CN115417809A - Preparation method of 4, 4-dipyrrole-2, 2-bipyridine - Google Patents
Preparation method of 4, 4-dipyrrole-2, 2-bipyridine Download PDFInfo
- Publication number
- CN115417809A CN115417809A CN202211078387.3A CN202211078387A CN115417809A CN 115417809 A CN115417809 A CN 115417809A CN 202211078387 A CN202211078387 A CN 202211078387A CN 115417809 A CN115417809 A CN 115417809A
- Authority
- CN
- China
- Prior art keywords
- mobile phase
- reaction
- dipyrrole
- volume
- bipyridine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 17
- 238000001514 detection method Methods 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000012065 filter cake Substances 0.000 claims description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- NWOFTVXCCAYBOK-UHFFFAOYSA-N 4,4-dibromo-2-pyridin-2-yl-3H-pyridine Chemical group BrC1(CC(=NC=C1)C1=NC=CC=C1)Br NWOFTVXCCAYBOK-UHFFFAOYSA-N 0.000 claims description 8
- 238000010828 elution Methods 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000002386 leaching Methods 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- 230000008034 disappearance Effects 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 abstract description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052763 palladium Inorganic materials 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000029936 alkylation Effects 0.000 abstract description 2
- 239000006227 byproduct Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 231100001261 hazardous Toxicity 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 230000005311 nuclear magnetism Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000006619 Stille reaction Methods 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a preparation method of 4, 4-dipyrrole-2, 2-bipyridine, which adopts alkylation to prepare the 4, 4-dipyrrole-2, 2-bipyridine in one step, thus realizing the high-efficiency synthesis of the compound, greatly improving the reaction yield and reducing the reaction period; the used raw materials are cheap and easily available, and can be supplied in large quantities, so that the reaction cost is reduced. The method avoids the use of hazardous reagents n-BuLi and tributyltin chloride, has simple operation, avoids the use of expensive catalysts such as palladium and the like, and simultaneously can not generate byproducts harmful to the environment.
Description
Technical Field
The invention relates to the technical field of chemical pharmacy and chemical synthesis, in particular to a preparation method of 4, 4-dipyrrole-2, 2-dipyridine.
Background
4, 4-dipyrrole-2, 2-dipyridine is used as an important chemical intermediate, is widely applied to various medicine synthesis, and can also be used as a ligand to participate in various coupling reactions. The structure of 4, 4-dipyrrole-2, 2-bipyridine is as follows:
the prior literature reports that the preparation method of 4, 4-dipyrrole-2, 2-dipyridine is mainly divided into two methods: firstly, the raw materials are synthesized into a tin reagent by using tributyltin chloride, and then the stille reaction is carried out, wherein two steps are needed for synthesis (shown in figure 1), and a flammable and explosive compound n-BuLi and a highly toxic compound tributyltin chloride are needed in the first step, so that the operation is difficult; the second step needs to use a palladium catalyst, the price is high, the waste palladium pollutes the environment, the synthesis yield is only 45 percent, the total yield of the two steps is only 39 percent, and the yield is lower. The second method has the advantages that the synthetic raw materials are not easy to obtain, and the second method also needs two-step synthesis (shown in figure 2), the second method is obtained by alkylation and then reduction reaction, and the yield is only 47%.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a preparation method of 4, 4-dipyrrole-2, 2-dipyridine, and the technical scheme is as follows:
in order to solve the technical problems, the invention provides a preparation method of 4, 4-dipyrrole-2, 2-dipyridine, which is characterized by comprising the following steps: the substrate 4, 4-dibromo-2, 2-bipyridyl is subjected to alkylation reaction under the action of tetrahydropyrrole, so that the product 4, 4-dipyrrole-2, 2-bipyridyl is synthesized in one step.
Specifically, the pyrrolidine is a reactant, and is also a base and a solvent of the reaction.
Specifically, the mass-to-volume ratio of the substrate to the pyrrolidine is 1: (10-20).
Specifically, the reaction temperature is 70 to 90 ℃.
Specifically, the reaction time is 10 to 24 hours.
Specifically, the preparation method further comprises the following steps: disappearance of the substrate was detected by TLC and purification treatment after LCMS detection of the product.
Specifically, the TLC detection adopts the conditions of petroleum ether/ethyl acetate =1/1, rfsm =0.4, and rfproduct =0.05.
Specifically, the LCMS detection condition is that the instrument is Shimadzu LC-30AD model, LCMS-2020; mobile phase A is water and 0.04 percent trifluoroacetic acid; mobile phase B is acetonitrile and 0.02 percent trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, the volume of the mobile phase A is 5%, and the volume of the mobile phase B is 95%;2min, the volume of the mobile phase A is 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
Specifically, the purification treatment comprises: cooling the reaction liquid to room temperature, slowly pouring the reaction liquid into 100mL of KOH (1 mol/L), stirring for 0.5-2 hours, separating out a large amount of white solid, leaching the filter cake with water after filtering, adding the leached filter cake into a special solvent, stirring, filtering after uniform stirring to obtain white solid powder, and drying the solid in vacuum.
Specifically, the special solvent is any one of dichloromethane, ethyl acetate, 1, 2-dichloroethane and methyl tert-butyl ether.
In the invention, a substrate 4, 4-dibromo-2, 2-bipyridyl is subjected to alkylation reaction in the presence of tetrahydropyrrole to synthesize a product 4, 4-dipyrrole-2, 2-bipyridyl in one step. Compared with the reduction synthesis method in the literature, the substrate 4, 4-dibromo-2, 2-bipyridine is cheap and easy to obtain, can be supplied in large quantity, reduces the reaction cost and improves the reaction yield; compared with a Stille cladding synthesis method in the literature, the method is simple to operate, and avoids the use of hazardous reagents n-BuLi and tributyl tin chloride. Tetrahydropyrrole is used as reactant, reaction solvent and base. The reaction is carried out in one step to obtain a target product, the feeding process is simple to operate, and the reaction temperature is 70-90 ℃. The method has the advantages of clean reaction, simple post-treatment, no need of complex purification process, simple pulping to obtain pure product, no need of column purification, high yield, shortened production period, reduced cost, and no generation of by-product harmful to environment.
Drawings
In order to more clearly illustrate the technical solution of the present invention, the drawings needed to be used in the present invention are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a prior art synthetic route;
FIG. 2 is another prior art synthetic route;
FIG. 3 is a synthetic scheme of the present invention.
Detailed Description
The technical solutions in the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A dry and clean 100mL reaction flask was charged with substrate (4, 4-dibromo-2, 2-bipyridine) (2g, 1eq) and tetrahydropyrrole (40mL, 20-fold volume) and the temperature was raised to 90 ℃ for 16 hours. TLC check for disappearance of starting material and LCMS check for complete conversion of starting material to product. The reaction solution is cooled to room temperature, slowly poured into 100mL of KOH (1 mol/L), stirred for 0.5 hour, a large amount of white solid is separated out, filtered, and the filter cake is rinsed by water. Adding the filter cake into a dichloromethane solvent, stirring, uniformly stirring, filtering to obtain white solid powder, and drying the solid in vacuum to obtain 1.6g of off-white solid, namely the product 4, 4-dipyrrole-2, 2-bipyridine, wherein the yield is 84.9 percent, and the analytical purity is 99.6 percent.
The nuclear magnetism of the product 4, 4-dipyrrole-2, 2-bipyridine is as follows: 1 HNMR(400MHz，CDCl3)δppm 8.27(d,J＝4Hz,2H),7.54(d,J＝2.4Hz,2H),6.38-6.40(m,2H),3.41-3.44(m,8H),2.01-2.04(m,8H)。
conditions for the above TLC detection: petroleum ether/ethyl acetate =1/1, rfsm =0.4, rfproduct =0.05.
Conditions for the LCMS assay described above: the instrument is Shimadzu LC-30AD, and the model is LCMS-2020; mobile phase A is water and 0.04 percent trifluoroacetic acid, and mobile phase B is acetonitrile and 0.02 percent trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, the volume of the mobile phase A is 5%, and the volume of the mobile phase B is 95%;2min, the volume of the mobile phase A accounts for 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
Example 2
A dry and clean 40mL reaction flask was charged with substrate (4, 4-dibromo-2, 2-bipyridine) (1g, 1eq) and tetrahydropyrrole (20mL, 20-fold volume), and the temperature was raised to 90 ℃ for 10 hours. TLC check for disappearance of starting material and LCMS check for complete conversion of starting material to product. And cooling to room temperature, slowly pouring the mixture into 40mL of KOH (1 mol/L) aqueous solution, stirring for 0.5 hour, separating out a large amount of off-white solid, filtering, and leaching a filter cake by using water. Adding dichloromethane solvent (10 times volume) into the filter cake, stirring, filtering to obtain white solid powder, and vacuum drying to obtain 768mg white solid, i.e. 4, 4-dipyrrole-2, 2-bipyridine, with yield of 81.6% and analytical purity of 99.4%.
The nuclear magnetism of the product 4, 4-dipyrrole-2, 2-bipyridine is as follows: 1 HNMR(400MHz，CDCl3)δppm 8.27(d,J＝4Hz,2H),7.54(d,J＝2.4Hz,2H),6.38-6.40(m,2H),3.41-3.44(m,8H),2.01-2.04(m,8H)。
conditions for the above TLC detection: petroleum ether/ethyl acetate =1/1, rfsm =0.4, rfproduct =0.05.
Conditions for the LCMS assay described above: the instrument is Shimadzu LC-30AD, and the model is LCMS-2020; the mobile phase A is water and 0.04 percent of trifluoroacetic acid, and the mobile phase B is acetonitrile and 0.02 percent of trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, the volume of the mobile phase A is 5%, and the volume of the mobile phase B is 95%;2min, the volume of the mobile phase A accounts for 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
Example 3
A dry and clean 40mL reaction flask was charged with substrate (4, 4-dibromo-2, 2-bipyridine) (1g, 1eq) and tetrahydropyrrole (10mL, 10 times by volume), and the temperature was raised to 90 ℃ for 10 hours. TLC detection starting material disappeared, LCMS detection starting material completely converted into product. Cooling to room temperature, slowly pouring into 40mL KOH (1 mol/L) aqueous solution, stirring for 0.5 hour, precipitating a large amount of off-white solid, filtering, and leaching the filter cake with water. Adding dichloromethane solvent (10 times volume) into the filter cake, stirring, filtering to obtain white solid powder, and vacuum drying to obtain 773mg white solid, i.e. product 4, 4-dipyrrole-2, 2-bipyridine, with yield of 81.6% and analytical purity of 99.4%.
The nuclear magnetism of the product 4, 4-dipyrrole-2, 2-bipyridine is as follows: 1 HNMR(400MHz，CDCl3)δppm 8.27(d,J＝4Hz,2H),7.54(d,J＝2.4Hz,2H),6.38-6.40(m,2H),3.41-3.44(m,8H),2.01-2.04(m,8H)。
conditions for the above TLC detection: petroleum ether/ethyl acetate =1/1, rfsm =0.4, rfproduct =0.05.
Conditions for LCMS detection as described above: the instrument is Shimadzu LC-30AD, and the model is LCMS-2020; the mobile phase A is water and 0.04 percent of trifluoroacetic acid, and the mobile phase B is acetonitrile and 0.02 percent of trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, mobile phase A accounting for 5% by volume, mobile phase B accounting for 95% by volume; 2min, the volume of the mobile phase A accounts for 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
Example 4
A dry and clean 40mL reaction flask was charged with substrate (4, 4-dibromo-2, 2-bipyridine) (1g, 1eq) and tetrahydropyrrole (20mL, 20 times by volume), and the temperature was raised to 70 ℃ for 24 hours. TLC detection starting material disappeared, LCMS detection starting material completely converted into product. Cooling to room temperature, slowly pouring into 40mL KOH (1 mol/L) aqueous solution, stirring for 0.5 hour, precipitating a large amount of off-white solid, filtering, and leaching the filter cake with water. Adding dichloromethane solvent (10 times volume) into the filter cake, stirring, filtering to obtain white solid powder, and vacuum drying to obtain 775mg white solid, i.e. 4, 4-dipyrrole-2, 2-bipyridine, with yield of 82.0% and analytical purity of 99.2%.
The nuclear magnetism of the product 4, 4-dipyrrole-2, 2-bipyridine is as follows: 1 HNMR(400MHz，CDCl3)δppm 8.27(d,J＝4Hz,2H),7.54(d,J＝2.4Hz,2H),6.38-6.40(m,2H),3.41-3.44(m,8H),2.01-2.04(m,8H)。
conditions for the above TLC detection: petroleum ether/ethyl acetate =1/1, rfsm =0.4, rfproduct =0.05.
Conditions for LCMS detection as described above: the instrument is Shimadzu LC-30AD, and the model is LCMS-2020; the mobile phase A is water and 0.04 percent of trifluoroacetic acid, and the mobile phase B is acetonitrile and 0.02 percent of trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, mobile phase A accounting for 5% by volume, mobile phase B accounting for 95% by volume; 2min, the volume of the mobile phase A is 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.
Claims (10)
1. A preparation method of 4, 4-dipyrrole-2, 2-bipyridine is characterized in that: the substrate 4, 4-dibromo-2, 2-bipyridyl is subjected to alkylation reaction under the action of tetrahydropyrrole, so that the product 4, 4-dipyrrole-2, 2-bipyridyl is synthesized in one step.
2. The method of claim 1, wherein: the tetrahydropyrrole is both a reactant, and a base and a solvent of the reaction.
3. The method of claim 1, wherein: the mass volume ratio of the fed materials of the substrate and the tetrahydropyrrole is 1: (10 to 20).
4. The method of claim 1, wherein: the reaction temperature is 70-90 ℃.
5. The production method according to claim 1, characterized in that: the reaction time is 10 to 24 hours.
6. The method of claim 1, wherein: the preparation method further comprises the following steps: disappearance of the substrate was detected by TLC and purification treatment after LCMS detection of the product.
7. The method of claim 6, wherein: the TLC detection adopts the conditions of petroleum ether/ethyl acetate =1/1, rfSM =0.4 and Rfproduct =0.05.
8. The method of claim 6, wherein: the conditions for LCMS detection are as follows: the instrument is Shimadzu LC-30AD, and the model is LCMS-2020; the mobile phase A is water and 0.04 percent of trifluoroacetic acid, and the mobile phase B is acetonitrile and 0.02 percent of trifluoroacetic acid; elution procedure: mobile phase A + mobile phase B =100%,0min, the volume of the mobile phase A is 5%, and the volume of the mobile phase B is 95%;2min, the volume of the mobile phase A is 95%; [ M + H ] + =295.2; the total flow rate is 1.5000mL/min; the column temperature was 40 ℃.
9. The method of claim 6, wherein: the purification treatment comprises the following steps: cooling the reaction liquid to room temperature, slowly pouring the reaction liquid into 100mL of KOH (1 mol/L), stirring for 0.5-2 hours, separating out a large amount of white solid, leaching the filter cake with water after filtering, adding the leached filter cake into a special solvent, stirring, filtering after uniform stirring to obtain white solid powder, and drying the solid in vacuum.
10. The method for producing according to claim 9, characterized in that: the special solvent is any one of dichloromethane, ethyl acetate, 1, 2-dichloroethane and methyl tert-butyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211078387.3A CN115417809A (en) | 2022-09-05 | 2022-09-05 | Preparation method of 4, 4-dipyrrole-2, 2-bipyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211078387.3A CN115417809A (en) | 2022-09-05 | 2022-09-05 | Preparation method of 4, 4-dipyrrole-2, 2-bipyridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115417809A true CN115417809A (en) | 2022-12-02 |
Family
ID=84202437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211078387.3A Pending CN115417809A (en) | 2022-09-05 | 2022-09-05 | Preparation method of 4, 4-dipyrrole-2, 2-bipyridine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115417809A (en) |
Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004052880A1 (en) * | 2002-12-09 | 2004-06-24 | Astrazeneca Ab | Pyridine derivatives as jnk inhibitors and their use |
| CN101687799A (en) * | 2007-04-16 | 2010-03-31 | 格吕伦塔尔有限公司 | Novel vanilloid receptor ligands and the use thereof for the production of pharmaceuticals |
| US20100184978A1 (en) * | 2007-06-20 | 2010-07-22 | Taku Asaumi | Bipyridine compound, transition metal complex, and method for production of conjugated aromatic compound using the transition metal complex |
| CN102304080A (en) * | 2011-05-13 | 2012-01-04 | 天津工业大学 | Method for preparing divinyl dipyridine compounds |
| CN102649797A (en) * | 2011-02-24 | 2012-08-29 | 江南大学 | Synthesis method of novel compound 4,4'-bis(trimethylsilyl)-2,2'-bipyridyl |
| CN102766088A (en) * | 2012-07-30 | 2012-11-07 | 无锡弗里斯特生物科技有限公司 | Novel process for synchronizing 4,4'-dibromo-2,2'-bipyridyl |
| US20130079320A1 (en) * | 2011-09-26 | 2013-03-28 | Gruenenthal Gmbh | Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands |
| CN103554094A (en) * | 2013-11-19 | 2014-02-05 | 郑州西格玛化工有限公司 | Method for preparing 2,2'-bipyridyl-4,4-(5-hexyl-2-thiophene) |
| CN104650049A (en) * | 2013-08-28 | 2015-05-27 | 广东东阳光药业有限公司 | Substitutive pyridine compound and application method and application thereof |
| CN105130885A (en) * | 2015-08-25 | 2015-12-09 | 江西师范大学 | Aromatic diamine containing bipyridyl structure and synthesis method thereof |
| CN109956931A (en) * | 2017-12-26 | 2019-07-02 | 迈第康(上海)生物医药科技有限公司 | Tetrahydropyrrole compound, preparation method, pharmaceutical composition and purposes |
| US20190345122A1 (en) * | 2018-05-08 | 2019-11-14 | Colorado State University Research Foundation | Methods for forming aryl carbon-nitrogen bonds using light and photoreactors useful for conducting such reactions |
| CN110801841A (en) * | 2019-11-27 | 2020-02-18 | 中国科学院大连化学物理研究所 | Catalyst for preparing 2, 2' -bipyridine by coupling synthesis of pyridine and preparation method and application thereof |
| US20200270212A1 (en) * | 2017-09-28 | 2020-08-27 | Kobelco Eco-Solutions Co., Ltd. | Electron donor, and method for synthesizing 4, 4'-bipyridine using electron donor |
| EP3789378A1 (en) * | 2019-09-06 | 2021-03-10 | Grünenthal GmbH | Piperidines or piperidones substituted with urea and heteroaryl |
| CN113336697A (en) * | 2021-06-04 | 2021-09-03 | 厦门大学 | CDK9 inhibiting compound and application thereof |
| CN113933501A (en) * | 2021-11-09 | 2022-01-14 | 吉林中科研伸科技有限公司 | Immunomagnetic bead and preparation method and application thereof |
-
2022
- 2022-09-05 CN CN202211078387.3A patent/CN115417809A/en active Pending
Patent Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004052880A1 (en) * | 2002-12-09 | 2004-06-24 | Astrazeneca Ab | Pyridine derivatives as jnk inhibitors and their use |
| CN101687799A (en) * | 2007-04-16 | 2010-03-31 | 格吕伦塔尔有限公司 | Novel vanilloid receptor ligands and the use thereof for the production of pharmaceuticals |
| US20100184978A1 (en) * | 2007-06-20 | 2010-07-22 | Taku Asaumi | Bipyridine compound, transition metal complex, and method for production of conjugated aromatic compound using the transition metal complex |
| CN102649797A (en) * | 2011-02-24 | 2012-08-29 | 江南大学 | Synthesis method of novel compound 4,4'-bis(trimethylsilyl)-2,2'-bipyridyl |
| CN102304080A (en) * | 2011-05-13 | 2012-01-04 | 天津工业大学 | Method for preparing divinyl dipyridine compounds |
| US20130079320A1 (en) * | 2011-09-26 | 2013-03-28 | Gruenenthal Gmbh | Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands |
| CN102766088A (en) * | 2012-07-30 | 2012-11-07 | 无锡弗里斯特生物科技有限公司 | Novel process for synchronizing 4,4'-dibromo-2,2'-bipyridyl |
| CN104650049A (en) * | 2013-08-28 | 2015-05-27 | 广东东阳光药业有限公司 | Substitutive pyridine compound and application method and application thereof |
| CN103554094A (en) * | 2013-11-19 | 2014-02-05 | 郑州西格玛化工有限公司 | Method for preparing 2,2'-bipyridyl-4,4-(5-hexyl-2-thiophene) |
| CN105130885A (en) * | 2015-08-25 | 2015-12-09 | 江西师范大学 | Aromatic diamine containing bipyridyl structure and synthesis method thereof |
| US20200270212A1 (en) * | 2017-09-28 | 2020-08-27 | Kobelco Eco-Solutions Co., Ltd. | Electron donor, and method for synthesizing 4, 4'-bipyridine using electron donor |
| CN109956931A (en) * | 2017-12-26 | 2019-07-02 | 迈第康(上海)生物医药科技有限公司 | Tetrahydropyrrole compound, preparation method, pharmaceutical composition and purposes |
| US20190345122A1 (en) * | 2018-05-08 | 2019-11-14 | Colorado State University Research Foundation | Methods for forming aryl carbon-nitrogen bonds using light and photoreactors useful for conducting such reactions |
| EP3789378A1 (en) * | 2019-09-06 | 2021-03-10 | Grünenthal GmbH | Piperidines or piperidones substituted with urea and heteroaryl |
| CN110801841A (en) * | 2019-11-27 | 2020-02-18 | 中国科学院大连化学物理研究所 | Catalyst for preparing 2, 2' -bipyridine by coupling synthesis of pyridine and preparation method and application thereof |
| CN113336697A (en) * | 2021-06-04 | 2021-09-03 | 厦门大学 | CDK9 inhibiting compound and application thereof |
| CN113933501A (en) * | 2021-11-09 | 2022-01-14 | 吉林中科研伸科技有限公司 | Immunomagnetic bead and preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| AHNEMAN, DEREK T.，等: "C-H functionalization of amines with aryl halides by nickel-photoredox catalysis", CHEMICAL SCIENCE, vol. 7, no. 12, pages 9 * |
| FRANCESCO DE BON，等: "Catalytic Halogen Exchange in Supplementary Activator and Reducing Agent Atom Transfer Radical Polymerization for the Synthesis of Block Copolymers", MACROMOLECULAR RAPID COMMUNICATIONS, vol. 42, no. 4, pages 19 * |
| 乐贵洲;黄乾明;邹平;: "中氮茚的合成研究进展", 有机化学, no. 09, pages 1060 - 1068 * |
| 朱文润;邓晓怡;魏江存;阙祖亮;: "3-二氢吡咯烷基螺环氧化吲哚及其衍生物的合成与表征", 井冈山大学学报(自然科学版), no. 01, pages 32 - 36 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104447443A (en) | Preparation method for apremilast and intermediate of apremilast | |
| CN108997128B (en) | Preparation method of pregabalin intermediate 3-nitromethyl-5-ethyl methylhexanoate | |
| CN108047187B (en) | Preparation method of xanthone | |
| CN108752186B (en) | Preparation method of 2-benzyl-5-trifluoromethylbenzoic acid | |
| CN115417809A (en) | Preparation method of 4, 4-dipyrrole-2, 2-bipyridine | |
| CN107056612B (en) | Synthesis method of trifluoropyruvate compound | |
| CN100439381C (en) | Di(acetylacetone)palladium(II)synthesis method | |
| CN106636241B (en) | Method for preparing esmollin intermediate by enzyme method | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN114644587A (en) | Synthesis process of intermediate bicyclic imine of anti-novel coronavirus pneumonia medicine Paxlovid | |
| CN108623493B (en) | Under mild condition with CO2N-formylation synthesis method for carbon source | |
| CN102942548A (en) | Delta-dodecalactone synthesis method | |
| CN111320664B (en) | Preparation method of 24-cholenenoic acid ethyl ester | |
| CN110655485A (en) | Preparation method of N-substituted indolone | |
| CN113004248A (en) | Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt | |
| CN107903158B (en) | Synthesis method of 1,2, 3-triphenylpropyl-1-ketone | |
| CN111592471B (en) | Method for synthesizing cephalosporin active ester intermediate through bromination reaction | |
| CN110963946A (en) | Preparation method of sodium methyl taurate | |
| CN111718245B (en) | Method for preparing deuterated chemicals through photocatalytic decarboxylation conversion | |
| CN112441921B (en) | Method for synthesizing 9-acetoxyl-9, 10-dihydrophenanthrene compound by virtue of iridium photocatalysis | |
| CN112500275B (en) | Preparation method of palladium acetylacetonate | |
| CN114133412B (en) | Preparation method of chiral 1, 2-bis [ (2-methoxyphenyl) phenylphosphinyl ] ethane | |
| CN115650322A (en) | Method for preparing nitrosyl ruthenium nitrate | |
| CN107857697B (en) | Synthesis method of 2-methyl-1, 3-diphenylpropan-1-one | |
| CN110790708B (en) | Preparation method of Ailixipine intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |