Novel synthesis method of nicosulfuron intermediate phenyl ester

Abstract

The invention discloses a novel method for synthesizing nicosulfuron intermediate phenyl ester, which comprises the following steps: by taking sulfonamide and diphenyl carbonate as substrates, sequentially adding alkali and a solvent, stirring and reacting at 0-100 DEG C for 5-30 minutes, desolventizing, adding acid to adjust the pH value, and performing suction filtration or centrifugal drying to obtain a finished product. The whole process of the key preparation process and the parameter conditions (including the ratio of reaction raw materials, alkali, solvent, reaction temperature and the like) of the synthesis process are optimized, and particularly, the biomass-based green solvent and organic alkali are innovatively used for replacing inorganic alkali; the method overcomes the problems of low yield (56-58% in terms of diphenyl carbonate) and large environmental peculiar smell in the traditional nicosulfuron esterification process, and improves the yield of the esterification process to 85% or above.

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 sulfonamide and diphenyl carbonate 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] 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 traditional intermediate phenyl ester synthesis process has a low yield (56-58% based on diphenyl carbonate), a long reaction time (10-12h), and a strong odor, resulting in a higher production cost of nicosulfuron than the amine ester method, and greatly reducing the production capacity of the device.

[0006] Therefore, the current industry is in urgent need of finding a new method for preparing nicosulfuron intermediate phenyl ester with simple operation steps and short reaction time. Summary of the invention

[0007] 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 synthesizing nicosulfuron intermediate phenyl ester. The present invention improves the overall process of the key preparation process and the parameter conditions of the synthesis process (including the ratio of reaction raw materials, base, solvent and reaction temperature, etc.), especially innovatively using biomass-based green solvents and organic bases instead of inorganic bases. Compared with the traditional nicosulfuron phenyl ester process, the new base / solvent catalytic system can increase the yield of the phenyl ester process to 85%, greatly shorten the reaction time, and improve the raw material conversion efficiency.

[0008] To achieve the above object, according to the present invention, a novel method for synthesizing nicosulfuron intermediate phenyl ester is provided, characterized in that it comprises the following steps: Sulfonamide and diphenyl carbonate are used as substrates, and a base and a solvent are added in sequence, and the mixture is stirred at 0-100°C for 5-30 minutes, and then the mixture is desolventized, acid is added to adjust the pH to 2-3, and the mixture is centrifuged and dried to obtain the finished product. More preferably, the mixture is stirred at 5-60°C for 20-30 minutes.

[0009] As further preferred embodiment of the present invention, in the step, the base is any one of aniline, ethylenediamine, triethylamine, n-butylamine and benzylamine.

[0010] As a further preferred embodiment of the present invention, in the step, the solvent is any one or a mixed solvent of two of the biomass-based green solvents butyl acetate, γ-valerolactone, 2-methyltetrahydrofuran and ethyl lactate.

[0011] As a further preferred embodiment of the present invention, in the step, the molar ratio of the diphenyl carbonate to the sulfonamide is 0.3-3.

[0012] As a further preferred embodiment of the present invention, in the step, it is characterized in that in the step, the molar ratio of the diphenyl carbonate to the base is 0.2-5.

[0013] Through the above technical scheme described in the present invention, compared with the original process of nicosulfuron phenyl ester synthesis process, a new method for synthesizing phenyl ester with high efficiency and convenience is provided. The method does not involve expensive metal catalysts and has good system compatibility. In addition, the new organic base catalysis replaces the traditional inorganic base catalysis system, and the reaction conditions are milder than the original process, which greatly reduces the potential danger of the process, and the yield of phenyl ester is increased from 56-58% of the original process to 85%. 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, base catalyst, solvent and reaction temperature, etc.), the reaction selectivity is good, the yield of phenyl ester intermediates is high, and the reaction time is short.

[0014] The present invention uses sulfonamide intermediate and diphenyl carbonate as raw materials to prepare phenyl ester intermediate. Compared with the existing technology, the present invention has the characteristics of high yield, 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: .

[0015] The synthesis reaction can ensure a high yield, and the synthesis steps are simple to operate. In summary, compared with the traditional nicosulfuron phenyl ester synthesis process, the present invention has the advantages of high yield, short reaction time, high selectivity, simple operation, and great industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is the liquid phase diagram of Example 1.

[0017] Figure 2 This is the liquid phase diagram of Example 2.

[0018] Figure 3 This is the liquid phase diagram of Example 3. DETAILED DESCRIPTION

[0019] 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.

[0020] The preparation method of the phenyl ester intermediate in the present invention is mainly achieved by the following steps: The method comprises the following steps: sequentially adding a sulfonamide intermediate, diphenyl carbonate, a green solvent and an organic base catalyst into a reactor equipped with a mechanical stirrer, replacing the atmosphere with nitrogen three times, stirring the reaction system at 0-100° C. and continuing the reaction for 5-30 minutes; after the reaction is completed, removing the solvent by distillation under reduced pressure, adjusting the pH value by adding hydrochloric acid, and then filtering and drying to obtain a phenyl ester product.

[0021] The above scheme is described in detail below with different reaction conditions.

[0022] Comparative Example 1 Steps: Take 1 mol (229.0 g) of the sulfonamide intermediate and 1.2 mol (256.8 g) of diphenyl carbonate and dissolve them in the green solvent acetone (2 L), then add 0.02 mol (1.86 g) of aniline, replace with nitrogen three times, and keep the reaction liquid in a reactor equipped with a mechanical stirrer at 40°C for 30 minutes. The liquid phase central control monitors the consumption of the raw materials. After the reaction, the solvent is removed by vacuum distillation, and hydrochloric acid is added to adjust the pH to 2-3. The phenyl ester product is filtered and dried to obtain 254.1 g of phenyl ester product with a yield of 72.8% and a liquid phase purity of 77.67%.

[0023] Comparative Example 2 Steps: Take 1 mol (229.0 g) of sulfonamide intermediate and 1.2 mol (256.8 g) of diphenyl carbonate and dissolve them in green solvent toluene (2 L), then add 0.02 mol (1.86 g) of aniline, replace with nitrogen three times, keep the reaction liquid in a reactor equipped with mechanical stirring at 40°C for 30 minutes, monitor the consumption of raw materials by liquid phase central control, and remove the solvent by reduced pressure distillation after the reaction, add hydrochloric acid to adjust the pH to 2-3, filter and dry to obtain the phenyl ester product, and obtain 238.1 g of phenyl ester product with a yield of 68.2% and a liquid phase purity of 72.67%.

[0024] Example 1 Synthesis of Nicosulfuron Intermediate Phenyl Ester Steps: 1 mol (229.0 g) of the sulfonamide intermediate and 1.2 mol (256.8 g) of diphenyl carbonate were dissolved in a green solvent 2-methyltetrahydrofuran (2 L), and then 0.02 mol (1.86 g) of aniline was added, and nitrogen was replaced three times. The reaction solution was kept warm at 40°C in a reactor equipped with a mechanical stirrer for 30 minutes. The consumption of the raw materials was monitored by the liquid phase central control. After the reaction was completed, the solvent was removed by reduced pressure distillation, and hydrochloric acid was added to adjust the pH to 2-3. The phenyl ester product was filtered and dried to obtain 298.1 g of phenyl ester product, with a yield of 85.4% and a liquid phase purity of 97.67%.

[0025] Example 2 Synthesis of Nicosulfuron Intermediate Phenyl Ester Take 1 mol (229.0 g) of the sulfonamide intermediate and 1.5 mol (321.0 g) of diphenyl carbonate and dissolve them in a mixed solvent of biomass-based green solvent glycerol and 2-methyltetrahydrofuran (V 丙三醇 :V 2-甲基四氢呋喃= 3:1, 2 L), and then 0.5 mol (36.6 g) of n-butylamine 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 30 minutes. The liquid phase monitored the consumption of the raw materials. After the reaction was completed, the solvent was removed by vacuum distillation, and hydrochloric acid was added to adjust the pH to 2-3. The phenyl ester product was filtered and dried to obtain 302.9 g of phenyl ester product with a yield of 86.8% and a liquid phase purity of 96.17%.

[0026] Example 3 Synthesis of Nicosulfuron Intermediate Phenyl Ester Take 1 mol (229.0 g) of sulfonamide intermediate and 1.5 mol (321.0 g) of diphenyl carbonate and dissolve them in biomass-based green solvent γ-valerolactone solvent (2 L), then add 3 mol (303.0 g) of triethylamine. After the reaction system is replaced with nitrogen three times, the reaction solution is reacted at 5°C in a reactor equipped with magnetic stirring for 30 minutes. The liquid phase monitors the consumption of the raw materials. After the reaction, the solvent is removed by reduced pressure distillation, and hydrochloric acid is added to adjust the pH to 2-3. The phenyl ester product is filtered and dried to obtain 296.7 g of phenyl ester product with a yield of 85.0% and a liquid phase purity of 97.38%.

[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 synthesizing nicosulfuron intermediate phenyl ester, characterized in that: The method comprises the following steps: taking sulfonamide and diphenyl carbonate as substrates, adding alkali and solvent in sequence, stirring and reacting at 0-100 DEG C for 5-30 minutes, desolventizing, adding acid to adjust pH to 2-3, and centrifugally drying to obtain a finished product.

2. A method for synthesizing a nicosulfuron intermediate phenyl ester as claimed in claim 1, characterized in that: In the step, the base is any one of aniline, ethylenediamine, triethylamine, n-butylamine and benzylamine.

3. A method for synthesizing a nicosulfuron intermediate phenyl ester as claimed in claim 1, characterized in that: In the step, the solvent is any one of the biomass-based green solvents butyl acetate, γ-valerolactone, 2-methyltetrahydrofuran and ethyl lactate, or a mixed solvent of two of them.

4. A method for synthesizing a nicosulfuron intermediate phenyl ester as claimed in claim 1, characterized in that: In the step, the molar ratio of the diphenyl carbonate to the sulfonamide is 0.3-3.

5. A method for synthesizing a nicosulfuron intermediate phenyl ester as claimed in claim 1, characterized in that: In the step, the molar ratio of the diphenyl carbonate to the base is 0.2-5.

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