Method for producing tribenuron-methyl

Abstract

FIELD: organic chemistry.SUBSTANCE: invention relates to the field of synthesis of organic compounds, specifically to a method for producing tribenuron-methyl of formula I, which is a highly selective systemic post-emergence herbicide from the class of sulfonylureas. The method involves the interaction of methyl 2-(chlorosulfonyl)benzoate with 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine and sodium or potassium cyanate in the presence of an organic base selected from pyridine, 2-methylpyridine or 3-methylpyridine, in cyclic organic carbonate selected from propylene carbonate, ethylene carbonate or a mixture thereof as a solvent to form a reactive a mass containing a tribenuron-methyl salt with an organic base used, followed by its treatment with water and acid to form the target product, isolate it and purify it.EFFECT: technical result of the invention is the production of a high-quality target product with a good yield and the improvement of the safety and environmental friendliness of the synthesis process.4 cl, 5 ex

Description

[0001] The invention relates to the field of synthesis of organic compounds, more specifically to the production of active ingredients of pesticides, in particular to a method for producing tribenuron-methyl (methyl 2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)methylcarbamoyl]sulfamoyl]benzoate (I), CAS registration number [101200-48-0]). This compound is a highly selective systemic post-emergence herbicide of the sulfonylurea class and is used in agriculture to control many broadleaf weeds in cereals (e.g., wheat, barley, oats) and other crops (e.g., sunflower, cotton) (see, e.g., Modern Crop Protection Compounds, Edited by Jeschke P. et al., 3rd Ed., Vol. 1: Herbicides. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA, 2019, p. 61). Tribenuron-methyl was developed and marketed by E. I. du Pont de Nemours and Company in 1987 (EP patent no. 0202830A1).

[0002]

[0003] All known modern methods for the preparation of tribenuron-methyl are complex and involve an initial multi-step synthesis of its two key precursors, which are substituted methyl 2-(X-sulfonyl)benzoates (X = NH2, NCO, Cl, NHCO2R (R = Me, Et), NHM (M = Na, K, Ca), etc.) (A) [available from saccharin or methyl anthranilate] and 2-Y-4-methoxy-6-methyl-1,3,5-triazines (Y = NHMe, N(Me)CO2Ph, etc.) (B) (Scheme 1). At the final stage of the synthesis, the sulfonylurea fragment of the target product I is created by using the reaction of one of the possible pairs of the corresponding starting compounds A and B with each other under suitable conditions (see, for example, patents EP No. 0202830A1, US No. 4394506A, US No. 4546179A, US No. 5153324A, US No. 5380843A, US No. 5886176A, WO No. 1997005121A1, WO No. 2003091228A2, WO No. 2017092469A1, CN No. 102391194A, CN No. 102718723A, CN No. 106478534A, CN No. 116640099A, CN No. 119306677A, RU No. 2103263C1, RU No. 2815938C1; H. Li et al., Jingxi Yu Zhuanyong Huaxuepin, 2007, 15(13), 23-24; B.Zhao et al., Nongyao, 2003, 42(7), 9-10; Y. Cui et al., Jingxi Huagong Zhongjianti (Fine Chem. Intermed.), 2013, 43(2), 22-24, 28; Y. Lu et al., Shijie Nongyao, 2007, 29(2), 12-14; Y. Lu et al., Jiangsu Huagong, 2007, 35(2), 40-42).

[0004]

[0005] Схема 1.

[0006] Based on the analysis of the available literature and patent data presented above, the current main industrial method for producing the target tribenuron-methyl involves phosgenation of sulfonamide (A, where X = NH2) to form a labile sulfonyl isocyanate (A, where X = NCO), followed by its reaction with the corresponding triazine (B, where Y = NHMe). The obvious disadvantages of this approach are the duration and rather harsh conditions of its implementation (elevated temperature (120-180°C) and pressure (up to 5 atm)) along with the need to use such hazardous feedstocks as phosgene, triphosgene, oxalyl chloride, butyl isocyanate, etc., which imposes rather stringent requirements for industrial safety measures during such a process and, obviously, complicates its implementation and reduces technical and economic indicators.

[0007] Another group of methods for producing tribenuron-methyl, based on the use of readily available sulfonamide (A, where X = NH2) and triazine (B, where Y = NHMe), includes a number of processes that do not explicitly employ the phosgenation reaction (the so-called "phosgene-free" methods). However, they also employ toxic chloroformates (methyl, ethyl, or phenyl chloroformate) and / or alkali and alkaline earth metal hydrides and alcoholates, which are hazardous to handle and store. This necessitates a) the use of anhydrous organic solvents and an inert gas atmosphere in such processes, b) strict control over the absence of moisture at all stages of such processes, and c) the use of specialized equipment, which significantly impacts their technical and economic performance.

[0008] Finally, two phosgene-free one-stage methods for obtaining the target tribenuron-methyl are known, based on the use of methyl 2-(chlorosulfonyl)benzoate (II) (hereinafter referred to as sulfochloride II) and 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine (III) (hereinafter referred to as aminotriazine III) as starting materials (Schemes 2, 3).

[0009] US Patent No. 4,546,179A discloses a method for producing the target tribenuron-methyl by reacting sulfochloride II with aminotriazine III in the presence of sodium or potassium cyanate or substituted quaternary ammonium cyanate (R4N + ) or phosphonium (R4P + ) or tertiary sulfonium (R3S +) at a temperature of 20-150°C for 0.5-8 h (Scheme 2). The reaction is carried out in an inert organic solvent selected from a chlorinated hydrocarbon (dichloromethane (DCM), chloroform, etc.), nitrile (acetonitrile, propionitrile), ketone (acetone, methyl ethyl ketone), ether (1,4-dioxane, tetrahydrofuran (THF), 1,2-dimethoxyethane, etc.), nitro compound (nitrobenzene), amide (N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), N-methylpyrrolidone (NMP)), sulfoxide (dimethyl sulfoxide (DMSO)) or mixtures thereof. In this case, in the case of using sodium or potassium cyanate, acetonitrile is preferably used as a solvent, and in the case of cyanates of substituted organic cations, DCM or THF, while the yield of the target product I is not indicated in this source.

[0010]

[0011] Scheme 2.

[0012] WO Patent No. 2003091228A2 discloses another variant of the above approach, which is implemented in two stages, including the primary generation in solution of a solvated (stabilized) zwitterionic salt B (Scheme 3) from the starting sulfochloride II and sodium, potassium or substituted quaternary ammonium cyanate (R4N + ) in the presence of pyridine or substituted pyridine as a catalyst and / or system stabilizer in solution at a temperature of -30-70°C, followed by the interaction of this salt B without isolation from this solution with aminotriazine III at a temperature of 0-100°C, which leads to the formation of the structure of the target tribenuron-methyl.

[0013]

[0014] Scheme 3.

[0015] This process is usually carried out in an inert organic solvent, which includes ethers (diethyl ether, diisopropyl ether, THF, 1,4-dioxane, methyl tert-butyl ether (MTBE), etc.), mono- and dialkyl ethers of glycols (monomethyl or monoethyl ether of propylene glycol or ethylene glycol, 1,2-dimethoxyethane, diglyme, triglyme, etc.), amides (DMF, DMAc, NMP), ketones (acetone, cyclohexanone, methyl isobutyl ketone (MIBK), etc.), nitriles (acetonitrile, propionitrile, etc.), sulfoxides and sulfones (DMSO and sulfolane) or mixtures thereof. In this case, the most preferred organic solvents are diisopropyl ether, MTBE, MIBK and acetonitrile, and the yield of the target sulfonylurea I is also not indicated in this patent.

[0016] To summarize the above, the disadvantages of the specified phosgene-free “cyanate” schemes for obtaining tribenuron-methyl (Schemes 2, 3) include the use of common organic solvents (MeCN, THF, MTBE, DCM, MIBK, DMF, etc.), which are not only toxic, carcinogenic and hazardous to handle flammable liquids (FL), which complicates work with them and requires compliance with special industrial safety measures, but are also classified as “volatile organic compounds” (VOC), i.e. compounds that pollute the atmosphere and contribute to the destruction of the planet's ozone layer, as well as causing other harm to the environment (see, e.g., D. Stoye: “Solvents”, Ullmann's Encyclopedia of Industrial Chemistry, 7th Ed., Vol. 33, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2011, pp. 619–688). Some of these solvents (e.g., MeCN, EtCN, THF, acetone, etc.) are also precursors, i.e.their turnover is subject to special control and accounting.

[0017] Considering the fact that in modern laboratory and industrial organic chemistry close attention is paid to the possibility of improving production processes in order to bring their performance closer to the basic principles of the “green chemistry” concept (PT Anastas and JC Warner, Green Chemistry: Theory and Practice, Oxford University Press, New York, 1998), an analysis of available published data has shown that one of such groups of “green” organic solvents that have become widespread in industrial chemistry throughout the world, the use of which in this process is unknown, but theoretically possible, are organic carbonates (diesters of carbonic acid) (see, for example, H.-J. Buysch: “Carbonic Esters”, Ullmann's Encyclopedia of Industrial Chemistry, 7th Ed., Vol. 7, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2011, p.45-71), in particular water-soluble cyclic organic carbonates (cyclic diesters of carbonic acid), such as ethylene carbonate (EC) and propylene carbonate (PC). These compounds are low-toxic and non-aggressive, commercially available and environmentally friendly polar aprotic organic solvents, the use of which is possible over a wide temperature range and which are generally recognized as “green” chemicals due to their low toxicity, high biodegradability, high boiling point, low vapor pressure, etc. (see, e.g., J.S. Bello Forero et al., Curr. Org. Synth., 2016, 13(6), 834-846).

[0018] Thus, it is obvious that the search for and optimization of new, highly scalable and efficient methods for producing the target tribenuron-methyl, allowing it to be obtained from available raw materials in a safer and more environmentally friendly way, is an urgent task.

[0019] The objective of the proposed technical solution is to improve the technical, economic and environmental performance of the process of obtaining tribenuron-methyl by using a new phosgene-free technology for its synthesis based on sulfochloride II and aminotriazine III in “green” cyclic organic carbonates.

[0020] The technical result is an improvement in the technical, economic and environmental performance of the process for obtaining tribenuron-methylase by eliminating the use of conventional hazardous and toxic organic solvents, which are simultaneously flammable liquids and VOCs, as a reaction medium, with their successful replacement by environmentally friendly cyclic organic carbonates, leading to a) an increase in the safety and environmental friendliness of the process, b) a decrease in the amount of toxic waste from the process, c) obtaining a high-quality target product with a good yield.

[0021] The technical result is achieved by using a method for producing tribenuron-methyl, which consists of reacting methyl 2-(chlorosulfonyl)benzoate (sulfochloride II) with 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine (aminotriazine III) and sodium or potassium cyanate in the presence of an organic base in a cyclic organic carbonate medium selected from propylene carbonate (PC), ethylene carbonate (EC) or a mixture thereof, with the formation of a reaction mass containing a salt of tribenuron-methyl with the organic base used, followed by its treatment with water and acid with the formation of the target product, its isolation and purification.

[0022] Pyridine, 2-methylpyridine or 3-methylpyridine is used as the organic base; formic acid, acetic acid, propionic acid, hydrochloric acid or sulfuric acid is used as the acid; in this case, an organic base is first added to a suspension of methyl 2-(chlorosulfonyl)benzoate and sodium or potassium cyanate in a cyclic organic carbonate medium, and then 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine is added, or 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine is first added to a suspension of methyl 2-(chlorosulfonyl)benzoate and sodium or potassium cyanate in a cyclic organic carbonate medium, and then an organic base is added.

[0023] Optimization of the process conditions showed that it is preferable to use from 1.3 to 1.7 molar equivalents of sulfochloride II (due to the latter's tendency to form saccharin as a by-product during the reaction), from 2.0 to 2.2 molar equivalents of sodium or potassium cyanate, from 3.0 to 7.0 molar equivalents of an organic base relative to aminotriazine III; while the process is preferably carried out in the temperature range from 20 to 85°C.

[0024] The invention is illustrated by the following examples 1-5 (Scheme 4).

[0025]

[0026] Scheme 4.

[0027] Example 1.

[0028] 4.33 g (0.018 mol) of sulfochloride II, 1.94 g (0.030 mol) of sodium cyanate and propylene carbonate are charged into the synthesis reactor and 3.37 g (0.043 mol) of pyridine are dosed to the resulting suspension with stirring. The reaction mass is stirred at room temperature for 1-1.5 h, 2.19 g (0.014 mol) of aminotriazine III are added to it and the holding is continued until the reaction is complete (HPLC control), after which it is treated with acetic acid to pH 4-4.5 and poured into water. The resulting precipitate of the product is filtered off, washed with water and dried. 3.48 g (62%) of tribenuron-methyl are obtained as a light yellow powder with a purity of at least 98.0% (according to HPLC); mp 142.2-145.1°C (decomp.). Spectral characteristics of the product: 1 H NMR (500 MHz, CDCl3, δ, ppm): 2.67 (s, 3H, CH3), 3.42 (s, 3H, NCH3), 3.94 (s, 3H, OCH3), 4.08 (s, 3H, OCH3), 7.65-7.71 (m, 3H, H-Ar), 8.39-8.42 (m, 1H, H-Ar), 13.97 (br s, 1H, NH); IR (powder, ν, cm -1): 3455 w, 3426 w, 3103 w, 3016 w, 2958 w, 2880 w, 1729 wed, 1713 wed, 1558 w, 1500 wed, 1465 wed, 1431 wed, 1396 wed, 1344 w, 1304 w, 1266 wed, 1225 w, 1193 w, 1170 wed, 1161 wed, 1136 w, 1117 wed, 1103 wed, 1059 wed, 1033 w, 1013 w, 994 w, 957 w, 891 w, 870 wed, 855 w, 812 m, 799 w, 770 w, 748 m, 729 w, 702 m; mass spectrum (APCI-): [MH] - 394.1.

[0029] Example 2.

[0030] 6.75 g (0.029 mol) of sulfonyl chloride II, 2.76 g (0.034 mol) of potassium cyanate and a mixture of 99 wt.% propylene carbonate and 1 wt.% ethylene carbonate are charged into the synthesis reactor and 6.72 g (0.085 mol) of pyridine are dosed to the resulting suspension with stirring. The reaction mixture is stirred at room temperature for 1-1.5 h, 2.62 g (0.017 mol) of aminotriazine III are added to it and the holding is continued until the reaction is complete (HPLC control), after which it is treated with formic acid to pH 4-4.5 and poured into water. The resulting precipitate of the product is filtered off, washed with water and dried. 4.37 g (65%) of tribenuron-methyl are obtained as a light yellow powder with a purity of at least 98.0% (according to HPLC).

[0031] Example 3.

[0032] 5.98 g (0.025 mol) of sulfochloride II, 2.43 g (0.037 mol) of sodium cyanate and a mixture of 50 wt.% propylene carbonate and 50 wt.% ethylene carbonate are charged into the synthesis reactor and 9.41 g (0.119 mol) of pyridine are dosed to the resulting suspension with stirring. The reaction mass is stirred at room temperature for 1-1.5 h, 2.62 g (0.017 mol) of aminotriazine III are added to it, the reaction mass is heated to a temperature of 70-75 °C and maintained at this temperature until the reaction is complete (HPLC control), after which it is cooled to room temperature, treated with propionic acid to pH 4-4.5 and poured into water. The resulting precipitate of the product is filtered off, washed with water and dried. 5.26 g (78%) of tribenuron-methyl are obtained as a light yellow powder with a purity of at least 98.0% (according to HPLC).

[0033] Example 4.

[0034] 4.35 g (0.019 mol) of sulfonyl chloride II, 1.95 g (0.030 mol) of sodium cyanate and ethylene carbonate are charged into the synthesis reactor. The contents of the reactor are heated to a temperature of 40-45°C and 5.32 g (0.057 mol) of 2-methylpyridine are dosed to the resulting suspension with stirring. The reaction mass is stirred at this temperature for 1-1.5 h, 2.20 g (0.014 mol) of aminotriazine III are added to it, the reaction mass is heated to a temperature of 80-85°C and maintained at this temperature until the reaction is complete (HPLC control), after which it is cooled to room temperature, treated with 10% hydrochloric acid to pH 4-4.5 and poured into water. The resulting precipitate is filtered, washed with water, and dried. This yields 4.26 g (76%) of tribenuron-methyl as a light yellow powder with a purity of at least 98.0% (according to HPLC).

[0035] Example 5.

[0036] 5.58 g (0.024 mol) of sulfonyl chloride II, 2.76 g (0.034 mol) of potassium cyanate, 2.62 g (0.017 mol) of aminotriazine III and a mixture of 1 wt.% propylene carbonate and 99 wt.% ethylene carbonate are charged into the synthesis reactor. The contents of the reactor are heated to 55-60 °C and 9.50 g (0.102 mol) of 3-methylpyridine are dosed to the resulting suspension with stirring. The reaction mass is stirred at this temperature until the reaction is complete (HPLC control), after which it is cooled to room temperature, treated with 30% sulfuric acid to pH 4-4.5 and poured into water. The resulting precipitate of the product is filtered off, washed with water and dried. 4.23 g (63%) of tribenuron-methyl are obtained as a light yellow powder with a purity of at least 98.0% (according to HPLC).

[0037] As a result of using the proposed method for obtaining tribenuron-methyl, it is possible to improve the technical, economic and environmental performance of the process for its production by eliminating the use of conventional hazardous and toxic organic solvents, which are simultaneously flammable liquids and VOCs, as a reaction medium, with their successful replacement by environmentally friendly cyclic organic carbonates, leading to a) increased safety and environmental friendliness of the process, b) a decrease in the amount of toxic waste from the process, c) obtaining a high-quality target product with a good yield.

Claims

1. A method for producing tribenuron-methyl, which consists of reacting methyl 2-(chlorosulfonyl)benzoate with 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine and sodium or potassium cyanate in the presence of an organic base selected from pyridine, 2-methylpyridine or 3-methylpyridine, in a cyclic organic carbonate selected from propylene carbonate, ethylene carbonate or a mixture thereof, as a solvent with the formation of a reaction mass containing a salt of tribenuron-methyl with the organic base used, followed by its treatment with water and acid with the formation of the target product, its isolation and purification.

2. The method according to paragraph 1, characterized in that formic, acetic, propionic, hydrochloric or sulfuric acid is used as the acid.

3. The method according to claim 1, characterized in that an organic base is first introduced into a suspension of methyl 2-(chlorosulfonyl)benzoate and sodium or potassium cyanate in a cyclic organic carbonate, and then 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine is added.

4. The method according to claim 1, characterized in that 2-(methylamino)-4-methoxy-6-methyl-1,3,5-triazine is first added to a suspension of methyl 2-(chlorosulfonyl)benzoate and sodium or potassium cyanate in a cyclic organic carbonate, and then an organic base is introduced.

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