Chemical Methodologies 6(2022) 604-611

Journal homepage: http://chemmethod.com

Original Research Article

Synthesis and Characterization of New 1,3,4-Thiadiazole

Derivatives Containing Azo Group from Acid Hydrazide and
Studying Their Antioxidant Activity
Zainab Amer* , Entesar O. Al-Tamimi
Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq

ARTICLE INFO ABSTRACT

Article history The present report describes the synthesis of new the synthetic route that
started by the reaction of acid hydrazide derivatives with ammonium
Submitted: 2022-03-20 thiocyanate to give compounds 1a-d. 1,3,4-thiadiazole derivatives 2a-d
Revised: 2022-04-13 were synthesized by the reaction compounds 1a-d with concentration
Accepted: 2022-05-18 sulfuric acid. Finally, the reaction 1,3,4-thiadiazole derivatives 2a-d with
Manuscript ID: CHEMM-2204-1489 sodium nitrate and hydrochloric acid in 0-5 °C to form diazonium salt, then
Checked for Plagiarism: Yes diazonium salt reacted with 4-dimethylaminobenzaldehyde to synthesize
Language Editor: azo compounds 3a-d. These new synthesized products were characterized
by FT-IR, 1H-NMR for some of them and were studied regarding the effect
Dr. Behrouz Jamalvandi
of preparing derivatives on antioxidant activity.
Editor who approved publication:
Dr. Abdolkarim Zare

DOI:10.22034/CHEMM.2022.338522.1489
KEYWORDS
1,3,4-Thiadiazole
Azo compound
Acid hydrazide
Antioxidant activity

GRAPHICAL ABSTRACT

* Corresponding author: Zainab Amer

 E-mail: zainabsallal34@gmail.com
© 2022 by SPC (Sami Publishing Company)
 Amer Z., et al./ Chem. Methodol., 2022, 6(8) 604-611
Introduction melting point apparatus was used to measure
The knowledge of chemistry of heterocyclic melting points. Shimadzu model FT-IR-8400S
compounds represents a basic point for the was used to take FT-IR measurements. 1H-NMR
development of new heterocyclic compounds that spectra were collected in D2O solution using a
have an important role in agrochemical, Bruker spectrophotometer ultra-shield at 400
pharmaceuticals and materials science [1]. MHz using TMS as an internal standard.
Structurally, diazoles are composed of five-
membered rings containing two nitrogen atom Synthesis of compounds 1a-d [22]
and other non-carbon atom of either oxygen or Zainab A. et al. [23] prepared acid hydrazide, a
Sulphur as heteroatoms like oxadiazoles and mixture of acid hydrazide (0.02 mol), ammonium
thiadiazol and play an important role in biological thiocyanate (0.02 mol) and concentrated
processes, especially heterocycles that contain hydrochloric acid (8 mL) in absolute ethanol (50
nitrogen, because of their wide use in medicinal mL) was refluxed for 20 h. The solvent was
scaffolds for active agents [2]. The 1,3,4- evaporated and residue poured on crushed ice
thiadiazole nucleus, which makes up the azole with stirring. Table 1 lists the physical properties
group, is a versatile pharmacophore and exhibits of the synthesized derivatives 1a-d.
a wide variety of biological activities. In addition
to the 1,3,4-thiadiazole, there are three other Synthesis of 1,3,4-thiadiazole 2a-d [22]
isomers: 1,2,3-thiadiazole, 1,2,4-thiadiazole and
Concentrated sulfuric acid (10 mL) was added to
1,2,5-thiadiazole. 1,3,4-thiadiazole its derivatives
substituted thiosemicarbazone 1a-d (0.05 mol).
have become interesting over the past few years
The mixture was heated on water bath 90 °C with
and found wide applications in pharmaceuticals,
stirring for 2 h, the mixture was then poured onto
dyes, photographic materials, agrochemicals and
ice-water and neutralized with concentrated
corrosion inhibition. They showed anticancer
ammonia solution with cooling; the formed
activity against different types of cancer, such as
precipitate was filtered and washed with ether
liver, cervical, colon, gastric, breast, melanoma,
and recrystallized from ethanol. Table 1 lists the
lung, colorectal, bone [3-6], antifungal [7, 8], anti-
physical properties of the synthesized 1,3,4-
inflammatory [9], antibacterial activity [10] and
thiadiazole 2a-d.
antiparasitic [11, 12]. Currently microbial
resistance to drugs is a concern in medicinal Synthesis of azo compounds 3a-d [24]
chemistry, which can be due to gene transfer or
excessive drug usage. Over the last few decades, In beaker 1, (0.02 mol) of 1,3,4-thiadiazole 2a-d
there has been an increase in drug resistance and was dissolved in 8 mL of concentrated
in the detection of hospital-acquired infections hydrochloric acid and cooled to 0 °C. 0.02 mol of
caused by multidrug resistant strains and this sodium nitrate was prepared in 10 mL water and
situation is considered a public health problem. this solution was poured to beaker 1 drop by
This drug resistance has compromised the drop in ice bath. The resulting mixture, i.e.
treatment of infectious diseases and at the same diazonium salt, remained in ice bath. The third
time has stimulated the search for new bioactive solution containing 0.02 mol of 4-
substances. The antibacterial and antifungal dimethylaminobenzaldehyde was dissolved in
properties associated with the thiadiazol nucleus sodium acetate (10 mL) in beaker 2. Beaker 1
have been widely researched as anti-microbial was added to beaker 2 and the addition should be
[13-15], antitumor [16, 17], anti-convulsant [18, gradual with keeping low temperature. The
19], antioxidant [20] and antidepressant [21]. resulting product was recrystallized. Table 2 lists
the physical properties of the synthesized azo
Materials and Methods compounds 3a-d.
All ingredients and solvents were obtained from
Fluka and Sigma-Aldrich. Gallen Kamp capillary
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 Amer Z., et al./ Chem. Methodol., 2022, 6(8) 604-611
Antioxidant activity [25] solution was measured using a
The solution was protected from light by spectrophotometer at 517 nm. The following
covering the test tubes with aluminum foil. DPPH equation was used to determine the potential to
(4 mg) was dissolved in 100 mL of ethanol. Some scavenge DPPH radicals.
of the produced compounds were used to make
various concentrations of 25, 50, 100 ppm. It was I% = (Absorption blank–Absorption
made by dissolving 1 mg of the chemical in 10 mL sample)/Absorption blank × 100
of ethanol to make 100 ppm, then diluting it to 50
Results and Discussion
and 25 ppm. The concentrations were made in
the same way. 1 mL of the diluted or normal Acid hydrazide derivatives were used to make
solution 25, 50, 100 ppm was added to 1 mL of new 1,3,4-thiadiazole 3a-d with an azo group
DPPH solution in a test tube. After 1 h of Scheme 1 and the mechanism of synthesis 1,3,4-
incubation at 37 °C, the absorbance of each thiadiazole Scheme 2.

Scheme 1: All synthesis compounds 1a-d, 2a-d and 3a-d

Scheme 2: The mechanism of synthesis 1,3,4-thiadiazole

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 Amer Z., et al./ Chem. Methodol., 2022, 6(8) 604-611
Stretching vibrations band to the NH2 group at stretching vibration bands for these compounds
3421-3301 cm-1 and absorption bands to the C=S were displayed in Table 1. Finally, in the FT-IR
group at 1118-1174 cm-1 were observed in the spectra of azo compounds containing 1,3,4-
FT-IR spectra of derivatives 1a-d [26]. These thiadiazole 3a-d stretching vibrations bands to
compounds' other stretching vibration bands the NH2 group disappeared and stretching
were shown in Table 1. The stretching vibration vibrations bands to the N=N azo group appeared
bands to the C=S group disappeared in the FT-IR at 1541-1546 cm-1 and stretching vibrations band
spectra of 1,3,4-thiadiazole derivatives 2a-d, but to the C=O aldehyde group appeared at 1731-
stretching vibration bands to the C=N thiadiazol 1747 cm-1.
ring at 1639-1649 cm-1 appeared and the other
Table 1: The physical properties and FT-IR spectral data cm-1 of synthesized compounds 1a-d and 2a-d
physical properties Major FT-IR absorption cm-1
υ(C=O)
υ(C-H)
υ(C-H) Imidazoline υ(C=O)
m.p. (°C)

Yield%

Aliphatic υ(NH2) Other

color

No. Structure of compounds Aromatic υ(C=O) Imide

Asy. bands
aliphatic
Sy.
Amide
185-187
Brown

2950 3440 1697 1797 υ (C=S)

1a -
75

2889 3310 1639 1772 1170

160-162

2979 3411 1712 1795 υ (C=S)

Gray

1b 3031
70

2896 3303 1674 1770 1170

υ(C=S)
1118
228-230
Brown

2977 3421 1706 1787

1c 3066 υ(NO2)
68

2831 3386 1663 1746

1375
1552
υ (C=S)
215-217
Brown

2947 3433 1697 1799 1174

1d 3014
78

2850 3396 1654 1772 υ (Cl)

748
210-212
Brown

2950 3433 1701 1795 υ (C=N)

2a -
60

2879 3390 1687 1768 1641

225-227
Brown

2906 3427 1797 υ (C=N)

2b 3012 1699
74

2877 3300 1768 1639

υ (C=N)
1645
207-209
Brown

2950 3431 1795

2c 3031 1718 υ (NO2)
82

2890 3301 1768

1396
1539
υ (C=N)
242-244
Brown

2990 3419 1795 1649

2d 3022 1697
70

2850 3352 1760 υ (Cl)

721

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 Amer Z., et al./ Chem. Methodol., 2022, 6(8) 604-611
The other stretching vibration bands for these percentage and compression with ascorbic acid.
compounds are shown in Table 2. 1H-NMR The decrease in absorbance at 517 nm was used
spectrum [27] of compounds 1a, 2b, 2c and 3b to measure the DPPH radical's ability to reduce.
are listed in Table 3. The procedure was used to Furthermore, organic compounds with an
measure antioxidant activity based on the DPPH electron donating group (NH2, OCH3, and OH) that
stable free radical sweep effect, the antioxidant can operate as free radical agents and resist
function of some selective synthesized of some oxidation have been extensively established.
produced compounds, and ascorbic acid. Figure 1 depicts that the molecule 1,3,4-
Table 4 shows some of the newly synthesized thidiazole (1b, 1d, and 2d) has the highest
compounds and antioxidant activity against antioxidant activity [28].
DPPH free radicals, with a high scavenging

Table 2: The physical properties and FT-IR spectral data cm-1 of synthesized compounds 3a-d
physical properties Major FT-IR absorption cm-1

Aldehyde

Aldehyde
Aromatic
Aliphatic
m.p.(°C)

υ(N=N)
Diazole
υ(C=N)

υ(C=O)

υ(C=O)
Yield%

υ(C-H)

υ(C-H)

υ(C-H)

Bands
Imide

Other
Color

Asy.
No. Structure of compounds Sy.
277-279
orange

2890
2966

3014

1546
1623

2773
1739

1770
1797
3a
67

-
186-188
Yellow

2821
2914

3020

1544
1649

2786
1743

1770
1795
3b
73

-
222-224

υ (NO2)
Orange

2871
2900

3035

1542
1652

2825
1747

1770
1793

1512
1386
3c
76

υ (Cl) 717
205-207
Orange

2890
2945

3026

1541
1652

2779
1731

1770
1797

3d
68

Table 3: 1H-NMR spectral data (δ ppm) for some compounds

Compound 1H-NMR data of δH in ppm

2.09 (S, 3H, CH3), 2.45-2.76 (t, 4H, CH2-CH2), 2.95 (S, 3H, N-CH3), 4.10 (S, 2H,
1a
CH2-CO), 3.92 (S, 1H, NH2), 7.89 (S, 1H, NH-C=S), 8.16 (S, 1H, NH-C=O).
2.39-2.59 (t, 4H, CH2-CH2), 3.0 (S, 3H, N-CH3), 4.16 (S, 2H, CH2-CO), 6.87-7.13
2b
(m, 5H, Ar-H), 3.56 (S, 1H, NH2).
2.52-2.78 (t, 4H, CH2-CH2), 2.95 (S, 3H, N-CH3), 4.27 (S, 2H, CH2-CO), 7.18-7.31
2c
(m, 4H, Ar-H), 4.0 (S, 1H, NH2).
1.3 (s, 6H, N(CH3)2), 2.32-2.67 (t, 4H, CH2-CH2), 3.12 (S, 3H, N-CH3), 4.23 (S, 2H,
3b
CH2-CO), 6.92-8.22 (m, 8H, Ar-H), 10.12 (S, 1H, CHO).

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Table 4: Scavenging % for some of prepare compounds
Compound No. Scavenging %
25 mg/mL 50 mg/mL 100 mg/mL
1b 37.00 57.57 73.28
1c 29.28 42.00 54.14
1d 67.92 81.35 87.64
2a 36.42 48.85 61.57
2b 27.71 38.07 59.00
2d 59.00 69.07 72.71
3a 43.00 50.28 59.07
3b* 28.71 36.28 50.57
Ascorbic acid 80.95 89.25 93.54

Figure 1: Scavenging comparison between the prepared compounds and ascorbic acid

Conclusion
Authors' contributions
The prepared new 1,3,4-thiadiazole containing
All authors contributed toward data analysis,
azo group from acid hydrazide derivatives were
drafting and revising the paper and agreed to
confirmed by using spectroscopic techniques (FT-
responsible for all the aspects of this work.
IR and 1H-NMR). The antioxidant activity of the
most compounds were strongly compressed with
Conflict of Interest
ascorbic acid.
We have no conflicts of interest to disclose.
Acknowledgments
ORCID:
The authors would like to extend their sincere
appreciation to the Deanship at Baghdad Zainab Amer
University College of Science, and thank everyone https://www.orcid.org/0000-0002-3578-6387
who helped them to complete this research.
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HOW TO CITE THIS ARTICLE

Zainab Amer, Entesar O. Al-Tamimi. Synthesis and Characterization of New 1,3,4-Thiadiazole Derivatives Containing Azo
Group from Acid Hydrazide And Studying Their Antioxidant Activity. Chem. Methodol., 2022, 6(8) 604-611
https://doi.org/10.22034/CHEMM.2022.338522.1489
URL: http://www.chemmethod.com/article_150963.html

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