الفهرس 
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Abstract
This study deals with the synthesis and reactions of the 6-iodo-2-ethoxy-4H-benzo[d][1,3]oxazin-4-one 3 and its derivatives. The benzoxazinone derivative 3 was synthesized by treatment of 2-amino-5-iodobenzoic acid 1 with ethyl chloroformate in pyridine to give the 2-ethoxycarbonylamino-5-iodobenzoic acid 2 followed by a ring closure in acetic anhydride (Scheme I). The benzoxazinone derivative 3 was used to prepare quinazolinone derivatives via reaction with different nitrogen nucleophiles.
Reaction of benzoxazinone derivative 3 with p-toluidine in refluxing ethanol afforded the corresponding quinazolinone derivative 4, while with o-anisidine in boiling ethanol yielded the urea derivative 5 (Scheme I).
Treatment of benzoxazinone 3 with p-aminoacetophenone and/or p-aminobenzophenone afforded iodophenylcarbamate derivatives 6a,b (Scheme I). Compound 6a was recycled in freshly distilled acetic anhydride to give the desired quinazolin-4(3H)-one 7, which on treating with benzaldehyde in refluxing ethanol gave chalcone 8 (Scheme I).
On the other hand, aminolysis of benzoxazinone 3 with piperidine and/or morpholine gave phenylcarbamate derivative 9 and carboxmide derivative 10, respectively (SchemeI).
When benzoxazinone derivative 3 was reacted with sodium azide in boiling acetic acid it yielded the tetrazol derivative 11 together the imidazole derivative 12 (Scheme I).
The 3-hydroxyquinazolinone derivative 13 was yielded on refluxing of benzoxazinone 3 with hydroxylamine hydrochloride in pyridine for 3 hrs (Scheme I). Moreover, hydrazinolysis of benzoxazinone derivative 3 yielded the 3-aminoquinazolinone derivative 14 (Scheme I).
On the other hand, when benzoxazinone 3 was allowed to react with formamide in boiling ethanol for 2 hours, the amino quinazolinone 15 was isolated (Scheme I).
In the context, 2-hydrazinylquinazolin-4(3H)-one 14 was expected to be highly reactive compound and is used as intermediate for synthesis of many heterocyclic compounds. The hydrazino and amino functions were suitably situated to react with different electrophilic reagents. Thus, the 2-hydrazinyl- quinazolin-4-one 14 reacted with benzaldehyde in boiling ethanol and [1,2,4,5]tetrazino[6,1-b]quinazolin-6-one 16 was produced (Scheme II). Moreover, interaction of 2-hydrazinylquinazolin-4-one 14 with phenylisothiocyanate yielded the [1,2,4,5]tetrazino[6,1-b]quinazolin-6-one derivative 17 (Scheme II).
Furthermore, phthalazine-1,4-dione derivative 18 was obtained by refluxing 2-hydrazinylquinazolin-4-one 14 with phthalic anhydride in glacial acetic acid (Scheme II).
Treatment of 2-hydrazinylquinazolin-4(3H)-one 14 with 1,3-dicarbonyl compounds namely, acetyl acetone and/or ethyl acetoacetate in boiling ethanol yielded pyrazolylquinazolione derivatives 19 and 20, respectively (Scheme II).
Moreover, interaction of 2-hydrazinylquinazolin-4(3H)-one 14 with ethyl chloroacetate yielded the quinazolinone derivative 21 (Scheme II).
The 2-amino-6-iodoquinazolin-4(3H)-one 15 was expected to be reactive compound and used as key starting martial for synthesis of many heterocyclic compounds. Thus, 2-amino- quinazolinone 15 was reacted with hydrazonyl chloride in dioxin and catalytic amount of triethyl amine to give pyrrolo[2,3-b]quinolin-4-one derivative 23 (Scheme I).
Treatment of 2-aminoquinazolin-4(3H)-one 15 with ethyl chloroacetate in presence of potassium carbonate in dry acetone for 24hrs gave quinazolinone derivative 24 (Scheme I). Ample chemical evidence for the structure 24 is forthcoming from preparing an authentic sample via the reaction of 2-amino-5-iodobenzoic acid 1 with formamide to give 6-iodoquinazolin-4(3H)-one 25 which on treatment with ethyl choloacetate in presence of potassium carbonate in dry acetone for 24hrs gave quinazolinone derivative 24 (Scheme I).
The acid hydrazide 26 was obtained by treatment of quinazolinone derivative 24 with hydrazine hydrate in refluxing ethanol (Scheme III). The acid hydrazides have been described as useful potential resources for preparation of heterocyclic rings of different ring sizes with one or several heteroatoms.
Condensation of the acid hydrazide 26 with benzaldehyde in absolute ethanol to give acetohydrazide 27 (Scheme III). When the acid hydrazide 26 was treated with cyclic anhydrides such as succinic anhydride and/or phthalic anhydride yielded quinazolinone derivatives 29 and 30, respectively (Scheme III).
Furthermore, The reaction of acid hydrazide 26 with acetyl acetone and/or ethyl acetoacetate in refluxing ethanol afforded the uncyclized quinazolinone derivatives 31a,b, respectively (Scheme III).
When a mixture of acid hydrazide 26 and phenylisocyanate and/or phenylisothiocyanate in dioxane was heated under reflux, the quinazolinone derivatives 34a, 34b respectively, were produced (Scheme III). Stirring of 34b in cold concentrated sulfuric acid yielded the 1,3,4-thiadiazole derivative 35 (Scheme III).
On the other hand, the acid hydrazide 26 reacted with benzoic acid in phosphorus oxychloride to give the 1,3,4-oxadiazol derivative 36 (Scheme III).
Treatment of acid hydrazide 26 with potassium thiocyanate in hydrochloric acid afforded the thiosemicarbazide derivative 37, which on refluxing in 4% aqueous sodium hydroxide for 3 hrs it yielded the triazole derivative 38 (Scheme III).
Moreover, when acid hydrazide 26 was subjected to react with carbon disulfide in dioxane and aqueous KOH under reflux conditions the respective oxadiazole derivatives 39 was obtained (Scheme III). Hydrazinolysis of oxadiazole derivatives 39 with hydrazine hydrate in refluxing dioxane afforded the triazine derivative 40 (Scheme III).
The antifungal activities of some of the synthesized compounds have been evaluated by the standardized disc–agar diffusion method and the results are depicted in Table 7. Compound 13 has moderate to high activity against all tested types of yeast and fungi, while most of tested compound have moderate to low activities towards one or two types of fungi.