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Chemical Synthesis

N-Acylbenzotriazoles

Benzotriazole has been commonly employed as a leaving group and has been used extensively as a novel synthetic auxiliary.1 Generally, N-acylbenzotriazoles are more stable than acid chlorides and can be used in many acylation reactions, often without diacylation or other side reactions that may complicate more traditional methods. These mild, regioselective and regiospecific reagents provide excellent alternatives to Friedel-Crafts and Vilsmeier-Haack acylation methodologies, and can be employed when the corresponding acid chlorides are not readily available. Recent facile acylations achieved with N-acylbenzotriazoles have led to 3-acylindoles and 2- or 3-acylpyrroles,2 α-substituted ß-ketonitriles,3 ß-oxo-sulfones,4 and primary, secondary or tertiary amides5 (Scheme 1).

Scheme 1
Scheme 1



N-Acylbenzotriazoles have also been shown to react with aryl isocyanates to form different classes of polycyclic heteroaromatics. Depending on the type of acylbenzotriazole and the number of isocyanates incorporated per acylbenzotriazole, quinolines, pyrimidino[5,4-c]quinolines, benzo[b]-1,8-naphthyridines, phenanthridines, and indolo[2,3-b]quinolines can all be synthesized (Scheme 2).6

Scheme 2
Scheme 2



1,2-Diketones are formed in moderate to excellent yields when N-acylbenzotriazoles are treated with SmI2 in THF. If acetonitrile is used as the solvent instead, a ring-opening reaction occurs, resulting in the formation of 1-acylamido-2-alkyl- (or aryl-) benzimidazoles (Scheme 3).7

Scheme 3
Scheme 3



C-Acylations of acetoacetic esters, followed by spontaneous deacetylation, lead to useful preparative methods for homologated acetic esters. Similar treatment of acetonyl ketones affords a variety of ß-diketones (Scheme 4).8



Scheme 4
Scheme 4



Product Name Product # 
1-(2-Butenoyl)-1H-benzotriazole, 97% 596361
1-Benzoyl-1H-benzotriazole, 97% 596590


References

  1. Review: Katritzky, A. R. and Belyakov, S. A Aldrichimica Acta 1998, 31, 35.
  2. Katritzky, A. R. et al. J. Org. Chem. 2003, 68, 5720.
  3. Katritzky, A. R. et al. J. Org. Chem. 2003, 68, 4932.
  4. Katritzky, A. R. et al. J. Org. Chem. 2003, 68, 1443.
  5. Katritzky, A. R. et al. J. Org. Chem. 2000, 65, 8210.
  6. Katritzky, A. R. et al. J. Org. Chem. 2000, 65, 8069.
  7. a) Wang, X. and Zhang, Y. Tetrahedron 2003, 59, 4201; b) Wang, X. and Zhang, Y. Tetrahedron Lett. 2002, 43, 5431.
  8. Katritzky, A. R. et al. J. Org. Chem. 2004, 69, 6617.