阅读说明：本技术 甲基硫菌灵的合成方法 (Synthetic method of thiophanate methyl ) 是由 顾思雨 张贤振 蒋磊 李昕 于 2020-06-24 设计创作，主要内容包括：本发明属于农药合成技术领域,具体涉及一种甲基硫菌灵的合成方法。本发明提供的甲基硫菌灵的合成方法,将异硫氰基甲酸甲酯的丙酮溶液滴加至邻苯二胺的丙酮-乙腈溶液中,保温反应,然后降温析晶,得到甲基硫菌灵晶体,少量异硫氰基甲酸甲酯与大量邻苯二胺接触,增加了异硫氰基甲酸甲酯与邻苯二胺的接触面积,避免了常规将邻苯二胺滴加至异硫氰基甲酸甲酯中分子接触不均匀的问题,使得反应过程更加可控,不会存在冲料现象；丙酮和乙腈为强极性溶剂,将邻苯二胺溶解在丙酮-乙腈混合溶剂中,并控制丙酮和乙腈的体积比为100:(11～15),改善了邻苯二胺溶解度,增加了异硫氰基甲酸甲酯与邻苯二胺接触时间,反应更加完全,提高了产能。(The invention belongs to the technical field of pesticide synthesis, and particularly relates to a synthetic method of thiophanate methyl. According to the synthetic method of thiophanate methyl, an acetone solution of methyl isothiocyanate is dripped into an acetone-acetonitrile solution of o-phenylenediamine for heat preservation reaction, then cooling and crystallization are carried out, so that thiophanate methyl crystals are obtained, a small amount of methyl isothiocyanate is contacted with a large amount of o-phenylenediamine, the contact area of the methyl isothiocyanate and the o-phenylenediamine is increased, the problem that molecules are not uniformly contacted in the conventional process of dripping o-phenylenediamine into the methyl isothiocyanate is solved, the reaction process is more controllable, and the phenomenon of material flushing is avoided; acetone and acetonitrile are strong polar solvents, o-phenylenediamine is dissolved in the acetone-acetonitrile mixed solvent, the volume ratio of the acetone to the acetonitrile is controlled to be 100 (11-15), the solubility of the o-phenylenediamine is improved, the contact time of methyl isothiocyanate and the o-phenylenediamine is increased, the reaction is more complete, and the productivity is improved.)

1. The method for synthesizing thiophanate methyl is characterized by comprising the following steps of:

(1) dropwise adding an acetone solution of methyl isothiocyanatecarboxylate into an acetone-acetonitrile solution of o-phenylenediamine, reacting for 50-70 min at a temperature of 65-70 ℃, cooling, crystallizing, filtering and washing to obtain thiophanate-methyl crystals, and collecting a first mother liquor;

(2) continuously cooling the first mother liquor, filtering to obtain a second mother liquor, and distilling to obtain an acetone-acetonitrile solvent;

in the step (1), the feeding molar ratio of the methyl isothiocyanate to the o-phenylenediamine is 1 (0.47-0.49), and the volume ratio of acetone to acetonitrile in the acetone-acetonitrile solution is 100 (11-15).

2. The method for synthesizing thiophanate methyl according to claim 1, wherein in step (1), the acetone solution of methyl isothiocyanate is added dropwise in the following manner:

heating the acetone-acetonitrile solution of o-phenylenediamine to 57-60 ℃, firstly dropwise adding the acetone solution of methyl isothiocyanate accounting for 1/4 of the total volume, controlling the dropwise adding time for 50-70 min, and stirring and reacting for 15-25 min after the dropwise adding is finished; and then heating the reaction system to 65-70 ℃, dropwise adding the rest acetone solution of methyl isothiocyanate, controlling the dropwise adding time to be 110-130 min, stirring, and carrying out heat preservation reaction for 50-70 min.

3. The method for synthesizing thiophanate methyl according to claim 1 or 2, wherein in the step (1), the cooling crystallization mode is as follows:

reducing the temperature from 65-70 ℃ to 10-30 ℃ in a gradient cooling mode of keeping the temperature and stirring for 30min every time the temperature is reduced by 5 ℃, and then standing for crystallization for 3-3.5 h.

4. The method for synthesizing thiophanate methyl according to claim 1 or 2, wherein the solvent used for washing in step (1) is a mixed solvent of the acetone-acetonitrile solvent obtained by distillation in step (2) and water.

5. The method for synthesizing thiophanate methyl according to claim 4, wherein the volume ratio of the acetone-acetonitrile solvent to the water is (10-20): 100.

6. The method for synthesizing thiophanate methyl according to claim 1 or 2, characterized in that in step (2), the temperature of the first mother liquor is reduced to less than 3 ℃.

7. The method for synthesizing thiophanate methyl according to claim 1 or 2, wherein in step (1), the concentration of the acetone solution of methyl isothiocyanate is (1-1.5) mol/L.

8. The method for synthesizing thiophanate methyl according to claim 1 or 2, wherein in step (1), the concentration of the acetone-acetonitrile solution of o-phenylenediamine is (1 to 1.5) mol/L.

9. The method for synthesizing thiophanate methyl according to claim 7, wherein in the step (1), the temperature of the acetone solution of methyl isothiocyanate is controlled to be 50-55 ℃ during the dropping process.

Technical Field

The invention belongs to the technical field of pesticide synthesis, and particularly relates to a synthetic method of thiophanate methyl.

Background

Thiophanate-methyl, chemical name is 1, 2-di- (3-methoxycarbonyl-2-thioureido) benzene, trade name is thiophanate-methyl, its pure product is white crystal, melting point is 172 ℃ (decomposition), it is hardly soluble in water, benzene, xylene, ether, methanol, acetone, chloroform, it is easily soluble in acetonitrile and dimethyl formamide, it is unstable in acid and alkaline medium, it is stable to light, low-toxic, it has high-efficient, spectrum and systemic characteristics, it has protection and therapeutic action. The thiophanate-methyl medicament is converted into carbendazim in plants to play a role in sterilization, has an action mechanism of interfering the formation of a spindle body in mitosis of pathogenic bacteria to influence cell division, and is widely applied to the prevention and control of diseases of cereals, vegetables, fruit trees and other economic crops.

Thiophanate methyl is prepared by reacting methyl isothiocyanate and o-phenylenediamine, generally, o-phenylenediamine suspension is dripped into methyl isothiocyanate solution, but because o-phenylenediamine cannot be completely dissolved in the suspension, the reaction is severe when the o-phenylenediamine is dripped, the phenomenon of material flushing is easy to occur to block a feeding pipeline, the reaction progress can be influenced, and the exertion of the capacity is severely restricted.

Disclosure of Invention

Therefore, the technical problem to be solved by the invention is to overcome the defects of material washing phenomenon and insufficient reaction in the existing thiophanate-methyl synthesis process, thereby providing a safe and reliable thiophanate-methyl synthesis method with complete reaction.

In order to solve the technical problems, the invention adopts the technical scheme that:

the invention provides a synthetic method of thiophanate methyl, which comprises the following steps:

(1) dropwise adding an acetone solution of methyl isothiocyanatecarboxylate into an acetone-acetonitrile solution of o-phenylenediamine, reacting for 50-70 min at a temperature of 65-70 ℃, cooling, crystallizing, filtering and washing to obtain thiophanate-methyl crystals, and collecting a first mother liquor;

(2) continuously cooling the first mother liquor, filtering to obtain a second mother liquor, and distilling to obtain an acetone-acetonitrile solvent;

in the step (1), the feeding molar ratio of the methyl isothiocyanate to the o-phenylenediamine is 1 (0.47-0.49), and the volume ratio of acetone to acetonitrile in the acetone-acetonitrile solution is 100 (11-15).

Preferably, in the method for synthesizing thiophanate-methyl, in the step (1), the acetone solution of methyl isothiocyanate is dropwise added in the following manner:

heating the acetone-acetonitrile solution of o-phenylenediamine to 57-60 ℃, firstly dropwise adding the acetone solution of methyl isothiocyanate accounting for 1/4 of the total volume, controlling the dropwise adding time for 50-70 min, and stirring and reacting for 15-25 min after the dropwise adding is finished; and then heating the reaction system to 65-70 ℃, dropwise adding the rest acetone solution of methyl isothiocyanate, controlling the dropwise adding time to be 110-130 min, stirring, and carrying out heat preservation reaction for 50-70 min.

Preferably, in the synthetic method of thiophanate-methyl, in the step (1), the cooling crystallization mode is as follows:

reducing the temperature from 65-70 ℃ to 10-30 ℃ in a gradient cooling mode of keeping the temperature and stirring for 30min every time the temperature is reduced by 5 ℃, and then standing for crystallization for 3-3.5 h.

Preferably, in the method for synthesizing thiophanate-methyl, the solvent used for washing in the step (1) is a mixed solvent of the acetone-acetonitrile solvent obtained by distillation in the step (2) and water.

Further preferably, in the method for synthesizing thiophanate-methyl, the volume ratio of the acetone-acetonitrile solvent to the water is (10-20): 100.

Preferably, in the method for synthesizing thiophanate-methyl, in the step (2), the temperature of the first mother liquor is reduced to be lower than 3 ℃.

Preferably, in the method for synthesizing thiophanate-methyl, in the step (1), the concentration of the acetone solution of methyl isothiocyanate is (1-1.5) mol/L.

Preferably, in the method for synthesizing thiophanate-methyl, in the step (1), the concentration of the acetone-acetonitrile solution of o-phenylenediamine is (1-1.5) mol/L.

Further preferably, in the synthetic method of thiophanate methyl, in the step (1), the temperature of the acetone solution of methyl isothiocyanate is controlled to be 50-55 ℃ in the dropping process.

The technical scheme of the invention has the following advantages:

1. the method for synthesizing thiophanate methyl comprises the steps of dropwise adding an acetone solution of methyl isothiocyanate into an acetone-acetonitrile solution of o-phenylenediamine, keeping the temperature at 65-70 ℃ for 50-70 min, cooling, crystallizing, filtering and washing to obtain thiophanate methyl crystals, and collecting a first mother solution; continuously cooling the first mother liquor, filtering to obtain a second mother liquor, and distilling to obtain an acetone-acetonitrile solvent; the feeding molar ratio of the methyl isothiocyanate to the o-phenylenediamine is 1 (0.47-0.49), and the volume ratio of acetone to acetonitrile in the acetone-acetonitrile solution is 100 (11-15).

According to the synthesis method, when methyl isothiocyanate is dripped into an o-phenylenediamine system, a small amount of methyl isothiocyanate is contacted with a large amount of o-phenylenediamine, so that the contact area of the methyl isothiocyanate and the o-phenylenediamine is increased, the problem of uneven molecular contact in conventional dripping of the o-phenylenediamine into the methyl isothiocyanate is solved, the reaction process is more controllable, and the phenomenon of material flushing is avoided; and moreover, acetone and acetonitrile are strong polar solvents, o-phenylenediamine is dissolved in an acetone-acetonitrile mixed solvent system, the volume ratio of the acetone to the acetonitrile is controlled to be (11-15), the solubility of the o-phenylenediamine is improved, the contact time of methyl isothiocyanate and the o-phenylenediamine is prolonged, the reaction is more complete, and the productivity is improved.

2. According to the synthetic method of thiophanate methyl, methyl isothiocyanate is dropwise added into an o-phenylenediamine system in batches at different temperature stages, so that violent reaction is avoided.

3. According to the synthetic method of thiophanate methyl, a gradient cooling mode is adopted in the cooling crystallization process, so that thiophanate methyl is separated out as much as possible, impurities generated by addition of o-phenylenediamine and monomolecular methyl isothiocyanate are prevented from being wrapped in the thiophanate methyl crystallization process, and the thiophanate methyl is higher in purity.

4. According to the synthetic method of thiophanate methyl, the solvent used for washing is a mixed solvent of an acetone-acetonitrile solvent obtained by distilling the second mother liquor and water, so that impurities generated by addition of o-phenylenediamine and monomolecular methyl isothiocyanate can be washed away, and the product purity is improved.

Detailed Description

In order to facilitate understanding of the objects, technical solutions and gist of the present invention, embodiments of the present invention will be described in further detail below. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, this embodiment is provided so that this disclosure will be thorough and complete and will fully convey the concept of the invention to those skilled in the art, and the present invention will only be defined by the appended claims.

The raw materials used in the examples of the present invention are all commercially available unless otherwise specified.