CN112724075A

CN112724075A - Preparation method of pyriproxyfen

Info

Publication number: CN112724075A
Application number: CN202011620211.7A
Authority: CN
Inventors: 李舸; 朱欲晓; 杨家岭
Original assignee: Xinyang Pingqiao District Rural Management Station; SHANGHAI KELY BIO-PHARMACEUTICAL CO LTD
Current assignee: Xinyang Pingqiao District Rural Management Station; SHANGHAI KELY BIO-PHARMACEUTICAL CO LTD
Priority date: 2020-12-31
Filing date: 2020-12-31
Publication date: 2021-04-30

Abstract

The invention relates to a preparation method of pyriproxyfen, which comprises the following steps: condensing 4-phenoxy phenol and propylene carbonate under the action of catalytic amount of alkali to obtain 1- (4-phenoxy phenyl) -2-propanol PPP; and continuously condensing the obtained PPP with 2-chloropyridine to obtain the pyriproxyfen. The method avoids the generation of the by-product is-PPP in the prior art, improves the product quality and yield, reduces the generation cost, is simple and practical, and has good industrialization prospect.

Description

Preparation method of pyriproxyfen

Technical Field

The invention belongs to the field of pesticides, and particularly relates to a preparation method of pyriproxyfen.

Background

Pyriproxyfen, also known as pyriproxyfen, is chemically 4-phenoxyphenyl- (RS) -2- (2-pyridyloxy) -propyl ether, of formula C₂₀H₁₉NO₃Relative molecular mass of 321.38, the chemical structural formula is as follows

Pyriproxyfen is an insect growth regulator having juvenile hormone activity and is developed by sumitomo chemical co. The insecticidal composition can be used for preventing and treating agricultural pests such as homoptera, thysanoptera, diptera, lepidoptera and the like, has high activity on cotton whitefly and greenhouse whitefly, and has good prevention and treatment effects on scale insects such as pear psylla chinensis, red garden scale and the like, green peach aphid, prodenia litura, potato beetle and other agricultural pests.

At present, the synthesis method of pyriproxyfen is divided into three steps: firstly, phenol and parachlorophenol are subjected to ether synthesis reaction to prepare p-phenoxy phenol; then reacting phenoxy phenol with propylene oxide under alkaline condition to obtain 1- (4-phenoxyphenyl) -2-propanol (PPP); and finally, condensing the PPP and 2-chloropyridine to obtain the final product. The reaction formula is as follows:

wherein, the synthesis of PPP by the reaction of the phenoxy phenol and the epoxypropane is a key step for synthesizing the pyriproxyfen. Mainly, the reaction generates PPP and also 12 to 15 percent of byproduct is-PPP. The reaction formula is as follows:

due to the close physical and chemical properties of is-PPP and PPP, it is difficult to remove. And the hydroxyl of is-PPP is primary alcohol, and is more active than the secondary alcohol of PPP, so that the hydroxyl is easier to condense with 2-chloropyridine. Therefore, the content of the obtained original drug is about 90 percent. Not only is the yield low and the quality poor, but also the surplus impurities are left on the land to cause environmental burden.

Disclosure of Invention

The invention aims to solve the technical problem of providing a method for preparing pyriproxyfen, which has the advantages of reasonable design, simple process, low cost and high overall yield.

The invention provides a preparation method of pyriproxyfen, which comprises the following steps:

condensing 4-phenoxyphenol and propylene carbonate at the molar ratio of 1:1-1:3 at the temperature of 30-120 ℃ under the action of catalytic amount of alkali to obtain 1- (4-phenoxyphenyl) -2-propanol PPP;

the molar ratio of the 4-phenoxy phenol to the propylene carbonate is 1:1-1:3, and the molar ratio of the 4-phenoxy phenol to the catalytic amount of alkali is 1:0.01-1: 0.2.

The alkali is at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide, cesium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide and magnesium tert-butoxide.

The reaction solvent of the 4-phenoxy phenol and the propylene carbonate is an alcohol solvent.

The alcohol solvent is at least one of methanol, ethanol, isopropanol and n-butanol.

And continuously condensing the obtained PPP and 2-chloropyridine under an alkaline condition to obtain the pyriproxyfen.

The molar ratio of the PPP to the 2-chloropyridine is 1:1-1: 3.

The reaction temperature of the PPP and the 2-chloropyridine is 60-120 ℃.

The reaction solvent of PPP and 2-chloropyridine is toluene or DMF.

Advantageous effects

(1) The invention uses the propylene carbonate as a raw material to replace propylene oxide, has mild synthesis reaction conditions, and completely avoids the generation of the byproduct is-PPP in the prior art.

(2) The invention adopts the common alcohol solvent as the solvent, can be recycled and reused, and reduces the discharge amount of waste water.

(3) The invention obviously improves the product quality, the content of the original medicine can reach more than 98 percent, and simultaneously effectively reduces the production cost.

(4) The invention has the advantages of easily available raw materials and low price, and is suitable for industrial batch production.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.

Example 1

Preparation of PPP

200 ml of n-butanol and 37.25 g of 4-phenoxyphenol (0.2 mol) were added to a 500 ml reaction flask, and after stirring and dissolution, 0.56 g (0.01 mol) of potassium hydroxide and 25.3 g (0.25 mol) of propylene carbonate were added in this order. Heating to 100 ℃, and keeping the temperature for 5 hours. The liquid chromatography detects that the 4-phenoxyl phenol completely reacts. The temperature is reduced to room temperature, and the n-butanol and the excessive propylene carbonate are distilled under reduced pressure until the mixture is dry. 100 g of water and 150 g of dichloromethane were added to the residue, and the mixture was stirred for 15 minutes and allowed to stand for separation. The organic phase was separated and dried over anhydrous sodium sulfate. Filtering, concentrating the filtrate at normal pressure, and recovering the dichloromethane solvent until the dichloromethane solvent is dried. The residue was recrystallized from isopropanol to yield 46.38 g of white crystalline powder with a content of 98.76% (by liquid chromatography) and a yield of 94.93%.

PPP structure characterization data: 1H NMR (400MHz, CDCl)₃)：1.26～1.28(3H,d,CH₃)，2.51～2.52(1H,m,CH)，3.71-3.79(2H,d,CH₂)，6.87～8.37(9H,m，Ar-H)。

Preparation of (di) pyriproxyfen

A500 ml reaction flask was charged with 150 ml of toluene and 24.5 g (0.1 mol) of PPP, and after stirring and dissolving, 6.72 g (0.12 mol) of potassium hydroxide was added. The mixture was heated to 60 ℃ and 13.62 g (0.12 mol) of 2-chloropyridine was added dropwise. Continuously heating to 90-100 ℃, and keeping the temperature to react for 10-12 hours. The liquid chromatography detects that the PPP reaction is complete. The temperature was reduced to room temperature, and 100 ml of saturated brine was added thereto for washing. The organic phase is separated off. The toluene and excess 2-chloropyridine were distilled to dryness under reduced pressure. The residue was recrystallized from anhydrous methanol to give 29.35 g of a white crystalline powder with a content of 99.32% (by liquid chromatography) and a yield of 91.33%.

Pyriproxyfen structural characterization data: 1H NMR (400MHz, CDCl)₃)：1.43～1.47(3H,d,CH₃)，4.02-4.06(2H,d,CH₂)，5.59～5.62(1H,m,CH)，8.12～8.37(13H,m，Ar-H)。

Example 2

Preparation of PPP

200 ml of ethanol and 37.25 g of 4-phenoxyphenol (0.2 mol) are added into a 500 ml reaction bottle, and after the mixture is heated, stirred and dissolved, 1.02 g (0.015 mol) of sodium ethoxide and 30.6 g (0.30 mol) of propylene carbonate are sequentially added. Heating to 80 ℃ for reflux, and keeping the temperature for reaction for 8 hours. The liquid chromatography detects that the 4-phenoxyl phenol completely reacts. The temperature is reduced to room temperature, and the ethanol and the excess propylene carbonate are distilled under reduced pressure to dryness. 100 ml of saturated brine and 150 ml of toluene were added, and the mixture was stirred for 15 minutes and then allowed to stand for separation. The organic phase was separated and dried over anhydrous sodium sulfate. Filtering, and distilling the filtrate under reduced pressure to recover the toluene solvent to dryness. The residue was recrystallized from isopropanol to yield 45.39 g of a white crystalline powder with a content of 99.12% (by liquid chromatography) and a yield of 92.90%.

Preparation of (di) pyriproxyfen

A500 ml reaction flask was charged with 150 ml of DMF and 24.5 g (0.1 mol) of PPP, and after stirring and dissolution, 6.0 g (0.15 mol) of sodium hydroxide was added. The mixture was heated to 50 ℃ and 17.03 g (0.15 mol) of 2-chloropyridine were added dropwise. Heating to 100 ℃ and 110 ℃, and keeping the temperature for reaction for 8-10 hours. The liquid chromatography detects that the PPP reaction is complete. The reaction mixture was poured into 500 g of ice water and extracted 3 times with 200 ml of ethyl acetate. The organic phases were combined. The ethyl acetate and excess 2-chloropyridine were distilled to dryness under reduced pressure. The residue was recrystallized from anhydrous methanol to give 30.17 g of a white crystalline powder with a content of 99.26% (by liquid chromatography) and a yield of 93.90%.

Claims

1. A preparation method of pyriproxyfen comprises the following steps:

condensing 4-phenoxyphenol and propylene carbonate at the molar ratio of 1:1-1:3 at the temperature of 30-120 ℃ under the action of catalytic amount of alkali to obtain 1- (4-phenoxyphenyl) -2-propanol PPP; and continuously condensing the obtained PPP and 2-chloropyridine under an alkaline condition to obtain the pyriproxyfen.

2. The method of claim 1, wherein: the molar ratio of the 4-phenoxy phenol to the propylene carbonate is 1:1-1:3, and the molar ratio of the 4-phenoxy phenol to the catalytic amount of alkali is 1:0.01-1: 0.2.

3. The production method according to claim 1 or 2, characterized in that: the alkali is at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide, cesium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide and magnesium tert-butoxide.

4. The method of claim 1, wherein: the reaction solvent of the 4-phenoxy phenol and the propylene carbonate is an alcohol solvent.

5. The method of claim 4, wherein: the alcohol solvent is at least one of methanol, ethanol, isopropanol and n-butanol.

6. The method of claim 1, wherein: the molar ratio of the PPP to the 2-chloropyridine is 1:1-1: 3.

7. The method of claim 1, wherein: the reaction temperature of the PPP and the 2-chloropyridine is 60-120 ℃.

8. The method of claim 1, wherein: the reaction solvent of PPP and 2-chloropyridine is toluene or DMF.