A Novel Method for Preparing Isocyanides from N-Substituted Formamides with Chlorophosphate Compounds

Abstract

Treatment of N-substituted formamides with chlorophosphate compounds such as PhOPOCl₂, EtOPOCl₂, Me₂NPOCl₂, and (PhO)₂POCl and tertiary amines such as triethylamine, pyridine, and N,N-diisopropylethylamine produced the corresponding isocyanides in high yields. This method can be used to prepare various alkyl and aryl isocyanides.

Key words

isocyanide - isonitrile - formamide - dehydration - dichlorophosphate - monochlorophosphate

References

• 1 Passerini M. Gazz. Chim. Ital.  1921,  51:  126 
• 2 Ugi I. Betz W. Fetzer U. Offerman K. Chem. Ber.  1961,  94:  2814 
• 3a Ugi I. Isonitrile Chemistry   Academic Press; New York (NY): 1971. 
• 3b Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 3c Ugi I. Dömling A. Combinatorial Chemistry   Fenniri H. Oxford University Press; Oxford: 2000.  p.287 
• 3d Dömling A. Curr. Opin. Chem. Biol.  2000,  4:  318 
• 3e Ugi I. Werner B. Dömling A. Targets Heterocycl. Syst.  2000,  1 
• 4a Fusetani N. Nat. Prod. Rep.  2004,  21:  94 
• 4b Garson MJ. Simpson JS. Nat. Prod. Rep.  2004,  21:  164 
• 5a Kitano Y. Ito T. Suzuki T. Nogata Y. Shinshima K. Yoshimura E. Chiba K. Tada M. Sakaguchi I.
  J. Chem. Soc., Perkin Trans. 1  2002,  2251 
• 5b Kitano Y. Yokoyama A. Nogata Y. Shinshima K. Yoshimura E. Chiba K. Tada M. Sakaguchi I. Biofouling  2003,  19:  187 
• 5c Nogata Y. Kitano Y. Yoshimura E. Shinshima K. Sakaguchi I. Biofouling  2004,  20:  87 
• 5d Kitano Y. Nogata Y. Shinshima K. Yoshimura E. Chiba K. Tada M. Sakaguchi I. Biofouling  2004,  20:  93 
• 5e Kitano Y. Akima C. Yoshimura E. Nogata Y. Biofouling  2011,  27:  201 
• 6a Baldwin JE. O’Neil IA. Synlett  1990,  603 
• 6b Launay D. Booth S. Clemens I. Merritt A. Bradley M. Tetrahedron Lett.  2002,  43:  7201 
• 6c Porcheddu A. Giacomelli G. Salaris M. J. Org. Chem.  2005,  70:  4218 
• 6d Kim S. Yi KY. Tetrahedron Lett.  1986,  27:  1925 
• 6e Creedon SM. Crowley HK. McCarthy DG. J. Chem. Soc., Perkin Trans. 1  1998,  1015 
• 6f Bose DS. Goud PR. Tetrahedron Lett.  1999,  40:  747 
• 8 Kuo C.-W. Zhu J.-L. Wu J.-D. Chu C.-M. Yao C.-F. Shia K.-S. Chem. Commun.  2007,  301 
• 9 Claremon DA. Phillips BT. Tetrahedron Lett.  1988,  29:  2155 
• 10 Minozzi M. Nanni D. Walton JC. Org. Lett.  2003,  5:  901 
• 11 Kitano Y. Chiba K. Tada M. Synthesis  2001,  437 
• 12 Kitano Y. Nogata Y. Matsumura K. Yoshimura E. Chiba K. Tada M. Sakaguchi I. Tetrahedron  2005,  61:  9969 
• 13 Cai L. Han Y. Ren S. Huang L. Tetrahedron  2000,  56:  8253 
• 14 Kobayashi K. Nakashima T. Mano M. Morikawa O. Konishi H. Chem. Lett.  2001,  40:  602 
• 15 Guirado A. Zapata A. Gómez JL. Trabalón L. Gálvez J. Tetrahedron  1999,  55:  9631 
• 16 Porcheddu A. Giacomelli G. Salaris M. J. Org. Chem.  2005,  70:  2361 
• 17 Maya F. Tour JM. Tetrahedron  2004,  60:  81 
• 18 Hosseini-Sarvari M. Sharghi H. J. Org. Chem.  2006,  71:  6652 

7

Chemicals whose acute toxicity by the oral absorption is 50 mg/kg or less are defined as specific controlled poisonous substances under the Poisonous and Deleterious Substances Control Law by National Institute of Health Sciences in Japan. Acute toxicities of POCl₃, EtOPOCl₂, and PhOPOCl₂ are the following according to MSDS of Tokyo Chemical Industry Co., Ltd. and Wako Pure Chemical Industries, Ltd.; POCl₃ 36 mg/kg (orl-rat), EtOPOCl₂ 220 mg/kg (orl-rat), PhOPOCl₂ 850 mg/kg (orl-mam).