A kind of method of synthesizing pyraclostrobin intermediate

Abstract

The invention discloses a method for synthesizing a pyraclostrobin intermediate. The synthetic method comprises the following steps: preparing an intermediate 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole from 4-chlorophenylhydrazine hydrochloride prepared with p-bromochlorobenzene and hydrazine hydrate as reaction raw materials; reacting o-nitrotoluene with chlorine in the presence of a catalyst so as to prepare o-nitrobenzyl chloride; and subjecting 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole and o-nitrobenzyl chloride to an etherification reaction so as to obtain the pyraclostrobin intermediate, i.e., an etherification product 2[(N-4-chlorophenyl)-3-pyrazolyl-oxymethyl]nitrobenzene. The synthetic method provided by the invention can greatly reduce the amount of waste water produced in the synthesis process of 4-chlorophenylhydrazine hydrochloride; with 4-chlorophenylhydrazine hydrochloride as a raw material, the produced intermediate 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole has HPLC content of no less than 98% and yield of no less than 90%; since chlorine is used for replacing bromine or hydrobromic acid to prepare o-nitrobenzyl bromide, production cost and environmental protection burden are controlled; and the etherification product with a content of no less than 98% and yield of no less than 90% is obtained.

Description

technical field

[0001] The present invention is a method for synthesizing pyraclostrobin intermediate, in particular to pyraclostrobin intermediate 2-[(N-4-chlorophenyl)-3-pyrazolyloxymethyl]nitrobenzene The synthetic method of the invention belongs to the synthetic field of organic compounds. Background technique

[0002] Pyraclostrobin is an effective broad-spectrum fungicide, and 2-[(N-4-chlorophenyl)-3-pyrazolyloxymethyl]nitrobenzene is used as an important synthetic intermediate in its synthesis process. The body can be prepared by reacting o-nitrobenzyl bromide with 1-(4-chlorophenyl)-3-pyrazolol. For example, as described in the patent document CN104592117A (a synthetic method of pyraclostrobin, 2015.05.06), p-chlorophenylhydrazine hydrochloride prepared from p-chloroaniline through diazotization, reduction and other steps , 1-(4-chlorophenyl)-3-pyrazolol is obtained by cyclization reaction and oxidation reaction, and then, o-nitrotoluene, bromination reagent, etc. ...

Examples

Embodiment 1

[0067] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0068](1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:1 as the reaction raw materials, add a phase transfer catalyst (tetrabutylammonium bisulfate), a solvent (aqueous solution of ethylene glycol with a concentration of 85%), and a catalyst ( Copper sulfate and cobalt chloride with a mass ratio of 1:1) react, wherein the concentration of hydrazine hydrate is 100%, the weight ratio of p-bromochlorobenzene to phase transfer catalyst and catalyst is 1:0.15:0.2, and p-bromochlorobenzene The weight ratio of benzene to solvent is 1:1;

[0069] The reaction process includes: slowly raising the temperature and controlling the temperature to 100° C., reflux reaction at normal pressure, and maintaining the temperature for 1 h. When the sample HPLC detects that p-chlorophenylhydrazine no longer increases, the reaction is stopped.

[0070] (1....

Embodiment 2

[0075] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0076] (1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:3 as reaction raw materials, add a phase transfer catalyst (tetrabutylammonium bromide and tetrabutylammonium bisulfate with a mass ratio of 2:1), solvent (Ethylene glycol dimethyl ether), catalyst (copper bromide) for the reaction, wherein the concentration of hydrazine hydrate is 55%, the weight ratio of p-bromochlorobenzene to phase transfer catalyst and catalyst is 1:0.08:0.12, and p-bromo The weight ratio of chlorobenzene to solvent is 1:12;

[0077] The reaction process includes: slowly raising the temperature and controlling the temperature to 150° C., maintaining the pressure for reaction, keeping the temperature for 10 h, and stopping the reaction when the sample HPLC detects that p-chlorophenylhydrazine no longer increases.

[0078] (1.2) After the reaction is complet...

Embodiment 3

[0083] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0084] (1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:4.5 as the reaction raw materials, and add a phase transfer catalyst (trioctylmethylammonium chloride, 15-crown-5 and PEG400), solvent (concentration is 85% propylene glycol ether aqueous solution), catalyst (cuprous chloride) to react, wherein, the concentration of hydrazine hydrate is 88%, p-bromochlorobenzene and phase transfer catalyst, the weight ratio of catalyst is 1:0.11:0.09, the weight ratio of p-bromochlorobenzene to solvent is 1:8.6;

[0085] The reaction process includes: slowly raising the temperature and controlling the temperature to 120° C., reflux reaction at normal pressure, maintaining the temperature for 9 hours, and stopping the reaction when the sample HPLC detects that p-chlorophenylhydrazine no longer increases.

[0086] (1.2) After the reaction is comp...

technical field

[0001] The present invention is a method for synthesizing pyraclostrobin intermediate, in particular to pyraclostrobin intermediate 2-[(N-4-chlorophenyl)-3-pyrazolyloxymethyl]nitrobenzene The synthetic method of the invention belongs to the synthetic field of organic compounds. Background technique

[0002] Pyraclostrobin is an effective broad-spectrum fungicide, and 2-[(N-4-chlorophenyl)-3-pyrazolyloxymethyl]nitrobenzene is used as an important synthetic intermediate in its synthesis process. The body can be prepared by reacting o-nitrobenzyl bromide with 1-(4-chlorophenyl)-3-pyrazolol. For example, as described in the patent document CN104592117A (a synthetic method of pyraclostrobin, 2015.05.06), p-chlorophenylhydrazine hydrochloride prepared from p-chloroaniline through diazotization, reduction and other steps , 1-(4-chlorophenyl)-3-pyrazolol is obtained by cyclization reaction and oxidation reaction, and then, o-nitrotoluene, bromination reagent, etc. ...

Examples

Embodiment 1

[0067] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0068](1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:1 as the reaction raw materials, add a phase transfer catalyst (tetrabutylammonium bisulfate), a solvent (aqueous solution of ethylene glycol with a concentration of 85%), and a catalyst ( Copper sulfate and cobalt chloride with a mass ratio of 1:1) react, wherein the concentration of hydrazine hydrate is 100%, the weight ratio of p-bromochlorobenzene to phase transfer catalyst and catalyst is 1:0.15:0.2, and p-bromochlorobenzene The weight ratio of benzene to solvent is 1:1;

[0069] The reaction process includes: slowly raising the temperature and controlling the temperature to 100° C., reflux reaction at normal pressure, and maintaining the temperature for 1 h. When the sample HPLC detects that p-chlorophenylhydrazine no longer increases, the reaction is stopped.

[0070] (1....

Embodiment 2

[0075] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0076] (1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:3 as reaction raw materials, add a phase transfer catalyst (tetrabutylammonium bromide and tetrabutylammonium bisulfate with a mass ratio of 2:1), solvent (Ethylene glycol dimethyl ether), catalyst (copper bromide) for the reaction, wherein the concentration of hydrazine hydrate is 55%, the weight ratio of p-bromochlorobenzene to phase transfer catalyst and catalyst is 1:0.08:0.12, and p-bromo The weight ratio of chlorobenzene to solvent is 1:12;

[0077] The reaction process includes: slowly raising the temperature and controlling the temperature to 150° C., maintaining the pressure for reaction, keeping the temperature for 10 h, and stopping the reaction when the sample HPLC detects that p-chlorophenylhydrazine no longer increases.

[0078] (1.2) After the reaction is complet...

Embodiment 3

[0083] The synthetic steps of p-chlorophenylhydrazine hydrochloride in the present embodiment are as follows:

[0084] (1.1) Use p-bromochlorobenzene and hydrazine hydrate with an equivalent ratio of 1:4.5 as the reaction raw materials, and add a phase transfer catalyst (trioctylmethylammonium chloride, 15-crown-5 and PEG400), solvent (concentration is 85% propylene glycol ether aqueous solution), catalyst (cuprous chloride) to react, wherein, the concentration of hydrazine hydrate is 88%, p-bromochlorobenzene and phase transfer catalyst, the weight ratio of catalyst is 1:0.11:0.09, the weight ratio of p-bromochlorobenzene to solvent is 1:8.6;

[0085] The reaction process includes: slowly raising the temperature and controlling the temperature to 120° C., reflux reaction at normal pressure, maintaining the temperature for 9 hours, and stopping the reaction when the sample HPLC detects that p-chlorophenylhydrazine no longer increases.

[0086] (1.2) After the reaction is comp...