Functionalization and Heteroannulation of Quinazolone Nucleus-Synthesis, Structure Elucidation and Bioactivity Evaluation
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Date
2008
Journal Title
Journal ISSN
Volume Title
Publisher
INSTITUTE OF CHEMICAL SCIENCES
Abstract
The research work documented in this dissertation presents the synthesis and
bioactivity evaluation of some quinazolin-4(3.H)-one based heterocyclic compounds. Part
first is concerned with the synthesis and synthetic methods both reported and newly
designed and developed, while the second part is about the bioassays evaluation of the
synthesized quinazolin-4(3H)-ones. 2-Aryl -4H-3,1-benzoxazin-4-one and methyl-Nacylanthranilates
were prepared as starting materials for further transformations into a
series of various 2,3-disubstituted quinazolin-4(3H)-ones.
Keeping in view the extensive applications of 2-aryl -4H-3,1-benzoxazin-4-one
as precursor in the quinazolin-4(3H)-ones chemistry, a new, cheaper andfacile one-pot
method for the synthesis of 2-aryl -4H-3,1-benzoxazin-4-one was developed making use
of readily available substituted benzoic acids. A faster and high- yielding microwaveassisted,
solvent free method was also developed for the synthesis of methyl-2-
[(trifluoroacetyl) amino] benzoate.
Both the 2-aryl -4H-3,1-benzoxazin-4-one and methyl-N-acylanthranilates
synthesized were then utilized for the synthesis of 3-amino, 2-alkyl/aryl quinazolin-
4(3H)-ones and 2,3-disubstituted quinazolin-4(3H)-ones. Consequently, a series of fifteen
(19-33) 3-amino- 2-alkyl/aryl substituted quinazolin-4(3H)-ones anda series of twenty
seven (46-62) 2,3-disubstituted quinazolin-4(3 H)-ones were synthesized.
The necessity of development of new, cheaper and faster methods was realised
and as a result, a simpler and less tedious three component one-pot method for the
synthesis of ten ( 22-31) 3-amino, 2-aryl quinazolin-4(3H)-ones was developed starting
from the available substituted benzoic acid.
As a consequenceof the effect of substituents on the reactivity of 2-aryl -4H-3,1-
benzoxazin-4-ones, three structurally novel quinazolin-4(3H)-ones (34-36) were
synthesized from substituted 2-phenyl-4H-3,1-benzoxazin-4-ones. It was found that
phenyl group substituted at position 2 failed to give any product. Reasons for the
observed effect onthe reactivity are proposed.
Keepingin view the importance of the nature and position of substituents in drug
discovery, a series of (37-62) 2, 3-disubstituted quinazolin-4(3H)-ones were synthesized
employing three different methods. The effect of substituents on the reactivity and the