Efficient synthesis and antibacterial activities of some novel 1,2,3-triazoles prepared from propargylic alcohols and benzyl azides

Article abstract of DOI:10.1002/jhet.1680

A simple and effective procedure for regioselective preparation of 1,2,3-triazoles from benzyl azides and propargylic alcohols is described using CuSO₄·5H₂O and sodium ascorbate. To screen the antibacterial activity of some newly synthesized triazole derivatives, minimum inhibitory concentration of 3d and 3k was evaluated against gram positive Staphylococcus aureus and Bacillus subtilis and gram negative Escherichia coli and Pseudomonas aeruginosa.

Full text of DOI:10.1002/jhet.1680

1298
Efficient Synthesis and Antibacterial Activities of Some Novel 1,2,3-
Vol 51
Triazoles Prepared from Propargylic Alcohols and Benzyl Azides
a
a
b
*
Rahman Hosseinzadeh, Mohammadreza Khadem Abolfazli, Mojtaba Mohseni,
Maryam Mohadjerani,b and Zahra Lasemic
aDepartment of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
bDepartment of Biology, Faculty of Science, University of Mazandaran, Babolsar, Iran
cIslamic Azad University, Firoozkouh Branch, Iran
*
E-mail: r.hosseinzadeh@umz.ac.ir
Received September 3, 2011
DOI 10.1002/jhet.1680
Published online 17 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
N3
H
N
N
N
HO
R
CuSO4 .5H2O
HO
R
+
R'
Sodium ascorbate
R.T , CH2Cl2 / H2O
R'
X
X
1
2
3
X : H, Br, OCH3
R,R' : CH3 , Ph , Fluorenyl, Ferrocenyl
A simple and effective procedure for regioselective preparation of 1,2,3-triazoles from benzyl azides and
propargylic alcohols is described using CuSO4.5H2O and sodium ascorbate. To screen the antibacterial
activity of some newly synthesized triazole derivatives, minimum inhibitory concentration of 3d and 3k was
evaluated against gram positive Staphylococcus aureus and Bacillus subtilis and gram negative Escherichia coli
and Pseudomonas aeruginosa.
J. Heterocyclic Chem., 51, 1298 (2014).
INTRODUCTION
variety of alkynes [11], only few articles have reported the
use of propargylic alcohols (especially tertiary propargylic
alcohols) for synthesis of triazoles. Therefore, we wish here
to report the synthesis of some new 1,2,3-triazoles by 1,3-
dipolar cycloaddition between azides and propargylic alco-
hols in the presence of CuSO4.5H2O and sodium ascorbate
at room temperature (Scheme 1). The antibacterial activity
of some novel triazoles (3d and 3k) will be also reported.
N-Heterocyclic compounds such as 1,2,3-triazoles have
shown important biological activities, and there are numer-
ous examples in the literature including anti-HIV activity
[1,2], antibacterial activity [3], antiallergic activity [4],
and selective b3 adrenergic receptor agonism [5]. 1,2,3-
Triazoles have also a range of important applications in
industries such as dyes, corrosion inhibition, photostabilizers,
photographic materials, and agrochemicals [6].
Several different methods have been described for
synthesis of 1,2,3-triazoles including the intramolecular
cyclization of bishydrazones or mixed hydrazones and
miscellaneous oxidations, as well as the 1,3-dipolar cyclo-
addition of azides to alkynes [6–8]. Huisgen’s dipolar
cycloaddition of organic azides and alkynes is the most
direct route to 1,2,3-triazoles [9]. However, because of
the high activation energy (ca. 24–26 kcal/mol), these
cycloadditions are often very slow even at elevated tem-
perature (80–120ꢀC for 12–24 h) and produce mixtures
of regioisomers. Recently, copper catalysts have been
reported for the construction of 1,2,3-triazoles. The ‘click’
chemistry reported by Sharpless group described that
the Cu(I)-catalyzed cycloaddition can be conducted at
room temperature and results in 1,4-disubstituted triazoles
in high regioselectivity [10].
RESULTS AND DISCUSSION
Initially, propargylic alcohols were easily synthesized
by treating trimethylsilyl acetylide with the ketones in dry
ether at À10ꢀC. Desilylation of corresponding propargyl
alcohols with K2CO3 in THF and methanol gave desired
products in good yields (Scheme 2).
There are a number of methods for the formation of
azides from halides [12]. We prepared azides from the
reaction between benzyl halides and NaN3 in DMSO at
room temperature [13].
To find the best conditions for the reaction of propargylic
alcohols and azides, the reaction of 1,1-diphenylprop-2-yn-
1-ol and benzyl azide was chosen as model reaction. Differ-
ent solvents and catalysts were screened, and the results are
summarized in Table 1. When 1,1-diphenylprop-2-yn-1-ol
(2a) and benzyl azide were treated with CuSO4.5H2O and
sodium ascorbate at room temperature in different solvents
Although several different methods have been described
for synthesis of 1,2,3-triazoles from azides and a wide
© 2014 HeteroCorporation

September 2014
Synthesis and Antibacterial Activities of Some Novel 1,2,3-Triazoles
1299
Scheme 1
same reaction conditions, very good yields of the triazole
products were obtained (Table 2, entries 9–14). It is inter-
esting to mention that all reactions were regioselective and
gave only expected 1,4-disubstituted triazoles in good yields.
To screen the antibacterial activity of newly synthesized
triazole derivatives, minimum inhibitory concentration
(MIC) was evaluated against gram positive Staphylococcus
aureus and Bacillus subtilis and gram negative Escherichia
coli and Pseudomonas aeruginosa. In addition, the finding
towards inhibition of microorganisms was correlated with
a standard antibiotic tetracycline (Table 3). The results
revealed that the triazole 3k inhibited growth of bacteria
at low concentration of 150 mg/mL, whereas the growth
inhibitory effects of the compound 3d on all bacteria were
shown at high concentration of 250 mg/mL (Table 3). How-
ever, the MIC values for both triazole compounds against
bacteria were high as compared with the standard antibiotic
tetracycline; these results suggest that the compound 3k
exhibited good antibacterial activities and can be further
developed for application as effective antimicrobial agent.
In conclusion, we have developed a simple and efficient
method for the [3 + 2]-cycloaddition of terminal pro-
pargylic alcohols with benzyl azides by CuSO4.5H2O and
sodium ascorbate. The most of 1,4-disubstituted-[1,2,3]-
triazole derivatives are novel compounds and were obtained
in high yields under mild conditions. The MIC of 3d and 3k
were evaluated against gram positive S. aureus and B. sub-
tilis and gram negative E. coli and P. aeruginosa, and the
results show that the compound 3k exhibited good antibac-
terial activities.
N3
H
N
N
N
HO
CuSO4 .5H2O
HO
R
+
R
R'
Sodium ascorbate
R.T , CH2Cl2 / H2O
R'
X
X
1
2
3
X : H, Br, OCH3
R,R' : CH3 , Ph , Fluorenyl, Ferrocenyl
(Table 1, entries 1–5), the best result was achieved in
CH2Cl2/H2O (1:1), and (1-benzyl-1H-1,2,3-triazol-4-yl)
diphenyl methanol (3a) was obtained in 95% yield after
5 h (Table 1, entry 5).
We have also examined the reactivity of some other
catalysts such as Cu(NO3)2.3H2O, CuCl2.2H2O, and Cu
(OAc)2.H2O for the preparation of triazole 3a. The results
show that these catalysts are not efficient to improve the
yield of product, and therefore, CuSO4.5H2O appeared to
be the most efficient catalyst. When 1a was treated with
2a without copper catalyst, no change took place (Table 1,
entry 9), implying that Cu catalyst is essential in this
reaction.
To show the generality of this method, a variety of pro-
pargylic alcohols and benzyl azides was treated with
CuSO4.5H2O (15 mol%) and sodium ascorbate (45 mol%)
in CH2Cl2/H2O (1/1) at room temperature, and results are
presented in Table 2.
As can be seen from Table 2, 1,1-diphenylprop-2-yn-1-ol
reacted with benzyl azide and 4-methoxybenzyl azide
under optimum reaction conditions to give the corresponding
triazoles in good yields (Table 2, entries 1 and 2). Electron-
withdrawing group on the aromatic ring in propargylic
alcohols did not have significant effects on the yields of
the reactions (Table 2, entries 3 and 4). Propargylic alcohols
with fluorenyl and ferrocenyl moieties also gave high yields
of the new triazole products (Table 2, entries 5–8). When
aliphatic propargylic alcohol such as 2-methylbut-3-yn-2-ol
and 1-ethynylcyclohexanol reacted with benzyl azide,
4-methoxybenzyl azide, and 4-bromobenzyl azide under the
EXPERIMENTAL
General.
All commercial chemicals were purchased from
Fluka and Merck and were used without further purification.
Tetracycline was purchased from Sigma-Aldrich (Germany),
Bacto trypto from Quelab (Montreal, Canada) and Yeast extract
from Merck. All the bacteria were purchased from PTTC
(Persian Type Culture Collection) and ATTC (American Type
Culture Collection). Melting points were determined with a
Stuart Scientific SMP1 and Electrothermal 9100 apparatus and
are uncorrected. IR spectra were recorded on a Bruker Vector
Scheme 2
O
OH
1. Et2O, -10 0C
Me3Si
Li
Me3Si
Ar
+
Ar'
Ar
2. H2O
Ar'
4
OH
K2CO3
H
Ar
THF, MeOH
Ar'
2
Ar, Ar'= Ph, Fluorenyl, Ferrocenyl
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1300
R. Hosseinzadeh, M. K. Abolfazli, M. Mohseni, M. Mohadjerani, and Z. Lasemi
Vol 51
Table 1
The solvent and catalyst optimization of reaction 1a and 2a to form 3a.a
N3
H
N
N
N
HO
HO
Conditions
+
Ph
Ph
Ph
Ph
1a
2a
3a
Entry
Catalyst
Solvent
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
CuSO4.5H2O
CuSO4.5H2O
CuSO4.5H2O
CuSO4.5H2O
CuSO4.5H2O
Cu(NO3)2.3H2O
CuCl2.2H2O
Cu(OAc)2.H2O
—
DMSO
DMF
CH3CN
24
24
24
24
5
5
5
5
24
40
40
trace
50
95
90
90
85
—
EtOAc/H2O (1:1)
CH2Cl2/H2O (1:1)
CH2Cl2/H2O (1:1)
CH2Cl2/H2O (1:1)
CH2Cl2/H2O (1:1)
CH2Cl2/H2O (1:1)
aA mixture of 1a, 2a, sodium ascorbate, and 15 mol% CuSO4.5H2O was stirred at room temperature.
bYields of isolated pure product 3a.
22 FT-IR spectrometer using potassium bromide pellets. The 1H-
NMR and 13C-NMR spectra were recorded on a Bruker Avance
III 400 MHz and Bruker Avance DRX 500 MHz spectrometer in
CDCl3. CHN analyses were obtained from a CHN Elemental
Analyzer LECO 600. The progress of the reactions was checked
by TLC chromatography on Merck silica-gel 60 F-254 plates.
Silica gel (70-230 mesh) was used for column chromatography.
À10ꢀC under argon to a stirred solution of ketone (22 mmol) in dry
ether. Then, the solution allowed warm up to room temperature.
After completion of the reaction as monitored by TLC, water
(30 mL) was added to the reaction mixture and then extracted with
ether (2 Â 30 mL). The organic layer was dried over anhydrous
sodium sulfate. After filtration, the solution concentrated under
reduced pressure, and the residue recrystallized from n-hexane-
dichloromethane to yield 9-(trimethylsililethynyl) alcohol.
1-(4-Chlorophenyl)-3-(trimethylsilyl)-1-phenylprop-2-yn-1-
ol. Yield 85%, pale yellow oil; 1H NMR (400 MHz, CDCl3):
d 0.38 (s, 9H), 3.31 (s, 1H), 7.34–7.45 (m, 5H), 7.63–7.72 ppm
(m, 4H); 13C NMR (100 MHz, CDCl3): d 0.02, 74.31, 92.50,
107.57, 126.09, 127.64, 128.00, 128.44, 128.47, 133.57,
143.58, 144.56. Anal. Calcd for C18H19ClOSi: C, 68.66; H,
6.08; found: C, 68.32; H, 5.90.
General procedure for the preparation of benzyl azide (1)
[11a]. To a solution of NaN3 (0.065g, 1 mmol) in dry DMSO
(2 mL) was added benzyl halide (1 mmol). The reaction mixture was
stirred at room temperature for 5 h. After completion of the reaction,
dichloromethane (30 mL) and water (30 mL) were added to the
reaction mixture, and the mixture was transferred into a separatory
funnel. Organic layer was washed with water (30 mL), dried over
anhydrous Na2SO4 and concentrated by a rotary evaporator.
Benzyl azide (1a).
Yield 98%, IR (KBr, υ cmÀ1): 2850,
9-(2-Trimethylsilylethynyl)-flouren-9-ol.
Yield 80%, mp
1
1
2100, 1720; H NMR (400 MHz, CDCl3): d 4.31 (s, 2H), 7.28–
7.39 ppm (m, 5H), 13C NMR (100 MHz, CDCl3): d 54.74,
128.21, 128.28, 128.81, 135.38.
120–122ꢀC [14]; H NMR (400 MHz, CDCl3): d 0.17 (s, 9H),
2.50 (s, 1H), 7.32–7.41 (m, 4H), 7.60 (d, J = 7.2 Hz, 2H),
7.69 ppm (d, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
À0.16, 75.05, 88.34, 104.82, 120.14, 124.33, 128.55, 129.63,
139.19, 147.06.
4-Methoxybenzyl azide (1b). Yield 80%, IR (KBr, υ cmÀ1):
1
2850, 2100, 1600; H NMR (400 MHz, CDCl3): d 3.84 (s, 3H),
4.29 (s, 2H), 6.95 (d, J = 8.8 Hz, 2H), 7.28 ppm (d, J = 8.8 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 54.39, 55.28, 114.22,
127.43, 129.78, 159.67.
1-Ferrocenyl-3-(trimethylsilyl)-1-phenylprop-2-yn-1-ol. Yield
82%, mp 119–121ꢀC [15]; IR (KBr, υ cmÀ1): 3565, 2321, 1500,
1
1420, 1250; H NMR (500 MHz CDCl3): d (ppm) = 0.31 (s, 9H),
4-Bromobenzyl azide (1c). Yield 98%, IR (KBr, υ cmÀ1):
3.07 (s, 1H), 4.15 (br.s, 1H), 4.21 (br.s, 1H), 4.30 (s, 5H), 4.34 (br.
s, 1H), 4.39 (br.s, 1H), 7.23 (t, J=7.4Hz, 1H), 7.29 (t, J=7.5Hz,
2H), 7.62 ppm (d, J= 7.9 Hz, 2H); 13C NMR (125 MHz, CDCl3): d
0.09, 65.10, 68.28, 68.50, 69.08, 71.7, 89.41, 96.84, 125.62,
127.59, 128.01, 143.90.
1
2830, 2100, 1500; H NMR (400 MHz, CDCl3): d 4.30 (s, 2H),
7.19 (d, J = 6.4 Hz, 2H), 7.51 ppm (d, J = 6.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 54.06, 122.31, 129.82, 131.98, 134.41.
General procedure for the preparation of trimethylsilylethynyl
alcohol (4).
To a stirred solution of trimethylsilylacetylene
General procedure for the preparation of propargylic
(2.5mL, 26mmol) in dry ether (25mL) was added a solution of
n-BuLi 1.5 M (16 mL, 24 mmol) during 0.5 h at À10ꢀC under
argon. Stirring was continued 1 h at the same temperature. The
resulting trimethylsilyl acetylide solution was added dropwise at
alcohols (2).
Trimethylsilylethynyl alcohols (12 mmol) was
reacted with K2CO3 (72 mmol) in MeOH (45 mL) and THF
(45 mL). After completion of the reaction, the solvent was
evaporated. The solid was dissolved in water–ethyl acetate
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2014
Synthesis and Antibacterial Activities of Some Novel 1,2,3-Triazoles
1301
Table 2
Preparation of 1,2,3-triazoles from benzyl azides and propargyl alcohols.
Entry
Azide
Alkynol
1,2,3-Triazole
Time (h)
5
Yield (%)a
1
2
3
PhCH2N3 1a
95
97
90
N
N
H
N
OH
OH
3a
2a
2a
4-MeOPhCH2N3 1b
5
N
H
N
N
OH
OH
MeO
3b
4-MeOPhCH2N3 1b
5
N
H
N
N
OH
OH
MeO
Cl
Cl
3c
2b
2b
4
4-BrPhCH2N3 1c
3
83
N
H
N
N
OH
OH
Br
Cl
Cl
3d
5
PhCH2N3 1a
6
85
N
H
N
N
OH
OH
3e
2c
2c
6
4-MeOPhCH2N3 1b
3
95
N
H
N
N
OH
OH
MeO
3f
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1302
R. Hosseinzadeh, M. K. Abolfazli, M. Mohseni, M. Mohadjerani, and Z. Lasemi
Vol 51
Table 2
(Continued)
Entry
7
Azide
Alkynol
1,2,3-Triazole
Time (h)
6
Yield (%)a
75
PhCH2N3 1a
N
N
H
N
OH
OH
Fe
Fe
3g
2d
8
4-MeOPhCH2N3 1b
4
90
N
H
N
N
OH
OH
MeO
Fe
Fe
3h
2d
9
PhCH2N3 1a
3
80
N
H
N
N
OH
Me
OH
Me
Me
Me
3i
2e
10
4-MeOPhCH2N3 1b
3
85
N
H
N
N
OH
OH
Me
MeO
Me
Me
Me
3j
2e
11
4-BrPhCH2N3 1c
3
88
N
H
N
N
OH
Me
OH
Me
Br
Me
Me
3k
2e
2f
12
PhCH2N3 1a
2
90
N
H
N
N
OH
OH
3l
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2014
Synthesis and Antibacterial Activities of Some Novel 1,2,3-Triazoles
1303
Table 2
(Continued)
Entry
Azide
4-MeOPhCH2N3 1b
Alkynol
1,2,3-Triazole
Time (h)
2
Yield (%)a
94
13
N
N
H
N
OH
OH
MeO
3m
2f
2f
14
4-BrPhCH2N3 1c
2
95
N
N
H
N
OH
OH
Br
3n
aAll of the products were identified by NMR, IR and elemental analysis.
bYields refer to isolated products.
(100 mL). After separation of organic layer, the solvent was
evaporated to give a solid, which recrystallized from n-hexane-
dichloromethane to obtain propargylic alcohols 2.
General procedure for preparation of triazoles (3). To a
solution of azide (1 mmol) in CH2Cl2/H2O (5 mL) were added
propargylic alcohol (1 mmol), sodium ascorbate (0.090 g, 45 mol
%) and CuSO4.5H2O (0.038 g, 15 mol%). The reaction mixture
was stirred at room temperature. After completion of the
reaction as monitored by TLC, dichloromethane (15 mL) and
water (15 mL) were added, and the reaction mixture was
transferred into a separatory funnel. Organic layer was washed
with water (30 mL) and saturated NaCl solution (30 mL), dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The crude product was purified by recrystallization by
using a mixture of n-hexane and dichloromethane.
1-(4-Chlorophenyl)-1-phenylprop-2-yn-1-ol (2b).
Yield
1
75%, pale yellow oil [16]; H NMR (400 MHz, CDCl3): d 2.92
(s, 1H), 3.12(s, 1H), 7.30–7.40 (m, 5H), 7.55–7.63 ppm (m,
4H); 13C NMR (100 MHz, CDCl3): d 73.85, 75.92, 85.96,
125.93, 127.51, 128.12, 128.44, 128.46, 133.75, 143.05, 144.05.
9-Ethynyl-9-flourenol (2c).
Yield 83%, mp 107–109ꢀC
1
[17]; H NMR (400 MHz, CDCl3): d 2.50 (s, 1H), 2.60 (s, 1H),
7.38 (dt, J = 9.3, 1.5 Hz, 2H), 7.44 (dt, J = 9.2, 1.6 Hz, 2H), 7.64
(dd, J = 8.8, 0.8 Hz, 2H), 7.73 ppm (dd, J = 8.8, 0.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d 7.41, 74.59, 83.85, 120.28, 124.27,
128.66, 129.89, 139.13, 146.60.
(1-Benzyl-1H-1,2,3-triazol-4-yl)diphenylmethanol (3a). Yield
1
95%, mp 135–136ꢀC [18]; H NMR (400 MHz, CDCl3): d 3.84(s,
1-Ferrocenyl-1-phenylprop-2-yn-1-ol (2d). Yield 78%, mp
1H), 5.51(s, 2H), 7.09 (s, 1H), 7.25–7.39 ppm (m, 15H); 13C NMR
(100 MHz, CDCl3): d 54.17, 65.33, 122.41, 127.19, 127.53,
127.89, 128.05, 128.75, 129.13, 134.55, 145.63, 158.44.
91–93ꢀC [15a]; IR (KBr, υ cmÀ1): 3520, 3250, 2350, 1518,
1
1350, 1100; H NMR (500 MHz CDCl3): d 2.81 (s, 1H), 3.19
(s, 1H), 4.18 (br.s, 1H), 4.26 (br.s, 1H), 4.32 (m, 6H), 4.48 (br.
s, 1H), 7.26–7.32 (m, 3H), 7.62 ppm (pseudo br.s, 2H); 13C
NMR (125 MHz, CDCl3): d 65.18, 68.35, 68.55, 69.11, 71.24,
86.87, 96.67, 125.55, 127.74, 128.10, 143.83. Anal. Calcd for
C19H16FeO: C, 72.18; H, 5.10; found: C, 72.30; H, 5.15.
(1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)diphenylmethanol
(3b).
Yield 97%, mp 134–135ꢀC; IR (KBr, υ cmÀ1): 3410,
1
3140, 3060, 2930, 2810, 1560, 1350, 750; H NMR (400 MHz,
CDCl3): d 3.82(s, 3H), 5.43(s, 2H), 6.90 (d, J = 8.8 Hz, 2H), 7.07
(s, 1H), 7.21(d, J = 8.8 Hz, 2H), 7.27–7.35 ppm (m, 10 H); 13C
NMR (100 MHz, CDCl3): d 53.74, 55.34, 62.87, 114.49, 122.23,
126.52, 127.50, 128.03, 129.50, 132.66, 145.68, 154.44, 159.90.
Anal. Calcd for C23H21N3O2: C, 74.37; H, 5.70; N, 11.31; found:
C, 74.23; H, 5.73; N, 11.27.
Table 3
(1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)(4-chlorophenyl)
(phenyl)methanol (3c). Yield 90%, mp 116–118ꢀC; IR (KBr,
υ cmÀ1): 3394, 2950, 2837, 1514, 1257, 823,765; 1H NMR
(400 MHz, CDCl3): d 3.82 (s, 3H), 4.02 (s,1H), 5.42 (s, 2H),
6.90 (d J = 8.4 Hz, 2H), 7.06 (s, 1H), 7.21 (d J = 8.4 Hz, 2H),
7.27–7.29 ppm (m, 9H); 13C NMR (100 MHz, CDCl3): d 53.79,
55.35, 76.34, 114.50, 122.17, 126.39, 127.10, 127.72, 128.16,
128.30, 128.71, 129.55, 133.37, 144.29, 145.25, 154.02,
159.92. Anal. Calcd for C23H20ClN3O2: C, 68.06; H, 4.97; N,
10.35; found: C, 68.02; H, 4.83; N, 10.18.
Minimum inhibitory concentration of the compounds 3d and 3k.
Minimum inhibitory concentration (mg/mL)
Strain
Compound 3d Compound 3k Tetracycline
E. coli
250
250
250
250
200
150
150
150
25
50
10
25
P. aeruginosa
S. aureus
B. subtilis
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1304
R. Hosseinzadeh, M. K. Abolfazli, M. Mohseni, M. Mohadjerani, and Z. Lasemi
Vol 51
(1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)(4-chlorophenyl)
CDCl3): d 30.45, 53.33, 68.41, 119.31, 122.79, 129.75, 132.20,
133.71, 156.33. Anal. Calcd for C12H14BrN3O: C, 48.67; H, 4.76;
N, 14.19; found: C, 48.68; H, 4.81; N, 14.18.
(phenyl) methanol (3d). Yield 83%, mp 123–125ꢀC; IR (KBr,
υ cmÀ1): 3422, 3155, 3060, 1609, 1591, 814, 762; 1H NMR
(400 MHz, CDCl3): d 4.54 (s, 1H), 5.38 (s, 2H), 7.08 (d J=8.4Hz,
2H), 7.11 (s, 1H), 7.22–7.30 (m, 9H), 7.47 ppm (d J= 8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 53.44, 60.48, 122.57, 122.94,
127.11, 127.74, 128.16, 128.18, 128.74, 129.59, 132.31, 133.36,
133.52, 144.28, 145.23, 154.30. Anal. Calcd for C22H17BrCl N3O2:
C, 58.11; H, 3.77; N, 9.24; found: C, 58.28; H, 3.66; N, 9.05.
9-(1-Benzyl-1H-1,2,3-triazol-4-yl)-9H-fluoren-9-ol (3e). Yield
85%, mp 140–141ꢀC; IR (KBr, υ cmÀ1): 3520, 3130, 3090, 2890,
1485, 750; 1H NMR (400 MHz, CDCl3): d 3.65 (s, 1H), 5.44
(s, 2H), 7.15 (s, 1H), 7.21–7.66 ppm (m, 13H); 13C NMR
(100 MHz, CDCl3): d 54.15, 63.86, 120.19, 120.45, 124.88,
128.06, 128.36, 128.73, 129.09, 129.46, 134.39, 139.58, 147.83,
150.82. Anal. Calcd for C22H17N3O: C, 77.86; H, 5.05; N, 12.38;
found: C, 77.42; H, 5.09; N, 12.08.
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)cyclohexanol (3l).
Yield
1
90%, mp 114–116ꢀC; IR (KBr, υ cm ): 3350, 2830, 2760, 1450,
715, 220; 1H NMR (400 MHz, CDCl3): d 1.31–1.94 (m, 10H), 2.70
(s, 1H), 5.48 (s, 2H), 7.25–7.38 ppm (m, 6H); 13C NMR (100 MHz,
CDCl3): d 25.35, 38.08, 40.89, 54.13, 69.47, 119.63, 128.10,
128.69, 129.09, 134.68, 156.14. Anal. Calcd for C15H19N3O: C,
70.01; H, 7.44; N, 16.33; found: C, 69.65; H, 7.62; N, 16.68.
1-(1-(4-Methoxybenzyl-1H-1,2,3-triazol-4-yl)cyclohexanol
(3m).
Yield 94%, mp 83–85ꢀC; IR (KBr, υ cmÀ1): 3420, 3210,
2890, 2784, 1509, 1210, 870; 1H NMR (400 MHz, CDCl3): d
1.50–1.97 (m, 10H), 2.55 (s, 1H), 3.80 (s, 3H), 5.42 (s, 2H), 6.89
(d, J=8.4Hz, 2H), 7.22 (d, J=8.4Hz, 2H), 7.34ppm (s, 1H); 13C
NMR (100 MHz, CDCl3): d 21.94, 25.35, 38.08, 53.69, 55.33,
69.49, 114.45, 119.33, 126.61, 129.72, 155.96, 159.88. Anal. Calcd
for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62; found: C, 66.70; H,
7.62; N, 14.56.
9-(1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)-9H-fluoren-9-
ol (3f). Yield 95%, mp 109–111ꢀC; IR (KBr, υ cmÀ1): 3312, 3145,
1
3065, 2839, 1614, 1453, 755; H NMR (400 MHz, CDCl3): d 3.71
1-(1-(4-Bromobenzyl-1H-1,2,3-triazol-4-yl)cyclohexanol
(3n). Yield 95%, mp 128–130ꢀC; IR (KBr, υ cmÀ1): 3382, 3123,
2928, 2854, 1344, 1144, 890; 1H NMR (400 MHz, CDCl3): d
1.53–1.96 (m, 10H), 2.00 (s, 1H), 5.47 (s, 2H), 7.16 (d, J=8.4Hz,
2H), 7.38 (s, 1H), 7.52 ppm (d, J= 8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 21.93, 25.32, 38.12, 53.47, 69.58, 119.47, 122.91, 129.73,
132.30, 133.68, 156.42. Anal. Calcd for C15H18BrN3O: C, 53.58; H,
5.40; N, 12.50; found: C, 53.54; H, 5.49; N, 12.46.
(s, 3H), 5.27 (s, 2H), 6.79 (d, J= 9.2 Hz, 2H), 7.10 (d, J=9.2Hz,
2H), 7.15 (s, 1H), 7.25 (dt, J=7.6, 1.2Hz, 2H), 7.34 (dt, J=7.6,
1.2 Hz, 2H), 7.58 (d, J=7.6 Hz, 2H), 7.60 ppm (d, J=7.6 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 53.58, 55.28, 78.59, 114.37,
120.15, 120.48, 124.96, 126.46, 128.31, 129.36, 129.65, 139.56,
148.00, 150.81, 159.73. Anal. Calcd for C23H19N3O2: C, 74.71; H,
5.18; N, 11.37; found: C, 74.32; H, 5.22; N, 11.29.
(1-Benzyl)-1H-1,2,3-triazol-4-yl)(phenyl)(ferrocenyl)methanol
(3g). Yield 75%, mp 115–116ꢀC; IR (KBr, υ cmÀ1): 3498, 3150,
3060, 2800, 1480, 1295, 790; 1H NMR (400 MHz, CDCl3): d 3.76
(s, 1H), 4.13–4.25 (m, 9H), 5.50 (d, J = 14.8 Hz, 1H), 5.53 (d,
J = 14.8 Hz, 1H), 7.22–7.45 ppm (m, 11H); 13C NMR (100 MHz,
CDCl3): d 53.43, 66.66, 68.22, 68.28, 68.64, 73.23, 121.15,
126.24, 127.17, 127.77, 127.84, 128.71, 129.13, 134.87, 145.29,
155.06. Anal. Calcd for C26H23FeN3O: C, 69.50; H, 5.16; N,
9.35; found: C, 69.23; H, 5.01; N, 9.15.
(1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)(phenyl)(ferrocenyl)
methanol (3h). Yield 90%, mp 141–142ꢀC; IR (KBr, υ cmÀ1):
3490, 2850, 1630, 1250, 499; 1H NMR (400 MHz, CDCl3): d 3.62
(s, 1H), 3.81 (s, 3H), 4.13–4.34 (m, 9H), 5.40 (d, J= 15.2 Hz, 1H),
5.44 (d, J= 15.2 Hz, 1H), 6.90 (d, J= 8.4 Hz, 2H), 7.18–7.30 (m,
6H), 7.46 ppm (d, J= 8.4 Hz, 2H); 13C NMR (400 MHz, CDCl3): d
53.62, 55.37, 67.87, 69.22, 69.66, 69.84, 73.14, 114.49, 120.85,
126.25, 126.80, 127.17, 127.79, 129.44, 145.01, 154.70, 159.86.
Anal. Calcd for C27H25FeN3O2: C, 67.65; H, 5.26; N, 8.77; found:
C, 67.28; H, 5.17; N, 8.55.
Antibacterial assay.
The in vitro biocidal screening,
antibacterial activities of the synthesized triazoles assayed onto
LB medium contained: Bacto™ Tryptone, 10.0 g/L; yeast extract,
5.0 g/L; NaCl, 5.0 g/L; and glucose, 1.0 g/L [20]. The medium
was dispensed into universal bottles and sterilized at 121ꢀC for
15min. The synthesized triazoles were dissolved into DMSO and
filter sterilized using a 0.22 mm Ministart (Sartorius). The sterile
synthesized stock solutions were added into LB medium to give a
final concentration of 1–300 mg/mL as required [21]. The
antibacterial activities of the triazoles compounds were compared
with known antibiotic tetracycline at the same concentration.
Minimum inhibitory concentrations of the compounds were
assayed using a standard method against some bacteria including
E. coli PTCC 1330, P. aeruginosa PTCC 1074, S. aureus ATCC
35923 and B. subtilis PTCC 1023. Late exponential phase of the
bacteria was prepared by inoculating 1% (v/v) of the cultures into
the fresh LB medium and incubating on an orbital shaker at 37ꢀC
and 100 rpm overnight. Before using the cultures, they were stan-
dardized with a final cell density of approximately 108 cfu/mL. A
1% (v/v) inoculums of each culture was inoculated into the LB
medium containing different concentration of the synthesized
compounds and incubated on the orbital shaker at 37ꢀC and
100 rpm. The compound sensitivity of the strains was assayed
for positive or negative growth after 24–48 h.
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3i) [19]. Yield
1
80%, mp 78–80ꢀC; H NMR (400 MHz, CDCl3): d 1.62 (s, 6H),
2.75 (s, 1H), 5.50 (s, 2H), 7.27–7.39 ppm (m, 6H); 13C NMR
(100 MHz, CDCl3): d 30.44, 54.21, 68.45, 119.13, 128.17, 128.77,
29.13, 134.56, 156.16.
2-(1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl)propan-2-ol
(3j).
Yield 85%, mp 86–88ꢀC [19]; 1H NMR (400 MHz,
CDCl3): d 1.59 (s, 6H), 2.87 (s, 1H), 3.79 (s, 3H), 5.41 (s, 2H),
6.88 (d, J = 8.4Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.34ppm
(s, 1H); 13C NMR (100MHz, CDCl3): d 30.43, 53.66, 55.34,
68.44, 114.44, 118.92, 126.58, 129.76, 156.00, 159.87.
Acknowledgment. We are thankful to the Research Council of
University of Mazandaran for the support of this work.
2-(1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)propan-2-ol
(3k).
Yield 88%, mp 115–117ꢀC; IR (KBr, υ (cmÀ1): 3200,
REFERENCES AND NOTES
2917, 2787, 2287, 1014, 954; 1H NMR (400 MHz, CDCl3): d
1.57 (s, 6H), 3.43 (s, 1H), 5.39 (s, 2H), 7.10 (d, J = 7.6 Hz, 2H),
7.39 (s, 1H), 7.44ppm (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz,
[1] Alvarez, R.; Velazquez, S.; San, F.; Aquaro, S.; De, C.; Perno, C.
F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J Med Chem 1994, 37, 4185.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2014
Synthesis and Antibacterial Activities of Some Novel 1,2,3-Triazoles
1305
[2] Velazquez, S.; Alvarez, R.; Perez, C.; Gago, F.; De, C.;
[11] (a) Kacprzak, K. Synlett 2005, 943. (b) Chassaing, S.; Kumarraja,
M.; Sani Souna Sido, A.; Pale, P.; Sommer, J. Org Lett 2007, 9, 883. (c)
Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Tetrahedron Lett 2009, 50,
2358. (d) Fletcher, J. T.; Walz, S. E.; Keeney, M. E. Tetrahedron Lett 2008,
49, 7030. (e) Lee, B. Y.;Park, S. R.; Jeon, H. B.; Kim, K. S. Tetrahedron Lett
2006, 47, 5105. (f) Ackermann, L.; Potukuchi, H. K.; Landsberg, D.; Vicente,
R. Org Lett, 2008, 10, 3081.
[12] Grundmann, C. In Houben-Wely, Methoden Der Organischen
Chemie; Muller, E., 4th Ed.; Thieme: Stuttgart, 1965; Vol 10/3, 777.
[13] Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 413.
[14] Dunn, J. A.; Hunks, W. J.; Ruffolo, R.; Rigby, S. S.; Brook,
M. A.; Mc. Glinehey, M. J. Organometallics 1999, 18, 3372.
[15] (a) Asgari, S. MSc Thesis, University of Mazandaran, Babolsar,
Iran, 2008. (b) Skibar, W.; Kopacka, H.; Wurst, K.; Salzmann, C.; Ongania,
K. H.; Fabrizi de Biani, F.; Zanello, P.; Bildstein, B. Organometallics 2004,
23, 1024.
[16] Saikachi, H.; Kitagawa, T. Yakugaku Zasshi, 1969, 89, 1626.
[17] Shapiro, S. L.; Sodoway, H.; Freedman, L. J Am Chem Soc
1955, 77, 4874.
[18] Zhang, L.; Chen, X.; Xue, P.; Herman H. Y.; Williams, I.
D.; Sharpless, K. B.; Fokin, V. V.; Jia, G. J Am Chem Soc 2005,
127, 15998.
[19] Kitamura, Y.; Taniguchi, K.; Maegawa, T.; Monguchi, Y.;
Kitade, K.; Sajiki, H. Heterocycles 2009, 77, 521.
[20] Smejkal, C. W.; Vallaeys, T.; Burton, S. K.; Lappin-Scott, H.
M. Lett Appl Microbiol 2001, 32, 273.
Balzarini, J.; Camarasa, M. J. Antivir Chem Chemother 1998, 9, 481.
[3] (a) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn,
M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester,
J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C.; W. Zurenko,
G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J Med Chem
2000, 43, 953. (b) Gallardo, H.; Conte, G.; Bryk, F.; Lourenço, M. C. S.;
Costa, M. S.; Ferreira, V. F. J Braz Chem Soc 2007, 18, 1285.
[4] Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J
Med Chem 1986, 29, 2262.
[5] Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore, M. R.;
Cascieri, M. A.; Colwell, L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.;
Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.; Fisher, M. H.;
Weber, A. E. Bioorg Med Chem Lett 2000, 10, 2111.
[6] Fan, W. Q.; Katritzky, A. R. In Comprehensive Heterocyclic
Chemistry II; Ress, C. W., Scriven, E. F. V., Eds.; Elsevier Science:
Oxford, 1996; Vol 4, pp 1–4.
[7] Fuks, R.; Viehe, H. G. In Chemistry of Acetylenes; Viehe, H.
G., Ed.; Marcel Dekker: New York, 1969; pp 425–593.
[8] Bastide, J.; Henri-Rousseau, O. In The Chemistry of the
Carbon-Carbon Triple Bond; Patai, S., Ed. Interscience Publisher:
London, 1978; pp 447–552.
[9] Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa,
A., Ed. Wiley: New York, 1984.
[10] (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew Chem Int
Ed 2001, 40, 2004. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Sharpless, K. B. Angew Chem Int Ed 2002, 41, 2596. (c) Tornꢀe, C.
W.; Christensen, C.; Meldal, M. J Org Chem 2002, 67, 3057. (d) Kolb,
H. C.; Sharpless, K. B. Drug Discov Today 2003, 8, 1128.
[21] Husain, A.; Nami, S. A. A.; Siddiqi, K. S. J Mol Struct 2010,
970, 117.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet