920-66-1

Basic information

• Product Name: 1,1,1,3,3,3-Hexafluoro-2-propanol
• Synonyms: 1,1,1,3,3,3-hexafluoro-2-propano;1,1,1,3,3,3-hexafluoro-2-propanolakahfip,hexafluoroisopropanol;2,2,2-Trifluoro-1-(trifluoromethyl)ethanol;2H-Hexafluoroisopropanol;Bis(trifluoromethyl)methanol;CF3CH(OH)CF3;Ethanol, 2,2,2-trifluoro-1-(trifluoromethyl)-;Hexafluoroisopropyl alcohol
• CAS NO: 920-66-1
• Molecular Formula: C₃H₂F₆O
• Molecular Weight: 168.04
• EINECS: 213-059-4
• Product Categories: Fluoro-Aliphatics ;Organics;Organic Fluorides;Fluoro series;organofluorine compounds;Alcohols;Building Blocks;C2 to C6;Chemical Synthesis;Organic Building Blocks;Oxygen Compounds;Acylation Reagent;1,2,4-Triazole,Triazoles
• Mol File: 920-66-1.mol
• Article Data: 30

Chemical Properties

• Melting Point: −4 °C(lit.)
• Boiling Point: 59 °C(lit.)
• Flash Point: 4,4°C
• Appearance: White to yellow/Solid
• Density: 1.596 g/mL at 25 °C(lit.)
• Vapor Pressure: 5.07E-07mmHg at 25°C
• Refractive Index: n20/D 1.275(lit.)
• Storage Temp.: Store at RT.
• PKA: pK1:9.42 (25°C)
• Water Solubility: 1000 g/L (25 ºC)
• Stability: Stable. Incompatible with strong acids, strong bases, alkali metals.
• BRN: 1841007
• CAS DataBase Reference: 1,1,1,3,3,3-Hexafluoro-2-propanol(CAS DataBase Reference)
• NIST Chemistry Reference: 1,1,1,3,3,3-Hexafluoro-2-propanol(920-66-1)
• EPA Substance Registry System: 1,1,1,3,3,3-Hexafluoro-2-propanol(920-66-1)

Safety Data

• Hazard Codes: C,Xi
• Statements: 20/22-34
• Safety Statements: 26-36/37/39-45-27
• RIDADR: UN 2922 8/PG 2
• WGK Germany: 2
• RTECS: UB6450000
• F: 27
• TSCA: T
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 920-66-1(Hazardous Substances Data)

Usage

Clinical application

Hexafluoroisopropanol(1,1,1,3,3,3-Hexafluoro-2-propanol) can be used to prepare a variety of high-end chemicals such as fluorosurfactants, fluorine-containing emulsifiers, fluorine-containing pharmaceuticals, and used as a solvent or cleaning agent for electronics industry. The drug can be used as a fluorinated solvent to increase the efficiency of the reaction of rhodium (I)-catalyzed [4 + 2] intramolecular addition reaction of ether bound alkynyl diene and the [5 + 2] cycloaddition of alkynyl vinyl cyclopropane. The drug is a liquid peptide chemical solvent, a highly soluble solvent for peptide and peptide intermediates. The drug can be used for the analysis of multiple polymers.

Hazards

1,1,1,3,3,3-Hexafluoro-2-propanol?derives from a propan-2-ol. It is a clear colorless oily liquid with an aromatic odor. (NTP, 1992) Combustible, may cause burns to skin, eyes and mucous membranes.

Preparation

1,1,1,3,3,3-Hexafluoro-2-propanol is prepared from hexafluoropropylene through hexafluoroacetone, which is then hydrogenated. (CF3)2CO + H2 → (CF3)2CHOH

Chemical Properties

Different sources of media describe the Chemical Properties of 920-66-1 differently. You can refer to the following data:
1. 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) is a clear, colorless, oily, combustible liquid. Odor is described as aromatic.
2. Colorless liquid

Uses

Different sources of media describe the Uses of 920-66-1 differently. You can refer to the following data:
1. Hexafluoroisopropanol is used to produce high-end chemicals, such as fluorinated surfactants, fluorinated emulsifier and fluorinated medicine, etc. HFIP is used as a solvent or cleaner in electronic industry.
2. 1,1,1,3,3,3-Hexafluoro-2-propanol effects the native state of proteins, denaturing them as well as stabilizing the α-helical conformation of unfolded proteins and polypeptides.
3. It is used as a polar solvent and exhibits strong hydrogen bonding properties.It dissolves substances that are hydrogen-bond acceptors, such as amides, ethers and a wide range of polymers, including those that are not soluble in the most common organic solvents.
4. Usually used for preparing hexafluoroalcohol-functionalized methacrylate polymers for lithographic/nanopatterning materials.

Definition

ChEBI: An organofluorine compound formed by substitution of all the methyl protons in propan-2-ol by fluorine. It is a metabolite of inhalation anesthetic sevoflurane.

General Description

1,1,1,3,3,3-Hexafluoro-2-propanol is a solution-phase peptide chemistry solvent. This fluorinated polar solvent of high ionizing power facilitates Friedel–Crafts-type reactions, using covalent reagents in the absence of a Lewis acid catalyst. It also enhances the efficiency of rhodium(I)-catalyzed [4+2] intramolecular cycloaddition of ether-tethered alkynyl dienes and [5+2] cycloaddition of alkynyl vinylcyclopropanes. 1,1,1,3,3,3-Hexafluoro-2-propanol clusters catalyzes the epoxidation of cyclooctene and 1-octene with hydrogen peroxide.

Air & Water Reactions

Water soluble.

Reactivity Profile

1,1,1,3,3,3-Hexafluoro-2-propanol is incompatible with acids, acid chlorides and oxidizing agents.

Fire Hazard

1,1,1,3,3,3-Hexafluoro-2-propanol is probably combustible.

Potential Exposure

A specialty solvent for some poly mers; a lavatory reagent.

Shipping

UN1760 Corrosive liquids, n.o.s., Hazard class: 8; Labels: 8-Corrosive material.

Purification Methods

Distil it from 3A molecular sieves, retaining the middle fraction. It has been prepared by reduction of hexafluoroacetone in tetrahydrofuran (THF), In this case hexafluoropropanol forms a stable 1:1 complex which distils at 99-100o/760mm (n 25 1.3283), The complex is decomposed by mixing with 20% oleum and distilling in a vacuum, and the distillate is redistilled to give pure hexafluoropropan-2-ol with b 59o/760mm. The 1H NMR shows a doublet at 4.52ppm (JH,H 2Hz). The benzoyl derivative, [10315-85-2] M 272.1, has m 53.9o after crystalllisation from pentane at -50o, and its IR has at 1760cm-1. [Middleton & Lindsey J Am Chem Soc 86 4948 1964, Urry et al. J Org Chem 32 347 1967.] It has very high peptide solubilising properties, alone or with CH2Cl2 [use as a solvent: Narita et al. Bull Chem Soc Jpn 61 281 1988, Biochemistry 29 2639 1990.] It is CORROSIVE, causes severe eye irritation.

Incompatibilities

HFIP is incompatible with acids, acid chlorides, and oxidizing agents.

Waste Disposal

May be incinerated. In accor dance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be dis posed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste contain ing this contaminant (≥100 kg/mo) must conform to EPA regulations governing storage, transportation, treatment, and waste disposal.

InChI:InChI=1/C11H3F5N2O2/c12-5-6(13)8(15)10(9(16)7(5)14)20-11(19)4-1-17-3-18-2-4/h1-3H

Synthetic route

Hexafluoroacetone (684-16-2) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With isopropyl alcohol at 240℃; for 6h; uncatalyzed Meerwein-Ponndorf-Verley reduction;	96%
With K(1+)*(C54H46P3Ru)(1-)*C10H8*(C2H5)2O; hydrogen In toluene at 85℃; under 4650.4 Torr; for 2h;
With sodium tetrahydroborate In water

1,1,1,3,3,3-hexafluoroisopropyl chloromethyl ether (26103-07-1) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + sevoflurane (28523-86-6)

Conditions	Yield
With hydrogenchloride; potassium fluoride; water; Aliquat HTA-1 at 100℃; for 3h; Product distribution / selectivity;	A 1.05 %Chromat. B 93%
With potassium fluoride; potassium hydrogenfluoride; water; Aliquat 175 at 100℃; for 3h; Product distribution / selectivity;	A 3.8 %Chromat. B 89%
With potassium fluoride; potassium hydrogenfluoride; water; benzyl triethyl ammonium dichloride at 100℃; for 3h; Product distribution / selectivity;	A 4 %Chromat. B 88%

chloro-trimethyl-silane (75-77-4) + Hexafluoroacetone (684-16-2) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 1,1,3,3,3-pentafluoro-2-trimethylsiloxypropene (53841-59-1)

Conditions	Yield
With magnesium In N,N-dimethyl-formamide at -20 - 0℃; for 1h; Title compound not separated from byproducts.;	A 3% B 80%

heptafluoropropan-2-ol (24427-67-6) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With ruthenium on active carbon; hydrogen fluoride; hydrogen at 0 - 25℃; under 7500.75 Torr; for 1h; chemoselective reaction;	76%

N-(2,2,2-trifluoro-1-trifluoromethyl-ethylidene)-benzamide (5022-41-3) + 1,1,1,3,3,3-Hexafluoro-propan-2-olatebenzyl-methyl-methylene-ammonium; → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 2-phenyl-4,4-bis(trifluoromethyl)-5-N-methylbenzylamino-2-oxazoline (93032-16-7)

Conditions	Yield
In pyridine for 25h; Product distribution; Irradiation;	A 60% B 35%

methyl(1,1,1,3,3,3-hexafluoro-2-propoxo){1,2-bis(diphenylphosphino)ethane}palladium (115981-43-6) → methane (34557-54-5) + ethene (74-85-1) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
In further solvent(s) Thermolysis of starting complex (diphenylmethane, vac., 150°C).; GLC.;	A 15% B 2% C 57%

piperidine (110-89-4) + Hexafluoroacetone (684-16-2) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 3-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)-5-(1H-1-trifluoromethyl-2,2,2-trifluoroethyl)-pyridine (108440-27-3) + 2,2’-(pyridine-3,5-diyl)bis(1,1,1,3,3,3-hexafluoropropan-2-ol) (108440-28-4)

Conditions	Yield
In 1,1,2-Trichloro-1,2,2-trifluoroethane at 90℃;	A n/a B 50.5% C 21.3%

methyl(1,1,1,3,3,3-hexafluoro-2-propoxo)(2,2'-bipyridine)nickel (115981-38-9) → methane (34557-54-5) + ethane (74-84-0) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
In further solvent(s) Thermolysis of soln. of metal complex in diphenylmethane (under vac., 150°C).; GLC.;	A 46% B 16% C <1

ethyl(1,1,1,3,3,3-hexafluoro-2-propoxo)(2,2'-bipyridine)nickel (115981-39-0) → ethane (74-84-0) + ethene (74-85-1) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
In further solvent(s) Thermolysis of starting compd. (diphenylmethane, vac., 150°C).; GLC.;	A 32% B 43% C <1

benzaldehyde (100-52-7) + Hexafluoroacetone (684-16-2) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + benzene (71-43-2)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); 1,3-bis{2,6-bis(diphenylmethyl)-4-methylphenyl}-imidazolin-2-ylidene In tetrahydrofuran at 40℃; Inert atmosphere;	A 11% B 31%

2,2,2-trifluoroethanol (75-89-8) + Dimethyl-phenyl-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-silane (151623-41-5) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + (2,2,2-trifluoroethoxy)dimethylphenylsilane (109629-96-1)

Conditions	Yield
With potassium 2,2,2-trifluoroethoxide at 30℃; Rate constant; μ = 0.05 M with potassium trifluoroacetate;

Hexafluoroacetone (684-16-2) → hexafluoroacetone hydrate (677-71-4) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 1,1,1,3,3,5,5,5-octafluoro-4-hydroxy-4-trifluoromethyl-pentan-2-one (52772-37-9) + 1,1,1,3,5,5,5-Heptafluoro-4-hydroxy-4-trifluoromethyl-pentan-2-one (115397-49-4)

Conditions	Yield
With tin(ll) chloride In N,N-dimethyl-formamide at 95℃; for 29h; sealed ampul;	A 3 % Chromat. B 25 % Chromat. C 62 % Chromat. D 4 % Chromat.
With tin(ll) chloride In N,N-dimethyl-formamide at 95℃; for 29h; sealed ampul;	A 3 % Chromat. B 25 % Chromat. C 62 % Chromat. D 4 % Chromat.
With tin(ll) chloride In N,N-dimethyl-formamide at 95℃; for 29h; sealed ampul;	A 3 % Chromat. B 25 % Chromat. C 25 % Chromat. D 4 % Chromat.

Dibenzo[a,j]acridine; compound with 1,1,1,3,3,3-hexafluoro-propan-2-ol → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + dibenz[a,j]acridine (224-42-0)

Conditions	Yield
In tetrachloromethane at 19.9℃; Thermodynamic data; Equilibrium constant;
In n-heptane at 19.9℃; Thermodynamic data; Equilibrium constant;

Dimethyl-phenyl-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-silane (151623-41-5) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + dimethylphenylsilanol (5272-18-4)

Conditions	Yield
With Na2CO3 buffer; sodium hydrogencarbonate In acetonitrile at 30℃; Rate constant; μ = 0.06 M (NaCl);

1,1,1,3,3,3-hexafluoropropan-2-yl 2-phenylethanoate → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + phenylacetic acid anion (7631-42-7)

Conditions	Yield
With potassium chloride; hydroxide In 1,4-dioxane; water at 25℃; Rate constant; also for the pig liver esterase catalysed hydrolysis;

(4-Nitro-phenyl)-acetic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 4-nitrobenzeneacetic acid (104-03-0)

Conditions	Yield
In hexane; chloroform Rate constant; Ambient temperature; antibody IgG 27H9 as catalyst; 15percent Bicine buffer (pH = 9.0);

1,1,1,3,3,3-hexafluoroisopropyl acrylate (2160-89-6) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + acrylic acid (79-10-7)

Conditions	Yield
With (3R,8R,9S)-10,11-dihydro-3,9-epoxy-6'-hydroxy-cinchonane In d7-N,N-dimethylformamide at -40℃;

1,1,1,3,3,3-hexafluoroisopropyl nitrite → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With nitric acid Kinetics; Equilibrium constant; Further Variations:; Temperatures; Pressures;

1,1,1,3,3,3-hexafluoroisopropyl chloromethyl ether (26103-07-1) + dichlorosevo (28523-85-5) + formaldehyde di[2,2,2-trifluoro-1-(trifluoromethyl)ethyl] acetal → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With sulfuric acid; water for 18h; Conversion of starting material; Heating / reflux;

Hexafluoroacetone (684-16-2) → 1,1,1-trifluoro-2-propanone (421-50-1) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + hydrogen fluoride (7664-39-3)

Conditions	Yield
With hydrogen; catalyst

1,1,1,3,3,3-hexafluoroisopropyl chloromethyl ether (26103-07-1) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With water at 90℃; for 1.5h; Product distribution / selectivity;	21.2 %Chromat.

chloro-trimethyl-silane (75-77-4) + Hexafluoroacetone (684-16-2) → trimethylsilyl fluoride (420-56-4) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + pentafluoroprop-1-en-2-ol (53841-56-8)

Conditions	Yield
Stage #1: chloro-trimethyl-silane; Hexafluoroacetone With magnesium In N,N-dimethyl-formamide at -20 - 0℃; for 1h; Stage #2: With sulfuric acid at -30 - 0℃; for 4h; Further stages. Title compound not separated from byproducts.;	A n/a B n/a C 7.1 g

C4H4F6O2 + sevoflurane (28523-86-6) → formaldehyde fluoromethyl [2,2,2-trifluoro-1-(trifluoromethyl)ethyl] acetal (194039-91-3) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

methyl 3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propionate (7594-51-6) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
With pyridine hydrochloride In N,N-dimethyl-formamide at 120℃; Product distribution / selectivity;

C3H2F6O*C3H7NO → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + N,N-dimethyl-formamide (68-12-2, 33513-42-7)

Conditions	Yield
In octanol at 24.84℃; Equilibrium constant;

C3H2F6O*C4H9NO (22868-56-0) → N,N-dimethyl acetamide (127-19-5) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
In octanol at 24.84℃; Equilibrium constant;

C2H6OS*C3H2F6O (22868-53-7) → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + dimethyl sulfoxide (67-68-5)

Conditions	Yield
In octanol at 24.84℃; Equilibrium constant;

C3H2F6O*C6H15O4P → triethyl phosphate (78-40-0) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1)

Conditions	Yield
In octanol at 24.84℃; Equilibrium constant;

C3H2F6O*C5H13N3 → 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + N,N,N',N'-tetramethylguanidine (80-70-6)

Conditions	Yield
In octanol at 24.84℃; Equilibrium constant;

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + cubyl trifluoromethanesulphonate (125762-86-9) → cubyl hexafluoroisopropyl ether

Conditions	Yield
for 0.0833333h; Ambient temperature;	100%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → 2,2,2-trifluoro-1-(trifluoromethyl)ethyl sulfamate

Conditions	Yield
With formic acid; isocyanate de chlorosulfonyle In 1-methyl-pyrrolidin-2-one; acetonitrile at 0 - 23℃; Inert atmosphere;	100%
With sulphamoyl chloride In N,N-dimethyl acetamide
With formic acid; isocyanate de chlorosulfonyle In dimethyl amine; acetonitrile at 0 - 20℃; for 16.1667h;
With formic acid; isocyanate de chlorosulfonyle In N,N-dimethyl acetamide; acetonitrile at 20℃; Cooling with ice;

C14H11NO2 (947697-83-8) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → C17H13F6NO3

Conditions	Yield
silver trifluoromethanesulfonate In 1,2-dichloro-ethane at 25℃;	100%

CH2Cl2:MeOH + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → 2,3,5-Tri-O-p-Methoxybenzyl-1,4-dideoxy-1,4-[[(2S,3S)-2,4-benzylidenedioxy-3-(sulfooxy)butyl]-episulfoniumylidene]-D-arabinitol + (2R,3S,4S)-2-(hydroxymethyl)tetrahydrothiophene-3,4-diol (160882-26-8)

Conditions	Yield
With potassium carbonate	A 100% B n/a

sodium tetrahydroborate (16940-66-2) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → Sodium Tris(1,1,1,3,3,3-hexafluoroisopropoxy)borohydride

Conditions	Yield
In tetrahydrofuran at 0℃;	100%

4-butoxy-2,2-bis-trifluoromethyl-oxetane (17129-00-9) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → C12H14F12O3 (1226778-14-8)

Conditions	Yield
at 25 - 35℃;	100%

Mo(N(2,6-diisopropylphenyl))(CHtBu)(CH2tBu)2 + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → Mo(N-2,6-i-Pr2C6H3)(CH2-t-Bu)3[OCH(CF3)2]

Conditions	Yield
In neat (no solvent) under N2 atm. (CF3)2CHOH was added to Mo complex and stirred for 10 min; excess alcohol was removed in vacuo;	99%

2-allyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl acetate (861104-99-6) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → C14H11F6NO2 (1567381-18-3)

Conditions	Yield
With acetylacetone at 58℃; for 38h; Time; Temperature;	99%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 2-allyl-2,3-dihydro-3-hydroxy-isoindol-1-one (128425-74-1, 41764-19-6) → C13H12F3NO2 (1567381-17-2)

Conditions	Yield
With acetylacetone at 58℃; for 38h;	99%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + cis-2-phenylcyclohexanol (2362-61-0, 16201-63-1, 17540-18-0, 34281-92-0, 37982-27-7, 40960-69-8, 40960-73-4, 98919-68-7, 1444-64-0) → 2-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)-7-phenyloxepane

Conditions	Yield
With 1,1'-(phenyl-λ3-iodanediyl)bis(2-methoxypyridin-1-ium)trifluoromethanesulfonate In 1,2-dichloro-ethane at 60℃; Molecular sieve; Inert atmosphere;	99%

titanium(IV) isopropylate (546-68-9) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → C12H16F12O4Ti

Conditions	Yield
at 70℃; for 2h; Inert atmosphere;	99%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 2-chloro-N-(phenylmethoxy)propanamide (1303507-91-6) + anthranil (271-58-9) → 1,1,1,3,3,3-hexafluoropropan-2-yl 2-((1-((benzyloxy)amino)-1-oxopropan-2-yl)amino)benzoate

Conditions	Yield
With sodium carbonate at 50℃; for 4h; Inert atmosphere; Schlenk technique;	99%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + 1-bromomethyl-4-nitro-benzene (100-11-8) → 1-((1,1,1,3,3,3-hexafluoropropan-2-yloxy)-methyl)-4-nitrobenzene (1278547-62-8)

Conditions	Yield
With sodium In N,N-dimethyl-formamide for 2h; Reflux;	98.8%

Methyl fluorosulfonate (421-20-5) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → 1,1,1,3,3,3-hexafluoro-2-methoxypropane (13171-18-1)

Conditions	Yield
at 25℃; Temperature;	98.8%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + methyl chloroformate (79-22-1) → carbonic acid methyl ester 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester

Conditions	Yield
With 1,1,1,3,3,3-hexafluoro-2-methoxypropane; triethylamine at 30℃; for 2h;	98.6%
With water at 40℃; Kinetics; solvolysis;

chlorosulfonic acid (7790-94-5) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → 1,1,1,3,3,3-hexafluoropropyloxysulfonic acid (1616761-45-5)

Conditions	Yield
at -15 - 140℃;	98%

indole (120-72-9) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → 1,1,1,3,3,3-hexafluoro-2-(1H-indol-3-yl)propan-2-ol (23814-16-6)

Conditions	Yield
With copper diacetate; 4,4'-di-tert-butyl-2,2'-bipyridine at 90℃; for 24h; Schlenk technique; regioselective reaction;	98%
With bis(1-methyl-1-phenylethyl)peroxide; copper(I) bromide In tert-butyl alcohol at 140℃; for 12h; Sealed tube;	54%

[Yb{N(SiMe3)2}3] (429658-02-6) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → [cis-(H2O)2(1,1,1,3,3,3-hexafluoro-iso-propoxide)2Yb(μ-1,1,1,3,3,3-hexafluoro-iso-propoxide)]2

Conditions	Yield
In toluene Inert atmosphere; Glovebox;	98%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + cis-2-(2-bromophenyl)cyclobutan-1-ol → 2-(2-bromophenyl)-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)tetrahydrofuran

Conditions	Yield
With 1,1'-(phenyl-λ3-iodanediyl)bis(2-methoxypyridin-1-ium)trifluoromethanesulfonate In 1,2-dichloro-ethane at 60℃; Molecular sieve; Inert atmosphere;	98%

1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) + (+/-)-cis-2-phenylcyclopentanol (2362-73-4, 38805-76-4, 38805-89-9, 38805-90-2, 38806-01-8, 42086-64-6) → 2-Phenylcyclopentanone (1198-34-1) + 2-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)-6-phenyltetrahydro-2H-pyran

Conditions	Yield
With 1,1'-(phenyl-λ3-iodanediyl)bis(2-methoxypyridin-1-ium)trifluoromethanesulfonate In 1,2-dichloro-ethane at 60℃; Molecular sieve; Inert atmosphere;	A n/a B 98%

N-Ac-Leu (1188-21-2) + 1,1,1,3',3',3'-hexafluoro-propanol (920-66-1) → C11H15F6NO3

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 4.5h;	98%

Upstream product

• 110-89-4 piperidine 
• 684-16-2 Hexafluoroacetone 
• 5022-41-3 N-(2,2,2-trifluoro-1-trifluoromethyl-ethylidene)-benzamide 
• 151623-41-5 Dimethyl-phenyl-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-silane 
• 2160-89-6 1,1,1,3,3,3-hexafluoroisopropyl acrylate 
• 26103-07-1 1,1,1,3,3,3-hexafluoroisopropyl chloromethyl ether 
• 28523-85-5 dichlorosevo 
• 115981-39-0 ethyl(1,1,1,3,3,3-hexafluoro-2-propoxo)(2,2'-bipyridine)nickel 
• 28523-86-6 sevoflurane 
• 2923-18-4 sodium 2,2,2-trifluoroacetate 
• 109-94-4 formic acid ethyl ester 
• 1864-94-4 phenyl formate 
• 2923-16-2 potassium trifluoroacetate 
• 3336-58-1 2,2,2-trifluoroacetic acid ammonia 

Downstream Products

• 23794-78-7 (4-Trifluoromethyl-phenyl)-carbamic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester 
• 288-88-0 1,2,4-Triazole 
• 90160-97-7 [1,2,4]Triazole-1-carboxylic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester 
• 67777-21-3 diphenyl 2,2,2-tri-fluoro-1-(trifluoromethyl)ethyl phosphite 
• 80764-79-0 1-methylcyclohexylhexafluoroisopropylether 
• 118334-96-6 1,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester 
• 97850-69-6 Bicyclo[2.2.1]hept-2-ene-2-carboxylic acid dimethylamide 
• 97850-71-0 Tricyclo[2.2.1.0^2,6]heptane-1-carboxylic acid dimethylamide 
• 153559-07-0 1,1,1,3,3,3-Hexafluoro-2-propyl methyl benzoylphosphonate 
• 98-11-3 benzenesulfonic acid 
• 98-66-8 4-chloro-benzenesulfonic acid 
• 138-42-1 p-nitrobenzenesulfonic acid 
• 80252-66-0 Methyl-phenyl-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-vinyl-silane 
• 80252-65-9 Dimethyl-((E)-styryl)-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-silane 

Relevant articles and documents

1,1,1,3,3,3-Hexafluoroisopropanol as a Remarkable Medium for Atroposelective Sulfoxide-Directed Fujiwara-Moritani Reaction with Acrylates and Styrenes

Axially chiral biaryls are ubiquitous structural motifs of biologically active molecules and privileged ligands for asymmetric catalysis. Their properties are due to their configurationally stable axis, and therefore, the control of their absolute configuration is essential. Efficient access to atropo-enantioenriched biaryl moieties through asymmetric direct C-H activation, by using enantiopure sulfoxide as both the directing group (DG) and chiral auxiliary, is reported. The stereoselective oxidative Heck reactions are performed in high yields and with excellent atropo-stereoselectivities. The pivotal role of 1,1,1,3,3,3-hexafluoropropanol (HFIP) solvent, which enables a drastic increase in yield and stereoselectivity of this transformation, is evidenced and investigated. Finally, the synthetic usefulness of the herein disclosed transformation is showcased because the traceless character of the sulfoxide DG allows straightforward conversions of the newly accessed, atropopure sulfoxide-biaryls into several differently substituted axially chiral scaffolds.

Preparation method of hexafluoroisopropyl methyl ether

The invention discloses a preparation method of 1,1,1,3,3,3-hexafluoroisopropyl methyl ether. The preparation method includes reacting trifluoroacetate with formate to obtain 1,1,1,3,3,3-hexafluoroisopropanol, and applying a methylation reagent to the 1,1,1,3,3,3-hexafluoroisopropanol to obtain the 1,1,1,3,3,3-hexafluoroisopropyl methyl ether. The preparation method has the advantages that raw materials are cheap and easy to obtain, the preparation process is mild and the method is simple to operate.

Method for synthesizing hexafluoroacetone and method for synthesizing hexafluoroisopropanol

The invention provides a method for synthesizing hexafluoroacetone and a method for synthesizing hexafluoroisopropanol. The method for synthesizing hexafluoroacetone comprises the following steps: generating first-step substitution reaction by virtue of hexachloroacetone and hydrogen fluoride under the effect of a first catalyst so as to generate a first product, wherein the temperature of the first-step substitution reaction is 70-80 DEG C, and the first catalyst is a trivalent chromium compound; and generating second-step substitution reaction by virtue of the first product and hydrogen fluoride under the effect of a second catalyst so as to generate hexafluoroacetone, wherein the temperature of the second-step substitution reaction is 350-400 DEG C, and the second catalyst is a trivalent chromium compound. The method for synthesizing hexafluoroisopropanol comprises the steps of carrying out all steps of the method for synthesizing hexafluoroacetone, and further carrying out reductive hydrogenation. According to the two methods, the problem that carbon is easily generated in a traditional process is solved.

Nickel N-heterocyclic carbene catalyzed C-C bond formation: A new route to aryl ketones

A novel nickel N-heterocyclic carbene catalyzed cross-coupling reaction of aryl aldehydes with boronic esters for the synthesis of aryl ketones was developed. This reaction provides a mild, practical method toward aryl ketones, which are versatile intermediates and building blocks in organic synthesis.

Manufacture of hexafluoroisopropanol

Hexafluoroisopropanol (CF3CHOHCF3) is manufactured in two steps from monochloromalonic acid or monochlomalonic acid esters by a reaction with a fluorinating agent, notably SF4, to form CF3CHClCF3 which is hydrolyzed to form CF3CHOHCF3. The hexafluoroisopropanol can be used as such, or, preferably, it is further reacted to form Sevoflurane, an anesthetic. Compounds of the formula CF3-CH(OY)-CF3 wherein Y is OTs, OMe, OTf or OTMS are also described.

HF-mediated equilibrium between fluorinated ketones and the corresponding α-fluoroalcohols

We have successfully obtained the first unambiguous spectroscopic proof of the structure of heptafluoropropan-2-ol by 13C NMR, which has been assumed from early 70s but without unequivocal evidence. Equilibrating relationship between fluorinated ketones and the corresponding hydrates as well as α-fluoroalcohols in anhydrous HF was at least qualitatively supported by our ab initio computation, and moreover, anhydrous HF as a convenient solvent was found to offer an effective new route for production of 1,1,1,3,3,3-hexafluoropropan-2-ol in industrial scales.

Hydrogen bonding between solutes in solvents octan-1-ol and water

The 1:1 equilibrium constants, K, for the association of hydrogen bond bases and hydrogen bond acids have been determined by using octan-1-ol solvent at 298 K for 30 acid-base combinations. The values of K are much smaller than those found for aprotic, rather nonpolar solvents. It is shown that the log K values can satisfactorily be correlated against αH 2?βH2, where αH 2 and βH2 are the 1:1 hydrogen bond acidities and basicities of solutes. The slope of the plot, 2.938, is much smaller than those for log K values in the nonpolar organic solvents previously studied. An analysis of literature data on 1:1 hydrogen bonding in water yields a negative slope for a plot of log K against αH 2?βH2, thus showing how the use of very strong hydrogen bond acids and bases does not lead to larger values of log K for 1:1 hydrogen bonding in water. It is suggested that for simple 1:1 association between monofunctional solutes in water, log K cannot be larger than about -0.1 log units. Descriptors have been obtained for the complex between 2,2,2-trifluoroethanol and propanone, and used to analyze solvent effects on the two reactants, the complex, and the complexation constant.

METHOD FOR PRODUCING FLUOROALKYL ALCOHOL

The present invention provides a method for producing a fluoroalkyl alcohol represented by general formula (6) wherein Rf1 and Rf2 are the same or different, each represents a CF3(CF2)n group (wherein n is an integer of 0 to 10) or a CH3(CH2)m group (wherein m is an integer of 0 to 10), and at least one of Rf1 and Rf2 represents a CF3(CF2)n group, the method comprising: decarboxylating a compound represented by general formula (1) wherein Rf1 and Rf2 are the same as above; and R1 represents an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an alkali metal, or M1/2 (wherein M represents an alkaline earth metal), in the presence of at least one member selected from the group consisting of pyridines, amines, quaternary ammonium salts, and quaternary phosphonium salts. According to the present invention, fluoroalkyl alcohol such as hexafluoroisopropyl alcohol can be easily produced with high selectivity, using an inexpensive starting material.

Continuous process to produce hexafluoroisopropanol

A continuous process for producing hexafluoroisopropanol is provided which comprises contacting hexafluoroacetone with hexafluoroisopropanol and hydrogen to produce a liquid feed stream; introducing the liquid feed stream to a reactor containing an immobilized hydrogenation catalyst to convert the hexafluoroacetone to hexafluoroisopropanol and provide a product stream; and recovering at least a portion of the hexafluoroisopropanol from the product stream. Preferably a portion of the product stream is recycled. The reactor can be a packed bed or stirred tank reactor.

One-pot synthesis of 3-fluoro-4-(trifluoromethyl)quinolines from pentafluoropropen-2-ol and their molecular modification

(Chemical Equation Presented) Pentafluoropropen-2-ol (PFP) was prepared by the reaction of hexafluoroacetone (HFA) with Mg/TMSCl. The one-pot tandem sequential reactions of PFP via Mannich addition with aldimines followed by Friedel-Crafts cyclization and aromatization afforded the title quinolines. A variety of corresponding 3-substituted quinolines were derived from the title quinoline by nucleophilic substitution of 3-fluorine with nucleophiles. A defluorinative transformation of the 4-trifluoromethyl group of the title quinoline with hydrazine afforded py razoloquinoline.