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Document Type : Original Article

Authors

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

Abstract

Synthesis of a new series of poly (N-substituted-maleimide-co-2,5- substituted-1,3.4-oxadiazole) was carried out. The first step includes preparation of copoly imine by reaction of different aldehydes with copoly acid hydrazide (1-15). The second step indicated the reaction of copoly imine with iodine in the presence of K2CO3 to give poly (N-substituted-maleimide-co-2,5-substituted-1,3.4-oxadiazole). All prepared compounds were characterized by softening points, FT-IR, and some of them by 1H-NMR and TGA, and then their Biological application was studied and some of the physical properties.

Graphical Abstract

Synthesis of a New Copoly 1,3,4-Oxadiazole from Copoly Imine with Iodine and Study of Their Biological Activity

Keywords

Main Subjects

Introduction

Aromatic polyimides (PIs) are considered to be high-performance polymer materials due to their high mechanical strength, good thermal stability, and chemical resistance [1]. Aromatic polyimides (PIs) are receiving more and more attention because of their gorgeous comprehensive properties, multi-path synthesis, diverse processing techniques, and wide application fields [2]. The most important products protected PI membranes [3–6], laminated resin [7], composite materials [8–10], coatings, adhesives [11], fibers [12], separation membranes [13], photosensitive materials [14], and liquid crystal alignment layers [15]. In recent years, the development of excessive performance PI substances has grown to be a new lookup hotspot [16].

1,3,4-Oxadiazole heterocyclic ring is one of the most essential heterocyclic moieties due to the fact of its versatile organic actions. In particular, heterocyclic compounds bearing such a ring are recognized to exert possible ant tubercular exercise [17], anti-inflammatory and analgesic activities [18], anti-viral pastime [19], anti-cancer exercise and antimicrobial undertaking [20,21]. Also, 1,3,4-oxadiazole bearing fused thiophene derivatives have antioxidant pastime [22]. In addition, 1,3,4-oxadiazole containing thiazole moiety suggests antimicrobial and cy-totoxic things to do [23]. It was once located that oxadiazole bearing chromene derivatives have po-tential antibacterial and antifungal residences [24]. Furthermore, pyridazine derivatives exhibit interesting anti-fungal exercise [25]. Furthermore, phenyl-bearing oxadiazole exerts versatile organic properties, such as antimicrobial and cytotoxic exercise [26,27], and anti-inttam-matory activity [28]. On the other hand, 5-substituted-2-mercapto-1,3,4-oxadiazoles exhibit analgesic, antitubercular and anticonvulsant homes [29].

Schiff bases are produced mainly by a condensation process between primary amines and carbonyl compounds. The general formula is RHC=NR, where R and R are alkyl, aryl, cycloalkyl, or heterocyclic groups, characterized by the azomethine group [30]. Chemically, a Schiff’s base is a nitrogen base of an aldehyde or ketone in which the carbonyl group is changed by imine or azomethine group. Schiff bases also characterized by appear a widely range biological activities (i.e., the anti-bacterial, anti-fungal, anti-cancer, anti-inflammatory, anti-viral, and anti-pyretic properties) [31,32]. Schiff bases of aliphatic aldehydes are unstable and readily polymerizable, while Schiff bases of aromatic aldehydes with an effective conjugation system are more stable [33].

The focus of this paper is on synthesis and characterization of poly (N-substituted-maleimide-co-2,5- substituted-1,3.4-oxadiazole) which was obtained by reaction of different aldehydes with copoly acid hydrazide to give copoly imine, and then reaction copoly imine with iodine in present K2CO3. The chemical structure and physical properties of the two poly (N-substituted-maleimide-co-2,5- substituted-1,3.4-oxadiazole) were characterized with FT-IR, NMR and TGA.

Materials and Methods

All chemicals used in this study were of the highest purity available which were supplied from Fluka, BDH, Sigma-Alderich chemicals, and CDH. FT-IR spectra had been recorded using a KBr disc on Shimadzu FT-IR8400 spectrophotometer in department of chemistry, college of science, university of Baghdad. A few of arranged compounds had been characterized by 1H-NMR spectroscopy which recorded on NMR in 400 MHz (Laboratory of Isfahan University) with DMSO-d6 as a dissolvable and tetra methyl saline as inside standard. The biological activity used to be performed by the Central Environmental Laboratory-Aljadiryah-University of Baghdad (anti-bacterial and anti-fungal). The anti-oxidant activity was performed in department of chemistry, college of science, University of Baghdad.

Preparation of copoly Schiff bases (1-15) [34]

A solution of different aldehydes (1 mmole) in absolute ethanol (20 ml) and glacial acetic acid (3 drops) was added to this solution. After that, copoly (maleimid-acryl acid hydrazide) (1 mmole) were added to the reaction mixture and refluxed for 6-8 hours. The product was left until the solvent evaporated, washed with distilled water. Purification of the product is completed through dissolving in DMF and re-precipitation from water. FT-IR spectral data (cm-1) and Physical properties are listed in Table 1.

Synthesis of copoly 1,3.4-oxadiazole (16-30) [35]

A solution of copoly imine (1 mmol) in DMSO (10 mL) was added to potassium carbonate (3 mmol), iodine (1.2 mmol) in sequence. The reaction mixture was stirred at 100 oC until the conversion was completed (8 h), washed with distilled water, dried and also purification of the product was completed through dissolving in DMF and re-precipitation from water. The physical properties and FT-IR spectral data (cm-1) are listed in Table 2.

 

Results and Discussion

In the following, our afford was toward the bioactive heterocyclic motif parade 1,3,4-oxadiazole ring.

Scheme 1: Synthesis of 1,3,4-oxadiazole derivatives

 

Preparation of copoly Schiff bases (1-15) [34]

The compounds were prepared from the reaction between copoly (maleimid- acryl acid hydrazide) with different aldehydes and glacial acetic acid in absolute ethanol. The FT-IR spectrum data of compounds 1-15 shows the appearance of characteristic bands at 3350-3200 cm-1, 1770-1750 cm-1, and 1680-1640 cm-1 due to ѵ(NH), ѵ(C=O) imide, ѵ(C=O) amide, consecutively and 1690-1640 cm-1, 1619-1600 cm-1, 1440-1400 cm-1, and 1336-1300 cm-1 due to ѵ(C=N), ѵ(C=C), and ѵ(N-N), ѵ(C-N), consecutively. These bonds and the other ones are presented in Table 1. Also, absorption bands disappear at (3400-3200) cm-1 due to ѵ(NH2). 1H-NMR spectrum of compounds (2) indicated signals at δ= 4.56 ppm (d, 2H, N- CH2-Ar); δ=1.88 ppm (s, 2H, CH-CH2); δ= 3.26 ppm (t, H, O=C-CH-CH2); δ= 3.34 ppm (t, H,O=C- CH-CH2 imid); δ= 3.47 ppm (m, H, O=C-CH-CH imid); δ= 7.21-7.57 ppm (m,9H,Ar-H); δ= 8.02 ppm (s, H, NH); and δ= 7.72 ppm (s, H, CH=N). The other signals are indicated in Table 3.

Preparation of copoly 1,3.4-oxadiazole (16-30) [35]

Compounds (1-15) reacted with K2CO3 and I2 in DMSO as to prepare compounds (16-30). The FT-IR spectrum of these compounds (16-30) illustrated the appearance of the absorption bands 3040 cm-1, 2916-2848 cm-1, 1740 cm-1, 1654 cm-1, 1327 cm-1, and 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 listed in Table 2. 1H-NMR spectrum of compound (16) showed signals at δ= 4.62 ppm (d, 2H, N- CH2-Ar); δ= 2.36 ppm (s, 2H, CH-CH2); δ= 3.32 ppm (t,H,O-C-CH-CH2); δ= 3.45 ppm (t, H,O=C- CH-CH2 imid); δ= 3.64 ppm (m, H, O=C-CH-CH imid); and δ= 7.22-8.66 ppm (m,12H,Ar-H). Furthermore, there was a signal at δ= 2.5 ppm due to the solvent (DMSO).

Biological Activity Antimicrobial activity [36]

Biological activity and antimicrobial susceptibility tests of some synthesized compounds were performed according to the well diffusion method. A number of synthesized compounds had been evaluated on two bacterial strains, one grampositive (Staphylococus aureus) and one gram-negative. (Klebsiella pneumonia). 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 depicted in Table 5. Likewise, 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 illustrated in the Table 5.

Table 3: 1HNMR spectral data (δ ppm) for some of the prepared compounds

Compound No.

1H- NMR spectral data (δ= ppm)

2

4.56 (d, 2H,N- CH2-Ar); 1.88 (s, 2H, CH-CH2); 3.26 (t, H, O=C-CH-CH2); 3.34 (t, H,O=C- C H-CH2 imid); 3.47 (m, H, O=C-CH-CH imid); 7.21-7.57(m,9H,Ar-H); 8.02 (s, H, NH); 7.72 (s, H, CH=N)

3

4.56 (d, 2H,N- CH2-Ar); 1.88 (s, 2H, CH-CH2); 3.26 (t, H, O=C-CH-CH2); 3.34 (t, H,O=C- CH-CH2 imid); 3.47 (m, H, O=C-CH-CH imid); 7.2-7.74 (m,9H,Ar-H); 8.65 (s, H, NH); 6.44 (s, H, CH=N); 5.98-6.05 (d,2H,CH=CH)

4

4.56 (d, 2H,N- CH2-Ar); 1.88 (s, 2H, CH-CH2); 3.26 (t, H ,O=C-CH-CH2); 3.34 (t, H,O=C- CH-CH2 imid); 3.47 (m, H, O=C-CH-CH imid); 7.24-7.32 (m,5H,Ar-H); 8.09-8.29 (m,4H,NO2- Ar-H); 8.01 (s,H,NH); 7.73 (s, H, CH=N)

5

0.96 (d,6H,CH-CH3); 3.58 (d, 2H,N-CH2-CH); 2.02-(m, H, CH2- CH-CH3); 1.88 (s, 2H, CH-CH2); 3.26 (t,H,O=C-CH-CH2); 3.34 (t, H,O=C- CH-CH2 imid); 3.47 (m, H, O=C-CH-CH imid); 7.21-7.74 (m,9H,Ar-H); 8.60 (s, H, NH); 6.43 (s, H, CH=N); 6.25 (d, H, CH=CH-CH); 5.98 (m,H,CH3-CH=CH)

16

4.62 (d, 2H,N- CH2-Ar); 2.36 (s, 2H, CH-CH2); 3.32 (t,H,O-C-CH-CH2); 3.45 (t, H,O=C- CH-CH2 imid); 3.64 (m, H, O=C-CH-CH imid); 7.22-8.66 (m,12H,Ar-H)

19

0.96 (d,6H,CH-CH3); 3.58 (d, 2H,N- CH2-CH); 2.02-(m, H, CH2- CH-CH3); 2.36 (s, 2H, CH-CH2); 3.32 (t,H,O-C-CH-CH2); 3.45 (t, H,O=C- CH-CH2 imid); 3.64 (m, H, O=C-CH-CH imid); 6.43 (m, H, O-C-CH=CH); 6.29 (m,H,CH3-CH=CH); 2.08 (d,3H,CH3-CH=CH)

20

0.92 (d,3H,CH-CH3); 3.52 (d, 2H,N- CH2-CH2); 1.59 (d, 2H,N-CH2- CH2-CH2); 1.32-(m, H, CH2- CH2-CH3); 2.36 (s, 2H, CH-CH2); 3.32 (t,H,O-C-CH-CH2); 3.45 (t, H,O=C- CH-CH2 imid); 3.64 (m, H, O=C-CH-CH imid); 7.03 (m, H, O-C-CH=CH); 7.16 (m,H,CH3-CH=CH); 2.08 (d,3H,CH3-CH=CH); 7.29-7.50 (m,4H,Ar-H)

23

0.93 (d,6H,CH-CH3); 3.58 (d, 2H,N- CH2-CH); 2.02-(m, H, CH2- CH-CH3); 2.36 (s, 2H, CH-CH2); 3.32 (t,H,O-C-CH-CH2); 3.45 (t, H,O=C- CH-CH2 imid); 3.64 (m, H, O=C-CH-CH imid); 8.19-8.36 (m,4H,Ar-H)

29

4.60 (d, 2H,N- CH2-Ar); 2.36 (s, 2H, CH-CH2); 3.32 (t,H,O-C-CH-CH2); 3.45 (t, H,O=C- CH-CH2 imid); 3.64 (m, H, O=C-CH-CH imid); 7.23-8.06 (m,9H,Ar-H)

 

Table 4: Antimicrobial for some the prepared compounds

No. of Compound

Anti-bacterial activity test

Anti-fungal activity test

Staphylococcus aureus

 (Gram-positive bacteria)

klebsiella pneumonia

 (Gram-negative bacteria)

Rhizosporium

Control

-

-

-

16

20

22

16

19

18

20

14

20

19

18

20

23

22

23

18

29

25

24

22

Amoxicillin

28

30

 

Flucanazole

 

 

14

 

Antioxidant activity [37]

On the basis of the radical scavenging effect of the stable DPPH free radical, the antioxidant function of some selective synthesis of some prepared compounds and a normal (vitamin C) was assessed using the process. In a test tube, 1 ml of the diluted or normal solution (6.25, 12.5, 25, 50, and 100 ppm) was applied to DPPH solution 1 ml. The absorbance of each solution was measured at 517 nm using a spectrophotometer after 1 hour of incubation at 37 °C. Some of the newly synthesized compounds showed antioxidant activity against DPPH free radicals and gave a good scavenging percentage. So, the compounds that gave antioxidants were selected, more tests were performed, and the (IC50) value was calculated as displayed in Figure 1.

Figure 1: The scavenging’s comparison between the prepared compounds and ascorbic acid

The IC50 Value of DPPH Radical Scavenging Activity [38]

The IC50 value was determined to assess the sample concentration required to inhibit 50% of the radical. The higher antioxidant activity, the lower the IC50 value of the compounds. Ascorbic acid is a standard and it has an IC50 value of 36.3 ppm.

Table 5: IC50 value of DPPH radical scavenging activity

Compound No.

Linear Equation

IC50

16

y = 1.0303x

48.52

19

y = 0.9905x

50.47

20

y = 0.9799x

51.02

23

y = 1.0198x

49.02

29

y = 1.082x

46.21

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 which reveals that weight loss was below 20 % up to 350°C. The maximum weight loss in the range 30 % to 79.28 % occurred between 400 to 500 °C. The total weight loss up to 800°C is 79.28%.

Figure 2: Thermal analysis (TG) of compound [29]

 

Conclusion

The synthesized compounds have been demonstrated with the aid of using spectroscopic methods (FT-IR and 1H-NMR). Some of the organized compounds gave a high efficiency. The biochemical studies published that the newly synthesized compounds brought about activators consequences on two types of microorganism, i.e. Staphylococcus aureus, Klebsiella pneumonia, and one type of fungal, i.e. Rhizosporium. Staphylococcus aureus indicated reasonable inhibition via the compounds 19 and 20 and excessive inhibition in compounds 16, 23, and 29. Klebsiella pneumonia confirmed average inhibition by means of the compounds 19 and 20, excessive inhibition in compounds 16, 23, and 29. Rhizosporium confirmed moderate inhibition in compounds 16, 19, and 23, and excessive inhibition in compounds 20 and 29. Based on what achieved, it can be stated that these organized compounds have a precise efficacy towards microorganism and fungi.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

 

Authors' contributions

All authors contributed toward data analysis, drafting, and revising the paper and agreed to be responsible for all the aspects of this work.

 

Conflict of Interest

We have no conflicts of interest to disclose.

ORCID:

Israa Sattar Gatea

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

HOW TO CITE THIS ARTICLE

Israa Sattar Gatea, Entesar. O. Al-Tamimi. Synthesis of a New Copoly 1,3,4-Oxadiazole from Copoly Imine with Iodine and Study of Their Biological Activity. Chem. Methodol., 2022, 6(6) 446-456

https://doi.org/10.22034/CHEMM.2022.335635.1465

URL: http://www.chemmethod.com/article_148298.html

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