CN111454228A - Production method of isoxaflutole - Google Patents

Production method of isoxaflutole Download PDF

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CN111454228A
CN111454228A CN202010562693.9A CN202010562693A CN111454228A CN 111454228 A CN111454228 A CN 111454228A CN 202010562693 A CN202010562693 A CN 202010562693A CN 111454228 A CN111454228 A CN 111454228A
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reacting
isoxaflutole
drying
generate
acid
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袁爱桃
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Hunan Kuangchu Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
    • B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
    • B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B01J2231/4261—Heck-type, i.e. RY + C=C, in which R is aryl
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B01J2531/025—Ligands with a porphyrin ring system or analogues thereof, e.g. phthalocyanines, corroles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/842—Iron

Abstract

The invention provides a production method of isoxaflutole, which comprises the following steps: s1, generating an intermediate I by using p-bromobenzotrifluoride under the action of mixed acid of concentrated sulfuric acid and concentrated nitric acid; s2, reacting the intermediate I with vinyl methyl ether under the action of a catalyst to generate an intermediate II; s3, reacting the intermediate II with sodium methyl mercaptide to generate an intermediate III; s4, reacting the intermediate III with cyclopropane formaldehyde under an alkaline condition, and introducing oxygen to generate an intermediate VI; s5, reacting the intermediate VI with ethyl orthoformate and acetic anhydride to generate an intermediate V; s6, reacting the intermediate V with hydrochloric acid through amine and sodium acetate to generate an intermediate IV; s7, reacting the intermediate IV with m-chloroperoxybenzoic acid to generate a product isoxaflutole. The method has the advantages of few synthesis steps, mild preparation conditions, economic raw materials, high yield, suitability for industrial mass production and wide application prospect.

Description

Production method of isoxaflutole
Technical Field
The invention relates to the technical field of organic synthesis, and particularly relates to a production method of isoxaflutole.
Background
Pesticides (i.e., "pesticides"), in effect, refer to chemicals and biopharmaceuticals used to control pests (pests, mites, pathogens, weeds, rodents, etc.) that harm the production of agriculture and animal husbandry, as well as to regulate crop growth. Various aids and the like for hygiene and for improving the properties of the active ingredient are also generally included.
Isoxazole herbicides are developed by the company rona-planck, p-phenylpyruvate dioxygenase inhibitors), have a broad spectrum of herbicidal activity, and can be used both pre-and post-emergence. The isochewable contone belongs to the group consisting of p-hydroxyphenylpyruvate-dioxygenase inhibitors (HPPD inhibitors). The herbicide is used for soil treatment in dry crop fields such as corn, deer and the like, is an organic heterocyclic selective systemic pre-emergence herbicide and mainly plays a role in absorption and conduction of young roots of weeds. After the sensitive weeds are absorbed, the formation of chlorophyll can be destroyed by inhibiting the p-phytylketoprofen dioxygenase, so that the harmful weeds lose green and wither, and finally the aim of selectively weeding is fulfilled. When applied or after applied, the active ingredients retained in the surface soil due to poor soil moisture content cannot control weeds in time. But still can not be decomposed for a long time, can still play a role in preventing and removing weeds when meeting rainfall or irrigation, and has killing and inhibiting effects even on sensitive weeds growing to 4-5 leaves. The duration of the isoniazid is moderate, the half-life period in soil is short, and generally, the isoniazid basically has no residue after 4 months, so that the isoniazid has no adverse effect on rear lane crops.
The synthesis method of isoxaflutole is classified according to the oxidation sequence of methylthio, and the synthesis method comprises a pre-oxidation method and a post-oxidation method. Pre-oxidation method: oxidizing methylthio into sulfone before cyclization, firstly synthesizing cyclopropyl methyl sulfonyl trifluoromethyl phenyl) propanedione, and then obtaining the target product isoxaflutole through one step or a plurality of steps. Post-oxidation method: the method comprises the steps of firstly synthesizing cyclopropyl methylthio trifluoromethyl benzoyl isoxazole, and then oxidizing methylthio to sulfone in the last step to obtain the target product isoxaflutole.
The traditional synthetic method is not complex, has more steps and lower yield of target products, namely, the raw materials are expensive, the condition requirements are strict, the cost is high, and the method is not suitable for industrial mass production. Therefore, it is necessary to develop a synthetic method which is suitable for industrial mass production, has mild conditions, simple method, few steps and low cost.
Disclosure of Invention
The invention aims to provide a production method of isoxaflutole, which has the advantages of few synthesis steps, mild preparation conditions, economic raw materials, high yield, suitability for industrial mass production and wide application prospect.
The technical scheme of the invention is realized as follows:
the invention provides a production method of isoxaflutole, and the synthetic route of the isoxaflutole is as follows:
Figure 719676DEST_PATH_IMAGE001
。
as a further improvement of the invention, the production method comprises the following steps:
s1, under the action of mixed acid of concentrated sulfuric acid and concentrated nitric acid, para-bromobenzotrifluoride is used for generating an intermediate I, and the structural formula is as follows:
Figure 527095DEST_PATH_IMAGE002
；
s2, reacting the intermediate I with vinyl methyl ether under the action of a catalyst to generate an intermediate II, wherein the structural formula is as follows:
Figure 42521DEST_PATH_IMAGE003
；
s3, reacting the intermediate II with sodium methyl mercaptide to generate an intermediate III, wherein the structural formula is as follows:
Figure 200970DEST_PATH_IMAGE004
；
s4, reacting the intermediate III with cyclopropane formaldehyde under alkaline condition, and introducing oxygen to generate an intermediate VI, wherein the structural formula is as follows:
Figure 457114DEST_PATH_IMAGE005
；
s5, reacting the intermediate VI with ethyl orthoformate and acetic anhydride to generate an intermediate V, wherein the structural formula is as follows:
Figure 119040DEST_PATH_IMAGE006
；
S6reacting the intermediate V with hydrochloric acid through amine and sodium acetate to generate an intermediate IV, wherein the structural formula is as follows:
Figure 54635DEST_PATH_IMAGE007
；
and S7, reacting the intermediate IV with m-chloroperoxybenzoic acid to generate the product isoxaflutole.
As a further improvement of the invention, the volume ratio of the concentrated sulfuric acid to the concentrated nitric acid in the mixed acid in the step S1 is 3: 1.
As a further improvement of the invention, the catalyst in step S2 is a mixture of iron phthalocyanine and triphenylphosphine in a mass ratio of 1: 3.
As a further improvement of the invention, the alkaline condition in step S4 is the addition of KOH, NaOH or Ba (OH)2One or more of them are mixed.
As a further improvement of the invention, the production method specifically comprises the following steps:
s1, slowly adding 20-50m L mixed acid into 1mol of p-bromobenzotrifluoride dropwise, heating to 60-75 ℃, keeping the temperature for reaction for 3-5h, adding water for quenching reaction, extracting the reaction system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate I;
s2, dissolving 0.05-0.1g of catalyst and 1mol of intermediate I by using 50-100m L of dichloromethane, slowly dripping 1.1-1.2mol of vinyl methyl ether into a system, carrying out reflux reaction for 2-4h, adding water to quench the reaction, extracting the system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate II;
s3, adding 1mol of the intermediate II into 1.2-1.5mol of methylene dichloride solution of sodium methyl mercaptide 50-100m L, reacting at room temperature for 1-2h, adding water to quench the reaction, extracting the system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate III;
s4, dissolving 1mol of intermediate III and 1.1-1.2mol of cyclopropane formaldehyde in 50-100m L toluene, heating to 45-60 ℃, adding 3-5mol of KOH, NaOH or Ba (OH)2One or more of the components are mixed, stirred and reacted for 2 to 4 hours, and then slowly added into the systemIntroducing oxygen, reacting for 0.5-1.5h, adding saturated sodium bicarbonate solution, extracting the system with ethyl acetate for 3 times, combining organic phases, drying, filtering, and concentrating to obtain a solid, namely an intermediate VI;
s5, mixing 1mol of the intermediate VI, 1.1-1.2mol of ethyl orthoformate and 50-100m of L acetic anhydride, stirring, heating, refluxing, reacting for 2-4h, evaporating the mixture, adding 10-20m of L toluene, and continuously evaporating the mixture to obtain a jelly, namely an intermediate V;
s6, mixing and dissolving 1mol of the intermediate V and 50-100m L ethanol, slowly adding 0.5-0.6mol of hydrochloric acid to react with amine at room temperature for 0.5-1h, adding 0.2-0.5mol of sodium ethoxide, continuously stirring for 0.5-1h, adding 0.5-0.6mol of hydrochloric acid to react with amine and 0.2-0.5mol of sodium ethoxide, after reacting for 1-3h, extracting the organic phase for 3 times by using ethyl acetate, washing the organic phase by using a saturated sodium bicarbonate solution, drying, filtering and concentrating to obtain a solid, namely an intermediate IV;
s7, dissolving 1mol of the intermediate IV in 50-100m L dichloromethane, adding 1.1-1.3mol of m-chloroperoxybenzoic acid, reacting at (-10) - (-20) DEG C for 1-3h, heating to room temperature, reacting for 5-10h, standing for layering, extracting an aqueous layer with dichloromethane, combining organic layers, washing with 1-3 mol/L sodium bisulfite solution and water respectively, drying, filtering, concentrating to obtain a solid, and recrystallizing with diethyl ether to obtain the product isoxaflutole.
As a further improvement of the invention, the drying method is to add a drying agent into the system, repeatedly fully oscillate and then stand.
As a further improvement of the invention, the drying agent is anhydrous magnesium sulfate or anhydrous sodium sulfate.
As a further improvement of the invention, the flow rate of the oxygen is 1-2m L/min.
As a further improvement of the invention, the concentration method is heating to remove the solvent or concentrating under reduced pressure.
The invention has the following beneficial effects: compared with the traditional Heck reaction catalyst, the economical Fe is adopted to replace the traditional expensive metal Pd, so that the cost of the catalyst is greatly reduced, and the prepared catalyst is economical and has high catalytic efficiency and can effectively catalyze the Heck reaction in the synthetic route;
the method has the advantages of few synthesis steps, mild preparation conditions, economic raw materials, high yield, suitability for industrial mass production and wide application prospect.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1A Process for the production of isoxaflutole
The synthetic route is as follows:
Figure 185533DEST_PATH_IMAGE001
the method specifically comprises the following steps:
s1, slowly dropping 20m L mixed acid (the volume ratio of concentrated sulfuric acid to concentrated nitric acid is 3: 1) into 1mol of para-bromobenzotrifluoride, heating to 60 ℃, keeping the temperature for reaction for 3 hours, adding 20m L, quenching the reaction, extracting the reaction system with ethyl acetate for 3 times (100 m L each time), combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate I, wherein the structural formula is as follows:
Figure 231987DEST_PATH_IMAGE002
；
s2, dissolving 0.05g of catalyst (a mixture of iron phthalocyanine and triphenylphosphine in a mass ratio of 1: 3) and 1mol of intermediate I by using 50m L dichloromethane, slowly dripping 1.1mol of vinyl methyl ether into the system, performing reflux reaction for 2 hours, adding 50m L water to quench the reaction, extracting the system by using ethyl acetate for 3 times, each time, and each time, wherein the amount is 100m L, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate II, and the structural formula of the intermediate II is as follows:
Figure 30309DEST_PATH_IMAGE003
；
s3, adding 1mol of intermediate II into 1.2mol of methylene chloride solution of sodium methyl mercaptide 50m L, reacting at room temperature for 1h, adding 50m L, quenching the reaction, extracting the system with ethyl acetate for 3 times, each time 100m L, combining organic phases, drying, filtering and concentrating to obtain a solid which is an intermediate III and has the structural formula:
Figure 136806DEST_PATH_IMAGE004
；
s4, dissolving 1mol of intermediate III and 1.1mol of cyclopropane formaldehyde in 50m of L toluene, heating to 45 ℃, adding 3mol of KOH, stirring for reaction for 2 hours, slowly introducing oxygen into the system at a flow rate of 1m of L/min, reacting for 0.5 hour, adding 50m of L saturated sodium bicarbonate solution, extracting the system for 3 times with ethyl acetate, 100m of L each time, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate VI, wherein the structural formula is as follows:
Figure 4268DEST_PATH_IMAGE008
；
s5, mixing 1mol of the intermediate VI, 1.1mol of ethyl orthoformate and 50m of L acetic anhydride, stirring, heating, refluxing, reacting for 2 hours, evaporating the mixture to dryness, adding 10m of L toluene, and continuously evaporating the mixture to dryness to obtain a jelly which is an intermediate V and has a structural formula as follows:
Figure 605144DEST_PATH_IMAGE009
；
s6, mixing and dissolving 1mol of intermediate V and 50m L ethanol, slowly adding 0.5mol of hydrochloric acid to react with amine at room temperature for 0.5h, adding 0.2mol of sodium ethoxide, continuously stirring for 0.5h, adding 0.5mol of hydrochloric acid to react with amine and 0.2mol of sodium ethoxide, after reacting for 1h, extracting an organic phase for 3 times by using ethyl acetate, each time, the organic phase is 100m L, washing the organic phase by using 50m L saturated sodium bicarbonate solution, drying, filtering and concentrating to obtain a solid, wherein the intermediate IV is intermediate IV and has the structural formula:
Figure 241662DEST_PATH_IMAGE010
；
s7, dissolving 1mol of intermediate IV in 70m L dichloromethane, adding 1.1mol of m-chloroperoxybenzoic acid to react at (-10) DEG C for 1h, heating to room temperature to react for 5h, standing for layering, extracting an aqueous layer with 100m L dichloromethane, combining organic layers, washing with 1 mol/L sodium bisulfite solution and water respectively, drying at 100m L each time, filtering, concentrating to obtain a solid, and recrystallizing with diethyl ether to obtain the product isoxaflutole, wherein the total yield is 92%.
1HNMR（400MHz，CDCl3）：=1.17（m，2H，）1.33（m，2H），2.44（m，1H），3.27（s，1H），7.54（d，J=8.2，1H），7.95（d，J=8.2，1H），8.10（s，1H），8.35（s，1H）。
MS-EI（m/z，%）：360（M+），303（35.4），280（100）。
The compound is isoxaflutole as judged by hydrogen spectrum and mass spectrum.
The drying method in the embodiment is to add a drying agent into the system, repeatedly and fully oscillate and then stand; the drying agent is anhydrous magnesium sulfate.
The method of concentration in this example was concentration under reduced pressure.
Example 2 production method of isoxaflutole
The method specifically comprises the following steps:
s1, slowly dripping 50m L mixed acid (the volume ratio of concentrated sulfuric acid to concentrated nitric acid is 3: 1) into 1mol of para-bromobenzotrifluoride, heating to 75 ℃, keeping the temperature for reaction for 5 hours, adding 50m L to quench the reaction, extracting the reaction system with ethyl acetate for 3 times (100 m L each time), combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate I;
s2, dissolving 0.1g of catalyst (a mixture of iron phthalocyanine and triphenylphosphine in a mass ratio of 1: 3) and 1mol of intermediate I by using dichloromethane, slowly dripping 1.2mol of vinyl methyl ether into the system, refluxing for 4 hours, adding 50m L water to quench the reaction, extracting the system by using ethyl acetate for 3 times (100 m L each time), combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate II;
s3, adding 1mol of the intermediate II into 1.5mol of methylene dichloride solution of sodium methyl mercaptide 100m L, reacting for 2 hours at room temperature, adding 50m L, quenching and reacting, extracting the system with ethyl acetate for 3 times, each time 100m L, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate III;
s4, dissolving 1mol of intermediate III and 1.2mol of cyclopropane formaldehyde in 100m of L toluene, heating to 60 ℃, adding 5mol of NaOH, stirring for reaction for 4 hours, slowly introducing oxygen into the system at a flow rate of 2m L/min, reacting for 1.5 hours, adding 100m of L saturated sodium bicarbonate solution, extracting the system for 3 times with ethyl acetate, each time of 100m L, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate VI;
s5, mixing 1mol of the intermediate VI, 1.2mol of ethyl orthoformate and 100m of L acetic anhydride, stirring, heating, refluxing, reacting for 4 hours, evaporating the mixture to dryness, adding 20m of L toluene, and continuing to evaporate the mixture to dryness to obtain a jelly which is an intermediate V;
s6, mixing and dissolving 1mol of the intermediate V and 100m L ethanol, slowly adding 0.6mol of hydrochloric acid to react with amine at room temperature for 1 hour, adding 0.5mol of sodium ethoxide, continuing stirring for 1 hour, adding 0.6mol of hydrochloric acid to react with amine and 0.5mol of sodium ethoxide, after reacting for 3 hours, extracting an organic phase for 3 times by using ethyl acetate, each time for 100m L, washing the organic phase by using 100m L saturated sodium bicarbonate solution, drying, filtering and concentrating to obtain a solid, namely an intermediate IV;
s7, dissolving 1mol of intermediate IV in 100m L dichloromethane, adding 1.3mol of m-chloroperoxybenzoic acid to react at (-20) DEG C for 3h, heating to room temperature to react for 10h, standing for layering, extracting a water layer with 100m L dichloromethane, combining organic layers, washing with 3 mol/L sodium bisulfite solution and water respectively, drying at 100m L each time, filtering, concentrating to obtain a solid, and recrystallizing with diethyl ether to obtain the product isoxaflutole, wherein the total yield is 90%.
The drying method in the embodiment is to add a drying agent into the system, repeatedly and fully oscillate and then stand; the drying agent is anhydrous sodium sulfate.
The method of concentration in this example was to remove the solvent by heating.
Example 3 Process for the production of isoxaflutole
The method specifically comprises the following steps:
s1, slowly dripping 35m L mixed acid (the volume ratio of concentrated sulfuric acid to concentrated nitric acid is 3: 1) into 1mol of para-bromobenzotrifluoride, heating to 68 ℃, keeping the temperature for reaction for 4 hours, adding 50m L to quench the reaction, extracting the reaction system with ethyl acetate for 3 times, each time being 100m L, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate I;
s2, dissolving 0.07g of catalyst (a mixture of iron phthalocyanine and triphenylphosphine in a mass ratio of 1: 3) and 1mol of intermediate I by using 70m L dichloromethane, slowly dripping 1.15mol of vinyl methyl ether into the system, performing reflux reaction for 3 hours, adding 50m L water to quench the reaction, extracting the system by using ethyl acetate for 3 times, each time, and each time, wherein 100m L is obtained, and combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate II;
s3, adding 1mol of the intermediate II into 1.35mol of methylene chloride solution of sodium methyl mercaptide 70m L, reacting at room temperature for 1.5h, adding 50m L, quenching with water, extracting the system with ethyl acetate for 3 times, each time for 100m L, combining organic phases, drying, filtering, and concentrating to obtain a solid, namely an intermediate III;
s4, 1mol of intermediate III and 1.15mol of cyclopropane-carboxaldehyde are dissolved in 70m L toluene, heated to 52 ℃, and 4mol of Ba (OH) are added2After stirring and reacting for 3 hours, slowly introducing oxygen into the system at the flow rate of 1.5m L/min, after reacting for 1 hour, adding 100m L saturated sodium bicarbonate solution, extracting the system with ethyl acetate for 3 times, each time 100m L, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate VI;
s5, mixing 1mol of the intermediate VI, 1.15mol of ethyl orthoformate and 70m of L acetic anhydride, stirring, heating, refluxing, reacting for 3 hours, evaporating the mixture to dryness, adding 15m of L toluene, and continuing to evaporate the mixture to dryness to obtain a jelly which is an intermediate V;
s6, mixing and dissolving 1mol of the intermediate V and 70m L ethanol, slowly adding 0.55mol of hydrochloric acid to react with amine at room temperature for 0.75h, adding 0.35mol of sodium ethoxide, continuously stirring for 0.75h, adding 0.55mol of hydrochloric acid to react with amine and 0.35mol of sodium ethoxide, after reacting for 2h, extracting an organic phase for 3 times by using ethyl acetate, each time, the organic phase is 100m L, washing the organic phase by using 100m L saturated sodium bicarbonate solution, drying, filtering and concentrating to obtain a solid, wherein the solid is an intermediate IV;
s7, dissolving 1mol of intermediate IV in 70m L dichloromethane, adding 1.2mol of m-chloroperoxybenzoic acid to react at (-15) DEG C for 2h, heating to room temperature to react for 7h, standing for layering, extracting a water layer with 100m L dichloromethane, combining organic layers, washing with 2 mol/L sodium bisulfite solution and water respectively, drying at 100m L each time, filtering, concentrating to obtain a solid, and recrystallizing with diethyl ether to obtain the product isoxaflutole with the total yield of 94%.
The drying method in the embodiment is to add a drying agent into the system, repeatedly and fully oscillate and then stand; the drying agent is anhydrous sodium sulfate.
The method of concentration in this example was concentration under reduced pressure.
Example 4 preparation of isoxaflutole suspension
The raw materials comprise: 20wt% of isoxaflutole, 5wt% of calcium stearate, 3wt% of Triton X305 (available from Dow chemical), 2wt% of magnesium stearate, 12wt% of xanthan gum, 15wt% of magnesium aluminum silicate and 43wt% of deionized water.
The preparation method comprises the following steps:
s1, adding calcium stearate, Triton X305 and magnesium stearate into deionized water, and fully and uniformly stirring to obtain a solution A;
s2, adding the prepared isoxaflutole into the solution A, adding xanthan gum and magnesium aluminum silicate after stirring, placing the mixture into a high-shear emulsifying machine, carrying out high-speed shearing and homogenizing emulsification, rotating at 10000r/min, grinding the homogenized and emulsified material in a grinding machine after the emulsification is finished, adding zirconium silicate beads into a grinding tank, adding zirconium beads according to the weight of 1.2 times of the material, grinding for 1h, introducing cooling circulating water, controlling the grinding temperature not to exceed 35 ℃ until the number of suspended particles with the particle size of 0.1-0.7 mu m reaches more than 98%, stopping grinding, placing the mixture into a stirrer, and mixing uniformly to obtain the isoxaflutole suspending agent.
Test example 1 Pre-emergent herbicidal action on harmful plants
Seeds of monocotyledonous and dicotyledonous weeds or crop plants are placed in sandy loam in lignocellulosic pots and covered with soil. The isoxaflutole suspension prepared in example 4 was then applied to the surface of a soil cover at an application rate of 600-. After treatment, the pots were placed in a greenhouse and kept under good growth conditions for the test plants. After a test period of 3 weeks, the degree of damage of the test plants was assessed visually by comparison with untreated controls (herbicidal activity in% 100% activity-plant death, 0% activity-analogous to control plants). At an application rate of 100 g/ha, at least 95% activity against abutilon (Abutilontheophilsta), Amaranthus retroflexus (Amaranthus retroflexus) and Echinochloa crus galli (Echinochloa crus galli). At an application rate of 120 g/ha, has at least 95% activity on green bristlegrass (Setaria viridis) and chickweed (Stellaria media).
Test example 2 post-emergence herbicidal action on harmful plants
Seeds of monocotyledonous and dicotyledonous weeds or crop plants are placed in sandy loam in lignocellulosic pots, covered with soil, and grown in the greenhouse under good growth conditions. After 2 to 3 weeks of sowing, the test plants are treated at the single-leaf stage. The isoxaflutole suspension prepared in example 4 was then sprayed onto green plant parts at an application rate of 600-. After the test plants have been kept in the greenhouse under optimum growth conditions for about 3 weeks, the activity of the formulations is assessed visually by comparison with untreated controls (herbicidal activity in percent (%): 100% activity is plant dead and 0% activity is similar to control plants). At an application rate of 55 g/ha, at least 90% activity on green bristlegrass, chickweed and pansy (Viola tricolor). At an application rate of 60 g/ha, at least 95% activity against abutilon, amaranthus retroflexus and cockspur grass.
Compared with the prior art, the catalyst prepared by the invention adopts economical Fe to replace the traditional expensive metal Pd in comparison with the traditional Heck reaction catalyst, so that the catalyst cost is greatly reduced, and the prepared catalyst is economical and has high catalytic efficiency and can effectively catalyze the Heck reaction in the synthetic route;
the method has the advantages of few synthesis steps, mild preparation conditions, economic raw materials, high yield, suitability for industrial mass production and wide application prospect.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims (9)

1. The production method of isoxaflutole is characterized in that the synthetic route of isoxaflutole is as follows:
Figure 682232DEST_PATH_IMAGE001
(ii) a The catalyst is a mixture of iron phthalocyanine and triphenylphosphine, and the mass ratio of the iron phthalocyanine to the triphenylphosphine is 1: 3.
2. The process for the production of isoxaflutole according to claim 1, wherein said process comprises the steps of:
s1, under the action of mixed acid of concentrated sulfuric acid and concentrated nitric acid, para-bromobenzotrifluoride is used for generating an intermediate I, and the structural formula is as follows:
Figure 147849DEST_PATH_IMAGE002
；
s2, reacting the intermediate I with vinyl methyl ether under the action of a catalyst to generate an intermediate II, wherein the structural formula is as follows:
Figure 203529DEST_PATH_IMAGE003
；
s3, reacting the intermediate II with sodium methyl mercaptide to generate an intermediate III, wherein the structural formula is as follows:
Figure 285755DEST_PATH_IMAGE004
；
s4, reacting the intermediate III with cyclopropane formaldehyde under alkaline condition, and introducing oxygen to generate an intermediate VI, wherein the structural formula is as follows:
Figure 85084DEST_PATH_IMAGE005
；
s5, reacting the intermediate VI with ethyl orthoformate and acetic anhydride to generate an intermediate V, wherein the structural formula is as follows:
Figure 936365DEST_PATH_IMAGE006
；
s6, reacting the intermediate V with hydrochloric acid through amine and sodium acetate to generate an intermediate IV, wherein the structural formula is as follows:
Figure 428526DEST_PATH_IMAGE007
；
and S7, reacting the intermediate IV with m-chloroperoxybenzoic acid to generate the product isoxaflutole.
3. The process of producing isoxaflutole according to claim 2, wherein the volume ratio of concentrated sulfuric acid to concentrated nitric acid in the mixed acid in step S1 is 3: 1.
4. The process for producing isoxaflutole according to claim 2, wherein the alkaline condition in step S4 is the addition of KOH, NaOH or Ba (OH)2One or more of them are mixed.
5. The production method of isoxaflutole according to claim 2, characterized in that the production method specifically comprises the following steps:
s1, slowly adding 20-50m L mixed acid into 1mol of p-bromobenzotrifluoride dropwise, heating to 60-75 ℃, keeping the temperature for reaction for 3-5h, adding water for quenching reaction, extracting the reaction system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate I;
s2, dissolving 0.05-0.1g of catalyst and 1mol of intermediate I by using 50-100m L of dichloromethane, slowly dripping 1.1-1.2mol of vinyl methyl ether into a system, carrying out reflux reaction for 2-4h, adding water to quench the reaction, extracting the system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain an oily substance which is an intermediate II;
s3, adding 1mol of the intermediate II into 1.2-1.5mol of methylene dichloride solution of sodium methyl mercaptide 50-100m L, reacting at room temperature for 1-2h, adding water to quench the reaction, extracting the system for 3 times by using ethyl acetate, combining organic phases, drying, filtering and concentrating to obtain a solid, namely an intermediate III;
s4, dissolving 1mol of intermediate III and 1.1-1.2mol of cyclopropane formaldehyde in 50-100m L toluene, heating to 45-60 ℃, adding 3-5mol of KOH, NaOH or Ba (OH)2Mixing one or more of the above, reacting for 2-4h under stirring, slowly introducing oxygen into the system, reacting for 0.5-1.5h, adding saturated sodium bicarbonate solution, extracting the system with ethyl acetate for 3 times, mixing the organic phases, drying, filtering, and concentrating to obtain solid as intermediate VI;
s5, mixing 1mol of the intermediate VI, 1.1-1.2mol of ethyl orthoformate and 50-100m of L acetic anhydride, stirring, heating, refluxing, reacting for 2-4h, evaporating the mixture, adding 10-20m of L toluene, and continuously evaporating the mixture to obtain a jelly, namely an intermediate V;
s6, mixing and dissolving 1mol of the intermediate V and 50-100m L ethanol, slowly adding 0.5-0.6mol of hydrochloric acid to react with amine at room temperature for 0.5-1h, adding 0.2-0.5mol of sodium ethoxide, continuously stirring for 0.5-1h, adding 0.5-0.6mol of hydrochloric acid to react with amine and 0.2-0.5mol of sodium ethoxide, after reacting for 1-3h, extracting the organic phase for 3 times by using ethyl acetate, washing the organic phase by using a saturated sodium bicarbonate solution, drying, filtering and concentrating to obtain a solid, namely an intermediate IV;
s7, dissolving 1mol of the intermediate IV in 50-100m L dichloromethane, adding 1.1-1.3mol of m-chloroperoxybenzoic acid, reacting at (-10) - (-20) DEG C for 1-3h, heating to room temperature, reacting for 5-10h, standing for layering, extracting an aqueous layer with dichloromethane, combining organic layers, washing with 1-3 mol/L sodium bisulfite solution and water respectively, drying, filtering, concentrating to obtain a solid, and recrystallizing with diethyl ether to obtain the product isoxaflutole.
6. The method for producing isoxaflutole according to claim 5, wherein the drying method comprises adding a drying agent to the system, shaking repeatedly and fully, and standing.
7. The process for the production of isoxaflutole according to claim 6, wherein the drying agent is anhydrous magnesium sulfate or anhydrous sodium sulfate.
8. The process for the production of isoxaflutole according to claim 5, wherein the flow rate of oxygen is from 1 to 2m L/min.
9. The process for the production of isoxaflutole according to claim 5, wherein the concentration is carried out by heating to remove the solvent or concentrating under reduced pressure.
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