Synlett 2010(5): 835-836  
DOI: 10.1055/s-0029-1219387
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

Chloroacetylchloride: A Versatile Reagent in Heterocyclic Synthesis

Ramesh Yella*
Department of Chemistry, Indian Institute of Technology Guwahati, 781 039 Guwahati, India
e-Mail: ramesh@iitg.ernet.in;
Further Information

Publication History

Publication Date:
23 February 2010 (online)

Introduction

Chloroacetylchloride is widely used in organic synthesis as a bifunctional reagent because acyl chloride (hard electrophile) easily forms esters [¹] or amides, [²-4] while the other end the chloromethyl site (soft electrophile) can form other linkages. [²-7] It is a convenient reagent for the preparation of heterocyclic compounds and is utilized as an important building block in the synthesis of natural and therapeutically active compounds. [¹0] [¹¹]

The reagent is used in the preparation of alachlor, butachlor, and the local anesthetic and antiarrhythmic drug lidocaine. [¹²] Furthermore, it is also used to produce phenacyl chloride, another chemical intermediate used as a tear gas via Friedel-Crafts acylation of benzene using AlCl3 as catalyst. [¹³] Chloroacetylchloride must be handled with precaution because it reacts readily with nucleophiles, such as amines, alcohols, and water generating hydrochloric acid, making it a lachrymator.

    References

  • 1 Baker RH. Bordwell FG. Org. Synth.  Coll. Vol. III:  1955,  141 
  • 2 Yella R. Ghosh H. Patel BK. Green Chem.  2008,  10:  1307 
  • 3 Zuo H. Li Z.-B. Ren F.-K. Falck JR. Lijuan M. Ahn C. Shin D.-S. Tetrahedron  2008,  64:  9669 
  • 4 Dandia A. Singh R. Khaturia S. J. Fluorine Chem.  2007,  128:  524 
  • 5 Gellis A. Boufatah N. Vanelle P. Green Chem.  2006,  8:  483 
  • 6 Bagdatli E. Akkus S. Yolacan C. Ocal N. J. Chem. Res.  2007,  302 
  • 7 Paczal A. Bényei AC. Kotschy A. J. Org. Chem.  2006,  71:  5969 
  • 8 Wei Q.-L. Zhang S.-S. Gao J. Li W.-H. Xu L.-Z. Yu Z.-G. Bioorg. Med. Chem. Lett.  2006,  14:  7146 
  • 9 Chalyk BA. Tverdokhlebov AV. Iminov RT. Tolmachev AA. Heterocycles  2009,  78:  2021 
  • 10 Harte AJ. Gunnlaugsson T. Tetrahedron Lett.  2006,  47:  6321 
  • 11 Huang C.-G. Chang B.-R. Chang N.-C. Tetrahedron Lett.  2002,  43:  2721 
  • 12 Reilly TJ. J. Chem. Ed.  1999,  76:  1557 
  • 13 Levin N. Hartung WH. Org. Synth., Coll. Vol. III  1955,  191