Document Type : Original Research Article
Authors
Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq
Abstract
In this work, new creatinine derivatives containing (1,2,4-triazole and 5-subs-1,2,4-triazole) ring have been prepared. In the first step, creatinine was reacted with different acid chloride to form 2-subs. amido creatinine 1[a-d]. In the second step, amido creatinine 1[a-d] was reacted with succinoyl chloride to produce imide derivatives 2[a-d]. In the third step, the imide componds prepared were reacted with hydrazine hydrate to give acid hydrazide derivatives 3(a-d). Finally, 1,2,4-triazole derivatives 4-7[a-d] were prepared from the reaction between acid hydrazide with different amide compounds by pellizzari reaction. These new synthesized products have been characterized by FT-IR, 1H-NMR for some of them and were studied regarding the effect of preparing derivatives on antioxidant.
Graphical Abstract
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Keywords
Main Subjects
Introduction
Creatinine is a break product of creatine phosphate in muscle [1]. Creatinine is transferred to the kidneys by blood plasma, eliminating from body by glomerular filtering and partial tubular secretion. The loss of a water molecule from creatine results in the formation of creatinine as a heterocyclic compound [2]. New heterocyclic compounds which contain creatinine were synthesized and antimicrobial activity [3], as well as the activity of GOT and GPT enzymes [4] were studid. Triazole is known as pyrrodiazole, one of the types of organic heterocyclic derivatives, was unsaturated containing five membered ring structure of tow carbon and three nitrogen atoms [5]. 1,2,4-Triazole is one of the very interesting types of compounds which attracted the attention of many chemists and biologists in organic synthesis, pharmaceutical and medicinal field because of their different biological activities like anticancer [6], anti-inflammatory [7], analgesic [8], anti-HIV [9], chronic pain [10], antibacterial [11], antimycobacterial [12], antiviral drugs [13] and antifungal [14]. Amaal S. et al. studied the synthesis of new polymers bearing 1,2,4-triazole ring on creatinine with their corrosion protection of stainless steely surfaces [15]. The pellizzari reaction is referred to the synthesis of 1,2,4-triazole derivatives from the reaction of amide and acyl hydrazide; this reaction firstly was prepared by pellizzari in 1911 [16].
Experimental
Materials and instruments
All materials and solvents were used from Fluka and Sigma-Aldrich without purification. Melting points were measured in Gallen Kamp capillary melting point instrument. FT-IR measurements were recorded on Shimadzu model FT-IR-8400 S. 1H-NMR spectra were obtained with Bruker spectrophotometer ultra-shield in 400 MHz and TMS as internal standard in D2O solution.
Methods
Synthesis of 2-subs-amido creatinine 1[a-d] [17]
The creatinine (0.02 mole) was dissolved in DMF (20 mL) and cooled at (0-5) C0, and (2-3) drops of triethylamine (TEA) were added. Different acid chlorides [acetyl chloride, benzoyl chloride, 4-nitrobenzoyl chloride and 2-chlorobenzoyl chloride] (0.02 mole) in DMF (20 mL) were slowly added, than staying with strong stirring for (3 hours) at room temperature. The obtained product was filtered, washed with ether and recrystallized from ethanol. The physical properties of synthesized compounds 1[a-d] are shown in Table 1.
Synthesis of imide derivatives 2[a-d] [18]
Creatinine amide 1[a-d] (0.02 mole) were dissolved respectively in DMF (20 mL) and (2-3) drops of triethylamine (TEA) were added. Equimolar of succinyl chloride was added dropwise to the solution, and then it was refluxed for (4-5) hours. The obtained product was filtered, washed with ether and recrystallized from ethanol. The physical properties of the synthesized compounds 2[a-d] are shown in Table 1.
Synthesis of acid hydrazide derivatives 3[a-d] [19]
Hydrazine hydrate (0.01 mole) was added to the solution of (0.01 mole) of imide compounds 2[a-d] in absolut ethanol (25 mL). This mixture was refluxed for (5-6) hours. The obtained product was filtered, washed with ether and recrystallized from ethanol. The physical properties of the synthesized derivatives 3[a-d] are shown in Table 1.
Synthesis of 1,2,4-triazole derivatives 4-7[a-d] [20]
Acid hydrazide derivatives 3[a-d] (0.001 mole) were dissolved in (25 mL) MDF and (0.001 mole) from different amide compounds [formamide, acetamide, benzamide and acrylamide] were added, and then it was refluxed for (5-6) hours. The product was collected and recrystallized from ethanol. The physical properties of synthesized compounds 3[a-d] are shown in Table 2.
Antioxidant activity [21]
DPPH (4 mg) was dissolved in 100 mL of ethanol, and the solution was kept protected from light by covering the test tubes with aluminum foil. Various concentrations of (25, 50, 100) ppm were prepared from some of the prepared compounds. It was prepared by dissolving 1 milligram of the compound and dissolving it with 10 mL of ethanol to prepare 100 ppm, then it was diluted to (50 and 25) ppm. Similar concentrations were prepared. In a test tube, 1 mL of the diluted or normal solution (25, 50, 100) ppm was applied to 1 mL of DPPH solution. The absorbance of each solution was measured at 517 nm using a spectrophotometer after 1 hour of incubation at 37 °C. The following equation was used to determine the potential to scavenge DPPH radicals.
I % = (Absorption blank – Absorption sample) / Absorption blank x 100.
Results and discussion
New 1,2,4-triazole derivatives 4-7[a-d] were prepared from creatinine by its reaction it with different acids chloride to produce 2-subs-amido creatinine 1[a-d]; then, they were reacted with succinyl chloride to produce 2-imido creatinine derivatives 2[a-d]. Hydrazine hydrate was reacted with imide derivatives 2[a-d] to form acid hydrazide derivatives 3(a-d). Finally, these compounds were reacted with different amides compounds to give 1,2,4-triazole derivatives 4-7[a-d] by pellizzari reaction (Scheme 1). FT-IR spectra of derivatives 1[a-d] were appeared stretching vibrations band to the (C=O) amide at (1647-1652) cm-1, and compounds 2[a-d] appeared band at (1768-1772) cm-1 and (1791-1797) cm-1 due to the symmetric and asymmetric stretching vibration of (C=O) imide the absorption band at (1800-1805) cm-1 due to (C=O) acid chloride[22]. FT-IR spectra of derivatives 3[a-d] resulted in the appearance of two absorption bands at (3242-3265) cm-1 and (3363-3419) cm-1 due to the stretching vibrations of (-NH2) group. Table 1 shows the other data of functional groups for compounds 1-3[a-d]. The FT-IR spectra of compounds 4-7[a-d] appeared stretching vibrations band to the (C=N) triazole ring [23] at (1622-1650) cm-1 and the other stretching vibration bands for this compounds were shown in Table 2. 1H-NMR spectrum of compounds (4a, 5b, 6c, 6d and 7a) are listed in Table 3. Antioxidant activity based on DPPH stable free radical sweep effect, the antioxidant function of some selective synthesized of some prepared compounds, and ascorbic acid were assessed using the process. The results listed in Table 4 show some of the new prepared derivatives and antioxidant activity against DPPH free radicals and give a good scavenging percentage and compression with ascorbic acid. The reduction ability of DPPH radical was determined by the decrease in absorbance at 517 nm. Further, it is well determined that organic molecules include an electron donating group (NH2, OCH3, and OH) that can act as free radical agents and are capable of opposing oxidization. Figure 1 shows that the highest antioxidant activity found in compound (3a, 4b, 5a and 7b) presents the highest scavenging activity on DPPH, whereas the other compounds exhibit moderate because we observed the presence of electron withdrawing groups such as (Cl, NO2 and Br) on phenyl ring exhibited lowest antioxidant activity [24].
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Conclusion
The prepared new 1,2,4-triazole derivatives on creatinine were confirmed by using spectroscopic techniques (FT-IR and 1HNMR). The antioxidant activity of the most compounds were strong compressed with ascorbic acid.
Acknowledgments
The authors would like to extend their sincere appreciation to the Deanship at Baghdad University College of Science, and thank everyone who helped them to complete this research.
Orcid:
Zainab Amer Sallal: https://orcid.org/0000-0002-3578-6387
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How to cite this article: Zainab Amer sallal*, Entesar O. Al-Tamimi. Modification and characterization of subs. triazole on creatinine and studying their antioxidant activity. Eurasian Chemical Communications, 2022, 4(2), 152-159. Link: http://www.echemcom.com/article_143424.html
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