A Diversified Assembly of 1,2,4-Oxadiazol-3-amines: Metallic Thiophile Catalyzed Chemoselective One-Pot Reaction of Aryl Isothiocyanates, Amidines/Guanidines, and Hydroxylamine

In loving memory of my grandfather, S. J. Jalani

Abstract

An efficient one-pot synthesis of 1,2,4-oxadiazol-3-amines from simple starting materials, isothiocyanates, amidines/guanidines, and hydroxylamine, is described. The reaction is facilitated by metallic-thiophile-assisted desulfurization of in situ formed amidino- or guanidinothiourea to give chemoselectively N-hydroxyguanidine intermediates that give exclusively various 1,2,4-oxadiazol-3-amines in good to excellent yields. The reaction mechanistic pathway may proceed through an intramolecular 5-exo-trig cyclization.

Key words

1,2,4-oxadiazol-3-amine - metallic thiophile - chemoselectivity - N-hydroxyguanidine

• References

• 1 Communication No.: PERD030512.
• 2 Vu CB, Corpuz EG, Merry TJ, Pradeepan SG, Bartlett C, Bohacek RS, Botfield MC, Eyermann CJ, Lynch BA, MacNeil IA, Ram MK, Van Schravendijk MR, Violette S, Sawyer TK. J. Med. Chem. 1999; 42: 4088
• 3 Orlek BS, Blaney FE, Brown F, Clark MS, Hadley MS, Hatcher J, Riley GJ, Rosenberg HE, Wadsworth HJ, Wyman P. J. Med. Chem. 1991; 34: 2726
• 4 Clitherow JW, Beswick P, Irving WJ, Scopes DI. C, Barnes JC, Clapham J, Brown JD, Evans DJ, Hayes AG. Bioorg. Med. Chem. Lett. 1996; 6: 833
• 5 Nicolaides DN, Fylaktakidou KC, Litinas KE, Hadjipavlou-Litina D. Eur. J. Med. Chem. 1998; 33: 715
• 6a Matsumoto J, Takahashi T, Agata M, Toyofuku H, Sasada N. Jpn. J. Pharmacol. 1994; 65: 51
• 6b Zhang HZ, Kasibhatla S, Kuemmerle J, Kemnitzer W, Ollis-Mason K, Qiu L, Crogan-Grundy C, Tseng B, Drewe J, Cai SX. J. Med. Chem. 2005; 48: 5215
• 7 Chimirri A, Grasso S, Montforte A.-M, Rao A, Zappala M. Farmaco 1996; 51: 125
• 8 Borg S, Vollinga RC, Labarre M, Payza K, Terenius L, Luthman K. J. Med. Chem. 1999; 42: 4331
• 9 Borg S, Estenne-Bouhtou G, Luthman K, Csoregh I, Hesselink W, Hacksell U. J. Org. Chem. 1995; 60: 3112
• 10 Jochims JC In Comprehensive Heterocyclic Chemistry II . Vol. 4. Katritzky AR, Rees CW, Scriven RF. V. Pergamon Press; Oxford: 1996. Chap. 4, 179-228 ; and references therein
• 11 Hemming K In Comprehensive Heterocyclic Chemistry III . Vol. 5. Katritzky AR, Rees CW, Scriven RF. V, Taylor RJ. K. Elsevier Science; Oxford: 2008. Chap. 4, 243-309 ; and references cited therein

For reviews, see:
• 12a Adib M, Jahromi AH, Tavoosi N, Mahdavi M, Bijanzadeh HR. Tetrahedron Lett. 2006; 47: 2965
• 12b Adib M, Mahdavi M, Mahmoodi N, Pirelahi H, Bijanzadeh HR. Synlett 2006; 1765
• 12c Kumita I, Niwa A. J. Pestic. Sci. (Tokyo, Jpn.) 2001; 26: 60
• 12d Westphal G, Schmidt R. Z. Chem. 1974; 14: 94
• 12e Piccionello AP, Pace A, Buscemi S, Vivona N. Org. Lett. 2009; 11: 4018
• 13 Adib M, Bagherzadeh S, Mahdavi M, Bijanzadeh HR. Mendeleev Commun. 2010; 20: 50
• 14 Kurz T, Lolak N, Geffken D. Tetrahedron Lett. 2007; 48: 2733

For reviews, see:
• 15a Domling A. Curr. Opin. Chem. Biol. 2002; 6: 306
• 15b Orru RV. A, de Greef M. Synthesis 2003; 1471
• 15c Hulme C, Gore V. Curr. Med. Chem. 2003; 10: 51
• 15d Zhu J. Eur. J. Org. Chem. 2003; 1133
• 15e Nair V, Rajesh C, Vinod AU, Bindu S, Sreekanth AR, Mathen JS, Balagopal L. Acc. Chem. Res. 2003; 36: 899
• 15f Ramon DJ, Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602 ; Angew. Chem. 2005, 117, 1628
• 15g Dondoni A, Massi A. Acc. Chem. Res. 2006; 39: 451
• 15h Domling A. Chem. Rev. 2006; 106: 17
• 15i D’Souza DM, Muller TJ. J. Chem. Soc. Rev. 2007; 36: 1095
• 15j Muller TJ. J. Top. Organomet. Chem. 2006; 19: 149
• 15k Multicomponent Reactions . Zhu V, Bienaymé H. Wiley-VCH; Weinheim: 2005
• 16 Cruzer F. J. Chem. Soc. 1956; 2345
• 17 Rajappa S, Advani BG. Indian J. Chem. 1970; 8: 1145

For reviews on guanylating reagents and their uses see:
• 18a Manimala JC, Anslyn EV. Eur. J. Org. Chem. 2002; 3909
• 18b Katritzky AR, Rogovoy BV. ARKIVOC 2005; (iv): 49
• 19a Franklin PX, Pillai AD, Rathod PD, Yerande S, Nivsarkar M, Padh H, Vasu KK, Sudarsanam V. Eur. J. Med. Chem. 2008; 43: 129
• 19b Sudarsanam V, Giordano A, Vasu KK, Thakar HM, Giri RS, Yerande S, Inamdar GS. WO 2006148113, 2007 ; Chem. Abstr. 2007, 147, 469324
• 19c Giordano A, Vasu KK, Thakar HM, Giri RS, Yerande S, Inamdar GS, Sudarsanam V. US 20090306073, 2009
• 20a Kaila JC, Baraiya AB, Pandya AN, Jalani HB, Vasu KK, Sudarsanam V. Tetrahedron Lett. 2009; 50: 3955
• 20b Kaila JC, Baraiya AB, Vasu KK, Sudarsanam V. Tetrahedron Lett. 2008; 49: 7220
• 21 Kaila JC, Baraiya AB, Pandya AN, Jalani HB, Vasu KK, Sudarsanam V. Tetrahedron Lett. 2010; 51: 1486
• 22 Kaila JC. PhD Thesis. Bhavnagar University; Gujarat India: 2009
• 23 Franklin PX, Pillai AD, Rathod PD, Yerande S, Nivsarkar M, Padh H, Vasu KK, Sudarsanam V. Eur. J. Med. Chem. 2008; 43: 129
• 24 Simanenko YS, Popov AF, Prokop’eva TM, Savelova VA, Belousova IA. Theor. Exp. Chem. 1994; 30: 2, 61
• 25 Stolle R, Laske V. Chem. Ber. 1899; 32: 2238
• 26 Compound 5l: Chemical formula C₁₁H₁₄N₄O, gray crystal. The crystal is of monoclinic shape and the symmetry group present is C2/c. Crystallographic data for compound 5l have been deposited in the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 794212. Copies of the data may be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone] or e-mail: [e-mail]].
• 27 Hullin RP, Miller J, Short WF. J. Chem. Soc. 1947; 394
• 28a Hodgkins JE, Ettlinger MG. J. Org. Chem. 1956; 21: 404
• 28b Hodgkins JE, Reeves WP. J. Org. Chem. 1964; 29: 3098
• 28c Dolman SJ, Wong R. J. Org. Chem. 2007; 72: 3969