Web of Science (Emerging Sources Citation Index), Scopus, ISC

Document Type : Original Research Article

Authors

Department of Chemistry, College of Sciences, Baghdad University, Baghdad, Iraq

Abstract

Aromatic polyimides (PIs) are receiving substantial interest because of their brilliant complete properties, multipath synthesis, various processing methods and wide application fields.   The current work aimed at the synthesis of a new series of 1,3,4-oxadiazole derivatives on poly (maleimid-co-methyl acylate). In first step poly (maleimid-co-MA) (1) was prepared using gebrail reaction to give poly (potassium maleimid-co-methyl acrylate) (2), then it reacted with different alkyl halide to obtain compounds (3-5) of free radical copolymerization.  In the second step it was treated with pure hydrazine (99%) to give compounds (6-8). The final step was the reaction of different carboxylic acid with copoly acid hydrazide in present phosphoryl chloride to give compounds (9-23) as shown in Scheme (1). All prepared compounds were characterized by Softening points (FT-IR), and some of them by HNMR and Thermal gravimetric analysis (TGA)). Further, their Biological application was investigated. Some of their physical characteristics are listed in Tables 1 and 2.

Graphical Abstract

Novel synthesis of 1,3,4 oxadiazole derivatives poly (maleimide-co-methyl acrylate) with some carboxylic acids and their biological activity

Keywords

Main Subjects

Introduction

Recently, the improvement of high-performance PI substances has found a significant status [1]. Aromatic polyimides (PIs) are receiving remarkable attention because of their brilliant complete properties, multi-path synthesis, various processing methods and wide application fields [2], the important products protecting PI membranes [3–6], composite materials [7–9], laminated resin [10], coatings, adhesives [11], separation membranes [12], fibers [13], photosensitive substances [14] and liquid crystal alignment layers [15].

Oxadiazoles are heterocyclic five-atom compounds containing one oxygen and atom two nitrogen atoms in their structure. Different types of oxadiazole isomers can be distinguished, occurring in the structure of many drugs [16]. The most promising formulations are 1,3,4-oxadiazole derivatives.  The first derivatives of 1,3,4-oxadiazole were prepared at the end of 19th century. The strategies for acquiring the new constructions have been multidirectional, which include the interactions of phosgene and the fantastic hydrazides, and the thermal cycle of the cyclization of 1,2-diacylhydrazines or 1-acylsemicarbazides with the help of drying action [17]. Scientists are currently using various methods to prepare 1,3,4-oxadiazole derivatives, some of which are improved prior methods, for example, reactions carbon disulfide with cyclooxygenase, cyclohydration, N-acylhydrazones, hydrazide or diacylhydrazines [18]. A massive increase in research on the 1,3,4-oxadiazole ring has been observed during the past two decades [19].

The 1,3,4-oxadiazole ring has demonstrated a wide range of pharmaceutical functions. According to the literature, for many years scientists around the world have been making new compounds with the basic 1,3,4-oxadiazole, which have confirmed an enormous spectrum of biological activity, including anti-inflammatory [20], antidepressant [21] analgesic [22], antidiabetic [24] and anticancer [24] effects. The unusual antimicrobial activity of compounds containing 1,3,4-oxadiazole ring in its structure has been also reported. Scientists have conducted research for an antifungal [25], antibacterial [26], and an antiviral [27] agent carrying a 1,3,4-oxadiazole scaffold.

Experimental

Materials

All chemical compounds used in this study were of the easiest purity accessible and derived from Fluka, BDH, and Sigma Aldrich chemical compounds. Softening points were determined on thermal microscope reichert thermover 160 (University of Baghdad college of science). FTIR spectra were recorded utilizing KBr disc on Shimadzu FTIR 8400 Fourier Transform Infrared spectrophotometer in the Department of Chemistry, College of Science, University of Baghdad. Some of the organized compounds were characterized through H-NMR spectra recorded on NMR in 400 MHz (Laboratory of Isfahan University) with tetramethyl saline as internal standard and DMSO as a solvent. Thermal analysis was performed using thermal analysis system consisting of TGA50 000801, which was carried out in the Laboratory of Isfahan University.

Synthesis of poly(maleimide-co-methylacrylate) (1) [28]

Copolymerization of maleimid (5 mmol) with methyl acrylate (5 mmol) was carried out in DMSO (50 mL) using AIBN (25 mg) as free radical initiator in bath water for 2h under nitrogen atmosphere. The copolymer MIMA was isolated by precipitation to methanol. The precipitated copolymer was washed with methanol several. The product used was purified by using dissolving in DMSO and reprecipitation from methanol. The physical properties are listed in Table 1.

Synthesis of poly (potassium maleimid-co-methyl acrylate) (2) [29]

Poly (maleimide-co-methylacrylate) (0.05 mole) was dissolved in absolute ethanol (30 mL) in presence of potassium hydroxide at 70-80 °C and refluxed for 6-8 hours. Next, the solution was allowed to dry. The products formed were purified by dissolving in DMF and rerecipitating with acetone. The physical properties are listed in Table 1.

Synthesis of poly (N-subs. maleimid-co-methyl acrylate) (3-5) [29]

The poly (potassium maleimid-co-methyl acrylate) (0.01 mole) was suspended in dioxane (30 mL); alkyl halide (0.01 mole) was then added to the solution drop by drop and stirred for 1 hour. The mixture was then left to dry. Next, the product was purified by dissolving in DMF and reprecipitation in ethanol. The physical properties are listed in Table 1.

Synthesis of poly (N-subs. maleimid-co- acryl acid hydrazide) (6-8) [30]

To a solution of poly (N-subs. maleimid-co-methyl acrylate) (1 mmol) in dioxane (30 mL), hydrazine hydrate (99%) (2 mmol) was added, then the resulting mixture was refluxed for 6hrs. The product was purified by dissolving in ethanol and reprecipitation from acetone. The physical properties are listed in Table 2.

Synthesis of poly (N-subs. maleimid-co- 1,3.4-oxadiazole)

A. From different aromatic carboxylic acids with POCl3 (9-20) [31]

Different aromatic carboxylic acids (1 mmol) and POCl3 (3 mL) were dissolved in chloroform (10 mL) and refluxed for 18 hours. The reaction combination was cooled and poured into beaten ice by stirring and getting neutralized with a solution of sodium carbonate (10%). The resulting solid was washed three times with water. The product was purified through dissolving in DMF and reprecipitated from the water. The physical properties are listed in Table 3.

B. From chloroacetic acid with POCl3 (21-23) [32]

To a stirred solution of phosphoryl chloride (15 mL), acid hydrazide compounds 6-8 (1 mmol) and chloroacetic acid (1mmol) were added at 0 oC, then reaction mixture was refluxed at 80 oC for 4 h. After the completion of the reaction, the reaction mixture was concentrated and poured into ice cold water (100 mL); the solid material was precipitated out which was filtered out and washed with water. The product was purified through dissolving in DMF and re-precipitated from the water. The physical properties are listed in Table 4.

 

Results and discussion

This work aimed at the reaction and synthesis of novel derivatives of 1,3.4-oxadiazole as shown in Scheme 1.

 

Alternating copolymer preparation of poly(maleimide-Co-methylacrylate)

Maleimide reacted with methylacrylate and AIBN as a catalyst to prepare compounds (1). The FTIR spectrum of these compounds (1) shows the appearance of the absorption bands [3213, 1724, 1741, 1398,1228] cm-1 due to ѵ (NH), ѵ (C=O) imide, ѵ (C=O) ester, ѵ (C-N) and ѵ (C-O-C) consecutively. These and other bands are shown in Table 1. 1HNMR spectrum of compound (1) showed signals at δ2.09 ppm (s, 2H, CH-CH2); δ 2.96 ppm (t, H, O=C-CH-CH2); δ 3.39 ppm (t, H, O=C- CH-CH2 imid); δ 3.34 ppm (m, H, O=C-CH-CH imid): δ 3.59 ppm (s, 3H, O-CH3,); δ 6.67 ppm (s, 1H, NH). Also, there was a signal at δ 2.5 ppm due to the solvent (DMSO).

Preparation of poly (potassium maleimid-co-methyl acrylate)

Poly(maleimide-Co-methylacrylate) reacted with KOH in ethanol as a catalyst to prepare compounds (2). The FTIR spectrum of these compounds (2) shows the appearance of the absorption bands [ 1755, 1739, 1373,1006] cm-1due to ѵ (C=O) imide, ѵ (C=O) ester, ѵ (C-N) and ѵ (C-O-C) consecutively. These and other bands are shown in Table 1. The disappearance of the absorption bands at (3213) cm-1 due to ѵ (NH) are also displayed.

Preparation of poly (N-subs. maleimid-co-methyl acrylate)

Poly (potassium maleimid-co-methyl acrylate) reacted with different alkyl halide in dioxane to prepare compounds (3-5). The FTIR spectrum of these compounds (1) shows the appearance of the absorption bands [2990-2818,1750-1741, 1693-1740, 1326-1373,1006-1260] cm-1 due to ѵ (C - H) aliphatic, ѵ (C=O) imide, ѵ (C=O) ester, ѵ (C-N) and ѵ (C-O-C) consecutively. These and other bands are shown in Table 1: 1HNMR signals for the compound (3) at δ0.96 ppm (d, 6H, CH-CH3); δ 3.64 ppm (d, 2H, N- CH2-CH); δ 2.03 ppm (m, H, CH2- CH-CH3); δ 2.09 ppm (s, 2H, CH-CH2); δ 2.96 ppm (t, H, O=C-CH-CH2); δ 3.39 ppm (t, H, O=C- CH-CH2 imid); δ 3.34 ppm (m, H, O=C-CH-CH imid): δ 3.59 ppm (s, 3H, O-CH3). Also, there was a signal at δ 2.5 ppm due to the solvent (DMSO).

Preparation of poly (N-subs. maleimid-co- acryl acid hydrazide)

Compounds 3-5 reacted with hydrazine hydrate (99%) in dioxane as a catalyst to prepare compounds (6-8). The FTIR spectrum of these compounds (6-8) shows the appearance of the absorption bands [3303-3326, 3234-3217,1730-1749, 1612-1620, 1398-1328,1434-1467]cm-1due to ѵ (NH2), ѵ (NH), ѵ (C=O) imide, ѵ (C=O) amid, ѵ (C-N) and ѵ (N-N) consecutively. Also, absorption bands disappear at (1228) cm-1 due to ѵ (C-O-C). These and other bands are shown in Table 2: 1HNMR signals for the compound (7) at δ1.96 ppm (s, 2H, CH-CH2); δ 2.96 ppm (t, H, O=C-CH-CH2); δ 3.39 ppm (t, H, O=C- CH-CH2 imid); δ 3.34 ppm (m, H, O=C-CH-CH imid): δ 3.90 ppm (s, 2H, NH-NH2); δ 4.46 ppm (d, 2H, N-CH2-Ar); δ 7.21-7.33 ppm (m, 5H, Ar-H); δ 7.50 ppm (s, 1H, O=C-NH-NH2). Also, there was a signal at δ 2.5 ppm due to the solvent (DMSO).

Preparation of 1,3.4-oxadiazole

Compounds (6-8) reacted with POCl3 in chloroform as to prepare compounds (9-20). The FTIR spectrum of these compounds (1) shows the appearance of the absorption bands [3040,2916-2848, 1740, 1654,1327,1256] cm-1 due to ѵ (C-H) arom., ѵ (C - H) aliphatic, ѵ (C=O) imide, ѵ (C=N), ѵ (C-N) and ѵ (C-O) consecutively. These and other bands are shown in Table 3: 1HNMR signals for the compound (9) at of δ2.96 ppm (s, 2H, CH-CH2); δ 3.30 ppm (t, H, O-C-CH-CH2); δ 3.41 ppm (t, H, O=C- CH-CH2 imid); δ3.64 ppm (m, H, O=C-CH-CH imid); δ 4.46 ppm (d, 2H, N-CH2-Ar); δ 7.23-7.93 ppm (m, 9H, Ar-H). Also, there was a signal at δ 2.5 ppm due to the solvent (DMSO).

Compounds (6-8) reacted with POCl3 as a catalyst to prepare compounds (21-23). The FTIR spectrum of these compounds (1) shows the appearance of the absorption bands [3040,2916-2848, 1740, 1654,1327,1256,667] cm-1 due to ѵ (C-H) arom., ѵ (C - H) aliphatic, ѵ (C=O) imide, ѵ (C=N), ѵ (C-N), ѵ (C-O) and ѵ (C-Cl) consecutively. These and other bands are shown in Table 4: 1HNMR signals for the compound (22) at δ 0.93 ppm ppm (d,6H, CH-CH3); δ 3.60 ppm (d, 2H, N- CH2-CH); δ 1.96 ppm (m, H, CH2- CH-CH3); δ 2.59 ppm (s, 2H, CH-CH2); δ 3.30 ppm (t, H, O-C-CH-CH2); δ 3.34 ppm (t, H, O=C- CH-CH2 imid); δ 3.44 ppm (m, H, O=C-CH-CH imid); δ 4.95 ppm (s, CH2-Cl). Also, there was a signal at δ 2.5 ppm due to the solvent (DMSO).

 

Biological activity [32]

Antimicrobial susceptibility tests of some synthesized compounds were performed according to the well diffusion method. A number of synthesized compounds were evaluated on two bacterial strains, one gram positive (Staphylococcus aurous) and one gram negative. (Escherichia coli). The samples were cultured on Muller Hinton agar medium at a temperature of 37 °C for a period of 24 hours, and the results were good for some compounds, as shown in Table 5. Also, one fungal strain like pathogenic fungal (Rhizosporium) was evaluated, where samples were planted on the medium of PDA at a temperature of 28 °C for a period of (3-5) days and some results were good, as shown in Table 6 and Figure 1.

[conc.] = 0.02 g/ml, Control = Solvent = DMSO, Inhibition Zone: (-) no inhibition; (6-10) mm weak; (11-18) mm moderate; (19-30) mm strong, (30-35) mm very strong.

 

 

Antioxidant activity [33]

DPPH Radical Scavenging Activity:

  • DPPH (1,1-Diphenyl-2-picryl-hydrazyl): 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 (100, 50, 25, 12.5 and 6.25) 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…etc.
  • Ascorbic acid (vitamin C): Similar concentrations were prepared.
  • The following equation was used to determine the potential to scavenge DPPH radicals:

 I%= (Abs blank – Abs sample) / Abs blank x 100 (Figure 2).

 

The IC50 value of DPPH radical scavenging activity [34]

The IC50 value was determined to assess the sample concentration required to inhibit 50% of the radical. The higher antioxidant activity lowers IC50 value of the compound (17) due to NO2, which is the preferred place of free radical attack. Ascorbic acid is a standard with an IC50 value of 36.3 ppm (Table 7).

 

Thermal gravimetric analysis

Thermal gravimetric evaluation (TGA) measures weight/mass change (loss or gain) and the rate of weight trade as a feature of temperature, time and atmosphere. Measurement is used principally to determine the thermal composition of materials and to predict their thermal stability, revealing that weight loss was below 20 % up to 200 C. The maximum weight loss in 40% occurred between 300 to 600 C. The total weight loss up to 800C is 80.6% (Figure 3).

 

Conclusion

The synthesized compounds have been demonstrated with the aid of using spectroscopic methods (FTIR and 1HNMR). Some of the organized compounds gave a top efficiency. The biochemical studies published that the newly synthesized compounds brought about activatory consequences on two types of micro-organism i.e. Staphylococcus aureus, Klebsiella pneumonia, and one type of fungal, i.e. Rhizosporium. Staphylococcus aureus showed reasonable inhibition via the compounds 18 and 26 and excessive inhibition in compounds 9,17 and 29. Klebsiella pneumonia confirmed average inhibition by means of the compounds 9 and 18, excessive inhibition in compounds 17,26 and 29,. Rhizosporium confirmed moderate inhibition in compounds 9,17 and
29 and excessive inhibition in compound 18,26. Based on what achieved, it can be stated that these organized compounds have precise efficacy towards micro-organism and fungi.

Acknowledgements

 The authors would like to extend their sincere appreciation to the Deanship at Baghdad University College of Science, and I want to thank everyone who helped me to complete this research.

Orcid:

Israa Sattar Gatea: https://www.orcid.org/0000-0002-5220-3825

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How to cite this article: Israa Sattar Gatea*, Entesar O. Al-Tamim.  Novel synthesis of 1,3,4 oxadiazole derivatives poly (maleimide-co-methyl acrylate) with some carboxylic acids and their biological activity. Eurasian Chemical Communications, 2022, 4(6), 544-556. Link:  http://www.echemcom.com/article_147318.html

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Copyright © 2022 by SPC (Sami Publishing Company) + is an open access article distributed under the Creative Commons Attribution License(CC BY)  license  (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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