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Synlett 2013; 24(2): 173-176
DOI: 10.1055/s-0032-1317958
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 1,2,4-Trioxepanes and 1,2,4-Trioxanes via H2O2-Mediated Reaction of Tertiary Carbinols

Makthala Ravi
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
,
Devireddy Anand
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
,
Ranjani Maurya
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
,
Parul Chauhan
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
,
Niraj K. Naikade
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
,
Sanjeev K. Shukla
b   Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow 226001, India
,
Prem P. Yadav*
a   Divisions of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India, Fax: +91(522)2623405   Fax: +91(522)2623938   eMail: pp_yadav@cdri.res.in   eMail: ppy_cdri@yahoo.co.in
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Publikationsverlauf

Received: 29. Oktober 2012

Accepted after revision: 08. Dezember 2012

Publikationsdatum:
21. Dezember 2012 (online)

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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.

Key words

1,2,4-trioxanes - 1,2,4-trioxepanes - hydrogen peroxide - carbinols - antimalarial

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 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