42916-66-5

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-Trifluoromethylphenyl)pentan-1-one is used as a reagent in the synthesis of 5,5-diarylpentadienamides. These compounds are TRPV1 antagonists, which are being developed as potential treatments for neuropathic pain. 1-(4-TRIFLUOROMETHYL-PHENYL)-PENTAN-1-ONE's role in the synthesis process is crucial for the development of these therapeutic agents.
Used in Enzyme Inhibition:
1-(4-Trifluoromethylphenyl)pentan-1-one is used as an inhibitor of the enzyme carbonyl reductase. By inhibiting this enzyme, the compound may have potential applications in modulating metabolic pathways and could be useful in the development of drugs targeting specific diseases or conditions related to carbonyl reductase activity.

Upstream product

• 693-03-8 n-butyl magnesium bromide 
• 455-18-5 4-CF₃C₆H₄CN 
• 693-04-9 butyl magnesium bromide 
• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 110-62-3 pentanal 
• 455-13-0 4-Iodobenzotrifluoride 
• 98-56-6 4-chlorobenzotrifluoride 
• 455-24-3 4-trifluoromethylbenzoic acid 
• 329-15-7 4-trifluoromethyl-phenyl acetyl chloride 
• 116332-61-7 N-methoxy-N-methyl-4-trifluoromethylbenzamide 
• 416839-38-8 4-trifluoromethylphenylboronic acid 1,3-propanediol ester 
• 120-92-3 cyclopentanone 
• 109-72-8 n-butyllithium 
• 124-38-9 carbon dioxide 

Downstream Products

• 709-63-7 1-(4-trifluoromethylphenyl)ethanone 
• 335281-14-6 5-propyl-4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamine 

Relevant academic research and scientific papers

A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.

Rhodium-Catalyzed Deoxygenation and Borylation of Ketones: A Combined Experimental and Theoretical Investigation

The rhodium-catalyzed deoxygenation and borylation of ketones with B2pin2 have been developed, leading to efficient formation of alkenes, vinylboronates, and vinyldiboronates. These reactions feature mild reaction conditions, a broad substrate scope, and excellent functional-group compatibility. Mechanistic studies support that the ketones initially undergo a Rh-catalyzed deoxygenation to give alkenes via boron enolate intermediates, and the subsequent Rh-catalyzed dehydrogenative borylation of alkenes leads to the formation of vinylboronates and diboration products, which is also supported by density functional theory calculations.

I-Pr2NMgCl·LiCl Enables the Synthesis of Ketones by Direct Addition of Grignard Reagents to Carboxylate Anions

The direct preparation of ketones from carboxylate anions is greatly limited by the required use of organolithium reagents or activated acyl sources that need to be independently prepared. Herein, a specific magnesium amide additive is used to activate and control the addition of more tolerant Grignard reagents to carboxylate anions. This strategy enables the modular synthesis of ketones from CO2 and the preparation of isotopically labeled pharmaceutical building blocks in a single operation.

Suzuki-Miyaura coupling of simple ketones via activation of unstrained carbon-carbon bonds

Here, we describe that simple ketones can be efficiently employed as electrophiles in Suzuki-Miyaura coupling reactions via catalytic activation of unstrained C-C bonds. A range of common ketones, such as cyclopentanones, acetophenones, acetone and 1-indanones, could be directly coupled with various arylboronates in high site-selectivity, which offers a distinct entry to more functionalized aromatic ketones. Preliminary mechanistic study suggests that the ketone α-C-C bond was cleaved via oxidative addition.

Co (II)-C12 alkyl carbon chain multi-functional ionic liquid immobilized on nano-SiO2 nano-SiO2@CoCl3-C12IL as an efficient cooperative catalyst for C–H activation by direct acylation of aryl halides with aldehydes

Nano-silica supported ionic liquids composed of alkyl carbon chain and transition metal chlorides anions have been prepared and successfully applied as a heterogeneous catalyst in the direct aldehyde C-H activation. Catalytic results indicated that nano-SiO2 supported ionic liquid consisting C12 alkyl carbon chain and CoCl3 anion nano-SiO2@CoCl3-C12IL showed excellent catalytic properties with good to excellent yields towards the desired aryl ketones. The excellent recyclability of the supported catalyst, mild reaction conditions, low catalyst loading, and operational simplicity are the important features of this methodology.

Photocatalytic E → Z isomerization of polarized alkenes inspired by the visual cycle: Mechanistic dichotomy and origin of selectivity

Iteratively executed with exquisite spatial and temporal control, the selective isomerization of polarized alkenes underpins a plethora of complex biological processes ranging from natural product biosynthesis through to the mammalian visual cycle. However, nature's proficiency conceals the inherent difficulties in replicating this contrathermodynamic transformation in the laboratory. Recently, we disclosed the first highly Z-selective isomerization of polarized alkenes, employing the cinnamoyl chromophore as a retinal surrogate under UV-irradiation (402 nm) with (-)-riboflavin (Vitamin B2) as an inexpensive, organic photocatalyst (J. Am. Chem. Soc. 2015, 137, 11254-11257). This study was inspired by the propensity of crystalline (-)-riboflavin in the eyes of vertebrates to invert the intrinsic directionality of retinal isomerization. Herein, we extend this methodology to include a bioinspired, catalytic E → Z isomerization of α,β-unsaturated nitriles, thereby mimicking the intermediate Opsin-derived, protonated Schiff base in the visual cycle with simple polarized alkenes. Replacement of the iminium motif by a cyano group is well tolerated and gives an additional degree of versatility for postisomerization functionalization. Broad substrate scope is demonstrated (up to 99:1 Z:E) together with evidence of mechanistic dichotomy via both singlet and triplet energy transfer mechanisms. Kinetic studies, temperature dependent photostationary state correlations and investigation of substituent-based electronic perturbation of the alkene identified polarization combined with increased Z-isomer activation barriers as the selectivity governing factors in catalysis. This investigation demonstrates the importance of internal structural preorganization on photostationary composition and explicates the augmented Z-selectivity upon hydrogen-alkyl exchange at the β-position of the alkene.

Continuous flow synthesis of ketones from carbon dioxide and organolithium or grignard reagents

We describe an efficient continuous flow synthesis of ketones from CO 2 and organolithium or Grignard reagents that exhibits significant advantages over conventional batch conditions in suppressing undesired symmetric ketone and tertiary alcohol byproducts. We observed an unprecedented solvent-dependence of the organolithium reactivity, the key factor in governing selectivity during the flow process. A facile, telescoped three-step-one-flow process for the preparation of ketones in a modular fashion through the in-line generation of organometallic reagents is also established.

1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogues: A promising class of monoamine uptake inhibitors

Dopamine, serotonin, and norepinephrine are essential for neurotransmission in the mammalian system. These three neurotransmitters have been the focus of considerable research because the modulation of their production and their interaction at monoamine receptors has profound effects upon a multitude of pharmacological outcomes. Our interest has focused on neurotransmitter reuptake mechanisms in a search for medications for cocaine abuse. Herein we describe the synthesis and biological evaluation of an array of 2-aminopentanophenones. This array has yielded selective inhibitors of the dopamine and norepinephrine transporters with little effect upon serotonin trafficking. A subset of compounds had no significant affinity at 5HT1A, 5HT1B, 5HT1C, D1, D2, or D3 receptors. The lead compound, racemic 1-(4-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one 4a, was resolved into its enantiomers and the S isomer was found to be the most biologically active enantiomer. Among the most potent of these DAT/NET selective compounds are the 1-(3,4-dichlorophenyl)- (4u) and the 1-naphthyl- (4t) 2-pyrrolidin-1-yl-pentan-1-one analogues.

PYROVALERONE ANALOGS AND THERAPEUTIC USES THEREOF

New compounds that bind to monoamine transporters are described. The compounds of the present invention can be racemic or pure R-or S-enantiomers. Certain preferred compounds of the present invention have a high selectively dopamine transporter versus the serotonin transporter. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.

Direct catalytic asymmetric aldol-Tishchenko reaction

A direct catalytic asymmetric aldol reaction of propionate equivalent was achieved via the aldol-Tishchenko reaction. Coupling an irreversible Tishchenko reaction to a reversible aldol reaction overcame the retro-aldol reaction problem and thereby afforde