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

Abstract

The present invention relates to a method for synthesizing an insect growth regulator substituting benzoyl urea, and more specifically, the present invention relates to a method for synthesizing hexaflumuron, flufenoxuron and diflubenzuron. In the method, 2, 6-difluorobenzonitrile is used as an initial raw material; after fluorination, hydrolyzation, esterification and addition, a compound substituting benzoyl urea is obtained. In the fluorination step of the method, high-activity potassium fluoride and quaternary ammonium salt catalysts are used, and thus, the time of the fluorination reaction is largely shortened; in the hydrolyzation step, alkali catalyzed hydrolysis reaction is adopted, and thus, specific requirements for devices are reduced; in the esterification step, phosgene is used for replacing oxalyl chloride, and thus, the cost of the esterification reaction is reduce; in the addition step, catalysts are used, and thus, the yield of the addition reaction is increased. The method has the advantages of high yield, simple step and inexpensive raw material, and is suitable for industrial production scales. By using the method of the present invention, the yield of diflubenzuron reaches 97%, the yield of hexaflumuron reaches 93%, and the yield of flufenoxuron reaches 86%.

Description

The synthetic method of substituted benzoyl urea insect growth regulator(IGR)

Technical field

The present invention relates to a kind of synthetic method of substituted benzoyl urea insect growth regulator(IGR), relate to the synthetic method of fluorine bell urea, flufenoxuron and diflubenzuron specifically.

Technical background

Benzoyl urea compound is the class effective insecticidal miticide that works that synthesizes by the inhibition insect chitin, or is referred to as insect growth regulator(IGR).Wherein common have U.S. DOW ELAN company at the fluorine bell urea (hexaflumuron) of exploitation in 1987, flufenoxuron, diflubenzuron etc.

The synthetic of this compounds is with 2 mostly, and the 6-dichlorobenzonitrile is a starting raw material, through fluoridize, hydrolysis esterification, addition and obtain substituted benzoyl urea compound, as follows as its reaction formula:

1) fluoridize:

2) hydrolysis:

3) esterification:

4) addition:

Wherein,

People such as Yu Dengbo are synthetic the diflubenzuron described in the agricultural chemicals vol.39 No.3 2000, promptly are to adopt aforesaid method to make.But the hydrolysis step 2 of this method) is to adopt 90% the vitriol oil, thereby conversion unit is required harshness, needs the acid-proof material prepared, and potential danger is bigger; The esterification of step 3) is to use oxalyl chloride, the cost height; The product that obtains need separate purification, complex steps.

For step 1), the method that is prepared fluoro benzonitrile by chloro-benzonitrile is disclosed among the CN85100467A, though improved productive rate, can reach 86%, but still not be very high than general method; And this method uses the perfluoroalkyl oxa-carboxylic acid derivative as catalyzer, and the Preparation of catalysts of this class open loop ethers is loaded down with trivial details, is unfavorable for industrial production.

For step 3), Zhao Yonghua is in the fluorine bell urea described in the agricultural chemicals vol.40 No.11 2001 synthetic, adopt oxalyl chloride with 2, the esterification of 6-difluorobenzamide, this method cost height, the different ester that obtains are at room temperature stable inadequately, for this reason, the author once attempted using cheap phosgene to replace oxalyl chloride, but reaction is difficult to carry out.

Chen Yingqi is in the flufenoxuron described in chemical reaction engineering and the technology vol.10 No.1 1994.12 synthetic, and the esterification of step 3) is to use oxalyl chloride, the cost height; It uses methylene dichloride as solvent, makes the product that obtains---and different ester is a yellow oil, needs further purification just can use at next step; And productive rate only is 74%.And in step 4), do not use catalyzer, the reaction times is long; And step 3) and step 4) are not used same solvent, the processing condition when having increased industrial production.

In sum, there is following defective in prior art:

The Potassium monofluoride that the fluoridizing of step 1) is to use calcining to obtain does not add catalyzer, and the reaction times reaches 20 hours, but productive rate is low to moderate 50%; Or use the perfluoroalkyl oxa-carboxylic acid derivative as catalyzer, this Preparation of catalysts is loaded down with trivial details, is unfavorable for industrial production;

Step 2) hydrolysis is to adopt 90% the vitriol oil, thereby conversion unit is required harshness, needs the acid-proof material prepared, and potential danger is bigger;

Oxalyl chloride is used in the esterification of step 3) usually, and the cost height is to use 6 times of phosgene; And the product that obtains needs to separate from solution purifies complex steps;

The addition of step 4) is to adopt fluorobenzene formyl isocyanic ester and substituted aniline addition under the condition of catalyst-free, and reaction yield is not high.

Summary of the invention

When the objective of the invention is to overcome the synthesizing substituted benzoyl urea insect growth regulator(IGR) of prior art, the fluoridation time is long, the one-tenth rate is low, hydrolysis reaction has particular requirement owing to used acid catalysis to equipment, operate dangerous property, and esterification cost height, product need separate, and addition reaction becomes the not high enough defective of rate, thereby provide a kind of highly active Potassium monofluoride and quaternary ammonium salt catalyst of having used, make the fluoridation time shorten greatly, thereby used alkali catalyzed hydrolysis to react the particular requirement that has reduced equipment, and use phosgene to replace oxalyl chloride, reduce the esterification cost, use catalyzer to improve the synthetic method of the substituted benzoyl urea insect growth regulator(IGR) of addition reaction productive rate.

The objective of the invention is to realize by the following technical solutions:

The invention provides a kind of synthetic method of substituted benzoyl urea insect growth regulator(IGR), it comprises the steps:

1) fluoridize: with 2, the mixture of 1 mole of 6-dichlorobenzonitrile, 1.5～2.0 moles of 450-550 order anhydrous potassium fluorides, solvent, catalyst A is in reactor, in 200 ℃ of heating 8～10 hours, filter,, obtain 2 the filtrate fractionation, the 6-difluorobenzonilyile, and reclaim solvent;

Described solvent is a tetramethylene sulfone;

Described catalyst A is the mixture of tetrabutylammonium chloride and methyl trioctylphosphine ammonium chloride, and wherein the shared weight percent of tetrabutylammonium chloride is 40～60wt%; Described catalyst A consumption is 2,1～3wt% of 6-dichlorobenzonitrile weight;

2) hydrolysis: with step 1) obtain 2,1 mole of 6-difluorobenzonilyile, catalyst B add in the reactor, splash into excessive hydrogen peroxide while stirring, keep temperature of reaction at 40 ℃, after dropwising, kept 1 hour in this temperature again, negative pressure is got rid of unreacted hydrogen peroxide, whizzer dries reactant, obtains 2,6-difluorobenzamide filter cake;

Described catalyst B is a kind of in sodium hydroxide, yellow soda ash or the sodium bicarbonate or is 1: 1 two kinds with weight ratio; Described catalyst B consumption is 2,1～3wt% of 6-difluorobenzonilyile weight;

3) esterification: with step 2) obtain 2,6-difluorobenzamide filter cake is dissolved in solvent, feeds excessive phosgene, reflux 4 hours generates 2, the 6-difluoro benzoyl isocyanate; Products therefrom can be directly used in next step without purification; Described solvent is a toluene;

4) addition: with step 3) obtain 2, the 6-difluoro benzoyl isocyanate is dissolved in toluene, adds equimolar substituted aniline and catalyzer C, 100～110 ℃ the reaction 4～6 hours, obtain the substituted benzoyl urea insect growth regulator(IGR);

Described substituted aniline is a 4-chloroaniline, 3,5-two chloro-4-(1,1,2,2-tetrafluoro oxyethyl group) aniline or 4-(2-chlorine 4-4-trifluoromethylphenopendant)-2-fluoroaniline;

Described catalyzer C is that triethylamine is or/and trolamine; Described catalyzer C consumption is 2,1～3wt% of 6-difluoro benzoyl isocyanate weight.

Its reaction formula is as follows:

Wherein,

Synthetic method provided by the invention compared with prior art, its advantage is:

1) to be different from prior art be to realize in the laboratory in the present invention, more is applicable to commercial production scale;

2) fluorination step employing quaternary ammonium salt of the present invention is a catalyzer, has used the particulate anhydrous potassium fluoride simultaneously, thereby has made two fluorobenzene eyeball yields up to 96%; And quaternary ammonium salt is the phase-transfer catalyst that widely uses, and is cheap, be easy to get, and is easy to suitability for industrialized production;

3) hydrolysing step of the present invention has adopted base catalysis, need not acid-proof equipment, and keeps high yield 92%;

4) esterif iotacation step of the present invention has adopted phosgene with low cost to replace oxalyl chloride, has reduced cost, and has kept high yield 91%; And the product that obtains need not purifying, can be directly used in next step reaction;

5) addition step of the present invention is used the solvent identical with esterif iotacation step, has simplified industrial operation; And this step adopts triethylamine or trolamine to make catalyzer, improved the productive rate of reaction, and the diflubenzuron yield is 97%, and fluorine bell urea yield is 93%, and the flufenoxuron yield is 86%.

Embodiment

Embodiment 1

1) fluoridizes: in the 1000L reactor, add the 500Kg tetramethylene sulfone, particulate Potassium monofluoride (450 order) 88.4Kg (1.5 kilomol) that adds spray-dried processing while stirring, 2,6-dichlorobenzonitrile 172Kg (1 kilomol), and the catalyst mixture 1.72Kg that forms by 40wt% tetrabutylammonium chloride and 60wt% methyl trioctylphosphine ammonium chloride, in 200 ℃ of heating 8 hours, filter, the sedimentary Repone K of elimination, the filtrate fractionation is obtained 2,6-difluorobenzonilyile 133.6Kg (0.96 kilomol), productive rate is 96.1%, content is 98.4%, and reclaims solvent sulfolane;

2) hydrolysis: with 2,6-difluorobenzonilyile 109.9Kg (0.79 kilomol), catalyzer sodium hydroxide 1.10Kg add in the reactor, the unlatching heat steam heats up, in 2 hours, drip 72.63Kg (2.14 kilomol) hydrogen peroxide, dropwise, 40 ℃ of insulations 1 hour, the hydrogen peroxide that negative pressure is excessive, reactant dries with whizzer, obtains 2,6-difluorobenzamide filter cake 114.4Kg (0.728 kilomol), productive rate is 92.2%, and content is 98.7%;

3) esterification: with 2,6-difluorobenzamide filter cake 98Kg (0.62 kilomol) and 417.2Kg toluene add in the reactor, feed phosgene 111.9Kg (1.13 kilomol), reflux 4 hours, generate 2,6-difluoro benzoyl isocyanate 103.0Kg (0.56 kilomol), productive rate 90.9%, products therefrom can be directly used in next step without purification;

4) addition: will go up 2 of step gained, 6-difluoro benzoyl isocyanate 62.2Kg (0.34 kilomol), 3,5-two chloro-4-(1,1,2,2-tetrafluoro oxyethyl group) aniline 94.5Kg (0.34 kilomol), and triethylamine 0.622Kg is dissolved in the 500Kg toluene, and 100 ℃ of reactions 6 hours, reaction solution was through centrifuging, collect filter cake, drying obtains fluorine bell urea 144.7Kg (0.31 kilomol), productive rate 92.3%, content 97.2%, filtrate is further concentrated, also can obtain fluorine bell urea 2.3Kg, counting productive rate is 93.8%.

Embodiment 2

1) fluoridizes: in the 1000L reactor, add the 500Kg tetramethylene sulfone, particulate Potassium monofluoride (550 order) 117.8Kg (2 kilomol) that adds spray-dried processing while stirring, 2,6-dichlorobenzonitrile 172Kg (1 kilomol), and the catalyst mixture 5.16Kg that forms by 60wt% tetrabutylammonium chloride and 40wt% methyl trioctylphosphine ammonium chloride, in 200 ℃ of heating 10 hours, filter, the sedimentary Repone K of elimination, the filtrate fractionation is obtained 2,6-difluorobenzonilyile 134.1Kg (0.965 kilomol), productive rate is 96.5%, content is 99.3%, and reclaims solvent sulfolane;

2) hydrolysis: with difluorobenzonilyile 109.9Kg (0.79 kilomol), catalyzer sodium hydroxide 1.10Kg and yellow soda ash 1.10Kg add in the reactor, the unlatching heat steam heats up, and Dropwise 5 1Kg in 2 hours (1.5 kilomol) hydrogen peroxide dropwises, 40 ℃ of insulations 1 hour, the hydrogen peroxide that negative pressure is excessive, reactant dries with whizzer, obtains difluorobenzamide filter cake 112.8Kg (0.718 kilomol), productive rate is 90.9%, and content is 98.5%;

3) esterification: with 2,6-difluorobenzamide filter cake 98Kg (0.62 kilomol) and 417.2Kg toluene add in the reactor, feed phosgene 198.0Kg (1.2 kilomol), reflux 4 hours, generate 2,6-difluoro benzoyl isocyanate 104.1Kg (0.57 kilomol), productive rate 91.8%, products therefrom can be directly used in next step without purification;

4) addition: will go up 2 of step gained, 6-difluoro benzoyl isocyanate 91.5Kg (0.5 kilomol), 4-(2-chlorine 4-4-trifluoromethylphenopendant)-2-fluoroaniline 153Kg (0.5 kilomol), and trolamine 1.83Kg is dissolved in the 500Kg toluene, 110 ℃ of reactions 4 hours, reaction solution is reduced to room temperature, filter, obtain clear crystal flufenoxuron 209.8Kg (0.43 kilomol), productive rate 85.1%, content 99.0% further concentrates filtrate, also can obtain flufenoxuron 2.2Kg, counting productive rate is 86.9%.

Embodiment 3

1) fluoridizes: in the 1000L reactor, add the 500Kg tetramethylene sulfone, particulate Potassium monofluoride (500 order) 106.0Kg (1.8 kilomol) that adds spray-dried processing while stirring, 2,6-dichlorobenzonitrile 172Kg (1 kilomol), and the catalyst mixture 3.44Kg that forms by 50wt% tetrabutylammonium chloride and 50wt% methyl trioctylphosphine ammonium chloride, in 200 ℃ of heating 9 hours, filter, the sedimentary Repone K of elimination, the filtrate fractionation is obtained 2,6-difluorobenzonilyile 133.7Kg (0.96 kilomol), productive rate is 96.2%, content is 98.8%, and reclaims solvent sulfolane;

2) hydrolysis: with 2,6-difluorobenzonilyile 109.9Kg (0.79 kilomol), catalyzer carbonic acid hydrogen sodium 1.65Kg and yellow soda ash 1.65Kg add in the reactor, the unlatching heat steam heats up, in 2 hours, drip 102Kg (3.0 kilomol) hydrogen peroxide, dropwise, 40 ℃ of insulations 1 hour, the hydrogen peroxide that negative pressure is excessive, reactant dries with whizzer, obtains 2,6-difluorobenzamide filter cake 115.1Kg (0.733 kilomol), productive rate is 92.8%, and content is 98.8%;

3) esterification: with 2,6-difluorobenzamide filter cake 98Kg (0.62 kilomol) and 417.2Kg toluene add in the reactor, feed phosgene 148.5Kg (1.51 kilomol), reflux 4 hours, generate 2,6-difluoro benzoyl isocyanate 106.1Kg (0.58 kilomol), productive rate 93.5%, products therefrom can be directly used in next step without purification;

4) addition: will go up 2 of step gained, 6-difluoro benzoyl isocyanate 91.5Kg (0.5 kilomol), 4-chloroaniline 63.5Kg (0.5 kilomol), and trolamine 1.37Kg and triethylamine 1.37Kg are dissolved in the 500Kg toluene, 105 ℃ of reactions 5 hours, reaction solution was reduced to room temperature, filtered, obtain white crystal diflubenzuron 148.8Kg (0.48 kilomol), productive rate 96.0%, content 98.0% further concentrates filtrate, also can obtain diflubenzuron 2.2Kg, counting productive rate is 97.4%.

Claims (1)

1, a kind of synthetic method of substituted benzoyl urea insect growth regulator(IGR), it comprises the steps:

1) fluoridize: with 2, the mixture of 1 mole of 6-dichlorobenzonitrile, 1.5～2.0 moles of 450-550 order anhydrous potassium fluorides, solvent, catalyst A is in reactor, in 200 ℃ of heating 8～10 hours, filter,, obtain 2 the filtrate fractionation, the 6-difluorobenzonilyile, and reclaim solvent;

Described solvent is a tetramethylene sulfone;

Described catalyst A is the mixture of tetrabutylammonium chloride and methyl trioctylphosphine ammonium chloride, and wherein the shared weight percent of tetrabutylammonium chloride is 40～60wt%; Described catalyst A consumption is 2,1～3wt% of 6-dichlorobenzonitrile weight;

2) hydrolysis: with step 1) obtain 2,1 mole of 6-difluorobenzonilyile, catalyst B add in the reactor, splash into excessive hydrogen peroxide while stirring, keep temperature of reaction at 40 ℃, after dropwising, kept 1 hour in this temperature again, negative pressure is got rid of unreacted hydrogen peroxide, whizzer dries reactant, obtains 2,6-difluorobenzamide filter cake;

Described catalyst B is a kind of in sodium hydroxide, yellow soda ash or the sodium bicarbonate or is 1: 1 two kinds with weight ratio; Described catalyst B consumption is 2,1～3wt% of 6-difluorobenzonilyile weight;

3) esterification: with step 2) obtain 2,6-difluorobenzamide filter cake is dissolved in solvent, feeds excessive phosgene, reflux 4 hours generates 2, the 6-difluoro benzoyl isocyanate; Products therefrom can be directly used in next step without purification;

Described solvent is a toluene;

4) addition: with step 3) obtain 2, the 6-difluoro benzoyl isocyanate is dissolved in toluene, adds equimolar substituted aniline and catalyzer C, 100～110 ℃ the reaction 4～6 hours, obtain the substituted benzoyl urea insect growth regulator(IGR);

Described substituted aniline is a 4-chloroaniline, 3,5-two chloro-4-(1,1,2,2-tetrafluoro oxyethyl group) aniline or 4-(2-chlorine 4-4-trifluoromethylphenopendant)-2-fluoroaniline;

Described catalyzer C is that triethylamine is or/and trolamine; Described catalyzer C consumption is 2,1～3wt% of 6-difluoro benzoyl isocyanate weight.