Fast Halogenation of Some N-Heterocycles by Means of N,N′-Dihalo-5,5-dimethylhydantoin

An instantaneous, selective and high-yielding halogenation process is reported. The method operates with imidazoles, pyrazoles, and indoles under benign reaction conditions. The developed process involves the use of N,N′-dihalo-5,5-dimethylhydantoins (halo=chlorine, bromine, iodine) as halogenation reagents that are activated by catalytic quantities of a strong Bronsted acid. Moreover, the halogenation process is switchable to produce either the mono- or di-halogenated products. Issues related to the reaction mechanism are investigated and a proposal for a reaction mechanism is disclosed.

[1]  M. Gandelman,et al.  Metal-Free Efficient, General and Facile Iododecarboxylation Method with Biodegradable Co-Products , 2011 .

[2]  M. Wigglesworth,et al.  Novel imidazobenzazepine derivatives as dual H1/5-HT2A antagonists for the treatment of sleep disorders. , 2010, Bioorganic & medicinal chemistry letters.

[3]  D. Boger,et al.  Total synthesis of lycogarubin C and lycogalic acid. , 2010, Organic letters.

[4]  Y. Ku,et al.  A simple and highly effective oxidative chlorination protocol for the preparation of arenesulfonyl chlorides , 2010 .

[5]  R. Ohmura,et al.  Direct oxidative conversion of alkyl halides into nitriles with molecular iodine and 1,3-diiodo-5,5-dimethylhydantoin in aq ammonia , 2009 .

[6]  R. Grubbs,et al.  Effects of NHC-backbone substitution on efficiency in ruthenium-based olefin metathesis. , 2009, Journal of the American Chemical Society.

[7]  B. Borhan,et al.  A simple and expedient method for the preparation of N-chlorohydantoins. , 2009, Tetrahedron letters.

[8]  J. Nath,et al.  Boric acid catalyzed bromination of a variety of organic substrates: an eco-friendly and practical protocol , 2008 .

[9]  M. Salunkhe,et al.  Regioselective Iodination of Arenes Using Iodine/NaBO3 · 4H2O System in Ionic Liquid , 2008 .

[10]  S. Waghmode,et al.  Regioselective, photochemical bromination of aromatic compounds using N-bromosuccinimide , 2008 .

[11]  V. Filimonov,et al.  1,3-Diiodo-5,5-dimethylhydantoin—An efficient reagent for iodination of aromatic compounds , 2007 .

[12]  S. Collins,et al.  A Highly Active Chiral Ruthenium-Based Catalyst for Enantioselective Olefin Metathesis , 2007 .

[13]  Zhong‐Xia Wang,et al.  Halogenation of Pyrazoles Using N‐Halosuccinimides in CCl4 and in Water , 2007 .

[14]  S. Nolan.  N-Heterocyclic Carbenes in Synthesis: NOLAN:N-HETEROCYCL. CARB. O-BK , 2006 .

[15]  E. Yashima,et al.  Oligoresorcinols fold into double helices in water. , 2006, Journal of the American Chemical Society.

[16]  Vidar R. Jensen,et al.  Quantitative Structure−Activity Relationships of Ruthenium Catalysts for Olefin Metathesis , 2006 .

[17]  L. D. Luca,et al.  Naturally Occurring and Synthetic Imidazoles: Their Chemistry and Their Biological Activities , 2006 .

[18]  R. Crabtree.  NHC ligands versus cyclopentadienyls and phosphines as spectator ligands in organometallic catalysis , 2005 .

[19]  V. Gracias,et al.  Synthesis of fused bicyclic imidazoles by sequential van Leusen/ring-closing metathesis reactions. , 2005, Organic letters.

[20]  J. Bode,et al.  N-heterocyclic carbene-catalyzed generation of homoenolates: gamma-butyrolactones by direct annulations of enals and aldehydes. , 2004, Journal of the American Chemical Society.

[21]  A. Ojida,et al.  Synthetic studies on (1S)-1-(6,7-dimethoxy-2-naphthyl)-1-(1H-imidazol-4-yl)-2-methylpropan-1-ol as a selective C17,20-lyase inhibitor , 2004 .

[22]  J. Borrell,et al.  2,7,12,17‐Tetra(p‐butylphenyl)‐3,6,13,16‐tetraazaporphycene: The First Example of a Straightforward Synthetic Approach to a New Class of Photosensitizing Macrocycles , 2003 .

[23]  I. Izzo,et al.  Synthesis of antifungal N-isoprenyl-indole alkaloids from the fungus Aporpium caryae ☆ , 2002 .

[24]  R. Wolf,et al.  SAR of 2,6-diamino-3,5-difluoropyridinyl substituted heterocycles as novel p38MAP kinase inhibitors. , 2002, Bioorganic & medicinal chemistry letters.

[25]  W. Herrmann.  N-Heterocyclische Carbene: ein neues Konzept in der metallorganischen Katalyse N-Heterocyclische Carbene, 31. Mitteilung. – 30. Mitteilung: Lit. [80] , 2002 .

[26]  W. Herrmann.  N-heterocyclic carbenes: a new concept in organometallic catalysis. , 2002, Angewandte Chemie.

[27]  Â. Pinto,et al.  Aromatic iodination in aqueous solution. A new lease of life for aqueous potassium dichloroiodate , 2001 .

[28]  K. Kirk,et al.  SYNTHESES OF (TRIFLUOROMETHYL)IMIDAZOLES WITH ADDITIONAL ELECTRONEGATIVE SUBSTITUENTS. AN APPROACH TO RECEPTOR-ACTIVATED AFFINITY LABELS , 1998 .

[29]  S. Pyne,et al.  Asymmetric Synthesis of 2-Acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazoles , 1997 .

[30]  O. Arrad,et al.  New Aspects on the Preparation of 1,3-Dibromo-5,5-dimethylhydantoin , 1995 .

[31]  S. Pyne,et al.  Asymmetric Synthesis of 2-Acetyl-4(5)-(1,2,4-trihydroxybutyl)imidazoles , 1995 .

[32]  Wei Zhang,et al.  Synthesis of imidazoles via hetero-Cope rearrangements , 1993 .

[33]  G. Olah,et al.  Synthetic methods and reactions. 181. Iodination of deactivated aromatics with N-iodosuccinimide in trifluoromethanesulfonic acid (NIS-CF3SO3H) via in situ generated superelectrophilic iodine(I) trifluoromethanesulfonate , 1993 .

[34]  K. Erickson,et al.  The preparation and spectral characterization of 2-haloindoles, 3-haloindoles, and 2,3-dihaloindoles , 1986 .

[35]  B. Iddon,et al.  A convenient synthesis of 4(5)-mono-, 4,5-di-, and 2,4,5-tri-substituted imidazoles☆ , 1986 .

[36]  K. Kirk.  4-Lithio-1-tritylimidazole as a synthetic intermediate. Synthesis of imidazole-4-carboxaldehyde , 1985 .

[37]  J. Wildeman,et al.  Chemistry of sulfonylmethyl isocyanides. 12. Base-induced cycloaddition of sulfonylmethyl isocyanides to carbon,nitrogen double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides , 1977 .

[38]  R. A. Corral,et al.  N-IODOHYDANTOINS. II. IODINATIONS WITH 1,3-DIIODO-5,5-DIMETHYLHYDANTOIN. , 1965, The Journal of organic chemistry.

[39]  E. Schulze,et al.  Ueber Basen der Oxalsäurereihe , 1880 .

[40]  H. Debus.  Ueber die Einwirkung des Ammoniaks auf Glyoxal , 1858 .