CN114621096A - Synthetic method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride - Google Patents
Synthetic method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride Download PDFInfo
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- CN114621096A CN114621096A CN202011443708.6A CN202011443708A CN114621096A CN 114621096 A CN114621096 A CN 114621096A CN 202011443708 A CN202011443708 A CN 202011443708A CN 114621096 A CN114621096 A CN 114621096A
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- Prior art keywords
- dimethyl
- reaction
- phenylenediamine dihydrochloride
- filtering
- nitro
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- NASDGWFCRRYTDH-UHFFFAOYSA-N 3,5-dimethylbenzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.CC1=CC(C)=C(N)C(N)=C1 NASDGWFCRRYTDH-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000010189 synthetic method Methods 0.000 title description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 238000001914 filtration Methods 0.000 claims abstract description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000019441 ethanol Nutrition 0.000 claims abstract description 11
- VSRYYONYIUUFFY-UHFFFAOYSA-N 2,4-dimethyl-6-nitroaniline Chemical group CC1=CC(C)=C(N)C([N+]([O-])=O)=C1 VSRYYONYIUUFFY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 238000001035 drying Methods 0.000 claims abstract description 6
- 239000012065 filter cake Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 238000004537 pulping Methods 0.000 claims abstract description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000007787 solid Substances 0.000 claims abstract description 4
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 4
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001308 synthesis method Methods 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 claims 3
- 239000012535 impurity Substances 0.000 abstract description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- 239000000047 product Substances 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
- C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
- C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The application discloses a method for synthesizing 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride, which comprises the following steps: step 1) reaction: adding 4-amino-5-nitro-m-xylene, water, absolute ethyl alcohol, 36% concentrated hydrochloric acid and 10% palladium carbon as a catalyst into a reaction container, replacing with nitrogen, introducing hydrogen, and heating to react completely; step 2) post-treatment: after the reaction is finished, filtering, adding ethanol for concentration, separating out a large amount of solid, adding ethanol for pulping, filtering, and drying a filter cake to obtain 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride. The method can obtain the 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride with the purity higher than 98.5 percent, and has better yield and less impurities.
Description
Technical Field
The invention belongs to the field of organic chemistry, and particularly relates to a synthesis method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride.
Background
3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride (compound 1 shown in the following formula) is an important pharmaceutical and chemical intermediate, and is generally obtained by reducing nitro through hydrogenation by 4-amino-5-nitro-m-xylene, but impurities such as compound 2 shown in the following formula are generated due to a side reaction of hydrogenation, the content of compound 2 in the product under a pressurized condition is generally about 8%, and the impurities have similar properties to the product, so that great problems are brought to refining, and the yield is influenced. Compound 1 and compound 2 are of the following structural formulae:
disclosure of Invention
The main purpose of the present application is to provide a method for synthesizing 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride.
The technical scheme is as follows:
a method for synthesizing 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride comprises the following steps:
step 1) reaction: adding 4-amino-5-nitro-m-xylene, water, absolute ethyl alcohol, 36% concentrated hydrochloric acid and 10% palladium carbon as a catalyst into a reaction container, replacing with nitrogen, introducing hydrogen, and heating to react completely;
step 2) post-treatment: after the reaction is finished, filtering, adding ethanol for concentration, separating out a large amount of solid, adding ethanol for pulping, filtering, and drying a filter cake to obtain 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride.
Further, in the step 1), water: the weight ratio of the absolute ethyl alcohol is 0.5-3: 1.
Further, in the step 1), 4-amino-5-nitro-m-xylene: the molar ratio of concentrated hydrochloric acid is 1: 2.
Further, the temperature rise in the step 1) is 40-55 ℃.
Further, the step 1) is carried out under normal pressure after hydrogen is introduced.
The method takes 4-amino-5-nitro-m-xylene as a raw material, directly controls an impurity compound 2 to be below 0.5 percent by controlling hydrogenation conditions, the adding amount of hydrochloric acid, reaction solvents, corresponding reaction temperature, hydrogenation pressure and the like, and after the reaction is finished, solid impurities such as palladium carbon and the like are removed by filtering by utilizing good solubility of product hydrochloride in water, the product is separated out by concentration and water removal, and the 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride with the purity higher than 98.5 percent can be obtained by ethanol pulping, wherein the yield is above 85.0 percent. The reaction formula is as follows:
Detailed Description
In order to make those skilled in the art better understand the technical solutions in the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. 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 application.
Example 1
Adding 92.4g of 4-amino-5-nitro-m-xylene, 462.0g of water, 462.0g of absolute ethyl alcohol, 111.2g of 36% concentrated hydrochloric acid, adding 11.1g of 10% Pd/C, introducing nitrogen for three times for replacement, introducing hydrogen, heating to 50-55 ℃, filtering after the reaction is finished, adding ethanol for concentration, separating out a large amount of products, adding ethanol for pulping, filtering, drying a filter cake to obtain 102.2g of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride, wherein the yield is 87.9%, and the purity is 99.6%.
Example 2
Adding 50g of 4-amino-5-nitro-m-xylene, 250g of water, 500g of absolute ethyl alcohol and 60.2g of 36% concentrated hydrochloric acid into a reaction bottle, adding 6.0g of 10% Pd/C, introducing nitrogen for three times for replacement, introducing hydrogen, heating to 50-55 ℃, filtering after the reaction is finished, adding ethanol for concentration, separating out a large amount of products, adding ethanol for pulping, filtering, and drying a filter cake to obtain 54.0g of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride, wherein the yield is 85.9%, and the purity is 98.6%.
Comparative example 1
Adding 50g of 4-amino-5-nitro-m-xylene and 500g of absolute ethyl alcohol into a reaction bottle, adding 6.0g of 10% Pd/C, introducing nitrogen for three times for replacement, introducing hydrogen for reaction at 1.0-1.5MPa for 24 hours, heating to 50-55 ℃, filtering after the reaction is finished, acidifying the filtrate with hydrochloric acid, filtering, and drying the filter cake to obtain 52.05g of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride, wherein the yield is 82.8% and the purity is 96.5%.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (5)
1. A method for synthesizing 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride is characterized by comprising the following steps:
step 1) reaction: adding 4-amino-5-nitro-m-xylene, water, absolute ethyl alcohol, 36% concentrated hydrochloric acid and 10% palladium carbon as a catalyst into a reaction container, replacing with nitrogen, introducing hydrogen, and heating to react completely;
step 2) post-treatment: after the reaction is finished, filtering, adding ethanol for concentration, separating out a large amount of solid, adding ethanol for pulping, filtering, and drying a filter cake to obtain 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride.
2. The synthesis process according to claim 1, characterized in that in step 1) the ratio of water: the weight ratio of the absolute ethyl alcohol is 0.5-3: 1.
3. The synthesis process according to claim 1, wherein in step 1) the ratio of 4-amino-5-nitro-m-xylene: the molar ratio of concentrated hydrochloric acid is 1: 2.
4. The synthesis method according to claim 1, wherein the temperature rise in the step 1) is 40-55 ℃.
5. The synthesis process according to claim 1, characterized in that the hydrogen gas in step 1) is fed in at atmospheric pressure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011443708.6A CN114621096A (en) | 2020-12-11 | 2020-12-11 | Synthetic method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011443708.6A CN114621096A (en) | 2020-12-11 | 2020-12-11 | Synthetic method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
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| Publication Number | Publication Date |
|---|---|
| CN114621096A true CN114621096A (en) | 2022-06-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011443708.6A Pending CN114621096A (en) | 2020-12-11 | 2020-12-11 | Synthetic method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
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|---|---|---|---|---|
| US5945425A (en) * | 1994-04-29 | 1999-08-31 | G.D. Searle & Co. | Method of using (H+ /K+)ATPase inhibitors as antiviral agents |
| US20060211720A1 (en) * | 2004-12-08 | 2006-09-21 | Glunz Peter W | Heterocyclic compounds as inhibitors of factor VIIa |
| CN102344411A (en) * | 2011-08-01 | 2012-02-08 | 宜兴市新宇化工有限公司 | Method for preparing 2,6-dimethoxy-3,5-diamido-pyridine hydrochloride |
| CN102584825A (en) * | 2011-01-17 | 2012-07-18 | 四川科伦药物研究有限公司 | Method for synthesizing valaciclovir hydrochloride |
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| CN106565509A (en) * | 2016-11-03 | 2017-04-19 | 江苏鼎龙科技有限公司 | Preparation method of 2-amino-4-methylamino methyl benzoate hydrochloride |
| CN107118161A (en) * | 2017-05-05 | 2017-09-01 | 湖北工业大学 | The synthetic method of the carboxylic acid of 2 n-propyl, 4 tolimidazole 6 |
| CN109369448A (en) * | 2018-10-23 | 2019-02-22 | 天津金玺科技发展有限公司 | A kind of method that bimetal composite oxide catalyzes and synthesizes azobenzene compound |
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2020
- 2020-12-11 CN CN202011443708.6A patent/CN114621096A/en active Pending
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