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Volumn 6, Issue 18, 2004, Pages 3035-3038

Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIOXANE DERIVATIVE; ALCOHOL; ALKENE; ALLYL COMPOUND; ANTIMALARIAL AGENT; ARTEMETHER; ARTEMISIN; CHLOROQUINE; KETONE DERIVATIVE; PEROXIDE; THIOL;

EID: 4544268106     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0492142     Document Type: Article
Times cited : (67)

References (19)
  • 11
    • 4544253018 scopus 로고    scopus 로고
    • note
    • Synthesis of 8-(4-Chloro-phenylsulfenylmethyl)-8-methyl-6,7,10-trioxa- spiro[4.5]decane (4d). A two-necked, 250 mL, round-bottomed flask was charged with a solution of 2-methyl-2-propen-1-ol (200 mg, 0.23 mL, 2.77 mmol) and AIBN (31 mg, 1.89 mmol) in acetonitrile (46 mL). The reaction vessel was flushed with oxygen for several minutes at 0 °C then stoppered and kept under a positive pressure of pure oxygen. The reaction mixture was vigorously stirred and UV irradiated (at 0 °C) using an externally mounted 100W BLAK-RAY UV lamp at a distance of 5-7 cm, with simultaneous addition of 4-chlorothiophenol (500 mg, 3.46 mol, 1.25 equiv) in acetonitrile (13 mL) over a period of 30 min. After completion of the addition, the reaction was left to continue stirring at 0 °C for 4-6 h or until consumption of starting materials (monitored by TLC). The reaction vessel was then cooled to -10 °C and flushed with nitrogen, and a solution of cyclopentanone (780 mg, 0.82 mL, 6.94 mmol) in dichloromethane (13 mL) was added, followed by catalytic amounts (ca. 15 mg) of tosic acid. The mixture was left stirring at -10 °C, and allowed to warm slowly to room-temperature overnight. Removal of the solvent in vacuo and purification by column chromatography yielded the endoperoxide (4d) as a white solid (391 mg, 46%). Full spectroscopic and compound characterization is contained in the Supporting Information. Caution: Since vapors of organic solvents may form explosive mixtures with oxygen in closed systems, all such reactions should be conducted behind safety shields. For safety precautions in working with peroxides, see reference 6b.


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