CN108658735A - A kind of Isosorbide-5-Nitrae-is bis-（Difluorophenoxymethyl）The synthetic method of benzene - Google Patents
A kind of Isosorbide-5-Nitrae-is bis-（Difluorophenoxymethyl）The synthetic method of benzene Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
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Abstract
The present invention provides a kind of synthetic methods of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae, include the following steps：(1) using bis- (difluoromethyl) benzene of Isosorbide-5-Nitrae as starting material, bis- (chlorodifluoramethyl-) benzene of Isosorbide-5-Nitrae are obtained by free radical substitution reaction under radical initiator effect with chlorine；(2) intermediate 1,4 bis- (chlorodifluoramethyl-) benzene are without refined, in organic solvent, directly carry out unimolecule free radical nucleophilic substitution with alkali, phenol, gained crude product is by being recrystallized to give bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae.This method reaction condition is mild, and products therefrom yield and purity are all higher, is suitable for large-scale production.
Description
Technical field
The invention belongs to organic chemical synthesis field, more particularly to the synthesis of a kind of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-
Method.
Background technology
Parylene series thin films, also known as parylene film, Chinese Parylene are advanced in the world today
A kind of coating material, it is polymerized by paraxylene ring disome and its derivative by vacuum vapor deposition.It is because with good
Good chemical stability, biocompatibility, the characteristics such as outstanding mechanical, electrical, hot property and moisture-proof, mould proof, anti-salt and extensive use
In numerous areas such as aerospace, military weapon, biological medicine, microelectromechanical systems and historical relic's protections.Parylene HT are thin
Film is the newest commercially produced product in Parylene series thin films, is state-of-the-art one kind coating material in the world today.Tool
Have the advantages that outside good chemical stability, biocompatibility, thermal stability possessed by other films, Parylene HT are thin
Film also has the advantages that lower dielectric constant, better heat-resisting ability, stronger anti-uv-ray, is suitable as high frequency
The protective materials of microwave device.Bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-can be as the presoma of Parylene HT, Neng Goutong
It crosses chemical vapour deposition technique and prepares Parylene HT films.
Currently, bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-can be synthesized by the following method：
《Chemical Vapor Deposition》, 327-331 pages of volume 19 (2013) report, Senkevich et al. with
Terephthaldehyde's diphenyl phthalate is raw material, and bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-have been synthesized by two-step reaction.Synthetic route is such as
Shown in lower：
This route can synthesize to obtain bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-, but the route reaction overlong time, institute
Reagent is needed also costly, to be not suitable for mass producing.
《Journal of Fluorine Chemistry》, 991-993 pages of volume 129 (2008), Dolbier et al. makes
It is raw material with bis- (chlorodifluoramethyl-) benzene of bis-phenol, Isosorbide-5-Nitrae-, sodium hydride, hexamethylphosphoramide carries out unimolecule freedom as solvent
Base nucleophilic substitution synthesizes polymer.Synthetic route is as shown below：
Such unimolecule free radical nucleophilic substitution can be used for synthesizing bis- (chlorodifluoramethyl-) benzene of Isosorbide-5-Nitrae-, but purity
The price of higher bis- (chlorodifluoramethyl-) benzene of Isosorbide-5-Nitrae-is more expensive, and the sodium hydride danger used in reaction is also larger, operates
Inconvenience is not suitable for industrialized production.
Invention content
Goal of the invention：The present invention provides that a kind of reaction time is short, low in raw material price, the bis- (difluoros of easy to operate Isosorbide-5-Nitrae-
Phenoxymethyl) benzene synthetic method.
Technical solution：The synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-of the present invention, includes the following steps：
(1) using bis- (difluoromethyl) benzene of 1.4- as starting material, under UV illumination, with chlorine in radical initiator
It is organic molten to be dried and evaporated removing using anhydrous magnesium sulfate for heating reflux reaction, washed reaction liquid in organic solvent under effect
Agent obtains bis- (chlorodifluoramethyl-) the benzene crude products of Isosorbide-5-Nitrae-；
(2) bis- (chlorodifluoramethyl-) the benzene crude products of Isosorbide-5-Nitrae-obtained the step (1) in organic solvent directly with alkali,
Phenol carries out unimolecule free radical nucleophilic substitution together, and gained crude product obtains Isosorbide-5-Nitrae-bis- (two after recrystallization is handled
Fluorophenoxymethyl) benzene.
Further, in the method for the present invention, organic solvent in step (1) be carbon tetrachloride, chloroform, chlorobenzene, trichloro-benzenes,
Monobromo-benzene or dibromobenzene, most preferably carbon tetrachloride.
Further, in the method for the present invention, the radical initiator in step (1) is benzoyl peroxide, peroxidating ten
Two acyls, the peroxidating trimethylacetic acid tert-butyl ester or azodiisobutyronitrile；The radical initiator and bis- (difluoromethyl) benzene of Isosorbide-5-Nitrae-
Mass ratio is (0.05-0.2): 1.
Further, in the method for the present invention, the temperature of heating reflux reaction is 60-100 DEG C in step (1), preferably 70-
80℃。
Further, in the method for the present invention, phenol, alkali in step (2) are bis- with starting material Isosorbide-5-Nitrae-in step (1)
The molar ratio of (difluoromethyl) is (1.2-1.6): (4.8-8): 1.
Further, in the method for the present invention, the alkali in step (2) is sodium methoxide, sodium hydroxide, potassium hydroxide, sodium carbonate
Or sodium bicarbonate；Most preferably sodium methoxide.
Further, in the method for the present invention, the organic solvent in step (2) is N-Methyl pyrrolidone, N, N- dimethyl
Formamide or sulfolane；Organic solvent and bis- (difluoromethyl) benzene of starting material Isosorbide-5-Nitrae-in step (1) in the step (2)
Mass ratio is (5-20): 1, preferably 15: 1.
Further, in the method for the present invention, the temperature of unimolecule free radical nucleophilic substitution is 80- in step (2)
140 DEG C, preferably 100-120 DEG C.
Further, in the method for the present invention, in step (2) in recrystallization process using ethyl acetate, petroleum ether, ethyl alcohol,
The mixing of one or more of dichloromethane, toluene is as solvent；The volume of recrystallization solvent needed for every gram of crude product is 5-
20ml。
Advantageous effect：Compared with prior art, the present invention haing the following advantages：
The synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-provided by the invention cheap, yield with cost of material
High, the advantages that reaction time is short, easy to operate, it is suitable for industrialized production.
Specifically, the method for the present invention has advantage following prominent compared with the existing technology：
(1) bis- (chlorine of Isosorbide-5-Nitrae-that bis- (difluoromethyl) benzene of chlorination reaction raw material Isosorbide-5-Nitrae-are moderate, are obtained by chlorination reaction
Difluoromethyl) benzene only needs easy post-processing, may participate in second step without specially treated reacts；
(2) nucleophilic substitution mild condition, cost of material are cheap, the reaction time is short, easy to operate, post-processing is simple.
Specific implementation mode
Below in conjunction with specific embodiment, exemplary illustration and help further understand essence of the invention, but embodiment is specific
Details does not represent whole technical solutions under present inventive concept, therefore should not be construed as to this hair merely to illustrate the present invention
Bright total technical solution limits, some increase or change, example for the technician, without departing from the unsubstantiality of present inventive concept
Such as simply change or replace with the technical characteristic with same or similar technique effect, belongs to the scope of the present invention.
Embodiment 1
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.25g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.07g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.07g, 3.17g benzene are added into flask
Phenol, 9.10g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.78g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.84g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 47.6%, purity 97.3% (GC).
Embodiment 2
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL chloroforms, 1 g dilauroyl peroxides, displacement are added into three-necked flask
Chlorine is blasted after air, and 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, blast in nitrogen displacement reaction solution
The chlorine of dissolving.After the completion of gas displacement, washing organic phase is until neutral.It is removed using hypo solution washing organic phase
Benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate dries organic phase.
It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.35g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene product and slightly produce
Product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.35g, 3.17g benzene are added into flask
Phenol, 9.10g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 24.78g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.89g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 48.1%, purity 97.0% (GC).
Embodiment 3
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL trichloro-benzenes, 0.5g peroxidating trimethylacetic acid uncles are added into three-necked flask
Butyl ester blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, blasts nitrogen and set
Change the chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.It is washed using hypo solution
Organic phase removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dry
Dry organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.98g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s)
Benzene product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.98g, 3.17g benzene are added into flask
Phenol, 9.10g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 25.66g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.51g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 44.3%, purity 96.7% (GC).
Embodiment 4
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL monobromo-benzenes, two isobutyl of 0.75g azos are added into three-necked flask
Nitrile blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.45g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.45g, 3.17g benzene are added into flask
Phenol, 9.10g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 20.13g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.28g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 42.1%, purity 96.4% (GC).
Embodiment 5
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.65g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.65g, 4.23g benzene are added into flask
Phenol, 7.28g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.23g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.08g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 40.1%, purity 97.4% (GC).
Embodiment 6
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.03g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.03g, 3.70g benzene are added into flask
Phenol, 12.13g sodium methoxides, 25g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 27.21g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.28g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 40.1%, purity 97.1% (GC).
Embodiment 7
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.22g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.22g, 3.70g benzene are added into flask
Phenol, 6.74g sodium hydroxides, 100g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will
Reaction solution instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.41g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 3.92g white crystals 1,
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 4-, yield 38.5%, purity 97.1% (GC).
Embodiment 8
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.27g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.27g, 3.70g benzene are added into flask
Phenol, 9.45g potassium hydroxide, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will
Reaction solution instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 19.51g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 3.98g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 39.1%, purity 96.2% (GC).
Embodiment 9
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.98g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.98g, 3.70g benzene are added into flask
Phenol, 17.85g sodium carbonate, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.65g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 3.08g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 30.3%, purity 96.7% (GC).
Embodiment 10
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.79g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.98g, 3.70g benzene are added into flask
Phenol, 14.15g sodium bicarbonates, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will
Reaction solution instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.67g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 2.77g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 27.2%, purity 96.5% (GC).
Embodiment 11
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 60 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.33g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.33g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 80 DEG C.After reaction, it is down to room temperature, will be reacted
Liquid instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It filters,
It is washed to washing lotion to be in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, crude product is obtained
27.67g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.28g white crystals 1,
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 4-, yield 42.1%, purity 98.5% (GC).
Embodiment 12
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 100 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.35g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.35g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 140 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 27.67g is recrystallized using 250ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 4.50g white crystals
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 44.2%, purity 98.7% (GC).
Embodiment 13
50g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 500mL carbon tetrachloride, 7.5g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 103.75g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s)
Benzene product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 103.75g, 37.0 g benzene are added into flask
Phenol, 91.0g sodium methoxides, 750g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 248.67g is recrystallized using 2500ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 49.53g white knots
Brilliant bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 48.7%, purity 99.1% (GC).
Embodiment 14
100g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 1000mL carbon tetrachloride, 15g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 254.78g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s)
Benzene product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 254.78g, 74.0 g benzene are added into flask
Phenol, 182.0g sodium methoxides, 1500g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will
Reaction solution instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 565.78g is recrystallized using 5000ml ethyl acetate, petroleum ether mixed solvent (V: V=2: 1), obtains 101.90g white knots
Brilliant bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 50.1%, purity 98.1% (GC).
Embodiment 15
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.35g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.35g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 24.64g is recrystallized using 250ml ethyl acetate solvents, obtains 2.76g white crystals Isosorbide-5-Nitrae-bis- (difluoromethoxy phenyl oxygen
Base) methylbenzene material, yield 27.1%, purity 90.7% (GC).
Embodiment 16
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.35g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.35g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 22.56g is recrystallized using 250ml petroleum ether solvents, and it is bis- (difluoro-methoxy phenoxy group) to obtain 3.06g white crystals Isosorbide-5-Nitrae-
Methylbenzene material, yield 30.1%, purity 89.7% (GC).
Embodiment 17
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.35g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.35g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.47g is recrystallized using 250ml alcohol solvents, obtains bis- (difluoro-methoxy phenoxy group) first of 2.76g white crystals Isosorbide-5-Nitrae-
Base benzene product, yield 27.1%, purity 85.1% (GC).
Embodiment 18
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.40g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.40g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.08g is recrystallized using 250ml dichloromethane solvents, obtains 1.33g white crystals Isosorbide-5-Nitrae-bis- (difluoromethoxy phenyl oxygen
Base) methylbenzene material, yield 13.1%, purity 80.2% (GC).
Embodiment 19
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.99g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.99g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.28g is recrystallized using 250ml toluene solvants, obtains bis- (difluoro-methoxy phenoxy group) first of 1.74g white crystals Isosorbide-5-Nitrae-
Base benzene product, yield 17.1%, purity 77.2% (GC).
Embodiment 20
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.78g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.78g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 24.29g is recrystallized using 250ml ethyl alcohol, petroleum ether mixed solvent (V: V=2: 1), obtains 4.76g white crystals Isosorbide-5-Nitrae-
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials, yield 46.8%, purity 97.2% (GC).
Embodiment 21
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.32g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.32g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.05g is recrystallized using 250ml dichloromethane, toluene Mixed Solvent (V: V=2: 1), obtains 2.39g white crystals 1,
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 4-, yield 23.3%, purity 90.2% (GC).
Embodiment 22
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.04g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.04g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 23.05g is recrystallized using 250ml toluene, petroleum ether mixed solvent (V: V=2: 1), obtains 4.12g white crystals Isosorbide-5-Nitrae-
Bis- (difluoro-methoxy phenoxy group) methylbenzene materials, yield 38.5%, purity 93.5% (GC).
Embodiment 23
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.25g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.25g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 24.25g is recrystallized using 250ml ethyl acetate, ethyl alcohol, petroleum ether mixed solvent (V: V: V=1: 1: 1), obtains 4.35g
White crystals Isosorbide-5-Nitrae-bis- (difluoro-methoxy phenoxy group) methylbenzene material, yield 40.6%, purity 95.5% (GC).
Embodiment 24
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.05g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.25g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.36g is recrystallized using 250ml dichloromethane, toluene, alcohol mixed solvent (V: V: V=1: 1: 1), it is white to obtain 1.63g
Color crystallizes bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 15.2%, purity 85.2% (GC).
Embodiment 25
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.95g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.95g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.36g is recrystallized using 250ml dichloromethane, toluene, alcohol mixed solvent (V: V: V=1: 1: 1), it is white to obtain 1.63g
Color crystallizes bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 15.2%, purity 85.2% (GC).
Embodiment 26
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 8.99g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 8.99g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.36g is recrystallized using 250ml ethyl acetate, petroleum ether, alcohol mixed solvent (V: V: V=1: 1: 1), obtains 4.35g
White crystals Isosorbide-5-Nitrae-bis- (difluoro-methoxy phenoxy group) methylbenzene material, yield 42.7%, purity 93.5% (GC).
Embodiment 27
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.17g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, be added into flask bis- (chlorodifluoramethyl-) the benzene crude products of 9.17 above-mentioned Isosorbide-5-Nitraes-, 3.70g phenol,
9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, by reaction solution
It instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It filters, water
It is washed till washing lotion to be in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, crude product is obtained
21.36g is recrystallized using 250ml ethyl acetate, petroleum ether, toluene Mixed Solvent (V: V: V=1: 1: 1), it is white to obtain 3.98g
Color crystallizes bis- (difluoro-methoxy phenoxy group) methylbenzene materials of Isosorbide-5-Nitrae-, yield 39.1%, purity 92.3% (GC).
Embodiment 28
5.0g1, bis- (difluoromethyl) benzene of 4-, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.32g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, be added into flask bis- (chlorodifluoramethyl-) the benzene crude products of 9.32 above-mentioned Isosorbide-5-Nitraes-, 3.70g phenol,
9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, by reaction solution
It instills in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It filters, water
It is washed till washing lotion to be in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, crude product is obtained
21.36g is tied again using 250ml ethyl acetate, petroleum ether, toluene, dichloromethane mixed solvent (V: V: V: V=1: 1: 1: 1)
Crystalline substance obtains bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 3.98g white crystals Isosorbide-5-Nitrae-, yield 39.1%, purity 92.3%
(GC)。
Embodiment 29
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.25g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.25g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.36g is recrystallized using 250ml ethyl acetate, petroleum ether, toluene, alcohol mixed solvent (V: V: V: V=1: 1: 1: 1),
Obtain bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 3.68g white crystals Isosorbide-5-Nitrae-, yield 36.2%, purity 91.5%
(GC)。
Embodiment 30
5.0g Isosorbide-5-Nitraes-bis- (difluoromethyls) benzene, 50mL carbon tetrachloride, 0.75g benzoyl peroxide first are added into three-necked flask
Acyl blasts chlorine after displaced air, 9h is stirred to react at 80 DEG C.After the completion of thin-layer chromatography monitoring reaction, nitrogen displacement is blasted
The chlorine dissolved in reaction solution.After the completion of gas displacement, washing organic phase is until neutral.Had using hypo solution washing
Machine mutually removes benzoyl peroxide, until starch potassium iodide paper is non-discolouring.Organic phase is separated, is washed 3 times.Anhydrous magnesium sulfate is dried
Organic phase.It is filtered to remove anhydrous magnesium sulfate, decompression boils off solvent, obtains 9.36g colorless oils Isosorbide-5-Nitrae-bis- (chlorodifluoramethyl-s) benzene
Product crude product.
Under nitrogen atmosphere, bis- (chlorodifluoramethyl-) the benzene crude products of the above-mentioned Isosorbide-5-Nitraes-of 9.36g, 3.70g benzene are added into flask
Phenol, 9.10g sodium methoxides, 75g N-Methyl pyrrolidones are stirred to react 8h in 100 DEG C.After reaction, it is down to room temperature, it will be anti-
It answers liquid to instill in deionized water dropwise, adjusts pH to 1-2 using 1mol/L dilute hydrochloric acid, a large amount of floccules are precipitated, stand 1h.It takes out
Filter, is washed to washing lotion and is in neutrality, gained khaki solid product is placed in 60 DEG C of air dry ovens and is dried overnight, is slightly produced
Product 21.36g uses 250ml ethyl acetate, petroleum ether, toluene, ethyl alcohol, dichloromethane mixed solvent (V: V: V: V: V=1: 1: 1
: 1: 1) it recrystallizes, obtains bis- (difluoro-methoxy phenoxy group) methylbenzene materials of 3.74g white crystals Isosorbide-5-Nitrae-, yield 36.8%,
Purity 90.1% (GC).
Claims (9)
1. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-, which is characterized in that this approach includes the following steps：
(1) it using bis- (difluoromethyl) benzene of 1.4- as starting material, under UV illumination, is acted in radical initiator with chlorine
Under in organic solvent heating reflux reaction, washed reaction liquid be dried and evaporated removing organic solvent using anhydrous magnesium sulfate, obtain
To bis- (chlorodifluoramethyl-) the benzene crude products of Isosorbide-5-Nitrae-；
(2) bis- (chlorodifluoramethyl-) the benzene crude products of Isosorbide-5-Nitrae-obtained the step (1) in organic solvent directly with alkali, phenol
Unimolecule free radical nucleophilic substitution is carried out together, and gained crude product obtains the bis- (difluorobenzenes of Isosorbide-5-Nitrae-after recrystallization is handled
Oxygroup methyl) benzene.
2. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1, which is characterized in that institute
It is carbon tetrachloride, chloroform, chlorobenzene, trichloro-benzenes, monobromo-benzene or dibromobenzene to state the organic solvent in step (1).
3. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1, which is characterized in that institute
It is benzoyl peroxide, dilauroyl peroxide, the peroxidating trimethylacetic acid tert-butyl ester or azo to state the radical initiator in step (1)
Bis-isobutyronitrile；The mass ratio of the radical initiator and bis- (difluoromethyl) benzene of Isosorbide-5-Nitrae-is (0.05-0.2): 1.
4. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1, which is characterized in that institute
The temperature for stating heating reflux reaction in step (1) is 60-100 DEG C.
5. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1,2,3 or 4, feature
It is, the molar ratio of starting material Isosorbide-5-Nitrae-bis- (difluoromethyls) is in the phenol, alkali, with step (1) in the step (2)
(1.2-1.6)∶(4.8-8)∶1。
6. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1,2,3 or 4, feature
It is, it is described：Alkali in step (2) is sodium methoxide, sodium hydroxide, potassium hydroxide, sodium carbonate or sodium bicarbonate.
7. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1,2,3 or 4, feature
It is, the organic solvent in the step (2) is N-Methyl pyrrolidone, n,N-Dimethylformamide or sulfolane；The step
Suddenly the mass ratio of organic solvent and bis- (difluoromethyl) benzene of starting material Isosorbide-5-Nitrae-in step (1) is (5-20) in (2): 1.
8. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1,2,3 or 4, feature
It is, the temperature of unimolecule free radical nucleophilic substitution is 80-140 DEG C in the step (2).
9. a kind of synthetic method of bis- (Difluorophenoxymethyl) benzene of Isosorbide-5-Nitrae-according to claim 1,2,3 or 4, feature
It is, using one kind in ethyl acetate, petroleum ether, ethyl alcohol, dichloromethane, toluene in recrystallization process in the step (2)
Or several mixing is as solvent；The volume of recrystallization solvent needed for every gram of crude product is 5-20ml.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000281599A (en) * | 1999-03-29 | 2000-10-10 | Central Glass Co Ltd | Production of 1,4-bis(chlorodifluoromethyl)benzene |
| CN103102242A (en) * | 2011-11-09 | 2013-05-15 | 元欣科技材料股份有限公司 | Simple high-efficiency preparation method of 1, 4-bis (chlorodifluoromethyl) benzene |
-
2018
- 2018-05-25 CN CN201810521682.9A patent/CN108658735A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000281599A (en) * | 1999-03-29 | 2000-10-10 | Central Glass Co Ltd | Production of 1,4-bis(chlorodifluoromethyl)benzene |
| CN103102242A (en) * | 2011-11-09 | 2013-05-15 | 元欣科技材料股份有限公司 | Simple high-efficiency preparation method of 1, 4-bis (chlorodifluoromethyl) benzene |
Non-Patent Citations (3)
| Title |
|---|
| JAY J. SENKEVICH: "Parylene AF-4 via the Trapping of a Phenoxy Leaving Group", 《CHEM. VAP. DEPOSITION》 * |
| WILLIAM R. DOLBIER JR.，等: "Novel fluoropolymers formed by an unprecedented SRN1 condensation polymerization mechanism", 《JOURNAL OF FLUORINE CHEMISTRY》 * |
| 沈新安: "《药物合成技术》", 31 August 2006, 河海大学出版社 * |
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