Applications of Baylis-Hillman methodology in the synthesis of chromene derivatives

Nocanda, Xolani Wittleton (2001) Applications of Baylis-Hillman methodology in the synthesis of chromene derivatives. PhD thesis, Rhodes University.

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Abstract

The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives" including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration.pvidence supporting this sequence has been obtained from the isolation ofBaylis-Hi1lman products from reactions involving the use of tertbutyldimethylsilyl- protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the "Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of dimeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis,of sulfurcontaining heterocyclic systems, and a range.of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiochromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiochromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. - Thiochromene and chromene derivatives were converted to the corresponding 3-carboxylic acids and coupled with a specially.prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing chromene and thiochromene tennini in ca. 60 % yield.

Item Type:Thesis (PhD)
Uncontrolled Keywords:Heterocyclic, Compounds, Chemistry
Subjects:Q Science > QD Chemistry
Divisions:Faculty > Faculty of Science > Chemistry
ID Code:2488
Deposited By: Mrs Carol Perold
Deposited On:17 Feb 2012 14:36
Last Modified:17 Feb 2012 14:36
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