Phosgene-free method for producing chlorprophams (o-isopropyl-n-(3-chlorophenyl)carbamate) and method for producing bis-n,n'-(3-chlorophenyl)-urea

Abstract

FIELD: agricultural chemistry.SUBSTANCE: group of inventions relates to a method for producing O-isopropyl-N-(3-chlorophenyl)carbamate (chlorpropham), which is used to destroy weeds and also as a plant growth regulator, as well as to a method for producing bis-N,N'-(3-chlorophenyl)urea. The method for obtaining bis-N,N'-(3-chlorophenyl)-urea consists of the interaction of urea and 3-chloroaniline at a molar ratio of urea to 3-chloroaniline equal to 1:(2–3) and a temperature of 132–180°C in an aromatic hydrocarbon environment. In this case, the interaction is carried out using catalysts: metal naphthenates in an amount of 0.05–0.20 of the mass of urea or without them, with the constant distillation of the released ammonia. The mixture of reagents is boiled for 5–80 hours, then the reaction mass is cooled, the precipitate is filtered off, the resulting filtrate is distilled by rectification, the aniline is returned back to the process, and the precipitate is dried and bis-N,N'-(3-chlorophenyl)-urea is isolated. Chlorpropham is obtained by reacting the obtained bis-N,N'-(3-chlorophenyl)-urea with isopropanol at a temperature of 120–170 °C and a molar ratio of bis-N,N'-(3-chlorophenyl)-urea to isopropanol of 1:(3–15).EFFECT: development of methods characterized by low toxicity of raw materials, ease of implementation and environmental friendliness.8 cl, 11 ex

Description

[0001] The invention relates to a new method for producing chlorpropham (O-isopropyl-N-(3-chlorophenyl)carbamate), a compound of formula I.

[0002]

[0003] Chlorpropham is a well-known herbicide used to kill weeds and as a plant growth regulator. Most of the chlorpropham produced is used in potato storage, as treating potato tubers with chlorpropham prevents their germination.

[0004] Several methods for preparing the compound of formula I have been described. The primary method for synthesizing chlorpropham, which is used on an industrial scale, involves the reaction of isopropyl alcohol with m-chlorophenyl isocyanate (patent DE2532982A1, IPC A01N 25 / 12, filed February 5, 1976). This method for producing chlorpropham is characterized by high yields, selectivity for the target product, and ease of its isolation. Despite the above advantages, the method has a number of disadvantages due to the use of m-chlorophenyl isocyanate. Isocyanates are highly reactive compounds that react, among other things, with water. In this regard, during storage and transportation of m-chlorophenyl isocyanate, it is necessary to exclude its contact with atmospheric moisture, which presents significant difficulties. In addition, meta-chlorophenyl isocyanate is toxic, and its synthesis uses an even more toxic compound – phosgene.The use of phosgene in synthesis leads to high costs for labor and environmental protection, requires special safety measures during production, and does not meet modern requirements for industrial organization.

[0005] Another method for producing chlorpropham (US Patent US2734911, IPC A01N 47 / 20, filed February 14, 1956) involves a reaction between m-chloroaniline and isopropyl chloroformate. This method produces good yields but has several drawbacks. The first is the release of hydrogen chloride during the synthesis process, which must be bound and disposed of. Another significant drawback of this method is the use of isopropyl chloroformate. Like meta-chlorophenyl isocyanate, isopropyl chloroformate is highly toxic, hydrolytically unstable, and is synthesized using phosgene.

[0006] A method for producing chlorpropham without using phosgenation products is described in the article (Yang X., Zhang Y., Ma D. / / Advanced Synthesis & Catalysis. - 2012. - Vol. 354. - No. 13. - Pp. 2443-2446). It consists of the reaction of 3-chlorobromobenzene, potassium cyanate, copper iodide and isopropyl alcohol. Chlorpropham is obtained by this method with a yield of 85%. This method cannot be implemented on an industrial scale, since it uses copper iodide and potassium cyanate. Their use leads to the formation of expensive waste containing compounds of copper, bromine and iodine.

[0007] Another phosgene-free method for producing chlorpropham is described in a patent (patent RU 2819162, IPC C07C 269 / 06; C07C 271 / 28, filed October 31, 2023). According to the patent, the target product is obtained in two stages. In the first stage, O-methyl-N-(3-chlorophenyl)carbamate is obtained from m-chloroaniline and dimethyl carbonate. The reaction is carried out under the catalysis of dibutyltin oxide in an excess of dimethyl carbonate. The target product is obtained in good yields. In the second stage, O-methyl-N-(3-chlorophenyl)carbamate is transesterified with isopropanol in the presence of sodium isopropoxide. The result is chlorpropham. Despite the good yields and the phosgene-free nature of the method, it has a number of drawbacks. The first drawback is the use of organotin catalysts, which are highly toxic and even residual amounts of them in herbicides are unacceptable. The second drawback of the method is the use of sodium isopropylate. Sodium alcoholates require special storage due to their hydrolytic instability.When reacting with water, they convert to sodium hydroxide, whose catalytic activity in carbamate transesterification reactions is much lower. The synthesis of sodium isopropylate itself also has a significant drawback, as it is produced by dissolving metallic sodium in isopropanol. The use of metallic sodium, as well as the release of hydrogen during the reaction, significantly increases the fire and explosion hazards of the process.

[0008] Analogues of the present invention are articles in which O-isopropyl-N-phenylcarbamate is obtained from N,N'-diphenylurea and isopropanol (Liu X., Werner T. / / Chemical Science. - 2021. - Vol. 12. - No. 31. - Pp. 10590-10597, Inaloo ID, Majnooni S. / / New Journal of Chemistry. - 2018. - Vol. 42. - No. 16. - Pp. 13249-13255 and Mantrov S.N., Chimishkyan A.L. / / Zhurn. phys. chemistry. 2005. Vol. 79. No. 5- pp. 804-807). All sources study only the reaction of unsubstituted N,N'-diphenylurea and isopropanol. The article (Liu X., Werner T.) proposes catalyzing the reaction with potassium tert-butoxide, which is unfavorable for industrial implementation, as potassium tert-butoxide cannot be regenerated, and its synthesis requires the use of metallic potassium, which is flammable and explosive. The article (Inaloo I.D., Majnooni S.B.) proposes using choline chloride mixed with zinc chloride as a catalyst.Given that choline chloride is an organic catalyst that cannot be regenerated, the industrial application of this method appears questionable. The article (S.N. Mantrov, A.L. Chimishkyan) describes only the kinetics of the reaction of alcohols, including isopropyl alcohol, with N,N'-diphenylurea without any catalysis, but provides no details of the synthesis.

[0009] Symmetrical diphenylureas, from which O-isopropyl-N-arylcarbamates and, first of all, bis-N,N'-(3-chlorophenyl)-urea can be made, are synthesized from urea and 3-chloroaniline (Rekunge DS, Khatri CK, Chaturbhuj GU / / Tetrahedron Letters. - 2017. - Vol. 58. - No. 45. - Pp. 4304-4307 and Chimishkyan A.L., Svetlova L.P., Leonova T.V., Gulyaev N.D. / / Journal of General Chemistry - 1984. - Vol. 54. - No. 7. - Pp. 1477 - 1481). The paper (Rekunge DS, Khatri CK, Chaturbhuj GU) proposes catalyzing the reaction with polysulfoborate. The authors of the closest analogous paper (Chimishkyan A.L., Svetlova L.P., Leonova T.V., Gulyaev N.D.) demonstrate that the reaction proceeds without a catalyst.

[0010] The closest technical solution to the claimed one is a method for producing N-aryl-O-alkyl carbamates (patent RU 2633358, IPC C07C 269 / 06; C07C 271 / 28, filed 11 / 25 / 2016), which consists in the interaction of alcohol R 1OH and symmetrical disubstituted urea II, where R denotes aryl groups, and R 1 means alkyl groups of a normal or branched structure with the number of carbon atoms from 1 to 4, in a continuous mode at atmospheric pressure in a medium of carbamate I with a reagent ratio of urea:aliphatic alcohol of 1:(10÷60) molar and a temperature of 140 to 250°C. The proposed method allows to increase the yield of N-aryl-O-alkyl carbamates of formula I and to exclude the use of solvents. N-aryl-O-alkyl carbamates of the general formula I are obtained in a column with packing and a heating jacket, operating continuously. In this case, it is proposed to feed a feed solution of diarylurea III, dissolved in the molten reaction product - N-aryl-O-alkyl carbamate, from the top of the column. Alcohol vapors are fed from the bottom of the column. During the reaction, excess alcohol leaves from the top of the column, and the resulting carbamate with unreacted diarylurea dissolved in it leaves the bottom of the column.

[0011] The disadvantage of this method is the complex method of its production and low yield in terms of loaded urea.

[0012] The objective of the present invention is to develop a phosgene-free method for producing chlorpropham (O-isopropyl-N-(3-chlorophenyl)carbamate) and a method for producing bis-N,N'-(3-chlorophenyl)urea, characterized by the availability and low toxicity of raw materials, ease of experimentation and environmental friendliness.

[0013] The problem is solved using a phosgene-free method for producing O-isopropyl-N-(3-chlorophenyl)carbamate (chlorpropham), a compound of formula I

[0014] ,

[0015] characterized by the fact that the reaction of urea and 3-chloroaniline is carried out at a molar ratio of urea to 3-chloroaniline equal to 1: (2-3) at a temperature of 132-180 ° C using catalysts: metal naphthenates in an amount of 0.05-0.20 of the weight of urea or without them, in a medium of aromatic hydrocarbons with constant distillation of the released ammonia, the mixture of reagents is boiled for 5-80 hours, then the reaction mass is cooled, the precipitate is filtered off, the resulting filtrate is distilled by rectification, aniline is returned back to the process, the precipitate is dried and bis-N, N'- (3-chlorophenyl) urea is isolated, then bis-N, N'- (3-chlorophenyl) urea is reacted with isopropanol at a temperature 120-170°C, in a molar ratio of bis-N,N'-(3-chlorophenyl)-urea to isopropanol of 1:(3-15) and O-isopropyl-N-(3-chlorophenyl)carbamate is obtained.

[0016] Preferably, the process of obtaining O-isopropyl-N-(3-chlorophenyl)carbamate is carried out in an autoclave for a reaction time of 2-15 hours.

[0017] Preferably, after the process is completed, the reaction mass is cooled and filtered from unreacted bis-N,N'-(3-chlorophenyl)-urea, isopropanol is distilled off on a rotary film evaporator, then 3-chloroaniline and O-isopropyl-N-(3-chlorophenyl)carbamate are isolated using vacuum distillation.

[0018] Preferably, the yield of O-isopropyl-N-(3-chlorophenyl)carbamate is 85-96% per reacted bis-N,N'-(3-chlorophenyl)urea.

[0019] The stated problem is also solved using a method for obtaining bis-N,N'-(3-chlorophenyl)-urea, characterized in that the interaction of urea and 3-chloroaniline is carried out at a molar ratio of urea to 3-chloroaniline equal to 1:(2-3) at a temperature of 132-180 °C using catalysts: metal naphthenates in an amount of 0.05-0.20 of the weight of urea or without them, in a medium of aromatic hydrocarbons with constant distillation of the released ammonia, the mixture of reagents is boiled for 5-80 hours, then the reaction mass is cooled, the precipitate is filtered off, the resulting filtrate is distilled by rectification, aniline is returned back to the process, the precipitate is dried and bis-N,N'-(3-chlorophenyl)-urea is isolated.

[0020] Preferably, cobalt, copper or zinc naphthenates are used as a catalyst.

[0021] Xylene, chlorobenzene, and o-dichlorobenzene are preferably used as aromatic hydrocarbons.

[0022] The yield of bis-N,N'-(3-chlorophenyl)-urea per reacted urea is preferably 55-72%.

[0023] The technical result of the proposed invention is a phosgene-free method for producing O-isopropyl-N-(3-chlorophenyl)carbamate and a method for producing bis-N,N'-(3-chlorophenyl)urea, which are distinguished by the availability and low toxicity of raw materials, ease of experimentation and environmental friendliness.

[0024] The method for producing O-isopropyl-N-(3-chlorophenyl)carbamate is preferably carried out in two stages. In the first stage, bis-N,N'-(3-chlorophenyl)urea is synthesized from urea and 3-chloroaniline, with or without metal naphthenate catalysts, in an aromatic hydrocarbon medium. In the second stage, which distinguishes the chlorpropham production method from known methods, the resulting bis-N,N'-(3-chlorophenyl)urea is reacted with isopropanol without the use of any catalysts.

[0025] The present method for preparing the compound of Formula I differs from previously known methods in that it utilizes m-chloroaniline, urea, and isopropanol, all readily available and inexpensive reagents. The advantages of the present method include the use of much less toxic reagents than phosgene, chloroformates, isocyanates, or organotin compounds, as well as the simple and standard design of the reaction units, which do not require additional protection of the starting compounds from moisture. The main waste product of the proposed process is ammonia, which can be recycled by converting it to urea.

[0026] A new method for synthesizing O-isopropyl-N-(3-chlorophenyl)carbamate involves reacting 3-chloroaniline (2-3 mole fractions) with urea (1 mole fraction) using naphthenate catalysts (cobalt, copper or zinc) (0.05 – 0.20 mass fractions relative to urea) or without a catalyst in an aromatic hydrocarbon medium (xylene, chlorobenzene, o-dichlorobenzene) at temperatures of 132-180°C for 5-80 hours in the first stage.

[0027] In the second stage, a reaction is carried out between bis-N,N'-(3-chlorophenyl)-urea (1 mole fraction) and isopropanol (3-15 mole fractions) in a steel autoclave at a temperature of 120-170°C for 2-15 hours. The resulting O-isopropyl-N-(3-chlorophenyl)carbamate is purified by vacuum distillation.

[0028] The invention can be illustrated by the following examples.

[0029] Example 1. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0030] 2.43 g (19.1 mmol) of m-chloroaniline, 0.52 g (8.7 mmol) of urea, and 30 ml of xylene are added to a single-neck flask equipped with a magnetic stirrer and reflux condenser. The reaction mixture is refluxed with stirring for 50 hours. After cooling, the product is filtered off, washed with petroleum ether (3 × 15 ml), and dried. 1.34 g of bis-N,N'-(3-chlorophenyl)-urea (55% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the xylene and m-chloroaniline fraction, and reused.

[0031] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0032] Example 2. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0033] 2.43 g (19.1 mmol) of m-chloroaniline, 0.52 g (8.7 mmol) of urea, and 30 ml of xylene are added to a single-neck flask equipped with a magnetic stirrer and reflux condenser. The reaction mixture is boiled with stirring until the evolution of ammonia ceases (80 hours). After cooling, the product is filtered, washed with petroleum ether (3 × 15 ml), and dried. 1.76 g of bis-N,N'-(3-chlorophenyl)-urea (72% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the xylene and m-chloroaniline fraction, and reused.

[0034] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0035] Example 3. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0036] 2.43 g (19.1 mmol, 2.7 ml) of m-chloroaniline, 0.38 g (6.37 mmol) of urea and 30 ml of o-dichlorobenzene are charged into a single-neck flask equipped with a magnetic stirrer and reflux condenser. The reaction mixture is boiled with stirring for 30 hours. After cooling, the product is filtered off, washed with petroleum ether (3 × 15 ml), dried. Recrystallized from ethanol. 1.06 g of bis-N,N'-(3-chlorophenyl)-urea (59% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the o-dichlorobenzene and m-chloroaniline fraction, and reused.

[0037] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0038] Example 4. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0039] 2.43 g (19.1 mmol) of m-chloroaniline, 0.46 g (7.64 mmol) of urea and 30 ml of xylene are charged into a single-neck flask equipped with a magnetic stirrer and reflux condenser. 92 mg of copper naphthenate are added and the reaction mixture is refluxed with stirring for 50 hours. After cooling, the product is filtered, washed with petroleum ether (3×15 ml), dried. Recrystallized from ethanol. 1.4 g of bis-N,N'-(3-chlorophenyl)-urea (65% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the xylene and m-chloroaniline fraction, and reused.

[0040] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0041] Example 5. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0042] 2.43 g (19.1 mmol) of m-chloroaniline, 0.52 g (8.66 mmol) of urea and 30 ml of xylene are charged into a single-neck flask equipped with a magnetic stirrer and reflux condenser. 26 mg of cobalt naphthenate are added and the reaction mixture is boiled with stirring for 30 hours. After cooling, the product is filtered, washed with petroleum ether (3×15 ml), dried. Recrystallized from ethanol. 1.8 g of bis-N,N'-(3-chlorophenyl)-urea (78% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the xylene and m-chloroaniline fraction, and reused.

[0043] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0044] Example 6. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0045] 2.43 g (19.1 mmol) of m-chloroaniline, 0.52 g (8.66 mmol) of urea and 30 ml of xylene are charged into a single-neck flask equipped with a magnetic stirrer and reflux condenser. 42 mg of cobalt naphthenate are added and the reaction mixture is boiled with stirring for 5 hours. After cooling, the product is filtered, washed with petroleum ether (3×15 ml), dried. Recrystallized from ethanol. 1.02 g of bis-N,N'-(3-chlorophenyl)-urea are obtained (42% based on unregenerated urea). The filtrate containing unreacted m-chloroaniline is distilled, collecting the xylene and m-chloroaniline fraction, and reused. Ethanol is evaporated after recrystallization. The remainder - urea - is returned to the process.

[0046] 1H NMR spectrum of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0047] Example 7. Synthesis of bis-N,N'-(3-chlorophenyl)-urea.

[0048] 2.43 g (19.1 mmol) of m-chloroaniline, 0.57 g (9.55 mmol) of urea and 30 ml of chlorobenzene are charged into a single-neck flask equipped with a magnetic stirrer and reflux condenser. 115 mg of zinc naphthenate are added and the reaction mixture is boiled with stirring for 60 hours. After cooling, the product is filtered off, washed with petroleum ether (3×15 ml), dried. Recrystallized from ethanol. 1.02 g of bis-N,N'-(3-chlorophenyl)-urea 1.61 (60% by urea) are obtained. The filtrate containing unreacted m-chloroaniline is distilled, collecting the chlorobenzene and m-chloroaniline fraction, and reused.

[0049] Spectrum 1 H NMR of bis-N,N'-(3-chlorophenyl)-urea (500 MHz, DMSO-d6) δ 7.03 (d, J = 6.0 Hz, 2H), 7.31-7.27 (m, 4H), 7.71 (s, 2H), 8.99 (s, 2H).

[0050] Example 8. Synthesis of O-isopropyl-N-(3-chlorophenyl)carbamate (chlorpropham).

[0051] 20 g (76.6 mmol) of bis-N,N'-(3-chlorophenyl)-urea and 13.78 g (229.8 mmol) of isopropanol are placed in a 100 ml stainless steel autoclave. The mixture is heated in an oil bath for 10 hours at a temperature of 140 °C. After the specified time, the reaction mixture is cooled and unreacted bis-N,N'-(3-chlorophenyl)-urea (2.3 g) is filtered off. Isopropanol is distilled off on a rotary film evaporator. The residue is distilled under vacuum. The first fraction (3-chloroaniline) - 100-115°C / 10-15 mmHg, the main fraction (chlorpropham) - 160-175°C / 10-15 mmHg. 12.6 g (94% of the reacted bis-N,N'-(3-chlorophenyl)-urea) O-isopropyl-N-(3-chloro)phenylcarbamate and 9.2 g of 3-chloroaniline are obtained.

[0052] Spectrum 1 H NMR of O-isopropyl N-(3-chlorophenyl)carbamate (500 MHz, DMSO-d6) δ 1.26 (d, J=6.2 Hz, 6H); 4.90 (dt, J=12.4, 6.2 Hz, 1H); 7.02 (d, J=7.7 Hz, 1H); 7.16-7.44 (m, 2H); 7.61 (s, 1H); 9.76 (br s, 1H).

[0053] Example 9. Synthesis of O-isopropyl-N-(3-chloro)phenylcarbamate (chlorpropham).

[0054] 20 g (76.6 mmol) of bis-N,N'-(3-chlorophenyl)-urea and 68.9 g (1.15 mol) of isopropanol are placed in a 150 ml stainless steel autoclave. The mixture is heated in an oil bath for 15 hours at a temperature of 120 °C. After the specified time, the reaction mixture is cooled and filtered from unreacted bis-N,N'-(3-chlorophenyl)-urea (2.0 g). Isopropanol is distilled off on a rotary film evaporator. The residue is distilled under vacuum. The first fraction (3-chloroaniline) - 100-115°C / 10-15 mmHg, the main fraction (chlorpropham) - 160-175°C / 10-15 mmHg. 13.1 g (96% of the reacted bis-N,N'-(3-chlorophenyl)-urea) O-isopropyl-N-(3-chloro)phenylcarbamate and 9.4 g of 3-chloroaniline are obtained.

[0055] Spectrum 1H NMR of O-isopropyl N-(3-chlorophenyl)carbamate (500 MHz, DMSO-d6) δ 1.26 (d, J=6.2 Hz, 6H); 4.90 (dt, J=12.4, 6.2 Hz, 1H); 7.02 (d, J=7.7 Hz, 1H); 7.16-7.44 (m, 2H); 7.61 (s, 1H); 9.76 (br s, 1H).

[0056] Example 10. Synthesis of O-isopropyl-N-(3-chloro)phenylcarbamate (chlorpropham).

[0057] 20 g (76.6 mmol) of bis-N,N'-(3-chlorophenyl)-urea and 60.0 g (1.0 mol) of isopropanol are placed in a 100 ml stainless steel autoclave. The mixture is heated in an oil bath for 2 hours at a temperature of 170 °C. After the specified time, the reaction mass is cooled and filtered from unreacted bis-N,N'-(3-chlorophenyl)-urea (3.5 g). Isopropanol is distilled off on a rotary film evaporator. The residue is distilled under vacuum. The first fraction (3-chloroaniline) - 100-115°C / 10-15 mmHg, the main fraction (chlorpropham) - 160-175°C / 10-15 mmHg. 10.6 g (85% of the reacted bis-N,N'-(3-chlorophenyl)-urea) O-isopropyl-N-(3-chloro)phenylcarbamate and 8.5 g of 3-chloroaniline are obtained.

[0058] Spectrum 1 H NMR of O-isopropyl N-(3-chlorophenyl)carbamate (500 MHz, DMSO-d6) δ 1.26 (d, J=6.2 Hz, 6H); 4.90 (dt, J=12.4, 6.2 Hz, 1H); 7.02 (d, J=7.7 Hz, 1H); 7.16-7.44 (m, 2H); 7.61 (s, 1H); 9.76 (br s, 1H).

[0059] Example 11 (based on the prototype). N-(3-chlorophenyl)-O-isopropylcarbamate.

[0060] The alcoholysis process is carried out in a heated flow column at a temperature of 250°C. A solution of di-(3-chlorophenyl)-urea in N-(3-chlorophenyl)-O-isopropylcarbamate, preheated to 200°C, is fed from the top of the column in a weight ratio of 1 to 20, respectively. Isopropanol vapor is fed from the evaporator at the bottom of the column at a rate such as to maintain a 60-fold molar excess of isopropanol in the column relative to di-(3-chlorophenyl)-urea. After passing the solution through the column, it is collected at the bottom of the column and cooled to a temperature of 60°C. Unreacted di-(3-chlorophenyl)-urea is filtered off, and the filtrate, which is a virtually pure product, is crystallized by cooling. The yield of N-(3-chlorophenyl)-O-isopropylcarbamate based on the loaded diphenylurea is 35%. Tm = 40-41°C.

[0061] NMR 1H spectrum (δ, ppm; J, Hz) (400 MHz in CDCl3): 1.30 (6H; d; 6.2 Hz, CH3-(iPr)); 5.02 (1H; sep; 6.2 Hz, CH-O); 6.62 (1H; s; -NH-); 7.02 (1H; d; 4.4 Hz, H4arom); 7.20 (2H, m, H5,6arom); 7.51 (1H, s, H2-arom).

[0062] From the given examples it follows that in the proposed method for producing O-isopropyl-N-(3-chlorophenyl)carbamate the yield is up to 96%, and bis-N,N'-(3-chlorophenyl)urea is also obtained with a high yield of up to 72%.

[0063] The proposed method for producing O-isopropyl-N-(3-chlorophenyl)carbamate is economical on an industrial scale.

Claims

1. A phosgene-free method for producing O-isopropyl-N-(3-chlorophenyl)carbamate (chlorpropham), a compound of formula I , characterized in that the reaction of urea and 3-chloroaniline is carried out at a molar ratio of urea to 3-chloroaniline equal to 1: (2-3), at a temperature of 132-180 ° C using catalysts: metal naphthenates in an amount of 0.05-0.20 of the weight of urea or without them, in a medium of aromatic hydrocarbons with constant distillation of the released ammonia, the mixture of reagents is boiled for 5-80 hours, then the reaction mass is cooled, the precipitate is filtered off, the resulting filtrate is distilled by rectification, aniline is returned back to the process, the precipitate is dried and bis-N,N'- (3-chlorophenyl)-urea is isolated, then the reaction of bis-N,N'- (3-chlorophenyl)-urea is carried out with isopropanol at a temperature of 120-170 ° C, in a molar ratio bis-N,N'-(3-chlorophenyl)-urea to isopropanol 1:(3-15) to obtain O-isopropyl-N-(3-chlorophenyl)carbamate.

2. The method according to claim 1, characterized in that the process of obtaining O-isopropyl-N-(3-chlorophenyl)carbamate is carried out in an autoclave for a reaction time of 2-15 hours.

3. The method according to paragraph 1, characterized in that after completion of the process, the reaction mass is cooled and filtered from unreacted bis-N,N'-(3-chlorophenyl)-urea, isopropanol is distilled off on a rotary film evaporator, then 3-chloroaniline and O-isopropyl-N-(3-chlorophenyl)carbamate are isolated using vacuum distillation.

4. The method according to claim 1, characterized in that the yield of O-isopropyl-N-(3-chlorophenyl)carbamate is 85-96% of the reacted bis-N,N'-(3-chlorophenyl)urea.

5. A method for producing bis-N,N'-(3-chlorophenyl)-urea, characterized in that urea and 3-chloroaniline are reacted at a molar ratio of urea to 3-chloroaniline equal to 1:(2-3), at a temperature of 132-180°C using catalysts: metal naphthenates in an amount of 0.05-0.20 of the urea weight or without them, in an aromatic hydrocarbon medium with continuous distillation of the released ammonia, the mixture of reagents is boiled for 5-80 hours, then the reaction mass is cooled, the precipitate is filtered off, the resulting filtrate is distilled by rectification, aniline is returned back to the process, the precipitate is dried and bis-N,N'-(3-chlorophenyl)-urea is isolated.

6. The method according to paragraph 5, characterized in that cobalt, copper or zinc naphthenates are used as a catalyst.

7. The method according to paragraph 5, characterized in that xylene, chlorobenzene, and o-dichlorobenzene are used as aromatic hydrocarbons.

8. The method according to any one of paragraphs 5-7, characterized in that the yield of bis-N,N'-(3-chlorophenyl)-urea per reacted urea is 55-72%.