الفهرس 
Chapter I : Chemistry of PhenoxathiinOnly 14 pages are availabe for public view
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Abstract
Our interest is directed towards the synthesis of new heterocyclic
systems with the aim of enhancement of the biological activity of such
compounds. Thus, we choose to synthesize phenoxathiin derivatives
containing pyridazine and acrylic acid moities.
This work is divided into three parts:
Part 1:
It involves the synthesis of 4-oxo-4-phenoxathiin-2-ylbut-2-enoic
acid (2) and studying its reactivity towards different reagents.
Compound (2) reacted with thiourea to give thiadiazole derivative 3
which in turn reacted with hydrazine hydrate and/ or hydroxylamine to
give fused systems (4,5).
Also, acid (2) reacted with aromatic amines to give the
corressponding acids (6a,b) followed by cyclization with acetic
anhydride to give furanones (7a,b). the latter were used for the synthesis
of pyridazinones (8a,b). Acid (2) reacted with phenylhydrazine to give
pyridazinone (9).
On the other hand, reactivity of acid (2) towards active methylene
compounds under Michael reaction conditions was studied. Thus,
reaction of acid (2) with diethyl malonate or ethyl acetoacetate or ethyl
cyanoacetate in the presence of sodium methoxide afforded pyranones
(10a-c). While, the same reaction when carried out in the presence of
ammonium acetate under the same reaction cnditions aforded (12a-c).
Each of compounds (10a-c) and (12a-c) were condensed with hydrazine
hydrate to give pyranopyridazinones (11a-c) and pyridopyridiazines
(13a-c) respectively.
Part (2):
This part focuses on the synthesis of 6-phenoxathiin-2-ylpyridazin-
3-ol (15) and its reactivity towards ethyl chloroacetate, chloroacetic acid.
Also, reaction of phthalyl and tosyl amino acids namely glycine and
alanine with pyridazine (15) was studied. Deprotection of amino acids
was achieved by treatment of (18a,b) with hydrazine hydrate.
Treatment of pyridazinone (15) with PCl5/POCl3 gave chloro
pyridazine (22). The latter was the main precursor for synthesis of fused
heterocyclic compounds like diazole, triazole and tetrazole derivatives.
Thus, chloropyridazine reacted with benzoylhydrazine to give triazolo
pyridazine (23).
Fusion of chloropyridazine (22) with anthranilic acid and
o-phenylene diamine afforded good yield of (24, 25). Treatment of (22)
with NaN3 afforded tetrazolopyridazine (26). Also, compound (22)
reacted with 2-aminoethanol to give compound (27) which cyclized with
thionyl chloride and dry benzene to give pyridazinium chloride (28). Free
base (29) was obtained by treatment of (28) with 15% aq . K2CO3.
On the other hand, chloropyridazine (22) reacted with glycine to
give the corresponding acid (30) which was cyclized by acetic anhydride
to afford imidazo pyridazine (31). Replacement of Cl atom by thio group
was achieved by reaction of chloropyridazine (22) with thioglycolic acid
and thiourea to afford (34) and (36) respectively. The acid 36 was further
heated with thiosemicarbazide and POCl3 to give thiadizole (35).
Also, Cl atom was replaced by alkoxy group or hydrazide group by
reaction of (22) with sodium methoxide or with hydrazine hydrate
respectively.
Part (3):
This part has been directed to cyclization reactions of hydrazide
(32) for the establishment of novel fused system containing phenoxathiin
moiety. Thus, hydrazide (32) was employed in synthesis of triazoles,
through its reaction with aromatic aldehydes, aliphatic acids and urea to
give (39-41), respectively.
Diazoles (42, 43) were obtained through reaction of (32) with
acetylacetone and ethyl acetoacetate respectively. Also, the triazines
(44,45) were obtained by reaction of (32) with diethyl oxalate and ethyl
chloroacetate respectively.
Also, the antimicrobial activities of some synthesized compounds
were investigated. It was found that some of these compounds have
remarkable biological activities against some bacteria and fungi.
The structure of the synthesized compounds was established by:
1- Elemental analysis
2- I.R.
3- 1H NMR
4- Mass spectra