CN115974729B - Preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride - Google Patents
Preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride Download PDFInfo
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- CN115974729B CN115974729B CN202310060963.XA CN202310060963A CN115974729B CN 115974729 B CN115974729 B CN 115974729B CN 202310060963 A CN202310060963 A CN 202310060963A CN 115974729 B CN115974729 B CN 115974729B
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- DTNQLYAGRKNWMQ-UHFFFAOYSA-N 2-(2,2-difluoroethoxy)-6-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)COC1=CC=CC(C(F)(F)F)=C1S(Cl)(=O)=O DTNQLYAGRKNWMQ-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000002904 solvent Substances 0.000 claims abstract description 16
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 16
- SUODCTNNAKSRHB-UHFFFAOYSA-N 2-ethylhexyl 3-sulfanylpropanoate Chemical compound CCCCC(CC)COC(=O)CCS SUODCTNNAKSRHB-UHFFFAOYSA-N 0.000 claims abstract description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000000460 chlorine Substances 0.000 claims abstract description 10
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 5
- VOGSDFLJZPNWHY-UHFFFAOYSA-N 2,2-difluoroethanol Chemical compound OCC(F)F VOGSDFLJZPNWHY-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000003682 fluorination reaction Methods 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 10
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical group [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 239000012025 fluorinating agent Substances 0.000 claims description 5
- 239000011775 sodium fluoride Substances 0.000 claims description 5
- 235000013024 sodium fluoride Nutrition 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 239000011698 potassium fluoride Substances 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 4
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical group Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 claims description 4
- YJUUZFWMKJBVFJ-UHFFFAOYSA-N 1,3-dimethylimidazolidin-4-one Chemical group CN1CN(C)C(=O)C1 YJUUZFWMKJBVFJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 21
- 239000005457 ice water Substances 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- VUYQBMXVCZBVHP-UHFFFAOYSA-N 1,1-difluoroethanol Chemical compound CC(O)(F)F VUYQBMXVCZBVHP-UHFFFAOYSA-N 0.000 description 5
- 239000005592 Penoxsulam Substances 0.000 description 5
- SYJGKVOENHZYMQ-UHFFFAOYSA-N Penoxsulam Chemical compound N1=C2C(OC)=CN=C(OC)N2N=C1NS(=O)(=O)C1=C(OCC(F)F)C=CC=C1C(F)(F)F SYJGKVOENHZYMQ-UHFFFAOYSA-N 0.000 description 5
- 239000004009 herbicide Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical group CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000192043 Echinochloa Species 0.000 description 3
- 230000002363 herbicidal effect Effects 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- -1 2, 2-difluoroethoxy Chemical group 0.000 description 2
- 108010000700 Acetolactate synthase Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- NGBMMSDIZNGAOK-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine-5-sulfonamide Chemical compound NS(=O)(=O)C1=NC=C2NN=NC2=N1 NGBMMSDIZNGAOK-UHFFFAOYSA-N 0.000 description 1
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical class O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 1
- DBJPBHJHAPAUQU-UHFFFAOYSA-N 5,8-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-amine Chemical compound COC1=CN=C(OC)N2N=C(N)N=C12 DBJPBHJHAPAUQU-UHFFFAOYSA-N 0.000 description 1
- 241000234653 Cyperus Species 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention relates to a preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, which comprises the steps of reacting a compound of formula I with 2-ethylhexyl 3-mercaptopropionate and sodium tert-butoxide to obtain a compound of formula II, reacting the compound of formula II with a fluorination reagent and a first catalyst to obtain a compound of formula III, reacting the compound of formula III with 2, 2-difluoroethanol in a second solvent under the action of alkali to obtain a compound of formula IV, dissolving the compound of formula IV in a third solvent, and reacting with chlorine to obtain the target product 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride. The synthetic method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride has the advantages of fewer reaction steps, simple reaction route, convenient operation, stable maintenance of the total yield of the target product 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride above 85% and higher yield.
Description
Technical Field
The invention relates to the technical field of pesticide synthesis, in particular to a preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride.
Background
Penoxsulam is a widely used post-emergence herbicide with the chemical name: 3- (2, 2-difluoroethoxy) -N- (5, 8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-yl) -alpha, alpha-trifluoro-tolyl-2-sulfonamide belongs to triazolopyrimidine sulfonamide herbicides, the action mechanism of the herbicide is the same as that of the existing sulfonylurea herbicides and imidazolinones, the herbicide acts through inhibiting acetolactate synthase (ALS), has good control effect on various barnyard grasses including barnyard grass, has a very wide weed killing spectrum, and can be used for preventing and killing barnyard grass, annual cyperus and various broadleaf weeds in paddy fields. Residual penoxsulam is susceptible to photodecomposition and microbial degradation, and thus penoxsulam is of great interest due to its low toxicity, high efficiency, and environmental friendliness. Penoxsulam is prepared by reacting 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride with 5, 8-dimethoxy- [1,2,4] triazolo [1,5-c ] pyrimidin-2-amine in an organic solvent by the action of a base.
As an important raw material for synthesizing penoxsulam, the synthetic route of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride is often complicated, the involved reaction steps are more, and the total yield is lower.
Therefore, it is desirable to provide a more suitable method for synthesizing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride.
Disclosure of Invention
First, the technical problem to be solved
In view of the above technical problems, the present invention provides a method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride, which aims to solve the problems of complicated synthetic route and low total yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in the prior art.
(II) technical scheme
In order to achieve the above purpose, the main technical scheme adopted by the invention comprises the following steps:
the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride comprises the following steps:
s1: reacting the compound shown in the formula I with 2-ethylhexyl 3-mercaptopropionate and sodium tert-butoxide in an aprotic reagent to obtain a compound shown in the formula II;
s2: dissolving a compound of the formula II and a fluorination reagent in a first solvent, and adding a first catalyst to react to obtain a compound of the formula III;
s3: reacting the compound shown in the formula III with 2, 2-difluoroethanol in a second solvent under the action of alkali to obtain a compound shown in the formula IV;
s4: and (3) dissolving the compound shown in the formula IV in a third solvent, and then reacting with chlorine under a certain temperature condition to obtain the target product 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, the molar ratio of the compound of the formula I, the 2-ethylhexyl 3-mercaptopropionate and the sodium tert-butoxide in the step S1 is preferably 1:2.5-4.2:0.3-0.8.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, the reaction temperature of the compound of the formula I, 2-ethylhexyl 3-mercaptopropionate and sodium tert-butoxide in the step S1 is 120-180 ℃ and the reaction time is 12-24h.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, preferably, in the step S2, after adding the first catalyst, heating to 100-220 ℃ for reacting for 2-3 hours to obtain the compound of the formula III;
the molar ratio of the compound of formula II, the fluorinating agent and the first catalyst is 1:1.5-1.8:0.3-0.7.
In the above-described method for producing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride, preferably, in step S2, the first solvent is 1, 3-dimethylimidazolidinone, the fluorinating agent is potassium fluoride or sodium fluoride, and the first catalyst is triphenylphosphine bromide or diisopropylethylamine.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, preferably, in the step S3, the molar ratio of the compound of the formula III, the 2, 2-difluoroethanol and the base is 1:0.8-1.2:1.5-2.7;
the compound of formula II is reacted with a fluorinating agent at a temperature of 50-90℃for 3-6h.
In the preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, preferably, in the step S3, the base is one or more of sodium hydroxide, sodium amide and sodium hydride; the second solvent is one or more of dimethylformamide, dimethyl sulfoxide and acetonitrile.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, the molar ratio of the compound of the formula IV to chlorine in the step S4 is preferably 1:5-15.
In the preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, preferably, in the step S4, the compound of the formula IV is dissolved in a third solvent and then reacts with chlorine gas for 2-3 hours at the temperature of 30-40 ℃ to obtain the target product 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride.
In the preparation method of 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride, preferably, in the step S4, the third solvent is one or more of chloralkane, water and acetic acid.
(III) beneficial effects
The synthetic method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride has the advantages of fewer reaction steps, simple reaction route, convenient operation, stable maintenance of the total yield of the target product 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride above 85% and higher yield.
Drawings
FIG. 1 is a synthetic scheme of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to the present invention.
Detailed Description
The invention is better explained with reference to the drawings and the detailed description which follow, for the sake of understanding.
Example 1
As shown in fig. 1, this example provides a method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride, comprising the steps of:
s1: synthesis of compounds of formula ii:
0.1mol of the compound of formula I, 0.3mol of 2-ethylhexyl 3-mercaptopropionate and 0.05mol of sodium tert-butoxide are added to 200ml of carbon tetrachloride, and the system is heated to 160℃and reacted for 16h. The yield of the compound of formula II was calculated to be 88%.
S2: synthesis of compounds of formula iii:
0.1mol of the compound of formula II, 0.16mol of sodium fluoride, 0.05mol of triphenylphosphine bromide and 3mol of 1, 3-dimethyl imidazolinone are added into a three-necked flask equipped with a rectifying column, stirred, heated and refluxed for reaction, and the reaction temperature is kept at 160 ℃ for 2.5 hours. After the reaction, colorless transparent liquid, i.e., the compound of formula III was distilled off, and the yield was calculated to be 90%.
S3: synthesis of compounds of formula iv:
0.3mol NaNH 2 Suspended in 250mL of dimethylformamide, cooled to 5 ℃, added with 0.15mol of difluoroethanol, heated to 70 ℃ and stirred for 1 hour. Then 0.15mol of the compound of formula III is slowly added dropwise, and the reaction is carried out for 3 hours after the addition. After the reaction is finished, pouring the reaction solution into 300mL of ice water, extracting with ethyl acetate, combining organic phases, washing with water to be neutral, and desolventizing to obtain the compound of the formula IV, wherein the yield of the compound of the formula IV is 91% through calculation.
S4: synthesis of compounds of formula v:
0.1mol of the compound of formula IV is dissolved in a mixed solvent of 100mL of acetic acid and 10mL of water, the temperature is raised to 30 ℃, 1mol of chlorine is introduced, the temperature is raised to 35 ℃, and the temperature is kept for 2.5 hours. After the reaction, the reaction system was poured into 300mL of ice water, extracted with ethyl acetate, and then combined and desolventized to obtain 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as a white solid, and the yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in this example was calculated to be 91%.
Example 2
This example provides a process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride comprising the steps of:
s1: synthesis of compounds of formula ii:
0.1mol of the compound of formula I, 0.25mol of 2-ethylhexyl 3-mercaptopropionate and 0.03mol of sodium tert-butoxide are added to 200ml of diethyl ether, and the reaction system is heated to 120℃and reacted for 12 hours. The yield of the compound of formula II was calculated to be 86%.
S2: synthesis of compounds of formula iii:
0.1mol of the compound of formula II, 0.15mol of sodium fluoride, 0.03mol of diisopropylethylamine and 4mol of 1, 3-dimethylimidazolidinone are added into a three-necked flask equipped with a rectifying column, stirred, heated and refluxed for reaction, and the reaction temperature is kept at 110 ℃ for 2 hours. After the reaction, a colorless transparent liquid, i.e., the compound of formula III, was distilled off, and the yield was calculated to be 87%.
S3: synthesis of compounds of formula iv:
0.225mol of sodium hydroxide is suspended in 250mL of dimethyl sulfoxide, cooled to 5 ℃, 0.12mol of difluoroethanol is added, the temperature is raised to 50 ℃, and the mixture is stirred for 1 hour. Then 0.15mol of the compound of formula III is slowly added dropwise, and the reaction is carried out for 2 hours after the addition. After the reaction is finished, pouring the reaction solution into 300mL of ice water, extracting with ethyl acetate, combining organic phases, washing with water to be neutral, and desolventizing to obtain the compound of the formula IV, wherein the yield of the compound of the formula IV is calculated to be 90%.
S4: synthesis of compounds of formula v:
0.1mol of the compound of formula IV is dissolved in a mixed solvent of 100mL of acetic acid and 10mL of water, the temperature is raised to 25 ℃, 0.5mol of chlorine is introduced, the temperature is raised to 30 ℃, and the temperature is kept for 2 hours. After the reaction, the reaction system was poured into 300mL of ice water, extracted with ethyl acetate, and then combined and desolventized to obtain 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as a white solid, and the yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in this example was calculated to be 89%.
Example 3
This example provides a process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride comprising the steps of:
s1: synthesis of compounds of formula ii:
0.1mol of the compound of formula I, 0.42mol of 2-ethylhexyl 3-mercaptopropionate and 0.08mol of sodium tert-butoxide are added to 200ml of carbon tetrachloride, and the system is heated to 180℃and reacted for 24 hours. The yield of the compound of formula II was calculated to be 85%.
S2: synthesis of compounds of formula iii:
0.1mol of the compound of formula II, 0.18mol of potassium fluoride, 0.07mol of diisopropylethylamine and 2.5mol of 1, 3-dimethylimidazolidinone are added into a three-necked flask equipped with a rectifying column, stirred, heated and refluxed to react, and the reaction temperature is kept at 220 ℃ for 3 hours. After the reaction, a colorless transparent liquid, i.e., the compound of formula III, was distilled off, and the yield was calculated to be 89%.
S3: synthesis of compounds of formula iv:
0.405mol of sodium hydride is suspended in 250mL of acetonitrile, cooled to 5 ℃, 0.18mol of difluoroethanol is added, the temperature is raised to 90 ℃, and the mixture is stirred for 2 hours. Then 0.15mol of the compound of formula III is slowly added dropwise, and the reaction is carried out for 4 hours after the addition. After the reaction is finished, pouring the reaction solution into 300mL of ice water, extracting with ethyl acetate, combining organic phases, washing with water to be neutral, and desolventizing to obtain the compound of the formula IV, wherein the yield of the compound of the formula IV is 88% through calculation.
S4: synthesis of compounds of formula v:
0.1mol of the compound of formula IV is dissolved in a mixed solvent of 100mL of acetic acid and 10mL of water, the temperature is raised to 30 ℃, 1.5mol of chlorine is introduced, the temperature is raised to 40 ℃, and the temperature is kept for 3 hours. After the reaction, the reaction system was poured into 300mL of ice water, extracted with ethyl acetate, and then combined and desolventized to obtain 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as a white solid, and the yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in this example was calculated to be 90%.
Example 4
This example provides a process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride comprising the steps of:
s1: synthesis of compounds of formula ii:
0.1mol of the compound of formula I, 0.3mol of 2-ethylhexyl 3-mercaptopropionate and 0.05mol of sodium tert-butoxide are added to 200ml of carbon tetrachloride, and the system is heated to 170℃and reacted for 14h. The yield of the compound of formula II was calculated to be 86%.
S2: synthesis of compounds of formula iii:
0.1mol of the compound of formula II, 0.16mol of potassium fluoride, 0.06mol of diisopropylethylamine and 3mol of 1, 3-dimethylimidazolidinone are added into a three-necked flask equipped with a rectifying column, stirred, heated and refluxed to react, and the reaction temperature is kept at 140 ℃ for 2 hours. After the reaction, a colorless transparent liquid, i.e., the compound of formula III, was distilled off, and the yield was calculated to be 87%.
S3: synthesis of compounds of formula iv:
0.15mol of sodium hydroxide and 0.1mol of sodium hydride are suspended in 250mL of dimethylformamide, cooled to 5 ℃, 0.15mol of difluoroethanol is added, the temperature is raised to 60 ℃, and stirring is carried out for 2 hours. Then 0.15mol of the compound of formula III is slowly added dropwise, and the reaction is carried out for 3 hours after the addition. After the reaction is finished, pouring the reaction solution into 300mL of ice water, extracting with ethyl acetate, combining organic phases, washing with water to be neutral, and desolventizing to obtain the compound of the formula IV, wherein the yield of the compound of the formula IV is 89% through calculation.
S4: synthesis of compounds of formula v:
0.1mol of the compound of formula IV is dissolved in 120mL of chloroalkane, the temperature is raised to 30℃and after 1.5mol of chlorine is introduced, the temperature is raised to 35℃and the temperature is kept for 2.5 hours. After the reaction, the reaction system was poured into 300mL of ice water, extracted with ethyl acetate, and then combined and desolventized to obtain 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as a white solid, and the yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in this example was calculated to be 88%.
Example 5
This example provides a process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride comprising the steps of:
s1: synthesis of compounds of formula ii:
0.1mol of the compound of formula I, 0.3mol of 2-ethylhexyl 3-mercaptopropionate and 0.05mol of sodium tert-butoxide are added to 200ml of carbon tetrachloride, and the system is heated to 170℃and reacted for 18h. The yield of the compound of formula II was calculated to be 87%.
S2: synthesis of compounds of formula iii:
0.1mol of the compound of formula II, 0.16mol of sodium fluoride, 0.03mol of triphenylphosphine bromide and 3mol of 1, 3-dimethyl imidazolinone are added into a three-necked flask equipped with a rectifying column, stirred, heated and refluxed for reaction, and the reaction temperature is kept at 210 ℃ for 2 hours. After the reaction, a colorless transparent liquid, i.e., the compound of formula III, was distilled off, and the yield was calculated to be 86%.
S3: synthesis of compounds of formula iv:
0.3mol NaNH 2 Suspended in a mixture of 150mL of dimethylformamide and 100mL of dimethyl sulfoxide, cooled to 5℃and 0.15mol of difluoroethanol was added thereto, and the mixture was heated to 80℃and stirred for 1 hour. However, the method is thatSlowly adding 0.15mol of the compound shown in the formula III dropwise, and reacting for 3 hours after the addition. After the reaction is finished, pouring the reaction solution into 300mL of ice water, extracting with ethyl acetate, combining organic phases, washing with water to be neutral, and desolventizing to obtain the compound of the formula IV, wherein the yield of the compound of the formula IV is calculated to be 90%.
S4: synthesis of compounds of formula v:
0.1mol of the compound of formula IV is dissolved in 150mL of water, the temperature is raised to 30℃and after 1mol of chlorine is introduced, the temperature is raised to 35℃and the temperature is kept for 2.5 hours. After the reaction, the reaction system was poured into 300mL of ice water, extracted with ethyl acetate, and then combined and desolventized to obtain 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as a white solid, and the yield of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride in this example was calculated to be 87%.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (9)
- The preparation method of the 2- (2, 2-difluoroethoxy) -6-trifluoromethyl benzenesulfonyl chloride is characterized by comprising the following steps:s1: reacting the compound shown in the formula I with 2-ethylhexyl 3-mercaptopropionate and sodium tert-butoxide in an aprotic reagent to obtain a compound shown in the formula II;s2: dissolving a compound of the formula II and a fluorination reagent in a first solvent, and adding a first catalyst to react to obtain a compound of the formula III; the fluorination reagent is potassium fluoride or sodium fluoride, the first solvent is 1, 3-dimethyl imidazolinone, and the first catalyst is triphenylphosphine bromide or diisopropylethylamine;s3: reacting the compound shown in the formula III with 2, 2-difluoroethanol in a second solvent under the action of alkali to obtain a compound shown in the formula IV;s4: and (3) dissolving the compound shown in the formula IV in a third solvent, and then reacting with chlorine under a certain temperature condition to obtain the target product 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride.
- 2. The process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S1 the molar ratio of the compound of formula I, 2-ethylhexyl 3-mercaptopropionate and sodium tert-butoxide is from 1:2.5 to 4.2:0.3 to 0.8.
- 3. The process for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S1, the reaction temperature of the compound of formula I, 2-ethylhexyl 3-mercaptopropionate and sodium t-butoxide is 120 to 180 ℃ and the reaction time is 12 to 24 hours.
- 4. The method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S2, after adding the first catalyst, heating to 100-220 ℃ for 2-3 hours to obtain the compound of formula III;the molar ratio of the compound of formula II, the fluorinating agent and the first catalyst is 1:1.5-1.8:0.3-0.7.
- 5. The process for the preparation of 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S3 the molar ratio of compound of formula III, 2-difluoroethanol and base is 1:0.8-1.2:1.5-2.7;the compound of formula II is reacted with a fluorinating agent at a temperature of 50-90℃for 3-6h.
- 6. The method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S3, the base is one or more of sodium hydroxide, sodium amide and sodium hydride; the second solvent is one or more of dimethylformamide, dimethyl sulfoxide and acetonitrile.
- 7. The process for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as claimed in claim 1, wherein in step S4, the molar ratio of the compound of formula IV to chlorine is 1:5-15.
- 8. The method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride according to claim 1, wherein in step S4, the compound of formula iv is dissolved in a third solvent and then reacted with chlorine gas at 30-40 ℃ for 2-3 hours to obtain the target product 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride.
- 9. The method for preparing 2- (2, 2-difluoroethoxy) -6-trifluoromethylbenzenesulfonyl chloride as claimed in claim 1, wherein in step S4, the third solvent is one or more of chloroalkane, water and acetic acid.
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