CN109574884A - A kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether - Google Patents
A kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether Download PDFInfo
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- CN109574884A CN109574884A CN201811599458.8A CN201811599458A CN109574884A CN 109574884 A CN109574884 A CN 109574884A CN 201811599458 A CN201811599458 A CN 201811599458A CN 109574884 A CN109574884 A CN 109574884A
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- Prior art keywords
- difluoroethoxy
- propyl thioether
- preparation
- trifluoromethyl propyl
- difluoroethanol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Abstract
The present invention relates to organic synthesis fields, more particularly to a kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether, including using difluoroethanol as raw material, it is reacted under the action of acid binding agent A with methylsufonyl chloride and generates 2,2- difluoroethanol methane sulfonate；2,2- difluoroethanol methane sulfonates generate 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether under acid binding agent B effect, with 2- hydroxyl -6- trifluoromethyl propyl thioether reactant.Preparation method provided by the invention provides double fluorine ethyoxyls by raw material of cheap difluoroethanol, prepares key intermediate 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether, greatly reduces production cost.
Description
Technical field
The present invention relates to organic synthesis fields, and in particular to a kind of 2- (2,2- difluoroethoxy) -6- trifluoromethyl
The preparation method of propyl thioether.
Background technique
1- (2,2- difluoroethoxy) -6- trifluoromethyl-N- ([1,2,4] triazole [1,5 DEG C] pyrimidine -2-) benzsulfamide
(penoxsu lam), chemical structure is as follows:
1- (2,2- difluoroethoxy) -6- trifluoromethyl-N- ([1,2,4] triazole [1,5-C] pyrimidine -2-) benzsulfamide
It is the Miao Houyong herbicide developed by Tao Nongke company, the U.S. (Dow Agro-Sciences), it is triazolo pyrimidine sulphonyl
Amine herbicide, by inhibiting acetolactate synthestase (ALS) to work.
Leather agent is removed with wide spectrum as rice field, can effectively prevent and kill off barnyard grass (including to propanil, dichloro quinolinic acid and anti-acetylcoenzyme
The barnyard grass of A carboxylase tool resistance), semen euphorbiae and annual sedge weed, and it is effective to numerous broadleaf weeds, as natural pond life is different
Stamen spends (Heteran thera I imosa), carp intestines (Eclipta prostrata), sesbania (Sesbaniaexaltata), bamboo
Save flower (Commelina diffusa), Monochoria vaginalis (Monochoria vaginalis) etc..Meanwhile it can also prevent and kill off in rice field
Anti- bensulfuron-methyl weeds, and there is residual activity to many broad-leaveds and sedge weed and barnyard grass etc., it is current rice field weeding
The most wide kind of degrass spectrum in agent.
1- (2,2- difluoroethoxy) -6- trifluoromethyl-N- ([1,2,4] triazole [1,5C] pyrimidine -2-) benzsulfamide
It is as Tao Nongke company, U.S. Dow Agro-Sciences) (US5858924) patent disclosed in United States Patent (USP)s in 1999
Involved in 1- (2,2- difluoroethoxy) -6- trifluoromethyl-N- ([1,2,4] triazole [1,5-C] pyrimidine -2-) benzene sulfonyl
It is that raw material sets out preparation that amine, which is by the not high 6- trifluoromethyl -2- fluoroaniline of expensive and Market Orientation,；In Tao Shi
It has been respectively mentioned in the other two parts of patents (US20050215570 and US20020037811) of company and has been made with methoxymethylene chlorine
The synthetic method of phenolic hydroxyl protecting group, but introducing for difluoroethoxy need to use expensive and not market-oriented 2,2- difluoro bromoethane
As reagent.Therefore, a kind of synthesis 1- (2,2- difluoroethoxy) -6- trifluoromethyl-at lower cost is needed currently on the market
The method of N- ([1,2,4] triazole [1,5-C] pyrimidine -2-) benzsulfamide key intermediate.
Summary of the invention
The technical problem to be solved by the present invention is providing a kind of 2- (2,2- difluoroethoxy) -6- trifluoromethyl third
The preparation method of base thioether.
The technical scheme to solve the above technical problems is that
A kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether, includes the following steps:
(1) it using difluoroethanol as raw material, is reacted under the action of acid binding agent A with methylsufonyl chloride and generates 2,2- difluoroethanol
Methane sulfonate；
(2) 2,2- difluoroethanol methane sulfonate are under acid binding agent B effect, with 2- hydroxyl -6- trifluoromethyl propyl
Thioether reactant generates 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether；
The reaction equation of above-mentioned reaction is as follows:
Preferably, the molar ratio of difluoroethanol, methylsufonyl chloride and acid binding agent A is 1:1.0~1.2 in the step (1):
1.0~1.5；In the further step (1) molar ratio of difluoroethanol, methylsufonyl chloride and acid binding agent be 1:1.05~
1.2:1.1~1.5.
Preferably, acid binding agent A is organic base in the step (1), is specifically selected from triethylamine, aniline, pyridine or diformazan
The organic bases such as yl pyridines.
Preferably, organic solvent used in the step (1) is selected from ethyl acetate, methylene chloride, dichloroethanes or first
Benzene etc.；Further, organic solvent quality used in the step (1) is 2~20 times of difluoroethanol quality.
Preferably, the step (1) further includes the steps that being added acid for adjusting pH after reaction to 6~7, the mesh of the step
Be to destroy extra methylsufonyl chloride.
Preferably, 2- hydroxyl -6- trifluoromethyl propyl thioether, 2,2- difluoroethanol methane sulphur in the step (2)
The molar ratio of acid esters and acid binding agent B are 1:1.0~1.1:1.0~1.5；Further, 2- hydroxyl -6- three in the step (2)
Trifluoromethylphenyl propyl thioether, 2,2- difluoroethanol methane sulfonate and acid binding agent B molar ratio be 1:1.0~1.1:1.2~
1.5。
Preferably, the acid binding agent B in the step (2) be inorganic base, specifically selected from sodium carbonate, potassium carbonate, lithium carbonate,
The inorganic bases such as saleratus or sodium bicarbonate.
Preferably, organic solvent used in the step (2) is alkali organic solvent and boiling point is higher than 130 DEG C；Specifically
Can be selected from DMF, N, the basic solvents such as accelerine or DMAC N,N' dimethyl acetamide；Further, the step (2)
Used in organic solvent quality be 2~20 times of 2- hydroxyl -6- trifluoromethyl propyl thioether quality.
The Chinese name of compound, which has with structural formula, in the present invention conflicts, and is subject to structural formula.
Preparation method provided by the invention provides double fluorine ethyoxyls by raw material of cheap difluoroethanol, and preparation is crucial
Intermediate 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether, greatly reduces production cost.
Detailed description of the invention
Fig. 1 is the mass spectrogram of final product 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether；
Fig. 2 is the hydrogen spectrogram of final product 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether.
Specific embodiment
Illustrate the present invention below in conjunction with example, but does not limit the present invention.In the art, technical staff is the present invention
Simple replacement or improvement belong in the technical solution protected of the present invention.
Embodiment 1:
82.05g (1.0mol) difluoroethanol, 136.97g (1.2mol) methylsufonyl chloride and 400g methylene chloride are added
In four-hole boiling flask, ice-water bath is cooled to 5 DEG C, is added dropwise 151.79g triethylamine (1.5mol), and 6h is added dropwise, keeps the temperature 1h after completion of dropwise addition；
15g hydrochloric acid (wt30%) is added dropwise and adjusts pH to 6~7,400g water is added and stirs 0.5h, layering, water layer is extracted with 200g methylene chloride
It takes, merges organic phase, precipitation obtains 157g difluoroethanol methane sulfonate (content 97.2%), yield 95.3%.
By 118.12g (0.5mol) 2- hydroxyl -6- trifluoromethyl propyl thioether and 500g DMF and 82.93g carbonic acid
Potassium (0.6mol) is added in dry four-hole boiling flask, is warming up to 120 DEG C, and 82.4g difluoroethanol methane sulfonate (content is added dropwise
97.2%, 0.50mol), 4h is added dropwise, keeps the temperature 2h after completion of dropwise addition；Cooling, filtering, filtrate 200g water washing, layering are organic
Phase precipitation obtains 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether crude product, then obtains through simple distillation
147.87g product (content 98.34%), yield 96.85%.
Embodiment 2:
82.05g (1.0mol) difluoroethanol, 120.27g (1.05mol) methylsufonyl chloride and 400g dichloroethanes are added
In four-hole boiling flask, ice-water bath is cooled to 10 DEG C, is added dropwise 111.3g triethylamine (1.1mol), and 5h is added dropwise, keeps the temperature 1h after completion of dropwise addition；
10g hydrochloric acid (wt30%) is added dropwise and adjusts pH to 6~7,400g water is added and stirs 0.5h, layering, water layer is extracted with 200g methylene chloride
It takes, merges organic phase, precipitation obtains 156g difluoroethanol methane sulfonate (content 97.3%), yield 94.8%.
By 118.12g (0.5mol) 2- hydroxyl -6- trifluoromethyl propyl thioether and 600g DMF and 96.75g carbonic acid
Potassium (0.7mol) is added in dry four-hole boiling flask, is warming up to 120 DEG C, and 90.52g difluoroethanol methane sulfonate (content is added dropwise
97.3%, 0.55mol), 5h is added dropwise, keeps the temperature 2h after completion of dropwise addition；Cooling, filtering, filtrate 200g water washing, layering are organic
Phase precipitation obtains 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether crude product, then obtains through simple distillation
148.44g product (content 98.77%), yield 97.65%.
Intermediate and product in the various embodiments described above, through mass spectrum and hydrogen spectrum confirmation.
What has been described above is only a preferred embodiment of the present invention, it is noted that for those of ordinary skill in the art
For, without departing from the concept of the premise of the invention, various modifications and improvements can be made, these belong to the present invention
Protection scope.
Claims (10)
1. a kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether, it is characterised in that including
Following steps:
(1) it using difluoroethanol as raw material, is reacted under the action of acid binding agent A with methylsufonyl chloride and generates 2,2- difluoroethanol methane
Sulphonic acid ester；
(2) 2,2- difluoroethanol methane sulfonate are under acid binding agent B effect, with 2- hydroxyl -6- trifluoromethyl propyl thioether
Reaction generates 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether；
The reaction equation of above-mentioned reaction is as follows:
2. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
Be characterized in that, in the step (1) molar ratio of difluoroethanol, methylsufonyl chloride and acid binding agent A be 1:1.0~1.2:1.0~
1.5。
3. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as claimed in claim 2,
Be characterized in that, in the step (1) molar ratio of difluoroethanol, methylsufonyl chloride and acid binding agent A be 1:1.05~1.2:1.1~
1.5。
4. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
It is characterized in that, acid binding agent A is organic base in the step (1), is specifically selected from triethylamine, aniline, pyridine or lutidines
Equal organic bases.
5. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
It is characterized in that, organic solvent used in the step (1) is selected from ethyl acetate, methylene chloride, dichloroethanes or toluene；Into one
Step, organic solvent quality used in the step (1) is 2~20 times of difluoroethanol quality.
6. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
It is characterized in that, states step (1) and further include the steps that being added acid for adjusting pH after reaction to 6~7.
7. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
Be characterized in that, 2- hydroxyl -6- trifluoromethyl propyl thioether in the step (2), 2,2- difluoroethanol methane sulfonate with
The molar ratio of acid binding agent B is 1:1.0~1.1:1.0~1.5.
8. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as claimed in claim 7,
Be characterized in that, 2- hydroxyl -6- trifluoromethyl propyl thioether in the step (2), 2,2- difluoroethanol methane sulfonate with
The molar ratio of acid binding agent B is 1:1.0~1.1:1.2~1.5.
9. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
It is characterized in that, the acid binding agent B in the step (2) is inorganic base, is specifically selected from sodium carbonate, potassium carbonate, lithium carbonate, bicarbonate
The inorganic bases such as potassium or sodium bicarbonate.
10. the preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether as described in claim 1,
It is characterized in that, organic solvent used in the step (2) is alkali organic solvent and boiling point is higher than 130 DEG C；The step
(2) organic solvent quality used in is 2~20 times of 2- hydroxyl -6- trifluoromethyl propyl thioether quality.
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| CN201811599458.8A CN109574884A (en) | 2018-12-26 | 2018-12-26 | A kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether |
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| CN201811599458.8A CN109574884A (en) | 2018-12-26 | 2018-12-26 | A kind of preparation method of 2- (2,2- difluoroethoxy) -6- trifluoromethyl propyl thioether |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013171712A1 (en) * | 2012-05-16 | 2013-11-21 | Janssen Pharmaceuticals, Inc. | Substituted 3, 4 - dihydro - 2h - pyrido [1, 2 -a] pyrazine - 1, 6 - dione derivatives useful for the treatment of (inter alia) alzheimer's disease |
| CN105294515A (en) * | 2015-11-13 | 2016-02-03 | 天津现代职业技术学院 | Preparation method of 2-(2',2'-difluoroethoxy)-6-(trifluoromethyl)benzene-1-sulfonyl chloride |
| CN105294520A (en) * | 2015-11-23 | 2016-02-03 | 大连九信生物化工科技有限公司 | 2-(2 ', 2'-difluoro-ethoxy)-6-trifluoromethyl-phenylpropyl sulfur ether synthesis process |
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2018
- 2018-12-26 CN CN201811599458.8A patent/CN109574884A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013171712A1 (en) * | 2012-05-16 | 2013-11-21 | Janssen Pharmaceuticals, Inc. | Substituted 3, 4 - dihydro - 2h - pyrido [1, 2 -a] pyrazine - 1, 6 - dione derivatives useful for the treatment of (inter alia) alzheimer's disease |
| CN105294515A (en) * | 2015-11-13 | 2016-02-03 | 天津现代职业技术学院 | Preparation method of 2-(2',2'-difluoroethoxy)-6-(trifluoromethyl)benzene-1-sulfonyl chloride |
| CN105294520A (en) * | 2015-11-23 | 2016-02-03 | 大连九信生物化工科技有限公司 | 2-(2 ', 2'-difluoro-ethoxy)-6-trifluoromethyl-phenylpropyl sulfur ether synthesis process |
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Address after: 223000 No. 2, Yannan Avenue, Yanhua new material industrial park, Huai'an City, Jiangsu Province Applicant after: HUAI'AN GUORUI CHEMICAL Co.,Ltd. Address before: 223100 No. 2 Guoqiao Road, Salt Chemical Zone, Hongze County, Huaian City, Jiangsu Province Applicant before: HUAI'AN GUORUI CHEMICAL Co.,Ltd. |
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Application publication date: 20190405 |
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