CN109970649B - Preparation method of 1, 2-dimethyl-3-phenylpyrazoline perchlorate - Google Patents
Preparation method of 1, 2-dimethyl-3-phenylpyrazoline perchlorate Download PDFInfo
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- CN109970649B CN109970649B CN201910206973.3A CN201910206973A CN109970649B CN 109970649 B CN109970649 B CN 109970649B CN 201910206973 A CN201910206973 A CN 201910206973A CN 109970649 B CN109970649 B CN 109970649B
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- dimethylhydrazine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
A method for preparing high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate by using industrial waste 1, 2-dimethylhydrazine as a raw material is an important intermediate of medicines and pesticides. In order to overcome the defects of instability of hydrazine compounds, more reaction byproducts and the like, the invention properly adds a related impurity protective agent and an antioxidant into the initial raw materials before reaction, and carries out mannich reaction in a higher alcohol solvent to obtain high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate powdery crystals, thereby avoiding the complex purification steps in industrial production caused by more residual types of final target impurities, solving the conventional method for industrially producing high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate, controlling and eliminating all impurity sources, realizing the advantages of commercial scale production, cost reduction, simple equipment and the like.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a technical method for preparing high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate by utilizing industrial waste 1, 2-dimethylhydrazine.
Background
China is a big country for producing monomethylhydrazine, and annual output is at the top of the world. Monomethylhydrazine is a very valuable compound widely used in various industries such as medicine, pesticide, chemical industry, aerospace, missile and the like, and the production of the raw material is greatly increased along with the large demand of the market.
In the industrial preparation of monomethylhydrazine, the by-products generated are 1, 1-dimethylhydrazine and 1, 2-dimethylhydrazine. 1, 1-dimethylhydrazine by-product is separated and sold, and is an important rocket fuel and pharmaceutical intermediate synthesis raw material. Currently there is no known commercial use of 1, 2-dimethylhydrazine other than as a research chemistry use. 0.5 ton of waste liquid with high concentration of 1, 2-dimethyl hydrazine is discharged per 1 ton of monomethylhydrazine, namely 2 kilotons of waste liquid is discharged per year from chemical plants with average annual output of 4 kilotons of monomethylhydrazine, the waste liquid is a highly toxic dangerous substance, is inflammable, can form explosive mixtures with steam and air, and is extremely easy to combust and explode or decompose highly toxic gases when encountering open fire and high heat. Therefore, the recovered waste liquid can only be incinerated or decomposed by an incinerator, which not only pollutes the environment, but also wastes resources.
Nitrogen-containing compounds are an important class of organic compounds. Among the nitrogen-containing five-membered heterocyclic compounds, compounds containing a pyrazole ring structural unit have a wide range of biological activities. The pyrazoline derivative can be used as an intermediate to synthesize a plurality of compounds with important biological activity, and the compounds have important functions in the fields of biological medicines, pesticides, dyes and the like. Therefore, the key to the effective conversion of industrial waste 1, 2-dimethylhydrazine to a commercially useful form is the interest in the development and production of high purity and high activity pyrazoline derivatives.
The conventional method for producing the 1, 2-dimethyl-5-phenylpyrazoline intermediate is to use the byproduct 1, 2-dimethylhydrazine as a starting material to react with paraformaldehyde and acetophenone through mannich reaction to obtain a target product. The hydrazine compounds used in the conventional method disclosed in US3818095 are unstable and are easily oxidized into complex systems of hydrazine derivatives, for example, 1, 2-dimethylhydrazine, which is a byproduct in the production of monomethylhydrazine, contains a small amount of easily oxidizable compounds such as 1, 1-dimethylhydrazine, 1-methylhydrazine, hydrazine hydrate and methylamines, and the by-products are used as starting materials to directly synthesize the target compounds, so that the crude intermediate products have complex components, and complex purification and separation steps such as ion exchange resin or electrodialysis are inevitably used in the final separation and purification steps, which increases the production cost.
The process by which the raw materials for the production of pyrazolines are obtained, in the first place, to obtain high-quality intermediates is very important. 1, 2-dimethyl-3-phenylpyrazoline is one of such intermediates. Another complicated ring-closing reaction, etc., in which 1, 2-dimethylhydrazine as a starting material contains other hydrazines and derivatives thereof such as dimethylamine and its oxide, generates various hydrazines.
The invention content is as follows:
the invention aims to solve the problems that the byproduct 1, 2-dimethylhydrazine in the industrial waste discharged during the synthesis of the monomethylhydrazine can be fully utilized, the environmental pollution and the waste of resources caused by such dangerous compounds are avoided, and the waste is changed into valuable in order to better realize the industrial waste liquid, and the invention provides a method for realizing the purpose of utilizing the industrial waste containing the byproduct 1, 2-dimethylhydrazine in the monomethylhydrazine production process through the conventional mannich reaction. In order to complete and overcome the defects, the method comprises the steps of properly adding a related impurity protective agent into the initial raw materials before reaction, then adding an antioxidant, carrying out mannich reaction in a higher alcohol solvent, acidifying by perchloric acid, cooling, crystallizing, centrifugally separating and drying in vacuum according to a conventional method to obtain high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate powdery crystals, avoiding the complicated purification steps in industrial production caused by various types of final target impurities, and avoiding separation and purification processes such as macroporous resin or electrodialysis. Solves the conventional method for industrially producing the high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate, and controls and eliminates all impurity sources.
The invention obtains the high-purity 1, 2-dimethyl-3-phenylpyrazoline chlorate intermediate after the technology is improved, simplifies the purification step, improves the product stability and reduces the cost. What should be pointed out is that the above effects can be obtained by the improved method selected by strict experimental data, and the invention gives important consideration to the aspects of the type of the compound added into the reaction system, the proportion of the original materials, the reaction time, the temperature control and the like, solves the problems existing in the conventional method for industrially producing the 1, 2-dimethyl-3-phenylpyrazoline chlorate intermediate, and controls and eliminates the impurity source. It has thus been surprisingly discovered that the process of the present invention allows for the cost-effective production of high purity 1, 2-dimethyl-3-phenylpyrazoline chlorate process.
The invention aims to solve the technical problems, the adopted technical scheme is that a related impurity protective agent which can react with key impurities without influencing a target product is added into a key industrial raw material 1, 2-dimethylhydrazine before reactants in a first working section are mixed, mixing treatment is carried out, a limited amount of antioxidant is added into a reactant mixed solution in a second working section for mannich reaction, and a final crude product is acidified by perchloric acid and then can be subjected to conventional methods of cooling crystallization, centrifugal separation, drying and the like to obtain a high-purity raw material drug intermediate 1, 2-dimethyl-3-phenylpyrazoline chlorate, and the method comprises the following steps: 1. the molecular formula of the component 1, 2-dimethylhydrazine is CH3NHNHCH3(ii) a The molecular formula of paraformaldehyde is (CH)2O)n(ii) a The molecular formula of the acetophenone is C6H5COCH3(ii) a The molecular formula of the target product 1, 2-dimethyl-3-phenylpyrazoline chlorate is C11N2H14ClO4(ii) a The related impurity protective agent is one or a mixture of two of amides, acetic acid and related salts thereof, formic acid and related salts thereof, sodium nitrite, acid anhydride, methyl formate or aldehydes and ketones; the antioxidant is at least one of resorcinol, phosphorous acid, vitamin C, 1-butyl-1-methylpyrrolidine chloride, quercetin, 6-butylphenol, chloro (1-butyl-3-methylimidazole), tert-butyl-p-diphenol and citric acid; the higher alcohol solvent is at least one of absolute ethyl alcohol, isopropanol, glycerol, methanol and glycol solvent.
The method of the invention and the existing known method for preparing 1, 2-dimethyl-3-phenylpyrazoline chlorate have many advantages described above, and the method realizes the values of changing waste into valuable, reducing the cost, realizing commercial large-scale production, and being simple in equipment and easy to operate.
Specific details of the process of the present invention are set forth in the following examples, which are provided as an example and are not to be construed as limiting the scope of the invention.
Detailed Description
Example 1
In a three-necked round-bottomed flask with mechanical stirrer, dropping funnel and reflux condenser, 60g (1mol) of 1, 2-dimethylhydrazine, 120g (1mol) of acetophenone, 30g (1mol) of formaldehyde and 300ml of absolute ethanol are added and mixed, then the reaction mixture is heated at the same temperature until 1, 2-dimethyl-5-phenylpyrazoline is formed, appropriate 70% perchloric acid is added dropwise for acidification and cooling filtration to obtain a brown solid, and the brown solid is washed, recrystallized by ethanol, filtered with suction and dried in vacuum at 60 ℃ to obtain yellow powder, 222g is obtained, the yield is 81.1% and the purity is 95.4%.
Example 2
In a three-neck round-bottom flask with a mechanical stirrer, a dropping funnel and a reflux condenser, 60g (1mol) of 1, 2-dimethylhydrazine is added with a small amount of benzaldehyde acetone mixed solution to be stirred and warmed for 20min, 120g of acetophenone (1mol), 30g of formaldehyde (1mol), a small amount of citric acid and 300ml of isopropanol are added to be mixed, then the reaction mixture is heated at the same temperature until 1, 2-dimethyl-3-phenylpyrazoline is formed, appropriate 70% perchloric acid is added dropwise to be acidified, cooled and filtered to obtain white solid, washing, crude products are recrystallized by isopropanol, suction filtration and vacuum drying at 60 ℃ to obtain white crystalline powder, 258g of the product is obtained, the yield is 94.3%, and the purity is 99.4%.
Example 3
In a three-neck round-bottom flask with a mechanical stirrer, a dropping funnel and a reflux condenser, 60g (1mol) of 1, 2-dimethylhydrazine is added with a small amount of acetic anhydride acetone solution to be stirred and warmed for 20min, 120g of acetophenone (1mol), 30g of formaldehyde (1mol), a small amount of tert-butyl-p-diphenol and citric acid are added, 300ml of isopropanol is added to be mixed, then the reaction mixture is heated at the same temperature until 1, 2-dimethyl-5-phenylpyrazoline is formed, appropriate 70% perchloric acid is added dropwise to be acidified, cooled and filtered to obtain white solid, washing, crude products are recrystallized by isopropanol, filtered, and vacuum drying is carried out at 60 ℃ to obtain white crystalline powder, 256g of products are obtained, the yield is 93.7%, and the purity is 99.5%.
Claims (2)
1. Taking 60g of 1, 2-dimethylhydrazine, adding a small amount of benzaldehyde acetone mixed solution into a three-neck round-bottom flask with a mechanical stirrer, a dropping funnel and a reflux condenser, stirring and warming for 20min, adding 120g of acetophenone, 30g of formaldehyde, a small amount of citric acid and 300ml of isopropanol, mixing, heating the reaction mixture at the same temperature until 1, 2-dimethyl-3-phenylpyrazoline is formed, dropwise adding a proper amount of 70% perchloric acid, acidifying, cooling and filtering to obtain a white solid, washing, recrystallizing a crude product with isopropanol, performing suction filtration, and performing vacuum drying at 60 ℃ to obtain white crystalline powder, thus obtaining 258g of a product.
2. Taking 60g of 1, 2-dimethylhydrazine, adding a small amount of acetic anhydride acetone solution into a three-neck round-bottom flask with a mechanical stirrer, a dropping funnel and a reflux condenser, stirring and warming for 20min, adding 120g of acetophenone, 30g of formaldehyde, a small amount of tert-butyl-p-diphenol and citric acid, adding 300ml of isopropanol, mixing, heating the reaction mixture at the same temperature until 1, 2-dimethyl-5-phenylpyrazoline is formed, dropwise adding a proper amount of 70% perchloric acid, acidifying, cooling and filtering to obtain a white solid, washing, recrystallizing a crude product with isopropanol, performing suction filtration, and performing vacuum drying at 60 ℃ to obtain white crystalline powder, thus obtaining 256g of the product.
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| CN115141146A (en) * | 2021-03-30 | 2022-10-04 | 东力（南通）化工有限公司 | Synthesis method of hypoglycemic active compound 1,2, 3-trimethyl-4- (p-chlorophenyl) -pyrazolium salt |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3818095A (en) * | 1972-04-12 | 1974-06-18 | Schering Corp | Compositions of 1,2-dilower alkyl-3(and/or4)-aryl-3-pyrazolines and salts thereof and method of lowering blood sugar levels with same |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3818095A (en) * | 1972-04-12 | 1974-06-18 | Schering Corp | Compositions of 1,2-dilower alkyl-3(and/or4)-aryl-3-pyrazolines and salts thereof and method of lowering blood sugar levels with same |
Non-Patent Citations (2)
| Title |
|---|
| a Convenient Synthesis of -△3-Pyrazolines.《Journal of the American Chemical Society》.1960,第3988-3992页. * |
| R. L. Hinman等.Alkylhydrazines in the Mannich Reaction * |
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