Synthesis of Isonitriles from N-Substituted Formamides Using Triphenylphosphine and Iodine

Abstract

Treatment of N-substituted formamides with the reagent combination of triphenylphosphine and molecular iodine, in the presence of a tertiary amine, quickly produces the corresponding isocyanides in high yields under ambient conditions. The process employs readily available and low-cost reagents, a convenient synthetic procedure, and mild reaction conditions for the synthesis of various alkyl and aryl isocyanides.

Key words

isonitriles - formamides - dehydration - triphenylphosphine - iodine

• References

• 1a Tobisu M, Chatani N. Chem. Lett. 2011; 40: 330
• 1b Lang S. Chem. Soc. Rev. 2013; 42: 4867
• 2a Dömling A. Chem. Rev. 2006; 106: 17
• 2b El Kaim L, Grimaud L. Tetrahedron 2009; 65: 2153
• 2c Fei X.-D, Ge Z.-Y, Tang T, Zhu Y.-M, Ji S.-J. J. Org. Chem. 2012; 77: 10321
• 2d Vlaar T, Ruijter E, Znabet A, Janssen E, de Kanter FJ. J, Maes BU. W, Orru RV. A. Org. Lett. 2011; 13: 6496
• 2e Liu B, Yin M, Gao H, Wu W, Jiang H. J. Org. Chem. 2013; 78: 3009
• 2f Geden JV, Pancholi AK, Shipman M. J. Org. Chem. 2013; 78: 4158
• 2g Suginome M, Ito Y. Adv. Polym. Sci. 2004; 171: 77
• 3a Wilson RM, Stockdill JL, Wu X, Li X, Vadola PA, Park PK, Wang P, Danishefsky SJ. Angew. Chem. Int. Ed. 2012; 51: 2834
• 3b Lygin AV, de Meijere A. Angew. Chem. Int. Ed. 2010; 49: 9094
• 3c Gulevich AV, Zhdanko AG, Orru RV. A, Nenajdenko VG. Chem. Rev. 2010; 110: 5235
• 4 Pirrung MC, Ghorai S. J. Am. Chem. Soc. 2006; 128: 11772
• 5a Ugi I, Fetzer U, Eholzer U, Knupfer H, Offermann K. Angew. Chem., Int. Ed. Engl. 1965; 4: 472
• 5b Weber WP, Gokel GW, Ugi IK. Angew. Chem., Int. Ed. Engl. 1972; 11: 530
• 6 Obrecht R, Herrmann R, Ugi I. Synthesis 1985; 400
• 7 Karl R, Lemmen P, Ugi I. Synthesis 1989; 718
• 8 For example, POCl₃ is included in the List of Hazardous Chemicals issued by the Chinese State Administration of Work Safety as well as the Highly Toxic Chemicals Directory jointly issued by eight ministries of the Chinese Government.
• 9 Kobayashi G, Saito T, Kitano Y. Synthesis 2011; 3225
• 10a Sureshbabu VV, Narendra N, Nagendra G. J. Org. Chem. 2009; 74: 153
• 10b Porcheddu A, Giacomelli G, Salaris M. J. Org. Chem. 2005; 70: 2361
• 10c Appel R, Kleinstück R, Ziehn K.-D. Angew. Chem., Int. Ed. Engl. 1971; 10: 132
• 11 Luo Q.-L, Lv L, Li Y, Tan J.-P, Nan W, Hui Q. Eur. J. Org. Chem. 2011; 6916
• 12 Price ratios are based on the amount of 25 g from the current J&K Scientific Catalog in China, calculated from the price per mole of each reagent. Price ratios calculated from other commercial chemicals catalogs were similar.
• 13a Godfrey SM, Kelly DG, McAuliffe CA, Mackie AG, Pritchard RG, Watson SM. J. Chem. Soc., Chem. Commun. 1991; 1163
• 13b Bricklebank N, Godfrey SM, Mackie AG, McAuliffe CA, Pritchard RG, Kobryn PJ. J. Chem. Soc., Dalton Trans. 1993; 101
• 13c Núñez R, Farràs P, Teixidor F, Viñas C, Sillanpää R, Kivekäs R. Angew. Chem. Int. Ed. 2006; 45: 1270 ; and references therein
• 13d Bae S, Lakshman MK. J. Org. Chem. 2008; 73: 1311
• 14a Bandgar BP, Kinkar SN, Chobe SS, Mandawad GG, Yemul OS, Dawane BS. Arch. Appl. Sci. Res. 2011; 3: 246
• 14b Hosseini-Sarvari M, Sharghi H. J. Org. Chem. 2006; 71: 6652
• 14c Nanjo T, Tsukano C, Takemoto Y. Org. Lett. 2012; 14: 4270
• 14d Wang W.-h, Zhang T, Xu P. J. Chin. Pharm. Sci. 2003; 12: 66
• 15a Guirado A, Zapata A, Gómez JL, Trabalón L, Gálvez J. Tetrahedron 1999; 55: 9631
• 15b Hahn FE, Plumed CG, Münder M, Lügger T. Chem. Eur. J. 2004; 10: 6285
• 15c Polisar JG, Norton JR. Tetrahedron 2012; 68: 10236
• 15d Ugi I, Meyr R. Chem. Ber. 1960; 93: 239
• 15e Zhang T, Xu P. Chin. J. Med. Chem. 2002; 16: 325