431-46-9

Usage

Uses

Used in Pharmaceutical Industry:
TRIFLUOROACETALDEHYDE METHYL HEMIACETAL is used as a chemical intermediate for the synthesis of various pharmaceuticals. Its unique properties allow it to be a key component in the development of new drugs, contributing to the advancement of medicinal chemistry.
Used in Agrochemical Industry:
In the agrochemical sector, TRIFLUOROACETALDEHYDE METHYL HEMIACETAL is utilized as an intermediate in the production of agrochemicals. Its role in this industry is crucial for the creation of effective pesticides and other agricultural chemicals that protect crops and enhance yield.
Used as a Solvent in Organic Chemistry:
TRIFLUOROACETALDEHYDE METHYL HEMIACETAL is employed as a solvent in various organic reactions. Its ability to dissolve a wide range of substances and facilitate chemical processes makes it a valuable asset in organic synthesis and research laboratories.

InChI:InChI=1/C3H5F3O2/c1-8-2(7)3(4,5)6/h2,7H,1H3/t2-/m1/s1

Upstream product

• 67-56-1 methanol 
• 75-90-1 2,2,2-Trifluoroacetaldehyde 
• 149-73-5 trimethyl orthoformate 
• 421-53-4 2,2,2-trifluoro-1,1-ethanediol 
• 75-46-7 trifluoromethan 
• 107-31-3 Methyl formate 
• 64-17-5 ethanol 
• 431-47-0 trifluoroacetic acid-methyl ester 
• 360-92-9 N,N-diethyl-2,2,2-trifluoroacetamide 
• 124-41-4 sodium methylate 

Downstream Products

• 105480-22-6 2-(1'-hydroxy-2',2',2'-trifluoroethyl)imidazole 
• 345959-36-6 1-(4-benzylpiperazin-1-yl)-2, 2, 2-trifluoroethanol 
• 402728-98-7 3,4-dimethyl-5-phenyl-2-(trilfuoromethyl)-1,3-oxazolane 
• 6776-45-0 N-(2,2,2-trifluoro-1-hydroxyethyl)-acetamide 
• 77342-37-1 1,1,1-trifluoropent-4-en-2-ol 
• 19687-12-8 3-(2,2,2-trifluoro-1-hydroxyethyl)cyclohexene 
• 911411-93-3 1-dibenzylamino-2,2,2-trifluoro-ethanol 
• 17049-74-0 tert-butyl (2,2,2-trifluoro-1-hydroxyethyl)carbamate 
• 304858-51-3 6-bromo-4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine 
• 344776-71-2 2-(1-hydroxy-2,2,2-trifluoroethyl)-3-hydroxy-6-methylpyridine 
• 84006-02-0 4,4'-(1H-trifluoroethylidene)bis(2-methylphenol) 
• 42415-20-3 trifluoroacetaldehyde methyl hemiacetal 
• 1064077-32-2 3-benzyloxy-2-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one 
• 116757-85-8 2,2,2-trifluoro-1-(indol-3-yl)ethanol 

Relevant academic research and scientific papers

SYNTHESIS OF FLUORO HEMIACETALS VIA TRANSITION METAL-CATALYZED FLUORO ESTER AND CARBOXAMIDE HYDROGENATION

This application is directed to use of transition metal-ligand complexes to hydrogenate fluorinated esters and carboxamides into fluorinated hemiacetals. Methods for synthesis of certain ligands are also provided.

Engineering Catalysts for Selective Ester Hydrogenation

The development of efficient catalysts and processes for synthesizing functionalized (olefinic and/or chiral) primary alcohols and fluoral hemiacetals is currently needed. These are valuable building blocks for pharmaceuticals, agrochemicals, perfumes, and so forth. From an economic standpoint, bench-stable Takasago Int. Corp.'s Ru-PNP, more commonly known as Ru-MACHO, and Gusev's Ru-SNS complexes are arguably the most appealing molecular catalysts to access primary alcohols from esters and H2 (Waser, M. et al. Org. Proc. Res. Dev. 2018, 22, 862). This work introduces economically competitive Ru-SNP(O)z complexes (z = 0, 1), which combine key structural elements of both of these catalysts. In particular, the incorporation of SNP heteroatoms into the ligand skeleton was found to be crucial for the design of a more product-selective catalyst in the synthesis of fluoral hemiacetals under kinetically controlled conditions. Based on experimental observations and computational analysis, this paper further extends the current state-of-the-art understanding of the accelerative role of KO-t-C4H9 in ester hydrogenation. It attempts to explain why a maximum turnover is seen to occur starting at 25 mol % base, in contrast to only 10 mol % with ketones as substrates.

Optimization and sustainability assessment of a continuous flow Ru-catalyzed ester hydrogenation for an important precursor of a β2-adrenergic receptor agonist

The development of a ruthenium-catalyzed continuous flow ester hydrogenation using hydrogen (H2) gas is reported. The reaction was utilized for the reduction of an important precursor in the synthesis of abediterol, a β2-adrenoceptor agonist that has undergone phase IIa clinical trials for the treatment of asthma and chronic obstructive pulmonary disorder. The reaction was investigated within a batch autoclave by using a design of experiments (DoE) approach to identify important parameter effects. The optimized flow process was successfully operated over 6 h with inline benchtop19F NMR spectroscopy for reaction monitoring. The protocol is shown to be high yielding (98% yield, 3.7 g h?1) with very low catalyst loading (0.065 mol%). The environmental impact of the Ru-catalyzed hydrogenation was assessed and compared to an existing stoichiometric lithium aluminum hydride (LAH) reduction and sodium borohydride (NaBH4) reduction. The process mass intensity (PMI) for the Ru-catalyzed hydrogenation (14) compared favorably to a LAH reduction (52) and NaBH4reduction (133).

METHOD FOR PRODUCING 1,2,2,2-TETRAFLUORO-ETHYL DIFLUOROMETHYL ETHER (DESFLURANE)

PROBLEM TO BE SOLVED: To provide a method for efficiently producing 1,2,2,2-tetrafluoro-ethyl difluoromethyl ether (desflurane), which is useful as an inhalation anesthetic, on an industrial scale. SOLUTION: By reacting hydrogen fluoride and trimethyl orthoformate to an equivalent (hemiacetal) of fluoral synthesized by hydrogenation reaction of methyl trifluoroacetate in the presence of a ruthenium catalyst, it can easily be converted to 1,2,2,2-tetrafluoro-ethyl methyl ether which is a synthetic intermediate of desflurane. The resulting 1,2,2,2-tetrafluoro-ethyl methyl ether can efficiently be derived to desflurane by chlorination followed by fluorination reaction. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Why does alkylation of the N-H functionality within M/NH bifunctional Noyori-type catalysts lead to turnover?

Molecular metal/NH bifunctional Noyori-type catalysts are remarkable in that they are among the most efficient artificial catalysts developed to date for the hydrogenation of carbonyl functionalities (loadings up to ～10-5 mol %). In addition, these catalysts typically exhibit high C=0/C=C chemo- and enantioselectivities. This unique set of properties is traditionally associated with the operation of an unconventional mechanism for homogeneous catalysts in which the chelating ligand plays a key role in facilitating the catalytic reaction and enabling the aforementioned selectivities by delivering/accepting a proton (H+) via its N-H bond cleavage/formation. A recently revised mechanism of the Noyori hydrogenation reaction (Dub, P. A et al. J. Am. Chem. Soc. 2014,136,3505) suggests that the N-H bond is not cleaved but serves to stabilize the turnover-determining transition states (TDTSs) via strong N-H···O hydrogen-bonding interactions (HBIs). The present paper shows that this is consistent with the largely ignored experimental fact that alkylation of the N-H functionality within M/NH bifunctional Noyori-type catalysts leads to detrimental catalytic activity. The purpose of this work is to demonstrate that decreasing the strength of this HBI, ultimately to the limit of its complete absence, are conditions under which the same alkylation may lead to beneficial catalytic activity.

POLYDENTATE LIGANDS AND THEIR COMPLEXES FOR MOLECULAR CATALYSIS

The present invention relates generally to novel achiral and chiral sulfur-, nitrogen- and phosphorus-containing ligands, designated as NNS-type, P(0)NS-type, PNS-type, SNNS-type, SNNP(0)-type, or SNNP-type polydentate ligands and transition metal complexes of these ligands. The catalysts derived from these ligands and transition metal complexes may be used in a wide range of catalytic reactions, including hydrogenation and transfer hydrogenation of unsaturated organic compounds, dehydrogenation of alcohols and boranes, various dehydrogenative couplings, and other catalytic transformations.

Air-Stable NNS (ENENES) Ligands and Their Well-Defined Ruthenium and Iridium Complexes for Molecular Catalysis

We introduce ENENES, a new family of air-stable and low-cost NNS ligands bearing NH functionalities of the general formula E(CH2)mNH(CH2)nSR, where E is selected from -NC4H8O, -NC4H8, or -N(CH3)2, m and n = 2 and/or 3, and R = Ph, Bn, Me, or SR (part of a thiophenyl fragment). The preparation and characterization of more than 15 examples of well-defined Ru and Ir complexes supported by these ligands that are relevant to bifunctional metal-ligand M/NH molecular catalysis are reported. Reactions of NNS ligands with suitable Ru or Ir precursors afford rich and diverse solid-state and solution chemistries, producing monometallic molecules as well as bimetallics in which the ligand coordinates to the metal via either bidentate (κ2[N,N'] or κ2[N',S]) or tridentate (κ3[N,N',S]) binding modes, depending on the basicity of the sulfur atom, CH2 chain length (m or n parameter), or identity of the transition metal. In the case of Ir, ligands bearing benzyl substituents lead to unprecedented κ4[N,N',S,C]-tetradentate core-structure complexes of the type [IrIIIHCl{κ4(N,N',S,C)-ligand}], resulting from ortho-metalation via C-H oxidative addition. Fourteen of these Ru and Ir complexes have been crystallographically characterized. Air- and moisture-stable complexes of the type trans-[RuIICl2{κ3[N,N',S]-ligand}(L)] (L = PPh3, PCy3, DMSO), and others, effect the selective hydrogenation of methyl trifluoroacetate into the important synthon trifluoroacetaldehyde methyl hemiacetal in basic methanol under relatively mild conditions (35-40 °C, 25 bar H2) with reasonable turnover numbers (i.e., > 1000), whereas the air-stable Ir monohydride complexes [IrIIIHCl{κ4(N,N',S,C)-ligand}] exhibit excellent catalytic activities and high chemoselectivity for the same reaction, reaching turnover numbers of >10 000.

PROCESS FOR PRODUCING A-FLUOROALDEHYDES

A production process of an α-fluoroaldehyde according to the present invention includes reaction of an α-fluoroester with hydrogen gas (H2) in the presence of a ruthenium complex. It is possible in the present invention to allow relatively easy industrial production of the α-fluoroaldehyde and to directly obtain, as stable synthetic equivalents of the α-fluoroaldehyde, not only a hydrate (as obtained by conventional techniques) but also a hemiacetal that is easy to purify and is of high value in synthetic applications. The present invention provides solutions to all problems in the conventional techniques and establishes the significantly useful process for production of the α-fluoroaldehyde.

Practical selective hydrogenation of α-fluorinated esters with bifunctional pincer-type ruthenium(II) catalysts leading to fluorinated alcohols or fluoral hemiacetals

Selective hydrogenation of fluorinated esters with pincer-type bifunctional catalysts RuHCl(CO)(dpa) 1a, trans-RuH2(CO)(dpa) 1b, and trans-RuCl2(CO)(dpa) 1c under mild conditions proceeds rapidly to give the corresponding fluorinated alcohols or hemiacetals in good to excellent yields. Under the optimized conditions, the hydrogenation of chiral (R)-2-fluoropropionate proceeds smoothly to give the corresponding chiral alcohol without any serious decrease of the ee value.

Taming of fluoroform: Direct nucleophilic trifluoromethylation of Si, B, S, and C centers

Fluoroform (CF3H), a large-volume by-product of the manufacture of Teflon, refrigerants, polyvinylidene fluoride (PVDF), fire-extinguishing agents, and foams, is a potent and stable greenhouse gas that has found little practical use despite the growing importance of trifluoromethyl (CF3) functionality in more structurally elaborate pharmaceuticals, agrochemicals, and materials. Direct nucleophilic trifluoromethylation using CF3H has been a challenge. Here, we report on a direct trifluoromethylation protocol using close to stoichiometric amounts of CF3H in common organic solvents such as tetrahydrofuran (THF), diethyl ether, and toluene. The methodology is widely applicable to a variety of silicon, boron, and sulfur-based electrophiles, as well as carbon-based electrophiles.