阅读说明：本技术 一种解毒喹的制备工艺及其制备系统 (Preparation process and preparation system of cloquintocet-mexyl ) 是由 徐西之 于 2021-05-10 设计创作，主要内容包括：本发明公开了一种解毒喹的制备工艺及其制备系统,其中制备工艺包括,将5-氯-8-羟基喹啉、二甲基亚砜、碳酸钾混合,搅拌均匀后,加入甲苯和碳酸钠,在温度为100～110℃下搅拌反应1～1.2h后,降温至65～70℃,加入氯乙酸甲酯,在60～72℃下反应1～1.5h,得到沉淀物,固液分离后,制得中间体5-氯-8-羟基喹啉氧基乙酸甲酯；将2-庚醇、溶剂、5-氯-8-羟基喹啉氧基乙酸甲酯混合均匀后,在压力为0.045～0.065MPa、温度为90～110℃的条件下,加入催化剂反应2～2.5h,温度降至50～55℃,再加入溶剂,温度迅速降至5～10℃,解毒喹结晶,经固液分离后即得解毒喹产品；本发明提供一种解毒喹的制备工艺,通过特定的溶剂和催化体系,实现较佳的产物纯度和较高得率,且工艺简单、反应条件温和过程容易控制。(The invention discloses a preparation process and a preparation system of cloquintocet-mexyl, wherein the preparation process comprises the steps of mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100-110 ℃ for reaction for 1-1.2 h, cooling to 65-70 ℃, adding methyl chloroacetate, reacting at the temperature of 60-72 ℃ for 1-1.5 h to obtain a precipitate, and carrying out solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinoline oxy methyl acetate; uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2-2.5 h under the conditions that the pressure is 0.045-0.065 MPa and the temperature is 90-110 ℃, cooling to 50-55 ℃, adding the solvent, rapidly cooling to 5-10 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; the invention provides a preparation process of cloquintocet-mexyl, which realizes better product purity and higher yield through a specific solvent and a specific catalytic system, and has the advantages of simple process and mild reaction conditions, and the process is easy to control.)

1. A preparation process of cloquintocet-mexyl is characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100-110 ℃ for reaction for 1-1.2 h, cooling to 65-70 ℃, adding methyl chloroacetate, reacting at the temperature of 60-72 ℃ for 1-1.5 h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2-2.5 h under the conditions that the pressure is 0.045-0.065 MPa and the temperature is 90-110 ℃, cooling to 50-55 ℃, adding the solvent, rapidly cooling to 5-10 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture composed of methanol, xylene and diethyl ether according to a volume ratio of 1: 1-2: 1, and the catalyst is a mixture composed of pyridine and sodium carbonate according to a mass ratio of 0.5-1: 1;

the molar ratio of the 2-heptanol to the solvent to the methyl 5-chloro-8-quinolinyloxyacetate to the catalyst is 1:4: 0.8-1: 0.02-0.04.

2. The process for preparing cloquintocet-mexyl as claimed in claim 1, wherein: the intermediate 5-chloro-8-hydroxyquinoline oxy methyl acetate is prepared, wherein the molar ratio of 5-chloro-8-hydroxyquinoline to dimethyl sulfoxide to toluene to potassium carbonate to sodium carbonate to methyl chloroacetate is 1: 3-4: 4-5: 0.1-0.2: 1.

3. A process for the preparation of cloquintocet-mexyl according to claim 1 or 2, characterized in that: the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1: 3: 4: 0.1:0.1:1.

4. The process for preparing cloquintocet-mexyl as claimed in claim 1, wherein: the methanol, the xylene and the diethyl ether are in a volume ratio of 1:2: 1.

5. The process for preparing cloquintocet-mexyl as claimed in claim 1, wherein: the catalyst is a mixture of pyridine and sodium carbonate according to a mass ratio of 0.5-1: 1.

6. A production system using the process for producing cloquintocet-mexyl according to any one of claims 1 to 5: the method is characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

the mixing and stirring unit (100) comprises a first reaction kettle (A) and a second reaction kettle (B), each reaction kettle comprises a containing component (101) and a mixing component (102) extending into the containing component (101), a discharge hole (101a) is formed in the lower end of the containing component (101), and a feed hole (101B) is formed in the upper end of the containing component (101);

the crystallization unit (200) comprises a kettle body unit (201), wherein an input port (201a) and an output port (201b) are formed in the kettle body unit (201), a crystallization cavity (M) is formed in the kettle body unit (201), a stirring assembly (202) and an extraction assembly (203) matched with the stirring assembly (202) are arranged in the crystallization cavity (M); and the number of the first and second groups,

the centrifugal separation unit (300) comprises a machine body assembly (301), wherein a centrifugal assembly (302) is arranged in the machine body assembly (301), and a material conveying pipe (301a) and a material discharging pipe (301b) are arranged on the machine body assembly (301);

conveying assembly (400), it is including connecting in first pipeline (401) between discharge gate (101a) and input port (201a) of first reation kettle (A), connect in second pipeline (402) between delivery outlet (201B) and conveying pipeline (301a), connect in third pipeline (403) of discharging pipe (301B) and second reation kettle (B) feed inlet (101B), connect with fourth pipeline (404) between second reation kettle (B) discharge gate (101a) and conveying pipeline (301a), and connect in fifth pipeline (405) between discharging pipe (301B) and stoving unit (500).

7. The system for preparing a process for preparing cloquintocet-mexyl as claimed in claim 6, wherein: the mixing and stirring unit (100) adopts a reaction kettle; the crystallization unit (200) adopts a crystallization kettle; the centrifugal separation unit (300) adopts a centrifugal separator; the drying unit (500) adopts a dryer.

8. The system for producing cloquintocet-mexyl as claimed in claim 6 or 7, wherein: the kettle body unit (201) comprises a tank body (201c), a cabin separation plate (201d) arranged in a lower end cavity of the tank body (201c), and a condensation cabin (201e) coated on the outer lower end of the tank body (201 c); wherein the content of the first and second substances,

a plurality of groups of bosses (201d-1) and circulation holes (201d-2) are uniformly distributed on the side wall of the plate body of the compartment plate (201 d);

the condensation chamber (201e) is provided with a condensation inlet (201e-1) and a condensation outlet (201 e-2).

9. The system for preparing a process for preparing cloquintocet-mexyl as claimed in claim 8, wherein: the stirring assembly (202) comprises a stirring shaft (202a) and a plurality of groups of stirring components (202b) arranged on the shaft body of the stirring shaft (202 a); wherein the content of the first and second substances,

one end of the stirring shaft (202a), which is far away from the stirring motor, is rotatably connected to the middle part of the plate body of the compartment plate (201d), and a containing groove (202a-1) for containing the stirring piece (202b) is formed in the side wall of the shaft body of the stirring shaft (202 a);

the stirring piece (202b) comprises a stirring plate (202b-1) and a supporting rod (202b-2) connected between the stirring plate (202b-1) and the stirring shaft (202a), one end of the stirring plate (202b-1) is hinged in the accommodating groove (202a-1), the other end of the stirring plate (202b-1) is provided with an inclined sliding surface (T), the side wall of the stirring plate (202b-1) is provided with a sliding groove (202b-11), one end of the supporting rod (202b-2) is hinged in the accommodating groove (202a-1), and the other end of the supporting rod is connected in the sliding groove (202b-11) in a sliding manner;

the stirring piece (202b) further comprises a limiting block (202b-3) and a limiting spring (202b-4), the limiting block (202b-3) is connected through the limiting spring (202b-4), the end part of the limiting block is provided with a wedge surface (X), and the limiting block (202b-3) can be matched with the free end of the stirring plate (202b-1) through the wedge surface (X).

10. The system for preparing a process for preparing cloquintocet-mexyl as claimed in claim 9, wherein: the extraction assembly (203) comprises a sleeve (203a) sleeved on the stirring shaft (202a) and an extraction frame (203b) connected to the end part of the sleeve (203 a); wherein the content of the first and second substances,

liquid discharge holes (203b-1) are uniformly distributed on the surface of the frame body of the extraction frame (203b), and the side wall of the end part of each liquid discharge hole (203b-1) is coated with a filter screen (203 b-2);

the boss (201a-1) can be fitted in the drain hole (203 b-1).

Technical Field

The invention belongs to the technical field of herbicide preparation, and particularly relates to a preparation process and a preparation system of cloquintocet-mexyl.

Background

The cloquintocet-mequindox is also called mequintocet-mequindox, the chemical name of the cloquintocet-mequindox is 1-methyl hexyl (5-chloro-8-quinolinyloxy) acetate, the appearance of the industrial product is light yellow solid powder, the melting point is 69.4 ℃, the cloquintocet-mequindox is stable in neutral and acidic environments, and the cloquintocet-mequindox is easy to hydrolyze under alkaline conditions.

The formulation of the cloquintocet-mexyl is missible oil or wettable powder, is mainly used for improving the tolerance of plants to herbicides, and can be used as herbicide antidotes. The purpose of using herbicide antidotes is: when the herbicide with low price, high efficiency and poor or no selectivity is applied, the herbicide can be used for protecting crops and fully playing the role of weed control, and the vast majority of weeds including weeds similar to the crops are controlled; under the conditions of sensitive crops, variety lands and poor soil and abnormal climate which are likely to damage the crops, the dosage of the herbicide is increased to prevent and control resistant weeds and most other weeds; and avoid the phytotoxicity to the crops; when the chemical injury is caused to crops due to excessive use, drift or misuse, the chemical injury is reduced and eliminated by using an antidote; eliminating residual toxicity of herbicide in soil, and prolonging the weed control period of the herbicide according to needs.

At present, compared with the cloquintocet-mexyl, the cloquintocet-mexyl synthesis process has the defects of more impurities, low purity and low yield, and influences the product quality. Part of the reason is that in the crystallization process of the preparation of the cloquintocet-mexyl, the separation and extraction processes of the crystals in the crystallization kettle are complicated, so that the crystallization process needs to be optimized.

Disclosure of Invention

This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.

The present invention has been made keeping in mind the above and/or other problems occurring in the prior art.

Therefore, the invention aims to overcome the defects in the prior art and provide a preparation process of cloquintocet-mexyl.

In order to solve the technical problems, the invention provides the following technical scheme: a preparation process of cloquintocet-mexyl comprises the steps of mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100-110 ℃ for reaction for 1-1.2 h, cooling to 65-70 ℃, adding methyl chloroacetate, reacting at the temperature of 60-72 ℃ for 1-1.5 h to obtain a precipitate, and carrying out solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinoline oxy methyl acetate; uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2-2.5 h under the conditions that the pressure is 0.045-0.065 MPa and the temperature is 90-110 ℃, cooling to 50-55 ℃, adding the solvent, rapidly cooling to 5-10 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the solvent is a mixture of methanol, xylene and diethyl ether according to a volume ratio of 1: 1-2: 1, and the catalyst is a mixture of pyridine and sodium carbonate according to a mass ratio of 0.5-1: 1; the molar ratio of the 2-heptanol to the solvent to the 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester to the catalyst is 1:4: 0.8-1: 0.02-0.04.

As a preferred scheme of the preparation process of the cloquintocet-mexyl, the invention comprises the following steps: the intermediate 5-chloro-8-hydroxyquinoline oxy methyl acetate is prepared, wherein the molar ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1: 3-4: 4-5: 0.1-0.2: 1.

As a preferred scheme of the preparation process of the cloquintocet-mexyl, the invention comprises the following steps: the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1: 3: 4: 0.1: 1.

As a preferred scheme of the preparation process of the cloquintocet-mexyl, the invention comprises the following steps: the volume ratio of the methanol to the dimethylbenzene to the diethyl ether is 1:2: 1.

As a preferred scheme of the preparation process of the cloquintocet-mexyl, the invention comprises the following steps: the catalyst is a mixture of pyridine and sodium carbonate according to the mass ratio of 0.5-1: 1.

Another object to be solved by the present invention is to provide a system for preparing cloquintocet-mexyl, which comprises a mixing and stirring unit, a crystallization unit, a centrifugal separation unit, a conveying assembly and a drying unit, wherein the mixing and stirring unit comprises a first reaction kettle and a second reaction kettle, each reaction kettle comprises an accommodating assembly and a mixing assembly extending into the accommodating assembly, the lower end of the accommodating assembly is provided with a discharge port, and the upper end of the accommodating assembly is provided with a feed port; the crystallization unit comprises a kettle body unit, wherein an input port and an output port are formed in the kettle body unit, a crystallization cavity is formed in the kettle body unit, a stirring assembly is arranged in the crystallization cavity, and an extraction assembly matched with the stirring assembly is arranged in the crystallization cavity; the centrifugal separation unit comprises a machine body assembly, wherein a centrifugal assembly is arranged in the machine body assembly, and a material conveying pipe and a material discharging pipe are arranged on the machine body assembly; the conveying assembly comprises a first pipeline connected between a discharge port and an input port of the first reaction kettle, a second pipeline connected between the output port and a conveying pipe, a third pipeline connected between a discharge pipe and a feed inlet of the second reaction kettle, a fourth pipeline connected between the discharge port of the second reaction kettle and the conveying pipe, and a fifth pipeline connected between the discharge pipe and the drying unit.

The preparation system of the cloquintocet-mexyl is characterized in that: the mixing and stirring unit adopts a reaction kettle; the crystallization unit adopts a crystallization kettle; the centrifugal separation unit adopts a centrifugal separator; the drying unit adopts a dryer.

The preparation system of the cloquintocet-mexyl is characterized in that: the kettle unit comprises a tank body, a cabin separation plate and a condensation cabin, wherein the cabin separation plate is arranged in a cavity at the lower end of the tank body, and the condensation cabin is coated at the lower end outside the tank body; wherein, a plurality of groups of bosses and circulation holes are uniformly distributed on the side wall of the plate body of the compartment plate; the condensing cabin is provided with a condensing inlet and a condensing outlet.

The preparation system of the cloquintocet-mexyl is characterized in that: the stirring component comprises a stirring shaft and a plurality of stirring components arranged on the shaft body of the stirring shaft; one end of the stirring shaft, which is far away from the stirring motor, is rotatably connected to the middle part of the plate body of the compartment plate, and a containing groove for containing the stirring piece is formed in the side wall of the shaft body of the stirring shaft; the stirring piece comprises a stirring plate and a supporting rod connected between the stirring plate and the stirring shaft, one end of the stirring plate is hinged in the accommodating groove, the other end of the stirring plate is provided with an inclined sliding surface, a sliding groove is formed in the side wall of the stirring plate, one end of the supporting rod is hinged in the accommodating groove, and the other end of the supporting rod is connected in the sliding groove in a sliding manner; still include stopper and spacing spring in the stirring piece, the stopper passes through spacing spring coupling, its tip has the scarf, the stopper can cooperate with the free end of stirring board through the scarf.

The preparation system of the cloquintocet-mexyl is characterized in that: the extraction assembly comprises a sleeve sleeved on the stirring shaft and an extraction frame connected to the end part of the sleeve; liquid discharge holes are uniformly distributed on the surface of a frame body of the extraction frame, and a filter screen is coated on the side wall of the end part of each liquid discharge hole; the boss can be matched in the liquid discharge hole.

The invention has the beneficial effects that:

the invention provides a preparation process of cloquintocet-mexyl, which realizes better product purity and higher yield through a specific solvent and a specific catalytic system, and has simple process, mild reaction conditions and easily controlled process; the preparation system based on the preparation process of the cloquintocet-mexyl is provided, the crystallization operation of the cloquintocet-mexyl is further improved by optimizing the structure of the crystallization kettle, and the preparation efficiency is further improved.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:

FIG. 1 is a schematic view of the overall system of a system for preparing cloquintocet-mexyl according to the present invention.

FIG. 2 is a schematic diagram of a crystallization kettle structure of the system for preparing cloquintocet-mexyl.

FIG. 3 is a schematic diagram of a side view of a crystallization kettle of the system for preparing cloquintocet-mexyl.

FIG. 4 is a schematic diagram of a partial S-enlarged structure of a crystallization kettle of the system for preparing cloquintocet-mexyl.

FIG. 5 is a schematic diagram of a partial Y-enlarged structure of a crystallization kettle of the system for preparing cloquintocet-mexyl.

FIG. 6 is a schematic diagram of the operation flow of the stirring component of the crystallization kettle of the system for preparing cloquintocet-mexyl.

FIG. 7 is a schematic diagram of a partial P-enlarged structure of a crystallization kettle of the system for preparing cloquintocet-mexyl.

FIG. 8 is a schematic view of a partial H-enlarged structure of a crystallization kettle of the system for preparing cloquintocet-mexyl.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.

And (3) analyzing the content of the cloquintocet-mexyl:

accurately weighing 0.05g of the cloquintocet-mexyl standard sample in a 50ml volumetric flask, and metering the volume by using acetonitrile. Then weighing about 0.1g of the sample into a 50ml volumetric flask, and fixing the volume by using acetonitrile.

And after the baseline of the instrument is stable, analyzing and sampling according to the sequence of the standard solution, the sample solution and the standard solution.

And calculating the mass fraction of the cloquintocet-mexyl through the measured peak areas of the average cloquintocet-mexyl in the two test sample solutions and the standard sample solution.

In the formula (I), the compound is shown in the specification,

a is the mass fraction of the cloquintocet-mexyl to be detected;

x1 is the average value of the peak area of the cloquintocet-mexyl in the sample solution;

x2 is the average value of the area of the grass vinegar peak in the standard sample solution;

m2 is the mass of the sample, g;

m1 is the mass of the standard, g;

p is the mass fraction of the grass-removing vinegar in the standard sample.

Example 1

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is a mixture of pyridine and sodium carbonate according to the mass ratio of 0.5: 1;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 2

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is dimethylbenzene, and the catalyst is sodium carbonate;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 3

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is pyridine;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 4

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is a mixture of sodium carbonate according to the mass ratio of 0.5: 1;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 5

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is a mixture of pyridine and sodium carbonate according to the mass ratio of 0.2: 1;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 6

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is a mixture of pyridine and sodium carbonate according to the mass ratio of 0.4: 1;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

Example 7

The embodiment provides a preparation process of cloquintocet-mexyl, which comprises the following specific steps:

(1) mixing 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, uniformly stirring, adding toluene and sodium carbonate, stirring at the temperature of 100 ℃ for reaction for 1h, cooling to 70 ℃, adding methyl chloroacetate, reacting at the temperature of 72 ℃ for 1h to obtain a precipitate, and performing solid-liquid separation to obtain an intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester;

wherein the mol ratio of the 5-chloro-8-hydroxyquinoline to the dimethyl sulfoxide to the toluene to the potassium carbonate to the sodium carbonate to the methyl chloroacetate is 1:4: 0.2: 1;

(2) uniformly mixing 2-heptanol, a solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, adding a catalyst to react for 2h under the conditions that the pressure is 0.055MPa and the temperature is 100 ℃, cooling to 50 ℃, adding the solvent, rapidly cooling to 6 ℃, crystallizing the cloquintocet-mexyl, and carrying out solid-liquid separation to obtain a cloquintocet-mexyl product; wherein the content of the first and second substances,

the solvent is a mixture of methanol, xylene and diethyl ether according to the volume ratio of 1:2:1, and the catalyst is a mixture of pyridine and sodium carbonate according to the mass ratio of 0.6: 1;

the mol ratio of the 2-heptanol, the solvent, the 5-chloro-8-hydroxyquinoline oxy methyl acetate and the catalyst is 1:4: 0.8: 0.02.

The yields of cloquintocet-mexyl products of examples 1-7 are shown in Table 1.

TABLE 1

Example 8

Referring to fig. 1 and 2, the present embodiment provides a system for preparing cloquintocet-mexyl according to the preparation process proposed in the above embodiments, and the system comprises a mixing and stirring unit 100, a crystallization unit 200, a centrifugal separation unit 300, a conveying assembly 400 and a drying unit 500. The first reaction kettle A in the mixing and stirring unit 100 is a primary reaction kettle and is used for mixing and stirring primary raw materials of 5-chloro-8-hydroxyquinoline, dimethyl sulfoxide and potassium carbonate, adding toluene and sodium carbonate after stirring uniformly, stirring and reacting for 1-1.2 hours at the temperature of 100-110 ℃, cooling to 65-70 ℃, adding methyl chloroacetate, and reacting for 1-1.5 hours at the temperature of 60-72 ℃; and the second reaction kettle B is used for the second stage of reaction in which the intermediate, 2-heptanol, the solvent and 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester are uniformly mixed, then a catalyst is added for reaction for 2-2.5 hours under the conditions that the pressure is O.045-0.065 MPa and the temperature is 90-110 ℃, the temperature is reduced to 50-55 ℃, and the solvent is added. The crystallization unit 200 is used for the second reaction process, namely the crystallization and precipitation process of the intermediate 5-chloro-8-hydroxyquinolinyloxyacetic acid methyl ester, the centrifugal separation unit 300 is used for further separating the solid-liquid mixture, the conveying unit 400 is used for conveying among the units, and is not limited to direct connection among the units, and the drying unit 500 is used for drying the generated fixed product, so that pure and dry cloquintocet solid is obtained.

Specifically, in the mixing and stirring unit 100, each reaction kettle includes an accommodating component 101 and a mixing component 102 extending into the accommodating component 101, a discharge port 101a is formed at the lower end of the accommodating component 101, and a feed port 101b is formed at the upper end of the accommodating component 101; the receiving assembly 101 may be understood as a tank body and other external components of the reaction tank, which are used to form an integral structure of the reaction tank, and the mixing assembly 102 is used for stirring and mixing the solution in the reaction tank, and is generally a stirring paddle assembly extending into the reaction tank. The inlet 101b on the containing assembly 101 has a plurality of sets of pipes for inputting different raw materials into the reaction kettle, and the outlet 101a is disposed at the lower end of the reaction kettle for discharging the reaction solution in the reaction kettle.

The crystallization unit 200 comprises a kettle body unit 201, wherein an input port 201a and an output port 201b are arranged on the kettle body unit 201, a crystallization cavity M is arranged in the kettle body unit 201, a stirring assembly 202 is arranged in the crystallization cavity M, and an extraction assembly 203 arranged by matching with the stirring assembly 202 is arranged; further, the reaction liquid output from the first reaction vessel a is conveyed into the vessel body unit 201 from the input port 201a of the vessel body unit 201 through the first pipeline 401, the stirring component 202 is used for mixing and stirring during crystallization, and the extraction component 203 is used for extracting a crystallization product.

The centrifugal separation unit 300 comprises a machine body assembly 301, wherein a centrifugal assembly 302 is arranged in the machine body assembly 301, and a material conveying pipe 301a and a material discharging pipe 301b are arranged on the machine body assembly 301; further, the solid-liquid mixture output from the crystallization unit 200 is fed into the feed pipe 301a of the body module 301 through the second pipe 402, and the centrifugal module 302 is used for solid-liquid separation of the intermediate, so as to reduce the generation of other impurities in the second-stage reaction.

The conveying assembly 400 comprises a first pipeline 401 connected between the discharge port 101a and the input port 201a of the first reaction vessel a, a second pipeline 402 connected between the output port 201B and the conveying pipeline 301a, a third pipeline 403 connected between the discharge port 301B and the feed port 101B of the second reaction vessel B, a fourth pipeline 404 connected between the discharge port 101a and the conveying pipeline 301a of the second reaction vessel B, and a fifth pipeline 405 connected between the discharge port 301B and the drying unit 500.

Preferably, the mixing and stirring unit 100 employs reaction kettles, wherein the first reaction kettle a and the second reaction kettle B have the same main structure, and the difference is the difference between a liquid inlet pipe for inputting raw materials and auxiliary components; the crystallization unit 200 adopts a novel crystallization kettle to improve the operation difficulty and loss of the intermediate in the crystallization process; the centrifugal separation unit 300 employs a centrifugal separator; the drying unit 500 employs a dryer.

Example 9

Referring to fig. 2 to 8, a ninth embodiment of the present invention is a specific structure of a novel crystallization kettle, which is different from the eighth embodiment: the kettle unit 201 comprises a tank 201c, a compartment plate 201d arranged in a lower end cavity of the tank 201, and a condensation chamber 201e coated on the outer lower end of the tank 201 c; wherein, a plurality of groups of bosses 201d-1 and circulation holes 201d-2 are uniformly distributed on the side wall of the plate body of the compartment plate 201 d; the condensation chamber 201e has a condensation inlet 201e-1 and a condensation outlet 201 e-2.

The kettle unit 201 is similar to the existing crystallization kettle in structure, and mainly includes a tank 201c and a condensing chamber 201e covering the outer side wall of the tank 201c, wherein the tank 201c is the main structure of the crystallization kettle and forms a reaction chamber for crystallization, and the condensing chamber 201e is an auxiliary chamber for maintaining the pressure or temperature in the tank. The difference is that a crystallization cavity M is arranged in the tank body 201c, a compartment plate 201d is arranged at the lower end of the crystallization cavity M to divide the crystallization cavity M into two parts, wherein a liquid discharge cavity M2 is formed between the compartment plate 201d and the bottom of the crystallization cavity M, a reaction cavity M1 is arranged at the upper part of the compartment plate 201d, and a flow hole 201d-2 on the partition plate communicates the reaction cavity M1 with the liquid discharge cavity M2, namely, the reaction liquid in the reaction cavity M1 can flow to the liquid discharge cavity M2 through the flow hole 201d-2, and the reaction liquid in the liquid discharge cavity M2 can be discharged through a liquid discharge port 201c-1 arranged at the bottom of the tank body 201 c. The compartment plate 201d is used in cooperation with the extraction assembly 203 to control the reasonable discharge of the reaction liquid.

The stirring assembly 202 comprises a stirring shaft 202a and a plurality of groups of stirring assemblies 202b arranged on the shaft body of the stirring shaft 202 a; one end of the stirring shaft 202a, which is far away from the stirring motor, is rotatably connected to the middle of the plate body of the compartment plate 201d, and the side wall of the shaft body of the stirring shaft 202a is provided with a containing groove 202a-1 for containing the stirring piece 202 b; the stirring piece 202b comprises a stirring plate 202b-1 and a supporting rod 202b-2 connected between the stirring plate 202b-1 and the stirring shaft 202a, one end of the stirring plate 202b-1 is hinged in the accommodating groove 202a-1, the other end of the stirring plate 202b-1 is provided with an inclined sliding surface T, a sliding groove 202b-11 is formed in the side wall of the stirring plate 202b-1, one end of the supporting rod 202b-2 is hinged in the accommodating groove 202a-1, and the other end of the supporting rod 202b-2 is connected in the sliding groove 202b-11 in a sliding manner; the stirring member 202b further comprises a limiting block 202b-3 and a limiting spring 202b-4, the limiting block 202b-3 is connected through the limiting spring 202b-4, the end portion of the limiting block 202b-3 is provided with a wedge surface X, and the limiting block 202b-3 can be matched with the free end of the stirring plate 202b-1 through the wedge surface X.

Specifically, the stirring assembly 202 mainly has two parts, namely a stirring shaft 202a and a stirring member 202b, wherein the stirring shaft 202a is connected to an output shaft of the stirring motor through a coupler, the stirring shaft 202a extends into the crystallization cavity M and rotates in the middle of the plate body of the compartment plate 201d, and the stirring member 202b is distributed in the accommodating groove 202a-1 on the shaft body of the stirring shaft 202 a. It should be noted that the receiving grooves 202a-1 are distributed along the axial side wall of the stirring shaft 202a, and have a plurality of groups, and may be distributed at the same height at equal intervals or may be distributed spirally at different heights.

Further, the stirring member 202b is a receiving and assembling structure, and is aimed at facilitating the extraction of the extracting assembly 203 from the bottom of the crystallization chamber M. The stirring device mainly comprises a stirring plate 202b-1, a supporting rod 202b-2 used for supporting the stirring plate 202b-1, and a limiting block 202b-3 used for fixing the stirring plate 202b-1 in a storage state. One end of the stirring plate 202b-1 is hinged in the receiving groove 202a-1, the other end is a free end, one end of the supporting rod 202b-2 is hinged at the end of the receiving groove 202a-1, and the other end is hinged in the sliding groove 202b-11 on the plate body of the stirring plate 202b-1, so that the supporting rod 202b-2 and the stirring plate 202b-1 can be linearly received in the receiving groove 202b-1 through the matching of the supporting rod 202b-2 and the sliding groove 202b-11, as shown in the attached drawings.

Still further, the end of the receiving groove 202b-1 is further provided with a limiting component for the stirring plate 202b-1 to facilitate the receiving and unfolding of the stirring plate 202b-1, in this embodiment, preferably, the limiting block 202b-3 is telescopically connected by a limiting spring 202b-4, and the end of the limiting block 202b-3 is provided with a wedge surface X, which can slide in cooperation with the inclined sliding surface T at the end of the stirring plate 202b-1 to facilitate the stirring plate 202b-1 to press the limiting block 202b-3, and is finally clamped in the receiving groove 202a-1 by the limiting block 202 b-3.

The extraction assembly 203 comprises a sleeve 203a sleeved on the stirring shaft 202a and an extraction frame 203b connected with the end part of the sleeve 203 a; wherein, the surface of the frame body of the extraction frame 203b is uniformly distributed with liquid discharge holes 203b-1, and the side wall of the end part of the liquid discharge hole 203b-1 is coated with a filter screen 203 b-2; the boss 201a-1 can be fitted into the drain hole 203 b-1.

Specifically, the sleeve 203a in the extraction assembly 203 is used to be sleeved on the stirring shaft 202a, and it should be noted that the inner pipe diameter of the sleeve 203a is slightly larger than the maximum diameter of the stirring shaft 202a, so that the sleeve 203a does not rotate synchronously with the stirring shaft 202 a. The sleeve 203a is integrally connected with the extraction frame 203b, the extraction frame 203b is of a rotary basket structure, the bottom of the extraction frame 203b is the same as the shape of the bulkhead 201d, further, liquid discharge holes 203b-1 are distributed on the frame body of the extraction frame 203b, the bosses 201a-1 can be matched with the liquid discharge holes 203b-1 one by one, and the liquid discharge holes 203b-1 can be blocked by the bosses 201a-1 to prevent the reaction liquid in the reaction chamber M1 from being discharged. And a screen 203b-2 is provided at the end of each drain hole 203b-1, the screen 203b-2 being used to block the discharge of solids from the drain hole 203 b-1.

As can be seen from the use of FIGS. 6 to 8, when the extraction module 203 is placed on the bulkhead 201d, the liquid drainage holes 203b-1 are blocked by the bosses 201a-1, the reaction solution can be always located in the reaction chamber M1, when the crystallization reaction is completed, the extraction module 203 (the sleeve 203a or the extraction frame 203b) is slightly moved upward, so that the liquid drainage holes 203b-1 can discharge the reaction solution, the liquid drainage holes 203b-1 flow into the liquid drainage chamber M2 and are discharged from the liquid drainage port 201c-1, the reaction solution in the reaction chamber M1 is continuously reduced, the solid intermediate pieces and a small amount of the reaction solution are held in the extraction frame 203b, and the extraction frame 203b is directly extracted.

In the upward extraction of the extraction frame 203b, the edge of the sleeve 203a pushes the inclined support bar 202b-2 to deflect, and the end of the support bar 202b-2 connected to the stirring plate 202b-1 pushes the stirring plate 202b-1 to deflect and be received in the receiving groove 202a-1, and when the end of the stirring plate 202b-1 contacts the end of the stopper 202b-3, the stopper 202b-3 is pressed and finally is caught in the receiving groove 202a-1 by the stopper 202 b-3. When the stirring member 202b is completely received, the extraction assembly 203 can be smoothly taken out along the stirring shaft 202a, so as to further process the intermediate body positioned in the extraction frame 203 b. When the device is used again, the extraction frame 203b can be put back, and the limiting block 202b-3 is shifted, so that the stirring plate 202b-1 is unfolded, and the process of stirring and crystallizing is carried out again.

It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.