350-92-5

Usage

Uses

Used in Pharmaceutical Industry:
3-PHENYL-1,1,1-TRIFLUOROPROPAN-2-ONE is used as a neuroprotective agent for its ability to protect cerebellar granule neurons (CGNs) from low K(+)-induced apoptosis. This makes it a promising candidate for the development of treatments targeting neurodegenerative diseases and conditions involving neuronal cell death.
Used in Research and Development:
In the field of scientific research, 3-PHENYL-1,1,1-TRIFLUOROPROPAN-2-ONE serves as a valuable compound for studying the mechanisms of neuronal apoptosis and the development of neuroprotective strategies. Its use in laboratory settings can contribute to a better understanding of neurodegenerative processes and the potential for novel therapeutic interventions.
Used in Chemical Synthesis:
As a trifluoromethyl ketone, 3-PHENYL-1,1,1-TRIFLUOROPROPAN-2-ONE may also find applications in the chemical synthesis of various compounds, particularly those requiring a trifluoromethyl group. Its unique chemical properties can be leveraged in the development of new pharmaceuticals, agrochemicals, or other specialty chemicals.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 42, p. 3315, 1999 DOI: 10.1021/jm980734aTetrahedron Letters, 28, p. 4259, 1987 DOI: 10.1016/S0040-4039(00)96479-7The Journal of Organic Chemistry, 54, p. 661, 1989 DOI: 10.1021/jo00264a029

InChI:InChI=1/C9H7F3O/c10-9(11,12)8(13)6-7-4-2-1-3-5-7/h1-5H,6H2

Upstream product

• 492-16-0 2-phenyl-2-trifluoroacetyl-acetonitrile 
• 1589-82-8 phenylmagnesium bromide 
• 76-05-1 trifluoroacetic acid 
• 108535-39-3 α-trifluoromethyl-β-phenylethanol 
• 383-63-1 ethyl trifluoroacetate, 
• 140-29-4 phenylacetonitrile 
• 6921-34-2 benzylmagnesium chloride 
• 100-44-7 benzyl chloride 
• 108-88-3 toluene 
• 136430-43-8 (Z)-(2-ethoxy-3,3,3-trifluoroprop-1-enyl)benzene 
• 770-09-2 benzyltrimethylsilane 
• 5409-59-6 1,4-diphenyl-3-butene-2-one 
• 28614-89-3 (E)-1,1-diphenyl-2-(2-phenylethylidene)hydrazine 
• 122-78-1 phenylacetaldehyde 

Downstream Products

• 428-84-2 5-benzyl-5-trifluoromethyl-imidazolidine-2,4-dione 
• 404-20-6 (+/-)-1,1,1-trifluoro-3-phenyl-2-aminopropane 
• 395-15-3 3-Bromo-3-phenyl-1,1,1-trifluoro-propan-2-one 
• 672-49-1 benzoic acid-(2-phenyl-1-trifluoromethyl-vinyl ester) 
• 7781-82-0 2-Benzyl-pentafluor-propen 
• 97531-21-0 (E)-4-Phenyl-3-trifluoromethyl-but-3-enoic acid ethyl ester 
• 127700-39-4 C₂₄H₃₁F₃N₂O₂S 
• 119197-24-9 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal 
• 119197-25-0 (Z)-2-phenyl-3-chloro-4,4,4-trifluoro-but-2-en-1-al 
• 158388-65-9 N-(1,1,1-trifluoro-3-phenyl-iso-propylidene)benzylamine 
• 340980-09-8 benzyl-3 trifluoro-4,4,4 butene-2 oate d-ethyle 
• 154841-04-0 2-Benzyl-1,1,1-trifluoro-but-3-en-2-ol 

Relevant academic research and scientific papers

Access to substituted trifluoromethyl ketones using the versatile synthetic intermediate (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine

The N,N-dimethylhydrazone of 1,1,1-trifluoroacetone, (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine, has been shown to undergo a diverse set of reactions following deprotonation with n-butyl-lithium; including alkylation, addition to ketones and aldehydes, as well as palladium-catalyzed cross-couplings with aryl bromides. Mild hydrolysis of the N,N-dimethylhydrazone products from these transformations affords the corresponding trifluoromethyl ketones in good to excellent yields.

Catalytic highly enantioselective transfer hydrogenation of β-trifluoromethyl nitroalkenes. An easy and general entry to optically active β-trifluoromethyl amines

In the presence of a thiourea catalyst, β-CF3 nitroalkenes react with Hantzsch esters in a highly enantioselective fashion, giving a broad range of β-CF3 amine precursors with a tertiary stereocentre at the β-position. This reaction

Highly efficient synthesis of chiral α-CF3 amines via Rh-catalyzed asymmetric hydrogenation

Highly enantioselective catalytic asymmetric hydrogenation of α-CF3-enamides has been achieved by employing rhodium-DuanPhos as the catalyst, which provides a readily accessible method for the synthesis of chiral trifluoromethylated amines. The reaction has a broad substrate scope; both aryl- and alkyl-substituted α-CF3-enamides worked smoothly and afford the corresponding chiral amines in high yields and excellent enantioselectivities (up to 99% ee).

Copper-Catalyzed Trifluoromethylation of Aliphatic N-Arylhydrazones: A Concise Synthetic Entry to 2-Trifluoromethylindoles from Simple Aldehydes

The copper-catalyzed C(sp2)-H trifluoromethylation of N,N-disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde-derived substrates. The success of the reactions relied on the choice of the N,N-diphenylamino group as the terminal hydrazone amino group where N,N-dialkylamino groups were preferred for (hetero)aromatic aldehyde-derived substrates. In addition, the trifluoromethylated N-arylhydrazones are shown to be ideal substrates for Fischer indole synthesis allowing a straightforward, three-step access to 2-trifluoromethylindole derivatives from simple aldehydes.

Economical and practical strategies for synthesis of α-trifluoromethylated amines

A powerful approach to synthesize α-trifluoromethylated amines has been developed. The method is operationally simple, broad in substrate scope and amenable to scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only provided a versatile approach to synthesize α-trifluoromethylated amines but also provides a new method for exploring the new reactivity of trifluoroacetic anhydride.

Highly selective trifluoroacetic ester/ketone metathesis: An efficient approach to trifluoromethyl ketones and esters

A highly selective and atom efficient 'trifluoroacetic ester/ketone metathesis' has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.

Stereoselective transformations of α-trifluoromethylated ketoximes to optically active amines by enzyme-nanometal cocatalysis: Synthesis of (s)-inhibitor of phenylethanolamine n-methyltransferase

One-pot cascade synthesis of optically active α-trifluoromethylated amines directly from ketoximes was accomplished with the use of Candida antarctica lipase B and catalysts prepared by atomic layer deposition (ALD). Compared to the commercial palladium catalyst, the ALD-prepared catalysts showed much higher activity and afforded various α-trifluoromethylated amides in good yields and with high enantioselectivity. One of the enantiopure amides was further hydrolyzed into the corresponding amine, which was treated as a crucial starting material for total synthesis of (S)-inhibitor of phenylethanolamine N-methyltransferase without loss of chiral information.

Chemoenzymatic dynamic kinetic resolution of α-trifluoromethylated amines: Influence of substitutions on the reversed stereoselectivity

Enzymatic resolution of α-trifluoromethylated amines via kinetic resolution (KR), dynamic kinetic resolution (DKR) employing CALB-Pd/Al 2O3, and a one-pot sequential process of KR/DKR/KR was investigated comparatively for the first time. Although CALB-catalyzed KR of α-trifluoromethylated amines with substituents of methyl (1a), isopropyl (1c), phenyl (1d) and benzyl group (1e) can provide good stereoselectivity factors E from 31 to >200 respectively, DKR and sequential process of KR/DKR/KR possess better practical application potential because of the higher conversion (62%-84%) and the similar enantiomeric excesses (90%-99%). The enantiopreference and inversion for the α-trifluoromethylated amines displayed by CALB were observed and explained by docking modes. Namely, for 1,1,1-trifluoro-2-propylamine (1a), the product amide with R-configuration was obtained, and the enantiopreference was converted to S for the amines (1b-1e) with substituents larger than methyl group. The catalysts recycle, and scale-up experiments were demonstrated successfully. All these results indicated the high efficiency and green feature of this enzymatic process, and its application significance.

Synthesis and application of benzyl-TMS derivatives as bench stable benzyl anion equivalents

The regioselective benzylic metalation of toluenes using BuLi/KO tBu/TMP(H) (LiNK metalation conditions) and subsequent transmetalation to Si by reaction with TMSCl provides a general one-pot procedure for the synthesis of substituted benzyltrimethylsilanes. ArCH 2Si(Me)3 derivatives are bench stable reagents yet can serve as benzyl anion equivalents under mild reaction conditions. Following activation with fluoride they can successfully participate in a wide range of additions to both non-enolizable and enolizable carbonyls. In addition, their use in the synthesis of isochromanones and trifluoromethylated amines is illustrated. The broad synthetic scope and mild practical conditions of use for ArCH2Si(Me)3 reagents demonstrate their general potential as benzyl anion equivalents.

Synthesis of trifluoromethyl ketones via tandem Claisen condensation and retro-Claisen C-C bond-cleavage reaction

A highly efficient, operationally simple approach to trifluoromethyl ketones has been developed that builds on the use of a tandem process involving Claisen condensation and retro-Claisen C-C bond cleavage reaction. Enolizable alkyl phenyl ketones were found to react readily with ethyl trifuoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones, which were quite different from the general Claisen condensation products, β-diketones. This procedure uses readily available starting materials and can be extended to the preparation of perfluoroalkyl ketones in excellent yield.