阅读说明：本技术 一种烟碱类化合物烯啶虫胺类似物的合成方法 (Synthetic method of nicotine compound nitenpyram analogue ) 是由 王卫华 郭辉 吴立言 于 2021-10-29 设计创作，主要内容包括：本发明涉及一种烟碱类化合物烯啶虫胺类似物的合成方法,具体包括以下步骤：1)不同缚酸剂对反应收率的影响；2)不同缚酸剂加入量对反应收率的影响；3)不同催化剂对反应收率的影响；4)中间产物A的水解：向500ml四口瓶内加入100g中间物A,200ml浓盐酸,缓慢升温至50℃,保温14小时,液相色谱分析仪检测反应进程,当中间产物A含量低于2％后,转入装有200ml水的1000ml四口瓶中,然后用液碱调节PH至6-7,降温至10℃以下,负压抽滤,水洗两次,烘干得到最终产物B74.6g,收率92％。本发明优点在于：提供了一种烟碱类化合物烯啶虫胺类似物的合成方法,方案设计合理,便于合成,对其合成路线进行了筛选、优化,为工业化生产提供了方向。(The invention relates to a synthetic method of a nicotine compound nitenpyram analogue, which specifically comprises the following steps: 1) influence of different acid-binding agents on reaction yield; 2) the influence of the addition of different acid-binding agents on the reaction yield; 3) the effect of different catalysts on the reaction yield; 4) hydrolysis of intermediate a: adding 100g of intermediate A and 200ml of concentrated hydrochloric acid into a 500ml four-mouth bottle, slowly heating to 50 ℃, keeping the temperature for 14 hours, detecting the reaction process by a liquid chromatographic analyzer, transferring the intermediate A with the content of less than 2 percent into a 1000ml four-mouth bottle filled with 200ml of water, adjusting the pH to 6-7 by using liquid alkali, cooling to below 10 ℃, carrying out suction filtration under negative pressure, washing twice, and drying to obtain a final product B74.6g with the yield of 92 percent. The invention has the advantages that: the synthetic method of the nicotine compound nitenpyram analogue is provided, the scheme design is reasonable, the synthesis is convenient, the synthetic route is screened and optimized, and the direction is provided for industrial production.)

1. A synthetic method of a nicotine compound nitenpyram analogue is characterized by comprising the following steps:

1) influence of different acid-binding agents on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches or slowly dropwise adding the sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine as an acid-binding agent, wherein the temperature is not higher than 45 ℃, and timing and preserving heat at 45 ℃ after the addition is finished; sampling from 6 hours later, detecting the reaction process by a liquid chromatography analyzer, and transferring into a 1000ml four-mouth bottle after the 2-chloro-5-chloromethylpyridine completely reacts; heating to 55 ℃, adding 200ml of dichloroethane and 400ml of water, stirring for half an hour, standing for layering, collecting an organic layer, extracting a water layer twice by using 100ml of dichloroethane, combining the organic layers, cooling to below 5 ℃, separating out a large amount of solids, performing suction filtration under negative pressure, washing the dichloroethane to obtain an intermediate A, drying, weighing, and obtaining the product yield by using different acid-binding agents;

2) influence of different acid-binding agent addition amounts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding potassium carbonate with different masses in batches, keeping the temperature not exceeding 45 ℃, timing at 45 ℃ and keeping the temperature after adding; sampling after 6 hours, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using potassium carbonate with different masses as an acid-binding agent to obtain the product yield;

3) effect of different catalysts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of catalyst into the flask, then slowly heating to 40 ℃, then adding potassium carbonate in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches, keeping the temperature at not more than 45 ℃, timing and preserving the heat at 45 ℃ after the completion of adding; sampling from 6 hours later, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using different catalysts to obtain the product yield;

4) hydrolysis of intermediate a: adding 100g of intermediate A and 200ml of concentrated hydrochloric acid into a 500ml four-mouth bottle, slowly heating to 50 ℃, keeping the temperature for 14 hours, detecting the reaction process by a liquid chromatographic analyzer, transferring the intermediate A with the content of less than 2 percent into a 1000ml four-mouth bottle filled with 200ml of water, adjusting the pH to 6-7 by using liquid alkali, cooling to below 10 ℃, carrying out suction filtration under negative pressure, washing twice, and drying to obtain a final product B74.6g with the yield of 92 percent.

Technical Field

The invention relates to a synthetic method of a nicotine compound nitenpyram analogue.

Background

Neonicotinoid pesticides are hot spots of research in recent years, are novel in structure, unique in action mode, broad in spectrum, high in efficiency, low in toxicity, low in residue, high in selectivity and environment-friendly, and are developed vigorously since the appearance. How to provide a synthetic method of a nicotine compound nitenpyram analogue becomes a research direction.

Disclosure of Invention

The invention aims to provide a synthetic method of a nicotine compound nitenpyram analogue so as to solve the problems in the background technology.

In order to solve the technical problems, the technical scheme provided by the invention is as follows: a synthetic method of a nicotine compound nitenpyram analogue specifically comprises the following steps:

1) influence of different acid-binding agents on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches or slowly dropwise adding the sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine as an acid-binding agent, wherein the temperature is not higher than 45 ℃, and timing and preserving heat at 45 ℃ after the addition is finished; sampling from 6 hours later, detecting the reaction process by a liquid chromatography analyzer, and transferring into a 1000ml four-mouth bottle after the 2-chloro-5-chloromethylpyridine completely reacts; heating to 55 ℃, adding 200ml of dichloroethane and 400ml of water, stirring for half an hour, standing for layering, collecting an organic layer, extracting a water layer twice by using 100ml of dichloroethane, combining the organic layers, cooling to below 5 ℃, separating out a large amount of solids, performing suction filtration under negative pressure, washing the dichloroethane to obtain an intermediate A, drying, weighing, and obtaining the product yield by using different acid-binding agents;

2) influence of different acid-binding agent addition amounts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding potassium carbonate with different masses in batches, keeping the temperature not exceeding 45 ℃, timing at 45 ℃ and keeping the temperature after adding; sampling after 6 hours, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using potassium carbonate with different masses as an acid-binding agent to obtain the product yield;

3) effect of different catalysts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of catalyst into the flask, then slowly heating to 40 ℃, then adding potassium carbonate in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches, keeping the temperature at not more than 45 ℃, timing and preserving the heat at 45 ℃ after the completion of adding; sampling from 6 hours later, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using different catalysts to obtain the product yield;

4) hydrolysis of intermediate a: adding 100g of intermediate A and 200ml of concentrated hydrochloric acid into a 500ml four-mouth bottle, slowly heating to 50 ℃, keeping the temperature for 14 hours, detecting the reaction process by a liquid chromatographic analyzer, transferring the intermediate A with the content of less than 2 percent into a 1000ml four-mouth bottle filled with 200ml of water, adjusting the pH to 6-7 by using liquid alkali, cooling to below 10 ℃, carrying out suction filtration under negative pressure, washing twice, and drying to obtain a final product B74.6g with the yield of 92 percent.

The invention has the advantages that: the synthetic method of the nicotine compound nitenpyram analogue is provided, the scheme design is reasonable, the synthesis is convenient, the synthetic route is screened and optimized, and the direction is provided for industrial production.

Drawings

FIG. 1 is a diagram of the synthetic chemical equation of the present invention.

FIG. 2 is a mass spectrum of the product of the present invention.

Detailed Description

The invention is illustrated below by means of specific examples, without being restricted thereto.

Examples

The experimental conditions for the specific implementation of the present invention are as follows:

common instruments: a four-neck flask, an electronic scale, a beaker, an electric heating jacket, a thermometer, a filter flask, a Buchner funnel, a separating funnel, a glass stopper, an iron support, a condenser tube, a single-neck flask, a vacuum pump, a rotary evaporator, a melting point instrument and the like.

An analytical instrument: liquid chromatography analyzer, mass spectrometer.

Experimental reagent

A synthetic method of a nicotine compound nitenpyram analogue specifically comprises the following steps:

1) influence of different acid-binding agents on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches or slowly dropwise adding the sodium hydroxide/sodium carbonate/potassium carbonate/triethylamine/pyridine as an acid-binding agent, wherein the temperature is not higher than 45 ℃, and timing and preserving heat at 45 ℃ after the addition is finished; sampling from 6 hours later, detecting the reaction process by a liquid chromatography analyzer, and transferring into a 1000ml four-mouth bottle after the 2-chloro-5-chloromethylpyridine completely reacts; heating to 55 ℃, adding 200ml of dichloroethane and 400ml of water, stirring for half an hour, standing for layering, collecting an organic layer, extracting a water layer twice by using 100ml of dichloroethane, combining the organic layers, cooling to below 5 ℃, separating out a large amount of solids, performing suction filtration under negative pressure, washing the dichloroethane to obtain an intermediate A, drying, weighing, and obtaining the product yield by using different acid-binding agents;

serial number	Acid-binding agent	Yield of
			1	Sodium hydroxide	71％
2	Sodium carbonate	80.5％
			3	Potassium carbonate	90％
4	Triethylamine	84％
			5	Pyridine compound	81％

It can be seen that the yield is highest using potassium carbonate as the acid-binding agent.

2) Influence of different acid-binding agent addition amounts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of tetramethylammonium hydroxide into the flask, then slowly heating to 40 ℃, then adding potassium carbonate with different masses in batches, keeping the temperature not exceeding 45 ℃, timing at 45 ℃ and keeping the temperature after adding; sampling after 6 hours, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using potassium carbonate with different masses as an acid-binding agent to obtain the product yield;

it can be seen that the yield of the potassium carbonate with the mass of 97g (0.7mol) is most reasonable, and the yield is not greatly influenced by increasing the input amount.

3) Effect of different catalysts on reaction yield: adding 82g of 2-chloro-5-chloromethylpyridine into a 500ml four-neck bottle with a thermometer and magnetons, then adding 150ml of butanone, slowly adding 86.5g of weighed triazine and 1.2g of catalyst into the flask, then slowly heating to 40 ℃, then adding potassium carbonate in an amount which is 1.5 times that of the 2-chloro-5-chloromethylpyridine in batches, keeping the temperature at not more than 45 ℃, timing and preserving the heat at 45 ℃ after the completion of adding; sampling from 6 hours later, detecting the reaction process by using a liquid chromatography analyzer, and performing other operations in the same step 1) by using different catalysts to obtain the product yield;

serial number	Catalyst and process for preparing same	Time (hours)	Yield of
				1	Tetramethyl ammonium hydroxide	10	87.8％
2	Tetramethyl ammonium chloride	10	82％
				3	Benzyl triethyl ammonium chloride	10	80％
4	Tetraethyl ammonium hydroxide	10	85％

It can be seen that the highest yield was obtained using tetramethylammonium hydroxide as catalyst.

4) Hydrolysis of intermediate a: adding 100g of intermediate A and 200ml of concentrated hydrochloric acid into a 500ml four-mouth bottle, slowly heating to 50 ℃, keeping the temperature for 14 hours, detecting the reaction process by a liquid chromatographic analyzer, transferring the intermediate A with the content of less than 2 percent into a 1000ml four-mouth bottle filled with 200ml of water, adjusting the pH to 6-7 by using liquid alkali, cooling to below 10 ℃, carrying out suction filtration under negative pressure, washing twice, and drying to obtain a final product B74.6g with the yield of 92 percent.

The experimental conclusion of the embodiment of the invention is as follows: the raw materials used in the experiment are low in price and easy to obtain; the synthesis steps are simple, safe, easy to operate, high in product purity and high in yield, and can be easily used for industrial production.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.