ON THE SYNTHESIS OF NAPHTHOQUINONES AND ANTHRAQUINONES

Abstract

The serendipitous isolation of 1-chloronaphthalene via a microwave promoted cyclisation of 2-allylphenyl 2,2,2-trichloroacetate during the investigation of catalytic activity of copper (I) complexes has resulted to a synthetically valuable scheme for the preparation of haloarenes. This Bull Hutching Quayle-Atom Transfer Radical Cyclisation Reaction (BHQ-ATRC) has herewith enabled the benzannulation of varied 2-allyl-phenyl-2,2,2-tri(bromo/chloro)acetates using a copper(I)chloride complex: chloro[1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene]copper(I), in a conventional thermal cyclisation reaction. The functionalised haloaromatics which were realised from cyclisation of the pivotal precyclised intermediates serve as precursors to the synthesis of plumbagin and juglone and analogues naphthoquinone antibiotics in three synthetic steps. 2-(Cyclohex-1-en-ylmethylphenyl 2’,2’,2’-tribromo/chloro)acetates were also cyclised and the resulting hydroquinone secured a tricyclic core motif found in anthracycline (e.g., -cytromicinone), a tetracycline anthraquinone, with an array of bioactivity including, anticancer, antibiotics and antiviral potentials. An application of a palladium-catalysed cross coupling reaction on the resulting haloarenes after the initial ATRC reaction generated intermediate boronic esters as disclosed. Extensive investigation of the optimum reaction conditions with a view of finding a suitable sequence for the formation of intermediate boronic esters which are easily converted to the intended hydroxyanthraquinones is discussed. Finally, a synthesis of new anthraquinones utilising a Suzuki cross coupling reaction is also reported. It was observed that the one-step cross coupling reaction proceeded efficiently enabling the synthesis of new anthraquinone candidates which themselves are shown to possess an extended - stacking coordination. These compounds could be beneficial in molecular recognition, electrical/optical science and possibly, in building up of molecular tweezers when they are evaluated.

Date of Award	31 Dec 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Peter Quayle (Supervisor) & Roger Whitehead (Supervisor)