CN112707799B - Method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer - Google Patents
Method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer Download PDFInfo
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- chlorophenoxy
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- BQYJATMQXGBDHF-UHFFFAOYSA-N difenoconazole Chemical class O1C(C)COC1(C=1C(=CC(OC=2C=CC(Cl)=CC=2)=CC=1)Cl)CN1N=CN=C1 BQYJATMQXGBDHF-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 35
- HPRGYUWRGCTBAV-UHFFFAOYSA-N 1-chloro-3-(4-chlorophenoxy)benzene Chemical compound C1=CC(Cl)=CC=C1OC1=CC=CC(Cl)=C1 HPRGYUWRGCTBAV-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 38
- 238000005911 haloform reaction Methods 0.000 claims abstract description 32
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 17
- 230000007062 hydrolysis Effects 0.000 claims abstract description 15
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 54
- -1 4-chlorophenoxy Chemical group 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- PQYCPVXNIJXBCU-UHFFFAOYSA-N 2-chloro-4-(4-chlorophenoxy)benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=CC=C1OC1=CC=C(Cl)C=C1 PQYCPVXNIJXBCU-UHFFFAOYSA-N 0.000 claims description 30
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 24
- 230000003301 hydrolyzing effect Effects 0.000 claims description 24
- 238000007142 ring opening reaction Methods 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 17
- 239000002585 base Substances 0.000 claims description 14
- 239000003513 alkali Substances 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 6
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical group [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- SATVIFGJTRRDQU-UHFFFAOYSA-N potassium hypochlorite Chemical compound [K+].Cl[O-] SATVIFGJTRRDQU-UHFFFAOYSA-N 0.000 claims description 4
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000002910 solid waste Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 239000000047 product Substances 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000004611 spectroscopical analysis Methods 0.000 description 13
- 239000005760 Difenoconazole Substances 0.000 description 9
- 239000012295 chemical reaction liquid Substances 0.000 description 8
- 238000004821 distillation Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 238000004949 mass spectrometry Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 238000004364 calculation method Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 238000004817 gas chromatography Methods 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 239000002304 perfume Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 2
- 244000241257 Cucumis melo Species 0.000 description 2
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- 241000223600 Alternaria Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002390 cell membrane structure Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940116318 copper carbonate Drugs 0.000 description 1
- GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 239000002920 hazardous waste Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- 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
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention relates to a method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer, which comprises the steps of hydrolysis, haloform reaction, decarboxylation reaction and the like. The preparation method can efficiently prepare the difenoconazole isomer into the 3,4' -dichlorodiphenyl ether. The method not only can effectively reduce solid wastes, change wastes into valuables, reduce the production cost and improve the economic benefit, but also can be applied to the synthesis of other drug intermediates.
Description
[ technical field ] A method for producing a semiconductor device
The invention belongs to the technical field of chemical synthesis. More particularly, the present invention relates to a method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomers.
[ background ] A method for producing a semiconductor device
The difenoconazole, also called difenoconazole, has a trade name of 'shigao', belongs to triazole bactericides, is a sterol demethylation inhibitor, has the characteristics of high efficiency, broad spectrum, low toxicity and low dosage, is an excellent variety of the triazole bactericides, has extremely strong systemic property, can destroy the cell membrane structure and function of pathogenic bacteria by inhibiting the biosynthesis of bacterial cell ergosterol, is used for crops such as fruit trees, vegetables, wheat, potatoes, beans, melons and the like, has good protection and treatment effects on various fungal diseases such as vegetables, melons and fruits and the like, has the characteristics of 'three-in-one' (no environmental pollution, no agricultural product pollution and no natural enemy killing), and is an ideal bactericide for preventing and treating the resistance diseases of crops such as scab, alternaria leaf spot and the like in China and all countries in the world at present.
3,4' -dichlorodiphenyl ether is an important organic synthetic raw material and a medical intermediate, has wide application, can be used for preparing perfumes, particularly soap perfumes and rose mixed perfumes, and can also be used for preparing synthetic resins, organic synthetic raw materials and organic high-temperature heat carriers. The preparation method comprises the steps of adding potassium carbonate and basic copper carbonate as a catalyst into 1, 3-dichlorobenzene and 4-chlorophenol in an N-methyl pyrrolidone solvent, heating to 170-173 ℃, heating for several hours, cooling, filtering, acidifying with hydrochloric acid until the pH value is 6-6.5, then distilling to remove water, distilling under reduced pressure (2kPa), removing residual 1, 3-dichlorobenzene and N-methyl pyrrolidone, and continuing to distill to obtain the product.
About 30% of the product and isomers in the difenoconazole waste liquid cannot be extracted, and only can be treated as hazardous waste or incinerated.
Aiming at the problems in the prior art, the inventor finally completes the invention through a large number of experimental researches and analytical summarization on the basis of summarizing the prior art.
[ summary of the invention ]
[ problem to be solved ]
The invention aims to provide a method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomers.
[ solution ]
The invention is realized by the following technical scheme.
The invention relates to a method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer.
The preparation method comprises the following preparation steps:
A. hydrolysis
Subjecting a difenoconazole isomer to the following hydrolytic ring-opening reaction in water in the presence of an acid to give [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone:
B. haloform reaction
In the presence of inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A and hypohalite are subjected to the following haloform reaction to obtain 2-chloro-4- (4-chlorophenoxy) -benzoate, and then the 2-chloro-4- (4-chlorophenoxy) -benzoic acid is obtained by acidification:
C. decarboxylation reaction
Subjecting the 2-chloro-4- (4-chlorophenoxy) -benzoic acid obtained in step B to decarboxylation in the presence of copper powder and quinoline to give 3,4' -dichlorodiphenyl ether:
according to a preferred embodiment of the invention, in the step a, the acid is mixed with the difenoconazole isomer in a molar ratio of 1-20: 1, carrying out hydrolytic ring-opening reaction in water at the temperature of 60-120 ℃ for 1-72 hours.
According to another preferred embodiment of the invention, in step a, the acid is one or more acids selected from hydrochloric acid, sulfuric acid, hydrobromic acid or phosphoric acid.
According to another preferred embodiment of the present invention, in step a, the weight ratio of water to the difenoconazole isomer is 1:1.1 to 1.8.
According to another preferred embodiment of the present invention, in step B, [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazol-4-one obtained in step a, a base and a hypohalite are mixed in a molar ratio of 1: 1-5: 1-10, stirring and reacting for 0.5-24 hours at the temperature of-20-50 ℃.
According to another preferred embodiment of the present invention, in step B, the hypohalite is sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite; the alkali is sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate.
According to another preferred embodiment of the invention, in step B, the hypohalite is replaced by chlorine and lye or by bromine and lye.
According to another preferred embodiment of the invention, in the step C, the decarboxylation reaction is carried out on the 2-chloro-4- (4-chlorophenoxy) -benzoic acid obtained in the step B, the copper powder and the quinoline according to the molar ratio of 1: 0.01-0.2: 2-20 at the temperature of 80-250 ℃ for 1-24 hours.
The invention also provides [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone prepared in step A, which has the following chemical formula:
and, the present invention also provides 2-chloro-4- (4-chlorophenoxy) -benzoic acid and 2-chloro-4- (4-chlorophenoxy) -benzoic acid salt prepared in step B, which have the following chemical formulas:
and
the present invention will be described in more detail below.
The invention relates to a method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer.
The preparation method comprises the following preparation steps:
A. hydrolysis
Subjecting a difenoconazole isomer to the following hydrolytic ring-opening reaction in water in the presence of an acid to give [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone:
in the step A, the acid and the difenoconazole isomer are mixed according to a molar ratio of 1-20: 1, carrying out hydrolytic ring-opening reaction in water at the temperature of 60-120 ℃ for 1-72 hours.
The acid is one or more acids selected from hydrochloric acid, sulfuric acid, hydrobromic acid or phosphoric acid, all of which are currently marketed products.
In the present invention, if the molar ratio of acid to difenoconazole isomer is less than 1:1, the reaction time is too long, which affects the productivity; if the molar ratio of acid to difenoconazole isomer is higher than 20: 1, the reaction is not obviously influenced and is relatively wasted; therefore, the molar ratio of the acid to the difenoconazole isomer is 1-20: 1 is reasonable; preferably 4 to 15: 1, more preferably 8 to 12: 1.
when the hydrolysis ring-opening reaction time is 1-72 hours, if the temperature of the hydrolysis ring-opening reaction is lower than 60 ℃, the reaction time is too long, and the productivity is influenced; if the temperature of the hydrolytic ring-opening reaction is higher than 120 ℃, impurities are generated; therefore, the temperature of the hydrolytic ring-opening reaction is suitably 60 to 120 ℃, preferably 68 to 110 ℃, more preferably 76 to 98 ℃;
when the temperature of the hydrolysis ring-opening reaction is 60-120 ℃, if the time of the hydrolysis ring-opening reaction is less than 1 hour, the reaction is incomplete; if the time for the hydrolytic ring-opening reaction is longer than 72 hours, time is wasted; therefore, the time of the hydrolytic ring-opening reaction is suitably 1 to 72 hours, preferably 8 to 66 hours, more preferably 12 to 58 hours;
in this step, the weight ratio of water to the difenoconazole isomer is 1:1.1 to 1.8. If the weight ratio exceeds the range, it is not feasible because a certain acid concentration must be ensured. Too much water, too low acid concentration and long reaction time; too little water, high acid concentration, and impurities.
After the hydrolytic ring-opening reaction is finished, the reactants are cooled to room temperature, and a mass spectrometry method is adopted, and the analysis result is shown in attached figure 1.
As is clear from FIG. 1, the hydrolytic ring-opening reaction gives [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone.
B. Haloform reaction
Reacting the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A with hypohalite in the presence of an inorganic base to obtain 2-chloro-4- (4-chlorophenoxy) -benzoate, and acidifying to obtain 2-chloro-4- (4-chlorophenoxy) -benzoic acid:
in step B, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in step A, a base and a hypohalite are mixed according to a molar ratio of 1: 1-5: 1-10, stirring and reacting for 0.5-24 hours at the temperature of-20-50 ℃.
The hypohalite is sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite; the alkali is sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate. The hypohalites used in the present invention are all products currently on the market.
The hypohalite is replaced by chlorine and alkali liquor, or by bromine and alkali liquor.
The lye is herein described as an aqueous solution of the alkali used in the present invention, the concentration of which is 5 to 40% by weight. When chlorine and alkali liquor are used for replacement, the molar ratio of chlorine to alkali is 1:2, and the dosage (the sum of the two molar numbers) of chlorine and alkali liquor is equal to the molar number of hypohalite; the case of substitution with bromine and alkali solution is the same as that of substitution with chlorine and alkali solution.
In this step, when the amount of [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazol-4-one and hypohalite is within the range, if the amount of the base is less than 1, the reaction is incomplete; if the amount of alkali is higher than 5, it is wasted; therefore, the amount of the base is suitably 1 to 5, preferably 1.6 to 4.5, more preferably 2.2 to 4.0;
when the amount of [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone and base is within the range mentioned, if the amount of hypohalite is less than 1, the reaction is incomplete; if the amount of hypohalite is above 10, it is wasted; therefore, the amount of the hypohalite is suitably 1 to 10, preferably 2 to 8, more preferably 3 to 6.0;
in this step, if the temperature of the haloform reaction is below-20 ℃, the reaction can also take place, but energy is wasted; if the temperature of the haloform reaction is higher than 50 ℃, the heat release is large, and the reaction is difficult to control; therefore, the temperature of the haloform reaction is suitably-20 to 50 ℃, preferably-10 to 40 ℃, more preferably-0 to 30 ℃;
under the condition of the temperature of-20 to 50 ℃, if the time of the haloform reaction is shorter than 0.5 hour, the reaction is incomplete; if the time of the haloform reaction is longer than 24 hours, time is wasted; therefore, the time of the haloform reaction is suitably 0.5 to 24 hours, preferably 1.5 to 20 hours, more preferably 3.0 to 16 hours;
after the reaction is finished, the reaction solution is acidified to have a pH of 1-2 at-20-50 ℃ by using industrial hydrochloric acid with a concentration of 10-31% by weight, then filtered, and dried at 80-100 ℃ until the water content is lower than 0.1% by weight, and the dried product is subjected to nuclear magnetic hydrogen spectrometry as described above, and the analysis result is shown in the attached figure 2.
As is clear from FIG. 2, this hydrolytic ring-opening reaction gives 2-chloro-4- (4-chlorophenoxy) -benzoic acid.
C. Decarboxylation reaction
Subjecting the 2-chloro-4- (4-chlorophenoxy) -benzoic acid obtained in step B to decarboxylation in the presence of copper powder and quinoline to give 3,4' -dichlorodiphenyl ether:
in the step C, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B are subjected to decarboxylation reaction for 1-24 hours at the temperature of 80-250 ℃ according to the molar ratio of 1: 0.01-0.2: 2-20.
In the present invention, the primary role of the copper powder in this decarboxylation reaction is the catalyst; the main role of quinoline in this decarboxylation reaction is as a solvent.
In this step, when the amount of 2-chloro-4- (4-chlorophenoxy) -benzoic acid and quinoline is within the above range, the reaction is not complete if the amount of copper powder is less than 0.01 part by weight, and is wasted if the amount of copper powder is more than 0.2 part by weight, so that the amount of copper powder is suitably 0.01 to 0.2 part by weight, preferably 0.04 to 0.16 part by weight, more preferably 0.06 to 0.13 part by weight;
when the amount of 2-chloro-4- (4-chlorophenoxy) -benzoic acid and copper powder is within the above range, if the amount of quinoline is less than 2 parts by weight, the solvent is too small and the reaction is difficult to proceed, and if the amount of quinoline is more than 20 parts by weight, it is excessive and wasted, and therefore, it is reasonable to use 2 to 20 parts by weight of quinoline, preferably 4 to 16 parts by weight, more preferably 6 to 12 parts by weight.
The copper powder used in the step is copper powder with the granularity of 100-300 meshes.
The copper powder and quinoline used in the present invention are commercially available products, and examples thereof include copper powder sold under the name "copper powder" by Shandong Xinyi hong chemical engineering Co., Ltd, and quinoline sold under the name "quinoline" by Shandong Hao Shunhi chemical Co., Ltd.
In the step, when the reaction temperature is 80-250 ℃, if the decarboxylation reaction temperature is lower than 80 ℃, the reaction does not occur; if the temperature of the decarboxylation reaction is higher than 250 ℃, the by-products generated by the reaction are obviously increased; therefore, the temperature of the decarboxylation reaction is suitably 80 to 250 ℃, preferably 100 to 220 ℃, and more preferably 130 to 190 ℃;
under the condition of the temperature of 80-250 ℃, if the time of the decarboxylation reaction is shorter than 1 hour, the reaction is incomplete; if the decarboxylation reaction time is longer than 24 hours, time is wasted; therefore, the decarboxylation reaction is suitably carried out for 1 to 24 hours, preferably 3 to 20 hours, more preferably 6 to 16 hours;
after the reaction, the reaction solution was mixed with ethyl acetate in a weight ratio of 1: 1-10 ethyl acetate is added for easier filtration, and the obtained filtrate is mixed with hydrochloric acid with the concentration of 10% -20% by weight according to the molar weight of the hydrochloric acid and quinoline of 1-1.5: 1, washing, distilling ethyl acetate out of an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, and then carrying out reduced pressure distillation at the temperature of 146 ℃ and the pressure of 5mmHg to obtain the 3,4' -dichlorodiphenyl ether, wherein the specific distillation operation can be referred to CN 101423460A.
The reaction product was subjected to nuclear magnetic hydrogen spectroscopy as described above, and the analysis results are shown in FIG. 3.
The results in FIG. 3 clearly show that the reaction product is 3,4' -dichlorodiphenyl ether.
The yield of the product prepared by the preparation method is calculated according to the following formula:
the weight of the added difenoconazole isomer is a, the weight of the 3,4' -dichlorodiphenyl ether prepared by hydrolysis reaction, haloform reaction and decarboxylation reaction is b, and the product yield is calculated according to the following formula:
(b×283.11)/(239.1×a)×100/％。
[ advantageous effects ]
The beneficial effects of the invention are:
the method for preparing 3,4 '-dichlorodiphenyl ether from the difenoconazole isomer can efficiently prepare the difenoconazole isomer into the 3,4' -dichlorodiphenyl ether. The method not only can effectively reduce solid wastes, change wastes into valuables, reduce the production cost and improve the economic benefit, but also can be applied to the synthesis of other drug intermediates.
[ description of the drawings ]
FIG. 1 is a mass spectrum of a product of a hydrolytic ring-opening reaction of step A of the preparation method of the invention;
FIG. 2 is a nuclear magnetic hydrogen spectrum of a haloform reaction product of step B of the preparation method of the present invention;
FIG. 3 is a nuclear magnetic hydrogen spectrum of a decarboxylation reaction product in step C of the preparation method of the present invention.
[ detailed description ] embodiments
The invention will be better understood from the following examples.
Example 1: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this example are as follows:
A. hydrolysis
In the presence of hydrochloric acid, the ratio by weight of water to difenoconazole isomer (400 g) is 1: 1.2 and at a temperature of 84 ℃, the acid is mixed with the difenoconazole isomer according to a molar ratio of 12: 1, carrying out hydrolytic ring-opening reaction in water for 48 hours, and detecting by a mass spectrometry method described in the specification after the hydrolytic reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of sodium hydroxide inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, and the base and sodium hypochlorite according to a molar ratio of 1: 3: 5 stirring at-20 ℃ to carry out a haloform reaction for 24 hours, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 15% by weight at 0-5 ℃ until the pH value is 1-2, then filtering, drying at 90 ℃ until the water content is below 0.1% by weight, detecting the obtained dried product by using a nuclear magnetic hydrogen spectrometry method described in the specification, wherein the product is 2-chloro-4- (4-chlorophenoxy) -benzoic acid;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B are subjected to decarboxylation reaction for 9 hours at the temperature of 155 ℃ according to the molar ratio of 1: 0.08: 8, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction solution according to the weight ratio of the reaction solution to the ethyl acetate of 1: 3 so as to be easier to filter, washing the filtered filtrate by using 15% by weight of hydrochloric acid according to the molar weight of the hydrochloric acid and quinoline of 1.1: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the distillation was carried out under reduced pressure at 146 ℃ and a pressure of 5mmHg to obtain 202 g of a product, which was 3,4' -dichlorodiphenyl ether by the nuclear magnetic hydrogen spectroscopy described in the specification of the present application.
The yield of this example, calculated according to the calculation described in the specification of the application, was 85.8% and the product, analysed by conventional gas chromatography, was 99.1% pure.
Example 2: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this example are as follows:
A. hydrolysis
In the presence of sulfuric acid, the ratio by weight of water to difenoconazole isomer (400 g) is 1: 1.5 and at a temperature of 60 ℃, the acid and the difenoconazole isomer are mixed according to a molar ratio of 1:1, performing hydrolytic ring-opening reaction in water for 15 hours, and detecting by using a mass spectrometry method described in the specification after the hydrolytic reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of sodium carbonate inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, the base and sodium hypochlorite hypohalite are mixed according to a molar ratio of 1: 2: 1, stirring at-10 ℃ for carrying out a haloform reaction for 18 hours, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 15% by weight at 10-25 ℃ until the pH value is 1-2, then filtering, drying at 85 ℃ until the water content is below 0.1% by weight, detecting the obtained dried product by using a nuclear magnetic hydrogen spectrometry method described in the specification, wherein the product is 2-chloro-4- (4-chlorophenoxy) -benzoic acid;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid and the copper powder obtained in the step B and the quinoline are subjected to decarboxylation reaction for 6 hours at the temperature of 160 ℃ according to the molar ratio of 1: 0.12: 7.5, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction solution according to the weight ratio of the reaction solution to the ethyl acetate of 1:2 so as to be easier to filter, washing the filtered filtrate by using hydrochloric acid with the concentration of 12% by weight according to the molar weight of the hydrochloric acid and quinoline of 1.2: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the distillation is carried out under reduced pressure at the temperature of 146 ℃ and the pressure of 5mmHg to obtain 198 g of product, and the product is 3,4' -dichlorodiphenyl ether by the nuclear magnetic hydrogen spectrometry method described in the specification of the application.
The yield of this example was 84% calculated according to the calculation described in the specification of the application, and the product was 99.2% pure by conventional gas chromatography.
Example 3: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this example are as follows:
A. hydrolysis
In the presence of hydrobromic acid at a concentration of 40% by weight, the ratio by weight of water to difenoconazole isomer (400 g) was 1:1.1 and at a temperature of 72 ℃, the acid is mixed with the difenoconazole isomer according to a molar ratio of 4: 1, carrying out hydrolysis ring-opening reaction in water for 32 hours, and detecting by a mass spectrometry method described in the specification after the hydrolysis reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of potassium hydroxide inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, the base and the potassium hypochlorite according to a molar ratio of 1: 4: 3, stirring at 0 ℃ to carry out a haloform reaction for 12 hours, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 20% by weight at 5-10 ℃ until the pH value is 1-2, then filtering, drying at 85 ℃ until the water content is below 0.1% by weight, detecting the obtained dried product by using a nuclear magnetic hydrogen spectrometry method described in the specification, wherein the product is 2-chloro-4- (4-chlorophenoxy) -benzoate;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the decarboxylation reaction is carried out on the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B according to the molar ratio of 1: 0.04: 10 at the temperature of 150 ℃ for 8 hours, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction solution according to the weight ratio of the reaction solution to the ethyl acetate of 1: 5 so as to be easier to filter, washing the filtered filtrate by using 10% by weight of hydrochloric acid according to the molar weight of the hydrochloric acid and quinoline of 1.2: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the distillation was carried out under reduced pressure at 146 ℃ and a pressure of 5mmHg to obtain 199 g of a product, which was 3,4' -dichlorodiphenyl ether by the nuclear magnetic hydrogen spectroscopy described in the specification of the present application.
The yield of this example, calculated according to the calculation described in the specification of the application, was 84.5% and the product, analysed by conventional gas chromatography, was 99.3% pure.
Example 4: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this embodiment are as follows:
A. hydrolysis
In the presence of phosphoric acid, the weight ratio of water to difenoconazole isomer (400 g) is 1: 1.6 and at a temperature of 120 ℃, the acid is mixed with the difenoconazole isomer according to a molar ratio of 16: 1, performing hydrolytic ring-opening reaction in water for 60 hours, and detecting by using a mass spectrometry method described in the specification after the hydrolytic reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of potassium carbonate inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, the base and sodium hypochlorite hypohalite are mixed according to a molar ratio of 1: 5: 10 stirring at 15 ℃ to carry out a haloform reaction for 8 hours, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 15% by weight at 0-10 ℃ until the pH value is 1-2, then filtering, drying at 85 ℃ until the water content is below 0.1% by weight, and detecting by using a nuclear magnetic hydrogen spectrometry method described in the specification, wherein the product is 2-chloro-4- (4-chlorophenoxy) -benzoate;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B are subjected to decarboxylation reaction for 5 hours at the temperature of 165 ℃ according to the molar ratio of 1: 0.12: 8, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction solution according to the weight ratio of the reaction solution to the ethyl acetate of 1: 4 so as to be easier to filter, washing the filtered filtrate by using 15% by weight of hydrochloric acid according to the molar weight of the hydrochloric acid and quinoline of 1.1: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the mixture was subjected to distillation under reduced pressure at 146 ℃ and a pressure of 5mmHg to obtain 185 g of a product, which was 3,4' -dichlorodiphenyl ether by NMR spectroscopy as described in the specification.
The yield of this example was 78.6% calculated according to the calculation described in the specification of the application, and the product was 98.9% pure by conventional gas chromatography.
Example 5: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this example are as follows:
A. hydrolysis
In the presence of hydrobromic acid, the ratio by weight of water to difenoconazole isomer (400 g) was 1: 1.3 and at a temperature of 96 ℃, the acid is mixed with the difenoconazole isomer according to a molar ratio of 20: 1, carrying out hydrolytic ring-opening reaction in water for 1 hour, and detecting by a mass spectrometry method described in the specification after the hydrolytic reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of cesium carbonate inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, the base and sodium hypobromite hypohalite are mixed according to a molar ratio of 1: 1: 8, stirring at the temperature of 32 ℃ to carry out a haloform reaction for 4 hours, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 20% by weight at the temperature of 0-5 ℃ until the pH value is 1-2, then filtering, drying at the temperature of 85 ℃ until the water content is below 0.1% by weight, and obtaining a dried product, wherein the dried product is 2-chloro-4- (4-chlorophenoxy) -benzoic acid detected by adopting a nuclear magnetic hydrogen spectrometry method described in the specification of the application;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B are subjected to decarboxylation reaction for 4.5 hours at the temperature of 165 ℃ according to the molar ratio of 1: 0.15: 12, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction liquid according to the weight ratio of the reaction liquid to the ethyl acetate of 1: 6 so as to be easier to filter, washing the filtered filtrate by using hydrochloric acid with the concentration of 15% by weight according to the molar weight of the hydrochloric acid and quinoline of 1.5: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the distillation was carried out under reduced pressure at 146 ℃ and a pressure of 5mmHg to obtain 195 g of a product, which was 3,4' -dichlorodiphenyl ether by nuclear magnetic hydrogen spectroscopy described in the specification of the present application.
The yield of this example was 82.8% calculated according to the calculation described in the specification of the application, and the product was 98.8% pure by conventional gas chromatography.
Example 6: preparation of 3,4' -dichlorodiphenyl ether from difenoconazole isomer
The implementation steps of this embodiment are as follows:
A. hydrolysis
In the presence of hydrochloric acid, the weight ratio of water to difenoconazole isomer (400 g) is 1: 1.8 and at a temperature of 108 ℃, the acid is mixed with the difenoconazole isomer according to a molar ratio of 8: 1, carrying out hydrolytic ring-opening reaction in water for 72 hours, and detecting by a mass spectrometry method described in the specification after the hydrolytic reaction is finished, wherein the product is [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone;
B. haloform reaction
In the presence of sodium carbonate inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A, the base and sodium hypobromite hypohalite are added according to a molar ratio of 1: 3: 6, stirring at 50 ℃ to carry out a haloform reaction for 0.5 hour, after the haloform reaction is finished, acidifying reaction liquid by using industrial hydrochloric acid with the concentration of 20% by weight at 10-20 ℃ until the pH value is 1-2, then filtering, drying at 85 ℃ until the water content is below 0.1% by weight, and obtaining a dried product, wherein the dried product is 2-chloro-4- (4-chlorophenoxy) -benzoate by adopting a nuclear magnetic hydrogen spectrometry method described in the specification;
C. decarboxylation reaction
In the presence of copper powder and quinoline, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, the copper powder and the quinoline obtained in the step B are subjected to decarboxylation reaction for 3 hours at the temperature of 180 ℃ according to the molar ratio of 1: 0.16: 15, after the decarboxylation reaction is finished, adding ethyl acetate into the reaction solution according to the weight ratio of the reaction solution to the ethyl acetate of 1: 3 so as to be easier to filter, washing the filtered filtrate by using 15% by weight of hydrochloric acid according to the molar weight of the hydrochloric acid and quinoline of 1.3: 1, evaporating ethyl acetate from an ethyl acetate layer at the temperature of 75-78 ℃ under normal pressure, then, the distillation is carried out under reduced pressure at the temperature of 146 ℃ and the pressure of 5mmHg, 190 g of product is obtained, and the product is 3,4' -dichlorodiphenyl ether by the nuclear magnetic hydrogen spectrometry method described in the specification of the application.
The yield of this example was 80.7% calculated according to the calculation described in the specification of the application, and the product was 98.7% pure by conventional gas chromatography.
Claims (10)
1. A method for preparing 3,4' -dichlorodiphenyl ether from difenoconazole isomer is characterized in that the preparation method comprises the following preparation steps:
A. hydrolysis
Subjecting the difenoconazole isomer to the hydrolytic ring-opening reaction in water in the presence of an acid as follows to give [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone:
B. haloform reaction
In the presence of inorganic base, the [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazole-4-ethanone obtained in the step A and hypohalite are subjected to the following haloform reaction to obtain 2-chloro-4- (4-chlorophenoxy) -benzoate, and then the 2-chloro-4- (4-chlorophenoxy) -benzoic acid is obtained by acidification:
C. decarboxylation reaction
And C, in the presence of copper powder and quinoline, carrying out decarboxylation reaction on the 2-chloro-4- (4-chlorophenoxy) -benzoic acid obtained in the step B at the temperature of 80-250 ℃ to obtain 3,4' -dichlorodiphenyl ether:
2. the method according to claim 1, wherein in step A, the acid is mixed with difenoconazole isomers in a molar ratio of 1-20: 1, carrying out hydrolytic ring-opening reaction in water at the temperature of 60-120 ℃ for 1-72 hours.
3. The process according to claim 1 or 2, wherein in step a, the acid is one or more acids selected from the group consisting of hydrochloric acid, sulfuric acid, hydrobromic acid, and phosphoric acid.
4. The process according to claim 1 or 2, characterized in that in step a, the weight ratio of water to difenoconazole isomer is 1:1.1 to 1.8.
5. The process according to claim 1, wherein in step B, [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazol-4-one obtained in step a, a base and a hypohalite are mixed in a molar ratio of 1: 1-5: 1-10, stirring and reacting for 0.5-24 hours at the temperature of-20-50 ℃.
6. The method according to claim 1 or 5, wherein in step B, the hypohalite is sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite; the alkali is sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate.
7. The process of claim 1 or 5, wherein in step B, the hypohalite is replaced with chlorine and a base solution, or with bromine and a base solution.
8. The process according to claim 1, wherein in step C, the 2-chloro-4- (4-chlorophenoxy) -benzoic acid, copper powder and quinoline obtained in step B are mixed in a molar ratio of 1: 0.01-0.2: performing decarboxylation reaction for 2-20 hours.
9. The process of claim 1 wherein [ 2-chloro-4- (4-chlorophenoxy) -phenyl ] -2- [1,2,4] triazol-4-one prepared in step a has the following formula:
10. 2-chloro-4- (4-chlorophenoxy) -benzoic acid salt prepared in step B by the process of claim 1, having the formula:
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