Synlett 2012(4): 595-600  
DOI: 10.1055/s-0031-1290332
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

TiCl4-Mediated Direct N-Alkylation of Sulfonamides with Inactive Ethers

Jiayan Chen, Ling Dang, Qiang Li, Yong Ye, Shaomin Fu, Wei Zeng*
School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641,P. R. of China
Fax: +86(20)22236337; e-Mail: zengwei@scut.edu.cn;
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Publikationsverlauf

Received 18 November 2011
Publikationsdatum:
06. Februar 2012 (online)

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.

    References and Notes

  • For selected reviews, see:
  • 1a Severin S. Doye S. Chem. Soc. Rev.  2007,  36:  1407 
  • 1b Hultzsch KC. Adv. Synth. Catal.  2005,  347:  367 
  • 1c Eilbracht P. Bärfacker L. Buss C. Hollmann C. Kitsos-Rzychon BE. Kranemann CL. Rische T. Roggenbuck R. Schmidt A. Chem. Rev.  1999,  99:  3329 
  • 1d Müller T. Beller M. Chem. Rev.  1998,  98:  675 
  • 2a Scozzafava A. Owa T. Mastrolorenzo A. Supuran CT. Curr. Med. Chem.  2003,  10:  925 ; and references cited therein
  • 2b Drew J. Science  2000,  287:  1960 
  • 2c Scozzafava A. Supuran CT. J. Med. Chem.  2000,  43:  3677 
  • For selected examples, see:
  • 3a Caddick S. Wilden JD. Wadman SJ. Bush HD. Judd DB. Org. Lett.  2002,  4:  2549 
  • 3b Sridhar R. Srinivas B. Kumar VP. Narender M. Rao KR. Adv. Synth. Catal.  2007,  349:  1873 
  • For selected examples, see:
  • 4a Yin J. Buchwald SL.
    J. Am. Chem. Soc.  2002,  124:  6043 
  • 4b Burton G. Cao P. Li G. Rivero R. Org. Lett.  2003,  5:  4373 
  • 4c Sherman ES. Fuller PH. Kasi D. Chemler SR. J. Org. Chem.  2007,  72:  3896 
  • 4d Wu T. Yin G. Liu G. J. Am. Chem. Soc.  2009,  131:  16354 
  • For selected examples, see:
  • 5a Shi F. Tse MK. Cui X. Gordes D. Michalik D. Thurow K. Deng Y. Beller M. Angew. Chem. Int. Ed.  2009,  48:  5912 
  • 5b Hamid MHSA. Allen CL. Lamb GW. Maxwell AC. Maytum HC. Watson AJA. Williams JMJ. J. Am. Chem. Soc.  2009,  131:  1766 
  • 5c Cui X. Shi F. Tse MK. Gördes D. Thurow K. Beller M. Deng Y. Adv. Synth. Catal.  2009,  351:  2949 
  • 5d Xu CP. Xia ZH. Zhuo BQ. Wang YH. Huang PQ. Chem. Commun.  2010,  46:  7834 
  • 5e Zhu M. Fujita K. Yamaguchi R. Org. Lett.  2010,  12:  1336 
  • For selected examples, see:
  • 6a Fukuyama T. Jow CK. Cheung M. Tetrahedron Lett.  1995,  36:  6373 
  • 6b Kan T. Fukuyama T. Chem. Commun.  2004,  353 
  • For selected examples, see:
  • 7a Noji M. Ohno T. Fuji K. Futaba N. Tajim H. Ishii K. J. Org. Chem.  2003,  68:  9340 
  • 7b Terrasson V. Marque S. Georgy M. Campagn JM. Prim D. Adv. Synth. Catal.  2006,  348:  2063 
  • 7c Qin H. Yamagiwa N. Matsunaga S. Shibasaki M. Angew. Chem. Int. Ed.  2007,  46:  409 
  • 7d Wang GW. Shen YB. Wu XL. Eur. J. Org. Chem.  2008,  4367 
  • 8 Roberts VM. Stein V. Reiner T. Lemonidou A. Li X. Lercher JA. Chem. Eur. J.  2011,  17:  5939 
  • 9a Albone DP. Challenger S. Derrick AM. Fillery SM. Irwin JC. Parsons CM. Takada H. Taylor PC. Wilson DJ. Org. Biomol. Chem.  2005,  3:  107 
  • 9b He L. Yu J. Zhang J. Yu XQ. Org. Lett.  2007,  9:  2277 
  • 10 Fu S. Lian X. Ma T. Chen W. Zheng M. Zeng W. Tetrahedron Lett.  2010,  51:  5834 
11

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).