1 fipronil
Developed by Planck Company in Rhone, France, and obtained the China patent (CN86 108643), which expired on February 19, 2006; At the same time, Bayer's preparation method of fipronil and its intermediates has also been patented in China (CN95 100789.0), and the patent will last until 20 15.
Fipronil is a broad-spectrum phenylpyrazole insecticide, which mainly blocks fluorine metabolism controlled by γ -aminobutyric acid. It has contact toxicity, stomach toxicity and moderate systemic action, and has high insecticidal activity against a series of pests such as LEPIDOPTERA, flies and COLEOPTERA, and has no cross resistance with existing pesticides. In 2005, the global sales of fipronil was US$ 420 million, ranking fourth among the sales of pesticide varieties.
At present, there are two main synthetic routes for industrial production of fipronil. One is obtained by diazotizing 2,6-dichloro -4- trifluoromethylaniline to obtain diazonium salt, and then reacting with 2,3-dicyanopropionate. Secondly, 2,6-dichloro -4- trifluoromethyl phenylhydrazine was used as raw material to react with fumaronitrile, and then the product was obtained by oxidation.
1.12,6-dichloro -4- trifluoromethylaniline
There are three main synthetic routes of 2,6-dichloro -4- trifluoromethylaniline: ① p-trifluoromethylaniline method. 2,6-dichloro -4- trifluoromethylaniline was obtained by direct chlorination of p-trifluoromethylaniline in solvent. This method is simple and convenient, but the price and production cost of trifluoromethylaniline are relatively high, so it is mainly used abroad. ② p-Chlorotrifluorotoluene method. N, N- dimethyl-p-trifluoromethylaniline was obtained by the reaction of p-chlorotrifluorotoluene with dimethylformamide and NaNH2 at a certain temperature and pressure, and then the target product was obtained by chlorination, demethylation and cyclization under illumination. This method has long steps and large amount of three wastes. ③ 3,4-dichlorotrifluorotoluene method. Using 3,4-dichlorotrifluoromethylaniline as raw material, it reacted with dimethylformamide and sodium hydroxide in autoclave, and the product was obtained by chlorination demethylation and cyclic chlorination under illumination. At present, many domestic scientific research institutions are developing this route. This route is more reasonable, the product quality is high, and the amount of three wastes is reduced to some extent.
1.22,6-dichloro -4- trifluoromethyl phenylhydrazine
At present, the main research direction is to deeply chlorinate p-chlorotrifluoromethylbenzene in the presence of ferric chloride to obtain 3,4,5-trichlorotrifluoromethylbenzene, and then react with hydrazine hydrate to obtain 2,6-dichloro -4- trifluoromethylphenylhydrazine.
1.32,3-Ethyl dicyanopropionate
There are two main synthesis methods of ethyl 2,3-dicyanopropionate: one-step method and one-step method. One-step production process is complex, which produces toxic substances harmful to human body and the amount of three wastes is relatively large. At present, one-step production is mainly adopted. The one-step synthesis process is as follows: mixing sodium cyanide with solvent anhydrous ethanol, fully dissolving, adding paraformaldehyde, and adding ethyl cyanoacetate after dissolution, wherein the feeding ratio of sodium cyanide, paraformaldehyde and ethyl cyanoacetate is1:1:0.91(m: m). Then acidifying with hydrochloric acid, extracting and washing to obtain a crude product, and finally rectifying to remove the solvent to obtain the product. At present, several enterprises in China, such as Taizhou Tianyuan Chemical Co., Ltd., use this method to produce ethyl 2,3-dicyanopropionate.
2 chlorfenapyr (chlorfenapyr)
Developed by American melamine company, the patent was granted in China (CN88106516.1), which will expire on July 28th, 2008. German BASF Company has obtained the provisional registration of technical chlorfenapyr and 10% chlorfenapyr suspension concentrate in China. At present, Jiangsu Longdeng Chemical Co., Ltd. and Guangdong Deli Biotechnology Company have relevant registrations.
Chlorfenapyr is a new pyrrole broad-spectrum insecticide and acaricide, which has strong permeability on plant surface, certain systemic activity, stomach toxicity and contact toxicity. It can control a variety of LEPIDOPTERA, Diptera, COLEOPTERA and Hemiptera pests and mites, and effectively control insects resistant to carbamate, organophosphorus and pyrethroid insecticides.
The main synthesis methods of chlorfenapyr are as follows: ①2- p-chlorophenyl -5- trifluoromethylpyrrole -3- nitrile reacts with bromine under illumination and then with sodium ethoxide to obtain it; ② Arylpyrrolonitrile reacts with chloromethyl ethyl ether in tetrahydrofuran under the action of potassium tert-butoxide; ③ Arylpyrrolonitrile reacts with diethoxymethane in the presence of DMF, phosphorus oxychloride and triethylamine. The main intermediate is aryl pyrrole nitrile, and the research at home and abroad mainly focuses on the route using 2- p-chlorophenyl -5- trifluoromethyl pyrrole -3- nitrile as raw material. 2. 1 2- p-chlorophenyl -5- trifluoromethylpyrrole -3- nitrile
There are many reports about the patents of aryl pyrrole -3- nitrile. Generally, foreign companies use 2- p-chlorophenyl glycine as raw material and trifluoroacetic anhydride as trifluoroacetylating agent to cyclize into 4- p-aminophenyl -2- trifluoromethylpyrazoline -5- one, and then react with 2- chloroacrylonitrile to produce 2- p-chlorophenyl -5- trifluoromethylpyrrole -3- nitrile. Foreign countries have applied for many patents in China, such as trifluoroacetylation with trifluoroacetic acid in the presence of phosphorus trichloride and triethylamine, or replacing trifluoroacetic acid with trifluoroacetyl chloride, and selecting appropriate polar solvents and bases.
Some researchers abroad also used p-chlorophenyl trifluoroacetamide nitrile as raw material to react with acyl halide in the presence of acid to generate acylated derivatives of oxazolidine, and then reacted with 2- chloroacrylonitrile under alkaline conditions to obtain 2- p-chlorophenyl -5- trifluoromethylpyrrole -3- nitrile.
Many domestic scientific research institutions have also done a lot of research, such as Zhengzhou University and Dalian University of Technology. N- p-chlorobenzyl trifluoroacetamide was obtained from p-chlorobenzylamine by reaction with trichloroacetic acid in the presence of phosphorus trichloride and trifluoroacetylation. Then chlorinating in the presence of phosphorus oxychloride to obtain p-chlorobenzyl chlorotrifluoroacetylimine; In the presence of alkali, 2- p-chlorophenyl -5- trifluoromethyl pyrrole -3- nitrile was obtained by 1 3 dipolar cycloaddition reaction between p-chlorobenzyl-trifluoroacetylimine and chloroacrylonitrile. Although this route has many steps, the raw materials are cheap and easy to get, and it has high application and development value in China.
It has been reported in China that 2- p-chlorophenyl -5- trifluoromethylpyrrole -3- nitrile was obtained by bromination of p-chlorophenylaminoacrylonitrile and trifluoromethylacetone. Although this method is simple, the source of raw materials is difficult.
3 Tetraflumethrin (Tetraflumethrin)
This variety was developed by Bayer Company, and was granted a patent by China (CN88 100834). The patent is valid until February 2008 1 1 day. Bayer Company has obtained the temporary registration of the original technical products of BIOLING in China, and the relevant domestic registered enterprises include Jiangsu Changzhou Kangtai Chemical Co., Ltd. and Yangnong Chemical Co., Ltd. Tetraflufenpropathrin is a pyrethroid insecticide with high efficiency and low toxicity, which has inhalation, contact killing and repellent activities and can quickly knock down mosquitoes. Used as raw materials for various mosquito-repellent incense and mosquito-repellent incense tablets, it can also effectively control flies, cockroaches and whiteflies, and its efficacy is much higher than that of s- bioallethrin. Because tetrafluoroborate has a high saturated vapor pressure at room temperature, it can also be used to prepare insecticidal products for field and tourism, thus expanding the application of sanitary insecticides from indoor to outdoor.
The synthesis of tetramethrin is mainly prepared by the reaction of 2,3,5,6-tetrafluorobenzyl alcohol with pyridine and dichlorochrysanthemyl chloride in toluene solvent. Tetrafluorobenzyl alcohol is a key intermediate, and dichlorochrysanthemyl chloride is a common intermediate of many pyrethroids, which are produced by many domestic enterprises such as Shandong Dacheng Pesticide Chemical Co., Ltd., so the synthesis of tetrafluorobenzyl alcohol, a key intermediate, is mainly introduced.
The synthesis of tetrafluorobenzyl alcohol is difficult. It is reported in foreign literature that there are two main routes to produce tetrafluorobenzyl alcohol: ① Synthesis of tetrafluorobenzyl alcohol from tetrafluorobenzoic acid or tetrafluorobenzaldehyde. According to the European patent, 1, 2,4,5-tetrafluorobenzene reacts with n-butyllithium, then with carbon dioxide to prepare 2,3,5,6-tetrafluorobenzoic acid, and then is reduced with LiAlH4 to prepare 2,3,5,6. The process of this method is relatively simple, but the reaction conditions are harsh and the source of raw materials is difficult. ② Some patent documents in Japan and China reported the synthesis of tetrafluorobenzyl alcohol from 2,3,5,6-tetrachloroterephthalonitrile. The specific process is as follows: taking dimethylformamide as solvent, tetrachloroterephthalonitrile and anhydrous potassium fluoride undergo nucleophilic substitution reaction to generate 2,3,5,6-tetrafluoronitrile; Then in the presence of 80% concentrated sulfuric acid, tetrafluoronitrile undergoes hydrolysis reaction to obtain tetrafluoroterephthalic acid; Tetrafluorobenzyl dimethyl alcohol is decarboxylated in the presence of tributylamine and sodium hydroxide to obtain tetrafluorobenzoic acid; Tetrafluorobenzoic acid reacts with thionyl chloride in the presence of toluene to obtain tetrafluorobenzoyl chloride, and tetrafluorobenzoyl chloride and sodium borohydride are catalytically reduced in the presence of tetrahydrofuran to obtain tetrafluorobenzyl alcohol.
At present, Jiangsu Yangnong Chemical Co., Ltd. and Jiangsu Hormone Research Institute can produce tetrafluorobenzyl alcohol.
Fenpixime ester; Phenylhydroxamic acid
This variety was developed by Japanese Pesticide Co., Ltd. and granted patent by China (CN86 10869 1), which expired on February 26th, 2006. Japan Pesticide Co., Ltd. also obtained the technical product of fenpropathrin, 13% propargyl & # 8226; Registration of various products, such as acaricide emulsion in water. Domestic Shandong Qixia Tongda Chemical Co., Ltd. and Jiangsu Longdeng Chemical Co., Ltd. also have preparations registered.
Zofenprox is an oxadiazole acaricide, which can directly kill mites at high dose, inhibit molting or oviposition at low dose, knock down and inhibit molting, and has no systemic effect. It can prevent and control many kinds of mites, especially tetranychus urticae and tetranychus urticae on various fruit trees. It has excellent activity on young mites and nymphs, is safe to natural enemies, has no adverse effect on bees, and has antifeedant effect on silkworm.
The synthesis of pyrazole amine is mainly based on 1, 3- dimethyl pyrazolone -5, and 1, 3- dimethyl -5- dichloropyridine acid -5 and 1, 3- dimethyl -5- phenoxypyrazole -5 are used to obtain 1, 3. The important intermediates are 1, 3- dimethylpyrazolone -5 and tert-butyl p-chloromethyl benzoate.
4. 1. 1.3- dimethyl pyrazolone -5
It is reported in domestic and foreign literatures that the synthesis of pyrazolone mainly adopts anhydrous methylhydrazine, and the cyclization of pyrazolone is carried out with anhydrous ethanol or methanol as solvent. Because anhydrous methylhydrazine is expensive and extremely unsafe to transport and use, domestic researchers choose aqueous methylhydrazine solution as the starting material to synthesize 1, 3- dimethyl pyrazolone -5. The specific process is that 40% methyl hydrazine aqueous solution reacts with ethyl acetoacetate at 75℃ to obtain the crude product 1, 3- dimethyl pyrazolone -5, and the product is purified by recrystallization with ether.
Other synthetic methods of 1, 3- dimethyl pyrazolone -5 are also introduced in foreign patent literature: ① using water as the reaction medium, methyl hydrazine sulfate is neutralized with sodium hydroxide aqueous solution, and the sodium sulfate by-product produced by neutralization is not separated, and the product directly reacts with ethyl acetoacetate; But the output is relatively low; ② Using ethanol as the reaction medium, methyl hydrazine sulfate was neutralized with ethanol solution of sodium hydroxide, and the by-product directly reacted with ethyl acetoacetate to obtain 1, 3- dimethyl pyrazolone -5 with high yield.
4.2 tert-butyl p-chloromethyl benzoate
The synthesis of this intermediate is relatively simple. In industrial production, tert-butyl alcohol is generally used as raw material to react with pyridine and p-chloromethyl benzoyl chloride at room temperature. After the reaction, a certain amount of water was added, and then the organic phase was extracted with toluene. After separating the organic layer, toluene was removed by distillation to obtain tert-butyl p-chloromethyl benzoate, and the refined product was obtained by further purification.
Azoxystrobin; Azoxystrobin
This variety was developed by Syngenta Company and granted a patent by China (CN 1047286), which will expire on February 8, 20 10. Registered sales in dozens of countries such as the United States, Europe and Japan. In 2005, the global sales of azoxystrobin reached $635 million.
Azoxystrobin is a new type of high-efficiency broad-spectrum methoxyacrylate bactericide, which is developed by imitating the chemical structure of the natural product strobilurin A. Azoxystrobin has good activity against almost all fungal diseases, such as powdery mildew, rust, rice leaf blight, scab, downy mildew, rice blast and dozens of other diseases. It has the functions of protection, treatment, eradication, permeation and systemic activity, and is suitable for sterilization and antibacterial of cereals, rice, various fruit trees and vegetables, and is safe for groundwater and environment.
There are two main synthetic routes of azoxystrobin: firstly, the intermediate (E)-3- methoxy -2-(2- hydroxyphenyl) methyl acrylate is synthesized, and then it reacts with 4,6-dichloropyrimidine and salicylaldehyde respectively to form the final product; ② 4,6-dichloropyrimidine first reacts with salicylonitrile, and then with (E)-3- methoxy -2-(2- hydroxyphenyl) methyl acrylate to obtain azoxystrobin. In these two methods, methyl (E)-3- methoxy -2-(2- hydroxyphenyl) acrylate is the key intermediate for the synthesis of azoxystrobin.
There are many synthetic routes of (E)-3- methoxy -2-(2- hydroxyphenyl) methyl acrylate reported in the literature, but the commonly used route with industrial prospect is mainly the route of obtaining methyl acrylate from o-hydroxyphenylacetic acid through three steps. The specific process is as follows: firstly, o-hydroxyphenylacetic acid reacts with acetic anhydride, and then reacts with trimethyl orthoformate under the protection of nitrogen to separate low-boiling substances and add the remaining mixture. Mixing sodium methoxide, tetrahydrofuran and methanol, cooling, adding them into the compound I obtained by the above reaction in batches under the protection of nitrogen, and then carrying out cyclization reaction to obtain (E)-3- methoxy -2-(2- hydroxyphenyl) methyl acrylate. It is reported 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 Japanese Ishihara Industrial Co., Ltd. and obtained the patent authorization from China (CN87 100436), which expired on June 27th, 2007. Japanese Ishihara Industrial Co., Ltd. has obtained the registration of nicosulfuron and various preparations in China, and the related domestic registered enterprises are Zhejiang Jinniu Pesticide Co., Ltd. (80% nicosulfuron wettable powder, 40g/L nicosulfuron suspension) and Tianjin Zhongnong Agricultural Production Materials Co., Ltd. (40g/L nicosulfuron suspension).
Nicosulfuron-methyl is an efficient and selective post-emergence herbicide in corn field, and it is the largest variety of sulfonylurea herbicides. In 2005, its global sales amounted to $238 million. Low-dose pesticide application after seedling can effectively control many annual gramineous weeds, broadleaf weeds and Cyperaceae weeds in corn fields, which are quickly absorbed by leaves and roots and quickly transmitted through xylem and phloem, so corn has good drug resistance and low toxicity to mammals.
Foreign patents reported that nicosulfuron was mainly prepared by the reaction of 2- amino-4,6-dimethoxypyrimidine with phosgene in the presence of triethylamine to generate the corresponding isocyanate, and then reacted with 2- sulfamoyl -N, N- dimethylnicotinamide in acetonitrile. Many other synthetic routes have been reported in the literature, but most of them involve 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 intermediate of sulfonylurea herbicides. It is the raw material for the synthesis of nicosulfuron, bensulfuron, pyrasulfuron, yumsulfuron and so on. The intermediate is synthesized by the reaction of guanidine nitrate and diethyl malonate. At present, the relatively mature industrial technology in China is the synthesis of guanidine nitrate and diethyl malonate. The 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 reacts with phosphorus oxychloride in the presence of solvent to obtain 2- amino-4,6-dichloropyrimidine; 2- amino-4,6-dimethoxypyrimidine was obtained by methoxylation of dichloropyrimidine with sodium methoxide. At present, some domestic enterprises use this method to produce, and a certain amount of' three wastes' are produced in the production process, which needs further improvement and perfection.
6.2 2- sulfamoyl -N, N- dimethylnicotinamide
The synthetic route of 2- sulfamoyl -N, N- dimethylnicotinamide reported in domestic literature mainly uses 2- chloronicotinic acid as raw material, and there are also patent reports that 2- hydroxy -2- cyanopyridine is used as raw material, but the raw material is scarce and expensive, which is not suitable for industrial production. It is reported in foreign patents that 2- chloronicotinic acid is used as raw material, and the sulfhydryl group at the 2-position is oxidized by chlorine, and then amidated with Al(CH3)3 and NH(CH3)2 at the 3-position to obtain the target product. On this basis, domestic researchers have improved and increased the yield, and now they have reached the level of industrial production. The specific process: 2- chloronicotinic acid, thionyl chloride and dimethylamine react to obtain 2- chloro -N, N- dimethylnicotinamide (I); 2- mercapto -3-N, N- dimethylnicotinamide (Ⅱ) was obtained from compound Ⅰ and Na2S & # 8226 by 9H2O and S heating reaction. Dissolving compound II in ammonia water, and then reacting with hydrogen peroxide and sodium hypochlorite under acidic conditions to obtain 2- sulfamoyl -N, N- dimethylnicotinamide. In this process, 2- chloronicotinic acid was used as raw material, and the target product was synthesized through four steps. The yield was over 86%, the reaction conditions were mild, and the organic solvent used in the reaction could be recycled.
Tebufenozide; Pyrimethalin
This variety was developed by Mitsubishi Chemical Co., Ltd. and granted a patent by China (CN88 102427), which will expire on April 23rd, 2008. Bipirik 10% wettable powder was temporarily registered in China (LS9302 1).
Zofenpyrad is a new type of pyrazolamide insecticide and acaricide, which has unique chemical properties and novel mode of action. It has the advantages of quick-acting, high efficiency, long duration, low toxicity, no systemic absorption, excellent cross-layer permeability and excellent selectivity to targets, and can prevent and control harmful mites in plants that have not been exposed to the pesticide, which is not available in other acaricides. It has no cross resistance with common acaricides, and also has certain control effect on aphids, leafhoppers, whiteflies, LEPIDOPTERA and Hemiptera pests.
Tebufenozide is mainly obtained by the reaction of pyrazolyl chloride with p-tert-butylbenzylamine, of which p-tert-butylbenzylamine is the key intermediate.
There are many literature reports on the synthesis of p-tert-butylbenzylamine, including: ① Mitsubishi Chemical Company of Japan can produce high-purity p-tert-butylbenzylamine mainly by the reduction reaction of p-tert-butylbenzaldehyde and ammonia under the action of catalyst, but the reaction needs to be carried out at high pressure, with high equipment requirements and large investment; (2) Delepine reaction was developed by domestic researchers. P-tert-butylbenzyl chloride reacted with urotropine, and the generated quaternary ammonium salt was hydrolyzed in methanol-hydrochloric acid to generate P-tert-butylbenzylamine. The method has relatively mild reaction conditions and is suitable for industrial production.
Researchers from Zhejiang University and Zhejiang University of Technology have repeatedly experimented with the Delaipine reaction. The specific process is as follows: p-tert-butyl benzyl chloride reacts with urotropine in solvent sec-butanol, then hydrochloric acid and methanol are added to continue the reaction, the reaction mixture is cooled and filtered. After the filtrate was concentrated to obtain a khaki solid, a certain amount of water was added to dissolve it, then it was alkalized with sodium hydroxide to precipitate a large amount of yellow liquid, and then the yellow liquid was extracted with chloroform to obtain p-tert-butylbenzylamine. The optimum reaction conditions were as follows: the reaction temperature was 40℃, and the ratio of p-tert-butyl benzyl chloride to urotropine was 1: 1.2(m:m).
8 nitenpyram (nitenpyram)
This variety was developed by Takeda Company, and obtained the patent authorization from China (CN88 1 04801.1), and the patent will expire on August12008. Domestic registered enterprises include Jiangsu Nantong Jiangshan Pesticide Chemical Co., Ltd. and Jiangsu Lianyungang Li Ben Pesticide Chemical Co., Ltd., but no foreign companies are registered in China.
Nitenpyram belongs to nicotinamide insecticides. It has unique chemical and biological properties, has nerve blocking effect on synaptic receptors of pests, and has excellent activity on many aphids, whiteflies and rice leafhoppers. It has the advantages of high efficiency, low toxicity, systemic absorption, no cross resistance and no phytotoxicity to crops. It is widely used to control various pests in rice, fruit trees, vegetables and tea.
The synthesis of nitenpyram is obtained by reacting 2-chloro-5-methylpyridine with N- ethyl-2- chloro -5- pyridine methylamine, then with the mixed solution of 1, 1- dimethylthio -2- nitroethylene and ethanol, and then with methylamine aqueous solution. The key intermediate is 2- chloro -5- chloromethylpyridine.
2- chloro -5- chloromethylpyridine is an important pesticide intermediate, which is not only used to synthesize nitenpyram, but also used as an intermediate of other important nicotinic pesticides such as imidacloprid, acetamiprid and thiacloprid. With the research of imidacloprid and nitenpyram, the research and production of 2- chloro -5- chloromethylpyridine are on the rise. The main methods of industrial production at home and abroad are as follows: ① 3- chloromethylpyridine is obtained from 3- methylpyridine by N- oxidation reaction, and then it is obtained by directional chlorination; (2) Cyclic method: benzylamine reacts with propionaldehyde to obtain 3- chloromethylpyridine through cyclic chlorination, and then chlorination is carried out; (3) Based on the direct cyclization of cyclopentadiene developed by Rayleigh Company in the United States, domestic researchers developed a ring-closing reaction of cyclopentadiene to directly prepare 2- chloro -5- chloromethylpyridine. The raw materials of this route are easily available and the production cost is relatively low. At present, Dalian Kaifei Chemical Co., Ltd., Jiangsu Chemical Pesticide Group Co., Ltd. and Jiangsu Kesheng Co., Ltd. mostly use this method for production; ④ Jiangsu Pesticide Research Institute has developed a production route with morpholine as raw material, and 2- chloro -5- chloromethylpyridine is synthesized from morpholine via N- propenylmorpholine, 1- chloro -2-(4- morpholine) -3- methylcyclobutyronitrile, 2- chloro -4- formylvaleronitrile, 2-chloro-5-methylpyridine and other intermediates. The method has the advantages of low raw material cost and less reaction.
9 bispyribac-sodium sodium (bispyribac-sodium-)
This variety was developed by Japanese Combinatorial Compound Company, and was granted a patent by China (CN88 108904.4). The patent is valid until February 22, 2008. Bispyribac-sodium sodium (PD200400 15) and 10% bispyribac-sodium sodium SC (PD200400 14) were also registered in China. Domestic registered enterprises include Jiangsu Hormone Research Institute Co., Ltd. and Shanghai Lingnong Chemical Co., Ltd. ..
Bispyribac-sodium is a pyrimidine salicylic acid broad-spectrum herbicide, which works by blocking the biosynthesis of branched-chain amino acids. It is mainly used in rice direct seeding field, which can effectively control annual and perennial gramineous and broad-leaved weeds, especially barnyard grass at 1~7 leaf stage, with extremely low dosage and broad application prospect. This pesticide has been registered in Japan, Europe and the United States.
There are two main routes for the synthesis of bispyribac-sodium sodium. A non-ester protection method, 2,6-dihydroxy benzoic acid and 2- substituted-4,6-dimethoxypyrimidine react under alkaline conditions to generate bispyribac-sodium sodium. The second method is ester protection. Firstly, 2,6-dihydroxy benzoic acid is esterified, and then the esterified product reacts with 2- substituted-4,6-dimethoxypyrimidine under alkaline conditions to generate bispyribac-sodium sodium ester, and then sodium bispyribac-sodium is obtained through catalytic hydrogenation and neutralization. The key intermediate is 2- substituted-4,6-dimethoxy pyrimidine, and 4,6-dimethoxy -2- methylthiopyrimidine is usually selected.
Literature reports that the main synthetic routes of 4,6-dimethoxy -2- methylthiopyrimidine are as follows: ① iodomethane method, which is prepared by the reaction of iodomethane with 4,6-dihydroxy -2- methylthiopyrimidine. The yield of this method is not high, and the price of sulfomethane is expensive; (2) dimethyl sulfate method, in which dimethyl sulfate reacts with 4,6-dihydroxy -2- mercaptopyrimidine. This method has low yield and large discharge of three wastes; ③ It is difficult for 3- amino-1, 3-dimethoxy -2- methylsulfonyl pyrimidine to be oxidized by hydrogen peroxide. ④ The researchers of Zhejiang University of Technology developed a synthetic route with diethyl malonate and thiourea as raw materials. In the presence of sodium methoxide, 4,6-dihydroxy -2- pyrimidine sodium sulfate was condensed, and then 4,6-dimethoxy -2- methylthiopyrimidine was obtained through a series of reactions such as methylation, chlorination and methoxylation. Although there are many steps, the reaction conditions are mild, the raw materials are cheap and easy to obtain, and it has industrial application prospects.
The synthesis of some pesticides and their intermediates is introduced above. These pesticides have some characteristics, that is, they are developed by foreign companies and patented in China. Meanwhile, these varieties have been or have been registered in China, and the patents have expired or will expire soon. 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 foundation for popularization 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 production enterprises should actively follow the legal protection status of foreign patented pesticides, strengthen the development and research of intermediates, expect to improve and perfect the synthesis process of intermediates, reduce the production cost of intermediates, and lay a solid foundation for the production of these pesticides with high efficiency, low toxicity and good market prospects.