334 © 2024 The Author(s). Published by College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License Ibn Al-Haitham Journal for Pure and Applied Sciences Journal homepage: jih.uobaghdad.edu.iq PISSN: 1609-4042, EISSN: 2521-3407 IHJPAS. 2024, 37(4) Synthesis and Antioxidant Characteristics of Novel Heterocyclic Derivatives from 2-Thiol-5-Phenyl-1,3,4-Oxadiazole Compounds Sumaya J. Abed1,2,* and Mohammed R. Ahmad2 1College of Dentistry, Al-Iraqia University, Baghdad, Iraq. 2Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq. *Corresponding Author. Received: 15 March 2023 Accepted: 21 June 2023 Published: 20 October 2024 doi.org/10.30526/37.4.3340 Abstract The 1,3,4-Oxadiazole-bearing compounds are among the most attractive classes for researchers because of their biological processes. The study used a current show of quinazoline- 4-one and oxazine-4-one derivatives (8-13) were synthesized. Firstly; the reaction of benzyl salicylate was reacted with hydrazine hydrate (99%) to give 2-hydroxybenzohydrazide (1) then the produced was reacted with carbon disulfide dissolved in absolute ethanol and potassium hydroxide to make 2-(5-mercapto-1,3,4-oxadiazol-2-yl)phenol (2). After that, compound (2) was treated with ethyl chloroacetate to give ethyl 2-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2- yl)thio)acetate (3). Hydrazine hydrate and compound (3) interacted to create 2-((5-(2- hydroxyphenyl)-1,3,4-oxadiazol-2-yl)thio) acetohydrazide (4) next combined with a different aromatic aldehyde substitution in absolute ethanol to produce derivatives of Schiff's bases (5-7). Lastly, preparations were made for the target compounds (8–13) by interacting chemicals (5-7) with anthranilic and salicylic acid. Using [FT-IR, 1H-NMR, and 13C-NMR] and measuring their physical properties, the newly synthesized compounds were recognized. We also examined the potential anti-oxidant properties of produced compounds. According to the obtained data, the synthesized compounds showed different inhibition activities against free radicals. Moreover, compounds (10 and 13) were found to be most effective against DPPH radicals, and higher than that of BHT. It has been concluded that the synthesized compounds have therapeutic potential for diseases mediated by oxidative stress. Keywords: Antioxidant activities, heterocyclic, oxadiazole, Schiff bases. 1. Introduction Due to their significant use as primary building blocks for active medicinal components, heterocyclic compounds are of tremendous interest to scientists [1]. Among them, 1,3,4- oxadiazole/thiadiazole derivatives were found to possess several biological activities, such as analgesic, anti-inflammatory [1,2], antibacterial [3], antioxidant [3,4], antifungicidal [5] and more biological characteristics [6]. Recent data has focused on the antiviral, antitubercular, anticancer, anti-inflammatory, antiparasitic, antioxidant, enzymatic inhibitory, antibacterial, and https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://orcid.org/0009-0007-0287-0682 mailto:Somaia.Jamal1105d@sc.uobaghdad.edu.iq https://orcid.org/0000-0002-2643-0813 mailto:dr.mohammed.riffat1957@gmail.com IHJPAS. 2024, 37(4) 335 antifungal potentials of compounds containing a 1,3,4-oxadiazole moiety [7-15]. To treat AIDS- related disorders, ralettegravir, an HIV integrase inhibitor, is administered along with other antiretroviral medications [16]. Fenadiazole treats anxiety and insomnia by having sedative and hypnotic effects [17]. Zibotentan is suggested for the treatment of prostate cancer in particular as well as colorectal, breast, ovarian, lung, and other malignancies [18]. Many substituted quinazoline and oxazine are known to possess diverse biological activities such as antimalarials, hypnotics, anticonvulsants, anti-protozoal agents, bacteriostatic and anti- fungal [19]. Additionally, comparable to a stronger antioxidant action than conventional substances can be produced by the inclusion of certain functional groups. A straightforward and effective approach to synthesize some new quinazoline-4-one and oxazin-4-one derivatives containing 1,3,4-oxadiazole ring is proposed in the current study in light of the significance of the described derivatives as bioactive compounds, as shown in Figure 1. Figure 1. Target molecule using in this work. In vitro models were used in this study to develop a method for producing and testing the antioxidant potency of these novel quinazoline-4-one and oxazin-4-one derivatives containing 1,3,4-oxadiazole ring. 2. Materials and Methods 2.1 Instrumentation All of the compounds used in this investigation were provided by the chemical companies Merck, BDH, Fluka, and Sigma Aldrich. The Department of Chemistry, College of Science, University of Baghdad, used an FTIR 8400s Fourier transitions infrared spectrometer (Shimadzu, Japan) to record the FTIR spectra using a KBr disc in the 4000-600 cm-1 spectral region. Gallenkamp electrothermal equipment was used to measure the melting point. TLC is a technique used to examine the pureness and homogeneity of synthetic substances. Bruker Ultra- shield (400 MHz) near magnetic resonance was used to record the 1H-NMR and 13C-NMR spectra. Also, the experiment carried out at Tehran University in Iran using DMSO-d6 as a solvent. 2.2 Synthesis of compound 2.2.1 Synthesis of 2-hydroxybenzohydrazide (1) Excess of hydrazine hydrate (99% 2.5 mL, 0.08 mole) was added to methyl salicylate (10 mL, 0.04 mole) in 50 mL circular bottom flask, and swirled for 2 hours after that refluxed for 20 hours. Then it pours into the petri dish, and the product has been recrystallized using ethanol [20, 21]. 2.2.2 Synthesis of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)phenol (2) IHJPAS. 2024, 37(4) 336 Absolute ethanol (50 mL) and potassium hydroxide (2.2 g, 0.03 mole) were collected in a flask with a dry circular bottom. The 2-hydroxybenzohydrazide (6 g, 0.03 mole) was placed and thoroughly mixed into it to make a clear mixture [22, 23]. Excess of carbon disulfide (11 mL, 0.15 mole) was poured to the above-mentioned clear solution and heated gently for (20 h), after checking the finish all H2S stopped. The excess solvent was dried after which it was chilled to room temperature. The substance was added to water, which was then treated with 5% HCl until the precipitates separated. To obtain the required product, the separated product was rinsed with cool water before being dried. 2.2.3 Synthesis of ethyl 2-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)thio)acetate (3) Substance (2) (2 g, 0.01 mole) was dissolved in DMF (20 mL) and triethyl amine (1 mL, 0.01 mole). Ethyl chloroacetate (2.4 mL, 0.02 mole) was added dropwise, the reaction mixture was refluxed for 18 h. The excess solvent was concentrated by heating, the obtained product was recrystallized from ethanol [24,25]. 2.2.4 Synthesis of 2-(((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide (4) Chemical (3) (1g, 0.003 mole) should be dissolved in absolute ethanol (25 mL) and excess (99%) hydrazine hydrate (0.5 mL, 0.03 mole) was added to the mixture gradually, the reaction was stirred for 4h and refluxed for 24 h and the result was washed several times by ethanol after the solution was put into a petri-dish [26–29]. 2.2.5 Synthesis of novel Schiff bases (5-7) from compound (4) A mixture of compound (4) (1 g, 0.003 mole) in DMSO (10 mL and various aromatic aldehydes (0.003 mole) in absolute ethanol (10 mL). Then, a few drops of glacial acetic acid were allowed to react for eight to twelve hours [30,31].The solvent was evaporated and water was used to wash the resulting precipitate. In Table 1, the physical characteristics of chemicals (5-7) were presented. 2.2.6 Synthesis of quinazoline-4-one derivatives )8-10) To the a 0.0007 mole solutions of Schiff bases (5-7) in THF (20 mL), anthranilic acid (0.1 g, 0,0007 mole) was then added slowly. The mixture was refluxed for (18 hrs.), after completion of the reaction, the solution was cooled to room temperature. After that, NaHCO3 (5%) was added. The precipitate was filtered and recrystallization from ethanol. 2.2.7 Synthesis of oxazin-4-one derivatives )11-13) Following that, a mixture of Schiff bases (5-7) (0.0003 mole) in THF (20 mL) was slowly supplemented with salicylic acid (0.0003 mole). When the reaction had taken place for 18 hours, the combination was refluxed, and the solution was then chilled to room temperature. Then, NaHCO3 (5%) was added. The precipitate was filtered and recrystallization from ethanol. 2.2.8 Quantify the antioxidant capacity using the DPPH technique The 1,1-diphenyl-2-picrylhydrazyl (DPPH) is an effective instrument for assessing a compound's antioxidant capacity and can be used to assess the antioxidant action of synthetic chemicals. One electron is transferred in the process mechanism, and hydrogen atoms are also moved. This experiment was carried out using a modified version of the Meda et al., technique [32]. In a nutshell, 0.3 mL of the samples were added in DMSO in addition to various concentrations ranging from 25 to 100 ppm, and 2.7 mL of a 50 ppm methanolic solution containing DPPH was added. All specimens were maintained at room temperature for an hour in the dark. The reduction of DPPH activity was assessed using a U-2900 Hitsechi UV-visible spectrophotometer, which assessed the absorbance at 517 nm. The percentage of inhabitation of DPPH activity was estimated using the next equation: (% Inhibition) (A0 - AE)/A0 ×100 IHJPAS. 2024, 37(4) 337 A0 represents the absorbance of the DPPH solution used as the control (without plant extract), and AE represents the absorbance of the DPPH solution with plant extract. Analogous methods were employed to assess ascorbic acid's effectiveness as a DPPH scavenger. 3. Results and Discussion According to the Scheme 1, new heterocyclic ring derivatives were included in this work. Scheme 1. New heterocyclic ring derivatives. 3.1 Synthesis of 2-hydroxybenzohydrazide (1) The compound (1) was created by stirring methyl salicylate with 99% hydrazine hydrate in ethanol. FT-IR spectra data for compound (1) shows the existence of the identifiable absorption band at (3319-3269) cm-1 belongs to v (NH2) group asym. and sym. respectively and identifiable absorption band at v(1643) cm-1 belongs to v(C=O) of amide group. 3.2 Synthesis of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)phenol (2) The 2-hydroxybenzohydrazide (1) reacted with carbon disulfide in alkali medium followed by acidification with hydrochloric acid. The FT-IR spectra data [33] for compound (2) showed the appearance of the characteristic absorption band at (1612) cm-1 belonging to v (C=N) and characteristic absorption band at (2594) cm-1 belonging to v (S-H) and disappearance of the absorption bands (3319-3269) cm-1 both of these are asym. and sym. Members of the v (NH2) group, respective. The 1H-NMR spectra of chemical (2) revealed signals at = (6.96-7.74) ppm resulting from (CH aromatic ring), a singlet single at = (14.56) ppm according to (-SH) proton, and a singlet single at (10.40) ppm according to (-OH) proton. In Figure 2, 13C-NMR spectrum of chemical (2) revealed signals at δ= (156.77) ppm, δ=(160.31) ppm, δ= (109.85) ppm, and signals δ= (117.51-133.93) ppm belong to (C-OH), (-N=C) oxadiazole ring carbon, (CH-C=N) and aromatic ring carbon respectively, as shown in Figure 3. IHJPAS. 2024, 37(4) 338 Figure 2. The 1H-NMR of compound (2). Figure 3. The 13C-NMR of compound (2). 3.3 Synthesis of ethyl 2-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)thio)acetate (3) In an alkaline medium, compound (2) and ethyl chloroacetate reacted to form compound (3). The FT-IR spectrum for chemical (3) revealed the formation of the particular absorption band at (1743) cm-1 that is assigned to v (C=O) of ester and the elimination of the absorption band (2594) cm-1 that is assigned to v (S-H). 3.4 Synthesis of 2-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide (4) Hydrazine hydrate was used to transform compound (3) into compound (4) in absolute ethanol. The typical absorbance bands for chemical (4) were seen in the FT-IR spectra, and they were found to belong to the v (NH2) asym. and sym., accordingly an identifiable absorption band at (1674) cm-1 belongs to v(C=O) of amide carbonyl group, and the disappearance of the absorption band (1743) cm-1 this, as a result of the ester carbonyl group, corresponds to v (C=O). Compound (4)'s 1H-NMR spectra [34] revealed signals between δ= (7.25-7.35) ppm according to (CH aromatic ring), a single at δ= (9.36) ppm according to (-NH) proton, a singlet single at δ= (9.37) ppm according to (-OH) proton, a single at δ= (4.14) ppm according to (-NH2) proton, as in Figure 4. Chemical (4)'s 13C-NMR spectra displayed a signal at δ= (154.16) ppm, δ=(169.53) ppm, δ= (170.22) ppm and signals δ = (128.68-136.75) ppm belong to (C-OH), (-N=C) oxadiazole ring carbon, (CO-NH) and aromatic ring carbon respectively, as shown in Figure 5. IHJPAS. 2024, 37(4) 339 Figure 4. The 1H-NMR of compound (4). Figure 5. The 13C-NMR of compound (4) 3.5 Synthesis of new Schiff bases (5-7) from chemical (4) The titled compounds were synthesized from the reaction between compound (4) in DMSO and convenient aromatic aldehydes in absolute ethanol in the presence of glacial acetic acid. Table 2 contains information on the FT-IR spectra of chemicals (5-7). The 1H-NMR spectrum of compound (5) displayed a singlet signal at δ = (4.03) ppm for (S-CH2) protons, δ = (11.04) ppm for (-NH) protons, singlet signal at δ = (8.64) ppm because of to (N=CH) imine proton, singlet signal at δ = (9.77) ppm because of to (O-H) protons and multi signals at δ= (7.18-8.39) ppm because of aromatic rings protons, as shown in Figure 6. Chemical (5)'s 13C-NMR spectra displayed a signal at = (40.87) ppm, δ=(146.01) ppm, δ=(168.82) ppm, δ= (174.95) ppm and signals δ = (115.16-138.91) ppm belong to (-SCH2), (NH-N=C), (-N=C) oxadiazole ring carbon, (CH2-C=O) and aromatic ring carbon respectively, as shown in Figure 7. The chemical (7)'s 1H-NMR spectrum displayed singlet signals at δ= (4.70) ppm resulting from (S-CH2) protons, δ= (11.94) ppm because of (-NH) protons, δ= (8.46) ppm because of (N=CH) imine proton, δ= (10.59) ppm because of to (O-H) protons, and δ= (7-7.96) ppm because of aromatic rings protons, as shown in Figure 8. The 13C-NMR spectrum of compound (7) showed a signals at δ= (40.84)ppm, δ=(144.55) ppm, δ=(167.02) ppm, δ= (173.86) ppm and signals δ = (117.76-138.21) ppm belong to (-SCH2), IHJPAS. 2024, 37(4) 340 (NH-N=C), (-N=C) oxadiazole ring carbon, (CH2-C=O) and aromatic ring carbon respectively, as shown in Figure 9. Figure 6. The 1H-NMR of compound (5). Figure 7. The 13C-NMR of compound (5). Figure 8. The 1H-NMR of compound (7). IHJPAS. 2024, 37(4) 341 Figure 9. The 13C-NMR of compound (7). 3.5 Synthesis of quinazoline-4-one derivatives )8-10) Equal amounts of the imine derivatives and anthranilic acid were refluxed in THF to synthesize the quinazoline-4-one derivatives (8–10). Physical characteristics of compounds (8- 10) are listed in Table 1. The FT-IR spectral data of compounds (8-10) showed the appearance of (N-H) for quinazoline ring stretching band at (3444-3467) cm-1, and the disappearance of (C=N) absorption bands at (1639-1685) cm-1. Table 3 contains a complete list of the FT-IR spectral data information. Chemical (10)'s 1H-NMR spectra revealed singlet signals at δ= 3.70 ppm due to (-S-CH2), δ=(6.09) ppm related to (-N-CH-) quinazoline ring proton, and δ=(6.68) ppm related to (-NH-C) quinazoline ring proton, as seen in Figure 10, there are multiple signals at δ= (7.53-8.27) ppm because of protons in aromatic rings, a signal at δ= (10.00) ppm because of a proton in the (O=C-NH) amide, and a singlet signal at δ= (9.66) ppm because of (O-H) protons. The chemical (10)'s 13C-NMR spectra displayed a signal at δ=(140.26) ppm, δ=(167.02) ppm, δ= (173.99) ppm, δ= (151.61) ppm and signals δ = (110.29-138.21) ppm belong to (NH-N-CH), (-N=C) oxadiazole ring carbon, (CH2-C=O), (C=O) amide quinazolin ring and aromatic ring carbon respectively, as shown in Figure 11. Figure 10. The 1H-NMR of compound (10). IHJPAS. 2024, 37(4) 342 Figure 11. The 13C-NMR of compound (10). 3.6 Synthesis of oxazin-4-one derivatives )11-13) Equal parts of the imine derivatives and salicylic acid were refluxed in THF to create the oxazin-4-one derivatives (11-13). Table (1) lists the physical features of compounds (11–13). Chemicals (11–13)'s FT–IR spectral data [35] revealed the formation of a carbonyl group stretching band at (1650–1683) cm-1 and disappearance of (C=N) absorption bands at (1639- 1685) cm-1. Table 3 contains a complete list of the FT-IR spectral data information. Compound (11)'s 1H-NMR spectrum revealed singlet signals at δ= (3.84) ppm resulting from (S-CH2), δ= (6.06) ppm because of the (-N-CH-) quinazoline ring proton, and δ= (6.08) ppm because of the (-NH-C-) quinazoline ring proton. There are many signals at δ= (7.16-7.79) ppm caused by aromatic rings protons, a signal at δ= (10.18) ppm caused by a (O=C-NH) amide proton, and a singlet signal at δ= (9.94) ppm caused by (O-H) protons, as illustrated in Figure 12. The chemical (11)'s 13C-NMR spectra displayed a signal at δ= (40.85) ppm, δ= (166.95) ppm, δ= (172.95) ppm, δ= (156.16) ppm and signals δ= (117.29-138.26) ppm belong to (CH2- C=O), (-N=C) oxadiazole ring carbon, (CH2-C=O), (C=O) amide quinazolin ring and aromatic ring carbon respectively, as shown in Figure 13. Figure 12. The 1H-NMR of compound (11). IHJPAS. 2024, 37(4) 343 Figure 13. The 13C-NMR of compound (11). Table 1. Physical properties of compounds (1-13). NO. Formula M.Wt g/mol M.P. ( ͦC ) Color Yield % 1 C7H8N2O2 152.15 Oily Pale brown 86 2 C8H6N2O2S 194.21 204-206 Pale yellow 77 3 C12H12N2O4S 280.30 Oily Blackish-green 69 4 C10H10N4O3S 266.28 Oily Brown 88 5 C17H13N5O5S 399.38 280-282 Orange 82 6 C19H19N5O3S 397.45 232-234 Mustard yellow 83 7 C17H13ClN4O3S 388.83 162-164 dark brown 80 8 C24H18N6O6S 518.50 298-300 Yellowish- orange 68 9 C26H24N6O4S 516.58 268-270 Brown 77 10 C24H18ClN5O4S 507.95 140-142 Dark beige 75 11 C24H17N5O7S 519.49 269-271 Orange 72 12 C26H23N5O5S 517.56 186-188 Reddish- orange 67 13 C24H17ClN4O5S 508.93 147-149 Light beige 70 Table 2. The FT-IR spectral data (cm-1) of compounds (5-7). No Compound structure FT-IR spectral data (cm-1) (O-H) (N-H) (C-H) Aliph. (C=O) (C=N) (C=C) Other Bands 5 2-((5-(2-hydroxyphenyl)-1,3,4 oxadiazol-2-yl)thio)-N'-(4- nitrobenzylidene)acetohydrazide 3429 3188 2945 2840 1683 1639 1521 NO2 asym. (1521) sym. (1344) 6 N'-(4-(dimethylamino)benzylidene)- 2-((5-(2-hydroxyphenyl)-1,3,4- oxadiazol -2-yl)thio)acetohydrazide 3433 3195 2966 2864 1685 1639 1554 7 N'-(4-chlorobenzylidene)-2-((5-(2- hydroxyphenyl)-1,3,4-oxadiazol-2- yl)thio)acetohydrazide 3433 3168 2995 2840 1714 1685 1591 C-Cl 819 IHJPAS. 2024, 37(4) 344 Table 3. The FT-IR spectral data (cm-1) of compounds (8-13). No Compound structure FT-IR spectral data (cm-1) (O-H) (N-H) (C-H) Aliph. (C=O) Ring (C=O) Amide (C=C) Arom. Other Bands 8 2-((5-(2-hydroxyphenyl)- 1,3,4-oxadiazol-2-yl)thio)-N- (2-(4-nitrophenyl)-4-oxo-1,4- dihydroquinazolin-3(2H)- yl)acetamide 3444 3276 2977 2937 1701 1605 1575 NO2 asym. (1521) sym. (1344) 9 N-(2-(4-(dimethylamino) phenyl)-4-oxo-1,4- dihydroquinazolin-3(2H)-yl)- 2-((5-(2-hydroxyphenyl)- 1,3,4-oxadiazol-2- yl)thio)acetamide 3467 3178 2979 2802 1625 1600 1523 10 N-(2-(4-chlorophenyl)-4-oxo- 1,4-dihydroquinazolin-3(2H)- yl)-2-((5-(2-hydroxyphenyl)- 1,3,4-oxadiazol-2- yl)thio)acetamide 3465 3182 2935 2852 1683 1641 1556 C-Cl 759 11 2-((5-(2-hydroxyphenyl)- 1,3,4-oxadiazol-2-yl)thio)-N- (2-(4-nitrophenyl)-4-oxo-2H- benzo[e][1,3]oxazin-3(4H)- yl)acetamide 3460 3191 2970 2850 1683 1641 1560 NO2 asym. (1521) sym. (1344) 12 N-(2-(4 (dimethylamino) phenyl)-4-oxo-2H- benzo[e][1,3]oxazin-3(4H)-yl)- 2-((5-(2-hydroxyphenyl)- 1,3,4-oxadiazol-2- yl)thio)acetamide 3463 3176 2916 2806 1650 1602 1552 13 N-(2-(4-chlorophenyl)-4-oxo- 2H-benzo[e][1,3]oxazin- 3(4H)-yl)-2-((5-(2- hydroxyphenyl)-1,3,4- oxadiazol-2-yl)thio)acetamide 3463 3193 2966 2852 1683 1639 1554 (C-Cl) 759 IHJPAS. 2024, 37(4) 345 3.8 The DPPH scavenging activity The radical scavenging activity of the synthesized compounds was measured by using a DPPH assay. According to Pyrzynska and Pkal, the antioxidant chemicals in this assay caused the DPPH radical to change color in this assay from purple to yellow. The reduced DPPH-H is created when the DPPH radical's odd electron pairs with a hydrogen radical from an antioxidant that scavenges free radicals to produce the reduction absorbance [36]. Additionally, according to previous data [37], sulfur compounds have strong antioxidant properties. In this study, compound (10) exhibited the highest antioxidant activities among other quinazoline-4-one compounds. Likewise, compound (13) showed higher antioxidant capacity than other oxazin-4- one derivatives. These results are consistent with those of other studies and suggest that the compounds (10 and 13) have chlorine as the electron-withdrawing substituent on the phenyl ring at position 4, thus exhibiting the highest inhibition [38]. Furthermore, the compounds (9 >12) presented a moderate scavenging activity and their IC50 at 100 ppm were 52.2% and 41.5%, respectively. However, compounds (11 and 8) were found to show lower activities when compared with other synthesized compounds, because of the presence of NO2 group on their aromatic ring [39]. In this instance, as shown in Table 4, certain functional groups and heterocyclic rings unmistakably play a significant role in both enhancing and lowering the antioxidant activity. This study used butylhydroxytoluene (BHT) and ascorbic acid as positive controls. Thus 9, 10, 12, and 13 at a concentration of 100 ppm presented a greater antioxidant effect than BHT (50 and 100 ppm). In addition, compounds 8 and 11 at a concentration of 100 ppm exhibited antioxidant activities comparable to that of BHT at 100 ppm. On the other hand, at every studied concentration, all synthetic substances displayed weaker antioxidant activity than those observed for ascorbic acid. Table 4. The DPPH radical scavenging assay. Synthesized Compounds & Positive Controls % Scavenging Activity at Different Concentrations IC50 25 ppm 50 ppm 100 ppm 8 7.1 ± 0.3f 12.7 ± 0.9fe 28.1 ± 0.3dc 178.1 9 12.7 ± 0.2fe 27.2 ± 0.7dc 52.2 ± 0.7b 95.2 10 25.1 ± 0.7d 39.5 ± 0.5c 64.8 ± 0.8ab 71.3 11 9.8 ± 0.6f 16.7 ± 0.2e 31.6 ± 0.2c 163.3 12 7.9 ± 0.4f 18.5 ± 0.4e 41.5 ± 0.5c 119.1 13 20.5 ± 0.5de 35.7 ± 0.1c 60.6 ± 0.2b 79.2 Ascorbic acid 65.6 ± 0.1ab 70.2 ± 0.2a 79.6 ± 0.2a -53.1 BHT 9.1 ± 0.1f 15.1 ± 0.0e 29.6 ± 0.3dc 174.6 *a, b, c means with different superscripts on the same column differ significantly (p < 0.05),*Data are expressed as mean ± standard deviation (n = 3),*BHT, Butylated hydroxyl toluene. 4. Conclusion Quinazoline-4-one and oxazine-4-one derivatives were synthesized, and their antioxidant characteristics were described in the current work. The process made it possible to synthesize a variety of chemicals with various functional groups in good quantities. Utilizing a DPPH radical scavenging experiment, the antioxidant capabilities were evaluated of the substances in this case. The current results showed that the compounds oxadiazole, Cl (10 and 13), and N(CH3)2 (9 and 12) showed antioxidant capabilities, showing that the group insertion may enable electron donation by the DPPH radical. Since BHT, a well-known antioxidant molecule, had a smaller impact, it may be concluded that both oxadiazole chemicals (10 and 13) with the Cl IHJPAS. 2024, 37(4) 346 group placed in the para-position to the aromatic ring have excellent antioxidant properties. Oxadiazole chemicals like 8 and 11 additionally displayed an overall antioxidant activity comparable to that obtained for the positive control (BHT), demonstrating the antioxidant capacity of the chemicals mentioned above. The findings of the present research allow us to suggest that these compounds be investigated further as a possible approach to therapy for treating oxidative stress-related disorders. Acknowledgment The authors express their gratitude to the Chemistry Department at the College of Science/ University of Baghdad for their assistance and collaboration for the completion of this research. Conflict of Interest The authors declare that they have no conflict of interest. Funding None. Ethical Clearance This study was approved by the scientific committee in the College of Science at the University of Baghdad for approving this study. References 1. Al-Adhami, H.; Al-Majidi, S.M. Synthesis, Characterization of Thiazolidin-4-one, Oxazolidin-4- One and Imidazolidin-4-One Derivatives from 6-Amino-1,3-Dimethyluracil and Evaluation of their Antioxidant and Antimicrobial Agent. Al-Qadisiyah Journal of Pure Science 2021, 26(4), 59-72. https://doi.org/10.29350/jops. 2. 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