Tetrabutylammonium iodide catalyzed hydroxylation of naphthoquinone derivatives with tert-butyl hydroperoxide as an oxidant
Graphical abstract
The hydroxylation of naphthoquinone derivatives using tetrabutylammonium iodide as a catalyst and tert-butyl hydroperoxide as an oxidant is reported. Based on this new protocol, the synthesis of the drug, parvaquone and lapachol was achieved.
Introduction
The quinone moiety are widely distributed in natural products [1] and exhibit various biological activities [2]. This privileged class of structures have been widely applied in the realm of chemistry, material science, nanotechnology and medicine [3]. On the other hand, owing to their unique visual and electron transfer properties [4], their efficacy has been exploited as dyes and pigments in industry [5]. In synthetic organic chemistry [6], quinones are frequently used as dienophiles for Diels–Alder reactions [7], strong oxidizingagents [8] (chloranil, DDQ, etc.) [9], and ligands [10] through the formation of π-complexes with transition metals [11]. Due to the high importance of these compounds, developing new synthetic methods for the functionalization of quinones have captured human attention for a long time.
The quinones-based hydroxyl fragment are a core structure in a number of biologically active natural products. These molecules have already shown anticancer, antibacterial and antifungal activities (Scheme 1) [12]. Some of them are currently used as drugs. For example, parvaquone has been approved for the treatment of a disease from Theileria parva [13] and malaria [14]. Atovaquone is used for the treatment of Pneumocystis pneumonia, toxoplasmosis, and malaria [14d]. Moreover, hydroxyl compounds are valuable building blocks that can be potential intermediates and precursors for further chemical transformations [15].
Because of their importance and usefulness, the construction of quinones-based hydroxy fragment have become a very important aspect of functionalization of quinones (Scheme 2) [16]. In 1921, Weitz reported the hydroxy group was introduced by a sequence of in situ Weitz-Scheffer-type epoxidation/epoxide cleavage reaction with H2O2/Na2CO3 /H2SO4 [17]. In 2013, Schwalbe showed that brominated naphthoquinones could be hydroxylated with nucleophilic substitution under KOH/MeOH [18]. In 2016, Martins has accomplished the Suzuki coupling reactions between 2-hydroxy-3-iodo-1,4-naphthoquinone and boronic acids to prepare several 2-hydroxy-3-aryl-1,4-naphthoquinones by palladium-catalysed [19]. However, most of the existing methods suffer from the requirement for strong alkaline or acidic conditions, metal- catalyzed, prehalogenation and fairly limited substrate scope. Therefore, the development of a new efficient hydroxylation method that can be applied to quinone derivatives is highly desirable.
Recently, we have developed the TBAI-TBHP catalyzed epoxidation of naphthoquinone derivatives in the presence of silicon dioxide [20]. Continuing our research interest on TBAI-TBHP catalyzed reactions and functionalization of naphthoquinone derivatives. Herein we demonstrate the hydroxylation of naphthoquinone derivatives using tetrabutylammonium iodide as a catalyst and tert-butyl hydroperoxide as an oxidant (Scheme 2).
Section snippets
Results and discussion
Initially, we chose 2-methyl-1,4-naphthoquinone (vitamin K3) as the model substrate to optimize the reaction conditions (Table 1). The reaction was undertaken in the presence of TBAI (20 mol%) and TBHP (3.5 equiv, 70% aqueous solution) in THF at 120 °C under sealed tube for 24 h. To our delight, the desired products 2a was obtained in 64% yield (Table 1, entry 1). Other oxidants, such as hydrogen peroxide (30% H2O2), di-tert-butyl peroxide (DTBP), potassium persulfate (K2S2O8) and Oxone, were
Conclusions
In conclusion, we have developed a novel and efficient TBAI-catalyzed hydroxylation of naphthoquinone derivatives by utilizing TBHP as the oxidant. This methodology allows the direct installation of hydroxyl groups on the quinone ring for the synthesis of the corresponding substituted 1,4- naphthoquinone and 1,4-benzoquinone derivatives. Furthermore, parvaquone and lapachol were synthesised by the methodology.
Acknowledgments
This work is supported by Science and Technology Department of Sichuan Province under grant number 2015JY0171.
References (22)
- et al.
J. Org. Chem.
(1998)et al.J. Am. Chem. Soc.
(2011)et al.J. Org. Chem.
(1998)et al.Organometallics
(2003) Chem. Rev.
(1997)Naturally Occurring Quinones IV
(1997)Chem. Rev.
(2006)Mini-Rev. Med. Chem.
(2005)(b)J. Koyama, Recent Pat. Anti-Infect. Drug Discovery, 2006, 1,... et al.Med. Chem.
(2011)- et al.
J. Am. Chem. Soc.
(2011)et al.J. Am. Chem. Soc.
(2011) - et al.
Biochim. Biophys. Acta.
(2010)et al.J. Phys. Chem. C.
(2013)et al.J. Am. Chem. Soc.
(2003) Handbook of Natural Colorants
(2009)- et al.
Angew. Chem., Int. Ed.
(2006) - et al.
J. Org. Chem.
(1990) - et al.
J. Braz. Chem. Soc.
(2011)
J. Coord. Chem.
Cited by (12)
Copper(I)-Mediated Divergent Synthesis of Pyrroquinone Derivatives and 2-Halo-3-amino-1,4-quinones
2023, Journal of Organic ChemistryCopper-catalyzed one-pot amine-alkylation of quinones with amines and alkanes
2021, Organic and Biomolecular ChemistryA comprehensive review of the disclosed approaches for the synthesis of Parvaquone, an anti-protozoan drug
2023, Journal of Chemical Sciences