2-Methylindole-3-carboxaldehyde

Chemical Properties

Brown powder

Uses

Reactant for preparation of:

• Tryptophan dioxygenase inhibitors pyridyl-ethenyl-indoles as potential anticancer immunomodulators
• Fluorescent sensors (BODIPY)
• Antimicrobial agents against methicillin-resistant Staphylococcus aureus
• G protein-coupled receptor CRTh2 antagonists
• Inhibitors of PI3 kinase-α
• Antitubercular agents
• Anti-inflammatory agents
• Mycobacterium tuberculosis protein tyrosine phosphatase B
• Glucocorticoid receptor ligands
• Agents stimulating neurite outgrowth

Uses

Reactant for preparation of:• ;Tryptophan dioxygenase inhibitors pyridyl-ethenyl-indoles as potential anticancer immunomodulators1• ;Fluorescent sensors (BODIPY)2• ;Antimicrobial agents against methicillin-resistant Staphylococcus aureus3• ;G protein-coupled receptor CRTh2 antagonists4• ;Inhibitors of PI3 kinase-α5• ;Antitubercular agents6• ;Anti-inflammatory agents7• ;Mycobacterium tuberculosis protein tyrosine phosphatase B8• ;Glucocorticoid receptor ligands9• ;Agents stimulating neurite outgrowth10

Synthesis Reference(s)

Chemical and Pharmaceutical Bulletin, 31, p. 2892, 1983 DOI: 10.1248/cpb.31.2892

General Description

Oxidative activation of 2-methylindole-3-carboxaldehyde via N-heterocyclic carbene organocatalysis generates heterocyclic ortho-quinodimethane as a key intermediate.

Synthesis

GENERAL PROCEDURE: Phosphorus oxychloride (POCl3, 1.73 mL, 18.6 mmol) was slowly added dropwise to stirred and ice-bath cooled N,N-dimethylformamide (DMF, 5.0 mL). The reaction mixture was stirred at 1-5 °C for 20 min before a solution of 2-methylindole (15.5 mmol) in DMF (5.0 mL) was slowly added. The resulting reaction mixture was gradually warmed to 35 °C and maintained at this temperature for 40 min. The mixture was then cooled to room temperature. Ice (about 10 g) was added to the mixture, followed by the addition of 5 M sodium hydroxide (NaOH) solution (31 mL, 155 mmol). The reaction mixture was heated at 95 °C for 30 min and then cooled to room temperature. Ice (~10 g) was again added to the mixture and the resulting reaction mixture was stirred for 30 minutes. 2-Methylindole-3-carbaldehyde was collected by filtration and washed several times with distilled water.

References

[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 12, p. 2895 - 2901
[2] Tetrahedron Letters, 2018, vol. 59, # 11, p. 1014 - 1018
[3] Chemical Biology and Drug Design, 2011, vol. 78, # 5, p. 864 - 868
[4] European Journal of Medicinal Chemistry, 2003, vol. 38, # 1, p. 75 - 87
[5] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167