Download PDF
Synthesis 2012; 44(20): 3225-3230
DOI: 10.1055/s-0032-1317113
paper
© Georg Thieme Verlag Stuttgart · New York

Phase-Transfer Catalysts in the O-Alkylation of 2-Hydroxynaphthoquinones

Xiao Lu
a   Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA, Fax: +1(706)5425358   Email: tlong@rx.uga.edu
,
Ali Altharawi
a   Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA, Fax: +1(706)5425358   Email: tlong@rx.uga.edu
,
Emily N. Hansen
a   Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA, Fax: +1(706)5425358   Email: tlong@rx.uga.edu
,
Timothy E. Long*
a   Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA, Fax: +1(706)5425358   Email: tlong@rx.uga.edu
b   Center for Drug Discovery, University of Georgia, Athens, GA 30602, USA
› Author Affiliations
Further Information

Publication History

Received: 21 June 2012

Accepted: 24 July 2012

Publication Date:
21 August 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

A mild procedure has been developed for the O-alkyl­ation of 2-hydroxynaphthoquinones by using phase-transfer catalysts. Optimal yields were obtained when 18-crown-6 (10 mol%) and tetrabutylammonium iodide (10 mol% ) were used as cocatalysts in refluxing tetrahydrofuran containing potassium carbonate. Variability in the product yields (0–82%) was attributed to differences in the reactivity of the alkylating agent and to resonance stabilization of the 2-hydroxynaphthoquinone anion. Comparisons of the UV–visible spectra suggest that the degree of electron delocalization has a marked effect on the outcome of the reaction. Quinoid π-electrons were more delocalized in the absence of a stabilizing counteraction, resulting in lower yields. In the presence of tetrabutylammonium iodide, reduced levels of electron delocalization were detected, possibly as a result of ion pairing between the tetrabutylammonium cation and the C-2 oxygen anion. Enhanced reactivity correlates to a lower level of delocalization, and a combination of both catalysts is necessary to facilitate the O-alkylation.

Key words

alkylations - quinones - phase-transfer catalysis - crown compounds