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DOI: 10.1055/s-0031-1290332
TiCl4-Mediated Direct N-Alkylation of Sulfonamides with Inactive Ethers
Publication History
Publication Date:
06 February 2012 (online)
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Abstract
A TiCl4-mediated intermolecular or intramolecular direct N-alkylation reaction of sulfonamides with inactive ethers as alkylating agents was successfully achieved. This method provides a novel approach towards N-alkyl sulfonamides from inactive ethers via an easy workup procedure.
Key words
N-alkylation - Lewis acid - N-alkyl sulfonamide - dialkyl ether - titanium tetrachloride
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
General Procedure
for the Transformation
Sulfonamide (0.50 mmol), ether
(12.0 equiv, 6.0 mmol) and Cl2CHCHCl2 (2.0
mL) were combined in a pressure tube equipped with a stir bar, the
mixture was stirred about 10 min, then TiCl4 (6.0 equiv,
3.0 mmol) was added, and the reaction mixture was heated to 120 ˚C
for the given time. After the starting material has disappeared
(monitored by TLC), the reaction mixture was cooled to r.t. and
treated with H2O (5.0 mL) to decompose the exceed TiCl4,
then filtered, and the filtrate was extracted with EtOAc (3 × 10
mL).
The combined organic layers was dried over Na2SO4 and concentrated
in vacuo, the corresponding residue was purified by flash column
chromatography (silica gel) to furnish the target product. All the
products are known compounds and are identified using ¹H
NMR, LRMS, and
IR by comparison with previously reported
data (see Supporting Information for complete details).