Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

header
Reach Us reach to JOCPR whatsapp-JOCPR +44 1625708989
All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Original Articles: 2022 Vol: 14 Issue: 8

Preparation, Diagnosis and Evaluation of Some New Synthetic Aromatic Derivatives with Their Antimicrobial Activity

Ammar Abdulghani Qasim Yahya*

Department of Dental Basic Sciences and Organic Chemistry, University of Mosul, Mosul, Iraq

Corresponding Author:
Ammar Abdulghani Qasim Yahya
Department of Dental Basic Sciences and Organic Chemistry, University of Mosul, Mosul,
Iraq

Received: 25-Mar-2022, Manuscript No. JOCPR-22-58416; Editor assigned: 28-Mar-2022, PreQC No. JOCPR-22-58416 (PQ); Reviewed: 11-Apr-2022, QC No. JOCPR-22-58416; Revised: 24-May-2022, Manuscript No.JOCPR-22-58416 (R); Published: 31-May-2022 DOI: 10.37532/0975-7384.2022.14(8).1-11

Abstract

The compound 2-aminobenzenethiol was reacted with malononitrile at RT to produce 2-(benzothiazol-2-yl) acetonitrile (H1), it was reacted with different carbonyl compounds to get derivatives of 2-(benzothiazol-2-yl)-3-(2-hydroxy-4-methoxyphenyl) acrylonitrile (H2-H10). It was also treated with sodium azide in the existence of the ZnCl2 to produce (H11-H14) on a side, while it was reacted some of the benzothiazole derivatives with sodium azide without a catalyst to produce (H15-H17) on the other side. The chemical compositions of the prepared compounds were diagnosed and confirmed by spectroscopies of UV, FT-IR and 1H-NMR. The effect of these compounds on some bacteria and a fungus was investigated, good results were obtained consequently.

Keywords

Benzothiazole; Triazole; Imidazotriazine

Introduction

The chemistry of heterocyclic is very important in everyday use; it has a wide range of applications in (Medicine and industrial) compounds. The benzothiazoles represent the basic structure of the various prepared compounds that have a wide spectrum of biological activities such as anti-cancer effects, necrosis inhibitors and fatty acids[1]. Some isoxazoles and pyrazolates have antimicrobial activities [2]. The therapeutic properties of heterocyclic compounds have also encouraged researchers in the field of clinical chemistry to preparmore derivatives [3]. Benzothiazole has a system of particular interest in the field of medicinal chemistry due to its remarkable pharmacological potential including anticancer, antimicrobial, anti-diabetic, etc. [4]. The misuse of antibiotics since the discovery of penicillin has recently led to the urgent need for new antibiotics, due to the emergence of bacterial strains that have great resistance to antibiotics; therefore, the use of plant extracts or pure natural compounds with conventional antibiotics is successful subject [5]. The applications of benzothiazole is a wide range of use, due to its limitless pharmacological effects, 2-aminobenzothiazole. It allows the combination with heterocyclic compounds to achieve a new pharmacological effect and reduce toxicity [6]. Benzotriazoles with triazole exhibit wide potentialities in medicine, since some of them have been shown to inhibit the growth of cancerous cells [7]. Infections affecting the digestive system may be the cause of disease and death. Medicines for nitrogenous cyclic compounds have expanded their applications and newly-used to treat anaerobic bacteria. There is a great interest in reducing nitroimidazole to produce highly effective drugs, in addition to their relationships between the formulation and mutagenesis [8]. The heterocyclic compounds are the basic and important units in medicinal chemistry; it contains the elements sulfur, oxygen and nitrogen, for example, thiophene, thiazole, furan, imidazotriazine, diazeridine, etc. Features of these reactions depend on the structure of reactants, intermediates and reaction medium (organic solvents, ionic liquids) [9].

Materials and Methods

The chemical reagents used in the preparation were purchased from Fluka and PDH. Melting points were measured using the device, which has not been corrected. The infrared spectra were measured by using ATR-Diamond. 1H-NMR spectra were measured by using a (Brucker 400 MHz) spectrometer using CDCl3/DMSO-d [6].

Experimental

Synthesis of 2-(benzothiazol-2-yl)acetonitrile (H1):(S1): The compound 2-aminobenzenethiol (5 g, 0.04 mol and malononitrile (2.64 g ,0.04 mol)) was dissolved in (30 ml) Absolute ethanol, (6 ml) of glacial acetic acid were added. Stirrer the mixture overnight at RT, filter and recrystallized with ethanol to get A Yellow precipitate has m.p.(100-101°C) with (85%). The FT-IR spectrum showed spectrum bands at (3055 cm-1 str. C-H Ar.), (2925 C-H alf. str.; 2200 cm-1 CN str.; 1652 cm-1 C=N str.; 1558 cm-1 , 1431 cm-1 C=C Ar. str.; 756 cm-1;C-S-C str. 1H-NMR spectrum showed signals between 7.15-8.1 ppm for four aromatic hydrogen and the signal at 4.3 ppm due to (2H, s).

(S2): General synthesis method of 2-(benzothiazol-2-yl)-3-phenylacrylonitrile derivatives [11-15] (H2-H10), (0.0015 moles) of the (H1) was dissolved in absolute ethanol (Table 1). 0.0015 moles of aromatic (aldehydes or ketones) were added to the mixture; (8-10) drops of piperidine were added. The mixture stirred for six hrs, at (RT), filters and recrystallized with ethanol (Figures 1 and 2).

Comp. R M.P. (ºC) Color Yield (%)
H2 4-NMe2 234-236 Deep red 95
H3 4-Br 104-105 Red 89
H4 4-Cl 152-153 Deep green 92
H5 4-OMe-2-OH 178-178 Orange 82
H6 2-NO2-2-OH 190-192 Hazel 79
H7 4-OH 101-102 Yellow 94
H8 2-OH 184-185 Yellow 98
H9 H 88-89 Pale Yellow 93
H10 4-OMe 144-146 Deep Yellow 97
H11 4-OMe 300-301 Brown 75
H12 4-NMe2 209-210 Red 67
H13 4-Cl 44-46 Green 53
H14 2-OH 214-216 Red 59
H15 4-OMe 135-137 Red 54
H16 4-Cl 114-116 Red 66
H17 2-OH 296-299 Red 48

Table 1: Physical properties of the synthesis compounds

Figure 1: FT-IR for compound (H1)

Figure 2: 1HNMR for compound (H1)

Figure 3 the FT-IR spectrum showed the bands of the (H2) compounds at (1612-1697cm-1str. C=H), for all of the synthesized compounds, it proofs the formation the compounds bands, other bands listed in Table 2. In the Figure 4, 1H-NMR spectrum of (H2) compound showed signals between 7.15-8.45 ppm for four aromatic hydrogen, a signal at 5.19 ppm, signal at 1.63 ppm (1H, s ) was attributed to (-CH) and a signal at 11 due to (OH,s) as shown in Table 2. The suggested mechanism for this reaction illustrated in the Figure 5.

Comp.
No.
I.R., υ (cm-1), KBr 1H-NMR
υ (ppm), CDCl3
OH C=C C=N -C=C Ar.
H2 - 1612 1568 1477  
H3 - 1610 1589 1431  
H4   1649 1558 1492 6.8 - 8.13 (m, 4H, Ar-H); 1.09 (s,CH)
H5 3440 1650 1569 1515  
H6 3477 1697 1610 1610  
H7 3276 1625 1590 1514  
H8  3236  1662  1604  1458 6.8 - 8.13 (m, 4H, Ar-H); 1.09- 3.31
(S,2H, NHNH); 4.35 (d, 2H, CH2); 10 (S,1H,OH)
H9 - 1639 1600 1448  
H10 - 1600 1591 1512 6.8 - 8.13 (m, 4H, Ar-H); 1.09- 3.31
(s,CH) 4.35 (s, 3H, OH3);

Table 2: Spectral data of compounds (H2- H10)

Figure 3: FT-IR for compound (H2)

Figure 4: 1HNMR for compound (H2)

Figure 5: Suggested Mechanism (H2-H10)

(S3a): General Synthesis method of Tetrazoles (H11-H14): (0.002 mol) of the compounds (H2-H10), sodium azide (0.003 mol), and (0.003 mol) of ZnCl2 were dissolved in (25 ml) DMF. The reaction was refluxed for 10 hrs. The mixture diluted with water, Filter and recrystallized with DMF. In the Figure 6 the FT-IR spectrum showed disappear the CN group at 2200 cm-1 and appeared the N3 group at (2400 cm-1) and the N=N group at (998 cm-1). However, while proccing the reaction without a catalyst use the (-C=C-) group disappeared at (1600-1658 cm-1) those are good evidence on the success the reaction, other FT-IR bands listed in Table 3.

Comp.
No.
I.R., υ (cm-1), KBr 1H-NMR
υ (ppm), CDCl3
NH C-H alf. C=C N=N
H11 3267 2927 1693 946  
H12 3060 2923 1652 937  
H13 3127 2895 1659 998  
H14 3051 2923 1652 956 6.8 - 8.13 (m, 4H, Ar-H); 1.09
(S,1H, NH); 4.35 (s, 1H, CH);

Table 3: Spectral data of compounds (H11-H14)

Figure 6: FT-IR for compound (H11)

(S3b): General synthesis method of Triazoles (H15-H17): 0.002 moles of the (H2-H10), compounds, and (0.003 mol) sodium azide was dissolved in (20 ml) DMF. The mixture was refluxed for 24 hrs. Diluted with Water, acidify until the precipitate formed with conc. HCl, Filter and recrystallized with DMF. In this reaction, the cyclation occurred on (-C=C-) instead of occurring on nitrile group. In the Figure 7 the FT-IR spectrum showed bands at (2187 cm-1) due to (N3) group, (3055 cm-1 C-H Ar. str.; 2200 cm-1 CN str. good evidence on the success the reaction, that are listed in Table 4. 1H-NMR spectrum of compound (H15), showed signals between 7.68-8.03 ppm for aromatic hydrogen, a signal at 2-2.3 ppm due to (N(CH3)2, s), a signal at 6.51 ppm due to (CH, s) and a signal at 11.41 ppm due to (NH , s) (Figure 8).

Comp No. I.R., υ (cm-1), KBr 1H-NMR, υ (ppm), d6-MSO
NH C-H alf. C=N N=N
H15 3265 2900 2187 945 2.0-2.3(N(CH3)2,6.51CH ,7.68 -8.03 Ar-CH,11.41 NH
H16 3298 2925 2059 952 6.58CH ,7.57 -7.89 Ar-CH ,11.24 NH
 H17 3200 2900 2360 833 3.5 (OCH3) ,6.69 CH ,7.78 -8.08 Ar-CH,11.45 NH

Table 4: Spectral data of compounds (H15–H17)

Figure 7: FT-IR for compound (H15).

Figure 8: FT-IR for compound (H15)

Antimicrobial Activity of some of the synthesized compounds: A preliminary evaluation of antibacterial and anti-fungus activity against types of bacteria like Escherichia coli, Bacillus subtilis (Gram-negative) and Candida albicans fungus. Those kinds of bacteria and (Figure 9) fungus have been choosing because of their wide importance in the clinical field, it causes many diseases their various resistances of the antibiotic and chemical drugs. All of the tested compounds were studied at different concentrations by using DMSO as a solvent (0.05, 0.001, 0.075, 0.005, and 0.0025 mg/ml) (Figure 10 and Table 4).

Figure 9: Inhibition zone of Bacillus subtilis

Figure 10: Inhibition zone of Esheriechia coli

The results showed that the most of the tested compounds have good antibacterial and antifungal activity since they have active groups in their molecules, as well as choosing different concentrations of these compounds. The inhibition zone is from (16 mm the lowest inhibition zone to 36 mm the highest inhibition zone of Fungus) (Figures 11 and 12). As for bacteria, it is about (10 mm the lowest inhibition zone to 32 mm the highest inhibition zone of Bacteria). According to the antibacterial studies, the efficacy of the compounds against Gram-positive bacteria is higher than Gram-negative bacteria [16]. The activities were illustrated in (Table 5).

 Comp.   (zone of inhibition in mm) (zone of inhibition in mm)
Conc. Gram. (-)
Bacteria
Escherichia coli
g/mlμ
Gram. (+) bacteria Bacillus   Candida albicans
H1 0.005 16 25 20
0.07 17 19 17
0.025 18 20 25
H4 0.01 16 20 36
0.005 15 17 35
0.15 25 31 -
H7 0.01 - - 17
0.005 - - -
0.15 16 25 27
H17 0.005 17 19 -
0.0025   25 -
0.075   19 -
Ampicillin   20 20 -
Streptomycin       25

Table 5: The antimicrobial activities

Figure 11: Inhibition zone of (H7), (H17) Bacillus subtilis.

Figure 12: Inhibition zone of Candida albicans

Conclusion

Hydrazones have become one of the most important heterocyclic in current chemistry research, due to its important pharmaceutical applications, especially in biological science, and medicinal chemistry. New derivatives of benzothiazole rings were synthesized in this research included a new methodology for a synthesis of hydrazones. All the synthesis derivatives were identified characteristic by some physical properties and surly analyzed by FTIR and1HNMR. All the derivatives exhibited good varied antimicrobial activity.

References

http://sacs17.amberton.edu/

rtp slot demo