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Synlett 2013; 24(2): 173-176
DOI: 10.1055/s-0032-1317958
DOI: 10.1055/s-0032-1317958
letter
Synthesis of 1,2,4-Trioxepanes and 1,2,4-Trioxanes via H2O2-Mediated Reaction of Tertiary Carbinols
Further Information
Publication History
Received: 29 October 2012
Accepted after revision: 08 December 2012
Publication Date:
21 December 2012 (online)
Abstract
A facile and efficient method for the synthesis of 1,2,4-trioxepanes and 1,2,4-trioxanes from different carbinols having cyclopropyl and phenyl substituents has been developed. The corresponding hydroxyhydroperoxides were synthesized from 30% H2O2 mediated reaction of carbinols in acidic conditions. This method provided access to novel 6,6-diaryl-substituted 1,2,4-trioxanes derived from benzilic acid.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1 World Malaria Report. World Health Organization; Geneva: 2011. ; http://www.who.int/-malaria/world_malaria_report_2011/en/
- 2 Klayman DL. Science 1985; 228: 1049
- 3a Jefford CW, Jaggi D, Boukouvalas J, Kohmoto S. J. Am. Chem. Soc. 1983; 105: 6498
- 3b Kepler JA, Philip A, Lee YW, Morey MC, Caroll FI. J. Med. Chem. 1988; 31: 713
- 3c Fujisaku T, Miura M, Nojima M, Kasabayashi S. J. Chem. Soc., Perkin Trans. 1 1989; 1031
- 3d Bloodworth AJ, Shah A. J. Chem. Soc., Chem. Commun. 1991; 947
- 3e Bunelle WH, Isbell TA, Barnes CL, Qualls S. J. Am. Chem. Soc. 1991; 113: 8168
- 3f Bloodworth AJ, Johnson KA. Tetrahedron Lett. 1994; 35: 8057
- 3g O’Neill PM, Pugh M, Davies J, Ward SA, Park BK. Tetrahedron Lett. 2001; 42: 4569
- 3h O’Neill PM, Mukhtar A, Ward SA, Bickley JF, Davies J, Bachi MD, Stocks PA. Org. Lett. 2004; 6: 3035
- 4 Singh C, Verma VP, Naikade NK, Singh AS, Hassam M, Puri SK. J. Med. Chem. 2008; 51: 7581
- 5 Singh C, Pandey S, Sharma M, Puri SK. Bioorg. Med. Chem. 2008; 16: 1816
- 6 Adam W, Duran N. J. Chem. Soc., Chem. Commun. 1972; 798
- 7 Singh C. Tetrahedron Lett. 1990; 31: 6901
- 8 Dussault PH, Trullinger TK, Noor-e-Ain F. Org. Lett. 2002; 4: 4591
- 9a Dussault PH, Davies DR. Tetrahedron Lett. 1996; 37: 463
- 9b Ushigoe Y, Torao Y, Masuyama A, Nojima M. J. Org. Chem. 1997; 62: 4949
- 9c Ushigoe Y, Kano Y, Nojima M. J. Chem. Soc., Perkin Trans. 1 1997; 5
- 9d Ahmed A, Dussault PH. Org. Lett. 2004; 6: 3609
- 10a Singh C, Misra D, Saxena G, Chandra S. Bioorg. Med. Chem. Lett. 1992; 2: 497
- 10b Singh C, Misra D, Saxena G, Chandra S. Bioorg. Med. Chem. Lett. 1995; 5: 1913
- 10c Singh C, Malik H, Puri SK. Bioorg. Med. Chem. Lett. 2004; 14: 459
- 10d Singh C, Malik H, Puri SK. J. Med. Chem. 2006; 49: 2794
- 10e Singh C, Kanchan R, Sharma U, Puri SK. J. Med. Chem. 2007; 50: 521
- 11 Wong HN. C, Hon MY, Tse CW, Yip YC, Tanko J, Hudlicky T. Chem. Rev. 1989; 89: 165
- 12 Singh C, Srivastav NC, Srivastav N, Puri SK. Tetrahedron Lett. 2005; 46: 2757
- 13 Representative Procedure for the Synthesis of 1,2,4-Trioxepane 5 To an ice-cooled (0–5 °C) solution of 1,3-diol 4 (1.00 g, 5.2 mmol) in CH2Cl2 (50 mL) was added 30% H2O2 (0.64 mL, 20.8 mmol) followed by dropwise addition of concd H2SO4 (0.14 mL, 2.6 mmol) with constant stirring, and the mixture was stirred at 0–5 °C for 3 h. The reaction mixture was diluted with cold H2O (25 mL), and the aqueous layer was extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were washed with sat. aq NaHSO3 solution (25 mL) and H2O (2 × 25 mL). The combined organic layer was dried (Na2SO4), the solution reduced to 50 mL under reduced pressure, and the crude hydroxyhydroperoxide was reacted with cyclohexanone (0.74 mL, 7.2 mmol) in the presence of PTSA (0.2 g, 1 mmol) with stirring for 1.5 h at 0–5 °C. The reaction mixture was concentrated in vacuo at r.t., and the crude product was purified by column chromatography over silica gel using 1.0% EtOAc–hexane as eluent to furnish 0.97g (65%) of 5 as a white solid.
- 14 Compound 5: mp 94–95 °C. FT-IR (KBr): 2933.9, 1659.3, 755.6 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.14–0.37 (m, 4 H), 1.03 (br s, 1 H), 1.33–1.57 (m, 8 H), 1.96 (br d, 2 H), 2.28 (br d, 1 H), 2.57 (br d, 1 H), 3.73–3.85 (m, 2 H), 7.25–7.37 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 1.02 (CH2), 1.36 (CH2), 20.43 (CH), 22.81 (CH2), 23.07 (CH2), 25.5 (2 × CH2), 32.73 (CH2), 41.12 (CH2), 59.17 (CH2), 87.86 (C), 106.19 (C),126.85 (CH), 127.05 (CH), 127.64 (CH), 141.31 (C). APCI-MS: m/z = 287 [M + H+]. Anal. Calcd for C18H24O3: C, 74.97; H, 8.39. Found: C, 74.91; H, 8.43.
- 15 Compound 13: yield 62%, white solid, mp 100–101 °C. FT-IR (KBr): 2937, 1661.2, 764.9 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.46–1.76 (m, 10 H), 4.54 (s, 2 H), 7.26–7.37 (m, 6 H), 7.43–7.46 (m, 4 H). 13C NMR (75MHz, CDCl3): δ = 24.01 (2 × CH2), 25.23 (CH2), 36.12 (2 × CH2), 74.80 (CH2), 85.72 (C), 111.33 (C), 126.22 (4 × CH), 127.16 (2 × CH), 128.16 (4 × CH), 144.88 (2 × C). APCI-MS: m/z = 311 [M + H]+. Anal. Calcd for C20H22O3: C, 77.39; H, 7.14. Found: C, 77.43; H, 7.20