One-pot preparation of isocyanides from amines and their multicomponent reactions: crucial role of dehydrating agent and base

A novel one-pot practical approach for the preparation of isocyanide directly from amine and its reaction has been developed. It employs formylation of amine, dehydration of formamide to isocyanide, and its multicomponent reactions (Ugi, Passerini, and Groebke–Blackburn–Bienayme reactions). This method provides a significant solution to known synthetic difficulties of isocyanides. In this approach, the nature and stoichiometric quantities of dehydrating agent and base, and the catalysis-function of by-products were found to play crucial roles.

[1]  Wei Wang,et al.  Chemistry and biology of multicomponent reactions. , 2012, Chemical reviews.

[2]  Xuechen Li,et al.  A fascinating journey into history: exploration of the world of isonitriles en route to complex amides. , 2012, Angewandte Chemie.

[3]  Ziwei Hu,et al.  Direct carboxamidation of indoles by palladium-catalyzed C-H activation and isocyanide insertion. , 2012, Chemical Communications.

[4]  J. Conrad,et al.  Microwave-assisted three-component reaction in conventional solvents and ionic liquids for the synthesis of amino-substituted imidazo[1,2-a]pyridines , 2012 .

[5]  B. Maes,et al.  Palladium-catalyzed synthesis of 4-aminophthalazin-1(2H)-ones by isocyanide insertion. , 2011, Organic letters.

[6]  Amit Agarwal,et al.  N-fused imidazoles as novel anticancer agents that inhibit catalytic activity of topoisomerase IIα and induce apoptosis in G1/S phase. , 2011, Journal of medicinal chemistry.

[7]  Chetna Madaan,et al.  Groebke-Blackburn-Bienaymé multicomponent reaction in scaffold-modification of adenine, guanine, and cytosine: synthesis of aminoimidazole-condensed nucleobases , 2011 .

[8]  Chetna Madaan,et al.  Towards molecular diversity: dealkylation of tert-butyl amine in Ugi-type multicomponent reaction product establishes tert-butyl isocyanide as a useful convertible isonitrile. , 2010, Organic & biomolecular chemistry.

[9]  A. Majee,et al.  Formylation without catalyst and solvent at 80 °C , 2010 .

[10]  B. Thakkar,et al.  A Highly Flexible and EfficientUgi-Type Multicomponent Synthesis of Versatile N-FusedAminoimidazoles , 2009 .

[11]  Dennis G Hall,et al.  Natural product synthesis using multicomponent reaction strategies. , 2009, Chemical reviews.

[12]  Tannya R. Ibarra-Rivera,et al.  Multicomponent reactions of convertible isonitriles. , 2009, The Journal of organic chemistry.

[13]  Chetna Madaan,et al.  An Efficient, Regioselective,Versatile Synthesis of N-Fused 2- and 3-Aminoimidazolesvia Ugi-Type Multicomponent Reaction Mediated by Zirconium(IV)Chloride in Polyethylene Glycol-400 , 2009 .

[14]  J. Sello,et al.  Catalysis of Ugi four component coupling reactions by rare earth metal triflates. , 2008, The Journal of organic chemistry.

[15]  P. Mirzaei,et al.  CATALYST-FREE THREE-COMPONENT REACTION BETWEEN 2-AMINOPYRIDINES (OR 2-AMINOTHIAZOLES), ALDEHYDES, AND ISOCYANIDES IN WATER , 2007 .

[16]  R. Orru,et al.  A resource-efficient and highly flexible procedure for a three-component synthesis of 2-imidazolines. , 2007, The Journal of organic chemistry.

[17]  M. Pirrung,et al.  Versatile, fragrant, convertible isonitriles. , 2006, Journal of the American Chemical Society.

[18]  Alexander Dömling,et al.  Recent developments in isocyanide based multicomponent reactions in applied chemistry. , 2006, Chemical reviews.

[19]  G. Giacomelli,et al.  Microwave-assisted synthesis of isonitriles: a general simple methodology. , 2005, The Journal of organic chemistry.

[20]  S. Puri,et al.  In vivo active antimalarial isonitriles. , 2002, Bioorganic & medicinal chemistry letters.

[21]  O. Schwarz,et al.  Synthesis and biological evaluation of new antimalarial isonitriles related to marine diterpenoids , 2002 .

[22]  I. Ugi,et al.  Multicomponent Reactions with Isocyanides. , 2000, Angewandte Chemie.

[23]  G. Jana,et al.  Total Synthesis of 9-Isocyanoneopupukeanane. , 1999, The Journal of organic chemistry.

[24]  T. Ishikawa,et al.  2-Chloro-1,3-dimethylimidazolinium Chloride. 1. A Powerful Dehydrating Equivalent to DCC , 1999 .

[25]  H. Bienaymé,et al.  A New Heterocyclic Multicomponent Reaction For the Combinatorial Synthesis of Fused 3-Aminoimidazoles. , 1998, Angewandte Chemie.

[26]  L. Weber,et al.  Synthesis of Imidazo[1,2-a] annulated Pyridines, Pyrazines and Pyrimidines by a Novel Three-Component Condensation , 1998 .

[27]  C. Blackburn,et al.  Parallel synthesis of 3-aminoimidazo[1,2-a]pyridines and pyrazines by a new three-component condensation , 1998 .

[28]  P. Scheuer Isocyanides and Cyanides as Natural Products , 1992 .

[29]  R. Herbert,et al.  Naturally occurring isocyanides. , 1988, Natural product reports.

[30]  P. Boullanger,et al.  Synthesis of 1-isocyano sugars , 1976 .

[31]  H. Walborsky,et al.  Synthesis of isonitriles , 1972 .

[32]  J. D. Jong,et al.  Isomerization of o-biphenylyl isocyanide into 1-azabenz b azulene and the formation of both from o-biphenylyl isothiocyanate , 1969 .

[33]  I. Ugi,et al.  Isonitrile, IX. α‐Addition von Immonium‐Ionen und Carbonsäure‐Anionen an Isonitrile , 1961 .

[34]  A. Gautier Ueber eine neue Reihe von Verbindungen, welche mit den Cyanwasserstoffsäure‐Aethern isomer sind , 1868 .

[35]  W. Lieke Ueber das Cyanallyl , 1859 .