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CN1508124A - Method for synthesizing lambda-cyhalothrin from p-fluorobenzoic aldehyde - Google Patents

Method for synthesizing lambda-cyhalothrin from p-fluorobenzoic aldehyde Download PDF

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CN1508124A
CN1508124A CNA021567662A CN02156766A CN1508124A CN 1508124 A CN1508124 A CN 1508124A CN A021567662 A CNA021567662 A CN A021567662A CN 02156766 A CN02156766 A CN 02156766A CN 1508124 A CN1508124 A CN 1508124A
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fluorobenzaldehyde
bromo
reaction
synthetic
glycol
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颜汉新
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Abstract

The method for synthesizing cyfluthrin includes five steps: A. making p fluorobenzaldehyde as raw material undergo the process of bromination reaction to obtain 3-bromo-4-fluorobenzaldehyde; B. making 3-bromo-4-fluorobenzaldehyde and ethanediol implement condensation reaction to obtain the correspondent aldehyde acetal; C. making said aldehyde acetal and sodium phenolate implement etherification reaction to obtain 3-phenoxy-4-fluorobenzaldehyde glycol acetal; D hydrolyzing the obtained glycol acetal to obtain 3-phenoxy-4-fluorobenzaldehyde; and E. making the obtained 3-phenoxy-4-fluorobenzaldehyde, dichlorochrysanthemum acyl chloride and sodium cyanide implement reaction so as to obtain the cyfluthrin.

Description

A kind of method with the synthetic cyfloxylate of p-Fluorobenzenecarboxaldehyde
The present invention relates to organic chemistry filed, particularly, the present invention relates to a kind of method with the synthetic cyfloxylate of p-Fluorobenzenecarboxaldehyde.
Cyfloxylate is also referred to as cyhalofop-butyl, is the pyrethroid insecticides of a kind of wide spectrum, efficient, low toxicity, and its molecular formula is: C 22H 18C 12FNO 3, chemical name is: 2, and 2-dimethyl-3-(2, the 2-dichloroethylene)-cyclopropanic acid acid-alpha-cyano-3-phenoxy group-4-fluorobenzene methyl ester.Cyfloxylate is widely used in being mixed with various agricultural chemicals; in the prior art; mainly by with the bromizating agent N-bromosuccinimide with the p-Fluorobenzenecarboxaldehyde bromination, with triethyl orthoformate protect aldehyde radical, steps such as reaction with phenol replacement bromine group under cuprous oxide catalysis agent effect prepare cyfloxylate; but; this method exists bromizating agent and the aldehyde radical protective material such as use to cost an arm and a leg; bromizating agent efficient is low, defectives such as cuprous oxide catalysis weak effect.
The method that the purpose of this invention is to provide a kind of synthetic cyfloxylate newly.
The inventor has carried out exploring for many years and studying to the method for synthetic cyfloxylate (being cyhalofop-butyl), the method for preparing cyhalofop-butyl is improved and innovated, the most outstanding characteristics of the inventive method are to have improved productive rate, have simplified post-processing step, have reduced cost.
Synthetic method of the present invention divided for five steps carried out:
The first step: with the p-Fluorobenzenecarboxaldehyde is raw material, adds bromine (liquid bromine) and chlorine and carries out bromination reaction, gets 3-bromo-4-fluorobenzaldehyde after washing, pickling;
Second the step: carry out condensation reaction by 3-bromo-4-fluorobenzaldehyde and ethylene glycol, the use toluene as solvent double as dewatering agent, through distill 3-bromo-4-fluorobenzaldehyde Glycol Acetal;
The 3rd the step: carry out etherification reaction by 3-bromo-4-fluorobenzaldehyde Glycol Acetal and sodium phenylate, through alkali cleaning, washing, extraction, steaming desolventize 3-phenoxy group-4-fluorobenzaldehyde Glycol Acetal;
The 4th step: after hydrolysis, underpressure distillation gets 3-phenoxy group-4-fluorobenzaldehyde by 3-phenoxy group-4-fluorobenzaldehyde Glycol Acetal;
The 5th step: carry out esterification by 3-phenoxy group-4-fluorobenzaldehyde and dichloro chrysanthemum acyl chlorides, sodium cyanide solution, through washing, steam desolventize the cyfloxylate product.
Further specify content of the present invention below.
The present invention uses liquid bromine to carry out direct bromination in the first step, and adopts aluminum chloride as catalyzer and feeding chlorine, and wherein, preferred mol ratio is a p-Fluorobenzenecarboxaldehyde: Br 2: Cl 2Be 1: (0.5-0.8): (0.5-0.8); Usually, direct and the phenyl aldehyde reaction with liquid bromine, bromination weak effect not only, and side reaction is a lot, and the inventor is surprised to find by research, constantly feeds chlorine in this reaction, can improve the bromination reaction effect, improved reaction yield, this may be because " changing thing mutually " that chlorine that feeds and bromine have formed bromine chloride, and this is changed thing mutually and have good bromination activity under the effect of catalyzer aluminum chloride; Because use liquid bromine more much lower than the bromizating agent N-bromosuccinimide cost that uses in the prior art, bromination reaction is more direct; Therefore, use this method of the present invention not only to improve productive rate, and simplified last handling process, reached the effect that reduces cost and increase yield;
In second step, the present invention makes spent glycol under the effect of catalyzer tosic acid, aldehyde radical in the 3-bromo-4-fluorobenzaldehyde is protected with acetal form so that carry out next step reaction, wherein preferred mol ratio is a 3-bromo-4-fluorobenzaldehyde: ethylene glycol is 1: (1.3-1.7), wherein make spent glycol lower than the triethyl orthoformate cost that uses in the prior art as aldehyde radical protection reagent, select for use toluene to replace ethanol of the prior art simultaneously as the dewatering agent in the solvent double as reflux, like this, by using water trap the moisture that generates in the condensation reaction can be come out, and a large amount of toluene that use can recycling use, use these measures to improve productive rate, reduced cost;
In the 3rd step, the present invention uses that prepared in reaction obtains 3-phenoxy group-4-fluorobenzaldehyde Glycol Acetal under 3-bromo-4-fluorobenzaldehyde Glycol Acetal and the effect of phenol sodium hydroxide, and wherein preferred mol ratio is a 3-bromo-4-fluorobenzaldehyde Glycol Acetal: phenol is 1: (1.3-1.5); The inventor finds under study for action, in this step reaction, temperature of reaction is very important, temperature of reaction improves, and helps reaction and carries out, therefore, the present invention has used higher solvent of boiling point such as diethylene glycol dimethyl ether to substitute the solvent dimethylformamide that uses in the prior art, make temperature of reaction can be controlled at 160-180 ℃, preferred 168-172 ℃, improved reaction yield; The present invention uses cuprous chloride to replace Red copper oxide of the prior art as catalyzer, has also improved reaction effect; In the post-reaction treatment process, use toluene extracts and with the post-treating method that sodium hydroxide solution washs, has simplified last handling process, has improved productive rate;
In the 4th step, the present invention uses toluene to divide the water layer in the abstraction reaction system three times, has reduced product loss;
In the 5th step, the present invention uses 3-phenoxy group-4-fluorobenzaldehyde and sodium cyanide and dichloro chrysanthemum acyl chlorides (chemical name: 3-(2, the 2-dichloroethylene)-2,2-dimethylcyclopropane carboxyl acyl chloride) (be called for short: PTC) prepared in reaction obtains cyfloxylate under the effect at phase-transfer catalyst, phase-transfer catalyst among the present invention can use for example tri-n-octyl methyl ammonium chloride, triethyl benzyl ammonia chloride or Tetrabutyl amonium bromide etc., the present invention uses toluene as solvent in this step, by under preferred temperature of reaction, reacting, obtained good reaction effect; In addition, the inventor also finds, in this step reaction, to splash into the product quality that sodium cyanide solution obtains better in batches, and yield also improves.
The reaction process of the inventive method can illustrate with following reaction formula:
(1) synthetic 3-bromo-4-fluorobenzaldehyde;
Figure A0215676600061
(2) synthetic 3-bromo-4-fluorobenzaldehyde Glycol Acetal;
Figure A0215676600062
(3) synthetic 3-phenoxy group-4-fluorobenzaldehyde Glycol Acetal;
(4) synthetic 3-phenoxy group-4-fluorobenzaldehyde;
Figure A0215676600064
(5) synthetic cyfloxylate;
Further specify the present invention below by embodiment.The preparation method who it should be understood that the embodiment of the invention is only used for illustrating the present invention, rather than limitation of the present invention, and the simple modifications to preparation method of the present invention under design prerequisite of the present invention all belongs to the scope of protection of present invention.Except as otherwise noted, the percentage ratio among the present invention is weight percentage.
Example 1: synthetic 3-bromo-4-fluorobenzaldehyde example I
In the 500ml four-hole boiling flask that thermometer, gas introduction tube, exhaust pipe agitator are housed, drop into the 200ml ethylene dichloride, the 125g aluminum trichloride (anhydrous), stirred 1.5 hours, material is cooled to 11-22 ℃, drops into the 100g p-Fluorobenzenecarboxaldehyde, the 75g bromine, after adding, temperature of charge is controlled at 18-22 ℃ and feeds 35.5g chlorine, and logical 10 hours approximately, after having led to, continue to stir 1-3 hour, stopped reaction is washed material and pickling, divides oil-yielding stratum, gets sorrel oily matter 160.1g then behind the distilling off solvent ethylene dichloride, content 92%, yield 90%.
Example 2: synthetic 3-bromo-4-fluorobenzaldehyde example II
In the 250ml four-hole boiling flask, drop into 100ml ethylene dichloride, 62.5g aluminum trichloride (anhydrous).Stir half an hour, the material reason is cooled to, drop into the 50g p-Fluorobenzenecarboxaldehyde, the 37.5g bromine.Add the back temperature of charge and be controlled at 18-30 ℃, feed 18g chlorine, logical 5 hours approximately, led to the back and continued to stir 1 hour.Stopped reaction is washed and pickling, divides oil-yielding stratum, and the distilling off solvent ethylene dichloride gets sorrel oily matter 79g, content 88%, yield 85%.
Example 3: the synthesizing glycol 3-bromo-4-fluorobenzaldehyde example I that contracts
In the 500ml flask of thermometer, reflux exchanger, agitator is housed, drop into 200ml toluene, 100g3-bromo-4-fluorobenzaldehyde, 45.8g ethylene glycol, 84mg tosic acid, reflux, the boiling that refluxes dewaters, temperature has been removed after the water for using the reflux temperature of solvent, steams toluene, decompression then, distillation is collected 132-135 ℃/35Pa fraction, yield 87%.
Example 4: the synthesizing glycol 3-bromo-4-fluorobenzaldehyde example II that contracts
In flask at the bottom of the 250ml garden, drop into 100ml toluene, 50g3-bromo-4-fluorobenzaldehyde, 23g ethylene glycol, 42mg tosic acid, reflux, the boiling that refluxes dewaters, temperature has been removed after the water for using the reflux temperature of solvent, steams toluene, decompression then, distillation is collected 132-140 ℃/35Pa fraction, yield 91%.
Example 5: the synthesizing glycol 3-phenoxy group-4 fluorobenzaldehyde example I that contracts
In the 500ml four-hole boiling flask of reflux exchanger, thermometer, agitator is housed; add the 200ml dehydrated alcohol; 20.2g sodium hydroxide heats under nitrogen protection, stirs; after treating that sodium hydroxide all dissolves; drop into 47.5g phenol, reflux 2 hours steams ethanol; add the 200ml diethylene glycol dimethyl ether, heat up and continue to steam the 10ml diethylene glycol dimethyl ether.Drop into ethylene glycol contract 3-bromo-4 fluorobenzaldehyde 96g and cuprous chloride 2.6g then; temperature is controlled at 168-172 ℃; under nitrogen protection, refluxed 8 hours; under negative pressure, steam then and remove diethylene glycol dimethyl ether; drop into 300ml toluene, with 5% sodium hydroxide solution washing secondary, oil reservoir boils off solvent toluene under negative pressure; get orange oily matter, yield 91.7%.
Example 6: the synthesizing glycol 3-phenoxy group-4 fluorobenzaldehyde example II that contracts
Under nitrogen 20.2g sodium hydroxide is dissolved in the 200ml dehydrated alcohol, drops into 47.5g phenol then, reflux steamed ethanol after 1 hour, added the 200ml diethylene glycol dimethyl ether, heated up and continued to steam the 10ml diethylene glycol dimethyl ether.Add 83g ethylene glycol contract 3-bromo-4 fluorobenzaldehydes and cuprous chloride 2.3g then; temperature is controlled at 150-180 ℃; under nitrogen protection, refluxed 8 hours; under negative pressure, steam diethylene glycol dimethyl ether then; drop into 300ml toluene, with 2% sodium hydroxide solution washing secondary, oil reservoir boils off solvent toluene under negative pressure; get orange oily matter, yield 86.7%.
Example 7: synthetic 3-phenoxy group-4-fluorobenzaldehyde example I
With the 100g ethylene glycol 3-phenoxy group-4-fluorobenzaldehyde that contracts, 300g water, 300ml ethanol, 70ml hydrochloric acid drops in the 250ml flask, stirred 5 hours under the room temperature, heat up then, divide the layer that deoils the ethanol evaporate to dryness, water layer methylbenzene extraction three times, merge oil reservoir, steam and remove toluene solvant, 140-143 ℃/35Pa fraction is collected in decompression, yield 92%, content 98.5%.
Example 8: synthetic 3-phenoxy group-4-fluorobenzaldehyde example II
With the 100g ethylene glycol 3-phenoxy group-4-fluorobenzaldehyde that contracts, 300g water, 300ml ethanol, 50ml hydrochloric acid drops in the 250ml flask, stirred 4 hours under the room temperature, heating up then steams ethanol, divides the layer that deoils, water layer methylbenzene extraction three times, merge oil reservoir, steam and remove toluene solvant, 135-148 ℃/35-45Pa fraction is collected in decompression, yield 94%, content 97.0%.
Example 9: synthetic cyfloxylate example I
The 17.4g sodium cyanide is dissolved in 61.7 water, drops into 16.8mg phase-transfer catalyst tri-n-octyl methyl ammonium chloride, 1/3 amount is dropped in the 500ml four-hole boiling flask after miscible, add 150ml toluene then, 3-phenoxy group-4-fluorobenzaldehyde 54.83g, the stirring reaction material, temperature of charge is at 25-27 ℃, drip remaining 2/3 (NaCN+H2O+PTC) solution, dripped 3 hours, and dripped dichloro chrysanthemum acyl chlorides 60g, dripped 3.5-4 hour, dripped 25-27 ℃ of insulation 10 hours, reaction finishes.Be washed to neutrality, oil reservoir gets cyfloxylate through steaming solvent.Yield 96%, content 95%.
Example 10: synthetic cyfloxylate example II
In the 500ml four-hole boiling flask that thermometer, stirring Lu are housed, add 22% sodium cyanide solution 79ml, toluene 150ml, 3-phenoxy group-4-fluorobenzaldehyde 54.83g, phase-transfer catalyst tri-n-octyl methyl ammonium chloride 16.8mg stirs, when material cools off 0-25 ℃, drip dichloro chrysanthemum acyl chlorides 60g, dripped 3-4 hour, and dripped the back and continue reaction 8 hours at 0-40 ℃, reaction finishes, be washed to neutrality, oil reservoir under reduced pressure steams solvent and gets cyfloxylate, yield 93%, content 90%.

Claims (9)

1. the method for a synthetic cyfloxylate comprises the steps:
(1). the synthetic 3-bromo-4-fluorobenzaldehyde under catalyst action by p-Fluorobenzenecarboxaldehyde and bromine;
(2). the condensation prepared 3-bromo-4-fluorobenzaldehyde Glycol Acetal under catalyst action by 3-bromo-4-fluorobenzaldehyde and ethylene glycol, use toluene as solvent and dewatering agent;
Figure A0215676600022
(3). synthetic 3-phenoxy group-4-fluorobenzaldehyde Glycol Acetal under catalyst action by 3-bromo-4-fluorobenzaldehyde Glycol Acetal and phenol, use diethylene glycol dimethyl ether as solvent;
Figure A0215676600023
(4). by the synthetic 3-phenoxy group of 3-bromo-4-fluorobenzaldehyde Glycol Acetal deprotection under acidic conditions-4-fluorobenzaldehyde;
Figure A0215676600024
(5). in the presence of phase-transfer catalyst, react synthetic cyfloxylate by 3-phenoxy group-4-fluorobenzaldehyde and sodium cyanide and dichloro chrysanthemum acyl chlorides;
Figure A0215676600031
2. according to the method for claim 1, it is characterized in that feeding chlorine in the reaction of step (1).
3. according to the method for claim 2, it is characterized in that using aluminum chloride as catalyzer in the reaction of step (1).
4. according to the method for claim 3, it is characterized in that the mol ratio of reaction mass in the step (1) is a p-Fluorobenzenecarboxaldehyde: Br 2: Cl 2, be 1: (0.5-0.8): (0.5-0.8).
5. according to the method for one of claim 1-4, it is characterized in that being reflected under the 160-180 ℃ of temperature of step (3) carry out.
6. according to the method for claim 5, it is characterized in that being reflected under the 168-172 ℃ of temperature of step (3) carry out.
7. according to the method for claim 6, it is characterized in that the reaction of step (3) uses cuprous chloride as catalyzer, use toluene to extract and wash in the post-reaction treatment.
8. the method for one of claim 1-4 is characterized in that the phase-transfer catalyst in the step (5) is a tri-n-octyl methyl ammonium chloride, triethyl benzyl ammonia chloride or Tetrabutyl amonium bromide.
9. the method for one of claim 1-4, it is characterized in that the mol ratio of reaction mass in the step (2) is a 3-bromo-4-fluorobenzaldehyde: ethylene glycol is 1: (1.3-1.7); The mol ratio of reaction mass is a 3-bromo-4-fluorobenzaldehyde Glycol Acetal in the step (3): phenol is 1: (1.3-1.5).
CNA021567662A 2002-12-18 2002-12-18 Method for synthesizing lambda-cyhalothrin from p-fluorobenzoic aldehyde Pending CN1508124A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009018740A1 (en) * 2007-08-03 2009-02-12 East China Normal Universtty Monohalogenated pyrethric acid alpha-cyano-4-fluoro-3-phenoxybenzyl ester and its preparation method and use
WO2010086876A3 (en) * 2009-01-09 2012-10-04 Aditya Birla Science & Technology Co. Ltd. Ether synthesis
CN103420872A (en) * 2013-08-26 2013-12-04 连云港市华通化学有限公司 Preparation method of lambda-cyhalothrin
CN108124868A (en) * 2017-12-25 2018-06-08 中山市小榄企业服务有限公司 Novel biological material for preventing and treating plant diseases and insect pests and processing equipment thereof
CN117049969A (en) * 2023-07-27 2023-11-14 阜新睿光氟化学有限公司 Preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009018740A1 (en) * 2007-08-03 2009-02-12 East China Normal Universtty Monohalogenated pyrethric acid alpha-cyano-4-fluoro-3-phenoxybenzyl ester and its preparation method and use
US8202904B2 (en) 2007-08-03 2012-06-19 East China Normal University α-cyano-4-fluoro-3-phenoxybenzyl meta-halo pyrethrate, a process for preparing the same and the uses thereof
WO2010086876A3 (en) * 2009-01-09 2012-10-04 Aditya Birla Science & Technology Co. Ltd. Ether synthesis
CN103420872A (en) * 2013-08-26 2013-12-04 连云港市华通化学有限公司 Preparation method of lambda-cyhalothrin
CN108124868A (en) * 2017-12-25 2018-06-08 中山市小榄企业服务有限公司 Novel biological material for preventing and treating plant diseases and insect pests and processing equipment thereof
CN117049969A (en) * 2023-07-27 2023-11-14 阜新睿光氟化学有限公司 Preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline

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