CN114315910A - Synthetic method of N-heterocyclic carbene allyl palladium chloride compound - Google Patents
Synthetic method of N-heterocyclic carbene allyl palladium chloride compound Download PDFInfo
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- CN114315910A CN114315910A CN202111473846.3A CN202111473846A CN114315910A CN 114315910 A CN114315910 A CN 114315910A CN 202111473846 A CN202111473846 A CN 202111473846A CN 114315910 A CN114315910 A CN 114315910A
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Abstract
The invention discloses a synthesis method of a nitrogen heterocyclic carbene allyl palladium chloride compound, belonging to the technical field of medical catalysts. The synthesis method of the N-heterocyclic carbene allyl palladium chloride compound comprises the following steps: weighing 1 equivalent of allyl palladium chloride dimer powder, adding 10-30 equivalents of solvent, stirring for the first time, slowly adding 2-2.5 equivalents of N-heterocyclic carbene ligand, naturally cooling, filtering the reaction solution, taking filtrate, evaporating under reduced pressure to dryness to obtain powder, adding n-hexane, stirring for the second time, filtering, taking filter cake, and drying to obtain the N-heterocyclic carbene allyl palladium chloride compound shown in formula 1 or formula 2. The invention provides a new synthesis idea and route, different target products can be synthesized by using different N-heterocyclic carbene ligands, the product yield is stable, and the properties and the purity can meet the requirements.
Description
Technical Field
The invention relates to a synthesis method of a nitrogen heterocyclic carbene allyl palladium chloride compound, belonging to the technical field of medical catalysts.
Background
The N-heterocyclic carbene has good electron-donating property and easily modified structure, and can be widely applied in the field of small molecule catalysis or transition metal catalysis as a ligand. Among them, the Suzuki-Miyaura coupling reaction with metallic palladium is one of the research hotspots.
The N-heterocyclic carbene allyl palladium chloride compounds mainly comprise allyl [1, 3-bis (2, 6-diisopropylphenyl) imidazole-2-subunit ] palladium chloride (II), allyl chloride [1, 3-bis (2, 6-di-isopropylphenyl) -4, 5-dihydroimidazole-2-yl ] palladium (II), allyl [1, 3-bis (mesitylene) imidazol-2-ylidene ] palladium (II) chloride, [1, 3-bis (2, 6-di-isopropylphenyl) -4, 5-dihydroimidazol-2-ylidene ] chloro [ 3-phenylallyl ] palladium (II), and [1, 3-bis (2, 6-diisopropylphenyl) imidazol-2-ylidene ] chloro [ 3-phenylallyl ] palladium (II), and the like. In the prior art, the synthesis method of the compound mainly uses argon-based azacyclo-imidazole hydrochloride or carbene as a raw material to react with allyl palladium chloride dimer or 3-phenyl allyl palladium chloride, and the solvent is tetrahydrofuran, isopropanol, acetone or diethyl ether. After the reaction is finished, impurities such as palladium black and the like generated in the reaction are removed by filtration, and the product is separated out or pulped by adding a poor solvent to achieve the purpose of purification. There are mainly four methods as follows:
first, 0.7g (1.64mmol) of 1, 3-bis (2, 6-diisopropylphenyl) imidazolium hydrochloride, 0.194g (1.73mmol) of potassium tert-butoxide, 0.3g of allylpalladium chloride dimer and 40ml of dry tetrahydrofuran were placed in a three-necked round-bottomed flask. The reaction was brought to room temperature and allowed to react for 12 h. And after the reaction is finished, filtering the reaction solution through silica gel to remove palladium black components, adding 100ml of n-hexane into the filtrate, directly separating out the product, filtering, leaching, drying a filter cake in vacuum, and recovering 0.82g of the product, wherein the yield is 87%. The hydrogen and carbon spectra are characterized by allylic [1, 3-bis (2, 6-di-cumyl) -4, 5-dihydroimidazol-2-yl ] palladium (II) chloride.
Secondly, adding potassium tert-butoxide and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium hydrochloride into a three-neck flask, using isopropanol as a solvent, stirring for 2h at 80 ℃ under the protection of nitrogen, recovering the room temperature after the reaction is finished, adding allyl palladium chloride dimer, continuing stirring for 2h, and obtaining the yield of 66% after treatment. The hydrogen spectrum is characterized by allylic [1, 3-bis (2, 6-di-cumyl) -4, 5-dihydroimidazol-2-yl ] palladium (II) chloride.
Thirdly, adding 1, 3-bis (2,4, 6-trimethylphenyl) -2-imidazolidinylidene and tetrahydrofuran into a three-neck flask, under the protection of inert gas, slowly adding allyl palladium chloride dimer, reacting for 1.5h, filtering, washing with tetrahydrofuran, drying a solvent, adding n-hexane, pulping, and filtering to obtain a filter cake, namely the target product, wherein the yield is 45%.
Fourthly, adding 1, 3-bis (2,4, 6-trimethylphenyl) -2-imidazolidine silver chloride, allyl palladium chloride dimer and dichloromethane serving as a solvent into a three-neck flask, magnetically stirring for 2 hours, filtering after the reaction is finished, spin-drying the filtrate, adding a mixed solution of n-hexane and ether in a volume ratio of 1:1, pulping, filtering, leaching with ether and n-hexane, and drying the filter cake in vacuum to obtain the target product, wherein the yield is 97%.
The drawbacks of the above four methods are: in each method, the yield, the character and the purity of the product are unstable after different substrates are replaced.
In view of the above, there is a need to provide a novel method for synthesizing N-heterocyclic carbene allyl palladium chloride compound, so as to overcome the defects of the prior art.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a synthetic method of a nitrogen heterocyclic carbene allyl palladium chloride compound.
The technical scheme for solving the problems is as follows: a synthetic method of a nitrogen heterocyclic carbene allyl palladium chloride compound comprises the following steps:
weighing 1 equivalent of allyl palladium chloride dimer powder, adding 10-30 equivalents of solvent, stirring for the first time, slowly adding 2-2.5 equivalents of N-heterocyclic carbene ligand, naturally cooling, filtering the reaction solution, taking filtrate, evaporating under reduced pressure to obtain powder, adding n-hexane for pulping, stirring for the second time, filtering, taking filter cake, drying to obtain N-heterocyclic carbene allyl palladium chloride compound shown in formula 1 or formula 2,
the principle of the synthesis method of the N-heterocyclic carbene allyl palladium chloride compound of the invention is illustrated as follows:
allyl Palladium chloride dimer, CAS registry number 12012-95-2, formula C6H10Cl2Pd2It is yellow crystal powder. The allyl palladium chloride dimer powder described above is commercially available, such as from Shaanxi ruike, at 98% specification.
The invention adopts the N-heterocyclic carbene ligand as the raw material to react with the allyl palladium chloride dimer, solves the problem of difficult preparation of carbene intermediate and silver chloride ligand, and has the advantages of clean and rapid reaction, simple post-treatment operation, high yield and good product properties. The side reaction caused by the deterioration of the raw materials in the reaction process is avoided, the feeding and post-treatment difficulty is greatly reduced, and the operation steps are simplified.
The reaction principle is shown below (exemplified with a compound of formula 3):
ligand A will partially dissociate in solution to B free carbene form, and free B will encounter allyl palladium chloride C to rapidly form the compound of formula 3, so that the reaction can gradually complete.
The synthesis method of the N-heterocyclic carbene allyl palladium chloride compound has the beneficial effects that:
1. the invention provides a new synthesis idea and a new synthesis route of the N-heterocyclic carbene allyl palladium chloride compound, different target products can be synthesized by using different N-heterocyclic carbene ligands, the product yield is stable, the properties and the purity can meet the requirements, and the defects of by-products generated in different reactions and reaction processes and inconvenience brought by different post-treatment modes are overcome.
2. The synthesis method disclosed by the invention is simple to operate, convenient to post-treat, stable in yield, good in product character, low in cost, wide in market prospect and suitable for large-scale popularization and application.
On the basis of the technical scheme, the invention can be further improved as follows.
Further, the solvent is any one of tetrahydrofuran, methyltetrahydrofuran, diethyl ether and methyl tertiary ether.
The adoption of the further beneficial effects is as follows: the technical scheme of the invention can be realized by the ether or benzene solvents.
Further, the time of the first stirring is 30min-60 min.
The adoption of the further beneficial effects is as follows: by adopting the parameters, the stirring is more uniform and thorough.
Further, the N-heterocyclic carbene ligand is 1, 3-bis [2, 6-bis (1-methylethyl) phenyl ] -2- (trichloromethyl) imidazolidine or 1, 3-bis [2,4, 6-trimethylphenyl ] -2- (trichloromethyl) imidazole.
The adoption of the further beneficial effects is as follows: the two compounds can be used as substrates of the invention to synthesize different target products, and the product yield is stable, the character and the purity can meet the requirements, thereby solving the inconvenience caused by different reactions, byproducts generated in the reaction process and different post-treatment modes.
Further, the temperature after natural cooling is 25-60 ℃.
Further, the reaction solution is filtered by using a diatomite sand core funnel.
Further, the n-hexane beating time is 1-2 h.
The adoption of the further beneficial effects is as follows: with the above parameters, the powder can be beaten.
Further, the time of the second stirring is 1-12 h.
The adoption of the further beneficial effects is as follows: by adopting the parameters, the stirring is more uniform and thorough.
Further, the drying temperature is 25-60 ℃, and the drying time is 2 h.
The adoption of the further beneficial effects is as follows: by adopting the parameters, the drying effect is better.
Further, the specific structure of the N-heterocyclic carbene allyl palladium chloride compound is shown as any one of formulas 3-8:
drawings
FIG. 1 is an NMR hydrogen spectrum of allyl [1, 3-bis (2, 6-di-cumyl) -4, 5-dihydroimidazol-2-yl ] palladium (II) chloride in example 1 of the present invention.
FIG. 2 is an NMR hydrogen spectrum of allyl chloride [1, 3-bis (2, 6-di-cumyl) -4, 5-imidazol-2-ylidene ] palladium (II) in example 2 of this invention.
FIG. 3 is an NMR hydrogen spectrum of allylic [1, 3-bis (2,4, 6-tri-methylphenyl) -4, 5-imidazol-2-ylidene ] palladium (II) chloride in example 3 of this invention.
Detailed Description
The principles and features of this invention are described below in conjunction with the following detailed drawings, which are given by way of illustration only and are not intended to limit the scope of the invention.
Example 1:
the synthesis method of allyl [1, 3-bis (2, 6-di-cumyl) -4, 5-dihydroimidazol-2-yl ] palladium (II) chloride of this example includes the following steps:
adding 5g (13.7mmol) of allyl palladium chloride dimer powder and 100ml of dry tetrahydrofuran into a 250ml three-neck round-bottom flask, stirring for half an hour in ice-water bath, slowly dropwise adding a mixed solution of 13.9g (27.3mmol) of 1, 3-bis [2, 6-bis (1-methylethyl) phenyl ] -2- (trichloromethyl) imidazolidine and 30ml of tetrahydrofuran, naturally recovering the room temperature after the dropping is finished, stirring for 5 hours, pouring the reaction solution into a sand core funnel filled with diatomite, filtering to obtain a filtrate which is a light yellow clear solution, carrying out reduced pressure distillation to obtain a white-like powder, adding n-hexane, pulping, filtering, transferring the filter cake into a single-neck bottle, drying at 35 ℃ for 2 hours, collecting 14.42g of the white powder, and obtaining the yield of 91.99%.
The NMR spectrum showed allyl [1, 3-bis (2, 6-di-cumyl) -4, 5-dihydroimidazol-2-yl ] palladium (II) chloride, as shown in FIG. 1. The data are as follows:
H1NMR(400MHz,C6D6)：7.14-7.16(m,2H)，7.05-7.12(m,4H)，4.27-4.37(m,1H),3.56-3.71(m,9H),2.95-2.97(d,1H),2.63-2.66(d,1H),1.50-1.51(d,6H),1.43-1.45(d,6H),1.37-1.40(d,2H),1.13-1.15(dd,12H)。
elemental analysis: c, 62.53; h, 7.21; n, 4.82; pd, 18.87.
Example 2
The synthesis method of allyl chloride [1, 3-bis (2, 6-di-cumyl) -4, 5-imidazole-2-subunit ] palladium (II) comprises the following steps:
adding 5g (13.7mmol) of allyl palladium chloride dimer powder and 100ml of dry tetrahydrofuran into a 250ml three-neck round-bottom flask, stirring for half an hour in ice-water bath, slowly dropwise adding a mixed solution of 13.86g (27.3mmol) of 1, 3-bis [2, 6-bis (1-methylethyl) phenyl ] -2- (trichloromethyl) imidazole and 20ml of tetrahydrofuran, naturally recovering the room temperature after the dropwise adding is finished, stirring for 5 hours, pouring the reaction solution into a sand core funnel filled with diatomite, filtering to obtain a light yellow clear solution, carrying out reduced pressure distillation to obtain a white-like powder, adding n-hexane, pulping, filtering, transferring a filter cake into a single-neck bottle, drying at 35 ℃ for 2 hours, collecting 14.04g of the white powder, and obtaining the yield of 90.00%.
NMR spectra showed allyl [1, 3-bis (2, 6-di-cumyl) -4, 5-imidazol-2-ylidene ] palladium (II) chloride, as shown in FIG. 2, with the following data:
H1NMR(400MHz,C6D6):7.18-7.22(m,2H),7.09-7.12(m,4H),6.67(s,2H),4.36-4.45(m,1H),3.71-3.73(dd,1H),3.32-3.38(m,2H),3.05-3.12(m,2H),2.99-3.00(dd,1H),2.64-2.67(d,1H)1.58-1.61(d,1H),1.39-1.44(dd,12H),1.02-1.06(dd,12H)。
elemental analysis: c, 62.72; h, 7.38; n, 4.97; pd, 18.72.
Example 3
The synthesis method of allyl chloride [1, 3-bis (2,4, 6-tri-methylphenyl) -4, 5-imidazole-2-subunit ] palladium (II) comprises the following steps:
adding 5g (13.7mmol) of allyl palladium chloride dimer powder and 100ml of dry tetrahydrofuran into a 250ml three-neck round-bottom flask, stirring for half an hour in ice-water bath, slowly dropwise adding a mixed solution of 11.57g (27.3mmol) of 1, 3-bis [2,4, 6-trimethylphenyl ] -2- (trichloromethyl) imidazole and 20ml of tetrahydrofuran, naturally recovering the room temperature after dropping, stirring for 5 hours, pouring the reaction solution into a sand core funnel filled with diatomite, filtering, obtaining a light yellow clear solution as a filtrate, distilling under reduced pressure to obtain white-like powder, adding n-hexane, pulping, filtering, transferring a filter cake into a single-neck flask, drying at 35 ℃ for 2 hours, collecting 12.41g of white powder, and obtaining the yield of 93.00%.
NMR spectra showed allylic [1, 3-bis (2,4, 6-tri-methylphenyl) -4, 5-imidazol-2-ylidene ] palladium (II) chloride with the following data:
H1NMR(400MHz,C6D6):7.15(s,2H)，6.74-6.76(d,4H)，4.42-4.52(m,1H),3.70-3.73(dd,1H),3.06-3.07(d,1H),2.68-2.71(d,1H),2.22-2.27(d,12H),2.06(s,6H)。
elemental analysis: c, 59.52; h, 5.87; n, 5.93; pd, 21.79.
In conclusion, the general synthetic route of the N-heterocyclic carbene allyl palladium chloride compound is explored, the synthesis of three compounds is verified, a product with stable yield and good properties is obtained, and the compound is effectively characterized by a nuclear magnetic hydrogen spectrum, element classification method and the like. The method has the advantages of simple feeding, low sensitivity, easy operation, convenient post-treatment, stable yield and good product properties. The method is applicable to the synthesis of the same kind of compounds.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. A synthetic method of a nitrogen heterocyclic carbene allyl palladium chloride compound is characterized by comprising the following steps:
weighing 1 equivalent of allyl palladium chloride dimer powder, adding 10-30 equivalents of solvent, stirring for the first time, slowly adding 2-2.5 equivalents of N-heterocyclic carbene ligand, naturally cooling, filtering the reaction solution, taking filtrate, evaporating under reduced pressure to obtain powder, adding n-hexane for pulping, stirring for the second time, filtering, taking filter cake, drying to obtain N-heterocyclic carbene allyl palladium chloride compound shown in formula 1 or formula 2,
2. the method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the solvent is any one of tetrahydrofuran, methyltetrahydrofuran, diethyl ether and methyl tertiary ether.
3. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the time for the first stirring is 30min to 60 min.
4. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound according to claim 1, wherein the N-heterocyclic carbene ligand is 1, 3-bis [2, 6-bis (1-methylethyl) phenyl ] -2- (trichloromethyl) imidazolidine or 1, 3-bis [2,4, 6-trimethylphenyl ] -2- (trichloromethyl) imidazole.
5. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the temperature after natural cooling is 25 ℃ to 60 ℃.
6. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the reaction solution is filtered by using a diatomite core funnel.
7. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the time for pulping the n-hexane is 1h-2 h.
8. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the time for the second stirring is 1h-12 h.
9. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the drying temperature is 25-60 ℃ and the drying time is 2 h.
10. The method for synthesizing the N-heterocyclic carbene allyl palladium chloride compound as claimed in claim 1, wherein the N-heterocyclic carbene allyl palladium chloride compound has a specific structure as shown in any one of formulas 3 to 8:
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| US20210198286A1 (en) * | 2018-09-03 | 2021-07-01 | Universiteit Gent | Method of preparing metal complexes of formula Z-M, in particular carbene-metal complexes |
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| US20210198286A1 (en) * | 2018-09-03 | 2021-07-01 | Universiteit Gent | Method of preparing metal complexes of formula Z-M, in particular carbene-metal complexes |
Non-Patent Citations (1)
| Title |
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| HAYATI TURKMEN ET AL.: "1,3-Diarylimidazolidin-2-ylidene (NHC) complexes of Pd(II):Electronic effects on cross-coupling reactions and thermal decompositions", 《JOURNAL OF ORGANOMETALLIC CHEMISTRY》 * |
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