95-20-5

Basic information

• Product Name: 2-Methylindole
• Synonyms: ALPHA-METHYLINDOLE;1H-INDOLE, 2-METHYL-;2-METHYL-1H-INDOLE;2-METHYLINDOLE;AURORA 15496;LABOTEST-BB LT01274391;METHYLINDOLE(2-);METHYLKETOLE
• CAS NO: 95-20-5
• Molecular Formula: C₉H₉N
• Molecular Weight: 131.17
• EINECS: 202-398-3
• Product Categories: Intermediates of Dyes and Pigments;Indoles and derivatives;Indole;Indoles;Simple Indoles;Building Blocks;Heterocyclic Building Blocks;Heterocycle-Indole series;fine chemical;intermediates;fine chemicals
• Mol File: 95-20-5.mol
• Article Data: 208

Chemical Properties

• Melting Point: 57-59 °C(lit.)
• Boiling Point: 273 °C(lit.)
• Flash Point: 141 °C
• Appearance: Yellow to reddish-purple or brown/Crystals, Flakes, or Crystalline Powder
• Density: 1,07 g/cm3
• Vapor Pressure: 0.0104mmHg at 25°C
• Refractive Index: 1.6070 (estimate)
• Storage Temp.: Freezer (-20°C)
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 17.57±0.30(Predicted)
• Water Solubility: Insoluble in water.
• Sensitive: Light Sensitive
• BRN: 109781
• CAS DataBase Reference: 2-Methylindole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methylindole(95-20-5)
• EPA Substance Registry System: 2-Methylindole(95-20-5)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-41
• Safety Statements: 36/37-24/25-39-26
• RIDADR: 3335
• WGK Germany: 3
• RTECS: NM0345000
• F: 8-10-13-23
• TSCA: Yes
• Hazardous Substances Data: 95-20-5(Hazardous Substances Data)

Usage

Chemical Properties

Colorless needle or yellow to reddish-purple or brown crystals, flakes. Has an animal type odor.Soluble in ethanol and ether, insoluble in water.

Uses

Different sources of media describe the Uses of 95-20-5 differently. You can refer to the following data:
1. 2-Methylindole is an intermediate in the synthesis of indole derivative with potential antifungal activities. It can be used as a raw material for the preparation of deacetylase (HDAC) inhibitor panobinostat.
2. 2-Methylindole is used as a reactant for 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, Michael addition reactions and in synthesis of cyclooxygenase-1 (COX-1)/cyclooxygenase-2 (COX-2) inhibitors.

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.

Definition

ChEBI: 2-Methylindole is a methylindole that is 1H-indole substituted by a methyl group at position 2. It derives from a hydride of a 1H-indole.

Application

2-Methylindole is used as a reactant Reactant for:Regioselective synthesis of oxopyrrolidine analogs via iodine-catalyzed Markovnikov addition reactionFriedel-Crafts alkylation reactionsPreparation of tryptophan dioxygenase inhibitors pyridyl-ethenyl-indoles as potential anticancer immunomodulatorsPreparation of plant-growth inhibitorsMichael addition reactionsSynthesis of cyclooxygenase-1 (COX-1)/cyclooxygenase-2 (COX-2) inhibitors

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

• 63176-44-3 2-methyl-1H-indole-3-carboxylic acid 
• 92112-25-9 2-anilino-propionaldehyde diethylacetal 
• 103205-34-1 2-(2-acetamidophenyl)acetic acid 
• 78-95-5 chloroacetone 
• 62-53-3 aniline 
• 100-63-0 phenylhydrazine 
• 67-64-1 acetone 
• 6872-06-6 2-methyl indoline 
• 103-02-6 acetone phenylhydrazone 
• 111-46-6 diethylene glycol 
• 1969-72-8 (2-nitrophenyl)acetone 
• 13637-43-9 2-methylthioindole 
• 75-16-1 methylmagnesium bromide 
• 52562-18-2 2-(prop-1-en-1-yl)aniline 

Downstream Products

• 4071-15-2 2-methyl-3-piperidinomethyl-indole 
• 1912-43-2 2-methyl-3-indoleacetic acid 
• 1136-87-4 3-(2-methyl-1H-indol-3-yl)propanoic acid 
• 87299-38-5 N-[1-[2-(2-Methyl-1H-indol-3-yl)-2H-quinolin-1-yl]-1-phenyl-meth-(E)-ylidene]-benzenesulfonamide 
• 86539-45-9 1-benzoyl-2,7-bis(2-methyl-3-indolyl)-1,2,7,8-tetrahydro-1,8-naphthyridine 
• 87299-43-2 C₄₂H₃₃N₅O₄S₂ 
• 7164-92-3 3-chloro-2-methyl-1H-indole 
• 76794-20-2 3-chloro-2-(methoxymethyl)-1H-indole 
• 76794-19-9 3,3-Dimethoxy-2-methyl-3H-indole 
• 31151-19-6 3-isopropyl-2-methyl-1H-indole 
• 109023-31-6 2-(5-Methyl-7,12-dihydro-7,12-diaza-indeno[1,2-a]fluoren-6-yl)-phenylamine 
• 109005-16-5 2'''-methyl-2,3'-2',3''-2'',3'''-tetraindolyl 
• 88919-84-0 2'-methyl-1H,1'H-2,3'-biindole 
• 40876-94-6 1-ethyl-2-methylindole 

Relevant articles and documents

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.

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.

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.

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.