Synthesis and antimicrobial evaluation of new thiazolyl-1,2,3-triazolyl-alcohol derivatives

Article abstract of DOI:10.1007/s00044-020-02540-5

A new series of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a-t) have been synthesized by a click reaction of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)ethanone (3a-e) with substituted ethynylbenzene (4a-c) followed by reduc

Full text of DOI:10.1007/s00044-020-02540-5

MEDICINAL
CHEMISTRY
RESEARCH
Medicinal Chemistry Research
https://doi.org/10.1007/s00044-020-02540-5
ORIGINAL RESEARCH
Synthesis and antimicrobial evaluation of new
thiazolyl-1,2,3-triazolyl-alcohol derivatives
Shivaji Jagadale1,2 Abhijit Chavan1 Abhijit Shinde1 Vilas Sisode3 Vivek D. Bobade4 Pravin C. Mhaske1
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Received: 20 January 2020 / Accepted: 30 March 2020
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
A new series of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a-t) have been synthesized by a
click reaction of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)ethanone (3a-e) with substituted ethynylbenzene (4a-c) followed
by reduction with sodiumboro hydride. The newly synthesized 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-
yl)ethanol derivatives were screened for in vitro antibacterial activityagainst a Gram negative strains, Escherichia coli
(National Collection of Industrial Microorganisms, NCIM 2574), a Gram positive strain Staphylococcus albus (NCIM 2178)
and in vitro antifungal activity against Candida albicans (NCIM 3100), Aspergillus niger (American Type Culture
Collection, ATCC 504), Rhodotorula glutinis (NCIM 3168), and Penicillium chrysogenum (NCIM 737). Eight thiazolyl-
1,2,3-triazolyl-alcohol derivatives 6a, 6i, 6j, 6k, 6m, 6n, 6o, and 6p, reported promissing antifungal activity against A. niger
with minimum inhibitory concentration (MIC) 31.25–62.5 µg/mL. Compounds 6d, 6m, and 6p showed good antibacterial
activity against S. albus. It was revealed that, 4-chlorophenyl and 4-fluorophenyl group at position-2 of thiazole ring reported
good activity against A. niger. The substantial antimicrobial activity of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-
triazol-1-yl)ethanol derivatives suggested that, these compounds could assist in the development of lead compounds as a
treatment against microbial infection.
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Keywords Thiazole 1,2,3-Triazole Click reaction Antibacterial activity Antifungal activity
Introduction
Combating infection has become one of the major chal-
lenges to global health, food security and development. The
resistance to antimicrobial drugs threatens the effective
prevention and treatment of an increasing range of bacterial
and fungal infections. Future health management such as
surgery, organ transplantation, cancer chemotherapy and
diabetes treatments will become a high risk issue without
efficient antibiotics (WHO report 2018, Aslam et al. 2018,
Fisher et al. 2018)
Azoles are an important class of heterocyclic compounds
which exhibit a large spectrum of biological activities
(Sheehan et al. 1999, Allen et al. 2015, Choi et al. 2014)
against infectious diseases. 1,3-Thiazole containing com-
pounds exhibit a broad spectrum of biological activities
(Mark et al. 2005) such as antifungal (Gaikwad et al. 2012,
Patil et al. 2015) antibacterial (Tomasic et al. 2015, Brvar
et al. 2012, Mhaske et al. 2017, Shelke et al. 2012) anti-
mycobacterial (Abhale et al 2015, 2016, 2017), antimalarial
(Bueno et al. 2016), antioxidant (Jaishree et al. 2012), anti-
inflammatory (Rostomet al. 2009), and antiviral (Liet al.
Supplementary information The online version of this article (https://
doi.org/10.1007/s00044-020-02540-5) contains supplementary
material, which is available to authorized users.
* Pravin C. Mhaske
mhaskepc18@gmail.com
1
Department of Chemistry—Postgraduation, S. P. Mandali’s Sir
Parashurambhau College (affiliated to Savitribai Phule Pune
University), Tilak Road, Pune 411 030, India
2
Department of Chemistry, S. K. Gandhi Arts, Amolak Science and
P. H. Gandhi Commerce College (affiliated to Dr. Babasaheb
Ambedkar Marathwada University, Aurangabad, Kada, Tal. Ashti,
District Beed 414202, India
3
Department of Chemistry, Abasaheb Garware College (affiliated to
Savitribai Phule Pune University), Pune, India
4
Department of Chemistry—Postgraduation, H. P. T. Arts and R.
Y. K. Science College (affiliated to Savitribai Phule Pune
University), Nashik 422005, India

Medicinal Chemistry Research
Fig. 1 Triazolyl-alcohol,
thiazolyl-triazolyl-alcohol
antifungal drugs and lead
compounds, and our new
proposed analogs (6a–t)
2008). 1,2,3-Triazole derivatives are therapeutically
important in medicinal chemistry and drug discovery
(Dheer et al. 2017, Bonandi et al. 2017), as they exhibit
significant biological activities such as antifungal (Bonandi
et al. 2017, Choi et al. 2014, Kathiravan et al. 2012),
antimicrobial (Calderon et al. 2016, Zhang B 2019) anti-
tubercular (Jadhav et al. 2017, Shaikh et al. 2015, Menen-
dez et al. 2013), antimalarial (Chu et al. 2019), anticancer
(Battula et al. 2017, Ma et al. 2015), anti-inflammatory
(Dmitry et al. 2014), and antiviral (Tian et al. 2018). Tria-
zole alcohols are vital pharmacophore of the azole anti-
fungal drugs (Bozorov et al. 2019, Hashemi et al. 2015,
Emamiet al. 2019) (Fig. 1). 1,2,3-Triazole clubbed with
antibacterial drugs such as Rifampicin–Tobramycin hybrids
showed potential antibacterial activity (Idowu et al. 2019).
The biological importance and structural modification of
thiazole and 1,2,3-triazole have made them a prominent
target for new antimicrobial lead compounds. 1,3-Thiazole
clubbed with other azole derivatives showed antibacterial,
antifungal, and antitubercular activities (Nalawade et al.
2019, Takate et al. 2019). The 1,3-thiazole and 1,2,3-tria-
zole tethered nucleus has received attention in recent years
due to their significant antimicrobial and antitubercular
(Shinde et al. 2018, 2019, Pardeshi et al. 2011, Shiradkar
2007) activities.
spectrometer instruments. Chemical shifts are reported from
internal tetramethylsilane standard and are reported in
δ units.
General procedure for synthesis of 2-azido-1-(4-
methyl-2-phenylthiazol-5-yl)ethanone (3a)
The mixture of 2-bromo-1-(4-methyl-2-phenylthiazol-5-yl)
ethanone (2a) (10 mmol) and sodium azide (0.715 g,
11 mmol) in dimethyl sulphoxide (10 mL) was stirred for
30 min. The progress of the reaction was monitored on thin
layer chromatography (TLC), after completion, the reaction
mixture was quenched in water (50 mL) and stirred for
20 min. The aqueous solution of reaction was extracted with
ethyl acetate (20 mL × 3), the organic layer was washed
with water, dried over anhydrous Na2SO4. Solvent was
removed under vacuum to afford 2-azido-1-(4-methyl-2-
phenylthiazol-5-yl)ethanone (3a), (yield 85%). The crude
product was used for further reaction. Derivative 3b–e was
synthesized by similar protocol (yield 80-88%).
General procedure for synthesis of 1-(4-methyl-2-
phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanone (5a)
Owing to the promising biological activities of thiazole
and 1,2,3-triazole derivatives and in continuation of our
search for new anti-infection agents, we report herein the
synthesis and antimicrobial evaluation of 1-(4-methyl-2-
aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol
derivatives.
The mixture of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)
ethanone (3a) (5 mmol), ethynylbenzene (4a), sodium
ascorbate (1 mmol) and copper sulfate (1 mmol) in DMF:
H2O (3:1) (4 mL) was stirred for 12–24 h. After comple-
tion of reaction (TLC), the reaction was quenched in water
and extracted with ethyl acetate (20 mL × 3), the organic
layer was washed with water, dried over anhydrous
Na2SO4, and solvent was removed under vacuum to afford
1-(4-methyl-2-phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-
triazol-1-yl)ethanone (5a). The crude product was purified
by column chromatography using ethyl acetate:hexane
(2:8) as eluent (yield 76%). Derivatives 5b–t was syn-
thesized using similar experimental procedure (yield
70–85%).
Materials and methods
Chemistry
1H NMR and 13C NMR spectra were recorded on Bruker at
either 500 MHz (1H NMR) and 126 MHz (13C NMR),

Medicinal Chemistry Research
General procedure for synthesis of 1-(4-methyl-2-
phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanol, (6a)
56.53 (CH2,−CH2−Triazole), 21.30 (CH3, Ar−CH3), 15.58
(CH3, Thiazole-CH3); HRMS: m/z = 377.1441 (M + H)+.
2-[4-(4-methoxyphenyl)-1,2,3-triazol-1-yl]-1-(4-
methyl-2-phenyl-1,3-thiazol-5-yl)ethanol, (6c)
To a solution of 1-(4-methyl-2-phenylthiazol-5-yl)-2-(4-
phenyl-1H-1,2,3-triazol-1-yl)ethanone (5a) in methanol
(10 mL), NaBH4 (5 mmol) was added portion wise at
5–10 °C for 15 min. The reaction mixture was stirred for
one hour. After completion of the reaction (TLC), solvent
was distilled under vacuum; the residue was dissolved in
water (20 mL) and extracted with ethyl acetate (20 mL × 3).
Organic layer was washed with water and dried over
anhydrous sodium sulfate. Solvent was removed under
vacuum to obtain 1-(4-methyl-2-phenylthiazol-5-yl)-2-(4-
phenyl-1H-1,2,3-triazol-1-yl)ethanol, (6a) (yield 84%).
Compounds 6b–t was synthesized by same experimental
procedure (yield 70–88%).
1
MF: C21H20N4O2S; yield: 78%; mp: 160–162 °C; H NMR
(500 MHz, DMSO-d6) δ 8.46 (s, 1H, Triazole-H), 7.89 (d,
J = 8.0 Hz, 2H, Ar-H), 7.77 (d, J = 8.8 Hz, 2H, Ar-H),
7.50–7.46 (m, 3H, Ar-H), 7.02 (d, J = 8.8 Hz, 2H, Ar-H),
6.50 (d, J = 4.3 Hz, 1H, OH), 5.37 (dt, J = 7.2, 5.1 Hz, 1H,
CH), 4.61 (qd, J = 13.8, 6.3 Hz, 2H, CH2), 3.79 (s, 3H, O-
CH3), 2.27 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz,
DMSO-d6) δ 164.87 (C, Thiazole-C2), 159.44 (C, C4′′),
149.17 (C, Thiazole-C4), 146.56 (C, Triazole-C4), 134.71
(C, C1′), 133.60 (C, Thiazole-C5), 130.53 (C, C4′), 129.68
(2CH, C2′, C6′), 126.93 (2CH, C2′′, C6′′), 126.23 (2CH,
C3′, C5′), 123.85 (CH, Triazole-C5), 121.83 (C, C1′′),
114.80 (2CH, C3′′, C5′′), 66.19 (CH, Thiazole−CHOH),
56.52 (CH2,−CH−Triazole), 55.62 (CH3, Ar−OCH3), 15.59
(CH3, Thiazole-CH3); HRMS: m/z = 393.1390 (M + H)+.
1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-(4-phenyl-
1,2,3-triazol-1-yl)ethanol, (6a)
MF: C20H17FN4OS; yield: 84%; mp: 138–140 °C; 1H NMR
(500 MHz, DMSO-d6) δ 8.63 (s, 1H, Triazole-H), 7.93 (d, J
= 7.9 Hz, 2H, Ar-H), 7.89 (d, J = 7.1 Hz, 2H, Ar-H),
7.54–7.47 (m, 5H, Ar-H), 7.38 (t, J = 7.4 Hz, 1H, Ar-H),
6.56 (d, J = 4.3 Hz, 1H, OH), 5.43 (dt, J = 7.2, 5.1 Hz, 1H,
CH), 4.68 (qd, J = 13.8, 6.3 Hz, 2H, CH2), 2.33 (s, 3H,
Thiazole-CH3); 13C NMR (126 MHz, DMSO-d6) δ 164.90
(C, Thiazole-C2), 149.19 (C, Thiazole-C4), 146.63 (C,
Triazole-C4), 134.68 (C, C1′), 133.59 (C, Thiazole-C5),
131.25 (C, C1′′), 130.54 (C,C4′), 129.68 (2CH, C2′, C6′),
129.40 (2CH, C3′′, C5′′), 128.30 (CH, Triazole-C5), 126.24
(2CH, C3′, C5′), 125.59 (2CH, C2′′, C6′′), 122.81 (CH, C4′′),
66.17 (CH, Thiazole−CHOH), 56.56 (CH2,−CH2−Tria-
zole), 15.60(CH3, Thiazole-CH3); HRMS: m/z = 363.1287
(M + H)+.
2-[4-(4-fluorophenyl)-1,2,3-triazol-1-yl]-1-(4-methyl-
2-phenyl-1,3-thiazol-5-yl)ethanol, (6d)
MF: C20H17FN4OS; yield: 84%; mp: 168–170 °C; 1H NMR
(500 MHz, DMSO-d6) δ 8.58 (s, 1H, Triazole-H), 7.92–7.87
(m, 4H, Ar-H), 7.48 (dd, J = 7.2, 4.5 Hz, 3H, Ar-H), 7.29
(dd, J = 9.9, 7.9 Hz, 2H, Ar-H), 6.51 (d, J = 4.3 Hz, 1H,
OH), 5.40 – 5.36 (m, 1H, -CH), 4.67–4.59 (m, 2H, –CH2),
2.33 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz, DMSO-
d6) δ 164.90 (C, Thiazole-C2), 163.19 and 161.24 (C, C4′′,
d, 1J = 245.7 Hz), 149.18 (C, Thiazole-C4), 145.77 (C,
Triazole-C4), 134.64 (C, C1′), 133.58 (C, Thiazole-C5),
130.54 (C, C4′), 129.68 (2CH, C2′, C6′), 127.83 and 127.80
4
(C, C1′′, d, J = 3.8 Hz), 127.63 and 127.56 (2CH, C2′′,
3
C6′′, d, J = 8.8 Hz), 126.24 (2CH, C3′, C5′), 122.73 (CH,
4
1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-[4-(4-
methylphenyl)-1,2,3-triazol-1-yl]ethanol, (6b)
Triazole-C5), 116.42 and 116.24 (2CH, C3′′, C5′′, d, J =
22.7 Hz), 66.16 (CH, Thiazole−CHOH), 56.58 (CH2,−CH2
−Triazole), 15.60 (CH3, Thiazole-CH3); HRMS: m/z =
381.1192 (M + H)+.
MF: C20H17BrN4OS; yield: 80%; mp: 150–152 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.51 (s, 1H, Triazole-H),
7.88 (dd, J = 7.7, 1.8 Hz, 2H, Ar-H), 7.73 (d, J = 8.1 Hz,
2H, Ar-H), 7.51–7.45 (m, 3H, Ar-H), 7.26 (d, J = 8.0 Hz,
2H, Ar-H), 6.51 (d, J = 4.3 Hz, 1H, OH), 5.38 (dt, J = 7.2,
5.1 Hz, 1H, CH), 4.62 (qd, J = 13.8, 6.3 Hz, 2H, CH2), 2.33
(s, 3H, Thiazole-CH3), 2.28 (s, 3H, Ar-CH3); 13C NMR
(126 MHz, DMSO-d6) δ 164.89 (C, Thiazole-C2), 149.18
(C, Thiazole-C4), 146.69 (C, Triazole-C4), 137.59 (C, C4′′),
134.69 (C, C1′), 133.59 (C, Thiazole-C5), 130.53 (C, C4′),
129.94 (2CH, C3′′, C5′′), 129.68 (2CH, C2′, C6′), 128.48
(CH, Triazole-C5), 126.23 (2CH, C3′, C5′), 125.53 (2CH,
C2′′, C6′′), 122.36 (C, C1′′), 66.18 (CH, Thiazole−CHOH),
1-[2-(4-bromophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
(4-phenyl-1,2,3-triazol-1-yl)ethanol, (6e)
MF: C20H17BrN4OS; yield: 75%; mp: 140–142 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.62 (s, 1H, Triazole-H),
7.94 (d, J = 8.6 Hz, 2H, Ar-H), 7.89 (d, J = 7.2 Hz, 2H, Ar-
H), 7.59 (d, J = 8.6 Hz, 2H, Ar-H), 7.50 (t, J = 7.7 Hz, 2H,
Ar-H), 7.38 (t, J = 7.4 Hz, 1H, Ar-H), 6.59 (d, J = 4.3 Hz,
1H, OH), 5.47–5.40 (m, 1H, -CH), 4.68 (qd, J = 13.8,
6.2 Hz, 2H, –CH2), 2.32 (s, 3H, Thiazole-CH3); 13C NMR
(126 MHz, DMSO-d6) δ 163.53 (C, Thiazole-C2), 149.34

Medicinal Chemistry Research
(C, Thiazole-C4), 146.64 (C, Triazole-C4), 135.31 (C, C1′),
135.03 (C, Thiazole-C5), 132.40 (C, C4′), 131.23 (C, C1′′),
129.73 (2CH, C3′, C5′), 129.40 (2CH, C3′′, C5′′), 128.30 (CH,
Triazole-C5), 127.92 (2CH, C2′, C6′), 125.59 (2CH, C2′′, C6′′),
122.81 (CH, C4′′), 66.16 (CH, Thiazole−CHOH), 56.51 (CH2,
–CH−Triazole), 15.56 (CH3, Thiazole-CH3); HRMS: m/z =
441.0385 (M + H) + 443.0371 (M + 2 + H)+.
7.97–7.91 (m, 4H, Ar-H), 7.59 (d, J = 8.6 Hz, 2H, Ar-H),
7.34 (t, J = 8.9 Hz, 2H, Ar-H), 6.59 (d, J = 4.3 Hz, 1H,
OH), 5.46–5.40 (m, 1H, -CH), 4.72–4.62 (m, 2H, –CH2),
2.33 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz, DMSO-
d6) δ 163.53 (C, Thiazole-C2), 163.19 and 161.25 (C,−C4′′,
d, 1J = 244.4 Hz), 149.33 (C, Thiazole-C4), 145.78 (C,
Triazole-C4), 135.27 (C, C1′), 135.04 (C, Thiazole-C5),
132.40 (C, C4′), 129.74 (2CH, C3′, C5′), 127.92 (2CH, C2′,
4
1-[2-(4-bromophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-methylphenyl)-1,2,3-triazol-1-yl]ethanol, (6f)
C6′), 127.81 and 127.79 (C, C1′′, d, J = 3.8 Hz), 127.63
3
and 127.56 (2CH, C2′′, C6′′, d, J = 8.8 Hz), 122.74 (CH,
2
Triazole-C5), 116.41 and 116.24 (2CH, C3′′, C5′′, d, J =
MF: C21H19BrN4OS; yield: 84%; mp: 182–184 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.56 (s, 1H, Triazole-H),
7.96–7.92 (m, 2H, Ar-H), 7.77 (d, J = 8.1 Hz, 2H, Ar-H),
7.61–7.57 (m, 2H, Ar-H), 7.30 (d, J = 8.0 Hz, 2H, Ar-H),
6.58 (d, J = 4.3 Hz, 1H, OH), 5.43 (dt, J = 7.1, 5.1 Hz, 1H,
-CH), 4.66 (qd, J = 13.8, 6.2 Hz, 2H, –CH2), 2.38 (s, 3H,
Thiazole-CH3), 2.32 (s, 3H, Ar-CH3); 13C NMR (126 MHz,
DMSO-d6) δ 163.51 (C, Thiazole-C2), 149.34 (C, Thiazole-
C4), 146.70 (C, Triazole-C4), 137.59 C, C4′′), 135.33 (C,
C1′), 135.03 (C, Thiazole-C5), 132.41 (C, C4′), 129.94
(2CH, C3′′, C5′′), 129.73 (2CH, C3′, C5′), 128.47 (CH,
Triazole-C5), 127.92 (2CH, C2′, C6′), 125.53 (2CH, C2′′,
C6′′), 122.37 (C, C1′′), 66.17 (CH, Thiazole−CHOH),
56.49 (CH2,−CH2−Triazole), 21.30 (CH3, Ar−CH3), 15.56
(CH3, Thiazole-CH3); HRMS: m/z = 455.0546 (M + H) +
457.0528 (M + 2 + H)+.
21.4 Hz), 66.15 (CH, Thiazole−CHOH), 56.53 (CH2,−CH
−Triazole), 15.57 (CH3, Thiazole-CH3); HRMS: m/z =
459.0299 (M + H)+. 461.0280 (M + 2 + H)+.
1-[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
(4-phenyl-1,2,3-triazol-1-yl)ethanol, (6i)
MF: C20H17ClN4OS; yield: 88%; mp: 163–165 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.58 (s, 1H, Triazole-H),
7.83 (dt, J = 4.2, 1.7 Hz, 4H, Ar-H), 7.70–7.66 (m, 2H, Ar-
H), 7.45 (t, J = 7.7 Hz, 2H, Ar-H), 7.34 (t, J = 7.4 Hz, 1H,
Ar-H), 6.54 (d, J = 4.3 Hz, 1H, OH), 5.39 (dt, J = 7.0,
5.1 Hz, 1H, -CH), 4.63 (qd, J = 13.8, 6.2 Hz, 2H, –CH2),
2.28 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz, DMSO-
d6) δ 163.61 (C, Thiazole-C2), 149.38 (C, Thiazole-C4),
146.64 (C, Triazole-C4), 135.33 (C, C4′), 132.74 (C, C1′),
132.65 (2CH, C2′, C6′), 131.23 (C, C1′′), 129.40 (2CH,
C3′′, C5′′), 128.31 (CH, Triazole-C5), 128.13 (2CH, C3′,
C5′), 125.59 (2CH, C2′′, C6′′), 123.77 (C, Thiazole-C5),
122.81 (CH, C4′′), 66.16 (CH, Thiazole−CHOH), 56.50
(CH2,−CH−Triazole), 15.56 (CH3, Thiazole-CH3); HRMS:
m/z = 397.0896 (M + H)+, 399.0867 (M + 2 + H)+.
1-[2-(4-bromophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-methoxyphenyl)-1,2,3-triazol-1-yl]ethanol, (6g)
MF: C21H19BrN4O2S; yield: 80%; mp: 160–162 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.51 (s, 1H, Triazole-H),
7.97–7.93 (m, 2H, Ar-H), 7.84–7.79 (m, 2H, Ar-H),
7.61–7.57 (m, 2H, Ar-H), 7.06 (d, J = 8.8 Hz, 2H, Ar-H),
6.58 (d, J = 4.3 Hz, 1H, OH), 5.42 (dt, J = 7.1, 5.0 Hz, 1H,
-CH), 4.65 (qd, J = 13.8, 6.3 Hz, 2H, –CH2), 3.84 (s, 3H,
O-CH3), 2.32 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz,
DMSO-d6) δ 163.50 (C, Thiazole-C2), 159.44 (C, C4′′),
149.34 (C, Thiazole-C4), 146.58 (C, Triazole-C4), 135.35
(C, C1′), 135.03 (C, Thiazole-C5), 132.41 (C, C4′), 129.73
(2CH, C3′, C5′), 127.92 (2CH, C2′, C6′), 126.94 (2CH,
C2′′, C6′′), 123.83 (CH, Triazole-C-5), 121.84 (C, C1′′),
114.80 (2CH, C3′′, C5′′), 66.18 (CH, Thiazole−CHOH),
56.48 (CH2,−CH2−Triazole), 55.62 (CH3, Ar−CH3), 15.56
(CH3, Thiazole-CH3); HRMS: m/z = 471.0498 (M + H)+,
473.0478 (M + 2 + H)+.
1-[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-methylphenyl)-1,2,3-triazol-1-yl]ethanol, (6j)
MF: C21H19ClN4OS; yield: 78%; mp: 198–200 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.51 (s, 1H, Triazole-H),
7.83 (d, J = 8.6 Hz, 2H, Ar-H), 7.73 (d, J = 8.0 Hz, 2H, Ar-
H), 7.68 (d, J = 8.6 Hz, 2H, Ar-H), 7.26 (d, J = 7.9 Hz, 2H,
Ar-H), 6.53 (d, J = 4.3 Hz, 1H, OH), 5.41 – 5.34 (m, 1H,
-CH), 4.62 (qd, J = 13.8, 6.2 Hz, 2H, –CH2), 2.33 (s, 3H,
Ar-CH3), 2.28 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz,
DMSO-d6) δ 163.59 (C, Thiazole-C2), 149.37 (C, Thiazole-
C4), 146.71 64 (C, Triazole-C4), 137.59 (C, C4′′), 135.35
(C, C-4′), 132.74 (C, C1′), 132.64 (2CH, C2′, C6′), 129.93
(2CH, C3′′, C5′′), 128.47 (CH, Triazole-C5), 128.13 (2CH,
C3′, C5′), 125.53 (2CH, C2′′, C6′′), 123.76 (C, Thiazole-C-
5), 122.37 (C, C1′′), 66.18 (CH, Thiazole−CHOH−), 56.48
(CH2,−CH2−Triazole), 21.30 (CH3, Ar−CH3), 15.56 (CH3,
Thiazole-CH3); HRMS: m/z = 411.1052 (M + H) +
0.413.1025 (M + 2 + H)+.
1-[2-(4-bromophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-fluorophenyl)-1,2,3-triazol-1-yl]ethanol, (6h)
MF: C20H16BrFN4OS; yield: 80%; mp: 184–186 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.63 (s, 1H, Triazole-H),

Medicinal Chemistry Research
1-[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-methoxyphenyl)-1,2,3-triazol-1-yl]ethanol, (6k)
= 244.4 Hz), 149.17 (C, Thiazole-C4), 146.64 (C, Triazole-
C4), 134.81 (C, Thiazole-C5), 131.24 (C, C1′′), 130.28 and
4
130.25 (C, C1′, d, J = 3.8 Hz), 129.40 (2CH, C3′′, C5′′),
MF: C21H19ClN4O2S; yield: 85%; mp: 178–180 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.50 (s, 1H, Triazole-H),
7.87 (d, J = 8.6 Hz, 2H, Ar-H), 7.81 (d, J = 8.8 Hz, 2H, Ar-
H), 7.74–7.71 (m, 2H, Ar-H), 7.06 (d, J = 8.8 Hz, 2H, Ar-
H), 6.57 (d, J = 4.3 Hz, 1H, OH), 5.42 (dt, J = 7.1, 5.1 Hz,
1H, -CH), 4.65 (qd, J = 13.8, 6.2 Hz, 2H, –CH2), 3.84 (s,
3H, Ar-OCH3), 2.32 (s, 3H, Thiazole-CH3); 13C NMR
(126 MHz, DMSO-d6) δ 163.59 (C, Thiazole-C2), 159.44
(C, C4′′), 149.37 (C, Thiazole-C4), 146.58 (C, Triazole-
C4), 135.37 (C, C4′), 132.74 (C, C1′), 132.64 (2CH, C2′,
C6′), 128.13 (2CH, C3′, C5′), 126.94 (2CH, C2′′, C6′′),
123.83 (C, C1′′), 123.76 (C, Thiazole-C5), 121.84 (CH,
Triazole-C5), 114.80 (2CH,C3′′, C5′′), 66.19 (CH, Thiazole
−CHOH), 56.46 (CH2,−CH−Triazole), 55.62 (CH3, Ar-
OCH3), 15.55 (CH3, Thiazole-CH3); HRMS: m/z =
427.1002 (M + H)+, 429.0974 (M + 2 + H)+.
128.55 and 128.48 (2CH, C2′, C6′, d, J = 8.8 Hz), 128.30
3
(CH, Triazole-C5), 125.59 (2CH, C2′′, C6′′), 122.80 (CH,
2
C4′′), 116.78 and 116.60 (2CH, C3′, C5′, d, J = 21.4 Hz),
66.15 (CH, Thiazole−CHOH), 56.55 (CH2,−CH2−Tria-
zole), 15.56 (CH3, Thiazole-CH3); HRMS: m/z = 381.1193
(M + H)+.
1-[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-[4-
(4-methylphenyl)-1,2,3-triazol-1-yl]ethanol, (6n)
MF: C21H19FN4OS; yield: 72%; mp: 172–174 °C; 1H NMR
(500 MHz, DMSO-d6) δ 8.55 (s, 1H, Triazole-H), 7.97 (dd,
J = 8.8, 5.4 Hz, 2H, Ar-H), 7.77 (d, J = 8.1 Hz, 2H, Ar-H),
7.36 (t, J = 8.8 Hz, 2H, Ar-H), 7.30 (d, J = 7.9 Hz, 2H, Ar-
H), 6.55 (d, J = 4.3 Hz, 1H, OH), 5.42 (dt, J = 7.2, 5.0 Hz,
1H, -CH), 4.65 (qd, J = 13.8, 6.3 Hz, 2H, –CH2), 2.37 (s,
3H, Ar-CH3), 2.31 (s, 3H, Thiazole-CH3); 13C NMR
(126 MHz, DMSO-d6) δ 163.73 (C, Thiazole-C2), 164.53
and 162.56 (C, C4′, d, 1J = 244.4 Hz), 149.16 (C, Thiazole-
C4), 146.70 (C, Triazole-C4), 137.59 (C, C4′′), 134.83 (C,
1-[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-fluorophenyl)-1,2,3-triazol-1-yl]ethanol, (6l)
MF: C20H16ClFN4OS; yield: 78%; mp: 162–164 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.63 (s, 1H, Triazole-H),
7.94–7.92 (m, 2H, Ar-H), 7.88 (d, J = 8.6 Hz, 2H, Ar-H),
7.73 (d, J = 8.6 Hz, 2H, Ar-H), 7.34 (t, J = 8.9 Hz, 2H, Ar-
H), 6.56 (d, J = 4.3 Hz, 1H, OH), 5.46 – 5.39 (m, 1H, -CH),
4.73–4.63 (m, 2H, –CH2), 2.33 (s, 3H, Thiazole-CH3); 13C
NMR (126 MHz, DMSO-d6) δ 163.61 (C, Thiazole-C2),
Thiazole-C5), 130.28 and 130.26 (C, C1′, d, J = 2.5 Hz),
4
129.93 (2CH, C3′′, C5′′), 128.55 and 128.48 (2CH, C2′,
3
C6′, d, J = 8.8 Hz), 128 48 (C, C1′′), 125.53 (2CH, C2′′,
C6′′), 122.36 (CH, Triazole-C5), 116.77 and 116.60 (2CH,
2
C3′, C5′, d, J = 21.4 Hz), 66.16 (CH, Thiazole−CHOH),
56.52 (CH2,−CH2−Triazole), 21.29 (CH3, Ar−CH3), 15.55
(CH3, Thiazole-CH3); HRMS: m/z = 395.1350 (M + H)+.
1
163.19 and 161.25 (C, C4′′, d, J = 244.4 Hz), 149.18 (C,
Thiazole-C4), 145.79 (C, Triazole-C4), 135.30 (C, C4′),
1-[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-[4-
133.58 C, C1′), 132.65 (2CH, C2′, C6′), 128.13 (2CH, C3′,
(4-methoxyphenyl)-1,2,3-triazol-1-yl]ethanol, (6o)
4
C5′), 127.81 and 127.79 (C, C1′′, d, J = 3.8 Hz), 127.63
3
and 127.57 (2CH, C2′′, C6′′, d, J = 8.8 Hz), 126.24 (C,
MF: C21H19FN4O2S; yield: 70%; mp: 123–125 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.46 (s, 1H, Triazole-H),
7.93 (dd, J = 8.8, 5.4 Hz, 2H, Ar-H), 7.76 (d, J = 8.8 Hz,
2H, Ar-H), 7.32 (t, J = 8.8 Hz, 2H, Ar-H), 7.02 (d, J =
8.8 Hz, 2H, Ar-H), 6.51 (d, J = 4.3 Hz, 1H, OH), 5.37 (dt, J
= 7.2, 5.1 Hz, 1H, -CH), 4.60 (qd, J = 13.8, 6.3 Hz, 2H,
–CH2), 3.79 (s, 3H, Ar-OCH), 2.26 (s, 3H, Thiazole-CH3);
13C NMR (126 MHz, DMSO-d6) δ 163.73 (C, Thiazole-
Thiazole-C5), 122.73 (CH, Triazole-C5), 116.41 and
116.24 (2CH, C3′′, C5′′, d, 2J = 21.4 Hz), 66.16 (CH,
Thiazole−CHOH), 56.58 (CH2,−CH2 − Triazole), 15.60
(CH3, Thiazole-CH3); HRMS: m/z = 415.0802 (M + H)+,
417.0774 (M + 2 + H)+.
1-[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-(4-
phenyl-1,2,3-triazol-1-yl)ethanol, (6m)
1
C2), 164.53 and 162.56 (C, C4′, d, J = 244.4 Hz), 159.44
(C, C4′′), 149.16 (C, Thiazole-C4), 146.57 (C, Triazole-
C4), 134.85 (C, Thiazole-C5), 130.28 and 130.26 (C, C1′,
d, 4J = 2.5 Hz), 128.55 and 128.48 (2CH, C2′, C6′, d, 3J =
8.8 Hz), 126.94 (2CH, C2′′, C6′′), 123.84 (C, C1′′), 121.83
(CH, Triazole-C5), 116.77 and 116.60 (2CH, C3′, C5′, d,
2J = 21.4 Hz), 114.80 (2CH, C3′′, C5′′), 66.17 (CH, Thia-
zole−CHOH), 56.51 (CH2,−CH2−Triazole), 55.62 (CH3,
Ar−OCH3), 15.55 (CH3, Thiazole−CH3); HRMS: m/z =
411.1294 (M + H)+.
1
MF: C20H17FN4OS; yield: 75%; mp: 160-162 °C; H NMR
(500 MHz, DMSO-d6) δ 8.62 (s, 1H, Triazole-H), 7.97 (dd,
J = 8.7, 5.4 Hz, 2H, Ar-H), 7.89 (d, J = 7.3 Hz, 2H, Ar-H),
7.49 (t, J = 7.7 Hz, 2H, Ar-H), 7.37 (dd, J = 17.7, 8.8 Hz,
3H, Ar-H), 6.57 (d, J = 4.3 Hz, 1H, OH), 5.47 – 5.40 (m,
1H, -CH), 4.67 (qd, J = 13.8, 6.3 Hz, 2H, –CH2), 2.31 (s,
3H, Thiazole-CH3); 13C NMR (126 MHz, DMSO-d6) δ
1
163.75 (C, Thiazole-C2), 164.53 and 162.56 (C, C4′, d, J

Medicinal Chemistry Research
2-[4-(4-fluorophenyl)-1,2,3-triazol-1-yl]-1-[2-(4-
fluorophenyl)-4-methyl-1,3-thiazol-5-yl]ethanol,
(6p)
DMSO-d6) δ 165.02 (C, Thiazole-C2), 149.01 (C, Thiazole-
C4), 146.69 (C, Triazole-C4), 140.32 (C, C4′), 137.58 (C,
C4′′), 134.06 (C, Thiazole-C5), 131.03 (C, C1′), 130.20
(2CH, C2′, C6′), 129.93 (2CH, C3′′, C5′′), 128.49 (CH,
Triazole-C5), 126.18 (2CH, C3′, C5′), 125.53 (2CH, C2′′,
C6′′), 122.35 (C, C1′′), 66.17 (CH, Thiazole−CHOH),
56.55 (CH2,−CH2−Triazole), 21.39 (CH3, Ar−CH3), 21.30
(CH3, Ar−CH3), 15.57 (CH3, Thiazole−CH3); HRMS: m/z =
391.1597 (M + H)+.
MF: C20H16F2N4OS; yield: 74%; mp: 182–184 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.58 (s, 1H, Triazole-H),
7.95–7.86 (m, 4H, Ar-H), 7.35–7.27 (m, 4H, Ar-H), 6.53
(d, J = 4.3 Hz, 1H, OH), 5.41 – 5.34 (m, 1H, -CH), 4.67 –
4.58 (m, 2H, –CH2), 2.27 (s, 3H, Thiazole-CH3); 13C NMR
(126 MHz, DMSO-d6) δ 163.75 (C, Thiazole-C2), 164.53
1
and 162.56 (C, C4′, d, J = 244.4 Hz), 163.19 and 161.25
2-[4-(4-methoxyphenyl)-1,2,3-triazol-1-yl]-1-[4-
methyl-2-(4-methylphenyl)-1,3-thiazol-5-yl]ethanol,
(6s)
1
(C, C4′′ J = 244.4 Hz), 149.15 (C, Thiazole-C4), 145.78
(C, Triazole-C4), 134.77 (C, Thiazole-C5), 130.27 and
4
130.25 (C, C1′, d, J = 2.5 Hz), 128.55 and 128.48 (2CH,
C2′, C6′, d,3J = 8.8 Hz), 127.82 and 127.79 (C, C1′′ d, 4J =
3.8 Hz), 127.63 and 127.56 (2CH, C2′′, C6′′, d, 3J =
8.8 Hz), 122.72 (CH, Triazole-C5), 116.77 and 116.60
(2CH, C3′, C5′, d, 2J = 21.4 Hz), 116.41 and 116.24 (2CH,
C3′′, C5′′, d,2J = 21.4 Hz), 66.15 (CH, Thiazole−CHOH),
56.56 (CH2,−CH2−Triazole), 15.56 (CH3, Thiazole−CH3).
HRMS: m/z = 399.1095 (M + H)+.
MF: C22H22N4O2S; yield: 86%; mp: 125–127 °C; 1H
NMR (500 MHz, DMSO-d6) δ 8.50 (s, 1H, Triazole-H),
7.82 (dd, J = 8.5, 3.0 Hz, 4H), 7.33 (d, J = 8.0 Hz, 2H,
Ar-H), 7.06 (d, J = 8.8 Hz, 2H, Ar-H), 6.51 (d, J =
4.3 Hz, 1H, OH), 5.41 (dt, J = 7.2, 5.0 Hz, 1H, -CH), 4.64
(qd, J = 13.8, 6.3 Hz, 2H, –CH2), 3.84 (s, 3H, Ar-OCH3),
2.40 (s, 3H, Ar-CH3), 2.31 (s, 3H, Thiazole-CH3); 13C
NMR (126 MHz, DMSO-d6) δ 165.02 (C, Thiazole-C2),
159.44 (C, C4′′), 149.01 (C, Thiazole-C4), 146.56 (C,
Triazole-C4), 140.32 (C, C4′), 134.08 (C, Thiazole-C5),
131.02 (C, C1′), 130.20 (2CH, C2′, C6′), 126.93 (2CH,
C2′′, C6′′), 126.18 (2CH, C3′, C5′), 123.85 (CH, Tria-
zole-C5), 121.82 (C, C1′′), 114.79 (2CH, C3′′, C5′′),
66.18 (CH, Thiazole−CHOH), 56.54 (CH2,−CH2−Tria-
zole), 55.61 (CH3, Ar−OCH3), 21.39 (CH3, Ar−CH3),
15.57 (CH3, Thiazole−CH3); HRMS: m/z = 407.1548
(M + H)+.
1-[4-methyl-2-(4-methylphenyl)-1,3-thiazol-5-yl]-2-
(4-phenyl-1,2,3-triazol-1-yl)ethanol, (6q)
1
MF: C21H20N4OS; yield: 86%; mp: 190–192 °C; H NMR
(500 MHz, DMSO-d6) δ 8.57 (s, 1H, Triazole-H), 7.84 (d, J
= 7.2 Hz, 2H, Ar-H), 7.77 (d, J = 8.1 Hz, 2H, Ar-H), 7.45
(t, J = 7.7 Hz, 2H, Ar-H), 7.34 (t, J = 7.4 Hz, 1H, Ar-H),
7.29 (d, J = 8.0 Hz, 2H, Ar-H), 6.48 (d, J = 4.3 Hz, 1H,
OH), 5.37 (dt, J = 7.2, 5.1 Hz, 1H, -CH), 4.62 (qd, J = 13.8,
6.3 Hz, 2H, –CH2), 2.35 (s, 3H, Ar-CH3), 2.26 (s, 3H,
Thiazole-CH3); 13C NMR (126 MHz, DMSO-d6) δ 165.05
(C, Thiazole-C2), 149.02 (C, Thiazole-C4), 146.62 (C,
Triazole-C4), 140.34 (C, C4′), 134.03 (C, Thiazole-C5),
131.24 (C, C1′′), 131.01 (C, C1′), 130.21 (2CH, C2′, C6′),
129.40 (2CH, C3′′, C5′′), 128.30 (CH, Triazole-C5), 126.19
(2CH, C3′, C5′), 125.59 (2CH, C2′′, C6′′), 122.79 (CH,
C4′′), 66.16 (CH, Thiazole−CHOH), 56.57 (CH2,−H2
−Triazole), 21.39 (CH3, Ar−CH3), 15.57 (CH3, Thiazole
−CH3); HRMS: m/z = 377.1440 (M + H)+.
2-[4-(4-fluorophenyl)-1,2,3-triazol-1-yl]-1-[4-methyl-
2-(4-methylphenyl)-1,3-thiazol-5-yl]ethanol, (6t)
MF: C21H19FN4OS; yield: 80%; mp: 168–170 °C; 1H NMR
(500 MHz, DMSO-d6) δ 8.58 (s, 1H, Triazole-H), 7.89 (dd,
J = 8.8, 5.5 Hz, 2H, Ar-H), 7.77 (d, J = 8.1 Hz, 2H, Ar-H),
7.29 (dd, J = 12.3, 4.7 Hz, 4H, Ar-H), 6.48 (d, J = 4.3 Hz,
1H, OH), 5.37 (dt, J = 7.1, 5.1 Hz, 1H, -CH), 4.67 – 4.57
(m, 2H, –CH2), 2.35 (s, 3H, Ar-CH3), 2.27 (s, 3H, Thiazole-
CH3); 13C NMR (126 MHz, DMSO-d6) δ 165.04 (C,
Thiazole-C2), 163.19 and 161.24 (C,−C4′′, d, 1J =
245.7 Hz), 149.01 (C, Thiazole-C4), 145.77 (C, Triazole-
C4), 140.33 (C, C4′), 134.00 (C, Thiazole-C5), 131.02 (C,
C1′), 130.20 (2CH, C2′, C6′), 127.83 and 127.81 (C, C1′′,
1-[4-methyl-2-(4-methylphenyl)-1,3-thiazol-5-yl]-2-
[4-(4-methylphenyl)-1,2,3-triazol-1-yl]ethanol, (6r)
1
MF: C22H22N4OS; yield: 80%; mp: 190–192 °C; H NMR
4
3
(500 MHz, DMSO-d6) δ 8.51 (s, 1H, Triazole-H), 7.77 (d, J
= 8.1 Hz, 2H, Ar-H), 7.73 (d, J = 8.1 Hz, 2H, Ar-H),
7.31–7.23 (m, 4H, Ar-H), 6.47 (d, J = 4.3 Hz, 1H, OH),
5.37 (dt, J = 7.2, 5.1 Hz, 1H, -CH), 4.61 (qd, J = 13.8,
6.3 Hz, 2H, –CH2), 2.35 (s, 3H, Ar-CH3), 2.33 (s, 3H, Ar-
CH3), 2.26 (s, 3H, Thiazole-CH3); 13C NMR (126 MHz,
d, J = 2.5 Hz), 127.62 and 127.56 (2CH, C2′′, C6′′, d, J =
7.6 Hz), 126.18 (2CH, C3′, C5′), 122.71 (CH, Triazole-C5),
2
116.41 and 116.24 (2CH, C3′′, C5′′, d, J = 21.4 Hz), 66.16
(CH, Thiazole−CHOH), 56.60 (CH2,−CH2−Triazole), 21.38
(CH3, Ar−CH3), 15.58 (CH3, Thiazole−CH3); HRMS: m/z =
395.1346 (M + H)+.

Medicinal Chemistry Research
Scheme 1 : Synthetic route of thiazolyl-1,2,3-triazolyl-ethanol, 6a–t
Biological activity
plates for fungal assay and allowed to solidify. During the
assay, standard fungal cultures were grown on Potato-
Dextrose broth. 500 µL of 48–72 h old fresh fungal spore
suspension was spread on the agar plates using a sterile
cotton swab to get uniform growth. With the help of well
borer, 5 mm diameter wells were punched on the agar
plates. The wells were filled with 80 µL of the samples and a
vehicle control, DMSO was added to one agar plate. A
standard plate with Fluconazole and Ravuconazole was
used as a positive control. The plates were incubated for a
period of 48–72 h at 30 °C. After the incubation period, the
plates were observed for the clear zone of inhibition. The
zones of inhibition were measured in mm using a measuring
scale and the mean was calculated. The experiments were
carried out in five replicates.
The micro-dilution susceptibility test in Sabouraud
Liquid Medium (Oxoid) was used for the determination of
minimum inhibition concentration (MIC). Stock solution of
the test compounds, Streptomycin, Fluconazole and Ravu-
conazole were prepared in DMSO at concentration of
1000 µg/mL. Two fold serial dilutions of the test com-
pounds solutions were prepared using broth. The final
concentration of the solutions was 500, 250, 125, 62.5,
31.25, 15.62, 7.81, and 3.90 µg/mL. The tubes were
inoculated with the test organisms and kept for incubation
for 48–72 h. at 30 °C. The lowest concentration showing no
growth was considered as MIC. Control experiment with
DMSO and un-inoculated media were run parallel to the test
Antibacterial activity
The in vitro antibacterial screening of the synthesized
thiazolyl-triazole derivatives (6a–t) was performed by the
well diffusion method (Wayne 2002, NCCLS 2000, Mali
et al. 2015). 500 µL of 24–48 h old fresh bacterial culture
were spread over the nutrient agar plates and the cultures
were inoculated using the sterile cotton swab. Using the
well borer, 5 mm diameter wells were punched on the agar
plates. The synthesized compounds were dissolved in
DMSO. The wells were filled with 80 µL of respective
synthesized compounds and a vehicle control, DMSO was
added to one agar plate and standard drug Streptomycin
used as positive control. The plates were incubated for
24–48 h at 37 °C. After the incubation period, the anti-
microbial activity was evaluated by measuring the zone of
inhibition in mm using a measuring scale and the average
was calculated. The experiments were carried out in five
replicates.
Antifungal activity
The in vitro antifungal activity of thiazolyl-triazole deriva-
tives (6a–t) was done by well diffusion method (Wayne
2002, NCCLS 2000, Mali et al. 2015). Mueller-Hinton agar
plates were prepared by pouring 20 mL in each sterile petri-

Medicinal Chemistry Research
compounds under similar conditions. All experiments were
carried in triplicates.
further confirmed by molecular ion peak (HRMS) at m/z:
395.1350 (M + H)+. Structure of all synthesized com-
pounds was confirmed accordingly.
Compounds 1-(4-methyl-2-phenylthiazol-5-yl)-2-(4-phe-
nyl-1H-1,2,3-triazol-1-yl)ethanol derivatives, 6a–t were
evaluated for antibacterial activity against Gram-negative
bacteria E. coli and Gram-positive bacteria S. albus using
well diffusion method (Wayne 2002, NCCLS 2000, Mali
et al. 2015). Standard drug Streptomycin and DMSO were
used as positive and negative control, respectively. The
in vitro antifungal activity was performed against R. gluti-
nis, P. chrysogenum, C. albicans and A. niger using the
well diffusion method. The antifungal drugs Fluconazole
and Ravuconazole were used as reference. All the test
solutions were prepared in DMSO at 1000 µg/mL con-
centrations and the wells were filled with 80 µL (80 µg) of
the samples. The result of antimicrobial activity in the zone
of inhibition (mm) has been presented in supporting infor-
mation (Table S1).
The antimicrobial activity result analysis of 1-(4-methyl-
2-phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanol derivatives, 6a–t revealed that, most of the com-
pounds showed moderate activity against E. coli and
moderate to good activity against S. albus. The preliminary
antifungal activity against R. glutinis, P. chrysogenum, C.
albicans and A. niger revealed that, most of the thiazolyl-
triazolyl-alcohol derivatives reported moderate to good
antifungal activity. The convincing antimicrobial activity
against bacterial and fungal strains of compounds 6a–t
leads us to determine that the microbial inhibition in a dose
dependent way with the concentrations ranges from 500 to
3.90 μg/mL. The in vitro antimicrobial screening results of
minimum inhibitory concentration in μg/mL are presented
in Table 1.
The antimicrobial activity analysis revealed that, the
thiazolyl-1,2,3-triazolyl-ethanol derivatives were less active
against the E. coli and S. albus. The analysis of antifungal
activity presented in Table 1 provided some lead com-
pounds that showed good antifungal activity against A.
niger.
The structure activity relationship revealed that, amongst
the 1-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-
triazol-1-yl)ethanol (6a–d), the compound 6a (R=H,
R1=H) showed comparable activity against A. niger with
respect to the standard drug Ravuconazole. Among the
compounds 6e-t, it was observed that compound with
R=Cl, exhibited better activity against A. niger irrespective
of different R’ groups. Compounds 6m (R=F, R1=H), 6n
(R=F, R1=CH3) showed good activity against A. niger with
MIC 62.5 µg/mL, and were found less active against other
strains. Compound 6o (R=F, R1=OCH3) showed good
activity against A. niger with MIC 31.25 µg/mL comparable
to standard antifungal Ravuconazole. The compound 6p
Results and discussion
Chemistry
The synthetic route for 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-
2-(4-aryl-1,2,3-triazol-1-yl)ethanol derivatives is presented
in Scheme 1. 1-(4-methyl-2-arylthiazol-5-yl)ethanone, 1a–e
on bromination with bromine in dichloromethane gave 2-
bromo-1-(4-methyl-2-arylthiazol-5-yl)ethanone
Bromo derivatives 2a–e on nucleophilic substitution reac-
2a–e.
tion with sodium azide in dimethyl sulphoxide gave 2-
azido-1-(4-methyl-2-arylthiazol-5-yl)ethanone, 3a–e.
A
click reaction of azide 3a–e with substituted aryl alkyne
4a–d in the presence of catalytic sodium ascorbate and
copper sulfate in DMF:water (3:1) gave 1-(4-methyl-2-
phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)etha-
none 5a–t, which upon reduction with NaBH4 in methanol
furnished target compounds 1-(4-methyl-2-phenylthiazol-5-
yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol, 6a–t. The
structure of newly synthesized thiazolyl-1,2,3-triazolyl-
ethanol, 6a–t was confirmed by H NMR, 13C NMR and
mass spectral analysis.
As a representative analysis, of thiazolyl-triazole deri-
vative 1-[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-
[4-(4-methylphenyl)-1,2,3-triazol-1-yl]ethanol (6n), the H
1
1
NMR spectrum revealed the two singlets in the aliphatic
region at δ 2.37 and 2.31 integrated for three protons each
corresponds to -CH3 at C-4 of thiazole and C-4 of phenyl
ring, respectively. A double doublet at δ 4.70–4.61 inte-
grated for one proton each corresponds to diastereotopic
methylene protons. A multiplet appeared at δ 5.44–5.40 and
a doublet at δ 6.55 integrated for one proton each was
assigned to methine proton and alcohol proton of
thiazole–CHOH-CH2 functional group, respectively. The
aromatic protons of fluoro substituted phenyl ring appeared
as a triplet at δ 7.97 and a double doublet at δ 7.36 while the
protons of 4-methyl substituted in the phenyl ring showed
two doublets at δ 7.77 and 7.31. A singlet at δ 8.55, was due
to the proton at C-5-position of 1,2,3-triazole ring. The 13C
NMR spectrum of compound 6n displayed four signals in
aliphatic region at δ 66.16, 56.52, 21.29, and 15.55 corre-
sponds to CH, CH2, Ar-CH3 and thiazole-CH3, respectively.
The carbons of 4-methyl substituted phenyl, 1,2,3-triazole
and thiazole resonated between δ 163.73 and 122.36. The
carbons of fluoro substituted phenyl ring showed typical C-
F coupling, they appeared as four doublets at δ 164.53 and
162.56 (d, 1J = 244.4 Hz), 116.77, and 116.60 (d, 2J =
3
21.4 Hz), 128.55 and 128.48 (d, J = 8.8 Hz), 130.28 and
130.26 (d, 4J = 2.5 Hz). Structure of compound 6n was

Medicinal Chemistry Research
Table 1 Antimicrobial activity
in Minimum Inhibitory
Concentration (μg/mL) of
compounds 6a–t
Comp.
R
R1
E.coli
S.albus
R. glutinis
P.chrysogenum
C. albicans
A.niger
6a
6b
6c
6d
6e
6f
H
H
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
7.81
>250
125
125
125
125
31.25
>250
>250
125
H
4-CH3
4-OCH3
4-F
>250
>250
>250
125
250
250
H
250
250
>250
125
H
62.5
125
250
Br
Br
Br
Br
Cl
Cl
Cl
Cl
F
H
125
250
>250
>250
>250
125
4-CH3
4-OCH3
4-F
250
>250
250
>250
>250
>250
250
250
6g
6h
6i
250
>250
>250
>250
>250
>250
>250
>250
250
250
125
H
>250
>250
>250
125
250
62.5
62.5
62.5
125
6j
4-CH3
4-OCH3
4-F
>250
250
125
6k
6l
250
125
>250
250
6m
6n
6o
6p
6q
6r
6s
6t
H
62.5
>250
125
125
62.5
62.5
31.25
62.5
125
F
4-CH3
4-OCH3
4-F
250
>250
>250
250
F
>250
62.5
250
250
F
62.5
125
>250
>250
125
CH3
CH3
CH3
CH3
H
>250
>250
>250
>250
NA
4-CH3
4-OCH3
4-F
250
250
125
>250
>250
7.81
NA
250
250
250
250
250
250
Streptomycin
Fluconazole
Ravuconazole
NA
NA
NA
NA
7.81
15.62
7.81
7.81
7.81
7.81
7.81
31.25
NA
NA
NA not applicable
MIC of active compounds are highlighted in bold
(R=F, R1=F) reported good activity against A. niger with
MIC 62.5 µg/mL. It is noteworthy that the compounds 6i,
6j, 6k, 6m, 6n, and 6p recorded two fold less activity while
compounds 6a and 6o were seen to exhibit comparable
activity against A. niger with Ravuconazole.
It is worth mentioning, among the twenty derivatives of
1-(4-methyl-2-phenylthiazol-5-yl)-2-(4-phenyl-1H-1,2,3-
triazol-1-yl)ethanol, 6a–t, compounds 6a and 6o found
comparatively active and compounds 6i, 6j, 6k, 6m, 6n, and
6p were found two fold less active against A. niger com-
pared with Ravuconazole.
1-[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]-2-[4-(4-
methoxyphenyl)-1,2,3-triazol-1-yl]ethanol, (6o) reported
comparable antifungal activity against A. niger with respect to
the standard drug Ravuconazole. It is concluded that, 4-
chlorophenyl and 4-fluorophenyl substituted at position-2 of
thiazole ring was found to be more active against A. niger.
Acknowledgements Authors are thankful to S. P. Mandali’s Bhide
Foundation, Pune for supporting biological activity facility. Central
Instrumentation facility, Savitribai Phule Pune University, Pune is also
acknowledged for spectral analysis. A D Shinde is grateful to CSIR-
India for award of SRF, Award No 08/319(0004/)17-EMR-1.
Compliance with ethical standards
Conclusion
Conflict of interest The authors declare that they have no conflict of
interest.
In conclusion, a series of 1-(4-methyl-2-aryl-1,3-thiazol-5-
yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a–t) have been
synthesized. The antimicrobial screening studies of com-
pounds 6a–t was undertaken to evaluate the effects of
substituent on the antimicrobial activities. Most of the
synthesized compounds exhibited good antifungal activity
against A. niger. The compounds 1-(4-methyl-2-phenylthia-
zol-5-yl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol, (6a) and
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
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