Synthesis of Novel Trisubstituted Imidazolines

Abstract

Imidazolines substituted at the 1- and either the 4-, or 5-position with phenyl and at the 2-position with alkyl or phenyl have been prepared in racemic form. They appear to be fairly stable compounds and potentially useful as scaffolds in medicinal chemistry.

dihydroimidazole - imidazoline - reductive amination - ring-closure - acylation

References

1a von Rauch M. Busch S. Gust R. J. Med. Chem.  2005,  48:  466 

1b Acharya AN. Ostresh JM. Houghten RA. J. Org. Chem.  2001,  66:  8673 

1c Concellón JM. Riego E. Suárez JR. García-Granda S. Díaz MR. Org. Lett.  2004,  6:  4499 

1d Ishihara M. Togo H. Synthesis  2007,  1939 

1e Vassilev LT. Vu BT. Graves B. Carvajal D. Podlaski F. Filipovic Z. Kong N. Kammlott U. Lukacs C. Klein C. Fotouhi N. Liu EA. Science  2004,  303:  844 

2

Evidence for acyl migration comes mainly from ^¹H NMR spectra of isolated 6. In particular, two broad singlets of D₂O-exchangeable protons were observed rather than the one singlet integrating to 2 H expected for amide 8.

3 Myers MC. Wang Jin L. Iera JA. Bang J.-k. Hara T. Saito S. Zambetti GP. Appella DH. J. Am. Chem. Soc.  2005,  127:  6152 

4 Moriya T. Takabe S. Maeda S. Matsumoto K. Takashima K. Mori T. Takeyama S. J. Med. Chem.  1986,  29:  333 

5a Brown DS. Elliott MC. Moody CJ. Mowlem TJ. Marino JP. Padwa A. J. Org. Chem.  1994,  59:  2447 

5b Barton DHR. Chern C.-Y. Tachdjian C. Heterocycles  1994,  37:  793 

6a Crowther AF. Mann FG. Purdie D. J. Chem. Soc.  1943,  58 

6b Wang J. Hou Y. Wu P. J. Chem. Soc., Perkin Trans. 1  1999,  16:  2277 

7 Yates P. J. Am. Chem. Soc.  1952,  74:  5376