Facile Conversion of Amino Acids into 1-Alkyl Imidazole-2-thiones, and Their Oxidative Desulfurization to Imidazoles with Benzoyl Peroxide

Abstract

Glycine was acylated with isothiocyanates and condensed to 3-alkyl 2-thiohydantoins, which were reduced with a mixture of sodium borohydride and lithium chloride and dehydrated to 1-alkyl imidazole-2-thiones. These were oxidatively desulfurized to imidazoles with benzoyl peroxide. No chromatography was required for model compounds. The methods developed were used to elaborate tyrosine to 1,4-di(p-methoxybenzyl)imidazole, a common intermediate in the syntheses of three imidazoles from the sponge Leucetta.

Key words

desulfurization - heterocycles - imidazoles - natural products - oxidation

References

• 1 Hofmann K. Imidazole and its Derivatives   Interscience Publishers; New York: 1953. 
• 2 Review: Trzhtsinskaya BV. Abramova ND. Sulfur Rep.  1991,  10:  389 
• 3 Xi N. Xu S. Cheng Y. Tasker AS. Hungate RW. Reider PJ. Tetrahedron Lett.  2005,  46:  7315 
• 4 Baran PS. Shenvi RA. Mitsos CA. Angew. Chem. Int. Ed.  2005,  44:  3714 
• 5 Loksha YM. El-barbary AA. El-badawi MA. Nielsen C. Pedersen EB. Synthesis  2004,  116 
• 6 Chang JH. Lee KW. Nam DH. Kim WS. Shin H. Org. Process Res. Dev.  2002,  6:  674 
• 7 Grivas S. Ronne E. Acta Chem. Scand.  1995,  49:  225 
• 8 Karkhanis DW. Field L. Phosphorus, Sulfur Relat. Elem.  1985,  22:  49 
• 9 Pesch J. Harms K. Bach T. Eur. J. Org. Chem.  2004,  2025 
• 10 Frachey G. Crestini C. Bernini R. Saladino R. Mincione E. Heterocycles  1994,  38:  2621 
• 11 Ashutosh Pandey ND. Mehrotra JK. Heterocycles  1979,  12:  1339 
• 12 Buran V. Massaroli GG. Boll. Chim. Farm.  1980,  119:  725 ; Chem. Abstr. 1981, 95, 62075y
• 13 Hayakawa I. Yamazaki K. Dohmori R. Koga N. Heterocycles  1978,  10:  241 
• 14 Jones RG. J. Am. Chem. Soc.  1952,  74:  1085 
• 15 Tanaka K. Shimazak M. Murakami Y. Chem. Pharm. Bull.  1982,  30:  2714 
• 16 Schoenherr HJ. Wanzlick HW. Chem. Ber.  1970,  103:  1037 
• 17 Jones RG. Kornfeld EC. McLaughlin KC. Anderson RC. J. Am. Chem. Soc.  1949,  71:  4000 
• 18 Kister J. Assef G. Mille G. Metzger J. Can. J. Chem.  1979,  57:  813 
• 19 Marckwald W. Ber. Dtsch. Chem. Ges.  1892,  25:  2354 
• 20 Kuhn N. Kratz T. Synthesis  1993,  561 
• 21 Markwalder JA. Pottorf RS. Seitz SP. Synlett  1997,  521 
• 22 Scott JE. Henderson G. Biochem. J.  1968,  109:  209 
• 23 Johnson JR. Buchanan JB. J. Am. Chem. Soc.  1951,  73:  3749 
• 24 Chang W.-J. Kulkarni MV. Sun C.-M. J. Comb. Chem.  2006,  8:  141 
• 25 Zhang X. Allan GF. Sbriscia T. Linton O. Lundeen SG. Sui Z. Bioorg. Med. Chem. Lett.  2006,  16:  5763 
• 26 Khodair AI. Nucleosides, Nucleotides Nucleic Acids  2001,  20:  1735 
• 27 Reyes S. Burgess K. J. Org. Chem.  2006,  71:  2507 
• 28 Muccioli GG. Fazio N. Scriba GKE. Poppitz W. Cannata F. Poupaert JH. Wouters J. Lambert DM. J. Med. Chem.  2006,  49:  417 
• 29 Marckwald W. Neumark M. Stelzner R. Ber. Dtsch. Chem. Ges.  1891,  24:  3278 
• 30 Edman P. Carlsberg Res. Commun.  1977,  42:  1 ; Chem. Abstr. 1977, 87, 163564x
• 31 Sun Y. Gao L.-P. Ding M.-W. Synth. Commun.  2006,  36:  1185 
• 32 Sun Y. Gao L.-P. Guo Z.-Q. Ding M.-W. Phosphorus, Sulfur Silicon Relat. Elem.  2006,  181:  2109 
• 33 Sundaram GSM. Venkatesh C. Ila H. Junjappa H. Synlett  2007,  251 
• 34 Wolfe DM. Schreiner PR. Eur. J. Org. Chem.  2007,  2825 
• 35 Kruse LI. Kaiser C. DeWolf WE. Finkelstein JA. Frazee JS. Hilbert EL. Ross ST. Flaim KE. Sawyer JL. J. Med. Chem.  1990,  33:  781 
• 36 Gonzalez M. A. Mota J. F. Monterrey IM. G. Requejo JL. J. Albarran JC. P. Mellet MC. O. Carbohydr. Res.  1986,  154:  49 
• 37 Yang C. Pittman CU. Synth. Commun.  1998,  28:  2027 
• 38 Brown HC. Ichikawa K. J. Am. Chem. Soc.  1961,  83:  4372 
• 39 Babler JH. Synth. Commun.  1982,  12:  839 
• 40 Nakamura S. Kawasaki I. Yamashita M. Ohta S. Heterocycles  2003,  60:  583 
• 41 Lipshutz BH. Huff B. Hagen W. Tetrahedron Lett.  1988,  29:  3411 
• 42 Lipshutz BH. Vaccaro W. Huff B. Tetrahedron Lett.  1986,  27:  4095 
• 43a Goodyer CLM. Chinje EC. Jaffar M. Stratford IJ. Threadgill MD. Bioorg. Med. Chem.  2003,  11:  4189 
• 43b

  The procedure was scaled up for the reaction of 4-methoxybenzylamine (25.92 g, 189 mmol), CaCO₃ (19.44 g, 194 mmol), and CSCl₂ (29 mL, 44 g, 383 mmol) in CHCl₃ (175 mL), and H₂O (175 mL). The isolate was distilled (bp 92.5-94 °C/0.2-0.3 Torr) to afford p-methoxybenzyl isothiocyanate (30.24 g, 89%) with spectral properties matching those of the chromatographed material from the literature.

• 44 Incesu Z. Benkli K. Akalin G. Kaplancikli ZA. Cell Biol. Int.  2004,  28:  267 
• 45 Brown HC. Choi YM. Narasimhan S. Inorg. Chem.  1981,  20:  4454