CN103508875B - A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) - Google Patents
A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) Download PDFInfo
- Publication number
- CN103508875B CN103508875B CN201210211036.5A CN201210211036A CN103508875B CN 103508875 B CN103508875 B CN 103508875B CN 201210211036 A CN201210211036 A CN 201210211036A CN 103508875 B CN103508875 B CN 103508875B
- Authority
- CN
- China
- Prior art keywords
- acid
- fluoroalanine
- tetra
- dialkyl group
- hydrolysis reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/06—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid amides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to technical field of organic chemistry, the invention provides a kind of 2,3, the synthetic method of 3,3-tetrafluoro propionic acid (I): under acid or alkaline conditions, in the presence of a catalyst or in catalyst-free system, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) hydrolysis obtains 2,3,3,3-tetrafluoro propionic acid (I).The features such as the present invention is easy and simple to handle, and production cost is low, and product purity is high, and reaction conditions is gentle, are suitable for suitability for industrialized production.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to a kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I).
Background technology
2,3,3,3-tetrafluoro propionic acid (I) is a kind of important fluoro-containing intermediate being widely used in medicine, pesticide field.
Japanese Patent JP2008280304 describes 1,1,2,3,3,3, and-R 1216 (IV) reacts preparation 2,3,3,3-tetrafluoro benzyl propionate (V) in the basic conditions and is then hydrolyzed the synthetic method generating I with benzylalcohol.Though the method step is simple, easy and simple to handle, starting raw material 1,1,2,3,3,3 ,-R 1216 is expensive, directly causes 2,3,3,3-tetrafluoro propionic acid production cost to remain high.Hemer, I.(j.Fluor.Chem.1986,34,241) one is developed with the bromo-1-of 1-chloro-1,2,2,2-tetrafluoropropane (VI) is starting raw material, reacts form zincon with zinc powder, then with carbon dioxide reaction carbonylate so that under zinc powder effect dechlorination prepare the synthetic method of I.The method carbonylate step needs anhydrous and oxygen-free to operate, and is unfavorable for extensive preparation and whole piece technique uses zinc powder to produce a large amount of waste residue in a large number causes environmental pollution.Starting raw material VI in addition in this technique industrially also not easily obtains.
Ishikawa reagent (III, N, N-diethyl-1,1,2,3,3,3-hexafluoro propylamine) is the fluoro reagent of an industrially widespread use, and the manufacturing enterprise of current domestic fluorinated veterinary antibiotic all uses this reagent to complete fluoro operation.The production capacity of domestic enterprise's fluorinated veterinary antibiotic is more than 2000 tons/year, and often produce 1 ton of this kind of microbiotic namely can produce nearly 1 ton containing N, N-dialkyl group-2,3, the by product of 3,3-tetra-fluoroalanine (II), has a strong impact on if these by products directly discharge to cause environment, carry out harmless treatment with high costs, exploitation is translated into useful Chemicals and has realistic meaning.
Summary of the invention
The object of the invention is to propose a kind of 2,3,3,3-tetrafluoro propionic acid synthesize method, by Ishikawa reagent by product N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is converted into has 2,3 of extensive use, 3,3-tetrafluoro propionic acid (I), turns waste into wealth, and simple to operate, cost is low.
A kind of 2,3,3,3-tetrafluoro propionic acid (I) synthetic methods of the present invention, under acid or alkaline conditions, in the presence of a catalyst or in catalyst-free system, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) hydrolysis obtains 2,3,3,3-tetrafluoro propionic acid (I)
Synthetic route is:
R in formula
1and R
2for identical or different C
1-C
10alkyl or C
3-C
10cycloalkyl,
Concrete preparation condition is:
(1) hydrolysis reaction uses water, C
1-C
10alcohols, C
1-C
10amides, C
1-C
10ethers or C
1-C
10the mixed solvent of alkyl carboxylic acid class single solvent or these solvents;
(2) acid that hydrolysis reaction uses is inorganic mineral acid, C
1-C
10alkyl carboxylic acid, halo C
1-C
10alkyl carboxylic acid, nitro replace C
1-C
10alkyl carboxylic acid, C
8-C
20aryl carboxylic acid, halo C
8-C
20aryl carboxylic acid, nitro replace C
8-C
20aryl carboxylic acid, strong-acid ion exchange resin, C
1-C
20alkylsulphonic acid, halo C
1-C
20alkylsulphonic acid, C
8-C
20aryl sulfonic acid, halo C
8-C
20aryl sulfonic acid, nitro fortified phenol;
(3) alkali that hydrolysis reaction uses is alkali metal hydroxide, alkoxyl group or aralkoxy metal base;
(4) reaction times is 1-1000 hour;
(5) temperature of reaction is 0-500 DEG C;
(6) N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) with the mol ratio of acid or alkali is: 1:1-1000;
(7) N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) with the weightmeasurement ratio of solvent is: 1:0.1-1000;
(8) N, N-dialkyl group-2,3; 3; 3-tetra-fluoroalanine (II) derives from commercial goods or contains N, N-dialkyl group-2,3; 3; the industrial production by product crude product of 3-tetra-fluoroalanine or this type of industrial production by product crude product purify after product or other sources containing N, N-dialkyl group-2,3; the sterling of 3,3-tetra-fluoroalanine or mixture;
(9) hydrolysis reaction carries out or uses the mixture of all kinds of mantoquita or silicate or all kinds of phase-transfer catalyst or this few compounds as catalyzer under catalyst-free system, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:0.0000001-100 with the mol ratio of catalyzer.
Wherein, reaction solvent is water, methyl alcohol, ethanol, Isosorbide-5-Nitrae-dioxane, DMF or Glacial acetic acid, or is single solvent, or is mixed solvent.
Wherein, the acid that hydrolysis reaction uses is sulfuric acid, the acid of nitric acid, perchloric acid, hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, hydrogen astatine, hydrogen telluric acid, hyperbromic acid, hydrogen fold acid iodide, metaperiodic acid, chloric acid, bromic acid, silicofluoric acid, chlorine plumbic acid, metaphosphoric acid, osmic acid, permanganic acid, selenic acid, ferric acid, hydrogen borate, fluosulfonic acid, cyanic acid, thiocyanic acid, hexafluoro-antimonic acid, fluorine antimony sulfonic acid, chlorine hydrofluoaluminic acid, 2,4,6-trinitrophenol, 2, all kinds of strong-acid ion exchange resin of 4,6-trinitrobenzoic acid, trifluoroacetic acid, trichoroacetic acid(TCA), methylsulfonic acid, Phenylsulfonic acid, oxalic acid, formic acid.
Wherein, the alkali that hydrolysis reaction uses is sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methylate, potassium methylate, sodium ethylate or potassium ethylate.
Wherein, hydrolysis time is 1-36 hour, and temperature of reaction is 50-150 DEG C.
Wherein, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:1-20 with the mol ratio of acid or alkali.
Wherein, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-15 with the weightmeasurement ratio of solvent.
Wherein, N that hydrolysis reaction uses, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) derives from the Ishikawa reagent by product in commercial goods or industrial production or the product after the purification of this by product.
Wherein, the mantoquitas such as the catalyzer that hydrolysis reaction is used is cuprous chloride, cupric chloride, copper sulfate, cuprous sulfate, cupric nitrate, cuprous nitrate, cupric phosphate, phosphoric acid are cuprous, neutralized verdigris, cuprous acetate, Tubercuprose, cuprous formate or for the silicate such as water glass, potassium silicate, ammonium silicate or use crown ether-like, quaternary ammonium salt, tertiary amines, quaternary ammonium bases, season the phase-transfer catalyst such as phosphonium salt class.
Wherein, in hydrolysis reaction, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:0.0001-10 with the mol ratio of catalyzer.
Described a kind of 2,3,3 of the present invention's proposition, 3-tetrafluoro propionic acid (I) synthetic method is under acid or alkaline condition, by N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is hydrolyzed and obtains 2,3 in alcohols, acid amides or ether solvent, 3,3-tetrafluoro propionic acid (I), yield 90-95%, content >=98%.The features such as this method has easy and simple to handle, and produce cost low, product purity is high, and reaction conditions is gentle, are suitable for suitability for industrialized production.
Its synthetic route is as follows:
In the present invention, acid used is hydrolyzed for conventional mineral acid (as sulfuric acid, hydrochloric acid) or alkylsulphonic acid (as methanesulfonic) or strong-acid ion exchange resin (as 731 Zeo-karbs); Alkali is conventional mineral alkali (as sodium hydroxide, potassium hydroxide) or metal alkoxides alkali (as sodium methylate).N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) under above-mentioned acid or alkali effect, with the mixed solvent of water, ethanol, methyl alcohol, Glacial acetic acid equal solvent or these solvents for reaction solvent, under 50-150 DEG C of temperature of reaction, react 5-36 hour, namely reaction has accused.N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) controls to control at 1:3-10 at the weightmeasurement ratio of 1:1-10, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) solvent with the mol ratio of acid or alkali.
Preferably reaction conditions of the present invention is:
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is hydrolyzed under hydrochloric acid effect.
Hydrolysis reaction uses ethanol and water mixed solvent, and volume ratio is 10:1.
Temperature of reaction controls at 90-120 DEG C.
Reaction times controls at 10-24 hour.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:5-10 with the mol ratio of acid or alkali.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-5 with the weightmeasurement ratio of solvent.
Embodiment
Specifically describe this patent further below by embodiment, but be not limited to these embodiments.
The preparation of example 1:2,3,3,3-tetrafluoro propionic acid (I).
By N, N-diethyl-2,3,3,3-tetra-fluoroalanine (II) (300g, 1.49mol), 37% hydrochloric acid (700ml), ethanol (1000ml), water (100ml) inserts in reaction flask, temperature rising reflux 10 hours, and reaction is finished, air distillation, collect 120 DEG C of cuts and namely obtain I 207g, yield 95%, purity 98.5%(gas chromatographic detection);
Preparation condition is:
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is hydrolyzed under hydrochloric acid effect.
Hydrolysis reaction uses ethanol and water mixed solvent, and volume ratio is 10:1.
Temperature of reaction controls at 90-120 DEG C.
Reaction times controls at 10-24 hour.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:5-10 with the mol ratio of acid or alkali.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-5 with the weightmeasurement ratio of solvent.
The preparation of example 2:2,3,3,3-tetrafluoro propionic acid (I).
By N, N-diethyl-2,3,3,3-tetra-fluoroalanine (300g, 1.49mol), 98% sulfuric acid (600ml), ethanol (1000ml), water (100ml) inserts in reaction flask, temperature rising reflux 12 hours, and reaction is finished, air distillation, collect 120 DEG C of cuts and namely obtain I 200g, yield 92%, purity 98.3%(gas chromatographic detection);
Preparation condition is:
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is hydrolyzed under hydrochloric acid effect.
Hydrolysis reaction uses ethanol and water mixed solvent, and volume ratio is 10:1.
Temperature of reaction controls at 90-120 DEG C.
Reaction times controls at 10-24 hour.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:5-10 with the mol ratio of acid or alkali.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-5 with the weightmeasurement ratio of solvent.
The preparation of example 3:2,3,3,3-tetrafluoro propionic acid (I)
By N, N-diethyl-2,3,3,3-tetra-fluoroalanine (II) (300g, 1.49mol), 98% sulfuric acid (600ml), ethanol (1000ml), water (100ml), Copper dichloride dihydrate (2.54g, 0.0149mol) are inserted in reaction flask, temperature rising reflux 5 hours, reaction is finished, and air distillation, collects 120 DEG C of cuts and namely obtain I 208g, yield 96%, purity 99.0%(gas chromatographic detection);
Preparation condition is:
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is hydrolyzed under hydrochloric acid effect.
Hydrolysis reaction uses ethanol and water mixed solvent, and volume ratio is 10:1.
Temperature of reaction controls at 90-120 DEG C.
Reaction times controls at 10-24 hour.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:5-10 with the mol ratio of acid or alkali.
N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-5 with the weightmeasurement ratio of solvent.
Claims (6)
1. tetrafluoro propionic acid (I) synthetic method, is characterized in that under acid or alkaline conditions, in the presence of a catalyst, N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) hydrolysis obtains 2,3,3,3-tetrafluoro propionic acid (I)
R in formula
1and R
2for identical or different C
1-C
10alkyl or C
3-C
10cycloalkyl,
Concrete preparation condition is:
(1) hydrolysis reaction uses water, C
1-C
10alcohols, C
1-C
10amides, C
1-C
10ethers or C
1-C
10the mixed solvent of alkyl carboxylic acid class single solvent or these solvents;
(2) acid that hydrolysis reaction uses is inorganic mineral acid, C
1-C
10alkyl carboxylic acid, halo C
1-C
10alkyl carboxylic acid, nitro replace C
1-C
10alkyl carboxylic acid, C
8-C
20aryl carboxylic acid, halo C
8-C
20aryl carboxylic acid, nitro replace C
8-C
20aryl carboxylic acid, strong-acid ion exchange resin, C
1-C
20alkylsulphonic acid, halo C
1-C
20alkylsulphonic acid, C
8-C
20aryl sulfonic acid, halo C
8-C
20aryl sulfonic acid, nitro fortified phenol;
(3) alkali that hydrolysis reaction uses is alkali metal hydroxide, alkoxyl group or aralkoxy metal base;
(4) N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:1-20 with the mol ratio of acid or alkali;
(5) N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) with the weightmeasurement ratio of solvent is: 1:0.1-1000;
(6) N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) derives from commercial goods or contains N, N-dialkyl group-2,3,3, the industrial production by product crude product of 3-tetra-fluoroalanine or this type of industrial production by product crude product purify after product or containing N, N-dialkyl group-2,3, the sterling of 3,3-tetra-fluoroalanine or mixture;
(7) hydrolysis reaction uses all kinds of mantoquita, and N, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:0.0001-10 with the mol ratio of catalyzer;
Hydrolysis reaction catalyzer used is that cuprous chloride, cupric chloride, copper sulfate, cuprous sulfate, cupric nitrate, cuprous nitrate, cupric phosphate, phosphoric acid are cuprous, neutralized verdigris, cuprous acetate, Tubercuprose, cuprous formate mantoquita;
Hydrolysis time is 1-36 hour, and temperature of reaction is 50-150 DEG C.
2. the one 2,3,3 according to right 1,3-tetrafluoro propionic acid (I) synthetic method, is characterized in that reaction solvent is water, methyl alcohol, ethanol, Isosorbide-5-Nitrae-dioxane, N, dinethylformamide or Glacial acetic acid, or be single solvent, or be mixed solvent.
3. the one 2 as described in right 1, 3, 3, 3-tetrafluoro propionic acid (I) synthetic method, it is characterized in that the acid that hydrolysis reaction uses is sulfuric acid, nitric acid, perchloric acid, hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, the acid of hydrogen astatine, hydrogen telluric acid, hyperbromic acid, hydrogen folds acid iodide, metaperiodic acid, chloric acid, bromic acid, silicofluoric acid, chlorine plumbic acid, metaphosphoric acid, osmic acid, permanganic acid, selenic acid, ferric acid, hydrogen borate, fluosulfonic acid, cyanic acid, thiocyanic acid, hexafluoro-antimonic acid, fluorine antimony sulfonic acid, chlorine hydrofluoaluminic acid, 2, 4, 6-trinitrophenol, 2, 4, 6-trinitrobenzoic acid, trifluoroacetic acid, trichoroacetic acid(TCA), methylsulfonic acid, Phenylsulfonic acid, oxalic acid, formic acid, strong-acid ion exchange resin.
4. one 2,3,3,3-tetrafluoro propionic acid (I) synthetic method as described in right 1, is characterized in that the alkali that hydrolysis reaction uses is sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methylate, potassium methylate, sodium ethylate or potassium ethylate.
5. one 2,3,3,3-tetrafluoro propionic acid (I) synthetic method as described in right 1, is characterized in that N, and N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) is 1:3-15 with the weightmeasurement ratio of solvent.
6. the one 2 as described in right 1,3,3,3-tetrafluoro propionic acid (I) synthetic method, it is characterized in that N that hydrolysis reaction uses, N-dialkyl group-2,3,3,3-tetra-fluoroalanine (II) derives from the Ishikawa reagent by product in commercial goods or industrial production or the product after the purification of this by product.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210211036.5A CN103508875B (en) | 2012-06-25 | 2012-06-25 | A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) |
| PCT/CN2013/000717 WO2014000415A1 (en) | 2012-06-25 | 2013-06-20 | 2,3,3,3-tetrafluoropropanoic acid (i) synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210211036.5A CN103508875B (en) | 2012-06-25 | 2012-06-25 | A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103508875A CN103508875A (en) | 2014-01-15 |
| CN103508875B true CN103508875B (en) | 2015-08-19 |
Family
ID=49782154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210211036.5A Expired - Fee Related CN103508875B (en) | 2012-06-25 | 2012-06-25 | A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN103508875B (en) |
| WO (1) | WO2014000415A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103254058B (en) * | 2013-04-19 | 2014-12-24 | 京山瑞生制药有限公司 | Process for synthesizing 2, 3, 3, 3-tetrafluoropropionic acid |
| CN106083560B (en) * | 2016-06-03 | 2019-01-25 | 山东国邦药业股份有限公司 | A method of preparing glycolic |
| CN107628939A (en) * | 2017-09-30 | 2018-01-26 | 湖北龙翔药业科技股份有限公司 | A kind of synthetic method of 2,3,3,3 tetrafluoro propionic acid |
| CN107986938A (en) * | 2017-11-30 | 2018-05-04 | 杭州师范大学 | A kind of preparation method of 2,3,3,3- tetrafluoropropenes |
| CN117402053A (en) * | 2017-12-08 | 2024-01-16 | 上海重兴化学科技有限公司 | Synthesis method of halogenated malonic acid |
| CN108440270A (en) * | 2018-04-18 | 2018-08-24 | 佛山市飞程信息技术有限公司 | A kind of synthetic method of 2,3,3,3- tetrafluoros propionic acid |
| CN111848480A (en) * | 2019-11-21 | 2020-10-30 | 天津科技大学 | Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof |
| CN114702401B (en) * | 2022-06-06 | 2022-08-23 | 山东国邦药业有限公司 | Method for treating florfenicol byproduct N, N-diethyl-2, 3,3, 3-tetrafluoro propionamide |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2795601A (en) * | 1956-01-03 | 1957-06-11 | Minnesota Mining & Mfg | Fluorinated 2-alkenoic acids, esters and amides |
| US2862024A (en) * | 1956-01-03 | 1958-11-25 | Minnesota Mining & Mfg | Fluorinated carbon compounds |
| CN1138020A (en) * | 1995-03-08 | 1996-12-18 | 大赛璐化学工业株式会社 | Process for producing carboxylic acid |
| CN101511767A (en) * | 2006-09-12 | 2009-08-19 | 霍尼韦尔国际公司 | Process for preparing fluorinated acids |
-
2012
- 2012-06-25 CN CN201210211036.5A patent/CN103508875B/en not_active Expired - Fee Related
-
2013
- 2013-06-20 WO PCT/CN2013/000717 patent/WO2014000415A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2795601A (en) * | 1956-01-03 | 1957-06-11 | Minnesota Mining & Mfg | Fluorinated 2-alkenoic acids, esters and amides |
| US2862024A (en) * | 1956-01-03 | 1958-11-25 | Minnesota Mining & Mfg | Fluorinated carbon compounds |
| CN1138020A (en) * | 1995-03-08 | 1996-12-18 | 大赛璐化学工业株式会社 | Process for producing carboxylic acid |
| CN101511767A (en) * | 2006-09-12 | 2009-08-19 | 霍尼韦尔国际公司 | Process for preparing fluorinated acids |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103508875A (en) | 2014-01-15 |
| WO2014000415A1 (en) | 2014-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103508875B (en) | A kind of synthetic method of 2,3,3,3-tetrafluoro propionic acid (I) | |
| CN102336654A (en) | Chloration method for phenoxyacetic acid and derivatives thereof | |
| CN107827757B (en) | Preparation method of m-bromofluorobenzene | |
| CN102241662A (en) | Synthetic method of thiophene-3-ethanol | |
| CN102070521A (en) | Method for preparing quinoline derivative | |
| CN104592030A (en) | Method for synthesizing phthalate compounds | |
| CN103724279B (en) | One step to form the loop prepares the convenient synthetic method of 2-methyl-4-amino-5-amino methylpyrimidine | |
| CN108929212B (en) | Preparation method of perfluorohexanone | |
| CN104513164B (en) | The preparation method of 4-halo-2-methyl-2-butene acetoacetic ester | |
| WO2015078235A1 (en) | Method for preparing medetomidine intermediate | |
| US9783476B2 (en) | Method of producing 2′-trifluoromethyl group-substituted aromatic ketone | |
| CN102701964B (en) | Method for synthesizing 4, 4' -biphenyldicarboxylic acid | |
| CN101160278B (en) | Method for the production of 1,3,5-trifluoro-2,4,6-trichlorobenzene from fluorobenzene derivatives | |
| CN107337576B (en) | Normal temperature catalytic synthesis of 2-bromo-5-fluorobenzotrifluoride | |
| CN101811924B (en) | Method for preparing phenylcyclohexane | |
| CN103288650B (en) | A kind of preparation method of hydrochloric acid MEM | |
| CN105732253A (en) | Preparation method of allyl aromatic compound | |
| CN102924276B (en) | Preparation method and intermediate hemiacetal of 2-methyl-2-acetoxy-3-butenyl-1-aldehyde | |
| CN109232313A (en) | A kind of synthetic method of malononitrile | |
| CN104098444A (en) | Preparation method of 2, 2-difluoroethanol | |
| CN108530301A (en) | A kind of synthetic method of tri- fluorin benzyl amines of 2,4,6- | |
| CN103086894B (en) | Synthesis method of electroplating additive 3-methyl-3-aminobutyne | |
| CN101519406A (en) | Novel synthetic method of alkyl formamine villaumite | |
| CN102531838A (en) | Method for preparing 3,3-dimethyl-1-butanol | |
| CN101805277A (en) | Preparation method of 2,2'-dithio-salicylic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150819 Termination date: 20190625 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |