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Vijay Kumar Yadav*
, Meena Bhandari and Satbir Singh
Department of Chemistry, School of Basic and Applied Sciences, K. R. Mangalam University, Gurugram, Haryana, India.
Corresponding Author E-mail: kumar.vijaychemistry@gmail.com
Article Publishing History
Article Received on : 12 Aug 2023
Article Accepted on :
Article Published : 06 Dec 2023
The condensation reaction of Benzil with semicarbazide followed by a triazine ring formation and then subsequent interaction with substituted aromatic aldehydes, resulted in synthesis of aromatic hydrazone derivatives (C1 – C4). These derivatives have been synthesized via greener method using acetic acid rather than conc. Sulfuric acid. The resultant compounds were analyzed using spectral (1H-NMR, IR) and elemental analysis. The in-vitro analysis of these compounds portrayed prominent activity against bacterial and fungal strains.
KEYWORDS:Antifungal activities; Antibacterial activities; Green synthesis; Hydrazones
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Copy the following to cite this article:Yadav V. K, Bhandari M, Singh S. Green Synthesis and Antimicrobial Activities of Some Aromatic Hydrazones. Orient J Chem 2023;39(6).
Yadav V. K, Bhandari M, Singh S. Green Synthesis and Antimicrobial Activities of Some Aromatic Hydrazones. Orient J Chem 2023;39(6). Available from: https://bit.ly/41pFhdv
Introduction
Hydrazones are the organic compounds with basic structure >C=NNH2. They are obtained by interaction of a carbonyl compound with a hydrazide (or hydrazine) in an organic solvent. However, recently there have been attractive developments leading to greener, efficient and economical methods for their synthesis such as – synthesis in aqueous medium, synthesis using grinding technique, microwave irradiation method, one-pot synthesis, biosynthesis, etc. 1-6. Hydrazones and their complexes receive focus of researchers as they demonstrate prominent reactivity and showcase significance in multiple areas of research i.e.; materialistic chemistry, pharmaceutics and biological significance viz., anti-oxidant, anti-tumor, anti-malarial, anti-cancer, anti-inflammatory and antimicrobial activities, etc. 7-14. The present scenario demands of newer drugs exhibiting microbial resistance against variety of pathogens including bacteria and fungi; along with easier synthetic approach 15,16. Herein this research paper, we have reported green synthesis and antimicrobial activities of some Hydrazone derivatives.
Materials and Methods
The commercially procured chemicals (from Sigma Aldrich/Merck) were used without purification. Hydrogen, Carbon and Nitrogen were analyzed on a Perkin-Elmer C, H, N and S II series 2400 analyzer. IR spectra were recorded on a Perkin Elmer FTIR spectrophotometer (Spectrum version 10.4.00) using KBr pellets in the range 4000-400 cm-1. 1H-NMR spectra were obtained on Bruker-Avance III 600 MHz using TMS as internal reference in DMSO-d6.
Green Synthesis of Thione (Scheme 1)
To a mixture of Benzil (1mmol) and thiosemicarbazide (1mmol); acetic acid was added and contents were refluxed in water for about 3 hours. The obtained precipitate was filtered under vacuum, washed with water twice, dried in an oven for about 3-4 hours to obtain solid orange-red compound A (m.p.: 221-223◦C, Yield: 94%).
Synthesis of Hydrazone (Scheme 1)
Thione (A, 2.5g, 9.42mmol) and hydrazine hydrate (5mL) in water were refluxed for about 4 hours and then Acetic acid was added to neutralize the pH. The obtained precipitate was filtered under vacuum, washed with water, dried in an oven for about 3-4 hours to obtain solid yellowish compound B (m.p.: 176-177◦C, Yield: 89%).
Synthesis of Hydrazone Derivatives (Scheme 1)
A mixture of Hydrazone (B, 1mmol) and aldehyde (R-CHO, 1mmol) in ethanol was refluxed for about 2 hours. Contents were cooled and the obtained precipitate was filtered under vacuum, washed twice with water and dried in electric oven for about 3-4 hours to obtain the final compounds C1-C4.
Results and Discussion
All the resultant hydrazine derivatives (C1-C4) were synthesized as shown in Scheme 1. In the very first step, A was prepared via a condensation pathway using acetic acid, skipping the use of conc. sulfuric acid. In the next step, compound A and hydrazine hydrate interacted to produce the Hydrazone B. In the final step, compound B and substituted aromatic aldehydes reacted to result in the formation of respective Hydrazone derivatives C1-C4. Final compounds were obtained in 83-91% yield. Physical and analytical results are given in Table 1.
Table 1: Analytical and physical data for compounds C1-C4.
S. No.
Compound
Molecular Formula
M.P. (°C)
% Observed Yield
(% Yield while using conc. H2SO4)
Elemental Analysis % found (% calcd.)
C
H
N
1.
Compound C1
C22H17N5O
271-272
86 (83)
72.13
(71.92)
4.47
(4.66)
18.88
(19.06)
2.
Compound C2
C24H22N6
262-263
91 (78)
73.19
(73.07)
5.78
(5.62)
21.11
(21.30)
3.
Compound C3
C23H19N5O
266-267
87 (82)
72.29
(72.42)
5.18
(5.02)
18.42
(18.36)
4.
Compound C4
C26H19N5O
310-311
83 (88)
74.68
(74.80)
4.63
(4.59)
16.64
(16.78)
IR Spectra (Table 2)
IR Spectra of the Hydrazone derivatives were observed in region of 4000-400 cm-1. These spectra were studied and analyzed based upon some key peaks as recorded 17-20. The presence of signals in spectra of all the derivatives C1-C4 in region 3250-3210 cm-1 correspond to ν(N-H) which was originally present in compound B, confirming that no deprotonation occurred during synthesis of final compounds 18. Presence of peaks in 1520-1515 cm-1 range assigned to ν(N=C), confirms the formation of azomethine link 20.
Signals in the region 1620-1595 cm-1and 1285-1245cm-1 are attributed to ν(C=C) and ν(C-C), respectively. Peaks observed in 1065-1050 cm-1region are assigned to ν(C-H, aromatic) present in all the compounds.
Table 2: IR spectral data for compounds C1-C4.
S. No.
Compound
υ(N-H)
υ(C=C)
υ(C=N)
υ(C-C)
υ(C-H)
1.
Compound C1
3240
1620
1515
1280
1060
2.
Compound C2
3210
1595
1505
1275
1050
3.
Compound C3
3250
1615
1510
1245
1055
4.
Compound C4
3245
1610
1520
1285
1065
1H-NMR Spectra (Table 3)
The presence of signals observed in 12.33-11.65 ppm region in the proton spectra of compounds C1, C2, C3 and C4can be attributed to –NH protons 17. Additionally, signals observed in the regions 9.68-8.20 ppm and 8.24-6.78 ppm are assigned to =CH and aromatic protons; respectively [19, 20]. Peak observed at 2.99 ppm in C2 and 3.75 ppm in C3 have been assigned to the methyl protons; whereas peaks observed at 11.44 ppm in C1 and 12.79 ppm in C4 have been assigned to the hydroxyl (-OH) protons.
Table 3: 1H-NMR spectral data for compounds C1-C4
S. No.
Compound
1H NMR (600 MHz, Me2SO–d6)
1.
Compound C1
δ 12.23 (1H, NH), 11.44 (1H, OH), 8.42 (1H, =CH-), 7.45-7.33 (11H, Ar-H), 7.23 (1H, Ar-H), 6.91–6.87 (2H, Ar-H)
2.
Compound C2
δ 11.65 (1H, NH), 9.68 (1H, =CH-), 7.56 (2H, Ar-H), 7.48 (3H, Ar-H), 7.41–7.38 (7H, Ar-H), 6.78 (2H, Ar-H), 2.99 (6H, CH3)
3.
Compound C3
δ 11.78 (1H, NH), 8.20 (1H, =CH-), 7.64 (2H, Ar-H), 7.44 (3H, Ar-H), 7.34 (7H, Ar-H), 6.98 (2H, Ar-H), 3.75 (3H, CH3)
4.
Compound C4
δ 12.79 (1H, OH), 12.33 (1H, NH), 9.35 (1H, =CH-), 8.24 (1H, Ar-H), 7.92 (2H, Ar-H), 7.63 (1H, Ar-H), 7.54 (2H, Ar-H), 7.49 (1H, Ar-H), 7.46–7.40 (8H, Ar-H), 7.33 (1H, Ar-H)
Antimicrobial Activities (Table 4, Figure 1)
The synthesized derivatives were tested for their antimicrobial significance against B. subtilis ATCC 6051, E. coli ATCC 8739, C. glabrata ATCC 15545 and A. niger ATCC 1015). Ciprofloxacin and Itraconazole were used as control drugs using Kirby-Bauer well diffusion method 21-23. Strains were swabbed on Sabouraud’s Dextrose Agar as MH (Muller Hinton) Agar medium and plates were incubated for about 48 hours at 28°C.
Anti-microbial evaluation reveals that the derivatives (C1-C4) show promising activities against all these pathogens. Compound C2 showcased the best activity against all the strains in comparison to other derivatives, which may be owed to the presence of the tertiary amino group. Overall; the derivatives showed better anti-fungal significance in comparison to their anti-bacterial activities.
Table 4: Antimicrobial activity results for compounds C1-C4
S. No.
Compound
MIC concentrations (µg/mL)
Bacterial Strain
Fungal Strain
B. subtilis ATCC 6051
E. coli
ATCC 8739
C. glabrata ATCC 15545
A. niger
ATCC 1015
1.
Compound C1
1000
750
500
500
2.
Compound C2
500
250
250
250
3.
Compound C3
750
750
750
500
4.
Compound C4
500
500
500
500
5.
Ciprofloxacin
25
25
—
—
6.
Itraconazole
—
—
10
5
Conclusion
In the present work; green syntheses of some Hydrazone derivatives have been reported. The use of organic solvents and sulfuric acid was eliminated as the reactions were carried out in aqueous medium. The anti-microbial evaluation of these compounds demonstrates significant biological activity against B. subtilis, E.coli, C. glabrata and A. niger. In comparison to other analogues, compound C2 showed best activities against the bacterial and fungal strains.
Acknowledgement
The reported work here received no funding.
Conflict of Interest
There are no conflicts of interest.
References
Pouramiri, B.; Seyedhosseini, S.R.; Nematollahi, M.H.; Faramarz, S.; Seyedi, F.; Ayati A.; Polycyclic Aromatic Compounds 2023, 43, 176.
This work is licensed under a Creative Commons Attribution 4.0 International License.
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