381-73-7

Basic information

• Product Name: Difluoroacetic acid
• Synonyms: DIFLUOROACETIC ACID;2,2-DIFLUOROACETIC ACID;1,1-DIFLUOROACETIC ACID;VITAS-BB TBB000649;Acetic acid, difluoro-;difluoro-aceticaci;Difluoroaceticacid98%;DIFLUOROACETATE
• CAS NO: 381-73-7
• Molecular Formula: C₂H₂F₂O₂
• Molecular Weight: 96.03
• EINECS: 206-839-0
• Product Categories: Pharmaceutical Intermediates;Small molecule;Organic Fluorides;Fluorinated Building Blocks;Fluorinating Reagents & Building Blocks for Fluorinated Biochemical Compounds;Synthetic Organic Chemistry;Chemical Synthesis;Organic Acids;Synthetic Reagents
• Mol File: 381-73-7.mol
• Article Data: 22

Chemical Properties

• Melting Point: -1 °C
• Boiling Point: 132-134 °C(lit.)
• Flash Point: 174 °F
• Appearance: Clear colorless to light brown/Liquid
• Density: 1.526 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.001mmHg at 25°C
• Refractive Index: n20/D 1.344(lit.)
• Storage Temp.: 2-8°C
• Solubility: 540.54g/L in organic solvents at 20 ℃
• PKA: pK1:1.33 (25°C)
• Water Solubility: 1000g/L at 37℃
• BRN: 1098588
• CAS DataBase Reference: Difluoroacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Difluoroacetic acid(381-73-7)
• EPA Substance Registry System: Difluoroacetic acid(381-73-7)

Safety Data

• Hazard Codes: C
• Statements: 34-35
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• RTECS: AG9900000
• TSCA: T
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 381-73-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Difluoroacetic acid is used as a reagent for the preparation of various organic compounds, such as 2-difluoromethylbenzimidazoles, -oxazoles, and -thiazoles, from ortho-substituted anilines. This application is facilitated by the use of triphenylphosphine as a mediator, which aids in the synthesis process.
Used in Chemical Synthesis:
Difluoroacetic acid is utilized as a building block in the synthesis of a wide range of fluorinated organic compounds. Its unique properties make it a valuable precursor in the development of new molecules with potential applications in various industries, including pharmaceuticals, agrochemicals, and materials science.
Used in Research and Development:
Due to its unique chemical structure and properties, difluoroacetic acid is often employed in research and development settings to study the effects of fluorination on the reactivity and stability of organic molecules. This helps in understanding the fundamental aspects of fluorine chemistry and its implications in various fields.

Flammability and Explosibility

Nonflammable

Purification Methods

Purify the acid by distilling over P2O5. The acid chloride is a fuming liquid b 25o/atm, and the amide has b 108.6o/35mm, m 52o (from *C6H6), and the anilide has b 90o/1mm, 114o/5mm, m 58o [Henne & Pelley J Am Chem Soc 74 1426 1952, Coffman et al. J Org Chem 14 749 1949, NMR: Meyer et al. J Am Chem Soc 75 4567 1953, pK: Wegscheider Z Phys Chem 69 614 1909]. [Beilstein 2 IV 455.]

InChI:InChI=1/C6H3ClFNO2/c7-5-4(6(10)11)1-3(8)2-9-5/h1-2H,(H,10,11)

Upstream product

• 598-39-0 1,1-difluoro-2-iodoethane 
• 1514-85-8 2,2-difluoromalonic acid 
• 618-80-4 2,6-dichloro-4-nitrophenol 
• 83193-04-8 2,2-difluoroacetate 
• 51-28-5 2,4-Dinitrophenol 
• 87-86-5 Pentachlorophenol 
• 354-08-5 bromodifluoroacetic acid 
• 54061-38-0 N,N-dimethylbenzylammonium ion 
• 401-67-2 2,2-difluoroacetic anhydride 
• 302-72-7 rac-Ala-OH 
• 369-22-2 tris-difluoromethyl-[1,3,5]triazine 
• 359-13-7 difluoroethanol 
• 7697-37-2 nitric acid 
• 75747-56-7 1,2-dichloro-3,3-difluoro-1-propene 

Downstream Products

• 454-31-9 ethyl difluoroacetate 
• 354-08-5 bromodifluoroacetic acid 
• 401-67-2 2,2-difluoroacetic anhydride 
• 377-38-8 tetrafluorosuccinic acid 
• 395-01-7 2,2-difluoro-1-phenylethanone 
• 76-04-0 2-chloro-2,2-difluoroacetic acid 
• 404-17-1 2,2-difluoro-N-phenylacetamide 
• 97988-87-9 N-Benzhydryl-2,2-difluoro-acetamide 
• 483303-76-0 N-[1-(2,2-difluoroethyl)-4-methylhexahydro-1,4-diazepin-6-yl]benzamide 
• 916910-97-9 N-(o-tolyl)-2,2-difluoroacetimidoyl chloride 
• 15208-43-2 2-(difluoromethyl)benzo[d]thiazole 
• 91437-09-1 2-(Difluoromethyl)benzoxazole 
• 91437-10-4 2-(difluoromethyl)-5-methylbenzo[d]oxazole 
• 705-09-9 2-(difluoromethyl)-1H-benzo[d]imidazole 

Relevant articles and documents

Preparation and properties of two novel selenoacetic acids: HCF 2C(O)SeH and ClCF2C(O)SeH

The novel selenocarboxylic Se-acids, HCF2C(O)SeH and ClCF 2C(O)SeH, were prepared by treating the corresponding carboxylic acids with Woollins' reagent. The boiling points were extrapolated from the vapor pressure curves to be 364 and 359 K for HCF2C(O)SeH and ClCF2C(O)SeH, respectively. Both compounds are unstable at ambient temperatures and decompose to the corresponding seleno anhydrides and release of H2Se. Hydrolysis results in formation of the carboxylic acids and hydrogen selenide, while diselenides presumably are obtained by oxidation. The conformational properties of these acids were studied by vibrational spectroscopy in combination with ab initio and DFT methods. IR vapor-phase spectra, Raman spectra of the neat liquids, and IR spectra of the Ar-matrix-isolated compounds deposited at two different nozzle temperatures were interpreted in terms of quenching conformational equilibria. The most stable structure of both acids was found to be syn-gauche in equilibrium with a second anti-syn form in HCF2C(O)SeH and with another two conformers, anti-gauche and anti-syn, in ClCF2C(O)SeH.

Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.

Synthesis process of difluoroacetic acid

The synthesis process comprises the following steps: adding dialkylamines in a dry reaction vessel, first organic solvent and volume concentration of 10 - 40% alkali liquor, dropwise adding dichloroacetyl chloride, carrying out heat preservation stirring after dropwise addition, organic subtraction pressure desolventizing and concentrating to obtain dichloroacetyl dialkylamine. Potassium fluoride, second organic solvent and dichloroacetyl dialkylamine were added to another reaction vessel, and the molar ratio @timetime@ and thermal insulation of the potassium fluoride, the solvent diethylene glycol and the dichloroacetyl 3:5:1 dialkylamine is @. The equimolar difluoroacetyl dialkylamine and the volume concentration were mixed with 10 - 30% lye, reflux was 4 - 10h, dichloroacetyl dialkylamine was recovered by distillation, and the bottoms of the bottoms were adjusted pH=1 with hydrochloric acid and distilled again to give difluoro acetic acid.

Synthetic method of difluoroacetic acid

The invention relates to a synthetic method of difluoroacetic acid, belonging to the technical field of organic fluorine chemical industry. According to the synthetic method of difluoroacetic acid, 1,1-difluoroethane (R152a) and hydrogen peroxide are taken as raw materials, difluoroacetic acid is prepared in one step, unreacted 1,1-difluoroethane (R152a) is recycled after recovery, the selectivityand conversion rate of the target product are high, and the synthetic method is non-corrosive to equipment, safe and environment-friendly. A catalyst used in the invention is a solid acid catalyst, has high catalytic efficiency, can be repeatedly used, can be easily separated from a reaction system after the reaction is finished, and is particularly suitable for preparing difluoroacetic acid from1,1-difluoroethane (R152a) and hydrogen peroxide. Raw materials adopted in the invention are common reagents and easily available and cheap; and reaction conditions are mild, and a reaction process is easy to control. The prepared difluoroacetic acid product has higher yield and is suitable for industrial production.

Preparation method of difluoroacetic acid

The invention relates to a preparation method of difluoroacetic acid, and belongs to the technical field of fluorine chemical engineering. According to the preparation method of the difluoroacetic acid, KMnO4/C solid catalysts are added into a fixed bed reaction kettle; nitrogen gas is introduced to perform replacement on the air in the reaction kettle; the temperature is raised to a fixed temperature; then, hydrogen peroxide and 2-chlorine-1,1-difluoroethane are introduced by a voltage stabilizing pump to perform contact reaction; after a product is separated, the product of difluoroacetic acid is finally obtained. The preparation method of the difluoroacetic acid has the advantages that the process is simple; the flow process is short; the technical flow process is simplified; the energyconsumption is greatly reduced; the method is suitable for industrialized production; the used raw materials are all common reagents, the resources of the materials are wide, and the price is low; the reaction process can be easily controlled; the obtained difluoroacetic acid product has high yield and has wide application and popularization values.

Practical Processes for Producing Fluorinated alpha-Ketocarboxylic Esters and Analogues Thereof

It is possible to produce a fluorine-containing α-ketocarboxylic ester hydrate by reacting a fluorine-containing α-hydroxycarboxylic ester with sodium hypochlorite or calcium hypochlorite of 21 mass % or greater in mass percentage of composition. Furthermore, it is possible to produce a fluorine-containing α-ketocarboxylic ester by reacting the hydrate with a dehydrating agent. Furthermore, it is possible to produce a fluorine-containing α-ketocarboxylic ester hemiketal by reacting the fluorine-containing α-ketocarboxylic ester hydrate with a lower alcohol or a trialkyl orthocarboxylate. Moreover, it is possible to produce a fluorine-containing α-ketocarboxylic ester by reacting the hemiketal with a dealcoholization agent.

Process for the Preparation of Difluroacetic Acid

A process is provided for the preparation of difluoroacetic acid from tetrafluoroethylene. The process comprises reacting tetrafluoroethylene with an aqueous solution of an inorganic base, optionally in the presence of an organic solvent.

PROCESS FOR PREPARING DIFLUOROACETIC ACID, SALTS THEREOF OR ESTERS THEREOF

A process for preparing difluoroacetic acid, salts thereof or esters thereof is described. The process can further include preparation of difluoroacetic acid, salts thereof or esters thereof, wherein the reaction occurs in the presence of water of a salt providing a fluoride anion and of monohalogenated or dihalogenated acetic acid, in acid, salified or esterified form, at least one halogen atom being other than the fluorine atom.

METHOD FOR PREPARING DIFLUOROACETIC ACID

A method for preparing difluoroacetic acid is described. The method can include: reacting a difluoroacetic acid ester with an aliphatic carboxylic acid which, after transesterification, results in the formation of difluoroacetic acid and the corresponding carboxylic acid ester, the carboxylic acid being selected such that the ester of the carboxylic acid has a lower boiling point than that of difluoroacetic acid; and removing the ester of the carboxylic acid by distillation as the ester forms, thus enabling the difluoroacetic acid to be recovered.

PROCESS FOR THE PREPARATION OF DIFLUOROACETIC ACID

A process is provided for the preparation of difluoroacetic acid from tetrafluoroethylene. The process comprises reacting tetrafluoroethylene with an aqueous solution of an inorganic base, optionally in the presence of an organic solvent.