my country has now become one of the major pesticide production and consumption countries in the world, but the production varieties are mainly traditional and imitation mid-to-low-end varieties. Compared with developed countries and regions, there is a considerable gap between my country's pesticide production and development, especially the low level of technological development. The creation and development of new pesticides itself is difficult, takes a long time, and requires high investment. Although after many years of research and development, my country has developed There are some innovative pesticides with independent intellectual property rights, but not many of them have actually entered the market. Faced with this situation, in addition to increasing the intensity of innovative research and development of pesticides in my country, we should also attach great importance to the development of some market prospects whose patents have expired or are about to expire. important pesticide varieties. This article will mainly introduce the development and production of some important pesticide varieties whose patents have expired soon or are about to expire, as well as the intermediates required for their synthesis, to provide reference for the domestic development and production of these pesticides and intermediates.
1 Fipronil (fipronil)
Developed by the French company Rh?ne-Poulenc, it was granted a Chinese patent (CN86108643). The patent for this compound was issued on December 19, 2006 Expired; at the same time, Bayer has also obtained a patent authorization (CN95100789.0) in my country for the preparation method of fipronil and its intermediates. This patent will be valid until 2015.
Fipronil is a phenylpyrazole broad-spectrum insecticide. It mainly hinders the fluoride metabolism controlled by gamma-aminobutyric acid in insects. It has contact killing, stomach poisoning and moderate systemic effects. , has high insecticidal activity against a series of pests such as Lepidoptera, flies and Coleoptera, and has no cross-resistance with existing insecticides. The global sales of fipronil in 2005 were US$420 million, ranking fourth among pesticide sales.
At present, there are two main synthetic routes for the industrial production of fipronil. One is to use 2,6-dichloro-4-trifluoromethylaniline as raw material, and then obtain the diazonium salt through diazotization. It is obtained by reacting with ethyl 2,3-dicyanopropionate; the second one is using 2,6-dichloro-4-trifluoromethylphenylhydrazine as raw material and reacting with fumaronitrile, and then oxidized to obtain the product.
1.1 2,6-Dichloro-4-trifluoromethylaniline
There are three main synthesis routes for 2,6-dichloro-4-trifluoromethylaniline: ① p-Trifluoromethylaniline method. Direct chlorination of p-trifluoromethylaniline in a solvent gives 2,6-dichloro-4-trifluoromethylaniline. This method is simple and convenient, but trifluoromethylaniline is relatively expensive and the production cost is relatively high. This method is mainly used in foreign countries. ② p-Chlorotrifluorotoluene method. p-Chlorotrifluorotoluene reacts with dimethylformamide and NaNH2 at a certain temperature and pressure to obtain N,N-dimethyl p-trifluoromethylaniline, which is then chlorinated under light, demethylated and ring chlorinated Obtain the target product. This method has longer steps and a larger amount of "three wastes". ③3,4-Dichlorotrifluorotoluene method. 3,4-Dichlorotrifluoromethylaniline is used as raw material, reacted with dimethylformamide and sodium hydroxide in a pressure kettle, and chlorinated, demethylated and ring chlorinated under light conditions to obtain the product. At present, many domestic scientific research institutions are researching and developing this route. This route is more reasonable, the product quality is high, and the amount of "three wastes" is reduced to a certain extent.
1.2 2,6-Dichloro-4-trifluoromethylphenylhydrazine
The current research direction is to use p-chlorotrifluoromethylbenzene as raw material, in trichlorination Deep chlorination in the presence of iron gives 3,4,5-trichlorotrifluorotoluene, which is then reacted with hydrazine hydrate to give 2,6-dichloro-4-trifluoromethylphenylhydrazine.
1.3 Ethyl 2,3-dicyanopropionate
The synthesis method of ethyl 2,3-dicyanopropionate mainly includes the step-by-step method and the one-step method. . The production process of the step-by-step method is relatively cumbersome. During the production process, highly toxic substances harmful to the human body are produced and the amount of "three wastes" is relatively large. Therefore, the one-step method is currently mainly used for production. The one-step synthesis process is as follows: Mix sodium cyanide and the solvent absolute ethanol. After fully dissolving, add paraformaldehyde. After dissolving, add ethyl cyanoacetate. The feeding ratio of sodium cyanide, paraformaldehyde, and ethyl cyanoacetate is: 1:1:0.91(m:m). Then use hydrochloric acid to acidify, then extract and wash with water to obtain the crude product, and finally distill to remove the solvent to obtain the product. At present, several domestic companies such as Taizhou Tianyuan Chemical Co., Ltd. use this method to produce ethyl 2,3-dicyanopropionate.
2 Chlorfenapyr
Developed by the American Cyanamid Company, it has been granted a Chinese patent (CN88106516.1). The patent will expire on July 28, 2008 . BASF of Germany has obtained provisional registration of fenfentrile technical product and 10% fenfentrile suspension in China. Currently, Jiangsu Longdeng Chemical Co., Ltd. and Guangdong Deli Biotechnology Co., Ltd. have relevant registrations in China.
Brofenil is a new type of azole broad-spectrum insecticide and acaricide. It has strong permeability on the surface of plants, has certain systemic activity, has both gastric poisoning and contact killing effects, and can control a variety of scales. Ptera, Diptera, Coleoptera, Hemiptera pests and mites, and can effectively control insects that are resistant to carbamate, organophosphorus and pyrethroid insecticides.
The main synthesis methods of bromiphenil are: ① 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile reacts with bromine under light, and then reacts with sodium ethoxide to obtain; ② aromatic Arylpyrrole nitrile reacts with chloromethyl ethyl ether in tetrahydrofuran under the action of potassium tert-butoxide; ③ Arylpyrrole nitrile is obtained by reacting with diethoxymethane in the presence of DMF, phosphorus oxychloride and triethylamine. The main intermediate is arylpyrrole nitrile, and domestic and foreign research mainly focuses on the route using 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile as raw material. 2.1 2-p-Chlorophenyl-5-trifluoromethylpyrrole-3-nitrile
There are many patent reports on arylpyrrole-3-nitrile, and foreign companies generally use 2-p-chlorophenylglycine As the raw material, trifluoroacetic anhydride is the trifluoroacetylating agent, and the ring is closed to form 4-p-aminophenyl-2-trifluoromethylpyrazolin-5-one, which is then reacted with 2-chloroacrylonitrile to form 2- p-Chlorophenyl-5-trifluoromethylpyrrole-3-nitrile. Many foreign patents have been applied for in my country. For example, trifluoroacetylation is carried out with trifluoroacetic acid in the presence of phosphorus trichloride and triethylamine, or trifluoroacetyl chloride is used instead of trifluoroacetic acid. There are also choices of appropriate polar solvents and Alkali etc.
Some foreign researchers also use p-chlorophenyltrifluoroacetamidonitrile as raw material, react with acid halides in the presence of acid to form acylated derivatives of oxazolamide, and then react with acylated derivatives of oxazolamide under alkaline conditions. The reaction of 2-chloroacrylonitrile gives 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile.
Many domestic scientific research institutions have also conducted a lot of research, such as Zhengzhou University and Dalian University of Technology, using p-chlorobenzylamine as the basic raw material, reacting with trichloroacetic acid in the presence of phosphorus trichloride, trifluoroacetyl Then, in the presence of phosphorus oxychloride, p-chlorobenzyl chlorotrifluoroacetimide is obtained by chlorination; in the presence of a base, p-chlorobenzyl chlorotrifluoroacetimide is obtained A 1,3 dipolar cycloaddition reaction occurs between amines and chloroacrylonitrile to obtain 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile in a regio-directional manner. Although this route has many steps, the raw materials are cheap and easily available, so it has high application and development value in China.
There are also some domestic literature reports that p-chlorophenyl aminoacrylonitrile was brominated and then cyclized with trifluoromethylacetone to obtain 2-p-chlorophenyl-5-trifluoromethylpyrrole-3 -Nitrile, although the method is simple, the source of raw materials is difficult.
3 Transfluthrin
This variety was developed by Bayer and has been granted a Chinese patent (CN88100834). The patent will expire on February 11, 2008 . Bayer has obtained temporary registration of Biolin technical in my country. The relevant domestic registration companies include Jiangsu Changzhou Kangtai Chemical Co., Ltd. and Yangnong Chemical Co., Ltd. Flufenthrin is a highly efficient and low-toxic pyrethroid insecticide for hygienic use. It has inhalation, contact and repellent activities, and has a rapid knockdown effect on mosquitoes. It is used as a raw material for a variety of mosquito coils and mosquito repellent tablets. , can also effectively control flies, cockroaches and whiteflies, and its efficacy is much higher than that of allethrin. Due to its relatively high saturated vapor pressure at room temperature, transfluthrin can also be used to prepare insecticide products for outdoor and travel use, thereby expanding the application of sanitary insecticides from indoors to outdoors.
The synthesis of transfluthrin is mainly made from 2,3,5,6-tetrafluorobenzyl alcohol as raw material, reacting with pyridine and dichlormethrin in the presence of toluene as the solvent. Among them, tetrafluorobenzyl alcohol is a key intermediate, and permethrin chloride is a universal intermediate for various pyrethroids. It has been produced by many domestic companies such as Shandong Dacheng Pesticide Chemical Co., Ltd., so the key intermediate tetrafluorobenzyl alcohol is mainly introduced. Synthesis of benzyl alcohol.
The synthesis of tetrafluorobenzyl alcohol is relatively difficult. Foreign literature reports that there are two main production routes: ① Using tetrafluorobenzoic acid or tetrafluorobenzaldehyde as raw materials to synthesize tetrafluorobenzyl alcohol, as described in the European patent, 1,2,4,5-Tetrafluorobenzene reacts with n-butyllithium, and then reacts with carbon dioxide to prepare 2,3,5,6-tetrafluorobenzoic acid, and then uses LiAlH4 to reduce it to prepare 2,3,5,6- Tetrafluorobenzyl alcohol. The process of this method is relatively simple, but the reaction conditions are harsh and the source of raw materials is difficult; ② Some Japanese and domestic patent literature reports use 2,3,5,6-tetrachloroterephthalonitrile as the raw material to synthesize tetrafluorobenzyl alcohol. The specific process uses dimethylformamide as the solvent, tetrachloroterephthalonitrile and anhydrous potassium fluoride undergo a nucleophilic substitution reaction to generate 2,3,5,6-tetrafluorobenzonitrile; then in the presence of 80% concentrated sulfuric acid Under the conditions, tetrafluorobenzonitrile undergoes hydrolysis reaction to obtain tetrafluoroterephthalic acid; tetrafluoroterephthalic acid undergoes decarboxylation reaction in the presence of tributylamine and sodium hydroxide to obtain tetrafluorobenzoic acid; tetrafluorobenzoic acid is used in toluene as a solvent In the case of tetrafluorobenzoyl chloride, an acid chlorination reaction occurs with thionyl chloride to obtain tetrafluorobenzoyl chloride. In the case of tetrahydrofuran as a solvent, tetrafluorobenzoyl chloride and sodium borohydride are catalytically reduced to obtain tetrafluorobenzyl alcohol.
At present, domestic Jiangsu Yangnong Chemical Co., Ltd. and Jiangsu Hormone Research Institute are able to produce tetrafluorobenzyl alcohol.
4 Fenpyfoximate
This variety was developed by Nippon Pesticide Co., Ltd. and was granted a Chinese patent (CN86108691). This patent expired on December 26, 2006. Nippon Pesticide Co., Ltd. has also obtained product registrations in China such as fenfenzofen technical product and 13% acetylinate aqueous emulsion. Domestic Shandong Qixia Tongda Chemical Co., Ltd. and Jiangsu Longdeng Chemical Co., Ltd. also have preparation registrations.
Mefenacet is a phenoxypyrazole acaricide. It can directly kill mites at high doses. It can inhibit molting or egg-laying at low doses. It has the effect of knocking down and inhibiting molting. It has no systemic effect and can control a variety of mites, especially spider mites and red spider mites on various fruit trees. It has excellent activity against young mites and nymphal mites, is relatively safe against natural enemies, has no adverse effects on bees, and is antifeedant to silkworms. effect.
The synthesis of fenpyrazofen mainly uses 1,3-dimethylpyrazolone-5 as raw material, through 1,3-dimethyl-5-chloropyrazole carbaldehyde-5, 1,3- Dimethyl-5-phenoxypyrazole carboxaldehyde-5 gives 1,3-dimethyl-5-phenoxypyrazole oxime-5, and then reacts with the intermediate p-chloromethylbenzoic acid tert-butyl ester to obtain Mefenacet. The important intermediates are 1,3-dimethylpyrazolone-5 and tert-butyl p-chloromethylbenzoate.
4.1 1.3-Dimethylpyrazolone-5
Domestic and foreign literature reports that the synthesis of pyrazolone mainly uses anhydrous methyl hydrazine, and uses absolute ethanol or methanol as the solvent Perform the cyclization reaction of pyrazolones. Since anhydrous methyl hydrazine is expensive and extremely unsafe to transport and use, domestic researchers chose aqueous methyl hydrazine solution as the starting material to synthesize 1,3-dimethylpyrazolone-5. The specific process is: 40 % methylhydrazine aqueous solution and ethyl acetoacetate were cyclized at 75°C to obtain crude 1,3-dimethylpyrazolone-5. The product was purified by recrystallization from diethyl ether.
Foreign patent documents also introduce other synthesis methods of 1,3-dimethylpyrazolone-5: ① Use water as the reaction medium, neutralize methylhydrazine sulfate with an aqueous solution of sodium hydroxide, Without isolating the sodium sulfate by-product produced by neutralization, it directly reacts with ethyl acetoacetate to obtain the product; but the yield is relatively low; ② Using ethanol as the reaction medium, neutralize methylhydrazine sulfate with an ethanol solution of sodium hydroxide, Without isolating by-products, it reacts directly with ethyl acetoacetate to obtain 1,3-dimethylpyrazolone-5 with a relatively high yield.
4.2 Tert-butyl p-chloromethylbenzoate
The synthesis of this intermediate is relatively simple. Industrial production generally uses tert-butyl alcohol as raw material, and it is combined with pyridine and p-chloromethylbenzene. Formyl chloride reacts at room temperature. After the reaction, a certain amount of water is added, and then the organic phase is extracted with toluene. After the organic layer is separated, the toluene is distilled off to obtain tert-butyl p-chloromethylbenzoate, which is further purified to obtain a refined product. .
5 Azoxystrobin
This variety was developed by Syngenta and has been granted a Chinese patent (CN1047286). The patent will expire on February 8, 2010 .
It is registered and sold in dozens of countries including the United States, Europe, and Japan. In 2005, global sales of azoxystrobin reached US$635 million.
Azoxystrobin is a new high-efficiency broad-spectrum methoxyacrylate fungicide produced by imitating the chemical structure of the natural product Strobilurin A. Azoxystrobin is effective against almost all fungal diseases such as powdery mildew, rust, It has good activity against dozens of diseases such as green spot, net spot, scab, downy mildew, and rice blast. It has protection, treatment, eradication, penetration and systemic activities. It is suitable for sterilization and antibacterial use of cereals, rice, various fruit trees and vegetables, and is safe for groundwater and the environment.
The synthesis route of azoxystrobin is mainly divided into two types: ① first synthesize the intermediate (E)-3-methoxy-2-(2-hydroxyphenyl) methyl acrylate, and then synthesize it with 4 , 6-dichloropyrimidine and salicylonitrile react to form the final product; ② 4,6-dichloropyrimidine reacts with salicylonitrile first and then with (E)-3-methoxy-2-(2-hydroxyphenyl) Methyl acrylate reacts to obtain azoxystrobin. Among the two methods, (E)-3-methoxy-2-(2-hydroxyphenyl)methyl acrylate is the key intermediate for the synthesis of azoxystrobin.
There are many synthetic routes for (E)-3-methoxy-2-(2-hydroxyphenyl)methyl acrylate reported in the literature, but the one that is commonly used and has industrial prospects is mainly o-hydroxyphenylacetic acid. It is a route to obtain methyl acrylate through a three-step reaction of raw materials. The specific process is as follows: react o-hydroxyphenylacetic acid and acetic anhydride first, and then react with trimethyl orthoformate under nitrogen protection to separate low-boiling point substances. After adding methanol to the remaining mixture, it is heated to reflux and then cooled to crystallize to obtain the intermediate product 3-(α-methoxy)methylenebenzofuran-2(3H)-one (Ⅰ); mix sodium methoxide, tetrahydrofuran and methanol After cooling, add the compound I obtained by the above reaction in batches under nitrogen protection, and then perform a cyclization reaction to obtain (E)-3-methoxy-2-(2-hydroxyphenyl) methyl acrylate. Some literature reports that solvents such as methyl acetate and N,N-dimethylformamide can be used to synthesize (E)-3-methoxy-2-(2-hydroxyphenyl)methyl acrylate.
6 Nicosulfuron (nicosulfuron)
This variety was developed by Japan's Ishihara Industrial Co., Ltd. and obtained a Chinese patent authorization (CN87100436). The patent arrived on January 27, 2007 Expect. Japan's Ishihara Industrial Co., Ltd. has obtained the registration of nicosulfuron technical material and various preparations in China. The relevant domestic registration companies include Zhejiang Jinniu Pesticide Co., Ltd. (80% nicosulfuron wettable powder, 40g/L nicosulfuron suspension agent) and Tianjin Zhongnong Chemical Agricultural Production Materials Co., Ltd. (40g/L nicosulfuron suspension).
Nicosulfuron-methyl is a high-efficiency selective post-emergence herbicide for corn fields. It is currently the largest sales variety among sulfonylurea herbicides, with global sales of US$238 million in 2005. Low-dose post-emergence use can effectively control a variety of annual grass weeds, broadleaf weeds and sedge weeds in corn fields. It is rapidly absorbed by leaves and roots, and is rapidly transmitted through xylem and phloem. Corn has a certain effect on this drug. With good drug resistance, the agent has low toxicity to mammals.
Foreign patent reports nicosulfuron mainly reacts with phosgene from 2-amino-4,6-dimethoxypyrimidine in the presence of triethylamine to generate the corresponding isocyanate, and then reacts with 2-aminosulfonate Acyl-N,N-dimethylnicotinamide is prepared by reacting in acetonitrile. Various other synthetic routes have also been reported in the literature, but most of them involve the important intermediates 2-amino-4,6-dimethoxypyrimidine and 2-sulfamoyl-N,N-dimethylnicotinamide.
6.1 2-Amino-4,6-dimethoxypyrimidine
2-Amino-4,6-dimethoxypyrimidine is an important component of sulfonylurea herbicides Intermediates, which are used as raw materials for the synthesis of nicosulfuron-methyl, are also used for the synthesis of bensulfuron-methyl, pyrimosulfuron-methyl, pyrimosulfuron-methyl, pyrimosulfuron-methyl, etc. The intermediate is mainly synthesized by the reaction of guanidine nitrate (hydrochloride) and diethyl malonate. At present, the relatively mature industrial technology developed in China is the synthesis of guanidine nitrate and diethyl malonate. Specific process: In the presence of catalyst sodium ethoxide, guanidine nitrate reacts with diethyl malonate to obtain 2-amino-4,6-dihydroxypyrimidine; 2-amino-4,6-dihydroxypyrimidine in the presence of solvent Under the reaction conditions, it reacts with phosphorus oxychloride to obtain 2-amino-4,6-dichloropyrimidine; dichloropyrimidine undergoes methoxylation reaction with sodium methoxide to obtain 2-amino-4,6-dimethoxypyrimidine.
At present, some domestic enterprises use this method to produce, and a certain amount of "three wastes" are produced during the production process, which needs further improvement and perfection.
6.2 2-Sulfamoyl-N,N-dimethylnicotinamide
Synthesis of 2-sulfamoyl-N,N-dimethylnicotinamide reported in domestic literature The route mainly uses 2-chloronicotinic acid as the raw material for synthesis, and there are also patent reports using 2-hydroxy-2-cyanopyridine as the raw material. However, the supply of this raw material is tight, the price is expensive, and it is not suitable for industrial production. Foreign patent reports use 2-chloronicotinic acid as raw material, oxidize the thiol group at the 2-position with chlorine gas, and then amidate the 3-position with Al(CH3)3 and NH(CH3)2 to obtain the target product. Domestic researchers have made improvements on this basis to increase the yield, and now it has reached the level of industrial production. Specific process: 2-chloronicotinic acid, thionyl chloride and dimethylamine react to obtain 2-chloro-N,N-dimethylnicotinic acid amide (Ⅰ); Compound Ⅰ reacts with Na2S 9H2O and S to obtain 2-chloro-N,N-dimethylnicotinamide (Ⅰ) 2-Mercapto-3-N,N-dimethylnicotinamide (II); Compound II is dissolved in ammonia water, and then reacts with hydrogen peroxide and sodium hypochlorite under acidic conditions to obtain 2-sulfamoyl-N,N- Dimethylnicotinamide. This process uses 2-chloronicotinic acid as raw material to synthesize the target product through four-step reactions. The yield can reach more than 86%. The reaction conditions are relatively mild, and the organic solvents used in the reaction can be recycled and reused.
7 Tebufenpyrad
This variety was developed by Mitsubishi Chemical Corporation of Japan and has been granted a Chinese patent (CN88102427). The patent will be issued on April 23, 2008. Expect. Bifenric 10% wettable powder has obtained provisional registration (LS93021) in China.
Mefenpyramide is a new type of insecticide and acaricide of the pyrazole amide class. It has unique chemical properties and a novel mode of action. It is quick-acting and highly effective against various mites in all growth stages. It has a long lasting effect, low toxicity, no systemic properties, excellent cross-layer penetration activity, excellent selectivity for target substances, and can control harmful mites on the parts of the plants that have been treated with the agent that are not exposed to the agent. This is Functions not found in other acaricides. It has no cross-resistance with commonly used acaricides and has certain control effects on aphids, leafhoppers, whiteflies and Lepidopteran and Hemiptera pests.
Mefenpyramide is mainly obtained from the reaction of pyrazolecarboxyl chloride and p-tert-butylbenzylamine, of which p-tert-butylbenzylamine is the key intermediate.
There are many reports on the synthesis of p-tert-butylbenzylamine, mainly including: ① Mitsubishi Chemical Company of Japan mainly uses p-tert-butylbenzaldehyde and ammonia to undergo a reduction reaction under the action of a catalyst. This method High purity p-tert-butylbenzylamine can be produced, but the reaction needs to be carried out under high pressure, which requires relatively high equipment and relatively large investment; ② Domestic researchers have developed the Delepine reaction to combine p-tert-butylbenzyl chloride with methenamine After the product reaction, the quaternary ammonium salt formed is hydrolyzed in methanol-hydrochloric acid to form p-tert-butylbenzylamine. The reaction conditions of this method are relatively mild and suitable for industrial production.
Domestic researchers from Zhejiang University and Zhejiang University of Technology conducted repeated experiments on the Delepine reaction. The specific process is as follows. tert-butylbenzyl chloride and methenamine were reacted in sec-butyl alcohol as the solvent, and then Add hydrochloric acid and methanol to continue the reaction. The reaction mixture is cooled and filtered. After the filtrate is concentrated to obtain an earthy yellow solid, a certain amount of water is added to dissolve it, and then alkalized with sodium hydroxide to precipitate a large amount of yellow liquid. The yellow liquid is then extracted with chloroform to obtain tert-Butylbenzylamine. The optimized reaction conditions are: the reaction temperature is 40°C, and the feeding ratio of p-tert-butylbenzyl chloride and methenamine is 1:1.2 (m:m).
8 Nitenpyram (nitenpyram)
This variety was developed by Takeda Corporation of Japan and obtained Chinese patent authorization (CN88104801.1). The patent will be effective on August 1, 2008 maturity. Relevant registered domestic companies include Jiangsu Nantong Jiangshan Pesticide Chemical Co., Ltd. and Jiangsu Lianyungang Liben Pesticide Chemical Co., Ltd. No foreign companies were found to be registered in China.
Nitenpyram belongs to the nicotinimide class of insecticides. It has unique chemical and biological properties and has a nerve-blocking effect on the synaptic receptors of pests. It is effective against various aphids, whiteflies, Rice leafhoppers show excellent activity, and have the advantages of high efficiency, low toxicity, systemic absorption, no cross-resistance, and no phytotoxicity to crops. They are widely used to control various pests in rice, fruit trees, vegetables, and tea.
The synthesis of nitenpyram is based on 2-chloro-5-methylpyridine as raw material, through N-ethyl-2-chloro-5-pyridylmethylamine, and then combined with 1,1-dimethyl It is obtained by reacting a mixture of thio-2-nitroethylene and ethanol, and then reacting with an aqueous solution of methylamine. The key intermediate is 2-chloro-5-chloromethylpyridine.
2-Chloro-5-chloromethylpyridine is an important pesticide intermediate. It is not only used to synthesize nitenpyrid, but also other important nicotine pesticides such as imidacloprid, acetamiprid, thiacloprid, etc. of intermediates. The research and production of 2-chloro-5-chloromethylpyridine emerged with the research of imidacloprid and nitenpyram. The main methods of industrial production at home and abroad are: ① Using 3-methylpyridine as raw material through N-oxide reaction to obtain 3-chloromethylpyridine, and then directional chlorination to obtain it; ② Ring method, using benzylamine and propionaldehyde to react, After ring chlorination, 3-chloromethylpyridine is obtained, and then through chlorination; ③ Domestic researchers, based on the direct cyclization of cyclopentadiene developed by Rayleigh Company in the United States, developed a method using cyclopentadiene as raw material through customs clearance. Ring reaction directly prepares 2-chloro-5-chloromethylpyridine. The raw materials of this route are easily available and the production cost is relatively low. Currently, domestic Dalian Kaifei Chemical Co., Ltd., Jiangsu Chemical Pesticide Group Co., Ltd., and Jiangsu Kesheng Co., Ltd. often use it. Produced by this method; ④ Jiangsu Pesticide Research Institute has developed a production route using morpholine as raw material, using morpholine as raw material through N-propenylmorpholine, 1-chloro-2-(4-morpholine)-3-methyl Cyclobutylnitrile, 2-chloro-4-formylvaleronitrile, 2-chloro-5-methylpyridine and other intermediates are used to synthesize 2-chloro-5-chloromethylpyridine. This method has the advantages of low raw material cost and mild reaction conditions. and other advantages, and has industrialization prospects.
9 Bispyribac-sodium
This variety was developed by Japan Combination Compounds Company and has been granted a Chinese patent (CN88108904.4). The patent will be issued in December 2008 Expires on the 22nd. Japan Combination Chemical Company has also obtained the registration of bispyrifen technical product (PD20040015) and 10% bispyrifen suspension (PD20040014) in China. Relevant registered companies in China include Jiangsu Hormone Research Institute Co., Ltd. and Shanghai Linnong Chemical Co., Ltd.
Dispyr is a pyrimidine-type salicylic acid broad-spectrum herbicide that works by hindering the biosynthesis of branched-chain amino acids. It is mainly used in direct rice fields and can effectively control annual and perennial grasses. Undergraduate and broad-leaf weeds, especially barnyard grass in the 1-7 leaf stage, can be controlled at a very low dosage and have broad application prospects. This pesticide has applied for registration in Japan, Europe and the United States and other countries.
There are two main routes for the synthesis of bispyramide. One is the non-ester protection method, which consists of 2,6-dihydroxybenzoic acid and 2-substituted-4,6-dimethoxypyrimidine in a base. The second is the ester group protection method, which is first esterified with 2,6-dihydroxybenzoic acid, and then the esterified product is reacted with 2-substituted-4,6-dimethoxypyrimidine under alkaline conditions. The ester of bisspyr is generated by the reaction under the following conditions, and then the ester of bisspyr is obtained through catalytic hydrogenation and neutralization. The key intermediate is 2-substituted-4,6-dimethoxypyrimidine, and 4,6-dimethoxy-2-methylthiopyrimidine is usually used.
The synthesis routes of 4,6-dimethoxy-2-methylthiopyrimidine reported in the literature mainly include: ①Methyl iodide method, methyl iodide and 4,6-dihydroxy-2-methylthio Preparation of pyrimidine reaction, the yield of this method is not high, and sulfomethane is expensive; ② Dimethyl sulfate method, dimethyl sulfate reacts with 4,6-dihydroxy-2-mercaptopyrimidine, the yield of this method is relatively low, and The emission of "three wastes" is large; ③3-amino-1,3-dimethoxy-2-methanesulfonylpyrimidine is prepared by oxidation with hydrogen peroxide. The source of raw materials for this method is difficult; ④Researchers from Zhejiang University of Technology developed The synthesis route uses diethyl malonate and thiourea as raw materials. It is condensed into 4,6-dihydroxy-2-pyrimidine sodium sulfate in the presence of sodium methoxide, and then undergoes methylation, chlorination, methoxylation, etc. A series of reactions yields 4,6-dimethoxy-2-methylthiopyrimidine. Although there are many steps, the reaction conditions are mild, the raw materials are cheap and easily available, and it has industrial application prospects.
The above describes the synthesis of some pesticides and their intermediates. These pesticides have some unique characteristics. They are developed by foreign companies and have obtained patent authorization in China. At the same time, these varieties are or have been produced in China. registered, and the patent has expired or is about to expire.
Once the patent expires, it can be copied. At the same time, because it has been registered or temporarily registered in China, it has a certain basis for promotion and application. After product development and production, it is easier to be accepted by the market, which can greatly shorten the time to enter the market. The key to the development of these pesticides lies in the development and research of important intermediates. Therefore, relevant domestic scientific research institutions and pesticide manufacturers should actively track the legal protection status of foreign patented pesticides, strengthen intermediate development research, and look forward to improving and perfecting the intermediate synthesis process. Reduce the production cost of intermediates and lay a solid foundation for the production of these high-efficiency, low-toxic pesticides with good market prospects.