CN107827822B - Method for synthesizing 2- (nitromethylene) imidazolidine by one-pot method - Google Patents
Method for synthesizing 2- (nitromethylene) imidazolidine by one-pot method Download PDFInfo
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Abstract
The invention provides a method for synthesizing 2- (nitromethylene) imidazolidine by a one-pot method, which comprises the following steps: adding 1, 1-dichloro-2-nitroethylene, fatty alcohol and alkali into a reaction container, and reacting at low temperature for 1-4 h to obtain an intermediate A; and then, adding ethylenediamine into the reaction container, heating for reaction for 5-15 h, naturally cooling to normal temperature, and performing post-treatment to obtain the 2- (nitromethylene) imidazolidine. The method has the advantages of easily available raw materials, short reaction steps, good reaction activity, mild operation conditions, green and environment-friendly process and low production cost; in addition, the method can obtain higher product yield and higher product purity, and can show favorable characteristics of environment-friendly process, simple operation steps, less equipment occupation, high equipment utilization rate and the like, so the method is particularly suitable for large-scale industrial production.
Description
Technical Field
The invention relates to a synthesis method of a fine chemical intermediate, in particular to a method for synthesizing 2- (nitromethylene) imidazolidine by a one-pot method.
Background
The 2- (nitromethylene) imidazolidine is an important fine chemical intermediate, and is mainly used as an important synthetic raw material of pesticides paichongding and cycloxaprid. Wherein the molecular formula of the 2- (nitromethylene) imidazolidine is as follows: c4H7N3O2The English name is: 2- (nitromethyl) imidazolidine; the CAS number is: 13623-98-8; the structural formula is as follows:
in the prior art, a series of synthetic methods of 2- (nitromethylene) imidazolidine are reported, however, the related synthetic methods reported in many documents are complex in process flow, poor in operability, low in product yield and high in production cost when used as an industrial production process. For example, a document in Journal of Medicinal Chemistry,2012,55(1),465-474 reports a preparation process of reacting 1, 1-dithiomethylnitroethylene with ethylenediamine to obtain 2- (nitromethylene) imidazolidine, however, the reaction process needs to be stirred overnight under ethanol reflux condition, and colorless toxic gas methyl mercaptan is generated during the reaction process, so the preparation process is not suitable for large-scale industrial production. For another example, chinese patent application CN103524489A discloses a synthesis process of 2-chloro-5- ((2- (nitromethylene) imidazolin-1-yl) methyl) pyridine, in which dichloronitroethylene is obtained by nitration and separation of vinylidene chloride, and then reacted with ethylenediamine to generate 2- (nitromethylene) imidazolidine, the yield is only 57%, and the irritative dichloronitroethylene needs to be separated; meanwhile, the synthesis process adopted by the chinese patent application requires that 1, 1-dichloro-2-nitroethylene is dripped into sodium methoxide for reaction, 1-dimethoxy-2-nitroethylene is obtained by separation, and then the obtained product is heated and refluxed with ethylenediamine for 24 hours to synthesize 2- (nitromethylene) imidazolidine, wherein the total separation yield of the obtained product is only 18%, and thus, the overall yield of the synthesis process is too low and the process operation is complex, and therefore, the synthesis process is not suitable for large-scale industrial production.
Therefore, in the actual industrial production process, a new synthesis method of 2- (nitromethylene) imidazolidine needs to be provided, so that the synthesis method can obtain higher product yield and higher product purity and can show the favorable characteristics of environment-friendly process, simple operation steps, less equipment occupation, high equipment utilization rate and the like.
Disclosure of Invention
In order to overcome the technical defects in the prior art, the invention aims to provide a synthesis method of 2- (nitromethylene) imidazolidine suitable for industrial production, and the inventor skillfully designs and implements a one-pot process, so that multi-step reactions can be smoothly completed in the same reaction vessel, and finally a product with higher purity can be obtained with higher yield.
Specifically, the invention provides a method for synthesizing 2- (nitromethylene) imidazolidine by a one-pot method, which comprises the following synthetic route:
and, comprising the steps of:
s1: adding 1, 1-dichloro-2-nitroethylene, fatty alcohol and alkali into a reaction container, and reacting at low temperature for 1-4 h to obtain an intermediate A; the intermediate A is not required to be separated, and the next reaction operation is directly carried out;
s2: and then, adding ethylenediamine into the reaction container, heating for reaction for 5-15 h, naturally cooling to normal temperature, and performing post-treatment to obtain the 2- (nitromethylene) imidazolidine.
Naturally cooling to normal temperature in S2, standing for a period of time to precipitate a large amount of solids, and performing post-treatment operations such as suction filtration and drying to obtain the target product 2- (nitromethylene) imidazolidine.
Preferably, in the above one-pot synthesis method of 2- (nitromethylene) imidazolidine, the fatty alcohol is selected from any one of the following: methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, isobutanol, ethylene glycol, propylene glycol and glycerol; further preferably, the fatty alcohol is selected from any one of: methanol, ethanol, n-propanol, n-butanol and sec-butanol.
Preferably, in the above one-pot synthesis method of 2- (nitromethylene) imidazolidine, the base is selected from any one of the following: sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, triethylamine, pyridine, piperidine, and sodium hydride. Therefore, the alkali used in the method provided by the invention can be organic alkali or inorganic alkali. Further, the alkali is more preferably sodium hydroxide or potassium hydroxide.
Preferably, in the above one-pot method for synthesizing 2- (nitromethylene) imidazolidine, the molar ratio of the base to the 1, 1-dichloro-2-nitroethylene is (2 to 4): 1; on the basis, the molar ratio of the base to the 1, 1-dichloro-2-nitroethylene is more preferably (2.5 to 3.5): 1.
preferably, in the one-pot synthesis method of 2- (nitromethylene) imidazolidine, the temperature of the low-temperature reaction described in S1 is from-20 ℃ to 30 ℃, more preferably from-10 ℃ to 20 ℃.
In the above one-pot method for synthesizing 2- (nitromethylene) imidazolidine, the temperature of the heating reaction in S2 is preferably 60 to 150 ℃, and more preferably 80 to 110 ℃.
In the above one-pot method for synthesizing 2- (nitromethylene) imidazolidine, the room temperature in S2 is preferably 10 to 35 ℃, and more preferably 10 to 25 ℃.
Compared with the synthesis process of 2- (nitromethylene) imidazolidine disclosed in the prior art, the method for synthesizing the 2- (nitromethylene) imidazolidine by the one-pot method provided by the invention has the following beneficial effects: the method has the advantages of easily available raw materials, short reaction steps, good reaction activity, mild operation conditions and green and environment-friendly process; specifically, in the method, the prepared intermediate A can be subjected to two-step synthesis unit operation in the same reaction container without further separation and purification, the equipment utilization rate is high, the post-treatment operation is simple, the reaction is finished, and after the solid is separated out by cooling, the target product is obtained by suction filtration; the method of the invention completes two-step reaction in the same reaction vessel, so that the solvent dosage is less, and multiple desolventizing recovery is not needed, therefore, the solvent dosage is obviously reduced, and the cost for synthesizing the 2- (nitromethylene) imidazolidine is greatly reduced. In a word, the method for synthesizing the 2- (nitromethylene) imidazolidine by the one-pot method can obtain higher product yield and higher product purity, and can show the favorable characteristics of environment-friendly process, simple operation steps, less equipment occupation, high equipment utilization rate and the like, so the method is particularly suitable for large-scale industrial production.
Detailed Description
The present invention will be further described with reference to specific embodiments, but the present invention is not limited to the following embodiments.
The method for synthesizing the 2- (nitromethylene) imidazolidine by the one-pot method comprises the following synthetic route:
and, comprising the steps of: s1: adding 1, 1-dichloro-2-nitroethylene, fatty alcohol and alkali into a reaction container, and reacting at low temperature for 1-4 h to obtain an intermediate A; s2: and then, adding ethylenediamine into the reaction container, heating for reaction for 5-15 h, naturally cooling to normal temperature, and performing post-treatment to obtain the 2- (nitromethylene) imidazolidine.
In a preferred embodiment, the fatty alcohol is selected from any one of the following: methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, isobutanol, ethylene glycol, propylene glycol and glycerol.
In a preferred embodiment, the base is selected from any one of the following: sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, triethylamine, pyridine, piperidine, and sodium hydride.
In a preferred embodiment, the molar ratio of the base to the 1, 1-dichloro-2-nitroethylene is (2 to 4): 1.
in a preferred embodiment, the temperature of the low temperature reaction described in S1 is between-20 ℃ and 30 ℃.
In a preferred embodiment, the temperature of the heating reaction described in S2 is 60 ℃ to 150 ℃.
In a preferred embodiment, the normal temperature in S2 is 10 ℃ to 35 ℃.
Example 1
Adding 1, 1-dichloro-2-nitroethylene (0.12mol) and 150mL of methanol into a 250mL three-neck flask, adding sodium hydroxide (0.4mol), cooling to 0 ℃, and reacting at the low temperature of 0 ℃ for 1h to generate an intermediate A; heating to 20 ℃, adding anhydrous ethylenediamine (0.18mol), and heating and refluxing at 80 ℃ for 6 hours; naturally cooling to normal temperature (20 ℃), carrying out suction filtration, and drying to obtain the 2- (nitromethylene) imidazolidine with the purity of 96% and the yield of 80% (calculated on 1, 1-dichloro-2-nitroethylene).
Example 2
Adding 1, 1-dichloro-2-nitroethylene (0.12mol) and 150mL of ethanol into a 250mL three-neck flask, adding potassium hydroxide (0.45mol), cooling to-5 ℃, and reacting at the low temperature of-5 ℃ for 2 hours to generate an intermediate A; heating to 35 ℃, adding anhydrous ethylenediamine (0.20mol), and heating and refluxing at 100 ℃ for 10 hours; naturally cooling to normal temperature (20 ℃), carrying out suction filtration, and drying to obtain the 2- (nitromethylene) imidazolidine with the purity of 97% and the yield of 84% (calculated on 1, 1-dichloro-2-nitroethylene).
Example 3
Adding 1, 1-dichloro-2-nitroethylene (0.12mol) and 150mL of propanol into a 250mL three-neck flask, adding potassium hydroxide (0.40mol), cooling to 0 ℃, and reacting at the low temperature of 0 ℃ for 3 hours to generate an intermediate A; heating to 40 ℃, adding anhydrous ethylenediamine (0.18mol), and heating and refluxing at 120 ℃ for 5 hours; naturally cooling to normal temperature (25 ℃), carrying out suction filtration, and drying to obtain the 2- (nitromethylene) imidazolidine with the purity of 97% and the yield of 75% (calculated on 1, 1-dichloro-2-nitroethylene).
Example 4
Adding 1, 1-dichloro-2-nitroethylene (0.12mol) and 150mL of methanol into a 250mL three-neck flask, adding potassium hydroxide (0.40mol), cooling to-5 ℃, and reacting at the low temperature of-5 ℃ for 3 hours to generate an intermediate A; heating to 35 ℃, adding anhydrous ethylenediamine (0.22mol), and heating and refluxing at 130 ℃ for reaction for 12 hours; naturally cooling to normal temperature (25 ℃), carrying out suction filtration, and drying to obtain the 2- (nitromethylene) imidazolidine with the purity of 96% and the yield of 82% (calculated by 1, 1-dichloro-2-nitroethylene).
Example 5
Adding 1, 1-dichloro-2-nitroethylene (0.12mol) and 150mL of n-butanol into a 250mL three-neck flask, adding sodium hydroxide (0.40mol), cooling to-10 ℃, and reacting at the low temperature of-10 ℃ for 4 hours to generate an intermediate A; heating to 20 ℃, adding anhydrous ethylenediamine (0.22mol), and heating and refluxing at 100 ℃ for 10 hours; naturally cooling to normal temperature (20 ℃), carrying out suction filtration, and drying to obtain the 2- (nitromethylene) imidazolidine with the purity of 97% and the yield of 85% (calculated on 1, 1-dichloro-2-nitroethylene).
Therefore, the purity of the 2- (nitromethylene) imidazolidine product synthesized by the method for synthesizing the 2- (nitromethylene) imidazolidine by the one-pot method provided by the invention is more than or equal to 96%, and the yield of the product is more than or equal to 75%, so that the method has a prospect suitable for industrial production.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (3)
1. A method for synthesizing 2- (nitromethylene) imidazolidine by a one-pot method is characterized by comprising the following synthetic route:
and, comprising the steps of:
s1: adding 1, 1-dichloro-2-nitroethylene, fatty alcohol and alkali into a reaction container, and reacting at low temperature for 1-4 h to obtain an intermediate A;
s2: then, adding ethylenediamine into the reaction container, heating for reaction for 5-15 h, naturally cooling to normal temperature, and performing post-treatment to obtain 2- (nitromethylene) imidazolidine;
the fatty alcohol is selected from any one of the following: methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, isobutanol, ethylene glycol, propylene glycol and glycerol;
the base is selected from any one of the following: sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, triethylamine, pyridine, piperidine, and sodium hydride;
the molar ratio of the alkali to the 1, 1-dichloro-2-nitroethylene is (2-4): 1;
the temperature of the low-temperature reaction in S1 is-20 ℃ to 30 ℃.
2. The one-pot process for the synthesis of 2- (nitromethylene) imidazolidine according to claim 1, wherein the temperature of the heating reaction in S2 is 60 to 150 ℃.
3. The one-pot method for synthesizing 2- (nitromethylene) imidazolidine according to claim 1, wherein the room temperature in S2 is 10 ℃ to 35 ℃.
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| CN104447690A (en) * | 2014-12-17 | 2015-03-25 | 上海生农生化制品有限公司 | Method for synthesizing chloronitropyridine methyleneimidazolidine through one-pot process |
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| US4025529A (en) * | 1975-09-08 | 1977-05-24 | Shell Oil Company | Preparation of nitroketene aminals |
| KR810001915B1 (en) * | 1980-09-17 | 1981-11-27 | 일동제약 주식회사 | Process for preparing amino alkyl furan deriatives |
| JPS6248681A (en) * | 1985-08-28 | 1987-03-03 | Nippon Tokushu Noyaku Seizo Kk | Production of nitromethylene derivative |
| AU3800793A (en) * | 1992-04-13 | 1993-11-18 | E.I. Du Pont De Nemours And Company | Arthropodical nitroethylenes and nitroguanidines |
| EP0605059A1 (en) * | 1992-12-31 | 1994-07-06 | Shell Internationale Researchmaatschappij B.V. | Nitromethylene compounds and their use as pesticides |
| JP2001500499A (en) * | 1996-09-11 | 2001-01-16 | クノル アクチエンゲゼルシャフト | Method for producing nizatidine |
| EP1997820A4 (en) * | 2006-03-09 | 2009-03-04 | Univ East China Science & Tech | Preparation method and use of compounds having high biocidal activities |
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| CN103524489A (en) * | 2012-07-04 | 2014-01-22 | 华东理工大学 | Synthesis process of 2-chlorin-5-((2-(nitryl methylene) imidazoline-1-yl) methyl) pyridine |
| CN104447690A (en) * | 2014-12-17 | 2015-03-25 | 上海生农生化制品有限公司 | Method for synthesizing chloronitropyridine methyleneimidazolidine through one-pot process |
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