The Reaction of Carbonyldiimidazole with Alcohols to Form Carbamates and N-Alkylimidazoles

Abstract

The reactions of non-benzylic primary and secondary aliphatic alcohols with carbonyldiimidazole (CDI) afford the corresponding carbamates but not N-alkylimidazoles. For benzylic primary alcohols, formation of N-alkylimidazoles proceeds reasonably at 170 °C in several different solvents and occurs by way of the initially formed carbamate. However, under these rather forcing conditions, or even at lower reaction temperatures, elimination is a significant side reaction for benzylic secondary alcohols with β-hydrogen atoms. With one exception, reactions of six N,N-disubstituted β-aminoalcohols with CDI to form N-alkylimidazoles proceed under relatively mild conditions and may occur by way of an aziridinium intermediate.

Keywords

alcohols - alkylations - carbonyldiimidazole (CDI) - carbamates - N-alkylimidazoles

References

• 1 Roth HJ. Kleeman A. Pharmaceutical Chemistry   John Wiley; New York: 1988.  p.218 
• 2a Rotstein DM. Kertesz DJ. Walker KAM. Swinney DC. J. Med. Chem.  1992,  35:  2818 
• 2b Jones CD. Winter MA. Hirsch KS. Stamm N. Taylor HM. Holden HE. Davenport JD. Krumkalns EV. Suhr RG. J. Med. Chem.  1990,  33:  416 
• 2c Heeres J. Backx LJ. Mostmans JH. Van Cutsem J. J. Med. Chem.  1979,  22:  1003 
• 3a Amemiya Y. Terada A. Wachi K. Miyazawa H. Hatakeyama N. Matsuda K. Oshima T. J. Med. Chem.  1989,  32:  1265 
• 3b Hasegawa T. Yoshida K. Hachiya K. Miyazaki M. Tsuruta H. Nambu F. Ohuchida S. Kawamura M. Synlett  1997,  511 
• 3c Kaulen J. Angew. Chem., Int. Ed. Engl.  1989,  28:  462 ; Angew. Chem.; 1989, 101, 507
• 3d Kato A. Ikeda Y. Sugita N. Nitta T. Enari H. Kashima A. Konno M. Niimura K. Chem. Pharm. Bull.  1995,  43:  2152 
• 4 Njar VCO. Synthesis  2000,  2019 
• 5 Fischer W. Synthesis  2002,  29 
• 6 Kamijo T. Yamamoto R. Harada H. Iizuka K. Chem. Pharm. Bull.  1983,  31:  1213 
• 7 Le Borgne M. Marchand P. Duflos M. Delevoye-Seiller B. Piessard-Robert S. Le Baut G. Hartmann RW. Palzer M. Arch. Pharm. Pharm. Med. Chem.  1997,  330:  141 
• 8 Whitten JP. McCarthy JR. Matthews DP. Synthesis  1988,  470 
• 9 Bertolini G. Pavich G. Vergani B. J. Org. Chem.  1998,  63:  6031 
• 10 Botta M. Summa V. Trapassi G. Monteagudo E. Corelli F. Tetrahedron: Asymmetry  1994,  5:  181 
• 11 Ogata M. Matsumoto H. Kida S. Shimizu S. Chem. Ind. (London)  1980,  85 
• 12 Aelterman W. Lang Y. Willemsens B. Vervest I. Leurs S. De Knaep F. Org. Process Res. Dev.  2001,  5:  467 
• 13 Cutugno S. Martelli G. Negro L. Savoia D. Eur. J. Org. Chem.  2001,  517 
• 14 Adolphi H, Steimmig A, and Spaenig H. inventors; Fr. Patent FR  1486817 19670630.  ; Chem. Abstr. 1968, 77228
• 15 O’Brien P. Towers TD. J. Org. Chem.  2002,  67:  304 
• 16 Mulvihill MJ. Cesario C. Smith V. Beck P. Nigro A. J. Org. Chem.  2004,  69:  5124 
• 17 Totleben MJ. Freeman JP. Szmuszkovicz J. J. Org. Chem.  1997,  62:  7319 
• 18 Freyne E. Raeymaekers A. Venet M. Sanz G. Wouters W. De Coster R. Van Wauwe J. Bioorg. Med. Chem. Lett.  1998,  8:  267