Indium-Mediated Cleavage of the Trityl Group from Protected 1H-Tetrazoles

Dedicated to the memory of Prof. Manfred Schlosser

Abstract

On treatment with indium metal in MeOH–THF, trityl groups undergo reductive removal from 1H-protected tetrazoles (including aliphatic, aromatic, and heteroaromatic substituents), affording the corresponding free tetrazoles in excellent yields, without any decomposition of the tetrazole ring or reduction of any other group.

Key words

tetrazole - indium - detritylation - cleavage

• References and Notes

• 1a Woo HG, Choi HT. Indium Properties, Technological Applications and Health Issues . Nova Science Publishers; New York: 2013
• 1b Perchyonok VT. Radical Reactions in Aqueous Media . Royal Society of Chemistry; Cambridge: 2010

For reviews, see:
• 2a Podlech J, Maier TC. Synthesis 2003; 633
• 2b Yadav JS, Antony A, George J, Subba RB. V. Eur. J. Org. Chem. 2010; 591
• 2c Shen ZL, Wang SY, Chok YK, Xu YH, Loh TP. Chem. Rev. 2013; 113: 271
• 3 Moody CJ, Pitts MR. Synlett 1999; 1575
• 4 Leeyoung P, Gyochang K, Soon BK, Kwan SK, Youseung K. J. Chem. Soc., Perkin Trans. 1 2000; 4462
• 5 Tomoko M, Hisao K, Takehisa K. Tetrahedron Lett. 2007; 48: 5027
• 6 Yadav JS, Subba BV, Madan C. New J. Chem. 2000; 24: 853
• 7 Daugherty A, Cassis L. Trends Cardiovasc. Med. 2004; 14: 117
• 8 Srimurugan S, Suresh P, Babu B, Hiriyanna SG, Pati HN. Chem. Pharm. Bull. 2008; 56: 383
• 9 García G, Rodríguez-Puyol M, Alajarín R, Serrano I, Sánchez-Alonso P, Griera M, Vaquero J, Rodríguez-Puyol D, Álvarez-Builla J, Díez-Marqués M. J. Med. Chem. 2009; 52: 7220
• 10a Yus M, Behloul C, Guijarro D. Synthesis 2003; 2179
• 10b Behloul C, Guijarro D, Yus M. Synthesis 2004; 1274
• 10c Behloul C, Guijarro D, Yus M. Tetrahedron 2005; 61: 6908
• 10d Behloul C, Guijarro D, Yus M. Tetrahedron 2005; 61: 9319
• 10e Behloul C, Guijarro D, Yus M. Synthesis 2006; 309
• 10f Behloul C, Guijarro D, Yus M. ARKIVOC 2007; (vii): 41
• 10g Behloul C, Bouchelouche K, Guijarro D, Najera C, Yus M. Synthesis 2014; 2065
• 10h Behloul C, Chouti A, Guijarro D, Najera C, Yus M. Synthesis 2015; 47: 507

For reviews, see:
• 11a Yus M. Chem. Soc. Rev. 1996; 25: 155
• 11b Ramón DJ, Yus M. Eur. J. Org. Chem. 2000; 225
• 11c Yus M. Synlett 2001; 1197
• 11d Yus M, Ramón DJ. Latv. J. Chem. 2002; 79
• 11e Ramón DJ, Yus M. Rev. Cubana Quim. 2002; 14: 76
• 11f Yus M In The Chemistry of Organolithium Compounds . Rappoport Z, Mareck I. J. Wiley and Sons; Chichester: 2004. Chap. 1

For a mechanistic study, see:
• 11g Yus M, Herrera RP, Guijarro A. Tetrahedron Lett. 2001; 42: 3455
• 11h Yus M, Herrera RP, Guijarro A. Chem. Eur. J. 2002; 8: 2574
• 11i Herrera RP, Guijarro A, Yus M. Tetrahedron Lett. 2003; 44: 1309
• 12 With the aim of trying to broaden the substrate scope, we tried to prepare some other tetrazoles functionalized with either ester or amide groups but, unfortunately, all our attempts were unsuccessful.
• 13 Typical Procedure In a typical procedure, a mixture of 5-phenyl-1-trityl-1H-tetrazole (1a, 0.230 g, 0.5 mmol) and indium powder (0.058 g, 0.5 mmol) in MeOH (6 mL) and THF (3 mL) was stirred at 78 °C for 26 h. Then the resulting mixture was cooled to r.t., hydrolyzed with 1 M HCl (2 mL), extracted with EtOAc (3 × 10 mL), dried over anhydrous MgSO₄, and evaporated (20 mbar). The resulting residue was purified by column chromatography (silica gel, hexane–EtOAc) to yield 5-phenyl-1H-tetrazole (2a, 0,134 g, 93%) as a white solid, mp 215–216 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 7. 55–7.62 (m, 3 H), 8.01–8.10 (m, 2 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 124.1 (2 × CH), 127.0 (C), 129.4 (CH), 131.3 (2 × CH), 155.3 (C).^10h
• 14 For all detailed procedures, see the attached Supporting Information.