CN1218935C - Substituted benzoyl urea insect growth regulator synthesizing method - Google Patents

Abstract

The invention relates to a synthesis method of a substituted benzoylurea insect growth regulator, in particular to a synthesis method of hexaflumuron, fluflubenzuron and diflubenzuron. The method uses 2,6-difluorobenzonitrile as a starting material to obtain substituted benzoylurea compounds through fluorination, hydrolysis, esterification and addition. This method uses highly active potassium fluoride and quaternary ammonium salt catalysts in the fluorination step, which greatly shortens the fluorination reaction time; uses a base-catalyzed hydrolysis reaction in the hydrolysis step to reduce the special requirements for equipment; in the esterification step Use phosgene instead of oxalyl chloride to reduce the cost of esterification reaction; use a catalyst in the addition step to increase the yield of the addition reaction. The method has the advantages of high yield, simple steps, cheap raw materials, and is more suitable for industrial production scale. Using this method, the yield of diflubenzuron was 97%, that of hexaflumuron was 93%, and that of diflubenzuron was 86%.

Description

Synthetic method of substituted benzoylurea insect growth regulator

technical field

The invention relates to a synthesis method of a substituted benzoylurea insect growth regulator, in particular to a synthesis method of hexaflumuron, fluflubenzuron and diflubenzuron.

technical background

Benzoylurea compounds are a class of effective insecticides and acaricides that act by inhibiting the synthesis of chitin in insects, or insect growth regulators. Among them, the most common ones are hexaflumuron (hexaflumuron), fluflubenzuron, and diflubenzuron developed by DOW ELAN Company of the United States in 1987.

Most of the synthesis of this type of compound uses 2,6-dichlorobenzonitrile as the starting material, through fluorination, hydrolysis, esterification, and addition to obtain substituted benzoylurea compounds, such as the reaction formula is as follows:

1) Fluorination:

2) Hydrolysis:

3) Esterification:

4) Bonus:

in,

The synthesis of diflubenzuron described in pesticide vol.39 No.3 2000 by Yu Dengbo et al. was obtained by the above method. But the hydrolysis of step 2) of this method is to adopt the concentrated sulfuric acid of 90%, thereby harsh to reaction equipment, needs the preparation of acid-proof material, potential danger is bigger; The esterification of step 3) is to use oxalyl chloride, cost High; the obtained product needs to be separated and purified, and the steps are cumbersome.

For step 1), CN85100467A discloses the method for preparing fluorobenzonitrile by chlorobenzonitrile, although the yield is improved compared with the general method, it can reach 86%, but it is still not very high; and the method uses perfluoroalkyl Oxacarboxylic acid derivatives are used as catalysts, and the preparation of such ring-opening ether catalysts is cumbersome and unfavorable for industrial production.

For step 3), Zhao Yonghua used oxalyl chloride to esterify 2,6-difluorobenzamide in the synthesis of hexaflumuron described in the pesticide vol.40 No.11 2001. The cost of this method is high, and the obtained iso Esters are not stable enough at room temperature. For this reason, the author tried to use cheap phosgene instead of oxalyl chloride, but the reaction was difficult.

In the synthesis of flufenuron described in Chen Yingqi's Chemical Reaction Engineering and Technology vol.10 No.1 1994.12, the esterification of step 3) uses oxalyl chloride, which has high cost; it uses dichloromethane as a solvent, so that the obtained The product, isoester, is a yellow oil that needs further purification before it can be used in the next step; and the yield is only 74%. And in step 4) no catalyst is used, the reaction time is too long; and step 3) and step 4) do not use the same solvent, which increases the process conditions during industrial production.

In summary, there are following defects in the prior art:

The fluorination of step 1) is to use potassium fluoride obtained by calcining without adding a catalyst, the reaction time is as long as 20 hours, but the yield is as low as 50%; or use perfluoroalkyl oxacarboxylic acid derivatives as catalysts, this The preparation of the catalyst is cumbersome and unfavorable for industrial production;

The hydrolysis of step 2) adopts 90% concentrated sulfuric acid, so the requirements for reaction equipment are harsh, and it needs to be prepared by acid-proof material, which is potentially dangerous;

The esterification of step 3) usually uses oxalyl chloride, which has a high cost and is 6 times that of using phosgene; and the obtained product needs to be separated and purified from the solution, and the steps are cumbersome;

The addition of step 4) adopts the addition of fluorobenzoyl isocyanate and substituted aniline under the condition of no catalyst, and the reaction yield is not high.

Contents of the invention

The purpose of the present invention is to overcome the long fluorination reaction time and low yield when synthesizing substituted benzoylurea insect growth regulators in the prior art, and the hydrolysis reaction has special requirements for equipment and dangerous operation due to the use of acid catalysis , and the disadvantages of high cost of esterification reaction, separation of products, and insufficient addition reaction rate, thus providing a catalyst using highly active potassium fluoride and quaternary ammonium salt, which greatly shortens the fluorination reaction time and uses A base-catalyzed hydrolysis reaction reduces the special requirements for equipment, and uses phosgene to replace oxalyl chloride, reduces the cost of esterification reaction, and uses a catalyst to increase the yield of addition reaction. A synthetic method for substituted benzoylurea insect growth regulators .

The purpose of the present invention is achieved through the following technical solutions:

The invention provides a kind of synthetic method that replaces benzoylurea insect growth regulator, and it comprises the steps:

1) Fluorination: heat a mixture of 1 mole of 2,6-dichlorobenzonitrile, 1.5-2.0 moles of anhydrous potassium fluoride of 450-550 mesh, solvent and catalyst A in a reaction kettle at 200°C for 8-10 hours , filtered, and the filtrate was fractionally distilled to obtain 2,6-difluorobenzonitrile, and the solvent was recovered;

Described solvent is sulfolane;

The catalyst A is a mixture of tetrabutylammonium chloride and methyltrioctylammonium chloride, wherein tetrabutylammonium chloride accounts for 40 to 60 wt% by weight; the amount of catalyst A is 2,6- 1～3wt% of dichlorobenzonitrile weight;

2) Hydrolysis: Add 1 mole of 2,6-difluorobenzonitrile obtained in step 1) and Catalyst B into the reactor, add excess hydrogen peroxide dropwise while stirring, keep the reaction temperature at 40°C, after the dropwise addition is completed , then keep at this temperature for 1 hour, remove unreacted hydrogen peroxide under negative pressure, dry the reactants in a centrifuge, and obtain 2,6-difluorobenzamide filter cake;

The catalyst B is one of sodium hydroxide, sodium carbonate, or sodium bicarbonate, or two of them in a weight ratio of 1:1; 3wt%;

3) Esterification: dissolving the 2,6-difluorobenzamide filter cake obtained in step 2) in a solvent, passing through excess phosgene, and heating to reflux for 4 hours to generate 2,6-difluorobenzoyl isocyanate; The resulting product can be directly used in the next step without purification; the solvent is toluene;

4) Addition: Dissolve the 2,6-difluorobenzoyl isocyanate obtained in step 3) in toluene, add equimolar substituted aniline and catalyst C, and react at 100-110°C for 4-6 hours to obtain substituted benzene Formylurea insect growth regulators;

The substituted aniline is 4-chloroaniline, 3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)aniline or 4-(2-chloro4-trifluoromethylbenzene Oxy)-2-fluoroaniline;

The catalyst C is triethylamine or/and triethanolamine; the dosage of the catalyst C is 1-3 wt% of the weight of 2,6-difluorobenzoyl isocyanate.

Its reaction formula is as follows:

in,

Compared with the prior art, the synthetic method provided by the invention has the advantages of:

1) The present invention is different from prior art and realizes in the laboratory, is more suitable for industrial production scale;

2) The fluorination step of the present invention adopts quaternary ammonium salt as a catalyst, and simultaneously uses fine-grained anhydrous potassium fluoride, so that the yield of difluorobenzonitrile is as high as 96%; and quaternary ammonium salt is a widely used phase transfer catalyst , cheap, easy to obtain, and easy to industrialized production;

3) The hydrolysis step of the present invention adopts alkali catalysis, does not need anti-acid equipment, and maintains a high yield of 92%;

4) The esterification step of the present invention adopts low-cost phosgene to replace oxalyl chloride, which reduces the cost and maintains a high yield of 91%; moreover, the obtained product can be directly used in the next step without purification;

5) The addition step of the present invention uses the same solvent as the esterification step, which simplifies industrial operations; and this step uses triethylamine or triethanolamine as a catalyst, which improves the yield of the reaction, and the yield of diflubenzuron is 97%. , the yield of hexaflumuron was 93%, and the yield of hexaflumuron was 86%.

Detailed ways

Example 1

1) Fluorination: Add 500Kg sulfolane to a 1000L reactor, and add 88.4Kg (1.5 kilomoles) of fine-grained potassium fluoride (450 mesh) which has been spray-dried while stirring, and 172Kg of 2,6-dichlorobenzonitrile (1 kilomole), and the catalyst mixture 1.72Kg that is made up of 40wt% tetrabutylammonium chloride and 60wt% methyltrioctylammonium chloride, in 200 ℃ of heating 8 hours, filter, filter the potassium chloride of precipitation , the filtrate was fractionally distilled to obtain 2,6-difluorobenzonitrile 133.6Kg (0.96 kilomoles), the productive rate was 96.1%, and the content was 98.4%, and the solvent sulfolane was recovered;

2) Hydrolysis: Add 109.9Kg (0.79 kilomoles) of 2,6-difluorobenzonitrile and 1.10Kg catalyst sodium hydroxide into the reactor, turn on the hot steam to raise the temperature, and add 72.63Kg (2.14 kilomoles) dropwise within 2 hours Hydrogen peroxide, after the dropwise addition, was incubated at 40°C for 1 hour, the excess hydrogen peroxide under negative pressure, and the reactant was dried with a centrifuge to obtain 114.4Kg (0.728 kilomoles) of 2,6-difluorobenzamide filter cake , the yield is 92.2%, and the content is 98.7%;

3) Esterification: 98Kg (0.62 kilomoles) of 2,6-difluorobenzamide filter cake and 417.2Kg toluene were added into the reaction kettle, 111.9Kg (1.13 kilomoles) of phosgene was passed through, heated and refluxed for 4 hours, and 2,6-difluorobenzoyl isocyanate 103.0Kg (0.56 kilomoles), yield 90.9%, the resulting product can be directly used in the next step without purification;

4) Addition: 62.2Kg (0.34 kilomoles) of 2,6-difluorobenzoyl isocyanate obtained in the previous step, 3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy Base) 94.5Kg (0.34 kilomoles) of aniline, and 0.622Kg of triethylamine were dissolved in 500Kg toluene, and reacted for 6 hours at 100°C. The reaction solution was centrifugally filtered, and the filter cake was collected and dried to obtain 144.7Kg (0.31 kilomole), productive rate 92.3%, content 97.2%, the filtrate is further concentrated, and hexaflumuron 2.3Kg can also be obtained, and the calculated productive rate is 93.8%.

Example 2

1) Fluorination: Add 500Kg sulfolane in a 1000L reactor, and add 117.8Kg (2 kilomoles) of fine-grained potassium fluoride (550 mesh) which has been spray-dried while stirring, and 172Kg of 2,6-dichlorobenzonitrile (1 kilomole), and the catalyst mixture 5.16Kg that is made up of 60wt% tetrabutylammonium chloride and 40wt% methyltrioctylammonium chloride, in 200 ℃ of heating 10 hours, filter, filter the potassium chloride of precipitation , the filtrate was fractionally distilled to obtain 2,6-difluorobenzonitrile 134.1Kg (0.965 kilomoles), the productive rate was 96.5%, and the content was 99.3%, and the solvent sulfolane was recovered;

2) Hydrolysis: Add 109.9Kg (0.79 kilomoles) of difluorobenzonitrile, 1.10Kg catalyst sodium hydroxide and 1.10Kg sodium carbonate to the reactor, turn on the hot steam to raise the temperature, and add 51Kg (1.5 kilomoles) dropwise within 2 hours Hydrogen peroxide, dropwise, was incubated at 40 DEG C for 1 hour, negative pressure was excessive hydrogen peroxide, and the reactant was dried with a centrifuge to obtain 112.8Kg (0.718 kilomoles) of difluorobenzamide filter cake, and the yield was 90.9%, the content is 98.5%;

3) Esterification: 98Kg (0.62 kilomoles) of 2,6-difluorobenzamide filter cake and 417.2Kg toluene were added into the reactor, 198.0Kg (1.2 kilomoles) of phosgene was passed through, heated and refluxed for 4 hours to generate 2,6-difluorobenzoyl isocyanate 104.1Kg (0.57 kilomoles), yield 91.8%, the resulting product can be directly used in the next step without purification;

4) Addition: 91.5Kg (0.5 kilomole) of 2,6-difluorobenzoyl isocyanate obtained in the previous step, 153Kg of 4-(2-chloro4-trifluoromethylphenoxy)-2-fluoroaniline (0.5 kilomol), and 1.83Kg of triethanolamine was dissolved in 500Kg toluene, reacted for 4 hours at 110 ℃, and the reaction solution was lowered to room temperature, and filtered to obtain 209.8Kg (0.43 kilomol) of colorless crystal fiflubenzuron, with a yield of 85.1 %, the content is 99.0%, and the filtrate is further concentrated to obtain 2.2Kg of flubenzuron, and the calculated yield is 86.9%.

Example 3

1) Fluorination: Add 500Kg sulfolane to a 1000L reactor, and add 106.0Kg (1.8 kilomoles) of fine-grained potassium fluoride (500 mesh) that has been spray-dried while stirring, and 172Kg of 2,6-dichlorobenzonitrile (1 kilomole), and the catalyst mixture 3.44Kg that is made up of 50wt% tetrabutylammonium chloride and 50wt% methyltrioctylammonium chloride, in 200 ℃ of heating 9 hours, filter, filter the potassium chloride of precipitation , the filtrate was fractionally distilled to obtain 2,6-difluorobenzonitrile 133.7Kg (0.96 kilomoles), the productive rate was 96.2%, and the content was 98.8%, and the solvent sulfolane was recovered;

2) Hydrolysis: 109.9Kg (0.79 kilomoles) of 2,6-difluorobenzonitrile, 1.65Kg of catalyst sodium bicarbonate and 1.65Kg of sodium carbonate were added to the reactor, and the hot steam was turned on to raise the temperature, and 102Kg ( 3.0 kilomoles) hydrogen peroxide, dropwise, at 40 ℃ of insulation 1 hour, negative pressure is excessive hydrogen peroxide, and reactant is dried with centrifuge, obtains 2,6-difluorobenzamide filter cake 115.1Kg ( 0.733 kilomol), the productive rate is 92.8%, and the content is 98.8%;

3) Esterification: 98Kg (0.62 kilomoles) of 2,6-difluorobenzamide filter cake and 417.2Kg toluene were added into the reaction kettle, 148.5Kg (1.51 kilomoles) of phosgene was passed through, heated and refluxed for 4 hours to generate 2,6-difluorobenzoyl isocyanate 106.1Kg (0.58 kilomoles), yield 93.5%, the resulting product can be directly used in the next step without purification;

4) Addition: 91.5Kg (0.5 kilomoles) of 2,6-difluorobenzoyl isocyanate obtained in the previous step, 63.5Kg (0.5 kilomoles) of 4-chloroaniline, 1.37Kg triethanolamine and 1.37 kilomoles triethylamine Kg was dissolved in 500Kg toluene, reacted at 105°C for 5 hours, the reaction solution was cooled to room temperature, and filtered to obtain 148.8Kg (0.48 kilomoles) of white crystal diflubenzuron, with a yield of 96.0% and a content of 98.0%. The filtrate was further concentrated, 2.2 Kg of diflubenzuron can also be obtained, and the calculated yield is 97.4%.

Claims (1)

1. A synthetic method of a substituted benzoyl urea insect growth regulator comprises the following steps:

1) fluorination: heating a mixture of 1 mol of 2, 6-dichlorobenzonitrile, 1.5-2.0 mol of 450-mesh 550-mesh anhydrous potassium fluoride, a solvent and a catalyst A in a reaction kettle at 200 ℃ for 8-10 hours, filtering, fractionating the filtrate to obtain 2, 6-difluorobenzonitrile, and recovering the solvent;

the solvent is sulfolane;

the catalyst A is a mixture of tetrabutylammonium chloride and methyl trioctyl ammonium chloride, wherein the tetrabutylammonium chloride accounts for 40-60 wt%; the amount of the catalyst A is 1-3 wt% of the weight of the 2, 6-dichlorobenzonitrile;

2) hydrolysis: adding 1 mol of 2, 6-difluorobenzonitrile obtained in the step 1) and a catalyst B into a reaction kettle, dripping excessive hydrogen peroxide while stirring, keeping the reaction temperature at 40 ℃, keeping the temperature for 1 hour after finishing dripping, removing unreacted hydrogen peroxide under negative pressure, and spin-drying a reactant by a centrifuge to obtain a 2, 6-difluorobenzamide filter cake;

the catalyst B is one or two of sodium hydroxide, sodium carbonate or sodium bicarbonate in a weight ratio of 1: 1; the amount of the catalyst B is 1-3 wt% of the weight of the 2, 6-difluorobenzonitrile;

3) esterification: dissolving the 2, 6-difluorobenzamide filter cake obtained in the step 2) in a solvent, introducing excessive phosgene, and heating and refluxing for 4 hours to generate 2, 6-difluorobenzoyl isocyanate; the obtained product can be directly used in the next step without purification;

the solvent is toluene;

4) addition: dissolving the 2, 6-difluorobenzoyl isocyanate obtained in the step 3) in toluene, adding equimolar substituted aniline and a catalyst C, and reacting at 100-110 ℃ for 4-6 hours to obtain a substituted benzoyl urea insect growth regulator;

the substituted aniline is 4-chloroaniline, 3, 5-dichloro-4- (1, 1, 2, 2-tetrafluoroethoxy) aniline or 4- (2-chloro-4-trifluoromethylphenoxy) -2-fluoroaniline;

the catalyst C is triethylamine or/and triethanolamine; the amount of the catalyst C is 1-3 wt% of the weight of the 2, 6-difluorobenzoyl isocyanate.