阅读说明：本技术 一种灭草松原药合成方法 (Method for synthesizing bentazone original drug ) 是由 孔繁蕾 张旺庚 田冬平 徐海燕 刘青 于 2020-07-18 设计创作，主要内容包括：本发明涉及灭草松原药合成技术领域,公开了一种灭草松原药合成方法,包括以下步骤：以邻苯二甲酸二丁酯为主要原料,经胺化、降解以及酯化得到邻氨基苯甲酸甲酯,再以邻氨基苯甲酸甲酯、五氧化二磷、伯胺、氯化亚砜和有机酸为原料,以三乙胺为搏酸剂,分批次多锅法制备邻异丙胺基磺酰胺基苯甲酸甲酯,邻异丙胺基磺酰胺基苯甲酸甲酯经过醇钠环合以及酸化反应,合成灭草松原药。本发明的合成方法使用邻苯二甲酸二丁酯为主要原料,不使用靛红酸酐,大大降低了制备成本,而且材料易得,并且采用分批次多锅法合成邻异丙胺基磺酰胺基苯甲酸甲酯,具有操作简便、三废少和收率高等特点,最终灭草松产品的收率在90％以上,纯度达95％以上。(The invention relates to the technical field of raw medicine synthesis of bentazone, and discloses a raw medicine synthesis method of bentazone, which comprises the following steps: dibutyl phthalate is used as a main raw material, methyl anthranilate is obtained through amination, degradation and esterification, then methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid are used as raw materials, triethylamine is used as a beating acid agent, the methyl o-isopropylamino sulfonamide benzoate is prepared through a batch multi-pot method, and the methyl o-isopropylamino sulfonamide benzoate is subjected to sodium alkoxide cyclization and acidification reaction to synthesize the bentazone drug. The synthesis method of the invention uses dibutyl phthalate as a main raw material, does not use isatoic anhydride, greatly reduces the preparation cost, has easily obtained materials, adopts a batch multi-pot method to synthesize the o-isopropylamino sulfonamide methyl benzoate, has the characteristics of simple and convenient operation, less three wastes, high yield and the like, and finally obtains the bentazone product with the yield of more than 90 percent and the purity of more than 95 percent.)

1. A synthetic method of a bentazone raw drug is characterized by comprising the following steps: dibutyl phthalate is used as a main raw material, methyl anthranilate is obtained through amination, degradation and esterification, then methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid are used as raw materials, triethylamine is used as a beating acid agent, the methyl o-isopropylamino sulfonamide benzoate is prepared through a batch multi-pot method, and the methyl o-isopropylamino sulfonamide benzoate is subjected to sodium alkoxide cyclization and acidification reaction to synthesize the bentazone drug.

2. The method for synthesizing a bentazone raw drug according to claim 1, wherein the triethylamine is prepared by the following steps: in the presence of hydrogen, gasifying ethanol and liquid ammonia, preheating in a preheater (150 +/-5 ℃), synthesizing in a first reactor (190 +/-2 ℃) and a second reactor (165 +/-2 ℃) filled with a copper-nickel-clay catalyst to generate a mixture of monoethylamine, diethylamine and triethylamine, condensing, spraying and absorbing ethanol to obtain a triethanolamine crude product, and finally separating, dehydrating and fractionating to collect 88-90 ℃ fractions to obtain triethylamine.

3. The method for synthesizing a bentazone raw drug according to claim 1, wherein the method for preparing thionyl chloride comprises the following steps: taking sulfur, liquid chlorine and liquid sulfur dioxide as raw materials and active carbon as a catalyst, and uniformly stirring at the temperature of 200-250 ℃ to obtain the synthetic thionyl chloride.

4. The method for synthesizing the bentazone drug as claimed in claim 1, wherein the methyl anthranilate is prepared by adding dibutyl phthalate and ammonia water into a reaction vessel, and then sequentially adding sodium chloride, ethanol and sodium carbonate to react at 50-70 ℃.

5. The method for synthesizing a imazapyr raw drug as claimed in claim 1, wherein the organic acid is any one of a halogenated acid, a hydroxy acid, a keto acid, an amino acid, oxalic acid or tartaric acid.

6. The method for synthesizing the imazapyr raw drug according to claim 1, wherein the methyl o-isopropylaminosulfonamide benzoate reacts in an alcohol solvent under the action of sodium alkoxide, wherein the alcohol solvent is methanol, the sodium alkoxide is sodium methoxide, and the cyclization reaction temperature is 60-70 ℃.

7. The method for synthesizing the bentazone bulk drug according to claim 1, wherein in the acidification reaction, amino acid is adopted for acidification, the acidification time is 5-10 min, and the raw bentazone bulk drug is obtained after acidification and neutral adjustment.

8. The method for synthesizing a imazapyr raw drug as claimed in claim 1, wherein the molar ratio of methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid is 1:1.2:0.8:1.1: 0.5.

Technical Field

The invention relates to the technical field of synthesizing a bentazone raw medicament, in particular to a method for synthesizing a bentazone raw medicament.

Background

The bentazone is a selective contact-type post-emergence herbicide, is used for treating stems and leaves of weeds in seedling stage, is mainly used for preventing and killing broadleaf weeds and cyperaceae weeds in crops such as rice, soybeans, peanuts, wheat and the like, and is ineffective for gramineous weeds.

The traditional synthesis method takes isatoic anhydride as a raw material to react with isopropylamine to generate N-isopropyl anthranilamide, then the N-isopropyl anthranilamide reacts with sulfur trioxide to form a compound, and the compound reacts with phosphorus oxychloride to obtain a product through ring closure. Accordingly, one skilled in the art provides a method for synthesizing a raw imazapyr to solve the problems set forth in the background art.

Disclosure of Invention

The invention aims to provide a method for synthesizing a bentazone raw drug, which aims to solve the problems in the background technology.

In order to achieve the purpose, the invention provides the following technical scheme:

a synthetic method of a bentazone raw drug comprises the following steps: dibutyl phthalate is used as a main raw material, methyl anthranilate is obtained through amination, degradation and esterification, then methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid are used as raw materials, triethylamine is used as a beating acid agent, the methyl o-isopropylamino sulfonamide benzoate is prepared through a batch multi-pot method, and the methyl o-isopropylamino sulfonamide benzoate is subjected to sodium alkoxide cyclization and acidification reaction to synthesize the bentazone drug.

As a still further scheme of the invention: the preparation method of the triethylamine comprises the following steps: in the presence of hydrogen, gasifying ethanol and liquid ammonia, preheating in a preheater (150 +/-5 ℃), synthesizing in a first reactor (190 +/-2 ℃) and a second reactor (165 +/-2 ℃) filled with a copper-nickel-clay catalyst to generate a mixture of monoethylamine, diethylamine and triethylamine, condensing, spraying and absorbing ethanol to obtain a triethanolamine crude product, and finally separating, dehydrating and fractionating to collect 88-90 ℃ fractions to obtain triethylamine.

As a still further scheme of the invention: the preparation method of the thionyl chloride comprises the following steps: taking sulfur, liquid chlorine and liquid sulfur dioxide as raw materials and active carbon as a catalyst, and uniformly stirring at the temperature of 200-250 ℃ to obtain the synthetic thionyl chloride.

As a still further scheme of the invention: before the methyl anthranilate is prepared, dibutyl phthalate and ammonia water are added into a reaction container, and then sodium chloride, ethanol and sodium carbonate are sequentially added to react at 50-70 ℃.

As a still further scheme of the invention: the organic acid is any one of halogenated acid, hydroxy acid, keto acid, amino acid, oxalic acid or tartaric acid.

As a still further scheme of the invention: the method comprises the following steps of reacting o-isopropylamino sulfonamide methyl benzoate in an alcohol solvent under the action of sodium alkoxide, wherein the alcohol solvent is methanol, the sodium alkoxide is sodium methoxide, and the cyclization reaction temperature is 60-70 ℃.

As a still further scheme of the invention: and in the acidification reaction, amino acid is adopted for acidification, the acidification time is 5-10 min, and the acidified solution is adjusted to be neutral to obtain the bentazone bulk drug.

As a still further scheme of the invention: the molar ratio of the methyl anthranilate to the phosphorus pentoxide to the primary amine to the thionyl chloride to the organic acid is 1:1.2:0.8:1.1: 0.5.

Compared with the prior art, the invention has the beneficial effects that: the synthesis method of the invention uses dibutyl phthalate as a main raw material, does not use isatoic anhydride, greatly reduces the preparation cost, has easily obtained materials, adopts a batch multi-pot method to synthesize the o-isopropylamino sulfonamide methyl benzoate, has the characteristics of simple and convenient operation, less three wastes, high yield and the like, and finally obtains the bentazone product with the yield of more than 90 percent and the purity of more than 95 percent.

Detailed Description

In embodiment 1 of the present invention, a method for synthesizing a bentazone raw drug comprises the following steps: dibutyl phthalate is used as a main raw material, methyl anthranilate is obtained through amination, degradation and esterification, then methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid are used as raw materials, triethylamine is used as a beating acid agent, the methyl o-isopropylamino sulfonamide benzoate is prepared through a batch multi-pot method, and the methyl o-isopropylamino sulfonamide benzoate is subjected to sodium alkoxide cyclization and acidification reaction to synthesize the bentazone drug.

Preferably: the preparation method of triethylamine is as follows: in the presence of hydrogen, gasifying ethanol and liquid ammonia, preheating in a preheater at 120 ℃, synthesizing in a first reactor with Cu-Ni-argil catalyst at 100 ℃ and a second reactor at 90 ℃ to produce a mixture of monoethylamine, diethylamine and triethylamine, condensing, spraying and absorbing with ethanol to obtain a triethanolamine crude product, and finally separating, dehydrating and fractionating to collect 88-90 ℃ fractions to obtain triethylamine.

Preferably: the preparation method of the thionyl chloride comprises the following steps: taking sulfur, liquid chlorine and liquid sulfur dioxide as raw materials and active carbon as a catalyst, and uniformly stirring at 220 ℃ to obtain the synthetic thionyl chloride.

Preferably: before the preparation of methyl anthranilate, dibutyl phthalate and ammonia water are added into a reaction container, and then sodium chloride, ethanol and sodium carbonate are sequentially added for reaction at 60 ℃.

Preferably: the organic acid is any one of halogenated acid, hydroxy acid, keto acid, amino acid, oxalic acid or tartaric acid.

Preferably: the o-isopropylamino sulfonamide methyl benzoate reacts in an alcohol solvent under the action of sodium alkoxide, wherein the alcohol solvent is methanol, the sodium alkoxide is sodium methoxide, and the cyclization reaction temperature is 65 ℃.

Preferably: in the acidification reaction, amino acid is adopted for acidification, the acidification time is 7min, and the obtained product is acidified and then is adjusted to be neutral to obtain the bentazone bulk drug.

Preferably: the molar ratio of methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid is 1:1.2:0.8:1.1: 0.5.

In embodiment 2 of the present invention, a method for synthesizing a bentazone raw drug comprises the following steps: dibutyl phthalate is used as a main raw material, methyl anthranilate is obtained through amination, degradation and esterification, then methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid are used as raw materials, triethylamine is used as a beating acid agent, the methyl o-isopropylamino sulfonamide benzoate is prepared through a batch multi-pot method, and the methyl o-isopropylamino sulfonamide benzoate is subjected to sodium alkoxide cyclization and acidification reaction to synthesize the bentazone drug.

Preferably: the preparation method of triethylamine is as follows: in the presence of hydrogen, gasifying ethanol and liquid ammonia, preheating in a preheater at 140 ℃, synthesizing in a first reactor filled with a copper-nickel-clay catalyst at 170 ℃ and a second reactor filled with a copper-nickel-clay catalyst at 150 ℃ to generate a mixture of monoethylamine, diethylamine and triethylamine, condensing, spraying and absorbing with ethanol to obtain a triethanolamine crude product, and finally separating, dehydrating and fractionating to collect 88-90 ℃ fractions to obtain triethylamine.

Preferably: the preparation method of the thionyl chloride comprises the following steps: taking sulfur, liquid chlorine and liquid sulfur dioxide as raw materials and active carbon as a catalyst, and uniformly stirring at 240 ℃ to obtain the synthetic thionyl chloride.

Preferably: before the preparation of methyl anthranilate, dibutyl phthalate and ammonia water are added into a reaction container, and then sodium chloride, ethanol and sodium carbonate are sequentially added for reaction at 65 ℃.

Preferably: the organic acid is any one of halogenated acid, hydroxy acid, keto acid, amino acid, oxalic acid or tartaric acid.

Preferably: the o-isopropylamino sulfonamide methyl benzoate reacts in an alcohol solvent under the action of sodium alkoxide, wherein the alcohol solvent is methanol, the sodium alkoxide is sodium methoxide, and the cyclization reaction temperature is 68 ℃.

Preferably: in the acidification reaction, amino acid is adopted for acidification, the acidification time is 9min, and the obtained product is acidified and then is adjusted to be neutral to obtain the bentazone bulk drug.

Preferably: the molar ratio of methyl anthranilate, phosphorus pentoxide, primary amine, thionyl chloride and organic acid is 1:1.2:0.8:1.1: 0.5.

The synthesis method of the invention uses dibutyl phthalate as a main raw material, does not use isatoic anhydride, greatly reduces the preparation cost, has easily obtained materials, adopts a batch multi-pot method to synthesize the o-isopropylamino sulfonamide methyl benzoate, has the characteristics of simple and convenient operation, less three wastes, high yield and the like, and finally obtains the bentazone product with the yield of more than 90 percent and the purity of more than 95 percent.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention are equivalent to or changed within the technical scope of the present invention.