Ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate
[CAS# 131707-24-9]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Ethyl ester compound
• Name: Ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate
• Synonyms: 1-Methyl-2-phenylthiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole
• Molecular Formula: C₁₉H₁₈BrNO₃S
• Molecular Weight: 420.32
• CAS Registry Number: 131707-24-9
• EC Number: 629-769-6
• SMILES: CCOC(=O)C1=C(N(C2=CC(=C(C=C21)O)Br)C)CSC3=CC=CC=C3

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 570.6±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 298.9±30.1 ºC (Calc.)^*
• Index of refraction: 1.64 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H332-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302

Discovory and Applicatios

Ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate is a synthetic organic compound that belongs to the substituted indole family. Its molecular formula is C₁₉H₁₈BrNO₄S, and its structure features an indole core substituted with various functional groups that confer distinct chemical and potential biological properties.

The indole nucleus is a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. In this compound, the indole ring is substituted at the 1-position with a methyl group, at the 2-position with a phenylsulfanylmethyl group (–CH₂SPh), at the 3-position with an ethyl ester of a carboxylic acid (–COOCH₂CH₃), at the 5-position with a hydroxyl group, and at the 6-position with a bromine atom. This combination of substituents results in a molecule that is chemically rich and functionally diverse.

The synthesis of this compound typically proceeds through functionalized indole precursors. A common strategy involves the selective substitution of a suitably protected indole scaffold, followed by bromination at the 6-position using reagents such as N-bromosuccinimide (NBS). The 5-hydroxy group may be introduced through electrophilic substitution or derived from a protected hydroxyl precursor. The phenylsulfanylmethyl group is usually installed via alkylation at the 2-position using a thiophenylmethyl halide and a base. The esterification at the 3-position can be accomplished by reacting an indole-3-carboxylic acid derivative with ethanol under acidic conditions.

The compound incorporates both electron-donating and electron-withdrawing groups, which influence its chemical behavior. The bromine atom, a halogen, is electron-withdrawing and can participate in further cross-coupling reactions, such as Suzuki or Heck reactions, making this compound a potential intermediate for more complex molecule synthesis. The hydroxyl group on the aromatic ring can undergo modifications like methylation or acylation, or form hydrogen bonds, contributing to solubility and potential interaction with biological targets.

From a medicinal chemistry perspective, substituted indoles are a prominent class of bioactive molecules found in many natural products and pharmaceuticals. Structural analogs of this compound have been investigated for anti-inflammatory, antimicrobial, anticancer, and CNS-related activity. The presence of a phenylsulfanyl group can improve lipophilicity and membrane permeability, while the ester moiety provides a site for metabolic transformation, potentially yielding active carboxylic acids or other derivatives in vivo.

The compound’s physicochemical profile is affected by the polar hydroxyl and ester groups and the lipophilic aryl and sulfur-containing substituents. It is likely soluble in organic solvents such as dichloromethane, chloroform, methanol, and ethyl acetate, while its aqueous solubility may be limited due to its nonpolar regions.

Characterization is achieved using various analytical techniques. In ²H NMR spectroscopy, signals are observed for the indole protons, the aromatic hydrogens of the phenyl ring, the methylene groups, the methyl group at the N₁ position, and the ethyl ester side chain. ³C NMR confirms the structure of the aromatic carbons, ester carbonyl, and other aliphatic carbons. IR spectroscopy reveals absorption bands corresponding to the hydroxyl group (O–H stretch), ester C=O, and C–S bond. Mass spectrometry provides the molecular ion peak and fragmentation patterns consistent with the presence of sulfur and bromine, both of which produce characteristic isotope distributions.

In summary, ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate is a structurally elaborate indole derivative that serves as a useful intermediate in synthetic chemistry and a potential scaffold for medicinal chemistry research. Its combination of functional groups allows for further chemical elaboration and investigation of biological activity.

References

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DOI: 10.1016/j.bmcl.2017.06.074

2014. Synthesis and Antiviral Activity of Ethyl 1,2-dimethyl-5-Hydroxy-1H-Indole-3-carboxylates and Their Derivatives. Pharmaceutical Chemistry Journal, 47(12).
DOI: 10.1007/s11094-014-1024-8

1994. Synthesis and some pharmacological properties of derivatives of indole and benzofuran containing the imidazole pharmacophore. Pharmaceutical Chemistry Journal, 28(2).
DOI: 10.1007/bf02220018