CN112321563A

CN112321563A - Preparation method of chlorantraniliprole key intermediate K acid

Info

Publication number: CN112321563A
Application number: CN202011066885.7A
Authority: CN
Inventors: 赵能选; 李兰杰; 胡晓峰; 王良良; 钱广; 朱杰; 朱红薇
Original assignee: Zhejiang Avilive Chemical Co ltd; Jiaxing University
Current assignee: Zhejiang Avilive Chemical Co ltd; Jiaxing University
Priority date: 2020-10-04
Filing date: 2020-10-04
Publication date: 2021-02-05

Abstract

The invention relates to a preparation method of chlorantraniliprole key intermediate K acid, which has few reaction sites and less impurity generation and can realize efficient and environment-friendly preparation of the K acid.

Description

Preparation method of chlorantraniliprole key intermediate K acid

Technical Field

The invention relates to a preparation method of chlorantraniliprole key intermediate K acid, which has few reaction sites and less impurity generation and can realize the preparation of efficient, green and environment-friendly K acid, and belongs to the field of synthesis of pesticide intermediates.

Background

Chlorantraniliprole is a novel o-aminobenzoyl insecticide which is released by DuPont company in 2007, and has the remarkable advantages of excellent insecticidal effect, small toxicity to non-target organisms, no cross resistance with the existing insecticide and the like, so once the product is released, the product obtains an unusual sale performance in the insecticide field and is in the high-speed expansion period of the market in recent years. The structural formula is as follows:

although the methods for preparing chlorantraniliprole that are reported and disclosed at present are not uncommon, the route that can be applied to large-scale preparation and has practical production value is also the route published by Dupont company, such as the following:

in this route, K acid is a key intermediate thereof. Under the current technological conditions, in the process of synthesizing a pyrazole ring, as the reaction sites of hydrazino and diethyl maleate on a pyridine ring are more, more impurities are generated, the condition control of the reaction in the step is more rigorous, the yield is not high, and the purity of an intermediate product is not ideal; in addition, in the subsequent oxidation reaction to build aromatic rings, an excess of inorganic peroxyacid salt is required, which results in the generation of large amounts of waste salts that are difficult to handle, leaving an environmental hazard.

Disclosure of Invention

The design purpose is as follows: the method avoids the defects in the background technology, and designs the preparation method of the chlorantraniliprole key intermediate K acid which has few reaction sites and less impurity generation and can realize the efficient, green and environment-friendly preparation of the K acid.

The design scheme is as follows: in order to achieve the above design objectives. Aiming at the defect that the prior route has more active sites for reaction during the addition of 1 and 4, thereby causing difficult-to-avoid side reaction, the invention develops a novel K acid preparation method, and the route is as follows:

compared with the background technology, the invention takes ethyl acetoacetate as raw material, and prepares the K acid through carbonyl protection, cyclization, deprotection, oxidation and bromination, and has the advantages of high cyclization yield, good selectivity and high product purity.

Drawings

FIG. 1 is a typical spectrum of the present invention.

Detailed Description

A preparation method of chlorantraniliprole key intermediate K acid comprises the following steps:

1. 142g (1 mol) of ethyl acetylacrylate, 93g (1.5 mol) of ethylene glycol, and 19g (0.1 mol) of p-toluenesulfonic acid (containing a portion of water of crystallization) were added to 350ml of toluene, heated to reflux on a device equipped with a water separator, and dehydrated for about 6 hours, and the disappearance of the reaction raw materials was detected by gas chromatography. After the reaction, the mixture was cooled to 10 ℃ or below, washed with 200ml of 2 water and 200ml of saturated salt water, the organic layer was separated, anhydrous sodium sulphate was added, the mixture was dried, filtered, the filter cake was washed with a small amount of toluene, and the layers were combined. The mixture was distilled under reduced pressure to obtain 179g of a light yellow oil having a substantially constant weight and a purity of about 95% by gas chromatography, and the oil was used in the next reaction without further separation.

2. Dissolving the yellow oily matter in 450ml of absolute ethyl alcohol, adding 68g (1.0 mol) of sodium ethoxide, and heating the system to reflux; and adding 100ml of absolute ethyl alcohol into the oily matter obtained in the previous step for dilution, and then dropwise adding the oily matter into a reflux system. Reflux was maintained during the addition. After the dropwise addition is finished (about 1.0-1.5 h.), the reflux state is kept for 45min, the temperature is reduced to below 30 ℃, most of ethanol is evaporated under reduced pressure, 450ml of chloroform is added, the filtration is carried out, a filter cake is washed by a small amount of chloroform, and the filtrates are combined. Reduced pressure and evaporated to dryness, and 400ml THF is added for dissolution to obtain orange red solution which is directly used for the next reaction.

3. Adding 135ml of 37% hydrochloric acid into the tetrahydrofuran solution in the last step, heating the system to reflux, keeping the reflux for 8h, detecting by TLC (thin layer chromatography), removing raw materials, cooling to room temperature, adding 400ml of chloroform, separating out a water layer, back-extracting the water layer twice by using 100ml of chloroform, combining organic layers, evaporating under reduced pressure to remove most of the solvent, dissolving the residual viscous red oily substance into 700ml of dioxane, and directly using the oily substance in the next step of reaction.

4、280gBr₂Slowly dripping into 10% sodium hydroxide solution at 0 deg.C to obtain fresh sodium hypobromite solution; adding 300ml of water into the dioxane solution, cooling to 0 ℃, and slowly dripping the prepared sodium hypobromite into the system, wherein the temperature in the dripping process is less than 5 ℃. After the dropwise addition, the reaction is continued to be stirred at 0 ℃ for 4h, after the reaction is finished, the pH is adjusted to be =1 by concentrated hydrochloric acid, the mixture is extracted three times by 500ml of 3 times dichloromethane, organic phases are combined, anhydrous sodium sulphate is dried, and the filtration is carried out. The solvent was distilled off under reduced pressure to give 163g of a pale red solid,¹h nmr showed no more significant impurities, 68% molar yield (based on ethyl acetylacrylate).

¹HNMR（DMSO），δ7.59（s,1H）,13.75（br s,1H）,8.40（d,1H）,8.18（d,1H）,7.74（dd,1H）。

5. Adding the light red solid obtained in the previous step into 500ml of acetonitrile, and adding POBr₃212g (0.8 mol), heating and refluxing for 2.5h under strong stirring, distilling at normal pressure, and distilling off about 380-420ml of organic solvent; adding 420g of sodium bicarbonate into 2000ml of water in another reaction bottle, stirring to form a suspension, adding the distilled mother liquor into the suspension under vigorous stirring, wherein a large amount of bubbles overflow, adding 800ml of dichloromethane into the system after gas generation stops, filtering the system in the presence of diatomite, washing a filter cake with dichloromethane, combining several layers, decoloring with active carbon for 2 times, filtering, and evaporating dichloromethane to obtain light brown oily liquid. The oily liquid was cooled to 5 ℃ with slow stirring to crystallize. 188g of light brown target product is obtained. The structure of the secondary product is confirmed by nuclear magnetism. FIG. 1 is a typical spectrum.

It is to be understood that: although the above embodiments have described the design idea of the present invention in more detail, these descriptions are only simple descriptions of the design idea of the present invention, and are not limitations of the design idea of the present invention, and any combination, addition, or modification without departing from the design idea of the present invention falls within the scope of the present invention.

Claims

1. A preparation method of chlorantraniliprole key intermediate K acid is characterized by comprising the following steps:

。