wherein feeding intake is recommended as organic pentavalent antimony compounds (IV): aryl boric acid compounds (VI): palladium carbon=1: (1～10): (0.03～0.15), preferred 1: (3～5): (0.05～0.1), the consumption of solvent c is counted the organic pentavalent antimony compounds of the every gram of 15～30ml (IV) with organic pentavalent antimony compounds (IV), Heating temperature is 20～80 ℃, reacted 6～48 hours, after the reaction solution cooling, through aftertreatment, obtain aryl-linking compound (V), wherein, solvent c is selected from tetrahydrofuran (THF), 1, the 4-dioxane, N, the N-N,N-DIMETHYLACETAMIDE, N, at least a in four kinds of solvents of dinethylformamide, perhaps at least a solvent and the water in four kinds of solvents is (5～20) according to volume ratio: the solution of 1 preparation;
Reaction equation is as follows:
Formula (IV) to formula (VI), R
1Be selected from following a kind of: hydrogen, halogen, aryl, heterocyclic radical, C
1-C
6Alkyl, C
1-C
6Alkyl oxy; R
2Be selected from following a kind of: hydrogen, C
1-C
6Alkyl, trifluoromethyl, trichloromethyl, aryl, heterocyclic radical; R
3Be selected from following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, halogen, CF
3, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkyl sulfenyl, C
1-C
6Alkyl acyl, C
1-C
6Alkyl ester group, hydroxyl C
1-C
6Alkyl; The Ar base is selected from aryl or heterocyclic radical;
Wherein, aryl is selected from following a kind of: phenyl, xenyl, naphthyl; Heterocyclic radical is selected from following a kind of: indyl, quinolyl, thienyl, furyl, pyrryl, pyridyl, imidazolyl, thiazolyl, pyrazinyl, oxazolyl.
Described R
1Preferred following a kind of: hydrogen, fluorine, bromine, chlorine, phenyl, methyl, ethyl, propyl group, sec.-propyl, butyl, methoxyl group, oxyethyl group; Described R
2Preferred following a kind of: hydrogen, methyl, ethyl, propyl group, trifluoromethyl, trichloromethyl, phenyl, pyridyl, thienyl, pyrazinyl; Described R
3Preferred following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, fluorine, chlorine, bromine, iodine, trifluoromethyl, methyl, ethyl, propyl group, sec.-propyl, butyl, the tertiary butyl, methoxyl group, oxyethyl group, methylthio group, formyl radical, methoxycarbonyl, methylol.
It is 5～10% palladium carbon that described palladium carbon is selected from massfraction.
Described aftertreatment is carried out as follows: when reaction solvent is pure organic solvent, and with the reaction solution direct filtration, filtrate solubilizing agent d dilution, constant volume; When reaction solvent is the mixed solution of organic solvent and water, the mixed solution dilute reaction solution of solubilizing agent d and water, wherein, solvent d and water volume ratio are 1 in the solvent d that adds and the mixed solution of water: (1～3), the mixed solution cumulative volume that adds and the volume ratio of reaction solution are 1: (1～5), behind filtration, separatory, dilution, the constant volume, get 1～2ml nitrogen and dry up, add solvent d dilution, constant volume again; Described solvent d is selected from following a kind of: acetonitrile, ether, trichloromethane, methylene dichloride, ethyl acetate, acetone.
Described organic pentavalent antimony compounds (IV) is prepared from through following steps:
(1) with the halogeno-benzene compounds shown in the formula (I) and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony compound shown in the formula (II), concrete operations are as follows: under inert gas atmosphere, in four-hole bottle, add magnesium chips and organic solvent a, and halogeno-benzene compounds (I) is dissolved in organic solvent a adds in the four-hole bottle by dropping funnel, reflux after 3 hours, drip the butter of antimony solution that is dissolved in organic solvent a again, molar ratio is recommended as halogeno-benzene compounds (I): magnesium chips: butter of antimony=(3～3.5): 3: (0.7～1), preferably (3.15～3.45): 3: (0.81～0.87), the consumption of organic solvent a is respectively: the amount of organic solvent a is the every gram magnesium chips of 9～20ml in when beginning reaction container, the amount of the organic solvent a of dissolving halogeno-benzene compounds is the every gram halogeno-benzene of a 1.5～4ml compounds, the amount of the organic solvent a of dissolving butter of antimony is the every gram butter of antimony of 8～12ml, drip and continue to reflux 3 hours, the cooling back is toward wherein dripping saturated aqueous ammonium chloride, separatory is got organic phase, dry, obtain being dissolved in the solution of organic trivalent antimony compound (II) of organic solvent a, wherein, organic solvent a is selected from tetrahydrofuran (THF), ether, at least a in the benzene;
(2) organic trivalent antimony compound (II) obtains the dibrominated pentavalent antimony compounds shown in the formula (III) with the liquid bromine reaction, concrete operations are as follows: with solution concentration to the 20～50ml of the organic trivalent antimony compound (II) that is dissolved in organic solvent a of gained in the step (1), preferred 30～40ml, under-5 ℃ to dropping liquid bromine wherein to colour-fast, stirring at room 2～5 hours, suction filtration, recrystallization obtains dibrominated pentavalent antimony compounds (III);
(3) dibrominated pentavalent antimony compounds (III) and organic carboxyl acid compounds R
2The COOH reaction obtains organic pentavalent antimony compounds (IV), and concrete operations are as follows: with the dibrominated pentavalent antimony compounds (III) and the organic carboxyl acid compounds R of step (2) gained
2COOH is dissolved among the organic solvent b, the consumption of organic solvent b is the every gram dibrominated of a 30～150ml pentavalent antimony compounds, after the stirring at room 0.5～1 hour, add triethylamine, stirring at room is 10～18 hours again, filter then, evaporate to dryness, recrystallization, obtain organic pentavalent antimony compounds (IV), wherein, molar ratio is recommended as dibrominated pentavalent antimony compounds (III): the organic carboxyl acid compounds: triethylamine=1: (2～2.5): (4～20), preferred 1: (2.2～2.4): (10～15), organic solvent b is selected from following a kind of: acetone, methyl alcohol, benzene, toluene, tetrahydrofuran (THF);
Reaction equation is as follows:
Formula (I) is to formula (IV), R
2Among the COOH, X is selected from halogen, preferred chlorine or bromine; R
1Be selected from following a kind of: hydrogen, halogen, aryl, heterocyclic radical, C
1-C
6Alkyl, C
1-C
6Alkyl oxy; R
2Be selected from following a kind of: hydrogen, C
1-C
6Alkyl, trifluoromethyl, trichloromethyl, aryl, heterocyclic radical; R
3Be selected from following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, halogen, CF
3, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkyl sulfenyl, C
1-C
6Alkyl acyl, C
1-C
6Alkyl ester group, hydroxyl C
1-C
6Alkyl; The Ar base is selected from aryl or heterocyclic radical;
Wherein, aryl is selected from following a kind of: phenyl, xenyl, naphthyl; Heterocyclic radical is selected from following a kind of: indyl, quinolyl, thienyl, furyl, pyrryl, pyridyl, imidazolyl, thiazolyl, pyrazinyl, oxazolyl.
Described organic carboxyl acid compounds is selected from following a kind of: formic acid, acetate, propionic acid, butyric acid, trifluoroacetic acid, trichoroacetic acid(TCA), phenylformic acid, pyridine carboxylic acid, thiophenic acid, pyrazine carboxylic acid.
Beneficial effect of the present invention is as follows:
(1) the invention provides the synthetic method of a new aryl-linking compound, organic pentavalent antimony compounds of using has the activity higher than aryl halides as electrophilic reagent in the Suzuki-Miyaura cross-coupling reaction, be a kind of surrogate of good aryl halides therefore;
(2) this heterogeneous catalyst catalysis of the use palladium carbon Suzuki-Miyaura of the invention reaction, not only cheap, and can recycling use, when reducing reaction cost, also guaranteed very high yield;
(3) the present invention has optimized existing Suzuki-Miyaura cross-coupling reaction condition, not only can obtain higher productive rate in inert gas atmosphere, and not adding inertia protection gas, directly also can reach higher yield in air atmosphere;
(4) the present invention uses organo-antimony compound in the Suzuki-Miyaura reaction as electrophilic reagent, can avoid the adding of alkali, not only eliminated the by-product salt that produces, also enlarged the scope of the reactant of Suzuki-Miyaura reaction, made alkali-sensitive compound also can carry out the Suzuki-Miyaura reaction.
Embodiment
The invention will be further described below in conjunction with embodiment:
Embodiment 1 synthetic 4-methyl diphenyl
At first prepare organic pentavalent antimony compounds Ph
3Sb (OOCCH
3)
2, by halogeno-benzene compounds PhCl and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony Compound P h
3Sb, organic trivalent antimony Compound P h
3Sb and liquid bromine reaction obtain dibrominated pentavalent antimony compounds Ph
3SbBr
2, dibrominated pentavalent antimony compounds Ph
3SbBr
2With organic carboxyl acid compounds CH
3The COOH reaction obtains organic pentavalent antimony compounds Ph
3Sb (OOCCH
3)
2, synthetic organic pentavalent antimony compounds Ph
3Sb (OOCCH
3)
2Reaction equation as follows:
The concrete operations step is:
(1) with PhCl and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain Ph
3Sb, concrete operations are as follows: under argon gas atmosphere, in the 250ml four-hole bottle, add the dry ether of crossing of 2.4g (0.1mol) magnesium chips and 40ml, the mixture of 12.4g (0.110mol) PhCl and 40ml ether is added drop-wise in the four-hole bottle by dropping funnel, reflux 3 hours (reflux temperature is the boiling temperature of solvent) preparation Grignard reagent PhMgCl; Then with 6.2g (0.027mol) SbCl
3Be added drop-wise in the Grignard reagent with the mixture of 50ml ether, keep faint backflow (being controlled at the boiling temperature of solvent), after dropwising, continue to reflux 3 hours, the cooling back is toward wherein dripping the saturated NH of 100ml
4The C1 aqueous solution is told organic phase, and water layer extracted with diethyl ether three times merge organic phase, use anhydrous Na
2SO
4Dry 4 hours, filter, obtain being dissolved in organic trivalent antimony Compound P h of ether
3The solution of Sb;
(2) Ph
3Sb and liquid bromine reaction obtain Ph
3SbBr
2, concrete operations are as follows: with the Ph that is dissolved in ether of step (1) gained
3The solution concentration of Sb is cooled to below-5 ℃ with cryosel to the 30ml, to dropping liquid bromine wherein to just colour-fast, stirring at room is 2 hours then, there is flaxen solid to separate out in the reaction solution, with toluene and sherwood oil recrystallization, gets white crystal dibrominated pentavalent antimony compounds Ph behind the suction filtration
3SbBr
2, productive rate 61.5%;
(3) Ph
3SbBr
2With organic carboxyl acid compounds CH
3The COOH reaction obtains Ph
3Sb (OOCCH
3)
2, concrete operations are as follows: get 0.51g (1mmol) Ph
3SbBr
2And 0.14g (2.3mmol) CH
3COOH is dissolved among the 30mlTHF (tetrahydrofuran (THF)), and stirring at room 0.5 hour adds 1ml (7mmol) triethylamine, and stirring at room 12 hours is filtered, and evaporate to dryness THF with methylene dichloride and sherwood oil recrystallization, gets white crystal Ph
3Sb (OOCCH
3)
2, productive rate 85.1%.
Organic pentavalent antimony compounds Ph with preparation
3Sb (OOCCH
3)
2With methylphenylboronic acid is obtained the 4-methyl diphenyl through Suzuki-Miyaura reaction under the catalysis of palladium carbon, the reaction equation of synthetic 4-methyl diphenyl is as follows:
Concrete operations are as follows: get 0.24g (0.5mmol) Ph
3Sb (OOCCH
3)
2And 0.20g (1.5mmol) (mole number of Pd is 0.025mmol to methylphenylboronic acid and 0.053g, all the other are carbon) massfraction is that 5% palladium carbon is in the 10ml round-bottomed bottle, add 7mlTHF, in air atmosphere, in 60 ℃ of following heated and stirred 24 hours, cooling, filter and use the ethyl acetate constant volume in the 25ml volumetric flask, get its 3ml solution again, the ethyl acetate constant volume is behind the volumetric flask of 10ml, advance GC and detect, productive rate is with Ph
3Sb (OOCCH
3)
2Count 109.8%.
Embodiment 2 synthetic 4-methoxyl group terphenyls
At first prepare organic pentavalent antimony compounds (Ph-Ph)
3Sb (OOCCH
3)
2, by halogeno-benzene compounds 4-bromo biphenyl and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony compound (Ph-Ph)
3Sb, organic trivalent antimony compound (Ph-Ph)
3Sb and liquid bromine reaction obtain dibrominated pentavalent antimony compounds (Ph-Ph)
3SbBr
2, dibrominated pentavalent antimony compounds (Ph-Ph)
3SbBr
2With organic carboxyl acid compounds CH
3The COOH reaction obtains organic pentavalent antimony compounds (Ph-Ph)
3Sb (OOCCH
3)
2, synthetic organic pentavalent antimony compounds (Ph-Ph)
3Sb (OOCCH
3)
2Reaction equation as follows:
The concrete operations step is:
(1) with halogeno-benzene compounds and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony compound, concrete operations are as follows: under nitrogen atmosphere, in the 250ml four-hole bottle, add the dry tetrahydrofuran (THF) of crossing of 2.4g (0.1mol) magnesium chips and 40ml, the mixture of 26.7g (0.115mol) 4-bromo biphenyl and 60ml tetrahydrofuran (THF) is added drop-wise in the four-hole bottle by dropping funnel, reflux 3 hours (reflux temperature is the boiling temperature of solvent), preparation Grignard reagent Ph-PhMgBr is then with 6.6g (0.029mol) SbCl
3Be added drop-wise in the Grignard reagent with the mixture of 50ml tetrahydrofuran (THF), keep faint backflow (being controlled at the boiling temperature of solvent), after dropwising, continue to reflux 3 hours, the cooling back is toward wherein dripping the saturated NH of 100ml
4C1 solution is told organic phase, and water layer extracted with diethyl ether three times merge organic phase, use anhydrous Na
2SO
4Dry 4 hours, filter, obtain being dissolved in organic trivalent antimony compound (Ph-Ph) of tetrahydrofuran (THF)
3The solution of Sb;
(2) organic trivalent antimony compound (Ph-Ph)
3Sb and liquid bromine reaction obtain dibrominated pentavalent antimony compounds (Ph-Ph)
3SbBr
2, concrete operations are as follows: with (Ph-Ph) that be dissolved in tetrahydrofuran (THF) of gained in the step (1)
3The solution concentration of Sb is cooled to below-5 ℃ with cryosel to the 30ml, to dropping liquid bromine wherein to just colour-fast, stirring at room is 2 hours then, there is flaxen solid to separate out in the reaction solution, with toluene and sherwood oil recrystallization, gets white crystal (Ph-Ph) behind the suction filtration
3SbBr
2, productive rate 73.6%;
(3) dibrominated pentavalent antimony compounds (Ph-Ph)
3SbBr
2With organic carboxyl acid compounds CH
3The COOH reaction obtains organic pentavalent antimony compounds, and concrete operations are as follows: get 0.74g (1mmol) (Ph-Ph)
3SbBr
2And 0.13g (2.2mmol) CH
3COOH is dissolved in the 40ml tetrahydrofuran (THF), and stirring at room added 1ml (7mmol) triethylamine after 0.5 hour, and stirring at room 12 hours is filtered, and the evaporate to dryness tetrahydrofuran (THF) with ethyl acetate and sherwood oil recrystallization, gets white crystal (Ph-Ph)
3Sb (OOCCH
3)
2, productive rate 80.3%.
Organic pentavalent antimony compounds Ph with preparation
3Sb (OOCCH
3)
2Obtain 4-methoxyl group terphenyl through the Suzuki-Miyaura reaction with methoxyphenylboronic acid under the catalysis of palladium carbon, the reaction equation of synthetic 4-methoxyl group terphenyl is as follows:
Concrete operations are as follows: get 0.35g (0.5mmol) (Ph-Ph)
3Sb (OOCCH
3)
2And 0.23g (1.5mmol) is to methoxyphenylboronic acid and 0.053g (the mole number 0.025mmol of Pd, all the other are carbon) massfraction is that 5% palladium carbon is in the 10ml round-bottomed bottle, add 6mlTHF, in nitrogen atmosphere, 50 ℃ of following heated and stirred 12 hours, cooling, filter methylene dichloride constant volume in the 25ml volumetric flask, get its 5ml solution again, the methylene dichloride constant volume is behind the volumetric flask of 10ml, advance GC and detect, the productive rate that obtains 4-methoxyl group terphenyl is with (Ph-Ph)
3Sb (OOCCH
3)
2Count 85.3%.
Embodiment 3 synthetic 4-bromo-4 '-chlordiphenyls
At first prepare organic pentavalent antimony compounds (p-BrC
6H
4)
3Sb (OOCCF
3)
2, by halogeno-benzene compounds 1, reaction obtains organic trivalent antimony compound (p-BrC with MAGNESIUM METAL under the anhydrous and oxygen-free condition for 4-dibromobenzene and butter of antimony
6H
4)
3Sb, organic trivalent antimony compound (p-BrC
6H
4)
3Sb and liquid bromine reaction obtain dibrominated pentavalent antimony compounds (p-BrC
6H
4)
3SbBr
2, dibrominated pentavalent antimony compounds (p-BrC
6H
4)
3SbBr
2With organic carboxyl acid compounds CF
3The COOH reaction obtains organic pentavalent antimony compounds (p-BrC
6H
4)
3Sb (OOCCF
3)
2, synthetic organic pentavalent antimony compounds (p-BrC
6H
4)
3Sb (OOCCF
3)
2Reaction equation as follows:
The concrete operations step is:
(1) with halogeno-benzene compounds and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony compound, concrete operations are as follows: under argon gas atmosphere, in the 250ml four-hole bottle, add the dry ether of crossing of 2.4g (0.1mol) magnesium chips and 40ml, with 24.8g (0.105mol) 1, the mixture of 4-dibromobenzene and 60ml ether is added drop-wise in the four-hole bottle by dropping funnel, reflux 3 hours (reflux temperature is the boiling temperature of solvent) preparation Grignard reagent p-BrC
6H
4MgBr is then with 6.2g (0.027mol) SbCl
3Be added drop-wise in the Grignard reagent with the mixture of 50ml ether, keep faint backflow (being controlled at the boiling temperature of solvent), after dropwising, continue to reflux 3 hours, the cooling back is toward wherein dripping the saturated NH of 100ml
4C1 solution is told organic phase, and water layer extracted with diethyl ether three times merge organic phase, use anhydrous Na
2SO
4Dry 4 hours, filter, obtain being dissolved in (the p-BrC of ether
6H
4)
3The solution of Sb;
(2) organic trivalent antimony compound (p-BrC
6H
4)
3Sb and liquid bromine reaction obtain dibrominated pentavalent antimony compounds (p-BrC
6H
4)
3SbBr
2, concrete operations are as follows: with (the p-BrC that is dissolved in ether of gained in the step (1)
6H
4)
3The solution concentration of Sb is cooled to below-5 ℃ with cryosel to the 30ml, to dropping liquid bromine wherein to just colour-fast, stirring at room is 2 hours then, there is flaxen solid to separate out in the reaction solution, with toluene and sherwood oil recrystallization, gets white crystal (p-BrC behind the suction filtration
6H
4)
3SbBr
2, productive rate 56.9%;
(3) dibrominated pentavalent antimony compounds (p-BrC
6H
4)
3SbBr
2With organic carboxyl acid compounds CF
3The COOH reaction obtains organic pentavalent antimony compounds, and concrete operations are as follows: get 0.75g (1mmol) (p-BrC
6H
4)
3SbBr
2And 0.27g (2.4mmol) CF
3COOH is dissolved among the 25mlTHF, and stirring at room 0.5 hour adds 1ml (7mmol) triethylamine, and stirring at room 12 hours is filtered, and evaporate to dryness THF with methylene dichloride and sherwood oil recrystallization, gets white crystal (p-BrC
6H
4)
3Sb (OOCCF
3)
2, productive rate 81.2%;
Organic pentavalent antimony compounds (p-BrC with preparation
6H
4)
3Sb (OOCCF
3)
2Obtain 4-bromo-4 '-chlordiphenyl through the Suzuki-Miyaura reaction with 4-chlorobenzene boric acid under the catalysis of palladium carbon, the reaction equation of synthetic 4-bromo-4 '-chlordiphenyl is as follows:
Concrete operations are as follows:
Get 0.41g (0.5mmol) (p-BrC
6H
4)
3Sb (OOCCF
3)
2And 0.24g (1.5mmol) is to 4-chlorobenzene boric acid and 0.074g (the mole number 0.035mmol of Pd, all the other are carbon) massfraction be 5% palladium carbon in the 10ml round-bottomed bottle, add 10mlN, dinethylformamide, under air atmosphere, 60 ℃ of following heated and stirred 36 hours, cooling was filtered in the 25ml volumetric flask, the acetonitrile constant volume, get its 3ml solution acetonitrile constant volume again behind the volumetric flask of 10ml, advance GC and detect, 4-the bromo-4 '-chlordiphenyl productive rate that obtains is with (p-BrC
6H
4)
3Sb (OOCCF
3)
2Count 95.8%.
Claims (10)
1, a kind of synthetic method of aryl-linking compound, it is characterized in that this method steps is as follows: the aryl boric acid compounds shown in organic pentavalent antimony compounds shown in the formula (IV) and the formula (VI) obtains the aryl-linking compound shown in the formula V through the Suzuki-Miyaura reaction under the catalysis of palladium carbon, concrete operations are as follows: at nitrogen, under argon gas or the air atmosphere, with organic pentavalent antimony compounds (IV), aryl boric acid compounds (VI), palladium carbon drops among the solvent c, the mol ratio of material of wherein feeding intake is organic pentavalent antimony compounds (IV): aryl boric acid compounds (VI): palladium carbon=1: (1～10): (0.03～0.15), the consumption of solvent c is counted the organic pentavalent antimony compounds of the every gram of 15～30ml (IV) with organic pentavalent antimony compounds (IV), Heating temperature is 20～80 ℃, reacted 6～48 hours, after the reaction solution cooling, through aftertreatment, obtain aryl-linking compound (V), wherein, solvent c is selected from tetrahydrofuran (THF), 1,-dioxane, N, the N-N,N-DIMETHYLACETAMIDE, N, at least a in four kinds of solvents of dinethylformamide, perhaps at least a solvent and the water in four kinds of solvents is (5～20) according to volume ratio: the solution of 1 preparation;
Reaction equation is as follows:
Formula (IV) to formula (VI), R
1Be selected from following a kind of: hydrogen, halogen, aryl, heterocyclic radical, C
1-C
6Alkyl, C
1-C
6Alkyl oxy; R
2Be selected from following a kind of: hydrogen, C
1-C
6Alkyl, trifluoromethyl, trichloromethyl, aryl, heterocyclic radical; R
3Be selected from following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, halogen, CF
3, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkyl sulfenyl, C
1-C
6Alkyl acyl, C
1-C
6Alkyl ester group, hydroxyl C
1-C
6Alkyl; The Ar base is selected from aryl or heterocyclic radical;
Wherein, aryl is selected from following a kind of: phenyl, xenyl, naphthyl; Heterocyclic radical is selected from following a kind of: indyl, quinolyl, thienyl, furyl, pyrryl, pyridyl, imidazolyl, thiazolyl, pyrazinyl, oxazolyl.
2, the synthetic method of a kind of aryl-linking compound according to claim 1 is characterized in that described R
1Be selected from following a kind of: hydrogen, fluorine, bromine, chlorine, phenyl, methyl, ethyl, propyl group, sec.-propyl, butyl, methoxyl group, oxyethyl group; Described R
2Be selected from following a kind of: hydrogen, methyl, ethyl, propyl group, trifluoromethyl, trichloromethyl, phenyl, pyridyl, thienyl, pyrazinyl; Described R
3Be selected from following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, fluorine, chlorine, bromine, iodine, trifluoromethyl, methyl, ethyl, propyl group, sec.-propyl, butyl, the tertiary butyl, methoxyl group, oxyethyl group, methylthio group, formyl radical, methoxycarbonyl, methylol.
3, the synthetic method of a kind of aryl-linking compound according to claim 1, the mol ratio that it is characterized in that the described material that feeds intake are organic pentavalent antimony compounds (IV): aryl boric acid compounds (VI): palladium carbon=1: (3～5): (0.05～0.1).
4,, it is characterized in that it is 5～10% palladium carbon that described palladium carbon is selected from massfraction according to the synthetic method of claim 1 or 3 described a kind of aryl-linking compounds.
5, the synthetic method of a kind of aryl-linking compound according to claim 1 is characterized in that described aftertreatment carries out as follows: when reaction solvent is pure organic solvent, and with the reaction solution direct filtration, filtrate solubilizing agent d dilution, constant volume; When reaction solvent is the mixed solution of organic solvent and water, the mixed solution dilute reaction solution of solubilizing agent d and water, wherein, solvent d and water volume ratio are 1 in the solvent d that adds and the mixed solution of water: (1～3), the mixed solution cumulative volume that adds and the volume ratio of reaction solution are 1: (1～5), behind filtration, separatory, dilution, the constant volume, get 1～2ml nitrogen and dry up, add solvent d dilution, constant volume again; Described solvent d is selected from following a kind of: acetonitrile, ether, trichloromethane, methylene dichloride, ethyl acetate, acetone.
6, the synthetic method of a kind of aryl-linking compound according to claim 1 is characterized in that described organic pentavalent antimony compounds (IV) is prepared from through following steps:
(1) with the halogeno-benzene compounds shown in the formula (I) and butter of antimony under the anhydrous and oxygen-free condition and the MAGNESIUM METAL reaction obtain organic trivalent antimony compound shown in the formula (II), concrete operations are as follows: under inert gas atmosphere, in four-hole bottle, add magnesium chips and organic solvent a, and halogeno-benzene compounds (I) is dissolved in organic solvent a adds in the four-hole bottle by dropping funnel, reflux after 3 hours, drip the butter of antimony solution that is dissolved in organic solvent a again, molar ratio is halogeno-benzene compounds (I): magnesium chips: butter of antimony=(3～3.5): 3: (0.7～1), the consumption of organic solvent a is respectively: the amount of organic solvent a is the every gram magnesium chips of 9～20ml in when beginning reaction container, the amount of the organic solvent a of dissolving halogeno-benzene compounds is the every gram halogeno-benzene of a 1.5～4ml compounds, the amount of the organic solvent a of dissolving butter of antimony is the every gram butter of antimony of 8～12ml, drip and continue to reflux 3 hours, the cooling back is toward wherein dripping saturated aqueous ammonium chloride, separatory is got organic phase, dry, obtain being dissolved in the solution of organic trivalent antimony compound (II) of organic solvent a, wherein, organic solvent a is selected from tetrahydrofuran (THF), ether, at least a in the benzene;
(2) organic trivalent antimony compound (II) obtains the dibrominated pentavalent antimony compounds shown in the formula (III) with the liquid bromine reaction, concrete operations are as follows: with solution concentration to the 20～50ml of the organic trivalent antimony compound (II) that is dissolved in organic solvent a of gained in the step (1), under-5 ℃ to dropping liquid bromine wherein to colour-fast, stirring at room 2～5 hours, suction filtration, recrystallization obtains dibrominated pentavalent antimony compounds (III);
(3) dibrominated pentavalent antimony compounds (III) and organic carboxyl acid compounds R
2The COOH reaction obtains organic pentavalent antimony compounds (IV), and concrete operations are as follows: with the dibrominated pentavalent antimony compounds (III) and the organic carboxyl acid compounds R of step (2) gained
2COOH is dissolved among the organic solvent b, the consumption of organic solvent b is the every gram dibrominated of a 30～150ml pentavalent antimony compounds, after the stirring at room 0.5～1 hour, add triethylamine, stirring at room is 10～18 hours again, filter then, evaporate to dryness, recrystallization, obtain organic pentavalent antimony compounds (IV), wherein, molar ratio is dibrominated pentavalent antimony compounds (III): organic carboxyl acid compounds: triethylamine=1: (2～2.5): (4～20), and organic solvent b is selected from following a kind of: acetone, methyl alcohol, benzene, toluene, tetrahydrofuran (THF);
Reaction equation is as follows:
Formula (I) is to formula (IV), R
2Among the COOH, X is selected from halogen; R
1Be selected from following a kind of: hydrogen, halogen, aryl, heterocyclic radical, C
1-C
6Alkyl, C
1-C
6Alkyl oxy; R
2Be selected from following a kind of: hydrogen, C
1-C
6Alkyl, trifluoromethyl, trichloromethyl, aryl, heterocyclic radical; R
3Be selected from following a kind of: hydrogen, hydroxyl, carboxyl, nitro, amino, aldehyde radical, halogen, CF
3, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkyl sulfenyl, C
1-C
6Alkyl acyl, C
1-C
6Alkyl ester group, hydroxyl C
1-C
6Alkyl; The Ar base is selected from aryl or heterocyclic radical;
Wherein, aryl is selected from following a kind of: phenyl, xenyl, naphthyl; Heterocyclic radical is selected from following a kind of: indyl, quinolyl, thienyl, furyl, pyrryl, pyridyl, imidazolyl, thiazolyl, pyrazinyl, oxazolyl.
7, the synthetic method of a kind of aryl-linking compound according to claim 6 is characterized in that described X is selected from chlorine or bromine.
8, the synthetic method of a kind of aryl-linking compound according to claim 6, it is following a kind of to it is characterized in that described organic carboxyl acid compounds is selected from: formic acid, acetate, propionic acid, butyric acid, trifluoroacetic acid, trichoroacetic acid(TCA), phenylformic acid, pyridine carboxylic acid, thiophenic acid, pyrazine carboxylic acid.
9, the synthetic method of a kind of aryl-linking compound according to claim 6 is characterized in that molar ratio described in the step (1) is halogeno-benzene compounds (I): magnesium chips: butter of antimony=(3.15～3.45): 3: (0.81～0.87).
10, the synthetic method of a kind of aryl-linking compound according to claim 6 is characterized in that molar ratio described in the step (3) is dibrominated pentavalent antimony compounds (III): organic carboxyl acid compounds: triethylamine=1: (2.2～2.4): (10～15).
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101973855A (en) * | 2010-09-09 | 2011-02-16 | 上海华理生物医药有限公司 | Novel 4,4'-di(alkoxy/aryloxy methyl) biphenyl and preparation thereof |
| CN102942429A (en) * | 2012-11-26 | 2013-02-27 | 大连理工大学 | Method for preparing aza or thia aryl biaryl compound by aid of palladium and carbon catalysts |
| CN105665017A (en) * | 2016-02-19 | 2016-06-15 | 江南大学 | Load type Pd catalyst used for Suzuky-Miyaura coupling reaction and preparation method thereof |
| CN108676033A (en) * | 2018-07-17 | 2018-10-19 | 江西扬帆新材料有限公司 | The synthetic method of antimony triphenyl |
| CN110734354A (en) * | 2019-10-15 | 2020-01-31 | 山西大学 | method for preparing biaryl compound from alcohol compound |
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2009
- 2009-09-02 CN CN200910090644A patent/CN101643378A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973855A (en) * | 2010-09-09 | 2011-02-16 | 上海华理生物医药有限公司 | Novel 4,4'-di(alkoxy/aryloxy methyl) biphenyl and preparation thereof |
| CN101973855B (en) * | 2010-09-09 | 2013-04-17 | 上海华理生物医药有限公司 | Novel 4,4'-di(alkoxy/aryloxy methyl) biphenyl and preparation thereof |
| CN102942429A (en) * | 2012-11-26 | 2013-02-27 | 大连理工大学 | Method for preparing aza or thia aryl biaryl compound by aid of palladium and carbon catalysts |
| CN105665017A (en) * | 2016-02-19 | 2016-06-15 | 江南大学 | Load type Pd catalyst used for Suzuky-Miyaura coupling reaction and preparation method thereof |
| CN105665017B (en) * | 2016-02-19 | 2017-12-12 | 江南大学 | A kind of Supported Pd-Catalyst for Suzuki Miyaura coupling reactions and preparation method thereof |
| CN108676033A (en) * | 2018-07-17 | 2018-10-19 | 江西扬帆新材料有限公司 | The synthetic method of antimony triphenyl |
| CN110734354A (en) * | 2019-10-15 | 2020-01-31 | 山西大学 | method for preparing biaryl compound from alcohol compound |
| CN110734354B (en) * | 2019-10-15 | 2020-12-25 | 山西大学 | Method for preparing biaryl compound from alcohol compound |
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