Synthesis of New 3-Substituted Quinazolin-4(3H)-one Compounds Via Linking of Some Five-Membered Ring Heterocyclic Moieties With Quinazolin-4(3H)-one Nucleus

Abstract

In this research new compounds containing quinazolin-4(3H)-one nucleus linked to heterocyclic moieties were synthesized using ethyl (4'-oxoquinazolin-3'-yl) acetate (2) as a synthon. This compound was synthesized via 4-quinazolinone's (1) reaction with ethyl chloroacetate in the existence of K2CO3 as a base and acetone as a solvent. The ethyl α-(4'-oxoquinazolin-3'-yl) acetate (2) was converted to the corresponding hydrazide through its reaction with hydrazine hydrate (85 %). Compound (3) was reacted with two of acyl chlorides to synthesize the diacyl hydrazine compounds (4,5). The compound (5) was cyclized to the corresponding 1,3,4-oxadiazole (6) in presence of phosphorous oxychloride. The formyl derivative (7) of the hydrazide (3) was synthesized via its reaction with formic acid and consequently cyclized by phosphorous oxychloride to the corresponding 1,3,4-oxadiazole (8). The hydrazide (3) was also converted to the thiosemicarbazide derivative (9) by its reaction with ammonium thiocyanate under acidic conditions. Whereas other substituted thiosemicarbazide derivatives (10-12) were synthesized by the reaction of hydrazide (3) with organic isothiocyanate compounds. The resultant compounds (11, 12) were cyclized under basic conditions (4% sodium hydroxide solution) to give 1,3,4-triazole-2-thiole derivatives (13,14), whereas the cyclization of compounds (10-12) was performed under the acidic medium (conc. H2SO4) to give 2substituted amino-1,3,4-thiadiazoles (15-17). On the other side, the hydrazide's (3) reaction with isocyanate compounds affords the semicarbazide compounds (18,19). These compounds were cyclized under the basic condition to afford 1,3,4-triazol-2-ol compounds (20,21). The structures of the synthesized compounds were corroborated depending on the physical and spectral data. keywords: quinazolinone; oxadiazole; thiadiazole; triazole; carbohydrazide. تابكرم ريضحت 3 نيلوزانيوك ضوعم -(3H)4طبر ربع ةديدج نوا ريغ ةقلحلا ةيسامخ عيماجملا ضعب نيلوزانيوكلا ةاون عم ةسناجتملا -(3H)4نوا 1 * و يقا رعلا دمحا دمحم 2 نيدلادعس دشرا دنر 1 * قا رعلا ,لصوملا ,لصوملا ةعماج ,مولعلا ةيلك ,ءايميكلا مسق 2 ا رعلا ,لصوملا ,لصوملا ةعماج ,تانبلل ةيبرتلا ةيلك ,ءايميكلا مسق ق Journal of Education and Science (ISSN 1812-125X), Vol: 30, No: 1, 2021 (158-172) Downloaded from https://edusj.mosuljournals.com/ 159 ةصلاخلا ي ت نيلوزانيوكلا ةاون ىلع يوتحت ةديدج تابكرم ريضحت ثحبلا نمض -(3H)4مادختساب ةسناجتم ريغ ةيقلح عيماجمب ةطبترم نوأ α ( -'4 نيلوزانيوكوسكوا -3'ةيلوا ةًدام ليثلأا تلاخ)لي ًً (2) نيلوزانيوكلا لعافت ربع بكرملا اذه رضح . -(3H)4نوأ (1) عم ةًدعاق مويساتوبلا تانوبراك دوجوب ليثلأا تلاخ ورولك و .اًبيذم نوتيسلاا ـلا بكرم لِّ وحُ α ( -'4 نيلوزانيوكوسكوا -3'ليثلأا تلاخ)لي لباقملا ديزا رديهلا ىلا (3) يئاملا نيزا رديهلا عم هلعافت للاخ نم (85%) . ديزا رديهلا مدختسا (3) ةديدج ةعومجم ريضحتل ةيلوا ةًدام نم ةاون ةنمضتملا تابكرملا نيلوزانيوكلا -(3H)4نوأ ديزا رديهلا ل ِّ خداُ .ةسناجتم ريغ ةيقلح عيماجمب ةطبترملا (3) يبكرم عم لًاعافت نيزا رديه ليسأ يئانثلا يبكرم ريضحتل ليسلأا ديرولك (4,5) بكرملا ةقلوح مت مث نمو ، (5) بكرم ىلا روفسفلا ديرولك يسكوأ دوجوب ـلا -4,3,1 داسكوا لوزايا .(6) ديزا رديهلا مدختسا امك (3) ديزا رديه ليمروفلا قتشم ريضحتل (7) ديرولك يسكوأ دوجوب قلوحتي يذلا ـلا ىلا روفسفلا -4,3,1 لوزاياداسكوأ (8) ديزا ريهلا ل وح كلذك . (3) ديزابراكيمسوياثلا بكرم ىلا (9) موينوملأا تانايسوياث عم هلعافتب رضح امنيب .ةيضماح فورظ تحت ديزابراكيمسوياثلا تاقتشم ت (10-12) ديزا رديهلا لعافتب (3) ةقلوح مت .ةيوضعلا تانايسوياثلا عم نيبكرملا (11,12) ( ةيدعاق فورظ تحت 4 نم % ـلا يبكرم نايطعيل )مويدوصلا ديسكورديه لولحم -4,3,1 لوزايا رت -2لوياث (13,14) تابكرملا قلوحتت امنيب (10-12) تابكرم يطعتل )زكرملا كيتيربكلا ضماح( ةيضماحلا فورظلا تحت -2 ضوعم ونيما -4,3,1ث لوزايادايا (15-17) ديزا رديهلا لعافتي ,ىرخا ةيحان نم . (3) ديزابراك يمسلا تابكرم يطعيل ةيوضعلا تانايسوزيلآا عم (18-19) ـلا تابكرم ىلا ةيدعاقلا فورظلا تحت قلوحتت يتلا -4,3,1 لوزايا رت -2لوا (20,21) اًدامتعا ةرضحملا تابكرملا بيكا رت تصخش . .ةيفيطلاو ةيئايزيفلا تانايبلا ىلع ةيحاتفملا تاملكلا : نونيلوزانيوكلا ؛لوزاياداسكوا ؛ ؛لوزاياداياث لوزايا رت ؛ ديزا رديهوبراك . INTRODUCTION There is a huge number of biologically active compounds that contains a heterocyclic core possessing various heteroatoms such as nitrogen, oxygen and sulfur. The biological importance of these compounds has drawn the attention of the chemists to synthesize interesting new derivatives containing heterocyclic moieties in order to improve their biological activity. Among these heterocyclic compounds is 4-quinazolinones which are of great heed owing to their discrete and wide biological activity and their importance in the pharmacological and medicinal fields, in addition to their diverse chemical applications. It has been found that the 4-quinazolinones own a broad spectrum of activity exemplified as anticancer [1-3], antifungal [4,5], antitumor [6-8], antipsychotic [9], antimicrobial [10], antioxidant [11,12], anti-HIV [14,15], anti-inflammatory and analgesic [16], antihypertensive [17] and anticonvulsant [18]. Furthermore, they were considered a fundamental part of many natural alkaloids [19,20]. On the other hand, it was found that many heterocyclic nuclei other than quinazoline-4(3H)-ones such as 1,3,4-oxadizole, 1,3,4-thiadiazole, and 1,3,4-triazole showed biological importance [21-23]. Because of the increase of the biological importance of the quinazoline-4(3H)-one derivatives, new quinazoline-4(3H)-one compounds were synthesized via linking of quinazoline-4(3H)-one nucleus with heterocyclic moieties at position 3 through a series of intermediates using ethyl α-(4'-oxoquinazolin-3-yl)acetate as a synthon.