CN111217779B - Synthetic method of 3-methyl-4-nitro-dibenzofuran - Google Patents
Synthetic method of 3-methyl-4-nitro-dibenzofuran Download PDFInfo
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- CN111217779B CN111217779B CN202010147833.6A CN202010147833A CN111217779B CN 111217779 B CN111217779 B CN 111217779B CN 202010147833 A CN202010147833 A CN 202010147833A CN 111217779 B CN111217779 B CN 111217779B
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
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Abstract
The invention discloses a method for synthesizing 3-methyl-4-nitro-dibenzofuran, which belongs to the technical field of organic synthesis and comprises the following steps: s1, reacting o-chlorophenol with alkali I to form a salt, then carrying out nucleophilic substitution reaction on the salt and 2-nitro-3-chlorotoluene to obtain a mixture I, and carrying out aftertreatment on the mixture I to obtain an intermediate 1; s2, dissolving the intermediate 1 and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride in an aprotic polar solvent, performing intramolecular ring closure reaction under the action of a Pd catalyst and alkali II to obtain a mixture II, and performing aftertreatment on the mixture II to obtain 3-methyl-4-nitro-dibenzofuran; the synthesis method is simple, the raw materials are cheap and easy to purify, and the problems of expensive raw materials and low yield of the traditional method are solved.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of 3-methyl-4-nitro-dibenzofuran.
Background
The nitro group in 3-methyl-4-nitro-dibenzofuran can be easily reduced into amino group, and then the extension of molecular conjugated ring can be realized by the reaction of Ullman, Buchwald-Hartwig, etc., and the compound can be widely used as a raw material in the synthesis reaction of photoelectric materials and in the field of organic light-emitting diodes (CN 110267943).
The synthesis method of 3-methyl-4-nitro-dibenzofuran reported so far is as follows:
in the method, the expensive 2-nitro-3-fluorotoluene is needed in the first step of reaction, and the yield of the second step of reaction is low and is only 52 percent, so the total cost of the synthesis method is high and the synthesis method is not beneficial to industrial production and preparation.
Disclosure of Invention
In order to solve the problems, the invention discloses a synthesis method of 3-methyl-4-nitro-dibenzofuran, which adopts cheap and easily obtained 2-nitro-3-chlorotoluene as a raw material and adopts novel N-heterocyclic carbene (NHC) ligand 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride which is stable to air and water to carry out intramolecular ring closure, improves the ring closure yield and is more suitable for industrial production.
A method for synthesizing 3-methyl-4-nitro-dibenzofuran comprises the following steps:
s1, reacting o-chlorophenol with alkali I to form a salt, then carrying out nucleophilic substitution reaction on the salt and 2-nitro-3-chlorotoluene to obtain a mixture I, and carrying out aftertreatment on the mixture I to obtain an intermediate 1;
s2, dissolving the intermediate 1 and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride in an aprotic polar solvent, performing intramolecular ring closure reaction under the action of a Pd catalyst and alkali II to obtain a mixture II, and performing aftertreatment on the mixture II to obtain 3-methyl-4-nitro-dibenzofuran;
the synthetic route is as follows:
preferably, the S1 reaction conditions are: reacting for 24-30 h at 150-160 ℃ under the protection of inert gas.
Preferably, the alkali I in S1 is KOH aqueous solution with the mass concentration of 50%, the molar ratio of 2-nitro-3-chlorotoluene to o-chlorophenol is 1: 1.3-1.8, and the mass ratio of the alkali I to the o-chlorophenol is 1-1.1: 1.
Preferably, the post-treatment of the mixture I in S1 specifically comprises the following steps: and cooling the mixture I to 50-60 ℃, adding methylcyclohexane for dissolving, filtering, washing the filtrate to be neutral, carrying out phase separation, concentrating an organic phase, distilling a concentrate, and recrystallizing a main fraction by the methylcyclohexane.
Preferably, the S2 reaction conditions are: reacting for 2-4 h at 100-125 ℃ under the protection of inert gas.
Preferably, the aprotic polar solvent in S2 is dimethylacetamide
Preferably, the base II in S2 is potassium carbonate.
Preferably, the Pd catalyst in S2 is palladium acetate.
Preferably, the amount ratio of S2 intermediate 1 to aprotic polar solvent is 1 g: 2-4 ml, the mass ratio of the intermediate 1 to the Pd catalyst is 19-59: 1, the mass ratio of the intermediate 1 to 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride is 5-15.5: 1, and the mass ratio of the intermediate 1 to the alkali II is 1: 1-1.1.
Preferably, the post-treatment of the mixture II in S2 specifically comprises the following steps: and concentrating the mixture II, pulping the concentrate by using ethanol, filtering, pulping the filter cake by using water and ethanol in sequence, filtering, drying the filter cake, removing the catalyst by passing through a column, desolventizing the liquid passing through the column at normal pressure, and recrystallizing by using toluene and ethanol.
Compared with the prior art, the invention has the following beneficial effects:
the synthesis method is simple, the raw materials are cheap and easy to purify, the problems of expensive raw materials and low yield of the traditional method are solved, and particularly, the cheap and easily-obtained 2-nitro-3-chlorotoluene is used as the raw material, the novel NHC ligand 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride is used for intramolecular ring closure, the ligand is stable to air and water, the ring closure yield is improved, the overall cost is reduced, and the method is more suitable for industrial production.
Drawings
FIG. 1 is a LC-MS spectrum of 3-methyl-4-nitro-dibenzofuran obtained in example 1.
Detailed Description
In order to make the technical solutions of the present invention better understood and implemented by those skilled in the art, the present invention is further described below with reference to the following specific embodiments and the accompanying drawings, but the embodiments are not meant to limit the present invention.
The invention provides a synthetic method of 3-methyl-4-nitro-dibenzofuran, which comprises the following steps:
s1, reacting o-chlorophenol with alkali I to form a salt, then carrying out nucleophilic substitution reaction on the salt and 2-nitro-3-chlorotoluene to obtain a mixture I, and carrying out aftertreatment on the mixture I to obtain an intermediate 1;
s2, dissolving the intermediate 1 and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride in an aprotic polar solvent, performing intramolecular ring closure reaction under the action of a Pd catalyst and alkali II to obtain a mixture II, and performing aftertreatment on the mixture II to obtain 3-methyl-4-nitro-dibenzofuran;
the synthetic route is as follows:
the synthesis method is specifically described below by examples 1 to 2.
Example 1
A synthetic method of 3-methyl-4-nitro-dibenzofuran specifically comprises the following steps:
the first step is as follows:
under the protection of inert gas, adding 1896g of 50% KOH aqueous solution into a reaction bottle, dropwise adding 1890g of o-chlorophenol in an ice water bath, stirring at room temperature for 1h after the dropwise adding is finished, adding 1700g of 2-nitro-3-chlorotoluene, heating to 150 ℃, reacting for 30h, and stopping heating. Cooling to 60 deg.C, adding 22000ml of methylcyclohexane, stirring for 0.5h, filtering, and washing the filtrate with hot water to neutrality. The organic phase was concentrated at 103 ℃ under atmospheric pressure, the residue was distilled and the main fraction was recrystallized from methylcyclohexane to give 11627.6 g of intermediate, 62.3% yield, GC > 99.3%.
The second step is that:
under the protection of inert gas, 1000ml of dimethylacetamide (DMAc), 1500 g of intermediate, 527g of potassium carbonate, 25.8g of palladium acetate and 97g of 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride are added into a reaction bottle, and the temperature is increased to 100 ℃ to react for 4 hours, so that the heating is stopped. Concentrating under reduced pressure, adding ethanol, stirring at room temperature for 0.5h, filtering, pulping the filter cake with water and ethanol respectively, drying the filter cake to constant weight, passing through a column to remove the catalyst, desolventizing the solution passing through the column at 85 ℃ under normal pressure, adding toluene and ethanol into the residue, and recrystallizing to obtain 360.7g of 3-methyl-4-nitro-dibenzofuran, wherein the yield is 83.7 percent and the HPLC is more than 99.9 percent. As shown in fig. 1, LC-MS 227.
Example 2
A synthetic method of 3-methyl-4-nitro-dibenzofuran specifically comprises the following steps:
the first step is as follows:
under the protection of inert gas, 810g of 50% KOH solution is added into a reaction bottle, 770g (1.3) of o-chlorophenol is dropwise added under ice bath, after the dropwise addition is finished, the reaction bottle is stirred for 1h at room temperature, 800g of 2-nitro-3-chlorotoluene is added, and the reaction bottle is heated to 160 ℃ to react for 24h and then stops heating. Cooling to 50 deg.C, adding 5000ml of methylcyclohexane, stirring for 0.5h, filtering, and washing the filtrate with hot water to neutrality. The organic phase was concentrated at 82 ℃ under atmospheric pressure, the residue was distilled and the main fraction was recrystallized from methylcyclohexane to give 1736.8 g of intermediate, 59.93% yield, GC > 99.0%.
The second step is that:
under the protection of inert gas, DMA600ml, intermediate I300 g, potassium carbonate 315g, palladium acetate 5.1g and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride 19.3g are added into a reaction bottle, and the temperature is increased to 125 ℃ for reaction for 2h, and the heating is stopped. Concentrating under reduced pressure, adding ethanol, stirring at room temperature for 0.5h, filtering, pulping the filter cake with water and ethanol respectively, drying the filter cake to constant weight, passing through a column to remove the catalyst, desolventizing the solution passing through the column at 110 ℃ under normal pressure, adding toluene and ethanol into the residue, and recrystallizing to obtain 206.1g of 3-methyl-4-nitro-dibenzofuran, wherein the yield is 79.7 percent, and the HPLC is more than 99.9 percent.
As can be seen from the above examples 1-2, in the first step of the invention, cheap and easily available 2-nitro-3-chlorotoluene is used as a raw material to successfully prepare the intermediate 1, so that the cost is saved; and in the second step, a novel NHC ligand 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride which is relatively stable to air and water is adopted for intramolecular ring closure, so that the ring closure yield is improved (79.7-83.7 percent), is higher than 52 percent in the background technology, and is more suitable for industrial production.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, it is intended that such changes and modifications be included within the scope of the appended claims and their equivalents.
Claims (8)
1. A method for synthesizing 3-methyl-4-nitro-dibenzofuran is characterized by comprising the following steps:
s1, reacting o-chlorophenol with alkali I to form a salt, then carrying out nucleophilic substitution reaction on the salt and 2-nitro-3-chlorotoluene to obtain a mixture I, and carrying out aftertreatment on the mixture I to obtain an intermediate 1;
s2, dissolving the intermediate 1 and 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride in an aprotic polar solvent, performing intramolecular ring closure reaction under the action of a Pd catalyst and alkali II to obtain a mixture II, and performing aftertreatment on the mixture II to obtain 3-methyl-4-nitro-dibenzofuran;
the synthetic route is as follows:
the reaction conditions of the S1 are as follows: reacting for 24-30 h at 150-160 ℃ under the protection of inert gas;
in S1, the alkali I is a KOH aqueous solution with the mass concentration of 50%, the molar ratio of 2-nitro-3-chlorotoluene to o-chlorophenol is 1: 1.3-1.8, and the mass ratio of the alkali I to the o-chlorophenol is 1-1.1: 1.
2. The method for synthesizing 3-methyl-4-nitro-dibenzofuran of claim 1, wherein the post-treatment of mixture i in S1 comprises the following steps: and cooling the mixture I to 50-60 ℃, adding methylcyclohexane for dissolving, filtering, washing the filtrate to be neutral, carrying out phase separation, concentrating an organic phase, distilling a concentrate, and recrystallizing a main fraction by the methylcyclohexane.
3. The method for synthesizing 3-methyl-4-nitro-dibenzofuran of claim 1, wherein the S2 reaction conditions are as follows: reacting for 2-4 h at 100-125 ℃ under the protection of inert gas.
4. The method of claim 1, wherein the aprotic polar solvent of S2 is dimethylacetamide.
5. The method of claim 1, wherein the base II in S2 is potassium carbonate.
6. The method of claim 1, wherein the Pd catalyst in S2 is palladium acetate.
7. The method of claim 1, wherein the amount of S2 intermediate 1 to aprotic polar solvent is 1 g: 2-4 ml, the mass ratio of the intermediate 1 to the Pd catalyst is 19-59: 1, the mass ratio of the intermediate 1 to 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride is 5-15.5: 1, and the mass ratio of the intermediate 1 to the alkali II is 1: 1-1.1.
8. The method for synthesizing 3-methyl-4-nitro-dibenzofuran of claim 1, wherein the post-treatment of mixture II in S2 comprises the following steps: and concentrating the mixture II, pulping the concentrate by using ethanol, filtering, pulping the filter cake by using water and ethanol in sequence, filtering, drying the filter cake, removing the catalyst by passing through a column, desolventizing the liquid passing through the column at normal pressure, and recrystallizing by using toluene and ethanol.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234987A (en) * | 2008-03-05 | 2008-08-06 | 东华大学 | Method for preparing 4,4'-di(2,4-dinitrophenoxy)diphenyl ether |
| CN109942527A (en) * | 2019-04-26 | 2019-06-28 | 新乡市润宇新材料科技有限公司 | A kind of synthetic method of 3- bromine dibenzofurans |
| CN110267943A (en) * | 2017-02-14 | 2019-09-20 | 出光兴产株式会社 | Novel compound, organic electroluminescent element using same, and electronic device |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234987A (en) * | 2008-03-05 | 2008-08-06 | 东华大学 | Method for preparing 4,4'-di(2,4-dinitrophenoxy)diphenyl ether |
| CN110267943A (en) * | 2017-02-14 | 2019-09-20 | 出光兴产株式会社 | Novel compound, organic electroluminescent element using same, and electronic device |
| CN109942527A (en) * | 2019-04-26 | 2019-06-28 | 新乡市润宇新材料科技有限公司 | A kind of synthetic method of 3- bromine dibenzofurans |
Non-Patent Citations (1)
| Title |
|---|
| 1，3－双(2，6－二烷基苯基) 氯化咪唑鎓盐的合成及其在Pd催化Suzuki－Miyaura偶联反应中的应用;于宏伟等;《精细石油化工进展》;20130331;第14卷(第2期);56-58页 * |
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