CN105152827A - Cross coupling reaction of arenesulphonate substrate and organic titanium - Google Patents
Cross coupling reaction of arenesulphonate substrate and organic titanium Download PDFInfo
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- CN105152827A CN105152827A CN201510494200.1A CN201510494200A CN105152827A CN 105152827 A CN105152827 A CN 105152827A CN 201510494200 A CN201510494200 A CN 201510494200A CN 105152827 A CN105152827 A CN 105152827A
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Abstract
The invention relates to a cross coupling reaction of an arenesulphonate substrate and organic titanium. The cross coupling reaction comprises steps as follows: A), after palladium acetate and indole phosphine ligands are utilized to generate a catalyst, the arenesulphonate substrate, aryl titanium, potassium phosphate and an organic solvent are added; B), the components react for 12-24 h at the temperature of 110-130 DEG C, and a biaryl compound is obtained. Compared with the Suzuki coupling reaction, the cross coupling reaction of the arenesulphonate substrate and organic titanium has the advantages that with addition of a small amount of alkali, organic titanium can be catalyzed to have the cross coupling reaction, and the reaction cost can be reduced. Besides, organic titanium is adopted as nucleophile for reaction, and compared with a Grignard reagent required to be stored in an organic solvent in the Kumada coupling reaction, solid organic titanium is easier to apply, has high stability, can be massively synthesized and is easy to store. Compared with organic tin in the Stille cross coupling reaction, organic titanium has lower toxicity and assists in improvement of applicability of the reaction.
Description
Technical field
The present invention relates to the cross-coupling reaction of tosic acid aryl ester and organic titanium.
Background technology
In 2002, Hayashi research group utilized organic titanium and aryl bromide and aryl triflate to carry out binding reaction first and generates aryl-linking compound.In recent years Gau research group and Kwong research group utilize the linked reaction of different palladium complex success catalysis aryl chlorides and organic titanium to synthesize various aryl-linking compound respectively.
Although aryl halide can carry out binding reaction with organic titanium generate aryl-linking compound, substrate spectrum is less, and applicability is to be improved.Aromatic yl sulphonate class substrate is the complementary substrate of aryl halide, in synthetic route, all can effectively supply or substituted aryl halogen as reaction substrate.So aromatic yl sulphonate class substrate and organic titanium are carried out cross-coupling reaction as successful, then effectively can improve the applicability of this new reaction.But the activity at the bottom of aromatic yl sulphonate class is very low, as far as we know, successful catalysis aromatic yl sulphonate class substrate and organic titanium is not also had now to carry out the example of cross-coupling reaction.
Summary of the invention
The present invention's relevant aromatic yl sulphonate class substrate and organic titanium carry out cross-coupling reaction, but aromatic yl sulphonate class substrate active is very low, need to utilize metallic palladium and indoles Phosphine ligands, and under the catalytic condition of a small amount of alkali, just reaction generates aryl-linking compound.
For achieving the above object, the technical solution adopted in the present invention is: acid chloride and indoles Phosphine ligands generate catalyzer, and aromatic yl sulphonate class substrate, aryl titanium and phosphoric acid Potassium are dissolved in Isosorbide-5-Nitrae-dioxan, in 110-130 DEG C of reaction 12-24 hour, obtain aryl-linking compound.
The mole number of above-mentioned catalyst acetic acid palladium and Phosphine ligands and mol ratio are 0.01mmol-0.025mmol:0.04mmol-0.1mmol, and the mole number of aromatic yl sulphonate class substrate, aryl titanium and phosphoric acid Potassium and mol ratio are 0.5mmol:1.0mmol-2.5mmol:0.125mmol.Catalyst levels is 2.0-5.0Pdmol%.
Above-mentioned aromatic yl sulphonate class substrate is 4-trimethylphenylmethane base p-toluenesulfonic esters, 3,5-xylyl p-toluenesulfonic esters, 3,4-xylyl p-toluenesulfonic esters, 3-methoxyphenyl p-toluenesulfonic esters, 4-methoxyphenyl p-toluenesulfonic esters, 4-fluorophenyl p-toluenesulfonic esters, 2,6-xylyl p-toluenesulfonic esters, 6-quinoline p-toluenesulfonic esters, 3,4-methylenedioxyphenyl p-toluenesulfonic esters, 2-methyl-6-benzothiazolyl p-toluenesulfonic esters.Aryl titanium is 4-methylbenzene titanium isopropylate, 4-anisole titanium isopropylate.
Above-mentioned Phosphine ligands is 2-[2-(dicyclohexylphosphontetrafluoroborate) phenyl] its structural formula of-1-Methyl-1H-indole:
The present invention has the following advantages:
(1) the present invention's relevant aromatic yl sulphonate class substrate and organic titanium carry out cross-coupling reaction, compare Suzuki linked reaction, and oneself the energy catalysis organic titanium of alkali adding minute quantity carry out cross-coupling reaction, can reduce reaction cost.
(2) utilize organic titanium to react as nucleophile, compare the lattice third constellations reagent must storing what organic solvent in Kumada linked reaction, solid-state organic titanium more easily applies and stability is high, can synthesize in a large number and store with easy what.
(3) compare the organotin in Stille cross-coupling reaction, the toxicity of organic titanium is lower, helps the applicability embodiment improving reaction.
Specific embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment one: the coupled reaction of aryl p-toluenesulfonic esters and 4-methylbenzene titanium isopropylate
In 20mLSchlenk pipe; add acid chloride (0.025mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 5mol%:20mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.
Tosic acid aryl ester (0.5mmol) is added subsequently, 4-methylbenzene titanium isopropylate (2.5mmol) and phosphoric acid Potassium (0.125mmol) when logical nitrogen.Finally add Isosorbide-5-Nitrae-dioxane (2.0mL), the oil bath pan then Schlenk pipe being placed in 110 DEG C of preheating reacts 18 to 24 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product aryl-linking compound, and isolated yield is as following table 1.
Table 1: tosic acid aryl ester and 4-methylbenzene titanium generate aryl-linking compound
Embodiment two: the coupled reaction of tosic acid aryl ester and 4-anisole titanium isopropylate
In 20mLSchlenk pipe; add acid chloride (0.025mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 5mol%:20mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.
Tosic acid aryl ester (0.5mmol) is added subsequently, 4-anisole titanium isopropylate (2.5mmol) and phosphoric acid Potassium (0.125mmol) when logical nitrogen.Finally add Isosorbide-5-Nitrae-dioxane (2.0mL), the oil bath pan then Schlenk pipe being placed in preheating 110 DEG C reacts 18 to 24 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product aryl-linking compound, and isolated yield is as following table 2.
Table 2: tosic acid aryl ester and 4-anisole titanium generate aryl-linking compound
Embodiment three: the coupled reaction of tosic acid heterocyclic aryl ester and organic titanium
In 20mLSchlenk pipe; add acid chloride (0.025mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 5mol%:20mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.
Tosic acid heterocyclic aryl ester (0.5mmol) is added subsequently, organic titanium (2.5mmol) and phosphoric acid Potassium (0.125mmol) when logical nitrogen.Finally add Isosorbide-5-Nitrae-dioxane (2.0mL), the oil bath pan then Schlenk pipe being placed in preheating 110 DEG C reacts 18 to 24 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product dibenzyl heterogeneous ring compound, and isolated yield is as following table 3.
Table 3: tosic acid heterocyclic aryl ester and organic benzene, organic titanium generate dibenzyl heterogeneous ring compound
Embodiment four: temperature is the coupled reaction of 130 DEG C
In 20mLSchlenk pipe; add acid chloride (0.025mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 5mol%:20mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.4-tertiary fourth aryl p-toluenesulfonic esters (0.5mmol) is added subsequently, 4-methylbenzene titanium isopropylate (2.5mmol) when logical nitrogen.Finally add Isosorbide-5-Nitrae-dioxane (2.0mL), the oil bath pan then Schlenk pipe being placed in preheating 130 DEG C reacts 14 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product dibenzyl heterogeneous ring compound, isolated yield 68%.
Embodiment five: the reaction adding different deal phosphoric acid Potassium
In 20mLSchlenk pipe; add acid chloride (0.025mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 5mol%:20mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.4-tertiary fourth aryl p-toluenesulfonic esters (0.5mmol) is added subsequently, 4-methylbenzene titanium isopropylate (2.5mmol) when logical nitrogen.Finally add four Hydrogen tetrahydrofuran solution (2.0mL), the oil bath pan then Schlenk pipe being placed in preheating 110 DEG C reacts 11 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product dibenzyl heterogeneous ring compound, and isolated yield is as following table 4.
Table 4: add the impact of different deal phosphoric acid Potassium on reaction
Embodiment six: acid chloride and part ratio are the reaction of 2mol%:8mol%
In 20mLSchlenk pipe; add acid chloride (0.01mmol) and Phosphine ligands (palladium: Phosphine ligands is made a gesture of measuring as 2mol%:8mol%); add the magnetic stirring bar being furnished with polytetrafluorethylecoatings coatings again; system is replaced into nitrogen protection; add triethylamine and 1.0mL methylene dichloride that 0.1mL newly distills, stir and take out the universe to form palladium complex under decompression after mild heat to micro-boiling.
3-methoxy aryl p-toluenesulfonic esters (0.5mmol) is added subsequently, 4-methylbenzene titanium isopropylate (2.5mmol) when logical nitrogen.Finally add Isosorbide-5-Nitrae-dioxane (2.0mL), the oil bath pan then Schlenk pipe being placed in preheating 110 DEG C reacts 24 hours.After completion of the reaction, reaction tubes is cooled room temperature, add about 10mL water to system, then add about 10mL ethyl acetate, organic layer is carried out gas chromatographic analysis.Thereafter divide again and respectively add about 10mL extraction into ethyl acetate for three to four times, be merged organic phase, under reduced pressure concentrate.Column chromatography obtains product dibenzyl heterogeneous ring compound, isolated yield 80%.
Claims (5)
1. the cross-coupling reaction of tosic acid aryl ester and organic titanium, is characterized in that, comprises step:
A), after acid chloride and indoles Phosphine ligands being generated catalyzer, aromatic yl sulphonate class substrate, aryl titanium, phosphoric acid Potassium and organic solvent is added,
B) in 110-130 DEG C of reaction 12-24 hour, aryl-linking compound is obtained.
2. according to claim 1 the cross-coupling reaction that describes, it is characterized in that: the mole number of described catalyst acetic acid palladium and Phosphine ligands and mol ratio are 0.01mmol-0.025mmol:0.04mmol-0.1mmol, the mole number of aromatic yl sulphonate class substrate, aryl titanium and phosphoric acid Potassium and mol ratio are 0.5mmol:1.0mmol-2.5mmol:0.125mmol.Catalyst levels is 2.0-5.0Pdmol%.
3. according to claim 1 or 2 the cross-coupling reaction that describes, it is characterized in that: described aromatic yl sulphonate class substrate is 4-trimethylphenylmethane base p-toluenesulfonic esters, 3,5-xylyl p-toluenesulfonic esters, 3,4-xylyl p-toluenesulfonic esters, 3-methoxyphenyl p-toluenesulfonic esters, 4-methoxyphenyl p-toluenesulfonic esters, 4-fluorophenyl p-toluenesulfonic esters, 2, one in 6-xylyl p-toluenesulfonic esters, 6-quinoline p-toluenesulfonic esters, 3,4-methylenedioxyphenyl p-toluenesulfonic esters, 2-methyl-6-benzothiazolyl p-toluenesulfonic esters.
4. according to claim 1 or 2 the cross-coupling reaction that describes, it is characterized in that: described aryl titanium is 4-methylbenzene titanium isopropylate, 4-anisole titanium isopropylate.
5. according to claim 1 or 2 the cross-coupling reaction that describes, it is characterized in that: described indoles Phosphine ligands is 2-[2-(dicyclohexylphosphontetrafluoroborate) phenyl]-1-Methyl-1H-indole, and its structural formula is:
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107324964A (en) * | 2017-06-22 | 2017-11-07 | 陕西师范大学 | A kind of synthetic method of biphenyl analog derivative |
| WO2017193288A1 (en) * | 2016-05-10 | 2017-11-16 | The Hong Kong Polytechnic University Shenzhen Research Institute | Synthesis of phosphine ligands bearing tunable linkage: methods of their use in catalysis |
| CN107445989A (en) * | 2016-06-01 | 2017-12-08 | 香港理工大学深圳研究院 | A kind of Phosphine ligands of indoles skeleton and its preparation method and application |
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| US20090326243A1 (en) * | 2008-06-30 | 2009-12-31 | The Hong Kong Polytechnic University | Ligands for transition-metals and methods of use |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20090326243A1 (en) * | 2008-06-30 | 2009-12-31 | The Hong Kong Polytechnic University | Ligands for transition-metals and methods of use |
Non-Patent Citations (4)
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| CHOY,PUI YING;CHOW,WING KIN: "PALLADIUM-CATALYZED SONOGASHIRA COUPLING OF ARYL MESYLATES AND TOSYLATES", 《CHEMISTRY- A EUROPEAN JOURNAL 》 * |
| LEE,DONG SHENG;CHOY,PUI YING: "PALLADIUM-CATALYZED DIRECT ARYLATION OF POLYFLUOROARENES WITH ARYL TOSYLATES AND MESYLATES", 《RSC ADVANCES》 * |
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| YANG,HSU-TANG;ZHOU,SHUANGLIU: "SYNTHESIS,STRUCTURES AND CHARACTERIZATIONS OF [ARTI(O-I-PR)3]2 AND EFFICIENT ROOM-TEMPERATURE ARYL-ARYL COUPLING OF ARYL BROMIDES WITH [ARTI(O-I-PR)3]2 CATALYZED BY THE ECONOMIC PD(OAC)2/PCY3 SYSTEM", 《ORGANOMETALLICS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017193288A1 (en) * | 2016-05-10 | 2017-11-16 | The Hong Kong Polytechnic University Shenzhen Research Institute | Synthesis of phosphine ligands bearing tunable linkage: methods of their use in catalysis |
| CN107445989A (en) * | 2016-06-01 | 2017-12-08 | 香港理工大学深圳研究院 | A kind of Phosphine ligands of indoles skeleton and its preparation method and application |
| CN107445989B (en) * | 2016-06-01 | 2020-05-29 | 香港理工大学深圳研究院 | Phosphine ligand with indole skeleton and preparation method and application thereof |
| CN107324964A (en) * | 2017-06-22 | 2017-11-07 | 陕西师范大学 | A kind of synthetic method of biphenyl analog derivative |
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