CN106588668A - 2-bromine-5-nitro-1,2,3,4-tetrahydro-1,4-methano-naphthalene-9-phenol and preparation method thereof - Google Patents
2-bromine-5-nitro-1,2,3,4-tetrahydro-1,4-methano-naphthalene-9-phenol and preparation method thereof Download PDFInfo
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- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
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- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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Abstract
The invention provides a chemical compound which can serve as an intermediate for benzovindiflupyr synthesis. The chemical compound is 2-bromine-5-nitro-1,2,3,4-tetrahydro-1,4-methano-naphthalene-9-phenol with the chemical formula as shown in formula (IV) in the specification. The invention further provides a method for preparing the chemical compound, 2-bromine-5-nitro-1,2,3,4-tetrahydro-1,4-methano-naphthalene-9-phenol. The method comprises: a chemical compound, [2,3]-epoxy-5-nitro-1,2,3,4-tetrahydro-1,4-methano-naphthalene, as shown in formula (III) reacts in a hydrobromic acid aqueous solution at 20 DEG C, and the chemical compound as shown in formula (IV) is prepared. The invention finds a novel method for producing a key intermediate for benzovindiflupyr and a preparation method thereof, thereby enabling the route for benzovindiflupyr synthesis to be more reasonable.
Description
Technical field
The present invention relates to a kind of bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- of new compound 2-
Phenol, and its preparation method and application.
Background technology
Benzo alkene fluorine bacterium azoles (benzovindiflupyr, also known as SYN545192, trade name Solatenol) are a kind of tools
There is the succinate dehydrogenase bactericide of new binding mode.Benzo alkene fluorine bacterium azoles wide spectrum, efficiently, makees with more efficient sterilization
With, foliage disease and soil surface characters can be extensively prevented and treated, it is important resistance management tool, it is in wheat, corn and extraordinary work
The outstanding prevention effect to Major Diseases is all presented on many crops such as thing.The product to wheat leaf blight, the cercospora black spot of peanut,
Take-all and wheat basal stem rot have good prevention effect, especially to wheat powdery mildew, corn southern leaf blight and gray mold
There is special efficacy, there is outstanding prevention effect to Asian Soybean Rust, be a great potential with existing bactericide no interactions resistance
Bactericide.
Benzo alkene fluorine bacterium azoles are taken the lead in the pyrazole amide series bactericidal agent developed by Syngenta Co., Ltd, and 2013, Du Pont was public
Department is also assisted in the market development of benzo alkene fluorine bacterium azoles.Now just reached and Du Pont's joint development by first.So far numerous patents are situated between
The chemical synthesis process of the benzo alkene fluorine bacterium azoles that continued, mainly there is WO2011131545, WO2011131544, WO2011131546,
WO2010049228 etc..
But the route reported at present is respectively present that yield is low, raw material is difficult to obtain, and intermediate stability is poor, operates
Complexity, severe reaction conditions, the shortcomings of be not suitable for large-scale industrial production.
The synthetic route reported in WO2011131546, is visible most short synthetic route in document so far, but
It is initiation material 6,6- dichloro fulvene is unstable, needs oneself to synthesize, thus step is still long, total recovery is than relatively low；Secondly should
Method is laboratory process, therefore is also unsuitable for large-scale industrial production.
Inventor has carried out 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids-(9- dichloromethylenes -1,2,3,4- four
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- bases)-acid amides be benzo alkene fluorine bacterium azoles chemical synthesis process exploration, there is provided Yi Zhongshou
Rate is high, and reaction condition is gentle, easy to operation, good product quality, the method for being suitable for large-scale industrial production, and this makes a living
Produce benzo alkene fluorine bacterium azoles and provide the higher selection of another kind of feasibility, and synthesized in the process in a kind of new compound
Bromo- 5- nitro -1 of mesosome 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol, intermediate may be used to synthesize benzo alkene fluorine
Bacterium azoles.
The content of the invention
The invention provides a kind of compound, can be described as the intermediate of synthesis benzo alkene fluorine bacterium azoles with the compound
Compound be bromo- 5- nitro -1 of 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol, shown in its chemical formula such as formula (IV)：
Present invention also offers one kind prepares the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- bridge methylenes of above compound 2-
The method of base-naphthalene -9- phenol, described method is compound [2,3]-epoxy -5- nitro -1 as shown in formula (III), 2,3,4-
Tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene at 20 DEG C, reacts in organic solvent in hydrobromic acid aqueous solution, and formula (IV) chemical combination is obtained
Thing.
Further, feed intake in described method material amount ratio be compound (III):Hydrobromic acid aqueous solution is 1:1-20,
Preferably 1:10, described consumption of organic solvent is 5-14 times, preferably 9 times of compound (III) quality.
Further, described hydrobromic acid aqueous solution concentration preferably 48% hydrobromic acid aqueous solution.
Further, described organic solvent be dichloromethane, ethyl acetate, tetrahydrofuran, acetonitrile, toluene or chlorobenzene, more
It is preferred that dichloromethane.
Further, described bromo- 5- nitro -1 of compound 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- are prepared
The method of phenol is：Described [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene is in 48% hydrobromic acid water
In solution, react in dichloromethane at 20 DEG C, formula (IV) compound is obtained.
In the method for preparing the described bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of compound 2--naphthalene -9- phenol
In, formula (III) compound can be obtained by following methods：5- nitro -1,4- dihydros -1,4- endo-methylene groups-naphthalene (II) and
Chloroperoxybenzoic acid, the reaction in halogenated hydrocarbon solvent generates [2,3]-epoxy -5- nitro -1, and 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene (III).The amount ratio of the material of compound (II) and metachloroperbenzoic acid is 1:1.1-1.6, preferably 1:1.5, instead
Answer solvent be dichloromethane, chloroform or, 1,2- dichloroethanes, preferably 1,2- dichloroethanes, reaction temperature is 25-80
DEG C, preferably 60 DEG C.
In the method for preparing described compound 5- nitros-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene, formula (II) chemical combination
Thing can be obtained but be not limited only to the method by following methods：2- amino -6- nitrobenzoic acids (I) and cyclopentadiene, in Asia
Under isoamyl nitrate and the concentrated sulfuric acid, the reaction in the mixed solvent of dichloromethane and acetone generates 5- nitro-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitraes-
Endo-methylene group-naphthalene (II).2- amino -6- nitrobenzoic acids (I), cyclopentadiene, feeding intake in isoamyl nitrite and the concentrated sulfuric acid
The amount ratio of material is 1:2-18:1.1-1.5:0.01, preferably 1:3:1.2:0.01.
In addition, present invention also offers bromo- 5- nitro -1 of formula (IV) compound 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group -
Naphthalene -9- phenol is in the application and preparation method for preparing benzo alkene fluorine bacterium azoles.
The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of compound 2--naphthalene -9- phenol (IV) may be used to prepare 5- ammonia
Base -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) are specific described finally to be obtained benzo alkene fluorine bacterium azoles
Formula (V) compound is with the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of the 2- shown in formula (IV) as former
Material, with Pd/C and organic base, obtains in alcoholic solvent under Hydrogen Vapor Pressure in 120 DEG C of reactions.
Described formula (IV) compound is 1 with the mass ratio of Pd/C:0.01-0.05, preferably 1:0.03, described Pd/C
Mass fraction is 5% or 10%；Described Hydrogen Vapor Pressure is 2.0MPa-3.5MPa, preferably 3.0MPa.
Further, described alcoholic solvent is absolute methanol or absolute ethyl alcohol, and described organic base is triethylamine.
Meanwhile, with bromo- 5- nitro -1 of 2- shown in formula (IV), 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol is original
Material, in addition to Pd/C, reacts in alcoholic solvent under Hydrogen Vapor Pressure with other catalyst at 120 DEG C, and formula (V) institute is also obtained
The compound for showing.Other described catalyst are Pt/C, Rh/C, Raney's nickel etc., and method is specific as follows:By formula (IV) compound and
Absolute methanol or absolute ethyl alcohol mixing after, add the catalyst such as Pd/C, Pt/C, Rh/C, Raney's nickel, under Hydrogen Vapor Pressure in
React at 120 DEG C.
Compound 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol (V) as above may be used to prepare
N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- bases -)-phthalimide (VI), finally benzene is obtained
And alkene fluorine bacterium azoles, specific described formula (VI) compound is with 5- amino -1 shown in formula (V), 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge
Methylene-naphthalene -9- phenol is raw material, reacts under high temperature fused state with phthalic anhydride and obtains.
Described formula (V) compound is 1 with the ratio of the amount of the material of phthalic anhydride:1.01-1.2, preferably 1:
1.05, described high temperature is 120 DEG C -150 DEG C, preferably 130 DEG C.
Compound N-(1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-O-phthalic as above
Acid imide (VI) may be used to prepare N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalyl
Imines (VII), finally benzo alkene fluorine bacterium azoles are obtained, specific described formula (VII) compound is with shown in formula (VI)
N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- bases -)-phthalimide is raw material, in ethyl acetate
With TCCA (TCCA), sodium bromide, 2, in 0 under the catalysis of 2,6,6- tetramethyl piperidines-nitrogen-oxide (TEMPO)
DEG C reaction generate formula (VII) shown in compound.
Described formula (VI):TEMPO:TCCA:The ratio of the amount of the material of sodium bromide is 1:0.01-0.1:1.0-1.5:0.1-
0.5, preferred proportion is compound (VI):TEMPO:TCCA:The ratio of the amount of the material of sodium bromide is 1:0.02:1.3:0.2.
Compound N-(1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-neighbour's benzene two as above
Carboximide (VII) may be used to prepare N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-neighbour
BIDA (VIII), finally benzo alkene fluorine bacterium azoles are obtained, specific described formula (VIII) compound is with formula
(VII) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalimide shown in is original
Material, reaction is generated shown in formula (VII) at 60 DEG C -65 DEG C under the protection of nitrogen with triphenylphosphine and carbon tetrachloride in acetonitrile
Compound.
Described formula (VII) is 1 with the ratio of triphenylphosphine and the amount of the material of carbon tetrachloride:3:2.
Compound N-(1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -) as above -
Phthalimide (VIII) may be used to prepare 9- (dichloro methene) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes (IX), final to use
To be obtained benzo alkene fluorine bacterium azoles, specific described formula (IX) compound be with shown in formula (VIII) N- (1,2,3,4- tetrahydrochysene-
Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5- bases -)-phthalimide be raw material, with alkaline reagent in alcoholic solvent
The reaction at 90 DEG C generates the compound shown in formula (IX).Described alcoholic solvent is methyl alcohol or ethanol, and described alkaline reagent is
40% methylamine water solution or 80% hydrazine hydrate solution.
Described formula (VIII) is 1 with the ratio of the amount of the material of alkaline reagent:1-8, preferably 1:4.
Compound 9- (dichloro methene) -1,2,3,4- tetrahydrochysenes -5- amino naphthalenes (IX) as above may be used to that benzene is obtained
And alkene fluorine bacterium azoles, specific described formula (X) compound is with the 9- (dichloro methene) -1,2,3,4- tetra- shown in formula (IX)
Hydrogen -5- amino naphthalenes are raw material, with 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- phosgenes 0 in organic solvent and triethylamine
Reaction at DEG C generates the compound shown in formula (X).Described organic solvent is ethyl acetate, butyl acetate, dichloromethane, 1,2-
Any one in dichloroethanes, toluene, dimethylbenzene or chlorobenzene, preferably dichloromethane.
Described formula (IX) is 1 with the ratio of the amount of the material of 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- phosgenes:
1.01。
Compound 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids shown in formula (X)-(9- dichloromethylene -1,2,
3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- bases)-acid amides method, comprise the steps：
1) preparation of 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol
Bromo- 5- nitro -1 of 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol are added in reactor, with anhydrous second
Alcohol or absolute methanol are solvent, add metallic catalyst I and co-catalyst II, and intensification stirring reaction 5-6 is little under Hydrogen Vapor Pressure
When, question response completely, by reacting liquid filtering, filtrate distillating recovering solvent, obtains 5- amino -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge methylene
Base-naphthalene -9- phenol, the metallic catalyst I be Pd/C, Rh/C, Pt/C or Raney's nickel etc., the co-catalyst II be triethylamine,
Any one in diisopropylethylamine or pyridine；
2) preparation of N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide
By step 1) 5- amino -1 that obtains, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol added in reactor, plus
Enter phthalic anhydride, heat up melting stirring reaction 1.5h under condition of no solvent, question response terminates, and organic solvent is added dropwise while hot
III, after being cooled to room temperature, filters, and obtains shallow white solid N- (1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5-
Base -)-phthalimide, described organic solvent II I is any one in dimethylbenzene, cyclopentanone, chlorobenzene or toluene；
3) preparation of N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalimide
By step 2) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalyl that obtains
Imines is added in reactor, with ethyl acetate as solvent, opens stirring, adds oxidant IV, sodium bromide and trichlorine different at 0 DEG C
Cyanurate, after question response terminates, saturated sodium thiosulfate solution, after stirring reaction 0.5h, reactant liquor water is added in reactor
A point liquid is washed, organic layer concentration obtains N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- carbonyl -5- bases -)-phthalyl
Imines, described oxidant IV is 2,2,6,6- tetramethyl piperidines-nitrogen-oxide or 4- hydroxyl -2,2,6,6- tetramethyl piperidines -
Any one in 1- oxygen radicals；
4) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-phthalimide
Preparation
By step 3) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-O-phthalic that obtains
Acid imide is added in reactor, with acetonitrile as solvent, adds triphenylphosphine, and after nitrogen displacement, the stirring that heats up is lower to add four chlorinations
Carbon, after question response terminates, reactant liquor concentration, in concentrate add methyl alcohol and stand refrigeration 3h after, filter, obtain N- (1,2,3,
4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-phthalimide；
5) preparation of 9- (dichloro methene) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes
By step 4) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-neighbour for obtaining
BIDA is added in reactor, and with ethanol as solvent, the stirring that heats up is lower to add alkaline reagent V, after question response terminates, instead
Liquid concentration and recovery solvent is answered, adds ethyl acetate, washing point liquid, organic layer concentration to obtain white solid 9- (dichloros in concentrate
Methene) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes, described alkaline reagent V is any in hydrazine hydrate solution or methylamine water solution
It is a kind of；
6) 3- difluoromethyls -1- methyl isophthalic acids H- pyrazoles -4- carboxylic acids-(9- dichloromethylene -1,2,3,4- tetrahydrochysene -1,4- bridges
Methylene-naphthalene -5- bases)-acid amides preparation
By step 5) tetrahydrochysene -5- amino naphthalenes of 9- (dichloro methene) -1,2,3,4- that obtain add in reactor, add molten
Agent VI and triethylamine, open stirring, and 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- phosgenes are added dropwise at 0 DEG C, and question response terminates
Afterwards, wash, point liquid, organic layer is dried, concentration obtains 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids-(9- dichloro methylenes
Base -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- bases)-acid amides, described solvent VI be ethyl acetate, butyl acetate, two
Any one in chloromethanes, 1,2- dichloroethanes, toluene, dimethylbenzene or chlorobenzene.
Wherein, step 1) described in metallic catalyst I be 5%Pd/C；The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- bridges of 2-
The mass ratio of methylene-naphthalene -9- phenol and metallic catalyst I is 1:0.01-0.05；Co-catalyst II is triethylamine；The bromo- 5- nitre of 2-
The mol ratio of base -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol and co-catalyst II is 1:2-5.
Step 1) described in Hydrogen Vapor Pressure be 2.0-3.5MPa, reaction temperature be 120 DEG C；Step 2) described in 5- ammonia
The mol ratio of base -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol and phthalic anhydride is 1:1.01-1.2, reaction temperature
Spend for 120-150 DEG C.
Step 2) described in organic solvent II I be dimethylbenzene, 5- amino -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -
The mass ratio of 9- phenol and dimethylbenzene is 1:2.
Step 3) described in oxidant IV be 2,2,6,6- tetramethyl piperidines-nitrogen-oxide, N- (1,2,3,4- tetrahydrochysene -1,
4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide and 2,2,6,6- tetramethyl piperidines-nitrogen-oxide mole
Than for 1:0.01-0.1.
Step 5) described in hydrazine hydrate solution concentration be 80%, N- (1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- two
Chloromethane thiazolinyl -5- bases -) mol ratio of-phthalimide and 80% hydrazine hydrate solution is 1:1-8, reaction temperature is 85-90
℃。
Step 5) described in methylamine water solution concentration be 40%, N- (1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- two
Chloromethane thiazolinyl -5- bases -) mol ratio of-phthalimide and 40% methylamine water solution is 1:1-8, reaction temperature is 85-90
℃。
The present invention provides the preparation of benzo alkene fluorine bacterium azoles and is prepared by following route, and reaction equation is expressed as follows：
By the way that using above-mentioned technology, compared with prior art, the contribution of the present invention is:
1) compound (III) directly obtains new compound (IV), and the change of the compound with hydrobromic acid aqueous solution reaction
Learn stable in properties, it is to avoid the presence of unstable intermediate, found it is a kind of it is new to produce benzo alkene fluorine bacterium azoles key in
Mesosome and its method for preparation, make the route of synthesis benzo alkene fluorine bacterium azoles more reasonable.
2) compound (IV) is using Pd/C catalysis reduction-debromination reactions, it is to avoid using the zinc that a large amount of solid wastes can be caused to produce
Powder, low cost, environmental friendliness.
3) in the preparation process of benzo alkene fluorine bacterium azoles, compound (V) is first protected with phthalic anhydride cheap and easy to get, last
Step reconnects expensive 1H- pyrazoles fragment, it is to avoid the waste of expensive reagent, and upper protection and the deprotection process of phthalic anhydride
Yield is high, easy to operation, and reaction condition is gentle, and good product quality is the method for being suitable for large-scale industrial production.
Specific embodiment
Illustrate technical scheme, but protection scope of the present invention not limited to this with specific embodiment below:
The synthesis of the bromo- 5- nitros-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of the 2- of embodiment 1-naphthalene-9- phenol (IV)
Feed intake material amount ratio be [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene (III):
48% hydrobromic acid aqueous solution=1:10
In the 500ml there-necked flasks equipped with mechanical agitation and thermometer, 48% hydrobromic acid aqueous solution of addition (177.2g,
1.05mol), at 20 DEG C, [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) are added dropwise
The dichloromethane solution 130ml of (14.3g, 0.07mol), after 1.5h, charging terminates, insulated and stirred 5min, is reacted with TLC tracking
Situation.After reaction terminates, a point liquid is stood, organic layer 25ml saturated sodium bicarbonate solutions are washed 2 times, then use 40ml saturated aqueous common salts
Wash once, point liquid, organic layer is dried concentration, the mixed solvent for obtaining khaki solid, crude product n-hexane and ethyl acetate is tied again
Brilliant to obtain bromo- 5- nitro -1 of white solid 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) obtain 13.1g after being dried
Compound (IV), 132.1 DEG C -133.2 DEG C of fusing point, yield 66.1%, its physicochemical data is as follows:1HNMR(d6-CDCl3)δ:7.96
(1H,dd,J1=0.97Hz, J2=8.41Hz), 7.51 (1H, d, J=7.30Hz), 7.31 (1H, dd, J1=7.37Hz, J2=
8.40Hz), 4.23 (1H, m, 1.96Hz), 4.09 (1H, s), 3.91 (1H, m, J=4.0Hz), 3.70 (1H, s), 2.77 (1H,
M, J=4.16Hz), 2.32 (1H, dd, J1=7.81Hz, J2=13.95Hz).
ESI-MS(M/Z):283,306 (M+Na)
The synthesis of the bromo- 5- nitros-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of the 2- of embodiment 2-naphthalene-9- phenol (IV)
Feed intake material amount ratio be [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene (III):
48% hydrobromic acid aqueous solution=1:5
48% hydrobromic acid aqueous solution inventory is 59.1g, and remaining inventory and operating process are with embodiment 1.Obtain the bromo- 5- of 2-
Nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 9.7g, yield 49.2%, 132.1 DEG C -133.3 of fusing point
DEG C, physicochemical data is with embodiment 1.
The synthesis of the bromo- 5- nitros-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of the 2- of embodiment 3-naphthalene-9- phenol (IV)
Feed intake material amount ratio be [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene (III):
48% hydrobromic acid aqueous solution=1:20
48% hydrobromic acid aqueous solution inventory is 236.2g, and remaining inventory and operating process are with embodiment 1.Obtain 2- bromo-
5- nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 11.8g, yield 59.6%, 132.1 DEG C of fusing point -
133.4 DEG C, physicochemical data is with embodiment 1.
The synthesis of the bromo- 5- nitros-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of the 2- of embodiment 4-naphthalene-9- phenol (IV)
Feed intake material amount ratio be [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene (III):
48% hydrobromic acid aqueous solution=1:1.
48% hydrobromic acid aqueous solution inventory is 11.8g, and remaining inventory and operating process are with embodiment 1.Obtain the bromo- 5- of 2-
Nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (IV) 4.1g, yield 20.7%, 131.9 DEG C -133.5 of fusing point
DEG C, physicochemical data is with embodiment 1.
The synthesis of [2,3]-epoxy-5- nitro-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 5-naphthalene (III)
Feed intake material amount ratio be 5- nitro -1,4- dihydros -1,4- endo-methylene groups-naphthalene (II):Metachloroperbenzoic acid=
1:1.5。
In the 1000ml there-necked flasks equipped with mechanical agitation, constant pressure funnel and thermometer, 75% m-chloro peroxide is added
Benzoic acid (86.3g, 0.375mol) and 1,2- dichloroethanes (500ml), open stirring, under room temperature, 5- nitro -1 are slowly added dropwise,
1,2- dichloroethanes (100ml) solution of 4- dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalenes (47.0g, 0.25mol), drips after 0.5h
Finish, then heat to 60 DEG C, at 60 DEG C 1.5h is stirred.After reaction terminates, 100ml saturated sodium sulfites are added in reactant liquor
Solution, after stirring 10min, filters, filtrate stratification.Organic layer saturated sodium bicarbonate solution 1000ml is washed till neutrality, then
Washed once with saturated common salt, vacuum distillation is reclaimed and obtain after 1,2- dichloroethanes [2,3]-epoxy -5- nitro -1,2,3,4- tetra-
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) 49.8g, yield 98.1%, G/C content 97.4%.[GC methods：Rich power 9790II type gas phase color
Spectrometer；Chromatographic column：SE-54；Injector：330℃；Detector：340℃；Column temperature：250℃].
The synthesis of [2,3]-epoxy-5- nitro-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 6-naphthalene (III)
Feed intake material amount ratio be 5- nitro -1,4- dihydros -1,4- endo-methylene groups-naphthalene (II):Metachloroperbenzoic acid=
1:1.1
The inventory of 75% metachloroperbenzoic acid metachloroperbenzoic acid is 63.3g, remaining inventory and operating condition
With embodiment 5, [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) 41.6g, yield are obtained
81.9%, G/C content 98.2%, vapor detection condition is with embodiment 5.
The synthesis of [2,3]-epoxy-5- nitro-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 7-naphthalene (III)
Feed intake material amount ratio be 5- nitro -1,4- dihydros -1,4- endo-methylene groups-naphthalene (II):Metachloroperbenzoic acid=
1:1.6
The inventory of 75% metachloroperbenzoic acid metachloroperbenzoic acid is 92.0g, and reaction temperature is 80 DEG C, remaining throwing
Doses and operating condition obtain [2,3]-epoxy -5- nitro -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (III) with embodiment 5
46.7g, yield 92.0%, G/C content 96.4%, vapor detection condition is with embodiment 5.
The synthesis of the 5- nitro-1,4- dihydros-1,4- endo-methylene groups of embodiment 8-naphthalene (II)
Feed intake material amount ratio be 2- amino -6- nitrobenzoic acids (I):Cyclopentadiene:Isoamyl nitrite:The concentrated sulfuric acid=
1:3:1.2:0.01
In the 500ml there-necked flasks equipped with mechanical agitation, constant pressure funnel and thermometer, 170ml dichloromethane is added
With the concentrated sulfuric acid (0.098g, 0.001mol), be added dropwise simultaneously at 40 DEG C isoamyl nitrite (14.1g, 0.12mol), 2- amino-
The acetone soln of 6- nitrobenzoic acids (18.2g, 0.1mol) and cyclopentadiene (19.8g, 0.3mol).Feed time control exists
1h, charging is warming up to 50 DEG C of stirring 3h after terminating, after reaction terminates, be cooled to room temperature, and reactant liquor is filtered with diatomite, and filtrate is dense
After contracting, with n-hexane refluxing extraction 3 times, merge n-hexane, after concentration 5- nitros-Isosorbide-5-Nitrae-dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene
(II) 14.9g, yield 74.6%, G/C content 97.3%.Vapor detection condition is with embodiment 5.
The synthesis of the 5- nitro-1,4- dihydros-1,4- endo-methylene groups of embodiment 9-naphthalene (II)
Feed intake material amount ratio be 2- amino -6- nitrobenzoic acids (I):Cyclopentadiene:Isoamyl nitrite:The concentrated sulfuric acid=
1:2:1.2:0.01
The inventory of cyclopentadiene is 13.2g, and remaining inventory and operating condition obtain 5- nitros-Isosorbide-5-Nitrae-two with embodiment 8
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (II) 11.4g, yield 60.9%, G/C content 98.4%.Vapor detection condition is with embodiment 5.
The synthesis of the 5- nitro-1,4- dihydros-1,4- endo-methylene groups of embodiment 10-naphthalene (II)
Feed intake material amount ratio be 2- amino -6- nitrobenzoic acids (I):Cyclopentadiene:Isoamyl nitrite:The concentrated sulfuric acid=
1:18:1.2:0.01
The inventory of cyclopentadiene is 118.8g, and remaining inventory and operating condition obtain 5- nitro-Isosorbide-5-Nitraes-with embodiment 8
Dihydro-Isosorbide-5-Nitrae-endo-methylene group-naphthalene (II) 14.7g, yield 70.6%, G/C content 96.8%.Vapor detection condition is with embodiment 5.
The synthesis of the 5- amino-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 11-naphthalene-9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of 2--naphthalene -9- phenol:5%Pd/C=1:
0.03, triethylamine consumption is 3 equivalents.
The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- is added in 500ml autoclaves
(2.83g, 0.01mol), catalyst 5%Pd/C 0.08g, triethylamine (3.0g, 0.03mol), absolute ethyl alcohol (300ml), in kettle
Hydrogen Vapor Pressure 3.0MPa, at 120 DEG C of temperature, stirs 5h, after raw material conversion completely, filters, and reclaims catalyst 5%Pd/C, filter
After liquid concentration, water and each 20ml of ethyl acetate are added, stirred under room temperature after 10min, stratification, organic layer is dried, concentration, obtains
5- amino -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 1.68g, yield 96.0%, G/C content 97.1%.[GC
Method：Rich power 9790II type gas chromatograph；Chromatographic column：SE-54；Injector：330℃；Detector：340℃；Column temperature：At 200 DEG C
Insulation 2min, 1 DEG C/min rise to 220 DEG C, keep 220 DEG C of 3min, and 5 DEG C/min rises to 250 DEG C, then keeps 250 DEG C of constant temperature].
The synthesis of the 5- amino-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 12-naphthalene-9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of 2--naphthalene -9- phenol:5%Pd/C=1:
0.1, triethylamine consumption is 5 equivalents.
The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- is added in 500ml autoclaves
(50.9g, 0.18mol), 5%Pd/C 0.51g, triethylamine (90.9g, 0.90mol), absolute ethyl alcohol (300ml), hydrogen in kettle
Pressure 3.5MPa, at 120 DEG C of temperature, stirs 6h, after raw material conversion completely, filters, and reclaims catalyst 5%Pd/C, and filtrate is dense
After contracting, water and each 200ml of ethyl acetate are added, stirred under room temperature after 10min, stratification, organic layer is dried, concentration, obtains 5-
Amino -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 25.2g, yield 80.0%, G/C content 93.2%.Gas phase is examined
Survey condition is with embodiment 11.
The synthesis of the 5- amino-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of embodiment 13-naphthalene-9- phenol (V)
The mass ratio that feeds intake is the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of 2--naphthalene -9- phenol:5%Pd/C=1:
0.05, triethylamine consumption is 3 equivalents.
The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- is added in 500ml autoclaves
(8.5g, 0.03mol), 5%Pd/C 0.43g, triethylamine (15.2g, 0.15mol), absolute methanol (300ml), hydrogen pressure in kettle
Power 2.0MPa, at 120 DEG C of temperature, stirs 5h, after raw material conversion completely, filters, and reclaims catalyst 5%Pd/C, filtrate concentration
Afterwards, water and each 50ml of ethyl acetate are added, is stirred under room temperature after 10min, stratification, organic layer is dried, concentration, obtains 5- ammonia
Base -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol (V) 4.9g, yield 93.3%, G/C content 92.8%.Vapor detection
Condition is with embodiment 11.
Embodiment 14N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide
(VI) synthesis.
Feed intake material amount ratio be 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol:Phthalic anhydride
=1:1.05.
Equipped with mechanical agitation, in the 500ml four-hole bottles of thermometer, 5- amino -1 is added, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (88.5g, 0.59mol) is warming up to 130 DEG C, stirs 1.5h,
Reaction terminate after, while hot be added dropwise toluene 200ml, finish, after naturally cooling to room temperature, filter, obtain N- (1,2,3,4- tetrahydrochysene -1,
4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide (VI) 167.3g, yield 96.2%, fusing point 148.9-149.7
℃。
Embodiment 15N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide
(VI) synthesis.
Feed intake material amount ratio be 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol:Phthalic anhydride
=1:1.01.
Equipped with mechanical agitation, in the 500ml four-hole bottles of thermometer, 5- amino -1 is added, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (85.8g, 0.58mol) is warming up to 150 DEG C, stirs 1.5h,
Reaction terminate after, while hot be added dropwise toluene 200ml, finish, after naturally cooling to room temperature, filter, obtain N- (1,2,3,4- tetrahydrochysene -1,
4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide (VI) 158.2g, yield 90.1%, fusing point 148.8-149.9
℃。
Embodiment 16N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide
(VI) synthesis.
Feed intake material amount ratio be 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol:Phthalic anhydride
=1:1.2.
Equipped with mechanical agitation, in the 500ml four-hole bottles of thermometer, 5- amino -1 is added, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge is sub-
Methyl-naphthalene -9- phenol (99.8g, 0.57mol), phthalic anhydride (100.6g, 0.68mol) is warming up to 120 DEG C, stirring
1.5h, after reaction terminates, is added dropwise while hot toluene 200ml, finishes, and after naturally cooling to room temperature, filters, and obtains N- (1,2,3,4- tetra-
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- bases -)-phthalimide (VI) 162.6g, yield 93.5%, fusing point 148.9-
149.9℃。
Embodiment 17N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalimide
(VII) synthesis.
Feed intake material amount ratio be N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-O-phthalic
Acid imide:TEMPO:TCCA:Sodium bromide=1:0.02:1.3:0.2
In the 500ml there-necked flasks equipped with mechanical agitation, thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- bases -)-phthalimide (10.0g, 32.8mmol) and ethyl acetate
(200ml), stirring is opened, TEMPO (0.1g, 0.65mmol), sodium bromide (0.66g, 6.5mmol), charging knot is added at 0 DEG C
Insulated and stirred 10min after beam, is then added dropwise the ethyl acetate solution (100ml) of TCCA (9.8g, 42.6mmol), charging knot after 1h
Beam, stirs 1h at 0 DEG C, after reaction terminates, saturated sodium bisulfite solution 10ml is added in reaction bulb, and under room temperature 1h is stirred,
Add water 200ml, after stirring 10min, stand a point liquid, organic layer concentration, obtain N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-
Naphthalene -9- carbonyl -5- bases -)-phthalimide (VII) 9.4g, yield 94.6%.
Embodiment 18N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-O-phthalic
The synthesis of acid imide (VIII)
Feed intake material amount ratio be N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-neighbour's benzene two
Carboximide:Triphenylphosphine:Carbon tetrachloride=1:3:2
In the 500ml there-necked flasks equipped with mechanical agitation, thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- carbonyl -5- bases -)-phthalimide (12.1g, 0.04mol), triphenylphosphine
After (31.4g, 0.12mol) and acetonitrile (100ml), nitrogen displacement three times, stirring is opened, carbon tetrachloride is added dropwise at 60 DEG C
(12.3g, 0.08mol), after completion of dropwise addition, insulated and stirred 1h, after reaction terminates, reactant liquor concentration, then add in concentrate
40ml methyl alcohol, after standing refrigeration 3h, filters, and obtains N- (1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5-
Base -)-phthalimide (VIII) 12.6g, yield 85.4%.
The synthesis of the 9- of embodiment 19 (dichloro methene) -1,2,3,4- tetrahydrochysenes -5- amino naphthalenes (IX)
Feed intake material amount ratio be N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -) -
Phthalimide:40% methylamine water solution=1:6
In the 500ml there-necked flasks equipped with mechanical agitation, thermometer and constant pressure funnel, N- (1,2,3,4- tetra- is added
Hydrogen-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- dichloro methene -5- bases -)-phthalimide (11.1g, 0.03mol) and ethanol
(100ml) 40% methylamine water solution (13.9g, 0.18mol), is added dropwise at 90 DEG C, charging terminates after 0.5h, then insulated and stirred
3h, after reaction terminates, reactant liquor concentration adds ethyl acetate (30ml) and water (50ml), point liquid, organic layer to do in concentrate
Dry, concentration, obtains tetrahydrochysene -5- amino naphthalenes (IX) 6.1g of 9- (dichloro methene) -1,2,3,4-, yield 85.1%.HPLC contents：
99.4%.[HPLC methods：Chromatographic column：XDB-C18 4.6mm×150mm×5μm；Mobile phase：Methyl alcohol：Water=65:35；Detection ripple
Long 216nm；Column temperature：30℃；Flow velocity 1.0ml/min]..
The synthesis of the 9- of embodiment 20 (dichloro methene) -1,2,3,4- tetrahydrochysenes -5- amino naphthalenes (IX)
Feed intake material amount ratio be N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -) -
Phthalimide:80% hydrazine hydrate solution=1:4
The consumption of 80% hydrazine hydrate solution is 7.4g (0.12mol), and remaining inventory and operating process are obtained with embodiment 19
Tetrahydrochysene -5- amino naphthalenes (IX) 6.3g of 9- (dichloro methene) -1,2,3,4-, yield 87.9%, HPLC contents 99.5%.Liquid phase is examined
Survey method is with embodiment 19.
3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- the carboxylic acids of embodiment 21 (9- dichloromethylene -1,2,3,4- tetrahydrochysenes -
1,4- endo-methylene groups-naphthalene -5- bases)-acid amides (IX) synthesis
Feed intake material amount ratio be 9- (dichloro methene) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes:3- difluoromethyl -1- first
Base -1H- pyrazoles -4- phosgenes:Triethylamine=1:1.01:2
In the 500ml there-necked flasks equipped with mechanical agitation, constant pressure funnel and tail gas absorber, 9- (dichloromethanes are added
Thiazolinyl) -1,2,3,4- tetrahydrochysenes -5- amino naphthalenes (23.9g, 0.1mol), dichloromethane 100ml and triethylamine (20.2g,
0.2mol), stirring is opened, 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- phosgenes is added dropwise at 0 DEG C, after charging terminates, protected
Temperature reacts complete to raw material conversion, and water 20ml is added in reaction bulb, is stirred at room temperature 10 minutes, stands a point liquid, organic layer
It is dried, concentrates, obtains 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids (9- dichloromethylene -1,2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-bridge
Methylene-naphthalene -5- bases)-acid amides (IX) 39.3g, yield 98.9%.HPLC purity (area normalization method) 98.7%, fusing point
148.7-149.2 DEG C, physicochemical data and document Tobler, H.；Walter,H.；Ehrenfreund,J.；Corsi,
C.WO2007/048556,2007(Syngenta)；Chem.Abstr.
2007,146,481833 reports are consistent.[HPLC methods：Chromatographic column：XDB-C18 4.6mm×150mm×5μm；Flowing
Phase：Acetonitrile：The phosphonic acids aqueous solution (1:1000)=70:30；Detection wavelength 255nm；Column temperature：40℃；Flow velocity 1.0ml/min].
Claims (10)
1. the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups of 2- of the chemical formula as shown in formula (IV)-naphthalene -9- phenol
2. the preparation of the bromo- 5- nitros-1,2,3,4- tetrahydrochysenes-1,4- endo-methylene groups of compound 2- described in claim 1-naphthalene-9- phenol
Method, it is characterised in that：Described method is compound [2,3]-epoxy -5- nitro -1,2,3,4- according to formula (III)
Tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene at 20 DEG C, reacts in organic solvent with hydrobromic acid aqueous solution, and formula (IV) compound is obtained
3. preparation method according to claim 2, it is characterised in that：Described hydrobromic acid aqueous solution is 48% hydrobromic acid water
Solution.
4. the preparation method according to Claims 2 or 3, it is characterised in that：Described organic solvent is dichloromethane, acetic acid
Any one in ethyl ester, tetrahydrofuran, acetonitrile or chlorobenzene.
5. the preparation method according to Claims 2 or 3 or 4, it is characterised in that：Feed intake material in described preparation method
Amount ratio is compound (III):48% hydrobromic acid aqueous solution is 1:1-20.
6. the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- described in claim 1 is being prepared such as formula
(X) the compound 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids shown in-(9- dichloromethylene -1,2,3,4- tetrahydrochysene -1,
4- endo-methylene groups-naphthalene -5- bases) application in-acid amides
7. the bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- described in claim 1 is being prepared such as formula
(X) the compound 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids shown in-(9- dichloromethylene -1,2,3,4- tetrahydrochysene -1,
4- endo-methylene groups-naphthalene -5- bases)-acid amides method, it is characterised in that：Comprise the steps：
1) preparation of 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol
By bromo- 5- nitro -1 of 2-, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol is added in reactor, with absolute ethyl alcohol or
Absolute methanol is solvent, adds metallic catalyst I and co-catalyst II, and intensification stirring reaction 5-6 hour, treats under Hydrogen Vapor Pressure
Reaction is complete, by reacting liquid filtering, filtrate distillating recovering solvent, obtains 5- amino -1, and 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -
9- phenol, the metallic catalyst I is Pd/C, Rh/C, Pt/C or Raney's nickel etc., and the co-catalyst II is triethylamine, diisopropyl
Any one in base ethamine or pyridine；
2) preparation of N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide
By step 1) 5- amino -1 that obtains, 2,3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol adds in reactor, adds adjacent
Phthalate anhydride, heat up melting stirring reaction 1.5h under condition of no solvent, and question response terminates, and organic solvent II I is added dropwise while hot,
After being cooled to room temperature, filter, obtain shallow white solid N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- phenol -5- bases -)-neighbour
BIDA, described organic solvent II I is any one in dimethylbenzene, cyclopentanone, chlorobenzene or toluene；
3) preparation of N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalimide
By step 2) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol -5- bases -)-phthalimide that obtains
In adding reactor, with ethyl acetate as solvent, stirring is opened, oxidant IV, sodium bromide and trichlorine isocyanide urea are added at 0 DEG C
Acid, after question response terminates, saturated sodium thiosulfate solution is added in reactor, after stirring reaction 0.5h, reactant liquor washing point
Liquid, organic layer concentration, obtains N- (1,2,3,4- tetrahydrochysene-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -9- carbonyl -5- bases -)-phthalimide,
Described oxidant IV is 2,2,6,6- tetramethyl piperidines-nitrogen-oxide or 4- hydroxyl -2,2,6,6- tetramethyl piperidine -1- oxygen
Any one in free radical；
4) system of N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-phthalimide
It is standby
By step 3) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- carbonyl -5- bases -)-phthalyl that obtains is sub-
Amine is added in reactor, with acetonitrile as solvent, adds triphenylphosphine, and after nitrogen displacement, the stirring that heats up is lower to add carbon tetrachloride, treats
After reaction terminates, reactant liquor concentration adds methyl alcohol in concentrate and stands after refrigeration 3h, filters, and obtains N- (1,2,3,4- tetra-
Hydrogen -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-phthalimide；
5) preparation of 9- (dichloro methene) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes
By step 4) N- (1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- dichloro methene -5- bases -)-neighbour's benzene two for obtaining
Carboximide is added in reactor, and with ethanol as solvent, the stirring that heats up is lower to add alkaline reagent V, after question response terminates, reactant liquor
Concentration and recovery solvent, adds ethyl acetate, washing point liquid, organic layer concentration to obtain white solid 9- (dichloro methylenes in concentrate
Base) -1,2,3,4- tetrahydrochysene -5- amino naphthalenes, described alkaline reagent V is any one in hydrazine hydrate solution or methylamine water solution
Kind；
6) 3- difluoromethyls -1- methyl isophthalic acids H- pyrazoles -4- carboxylic acids-(9- dichloromethylene -1,2,3,4- tetrahydrochysene -1,4- bridge methylenes
Base-naphthalene -5- bases)-acid amides preparation
By step 5) tetrahydrochysene -5- amino naphthalenes of 9- (dichloro methene) -1,2,3,4- that obtain are added in reactor, add solvent VI
And triethylamine, stirring is opened, 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- phosgenes, after question response terminates, water are added dropwise at 0 DEG C
Wash, point liquid, organic layer is dried, concentration, obtain 3- difluoromethyl -1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids-(9- dichloromethylene -1,2,
3,4- tetrahydrochysenes-Isosorbide-5-Nitrae-endo-methylene group-naphthalene -5- bases)-acid amides, described solvent VI be ethyl acetate, butyl acetate, dichloromethane,
Any one in 1,2- dichloroethanes, toluene, dimethylbenzene or chlorobenzene.
8. method according to claim 7, it is characterised in that：Step 1) described in metallic catalyst I be 5%Pd/C；2-
The mass ratio of bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol and metallic catalyst I is 1:0.01-
0.05；Co-catalyst II is triethylamine；The bromo- 5- nitros -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol of 2- and co-catalysis
The mol ratio of agent II is 1:2-5.
9. method according to claim 7, it is characterised in that：Step 1) described in Hydrogen Vapor Pressure be 2.0-3.5MPa,
Reaction temperature is 120 DEG C；Step 2) described in 5- amino -1,2,3,4- tetrahydrochysenes -1,4- endo-methylene groups-naphthalene -9- phenol and adjacent benzene two
The mol ratio of formic anhydride is 1:1.01-1.2, reaction temperature is 120-150 DEG C.
10. the preparation method of the preparation of benzo alkene fluorine bacterium azoles, it is characterised in that：Reaction equation is expressed as follows：
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| CN102858750A (en) * | 2010-04-20 | 2013-01-02 | 先正达参股股份有限公司 | Process for the preparation of pyrazole carboxylic acid amides |
| CN104926736A (en) * | 2015-05-29 | 2015-09-23 | 重庆紫光化工股份有限公司 | Synthesis methods for azoxystrobin and intermediate thereof |
| CN106588745A (en) * | 2016-12-02 | 2017-04-26 | 杭州百昂锐地科技有限公司 | Intermediate of benzovindiflupyr and preparation method and application thereof |
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| CN102858750A (en) * | 2010-04-20 | 2013-01-02 | 先正达参股股份有限公司 | Process for the preparation of pyrazole carboxylic acid amides |
| CN104926736A (en) * | 2015-05-29 | 2015-09-23 | 重庆紫光化工股份有限公司 | Synthesis methods for azoxystrobin and intermediate thereof |
| CN106588745A (en) * | 2016-12-02 | 2017-04-26 | 杭州百昂锐地科技有限公司 | Intermediate of benzovindiflupyr and preparation method and application thereof |
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| CN106588745A (en) * | 2016-12-02 | 2017-04-26 | 杭州百昂锐地科技有限公司 | Intermediate of benzovindiflupyr and preparation method and application thereof |
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