Preparation method of nicosulfuron

Abstract

The invention discloses a novel method for preparing nicosulfuron, which comprises the following steps: taking pyrilamine and phenyl ester as substrates, sequentially adding a solvent and a small molecular auxiliary agent, stirring and reacting in the solvent at 0-100 DEG C for 10 minutes, desolventizing and separating to obtain nicosulfuron wet powder, and drying to obtain a finished product. According to the preparation method disclosed by the invention, the problem of long six-step condensation time of traditional nicosulfuron is solved by optimizing the whole flow of a key preparation process and parameter conditions (including the ratio and the adding sequence of reaction raw materials, a catalyst, reaction temperature and time and the like) of a synthesis process and particularly innovatively adding a small-molecule auxiliary agent; and the productivity and the equipment utilization rate are improved.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical preparation, and more specifically, relates to a new method for preparing nicosulfuron. The method uses pyrimidine amine and phenyl ester as raw materials to prepare nicosulfuron. Background Art

[0002] Nicosulfuron, whose chemical name is 2-(4,6-dimethoxypyrimidin-2-ylcarbamylaminosulfonyl)-N,N-dimethylnicotinamide (English name Nicosulfuron), is a sulfonylurea herbicide variety for corn fields discovered by Ishihara Sangyo Co., Ltd. in Japan in the mid-1980s. It is widely popular due to its high safety for corn, outstanding weed control effect, strong miscibility, and ultra-low per-acre usage.

[0003] Since Dr. G. Levitt of DuPont discovered the sulfonylurea herbicide for the first time in 1975, and patented the wheat field herbicide chlorimuron-methyl in 1976, the era of super-efficient herbicides has begun. In 1987, Ishihara Sangyo Co., Ltd. of Japan and DuPont of the United States jointly developed nicosulfuron. Sulfonylurea herbicides are composed of active groups, hydrophobic aromatic groups, and sulfonylurea bridges. They can destroy the internal structure and physiological balance of plants and cause plant death, that is, by inhibiting acetolactate synthase, preventing the synthesis of branched-chain amino acids valine, leucine and isoleucine, and then preventing cell division, so that sensitive plants cannot grow normally, stems and leaves turn green, and gradually die.

[0004]

[0005] Chemical structure of Nicosulfuron At present, there are three main routes for the production of nicosulfuron: the amine ester route, the light-fixing route and the phenyl ester route. Among them, the nicosulfuron product obtained by the phenyl ester route has a higher purity (≥97%) and does not require the use of highly toxic phosgene or ethyl chloroformate. However, in the phenyl ester process, the condensation reaction and heat preservation time of the intermediate phenyl ester and pyrimidine amine are relatively long (8-10h), which reduces the production capacity and production efficiency.

[0006] Therefore, the current industry is in urgent need of finding a new synthetic method for preparing nicosulfuron with simple operating steps and short reaction time.

[0007] . Summary of the invention

[0008] In view of the above defects or improvement needs of the prior art, the purpose of the present invention is to provide a new method for preparing Nicosulfuron. The present invention improves the overall process of the key preparation process and the parameter conditions of the synthesis process (including the ratio and addition order of the reaction raw materials, catalyst, reaction temperature and time, etc.), especially the innovative addition of a small molecule co-catalyst. Compared with the traditional phenyl ester method for the synthesis of Nicosulfuron, a catalytic amount of a cheap and readily available non-metallic catalyst is added to the system, which reduces the reaction energy barrier and activation energy, greatly shortens the reaction time, and improves the raw material conversion efficiency.

[0009] To achieve the above object, according to the present invention, a new method for preparing nicosulfuron is provided, characterized in that it comprises the following steps: With pyrimidine amine and phenyl ester as substrates, a solvent and a small molecule co-catalyst are added in sequence, the mixture is stirred and reacted at 0-100° C. in the solvent for 1-10 minutes, and then the nicosulfuron wet powder is separated by desolventizing, and the finished product is obtained by drying.

[0010] As a further preferred embodiment of the present invention, in the step, the catalyst is any one of N-bromosuccinimide, triisopropyl orthoformate, triethyl orthoformate, and trimethyl orthoformate.

[0011] As a further preferred embodiment of the present invention, in the step, the solvent is any one of methanol, 1,2-dichloroethane, acetone, tetrahydrofuran, ethanol and toluene, or a mixed solvent of two thereof.

[0012] As a further preferred embodiment of the present invention, in the step, the molar ratio of the phenyl ester to the pyrimidine amine is 1:3 to 3:1.

[0013] As a further preferred embodiment of the present invention, in the steps, the novel method for preparing nicosulfuron is characterized in that, in the steps, the molar ratio of phenyl ester to the catalyst is 1000:1 to 50:1.

[0014] Through the above technical scheme described in the present invention, compared with the traditional nicosulfuron synthesis route of phenyl ester method, a new method for synthesizing nicosulfuron with high efficiency and convenience is provided. The method does not involve expensive metal catalysts, and the amount of small molecule co-catalyst added is small, the cost is low, and the reaction selectivity is better. In addition, under the new catalytic system, the reaction conditions are milder than those of the original process, which greatly reduces the potential danger of the process. Therefore, the raw materials used in the preparation method of the present invention are cheap and easy to obtain, and the industrialization prospect is huge. By optimizing the reaction conditions (especially the ratio of reactants, catalysts, reaction temperature and time, etc.), the reaction selectivity is good and the nicosulfuron yield is high.

[0015] The present invention uses phenyl ester and pyrimidine amine as raw materials to prepare nicosulfuron. Compared with the existing technology, it has the characteristics of short reaction time, high synthesis efficiency, low cost, simple operation and no need to use highly toxic controlled chemicals. The main reactions involved are as follows: .

[0016] The synthesis reaction can ensure a high yield, and the synthesis steps are simple to operate. In summary, compared with the key step condensation reaction of the traditional phenyl ester method for synthesizing nicosulfuron, the present invention has the advantages of short reaction time, high selectivity, simple operation, great industrial application value, and avoiding the use of highly toxic chemicals. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the liquid phase diagram of Example 1.

[0018] Figure 2 This is the liquid phase diagram of Example 2.

[0019] Figure 3 This is the liquid phase diagram of Example 3. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0021] The preparation method of Nicosulfuron in the present invention is mainly achieved by the following steps: The method comprises the following steps: adding phenyl ester, pyrimidine amine, solvent and small molecule promoter in a reactor equipped with mechanical stirring, replacing the nitrogen atmosphere three times, stirring the reaction system at 0-100° C. and continuing the reaction for 1-10 minutes; after the reaction is completed, removing the solvent by distillation under reduced pressure, and drying to obtain the nicosulfuron finished product.

[0022] The above scheme is described in detail below with different reaction conditions.

[0023] Comparative Example 1: Preparation of Nicosulfuron Take 1 mol (108.0 g) of phenyl ester and 2.0 mol (310.3 g) of pyrimidineamine and dissolve them in an organic solvent (2 L) of dichloromethane. Then add 0.05 mol (13.9 g) of tetrabutylammonium chloride. After the reaction system is replaced with nitrogen three times, the reaction solution is reacted at 5 ° C in a reactor equipped with a magnetic stirrer for 65 min. The liquid phase monitors the consumption of the raw materials. After the reaction is completed, the solvent is removed by reduced pressure distillation to obtain 172.8 g of the product with a yield of 42.1% and a liquid phase purity of 86.8%.

[0024] Example 1: Preparation of Nicosulfuron Steps: Take 1 mol (349.4 g) of phenyl ester and 1.2 mol (186.2 g) of pyrimidineamine and dissolve them in an organic solvent acetone (2 L), then add 0.01 mol (1.78 g) of NBS, replace the gas with nitrogen three times, and keep the reaction liquid in a reactor equipped with a mechanical stirrer at 40°C for 2 minutes. The liquid phase central control monitors the consumption of the raw materials. After the reaction, the solvent is removed by reduced pressure distillation to obtain 355.2 g of the product with a yield of 86.5% and a liquid phase purity of 97.86%.

[0025] Example 2: Preparation of Nicosulfuron Take 1 mol (349.4 g) of phenyl ester and 1.5 mol (232.7 g) of pyrimidine amine and dissolve them in a mixed solvent of organic solvent water and tetrahydrofuran (V THF' :V H2O = 3:1, 2 L), and then 0.02 mol (1.48 g) of triethyl orthoformate was added. After the reaction system was replaced with nitrogen three times, the reaction solution was reacted at 60°C in a reactor equipped with a magnetic stirrer for 8 min. The liquid phase was monitored to see if the raw materials were consumed. After the reaction was completed, the solvent was removed by reduced pressure distillation to obtain 365.7 g of the product with a yield of 89.1% and a liquid phase purity of 96.9%.

[0026] Example 3: Preparation of Nicosulfuron Take 1 mol (108.0 g) of phenyl ester and 2.0 mol (310.3 g) of pyrimidineamine and dissolve them in an organic solvent (2 L) of dichloromethane. Then add 0.05 mol (5.3 g) of trimethyl orthoformate. After the reaction system is replaced with nitrogen three times, the reaction solution is reacted at 5 ° C in a reactor equipped with a magnetic stirrer for 5 min. The liquid phase monitors the consumption of the raw materials. After the reaction, the solvent is removed by reduced pressure distillation to obtain 345.7 g of the product with a yield of 84.2% and a liquid phase purity of 98.58%.

[0027] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing nicosulfuron, characterized in that: The method comprises the following steps: taking pyrimidine amine and phenyl ester as substrates, sequentially adding a solvent and a small molecule co-catalyst, stirring and reacting in the solvent at 0-100 DEG C for 1-10 minutes, then desolventizing and separating to obtain nicosulfuron wet powder, and drying to obtain a finished product.

2. The method for preparing Nicosulfuron according to claim 1, characterized in that: In the step, the small molecule co-catalyst is any one of N-bromosuccinimide, triisopropyl orthoformate, triethyl orthoformate, and trimethyl orthoformate.

3. The method for preparing Nicosulfuron according to claim 1, characterized in that: In the step, the solvent is any one of methanol, 1,2-dichloroethane, acetone, tetrahydrofuran, ethanol and toluene, or a mixed solvent of two of them.

4. The method for preparing Nicosulfuron according to claim 1, characterized in that: In the step, the molar ratio of the pyrimidine amine to the phenyl ester is 1:3 to 3:

1.

5. The method for preparing Nicosulfuron according to claim 1, characterized in that: In the step, the molar ratio of the pyrimidine amine to the small molecule co-catalyst is 1000:1 to 50:1.

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