95-20-5

Usage

Uses

Used in Pharmaceutical Industry:
2-Methylindole is used as an intermediate in the synthesis of indole derivatives with potential antifungal activities. It is also used as a raw material for the preparation of deacetylase (HDAC) inhibitor panobinostat.
Used in Chemical Synthesis:
2-Methylindole is used as a reactant for various chemical reactions, including:
Regioselective synthesis of oxopyrrolidine analogs via iodine-catalyzed Markovnikov addition reaction
Friedel-Crafts alkylation reactions
Preparation of tryptophan dioxygenase inhibitors, pyridyl-ethenyl-indoles, as potential anticancer immunomodulators
Preparation of plant-growth inhibitors
Michael addition reactions
Synthesis of cyclooxygenase-1 (COX-1)/cyclooxygenase-2 (COX-2) inhibitors
These applications highlight the versatility of 2-Methylindole in different industries, particularly in the development of pharmaceuticals and chemical synthesis processes.

Preparation

2-Methylindole was synthesized from 2-Acetamidotoluene by the following procedure. 2-Acetamidotoluene was added to the mixture of anhydrous ether and sodium amide, heated to 240-260°C under the protection of nitrogen flow, kept for 10min, a large amount of gas was generated in the reaction, and the reaction ended when the gas stopped escaping, and cooled. Ethanol and warm water were added and heated to decompose the sodium derivative of 2-Methylindole and excess sodium amide. After cooling, it was extracted with ether. The extract was concentrated and then distilled, and the fractions at 119-126°C (0.4-0.53kPa) were collected to obtain 2-Methylindole with a yield of 80%-83%. The product can be purified by methanol recrystallization.

Synthesis Reference(s)

Journal of the American Chemical Society, 98, p. 2674, 1976 DOI: 10.1021/ja00425a051Organic Syntheses, Coll. Vol. 3, p. 597, 1955Tetrahedron Letters, 9, p. 3499, 1968

Purification Methods

Crystallise it from *benzene. It has also been purified by zone melting. The picrate has m 139o (from Et2O or Et2O/MeOH). [Cohen et al. J Am Chem Soc 82 2184 1960, Beilstein 20 III/IV 3202, 20/7 V 59.]

InChI:InChI=1/C9H9N/c1-7-6-8-4-2-3-5-9(8)10-7/h2-6,10H,1H3

Upstream product

• 91-22-5 quinoline 
• 83-34-1 3-Methylindole 
• 22582-52-1 3-acetyl-2-methylindole 
• 63176-44-3 2-methyl-1H-indole-3-carboxylic acid 
• 114187-77-8 3-(1-hydroxyimino-ethyl)-indolin-2-one 
• 5435-44-9 (E)-3-Ureido-but-2-enoic acid ethyl ester 
• 41902-73-2 4-isopropylidenehydrazino-benzoic acid 
• 6305-95-9 2-chlorophenylacetone 
• 925-90-6 ethylmagnesium bromide 
• 103-02-6 acetone phenylhydrazone 
• 120-66-1 N-(2-methylphenyl)acetamide 
• 141-52-6 sodium ethanolate 
• 54006-71-2 2-[(2-methyl-3-indolyl)carbonyl]benzoic acid 
• 61995-50-4 bis(2-methyl-1H-indol-3-yl)methane 

Downstream Products

• 4071-15-2 2-methyl-3-piperidinomethyl-indole 
• 26211-73-4 (2-methyl-1H-indol-3-yl)phenylmethanone 
• 1912-43-2 2-methyl-3-indoleacetic acid 
• 37128-50-0 (2-methyl-1H-indol-3-yl)-3-pyridinylmethanone 
• 855926-72-6 bis-(2-methyl-indol-3-yl)-phenyl-acetonitrile 
• 102594-06-9 2-methyl-3-[1,2-diphenyleth-1-enyl]-1H-indole 
• 118-12-7 1,3,3-Trimethyl-2-methyleneindoline 
• 54006-71-2 2-[(2-methyl-3-indolyl)carbonyl]benzoic acid 
• 525-58-6 3-[3H-indol-3-ylidenemethyl]-1H-indole 
• 602-04-0 tris(2-methyl-1H-indol-3-yl)methane 
• 40876-94-6 1-ethyl-2-methylindole 
• 109809-52-1 2-methyl-3-(2-nitro-1-phenylethyl)-1H-indole 
• 61995-49-1 3-benzhydrylidene-2-methyl-3H-indole; hydrochloride 
• 63170-99-0 2-methyl-3-trityl-indole 

Relevant academic research and scientific papers

Gold nanoparticles catalyst with redox-active poly(aniline sulfonic acid): Application in aerobic dehydrogenative oxidation of cyclic amines in aqueous solution

The catalysis of poly(2-methoxyaniline-5-sulfonic acid) (PMAS)/gold nanoparticles catalyst was demonstrated for the dehydrogenative oxidation reaction of 2-substituted indoline and dihydropyridine under molecular oxygen in aqueous solution. This catalyst was recyclable. Redox mediating function of PMAS was revealed by following the UV-vis spectra.

Rhodium(III)-Catalyzed Synthesis of Indole Derivatives from Pyrimidyl-Substituted Anilines and Diazo Compounds

An efficient method for the synthesis of indole derivatives from readily available pyrimidyl-substituted anilines and diazo compounds via rhodium(III)-catalyzed C-H bond activation has been developed. This cyclization reaction displays excellent functional group compatibility and regioselectivity, which overcomes some drawbacks of the classical indole synthetic methods and provides a facile approach for the construction of multi-substituted indole derivatives. The redox-neutral intermolecular annulation procedure comprises tandem C-H bond activation, cyclization, and condensation steps, releasing water and nitrogen as by-products.

Nickel-Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines

A nickel-catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium-catalyzed process in that the nickel–carbon bond is converted into a C?H bond to release the product through protonation instead of hydride donation followed by C?H reductive elimination on Pd.

Sterically Controlled Ru(II)-Catalyzed Divergent Synthesis of 2-Methylindoles and Indolines through a C-H Allylation/Cyclization Cascade

A ruthenium-catalyzed synthesis of 2-methylindole was accomplished via a C-H allylation/oxidative cyclization cascade. Strategically, β-hydride elimination from the σ-alkyl-Ru intermediate has been suppressed by steric hindrance from a remote position. Hence, 2-methylindolines from the corresponding ortho-substituted anilines were achieved via protodemetalation in lieu of β-hydride elimination under a modified reaction condition. This mild intermolecular annulation cascade proceeds smoothly by a redox-neutral ruthenium catalyst without stoichiometric metal oxidants, such as silver(I) or copper(II) salts, providing excellent functional group tolerance.

Homogeneously-catalysed hydrogen release/storage using the 2-methylindole/2-methylindoline LOHC system in molten salt-organic biphasic reaction systems

Ir-Complex catalysed hydrogen release/storage using a 2-methylindole/2-methylindoline Liquid Organic Hydrogen Carrier (LOHC) system is shown to be effective in a temperature range of 120 to 140 °C. In the form of a liquid-liquid biphasic reaction system with molten [PPh4][NTf2] as catalyst immobilisation phase, the applied cationic Ir-complex can be easily separated and recycled enabling a small amount of ionic catalyst solution to store/release a large amount of hydrogen.

Asymmetric transfer hydrogenation of heterocycle-containing acetophenone derivatives using N-functionalised [(benzene)Ru(II)(TsDPEN)] complexes

The application of enantiomerically-pure ruthenium(II) catalysts containing N - functionalised TsDPEN ligand to the asymmetric transfer hydrogenation of 15 examples of α-heterocyclic acetophenone derivatives is reported. Products of up to 99% ee were formed.

Cobalt-Catalyzed Dearomatization of Indoles via Transfer Hydrogenation to Afford Polycyclic Indolines

A cobalt-catalyzed dearomatization of indoles via transfer hydrogenation with HBpin and H2O has been developed. This reaction offered a straightforward platform to access hexahydropyrido[1,2-a]indoles in high regio- and chemoselectivity. A preliminary reaction mechanism was proposed on the basis of deuterium-labeling experiments, and a cobalt hydride species was involved in the reaction.

Metal–Organic Layers Hierarchically Integrate Three Synergistic Active Sites for Tandem Catalysis

We report the design of a bifunctional metal–organic layer (MOL), Hf12-Ru-Co, composed of [Ru(DBB)(bpy)2]2+ [DBB-Ru, DBB=4,4′-di(4-benzoato)-2,2′-bipyridine; bpy=2,2′-bipyridine] connecting ligand as a photosensitizer and Co(dmgH)2(PPA)Cl (PPA-Co, dmgH=dimethylglyoxime; PPA=4-pyridinepropionic acid) on the Hf12 secondary building unit (SBU) as a hydrogen-transfer catalyst. Hf12-Ru-Co efficiently catalyzed acceptorless dehydrogenation of indolines and tetrahydroquinolines to afford indoles and quinolones. We extended this strategy to prepare Hf12-Ru-Co-OTf MOL with a [Ru(DBB)(bpy)2]2+ photosensitizer and Hf12 SBU capped with triflate as strong Lewis acids and PPA-Co as a hydrogen transfer catalyst. With three synergistic active sites, Hf12-Ru-Co-OTf competently catalyzed dehydrogenative tandem transformations of indolines with alkenes or aldehydes to afford 3-alkylindoles and bisindolylmethanes with turnover numbers of up to 500 and 460, respectively, illustrating the potential use of MOLs in constructing novel multifunctional heterogeneous catalysts.

Highly Ordered Mesoporous Cobalt Oxide as Heterogeneous Catalyst for Aerobic Oxidative Aromatization of N-Heterocycles

N-heterocycles are key structures for many pharmaceutical intermediates. The synthesis of such units normally is conducted under homogeneous catalytic conditions. Among all methods, aerobic oxidative aromatization is one of the most effective. However, in homogeneous conditions, catalysts are difficult to be recycled. Herein, we report a heterogeneous catalytic strategy with a mesoporous cobalt oxide as catalyst. The developed protocol shows a broad applicability for the synthesis of N-heterocycles (32 examples, up to 99 % yield), and the catalyst presents high turnover numbers (7.41) in the absence of any additives. Such a heterogenous approach can be easily scaled up. Furthermore, the catalyst can be recycled by simply filtration and be reused for at least six times without obvious deactivation. Comparative studies reveal that the high surface area of mesoporous cobalt oxide plays an important role on the catalytic reactivity. The outstanding recycling capacity makes the catalyst industrially practical and sustainable for the synthesis of diverse N-heterocycles.

Ruthenium-Catalyzed Dehydrogenation Through an Intermolecular Hydrogen Atom Transfer Mechanism

The direct dehydrogenation of alkanes is among the most efficient ways to access valuable alkene products. Although several catalysts have been designed to promote this transformation, they have unfortunately found limited applications in fine chemical synthesis. Here, we report a conceptually novel strategy for the catalytic, intermolecular dehydrogenation of alkanes using a ruthenium catalyst. The combination of a redox-active ligand and a sterically hindered aryl radical intermediate has unleashed this novel strategy. Importantly, mechanistic investigations have been performed to provide a conceptual framework for the further development of this new catalytic dehydrogenation system.