913955-35-8

Basic information

• Product Name: 3-Methyl-2-(trifluoromethyl)-1H-indole
• Synonyms: 3-METHYL-2-TRIFLUOROMETHYLINDOLE;3-Methyl-2-(trifluoromethyl)-1H-indole
• CAS NO: 913955-35-8
• Molecular Formula: C₁₀H₈F₃N
• Molecular Weight: 199.17
• Mol File: 913955-35-8.mol

Chemical Properties

• Melting Point: 73-74 °C
• Boiling Point: 266 °C
• Flash Point: 115 °C
• Appearance: /
• Density: 1.313
• Vapor Pressure: 0.0141mmHg at 25°C
• Refractive Index: 1.55
• Storage Temp.: 2-8°C
• PKA: 14.92±0.30(Predicted)
• CAS DataBase Reference: 3-Methyl-2-(trifluoromethyl)-1H-indole(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Methyl-2-(trifluoromethyl)-1H-indole(913955-35-8)
• EPA Substance Registry System: 3-Methyl-2-(trifluoromethyl)-1H-indole(913955-35-8)

Safety Data

• Hazardous Substances Data: 913955-35-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Methyl-2-(trifluoromethyl)-1H-indole is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its unique structure and functional groups make it a valuable building block for the development of new drugs with potential therapeutic applications.
Used in Chemical Research:
3-Methyl-2-(trifluoromethyl)-1H-indole is also utilized in chemical research as a model compound to study the reactivity and properties of indole derivatives. This helps researchers to better understand the behavior of similar compounds and develop new synthetic methods or applications.
Used in Material Science:
3-Methyl-2-(trifluoromethyl)-1H-indole may also find applications in material science, particularly in the development of new materials with specific properties. For example, its incorporation into polymers or other materials could lead to the creation of novel materials with improved characteristics, such as enhanced stability or specific binding affinities.

InChI:InChI=1/C10H8F3N/c1-6-7-4-2-3-5-8(7)14-9(6)10(11,12)13/h2-5,14H,1H3

Upstream product

• 887144-97-0 Togni's reagent 
• 83-34-1 3-Methylindole 
• 887144-94-7 Togni's reagent II 
• 421-83-0 trifluoromethane sulfonyl chloride 
• 100074-04-2 1-fluoro-4-(pent-4-en-1-yl)benzene 
• 1961266-44-3 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethanesulfonate 
• 2926-30-9 sodium triflate 
• 2926-29-6 Langlois reagent 
• 129946-88-9 Umemoto's reagent 
• 2314-97-8 iodotrifluoromethane 

Downstream Products

• 913955-36-9 (4-chloro-phenyl)[3-methyl-2-(trifluoromethyl)-1H-indol-1-yl]-methanone 
• 132502-93-3 2-trifluoromethyl-indole-3-acetic acid 
• 934843-29-5 dimethyl-2-{[1-(4-chlorobenzoyl)-2-(trifluoromethyl)indol-3-yl]methyl}malonate 
• 929075-62-7 [3-(bromomethyl)-2-(trifluoromethyl)-1H-indol-1-yl](4-chlorophenyl)methanone 

Relevant articles and documents

Nickel-Catalyzed C–H Trifluoromethylation of Electron-Rich Heteroarenes

The first example of a nickel-catalyzed C–H trifluoromethylation of electron-rich heteroarenes, including imidazopyridines, indoles and thiophenes, has been developed with the commercially available and relatively inexpensive industrial raw material iodotrifluoromethane (CF3I) as the trifluoromethylating reagent. The synthetic potential of this method is demonstrated by its successful application to the direct trifluoromethylation of the biologically active molecules melatonin and zolmitriptan. (Figure presented.).

Reductant-Induced Free Radical Fluoroalkylation of Nitrogen Heterocycles and Innate Aromatic Amino Acid Residues in Peptides and Proteins

A series of fluoroalkylated cyclic λ3-iodanes and their hydrochloride salts was prepared and used in a combination with sodium ascorbate in buffer or aqueous methanol mixtures for radical fluoroalkylation of a range of substituted indoles, pyrroles, tryptophan or its derivatives, and Trp residues in peptides. As demonstrated on several peptides, the aromatic amino acid residues of Trp, Tyr, Phe, and His are targeted with high selectivity to Trp. The functionalization method is biocompatible, mild, rapid, and transition-metal-free. The proteins myoglobin, ubiquitin, and human carbonic anhydrase I were also successfully functionalized.

Control of site selectivity in trifluoromethylation of alkenes bearing a pendant indolyl group: Synthesis of CF3-containing tetrahydrocarbazoles

We present a tetrahydrocarbozole-forming carbo-trifluoromethylation of indoles bearing an alkenyl group at the C3 position. The reaction proceeded selectively with the combination of TsOH·H2O as a catalyst and CH2Cl2 as a solvent. The site-selectivity could be altered by changing the reaction solvent; the use of THF instead of CH2Cl2 increased the formation of aromatic trifluoromethylation products.

Trifluoromethylation of heterocycles via visible light photoredox catalysis

A method has been developed for the visible light-induced trifluoromethylation of heterocyclic compounds. A variety of electron-rich heterocycles were transformed into trifluoromethylated products by using CF 3I as the trifluoromethyl radical source and Ru(bpy) 3Cl2 as the photocatalyst under mild reaction conditions. This operationally simple and eco-friendly process can introduce trifluoromethyl groups without prefunctionalization.

Exploring the Structure and Performance of Cd–Chalcogenide Photocatalysts in Selective Trifluoromethylation

The field of heterogeneous photoredox catalysis has grown substantially and impacted organic synthesis because of the affordability and reusability of catalysts. This study reports radical trifluoromethylation with Cd–chalcogenide semiconductors. Cd semiconductors, particularly CdSe, are readily available, commercial, visible-light-responsive, heterogeneous photocatalysts. The potential of readily available Cd semiconductors, particularly CdSe, is confirmed by their increased photocatalytic activity toward trifluoromethylation with various substrates, such as (hetero)arenes and vinylic amides/acids, via addition, cyclization, and decarboxylation under visible light. The economic significance of this strategy is also highlighted through the scalable synthesis of biologically active molecules followed by catalyst reuse. Moreover, these catalysts are relatively inexpensive compared with transition metal-based homogeneous photocatalysts, presently used in organic synthesis.

Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating Reagents

The development of two highly reactive electrophilic trifluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide (1g) and (trifluoromethyl)(3-chlorophenyl)bis(carbomethoxy)methylide (1j) through structure-activity study was described. Under mild conditions, reagent 1g reacted with β-ketoesters and silyl enol ethers to give α-trifluoromethylated-β-ketoesters or α-trifluoromethylated ketones in high yields. In addition, reagent 1g could serve as a trifluoromethyl radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoromethylation of electron-rich indoles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with styrene derivatives. On the other hand, as a complimentary, under reductive coupling conditions, reagent 1j reacted with a variety of (hetero)aryl iodides for the formation of trifluoromethylated (hetero)arenes.

Photoinduced Trifluoromethylation of Arenes and Heteroarenes Catalyzed by High-Valent Nickel Complexes

We describe a series of air-stable NiIII complexes supported by a simple, robust naphthyridine-based ligand. Access to the high-valent oxidation state is enabled by the CF3 ligands on the nickel, while the naphthyridine exhibits either a monodentate or bidentate coordination mode that depends on the oxidation state and sterics, and enables facile aerobic oxidation of NiII to NiIII. These NiIII complexes act as efficient catalysts for photoinduced C(sp2)?H bond trifluoromethylation reactions of (hetero)arenes using versatile synthetic protocols. This blue LED light-mediated catalytic protocol proceeds via a radical pathway and demonstrates potential in the late-stage functionalization of drug analogs.

Solid-State Radical C?H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials

The application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C?H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C?H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.

Nickel(IV)-Catalyzed C-H Trifluoromethylation of (Hetero)arenes

This Article describes the development of a stable NiIV complex that mediates C(sp2)-H trifluoromethylation reactions. This reactivity is first demonstrated stoichiometrically and then successfully translated to a NiIV-catalyzed C-H trifluoromethylation of electron-rich arene and heteroarene substrates. Both experimental and computational mechanistic studies support a radical chain pathway involving NiIV, NiIII, and NiII intermediates.

CATALYST-FREE AND REDOX-NEUTRAL INNATE TRIFLUOROMETHYLATION AND ALKYLATION OF (HETERO)AROMATICS ENABLED BY LIGHT

The present disclosure relates to reagents and method for performing trifluoromethylation, difluoromethylation or alkylation of aromatic or heteroaromatic rings in a redox-neutral manner without any catalyst which are enabled by light. In addition, there are methods for synthesizing the starting reagents used in the trifluoromethylation, difluoromethylation or alkylation reactions.