Iodine-mediated C-N and N-N bond formation: A facile one-pot synthetic approach to 1,2,3-triazoles under metal-free and azide-free conditions

Article abstract of DOI:10.1039/c9ra06005g

A novel strategy towards the synthesis of 1,4-disubstituted 1,2,3-triazoles via C-N and N-N bond formation has been demonstrated under transition metal-free and azide-free conditions. These 1,2,3-triazoles were obtained in a regioselective manner from commercially available anilines, aryl alkenes/aryl alkynes and N-tosylhydrazines using I₂ under O₂ atmosphere. Broad substrate scope, milder reaction conditions, good to moderate yields and clean protocol are the notable features of the method. Moreover, this protocol is amenable for the generation of a library of medicinally important key building blocks.

Full text of DOI:10.1039/c9ra06005g

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Iodine-mediated C–N and N–N bond formation:
a facile one-pot synthetic approach to 1,2,3-
triazoles under metal-free and azide-free
conditions†
Cite this: RSC Adv., 2019, 9, 27021
a
Geeta Sai Mani,a Kavitha Donthiboina,a Siddiq Pasha Shaik,b Nagula Shankaraiah
*
abc
*
and Ahmed Kamal
A novel strategy towards the synthesis of 1,4-disubstituted 1,2,3-triazoles via C–N and N–N bond formation
has been demonstrated under transition metal-free and azide-free conditions. These 1,2,3-triazoles were
obtained in a regioselective manner from commercially available anilines, aryl alkenes/aryl alkynes and
N-tosylhydrazines using I2 under O2 atmosphere. Broad substrate scope, milder reaction conditions,
good to moderate yields and clean protocol are the notable features of the method. Moreover, this
protocol is amenable for the generation of a library of medicinally important key building blocks.
Received 2nd August 2019
Accepted 21st August 2019
DOI: 10.1039/c9ra06005g
rsc.li/rsc-advances
as being conditioning agents for plant growth.5j Additionally,
the 1,2,3-triazole moiety is an ideal linker that has been widely
Introduction
utilized in the recent past to bridge the two components in
order to get the synergistic effect of the combined molecules
and it is relatively resistant to hydrolysis reactions.6 Beyond
pharmaceutical applications, the structural features of 1,2,3-
triazole facilitate to mimic various functional groups justifying
its use as a bioisostere in the synthesis of biologically active
molecules.7 Moreover, due to the hydrogen-bonding ability of
1,2,3-triazole connecting to a poorly soluble drug could enhance
their solubility aspects and accordingly a better pharmacoki-
netic prole is achieved.8 Owing to their utility, a wide range of
applications and many novel synthetic protocols have been
developed by many researchers for the regioselective formation
of this ve-membered heterocycle and it is highly exploring
motif in organic synthesis.
Nitrogen-containing heterocyclics constitute a major class of
bioactive organic compounds which are essential for life and
widely distributed in natural products and synthetic pharma-
ceuticals.1 They form a structural part of vitamins, hormones,
etc and are fundamental for metabolism in living cells.2 Their
unique ability to serve as biomimetics and reactive pharmaco-
phores has facilitated their use as low molecular weight lead
molecules in drug design.3 Particularly, 1,2,3-triazole contrib-
utes a noteworthy role among the pharmaceutically important
nitrogen-containing heterocyclic scaffolds due to its broad
spectrum of biological activities. Active pharmaceuticals based
on
1,2,3-triazoles
including
tert-butyldimethylsilylspir-
oaminooxathioledioxide (TSAO, non-nucleoside reverse tran-
scriptase inhibitor),4a carboxyamidotriazole (CAI, anticancer),4b
cefatrizine4c and tazobactum (b-lactam antibiotic)4d are shown
in Fig. 1. Over the past few years, our research group has
signicantly developed many novel 1,2,3-triazole bearing
molecules with anticancer activities.4e–k Moreover, they are also
reported to have anti-inammatory,5a anticonvulsant,5b anti-
viral,5c antihistaminic,5d antileishmanial,5e peptidomimetic
tyrosinase inhibitory,5f hepatitis C virus inhibitory,5g neuro-
leptic5h and adenosine receptor inhibitory5i properties, as well
Numerous methodologies have been reported previously and
still, many researchers are working for the development of
effective new routes for the synthesis of 1,2,3-triazoles due to
their valuable drug-like nature. The classical methods include
Huisgen's thermally induced 1,3-dipolar cycloaddition of
aDepartment of Medicinal Chemistry, National Institute of Pharmaceutical Education
and Research (NIPER), Hyderabad 500037, India. E-mail: shankar@niperhyd.ac.in
bMedicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India. E-mail: ahmedkamal@iict.res.in
cSchool of Pharmaceutical Education and Research (SPER) Jamia Hamdard, New
Delhi, 110062, India
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c9ra06005g
Fig. 1 Representative biologically active molecules containing 1,2,3-
triazole.
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alkynes and azides.9 However, it is well-known that this method researchers owing to its advantages viz. relatively inexpensive,
suffers from the limited substrate scope and poor regiose- efficient and a green alternative to transition metals.19 On the
lectivity. Subsequently, Sharpless and Meldel groups indepen- other hand, iodine is also reported to provide a mild and effi-
dently proposed a copper-catalyzed azide–alkyne cycloaddition cient approach involved in numerous oxidative transformations
(CuAAC) for the synthesis of 1,2,3-triazoles which is a highly for the formation of C–C, C–N and N–N bonds.20 As a part of our
regioselective and straight forward method.10 This approach research program in the development of medicinally active
made 1,2,3-triazole more accessible in organic synthesis. Later, molecules in an eco-friendly manner herein, we developed
numerous methods have been developed for the synthesis of a novel method for the synthesis of 1,2,3-triazoles regiose-
1,2,3-triazoles comprising the use of metal triates,11 expensive lectively in a one-pot manner by using I2/O2 and DMSO as
metal catalyst complexes,12 organocatalysts,13 ionic liquids,14 a solvent from readily accessible anilines, aryl alkynes or aryl
microwaves,15 polymers,16 bases,17 etc. However, most of these alkenes and N-tosylhydrazine as substrates.
reported methods utilized heavy metals (Cu, Pd, Ru, Ir) which
limit their use in the biological, environmental point of views
due to their hazardous nature and toxicity prole. Moreover,
Results and discussion
organic azides are also exploited which are likely to explode and
difficult to handle on large scale. Consequently, a great deal of
interest was diverted towards the development of simple, metal-
free and azide-free approaches for the synthesis of these
attractive scaffolds,18 because metal free approaches are very
lucrative on account of being inexpensive and environmentally
benign nature. However, regioselective construction of C–N,
N–N bonds is quite difficult in the absence of transition metals.
In this context, molecular iodine has grabbed much attention of
At the onset to test the feasibility of the reaction, a selected
model reaction was performed using 4-methyl aniline (1p),
phenylacetylene (2a) and N-tosyl hydrazine (3a) in DMSO with
iodine (1.0 equiv.) at room temperature for 24 h, resulting in no
desired product 4p was observed (entry 1, Table 1). To our
delight, 4p was obtained in low yield (10%) when we performed
the reaction at 100 ꢀC for 12 h (entry 2, Table 1). In order to
improve the yield of 4p, we further screened different oxidants,
solvents, catalysts, amount of catalyst as well as reaction
Table 1 Optimisation of the reaction conditionsa
Entry
Additive (equiv.)
Oxidant (equiv.)
Solvent
Temperature (ꢀC)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
KI (1.0)
NIS (1.0)
TBAI (1.0)
—
I2 (1.0)
I2 (1.2)
I2 (1.5)
I2 (0.8)
I2 (1.2)c
I2 (1.2)c
I2 (1.2)c
I2 (1.2)c
—
—
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
toluene
DMF
1,4-Dioxane
CH3CN
DMSO
DMSO
DMSO
DMSO
—
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
rt
24
12
6
6
6
6
6
6
6
6
6
6
6
6
24
6
6
6
NF
10
76
68
56
26
38
NF
56
32
12
10
34
28
NF
trace
82
78
71
86
89
68
87
100
100
100
100
100
100
100
100
100
80
100
100
100
100
100
100
100
100
100
120
80
O2
TBHP (1)
Oxone (1)
PhI(OAc)2(1)
K2S2O8 (1)
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
6
6
4
12
4
O2
O2
O2
O2
150
a
All reactions were performed with 1p (1 mmol), 2a (1.1 mmol), and 3a (1.5 mmol) in presence of I2 (1.2 equiv.) and under O2 at 120 ꢀC for 6 h.
Isolated yields. Iodine was added to a solution of 1p (1 mmol), 2a (1.1 mmol) and allowed to stir for 1 h followed by addition of 3a (1.5
b
c
mmol) under O2 at 120 ꢀC for 4 h. NF – Not Formed. TBHP ¼ tert-butyl hydroperoxide (70% in water), DMSO ¼ dimethyl sulfoxide, DMF –
dimethyl formamide.
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temperature. Interestingly, reaction yield was increased to provided 62%, 65%, and 56% respectively. However, an electron
a greater extent providing the formation of 4p with 76% yield, donating groups like phenoxy, methyl, and methoxy containing
ꢀ
when the reaction mixture was heated to 100 C for 6 h in the anilines 4l–q showed high reactivity with excellent yields as
presence of oxygen (entry 3, Table 1). Encouraged by the above shown in Table 2. Moreover, the position of substituents on the
result, common oxidants namely TBHP, oxone, PhI(OAc)2, aromatic ring of anilines had a little inuence on the yield of the
K2S2O8 (entries 4–7, Table 1) were screened and O2 was found to products. 2-Naphthylamine (1r) was also readily participated in
be a suitable oxidant. DMSO played a crucial role in this reac- the reaction to afford product 4r in 68% yield. Interestingly, the
tion and found to be the best solvent when compared to other reaction proceeded with benzylamine (4s) under optimized
tested solvents such as DMF, 1,4-dioxane and CH3CN found to condition albeit at lower yield (25%). Unluckily, the complex
deliver the required product with inferior yields (entries 9–11, mixture was observed when we attempted this protocol with
Table 1). In non-polar solvent such as toluene, under optimized aliphatic and propargyl amine. Furthermore, heteroaryl aniline
reaction conditions, product 4p was not formed (entry 8, Table such as 8-aminoquinoline (1t) was also served well to generate
1). Next, we screened various iodine-containing catalysts such the corresponding product in good yield (4t, 65%). In addition,
as potassium iodide (KI), N-iodosuccinimide (NIS) and tetra- 8-aminoquinoline is a core structure in many antimalarial
butylammonium iodide (TBAI) in DMSO to check the feasibility drugs (primaquine, pamaquine, etc).21 The antimalarial prop-
of the reaction (entry 12–14, Table 1).
erties of a molecule can be readily modulated with respect to
However, all the tested iodine sources were found to be structure–activity parameters by attaching new fragments on
ineffective as they deliver the product 4p with reduced yields. a conventional 8-aminoquinoline pharmacophore, for example,
While in the absence of iodine, product 4p was not produced compound 4t. By applying this efficient method, a tail fragment
(entry 15, Table 1). The desired product 4p was obtained in trace can be easily incorporated on established pharmacophore in
amounts in the absence of solvent (entry 16, Table 1). The a one-pot manner.
reduced yield of 4p is due to the low solubility of reactants. Aer
With the consistent results of this protocol, we have also
establishing a suitable oxidant, solvent, and catalyst for the applied this new approach towards a range of aryl alkynes 2a–j
synthesis of 1,2,3-triazole, we focussed our interest in the (Table 2). To our delight, aromatic ring of aryl alkyne bearing
quantity of iodine. Interestingly, improvement in the yield of 4p electron rich and electron decient groups reacted smoothly
was observed when the stoichiometric amount of iodine was under these optimized conditions to furnish the corresponding
increased to 1.2 equiv. (entry 17, Table 1). The molecular iodine 1,2,3-triazoles 4u–ad with moderate to good yields as shown in
was revived in situ from iodide anions. Hence, the reaction Table 2. Aryl alkynes substituted with electron donating groups
proceeded well only with 1.2 equiv. of iodine. However, a further like hydroxyl (2f), methoxy (2g), methyl (2h) and ethyl (2i)
increase in the amount of iodine (entry 18, Table 1) did not participated efficiently to offer the corresponding products 4z
improve the yield. Further, reaction efficiency was improved to (70%), 4aa (82%), 4ab (81%), 4ac (83%) respectively in good
a smaller extent providing an increased yield of 4p with 86%, yields (Table 2). However, the substrates with electron with-
when iodine (1.2 equiv.) was added to a solution of 1p (1 mmol), drawing uoro, chloro, bromo, triuoromethyl (2a–e) groups
2a (1.1 mmol) and stirred at 100 ꢀC for 1 h under oxygen delivered the corresponding 1,2,3-triazoles with moderate yields
atmosphere followed by addition of 3a (1.5 mmol) (entry 20, and longer reaction times (4u–y, Table 2). Investigation with 2-
Table 1). To our delight, the yield of 4p was increased to 89%, ethynyl pyridine (2j) was also found to be fruitful with the
when the reaction was performed with 1.2 equiv. of iodine at current strategy but the reaction proceeded sluggishly to offer
120 ꢀC for 4 h (entry 21, Table 1). Further, increase or decrease the corresponding product 4ad in low yield i.e. 32% (Table 2).
in the temperature leads to a negative impact on the yield of 4p However, the extension of the reaction towards aliphatic
(entries 22–23, Table 1). Therefore, systematic screening of the alkynes and propargyl derivatives were failed to yield the
reaction conditions revealed that iodine (1.2 equiv.)/O2 atmo- desired products. Subsequently, we performed the reaction with
ꢀ
sphere in DMSO at 120 C is the optimal choice for the forma- substituted anilines, substituted aryl alkynes, and N-tosyl
tion of 1,2,3-triazoles.
hydrazine. The reaction proceeded efficiently as expected to
Aer achieving the optimized conditions, we have explored deliver the corresponding products 4ae–ag in decent yields
the generality and substrate scope of the present protocol. (Table 2).
Hence, a diverse range of anilines 1a–t were treated with phe-
Encouraged by the above results, in order to expand the
nylacetylene (2a) and N-tosyl hydrazine (3a) under optimized synthetic applicability of the present protocol, we replaced the
reaction conditions to afford the corresponding products 4a–t terminal aryl alkyne functionality with terminal aryl alkene. To
in a moderate to good yields (25–89%, Table 2). As shown in our delight, the reactions proceeded successfully under stan-
Table 2, it was observed that electron with-drawing group dard conditions. Aryl alkenes and anilines bearing electron
bearing anilines including halo groups like uoro, chloro, donating and electron withdrawing groups reacted efficiently to
bromo, and iodo (4b–h) were well tolerated to furnish the deliver a valuable 1,2,3-triazoles 4a, 4c, 4m, 4u, 4ab and 4af as
desired products with good yields. It was noted that the corre- shown in Table 3. Electronic nature of aryl alkenes had a little
sponding products obtained in these reactions act as potential inuence on the reaction efficiency, by affording all the desired
substrates for further functionalizations. Substrates having products in a moderate to good yields (62–76%).
electron decient triuoromethyl (4i), nitro (4j), and ester (4k)
To further elucidate the synthetic competence of our
groups displayed good tolerance towards the reaction yields protocol, a gram scale reaction was performed using 1a (2 g,
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Table 2 Substrate scope for I2 catalysed synthesis of 1,2,3-triazoles from diverse amines, phenyl acetylene and N-tosylhydrazinea
a
All reactions were performed with 1 (1 mmol), 2a (1.1 mmol), 3 (1.5 mmol) and I2 (1.2 mmol) in DMSO (3 mL) at 120 ꢀC for 4–6 h.
Table 3 Substrate scope for synthesis of 1,2,3-triazoles from diverse anilines, diverse aryl alkenes and N-tosylhydrazinea
a
All reactions were performed with 1 (1 mmol), 5 (1.1 mmol), 3 (1.5 mmol) and I2 (1.2 mmol) in DMSO (3 mL) at 120 ꢀC for 4–6 h.
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21.27 mmol), 3 (5.93 g, 31.91 mmol) with 2a (2.38 g, 23.40
mmol) and 5a (2.43 g, 23.40 mmol) under standard optimal
conditions. To our delight, reaction forwarded smoothly to
afford the corresponding product 4a in 75% (3.52 g) and 67%
(3.16 g) isolated yields with 2a and 5a respectively (Scheme 1).
Scalability of this protocol has the potential for utility in
industrial scale-up operations.
In order to understand the possible reaction mechanism,
a series of control experiments were carried out subsequently
(Scheme 2). In this context, we performed the reaction with
phenylacetylene (2a) or styrene (7a) under optimized reaction
conditions in the absence of aniline (1a) and tosyl hydrazine (3)
to afford phenylglyoxal (D) in a quantitative yield (Scheme 2a).
Assuming that the reaction proceeds through a-iodo ketone (A)
and phenylglyoxal (D) intermediates.22 Next, they were treated
with aniline (1a), N-tosyl hydrazine (3) under standard reaction
conditions, which deliver the corresponding product 4a with
good yields (Scheme 2b and c). Moreover, aniline (1a) reacted
with an a-iodo ketone (A) under standard optimised conditions
to afford a phenylaminoethanone (B) intermediate which was
cyclized to afford 4a in the presence of tosyl hydrazine (3) under
optimized reaction conditions (Scheme 2d). It was found that
phenyl acetylene (2a) or styrene (7a) with molecular iodine and
DMSO in the presence of oxygen affords phenylglyoxal (D),
Scheme 3 Plausible mechanism for the iodine-catalyzed synthesis of
1,2,3-triazoles.
intermediate F. The reaction of intermediate F with N-tosyl
hydrazine affords 1,2,3-triazole with 80% yield (Scheme 2e).
Furthermore, intermediate C which was synthesized by a liter-
ature report,23 could be smoothly cyclized and aromatized
through N–N bond formation to afford the triazole product 4a
with a 90% yield in the presence of iodine and 25% in the
absence of iodine (Scheme 2f). However, these reactions were
proceeded well under optimised reaction temperature and not
fruitful when these reactions were performed at lower temper-
subsequent addition of aniline affords
a
condensed
ꢀ
atures i.e. at rt and 60 C.
Based on the control experiments and literature reports,
a plausible mechanistic pathway for the formation of 1,4-
substituted 1,2,3-triazole is depicted in Scheme 3. Initially,
phenylacetylene (2a) or styrene (7a) is converted into a-iodoa-
cetophenone (A) through consequent iodination followed by
oxidation with I2/O2 system. Next, in the pathway a, interme-
diate A undergoes nucleophilic amination directly with aniline
to give an intermediate B. Subsequently, intermediate B
undergoes condensation with N-tosylhydrazine (3) and afforded
the intermediate C which upon oxidative cyclization and
aromatization in the presence of iodine and molecular oxygen
gave the desired triazole 4a. Alternatively, in pathway b, a-
iodoacetophenone (A) converted into phenylglyoxal (D) via
Kornblum oxidation24 in DMSO which act as oxygen donor in
the reaction process then upon condensation with aniline (1a)
provided a C-acylimine intermediate followed by a subsequent
condensation with N-tosylhydrazine to afford an intermediate
G, which further undergo cyclization and aromatization in the
presence of iodine and oxygen to afford the desired triazole 4a.
Molecular iodine can be readily regenerated in situ by the
oxidation of iodide anions with DMSO.
Scheme 1 Gram scale synthesis of 4a.
Conclusion
In summary, we have developed an efficient I2/O2 mediated
protocol for the synthesis of 1,4-disubstituted 1,2,3-triazoles in
a regioselective manner from commercially available anilines,
aryl alkynes or aryl alkenes, and N-tosyl hydrazine through C–N,
N–N bond formation. Advantages of the presented methodology
are broad substrate scope, milder reaction conditions,
Scheme 2 Control experiments (a)–(f).
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operational simplicity and cost-effective. Importantly, gram ꢀC);23a 1H NMR (500 MHz, CDCl3): d 8.16 (s, 1H), 7.92 (d, J ¼
scale synthesis was also accomplished which makes this 7.5 Hz, 2H), 7.78 (dd, J ¼ 8.6, 4.5 Hz, 2H), 7.47 (t, J ¼ 7.4 Hz, 2H),
protocol for the utilization in the synthesis of biologically 7.37 (dd, J ¼ 24.3, 17.0 Hz, 1H), 7.27 (d, J ¼ 2.8 Hz, 1H), 7.24 (d, J
important molecules.
¼ 8.2 Hz, 1H); 13C NMR (125 MHz, DMSO): d 162.18 (d, J ¼ 234.4
Hz), 147.79, 133.71 (d, J ¼ 2.7 Hz), 130.69, 129.49, 128.75,
125.82, 122.86 (d, J ¼ 8.8 Hz), 120.39, 117.28 (d, J ¼ 23.2 Hz),
HRMS (ESI): m/z calcd for C14H11FN3 [M + H]+ 240.0937, found
240.0943.
Experimental section
General information
All the reagents and chemicals were obtained from commercial
sources and used without further purication. Analytical thin
layer chromatography (TLC) was performed with silica gel
MERCK silica gel 60-F254 (0.5 mm) precoated glass plates. TLC
plates were visualized by exposure to ultraviolet light. Column
chromatography was performed using 100–200 mesh silica gel,
and the eluent was as a mixture of ethyl acetate and n-hexane.
1H and 13C NMR spectra were recorded with a Bruker 500 MHz
NMR instrument in CDCl3 or DMSO-d6 with tetramethylsilane
(TMS) as an internal standard. Chemical shis (d) and coupling
constants (J) are reported in parts per million (ppm), Hertz (Hz)
respectively. The peak patterns are indicated as follows: s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd,
doublet of doublet; dt, doublet of triplet; td, triplet of doublet;
ddd, doublet of doublet of doublet. Melting points were deter-
mined using an electrothermal apparatus (Model IA9200) and
are uncorrected. High-resolution mass spectra (HRMS) were
recorded on LC-QTOF mass spectrometer.
1-(4-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (4c)
178 mg (70%) of 4c was obtained as a white solid; Rf ¼ 0.516
(ethyl acetate/n-hexane, 1 : 1); mp. 221–224 ꢀC (lit. 222–224
ꢀC);23a 1H NMR (500 MHz, DMSO): d 9.35 (s, 1H), 8.05–7.99 (m,
2H), 7.95 (dd, J ¼ 8.2, 1.2 Hz, 2H), 7.77–7.70 (m, 2H), 7.52 (dd, J
¼ 10.6, 4.7 Hz, 2H), 7.44–7.37 (m, 1H); 13C NMR (125 MHz,
DMSO): d 147.94, 135.93, 133.45, 130.62, 130.42, 129.52, 128.82,
125.84, 122.16, 120.21; HRMS (ESI): m/z calcd for C14H11ClN3 [M
+ H]+ 256.0642, found 256.0641.
1-(4-Bromophenyl)-4-phenyl-1H-1,2,3-triazole (4d)
227 mg (76%) of 4d was obtained as a white solid; Rf ¼ 0.586
(ethyl acetate/n-hexane, 1 : 1); mp. 222–224 ꢀC (lit. 216–217
ꢀC);23a 1H NMR (500 MHz, CDCl3): d 8.18 (s, 1H), 7.97–7.85 (m,
2H), 7.75–7.66 (m, 4H), 7.47 (dt, J ¼ 12.5, 3.2 Hz, 2H), 7.42–7.36
(m, 1H); 13C NMR (125 MHz, CDCl3): d 141.64, 136.07, 132.97,
130.02, 128.98, 128.61, 125.91, 122.43, 121.91, 117.34; HRMS
(ESI): m/z calcd for C14H1181BrN3 [M + H]+ 302.0116, found
302.0118.
General procedure for the synthesis of 1,4-disubstituted 1,2,3-
triazoles (4a–ag)
In a 25 mL round-bottomed ask, aryl alkyne (1.1 mmol)/aryl
1-(3-Fluorophenyl)-4-phenyl-1H-1,2,3-triazole (4e)
alkene (1.1 mmol), arylamine (1 mmol) and iodine (1.2 mmol) in
ꢀ
169 mg (71%) of 4e was obtained as a solid; Rf ¼ 0.586 (ethyl
DMSO were reuxed at 120 C under molecular dioxygen atmo-
acetate/n-hexane, 1 : 1); mp. 179–182 C (lit. 185–187 C);25a 1H
NMR (500 MHz, CDCl3): d 8.19 (s, 1H), 7.92 (dd, J ¼ 10.2, 8.9 Hz,
2H), 7.62–7.57 (m, 2H), 7.56–7.50 (m, 1H), 7.47 (t, J ¼ 7.6 Hz,
2H), 7.38 (td, J ¼ 7.1, 1.1 Hz, 1H), 7.19–7.14 (m, 1H); 13C NMR
(125 MHz, CDCl3): d 163.15 (d, J ¼ 252.5 Hz), 148.66, 138.25 (d, J
¼ 10.3 Hz), 131.23 (d, J ¼ 9.0 Hz), 129.95, 128.97, 128.63, 125.93,
117.44, 115.81 (d, J ¼ 3.3 Hz), 115.67 (d, J ¼ 21.2 Hz), 108.29 (d, J
¼ 26.2 Hz); HRMS (ESI): m/z calcd for C14H11FN3 [M + H]+ 240.
0937, found 240.0941.
ꢀ
ꢀ
sphere for 1 h followed by an addition of N-tosyl hydrazine (1.5
mmol), continued to reux at 120 ꢀC for 3–5 h. Aer completion of
the reaction (monitored with TLC), the reaction mixture was
quenched with a saturated solution of sodium thiosulfate and
extracted with ethyl acetate. The combined organic layers were
washed with water and brine, dried over anhydrous Na2SO4,
ltered and concentrated under reduced pressure. The residue
obtained was puried by silica gel column chromatography using
ethyl acetate–hexane as an eluent in increasing polarity to afford
the desired 1,4-disubstituted 1,2,3-triazoles 4a–ag.
1-(3-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (4f)
1,4-Diphenyl-1H-1,2,3-triazole (4a)
191 mg (75%) of 4f was obtained as an yellow solid; Rf ¼ 0.500
(ethyl acetate/n-hexane, 1 : 1); mp. 172–174 ꢀC (lit. 167–170
ꢀC);25a 1H NMR (500 MHz, CDCl3): d 8.19 (s, 1H), 7.93–7.88 (m,
2H), 7.84 (t, J ¼ 2.0 Hz, 1H), 7.71 (ddd, J ¼ 8.0, 2.0, 1.1 Hz, 1H),
7.49 (dd, J ¼ 7.3, 4.8 Hz, 1H), 7.47 (d, J ¼ 1.7 Hz, 1H), 7.46–7.42
(m, 2H), 7.40–7.36 (m, 1H); 13C NMR (125 MHz, CDCl3):
d 148.70, 137.85, 135.66, 130.87, 129.96, 128.97, 128.82, 128.63,
125.92, 120.75, 118.48, 117.44; HRMS (ESI): m/z calcd for
176 mg (80%) of 4a was obtained as a white solid; Rf ¼ 0.420
(ethyl acetate/n-hexane, 1 : 1); mp. 173–175 ꢀC (lit. 181–183
ꢀC);23a 1H NMR (500 MHz, CDCl3): d 8.21 (s, 1H), 7.96–7.90 (m,
2H), 7.80 (dd, J ¼ 8.5, 1.0 Hz, 2H), 7.56 (dd, J ¼ 10.7, 5.0 Hz, 2H),
7.49–7.44 (m, 3H), 7.38 (t, J ¼ 7.4 Hz, 1H); 13C NMR (125 MHz,
CDCl3): d 137.09, 130.13, 129.80, 128.94, 128.84, 128.50, 125.92,
120.58, 117.66; HRMS (ESI): m/z calcd for C14H12N3 [M + H]+
222.1031, found 222.1031.
C
14H11ClN3 [M + H]+ 256. 0642, found 256.0645.
1-(4-Fluorophenyl)-4-phenyl-1H-1,2,3-triazole (4b)
1-(2-Bromophenyl)-4-phenyl-1H-1,2,3-triazole (4g)
172 mg (72%) of 4b was obtained as a white solid; Rf ¼ 0.587 224 mg (75%) of 4g was obtained as a solid; Rf ¼ 0.482 (ethyl
(ethyl acetate/n-hexane, 1 : 1); mp. 203–205 ꢀC (lit. 209–210 acetate/n-hexane, 1 : 1); mp. 99–100 ꢀC (100–101 ꢀC);25b 1H NMR
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(500 MHz, CDCl3): d 8.17 (s, 1H), 7.95–7.91 (m, 2H), 7.78 (dd, J ¼ (m, 5H), 7.42–7.35 (m, 3H), 7.19 (t, J ¼ 7.4 Hz, 1H), 7.08 (dd, J ¼
8.1, 1.3 Hz, 1H), 7.62 (dd, J ¼ 7.9, 1.6 Hz, 1H), 7.51 (td, J ¼ 7.7, 10.9, 7.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): d 158.85, 156.11,
1.4 Hz, 1H), 7.49–7.45 (m, 2H), 7.43–7.40 (m, 1H), 7.39–7.35 (m, 148.40, 138.38, 130.92, 130.09, 128.86, 128.53, 125.93, 124.34,
1H); 13C NMR (125 MHz, CDCl3): d 147.02, 136.93, 132.28, 119.61, 118.33, 117.68, 114.72, 110.62; HRMS (ESI): m/z calcd for
131.32, 130.51, 129.87, 129.00, 128.83, 124.40, 123.05, 120.59,
118.02; HRMS (ESI): m/z calcd for C14H11BrN3 [M + H]+
300.0136, found 300.0099.
C
20H16N3O [M + H]+ 314.1293, found 314.1300.
1-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (4m)
208 mg (83%) of 4m was obtained as a off white solid; Rf ¼ 0.206
1-(2-Iodophenyl)-4-phenyl-1H-1,2,3-triazole (4h)
(ethyl acetate/n-hexane, 1 : 1); mp. 163–165 ꢀC (lit. 162–164
1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 8.24 (s, 1H), 7.93 (s, 2H),
269 mg (78%) of 4h was obtained as a pale yellow solid; Rf ¼
0.550 (ethyl acetate/n-hexane, 1 : 1); mp. 159–162 ꢀC (lit. 156–
158 ꢀC);25b 1H NMR (500 MHz, CDCl3): d 8.08 (d, J ¼ 5.0 Hz, 1H),
8.02 (dd, J ¼ 8.0, 1.0 Hz, 1H), 7.95–7.91 (m, 2H), 7.55–7.51 (m,
1H), 7.50 (d, J ¼ 2.0 Hz, 1H), 7.49–7.44 (m, 2H), 7.39–7.35 (m,
1H), 7.28–7.23 (m, 1H); 13C NMR (125 MHz, CDCl3): d 147.65,
140.32, 140.10, 131.55, 130.26, 129.33, 128.96, 128.37, 127.88,
125.94, 121.61, 93.91; HRMS (ESI): m/z calcd for C14H11IN3 [M +
H]+ 347.9998, found 348.0010.
7.69 (d, J ¼ 8.8 Hz, 2H), 7.47 (dd, J ¼ 16.9, 10.5 Hz, 2H), 7.37 (t, J
¼ 7.4 Hz, 1H), 7.03 (d, J ¼ 8.7 Hz, 2H), 3.87 (s, 3H); 13C NMR (125
MHz, CDCl3): d 159.96, 130.58, 130.22, 128.94, 128.74, 128.45,
126.70, 125.88, 122.25, 114.87, 55.46; HRMS (ESI): m/z calcd for
C
15H14N3O [M + H]+ 252.1137, found 252.1137.
1-(3,4-Dimethoxyphenyl)-4-phenyl-1H-1,2,3-triazole (4n)
238 mg (85%) of 4n was obtained as a pale brown solid; Rf ¼
0.160 (ethyl acetate/n-hexane, 1 : 1); mp. 147–149 ꢀC (lit. 151–
153 ꢀC);25d 1H NMR (500 MHz, CDCl3): d 8.16 (s, 1H), 7.91 (d, J ¼
7.5 Hz, 2H), 7.45 (t, J ¼ 7.4 Hz, 2H), 7.40 (d, J ¼ 2.4 Hz, 1H), 7.36
(t, J ¼ 7.4 Hz, 1H), 7.21 (dd, J ¼ 8.6, 2.4 Hz, 1H), 6.96 (d, J ¼
8.6 Hz, 1H), 3.97 (s, 3H), 3.94 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 165.66, 163.65, 161.12, 150.17, 143.51, 137.47, 125.86,
125.03, 123.36, 105.05, 55.82; HRMS (ESI): m/z calcd for
4-Phenyl-1-(3-(triuoromethyl)phenyl)-1H-1,2,3-triazole (4i).
179 mg (62%) of 4i was obtained as a white solid; Rf ¼ 0.560
(ethyl acetate/n-hexane, 1 : 1); mp. 152–154 ꢀC (lit. 144–146
ꢀC);25c 1H NMR (500 MHz, CDCl3): d 8.26 (s, 1H), 8.08 (s, 1H),
8.04 (d, J ¼ 7.5 Hz, 1H), 7.92 (d, J ¼ 7.3 Hz, 2H), 7.71 (m, J ¼
7.8 Hz, 2H), 7.47 (t, J ¼ 7.6 Hz, 2H), 7.39 (t, J ¼ 7.4 Hz, 1H); 13
C
NMR (125 MHz, CDCl3): d 137.43, 132.50 (q, J ¼ 33.3 Hz), 130.61,
129.87, 129.00, 128.71, 125.94, 125.35 (q, J ¼ 3.3 Hz), 123.56,
123.38 (q, J ¼ 272.7 Hz), 117.34 (q, J ¼ 3.8 Hz), HRMS (ESI): m/z
calcd for C15H11F3N3 [M + H]+ 290.0905, found 290.0916.
C
16H16N3O2 [M + H]+ 282.1243, found 282.1231.
4-Phenyl-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (4o)
1-(3-Nitrophenyl)-4-phenyl-1H-1,2,3-triazole (4j)
270 mg (87%) of 4o was obtained as pale yellow solid; Rf ¼ 0.152
(ethyl acetate/n-hexane, 1 : 1); mp. 119–122 C (110–112 C);25d
1H NMR (500 MHz, CDCl3): d 8.16 (s, 1H), 7.91 (d, J ¼ 7.5 Hz,
2H), 7.46 (t, J ¼ 7.5 Hz, 2H), 7.36 (dd, J ¼ 18.3, 11.1 Hz, 1H), 7.02
(d, J ¼ 20.3 Hz, 2H), 3.95 (s, 6H), 3.90 (s, 3H); 13C NMR (125
MHz, CDCl3): d 153.96, 138.35, 132.92, 130.16, 128.94, 128.49,
125.86, 118.14, 98.55, 61.06, 56.47; HRMS (ESI): m/z calcd for
ꢀ
ꢀ
172 mg (65%) of 4j was obtained as an yellow solid; Rf ¼ 0.379
(ethyl acetate/n-hexane, 1 : 1); mp. 198–200 C (198–200 C);25b
1H NMR (500 MHz, DMSO): d 9.57 (s, 1H), 8.80 (t, J ¼ 2.1 Hz,
1H), 8.48 (ddd, J ¼ 8.1, 2.1, 0.7 Hz, 1H), 8.40–8.34 (m, 1H), 7.97
(dt, J ¼ 14.8, 4.7 Hz, 3H), 7.54 (dd, J ¼ 10.6, 4.8 Hz, 2H), 7.45–
7.39 (m, 1H); 13C NMR (125 MHz, DMSO): d 149.08, 148.09,
137.71, 132.12, 130.40, 129.56, 128.97, 126.44, 125.87, 123.62,
120.53, 115.08; HRMS (ESI): m/z calcd for C14H11N4O2 [M + H]+
267.0882, found 267.0885.
ꢀ
ꢀ
C
17H18N3O3 [M + H]+ 312.1348, found 312.1357.
4-Phenyl-1-(p-tolyl)-1H-1,2,3-triazole (4p)
209 mg (89%) of 4p was obtained as a white solid; Rf ¼ 0.580
(ethyl acetate/n-hexane, 1 : 1); mp. 173–175 ꢀC (lit. 169–171
Ethyl 4-(4-phenyl-1H-1,2,3-triazol-1-yl)benzoate (4k)
1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 8.16 (s, 1H), 7.91 (d, J ¼
164 mg (56%) of 4k was obtained as a white solid; Rf ¼ 0.448
(ethyl acetate/n-hexane, 1 : 1); mp. 175–178 ꢀC (lit. 181–183
ꢀC)18c; 1H NMR (500 MHz, CDCl3): d 8.34–8.17 (m, 3H), 7.92 (dd,
J ¼ 7.6, 6.3 Hz, 4H), 7.48 (t, J ¼ 7.5 Hz, 2H), 7.39 (t, J ¼ 7.4 Hz,
1H), 4.43 (q, J ¼ 7.1 Hz, 2H), 1.44 (t, J ¼ 7.1 Hz, 3H); 13C NMR
(125 MHz, CDCl3): 13C NMR (125 MHz, CDCl3): d 165.44, 148.77,
140.04, 131.30, 130.63, 129.92, 129.00, 128.68, 125.96, 119.84,
117.35, 61.35, 14.59; HRMS (ESI): m/z calcd for C17H16N3O2 [M +
H]+ 294.1240, found 294.1243.
7.5 Hz, 2H), 7.66 (d, J ¼ 8.3 Hz, 2H), 7.45 (t, J ¼ 7.6 Hz, 2H), 7.37
(d, J ¼ 7.4 Hz, 1H), 7.33 (d, J ¼ 8.2 Hz, 2H), 2.43 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 148.12, 138.99, 134.81, 130.29, 130.21,
128.93, 128.43, 125.91, 120.49, 117.91, 21.10; HRMS (ESI): m/z
calcd for C15H14N3 [M + H]+ 236.1188, found 236.1188.
1-(2,6-Dimethylphenyl)-4-phenyl-1H-1,2,3-triazole (4q)
219 mg (88%) of 4q was obtained as a pale white solid; Rf ¼
1
ꢀ
0.519 (ethyl acetate/n-hexane, 1 : 1); mp. 122–124 C; H NMR
(500 MHz, CDCl3): d 7.94 (s, 1H), 7.93–7.90 (m, 2H), 7.45 (t, J ¼
1-(3-Phenoxyphenyl)-4-phenyl-1H-1,2,3-triazole (4l)
253 mg (81%) of 4l was obtained as a white solid; Rf ¼ 0.519 7.6 Hz, 2H), 7.36 (dd, J ¼ 10.9, 3.9 Hz, 1H), 7.28–7.20 (m, 3H),
(ethyl acetate/n-hexane, 1 : 1); mp. 137–139 ꢀC; 1H NMR (500 2.39 (s, 3H), 2.22 (s, 3H); 13C NMR (125 MHz, CDCl3): d 147.55,
MHz, CDCl3): d 8.15 (s, 1H), 7.90 (d, J ¼ 7.4 Hz, 2H), 7.53–7.43 136.88, 136.33, 131.32, 130.61, 130.47, 130.42, 128.92, 128.29,
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126.48, 125.83, 121.12, 20.82, 17.57; HRMS (ESI): m/z calcd for
C
4-(4-Bromophenyl)-1-phenyl-1H-1,2,3-triazole (4w)
16H16N3 [M + H]+ 250.1344, found 250.1346.
210 mg of 4w was obtained as a white solid; Rf ¼ 0.630 (ethyl
1
acetate/n-hexane, 1 : 1); mp. 205–208 C (lit. 212–214 C)22a; H
NMR (500 MHz, DMSO): d 9.37 (s, 1H), 7.96 (d, J ¼ 7.7 Hz, 2H),
7.92 (d, J ¼ 8.5 Hz, 2H), 7.73 (d, J ¼ 8.4 Hz, 2H), 7.65 (t, J ¼
7.9 Hz, 2H), 7.54 (t, J ¼ 7.4 Hz, 1H); 13C NMR (125 MHz, DMSO):
d 146.75, 139.16, 137.05, 132.48, 130.45, 130.01, 129.32, 127.78,
122.36, 121.74, 120.54; HRMS (ESI): m/z calcd for C14H11BrN3 [M
+ H]+ 300.0136, found 300.0140.
ꢀ
ꢀ
1-(Naphthalen-2-yl)-4-phenyl-1H-1,2,3-triazole (4r)
184 mg (68%) of 4r was obtained as a white solid; Rf ¼ 0.500
(ethyl acetate/n-hexane, 1 : 1); mp. 186–189 ꢀC (lit. 182–184
ꢀC);25d 1H NMR (500 MHz, CDCl3): d 8.35 (s, 1H), 8.24 (s, 1H),
8.03 (d, J ¼ 8.6 Hz, 1H), 8.01–7.91 (m, 5H), 7.64–7.55 (m, 2H),
7.49 (t, J ¼ 7.3 Hz, 2H), 7.39 (t, J ¼ 7.3 Hz, 1H); 13C NMR (125
MHz, CDCl3): d 134.38, 133.26, 133.02, 130.16, 129.87, 129.04,
128.68, 128.37, 128.00, 127.56, 127.12, 126.09, 118.98, 118.58,
118.23; HRMS (ESI): m/z calcd for C18H14N3 [M + H]+ 272.1188,
found 272.1194.
4-(3-Bromophenyl)-1-phenyl-1H-1,2,3-triazole (4x)
206 mg (69%) of 4x was obtained as a white solid; Rf ¼ 0.655
(ethyl acetate/n-hexane, 1 : 1); mp. 148–151 ꢀC (lit. 148–150
1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 8.20 (s, 1H), 8.06 (dd, J ¼
1-Benzyl-4-phenyl-1H-1,2,3-triazole (4s)
5.7, 4.0 Hz, 1H), 7.88–7.84 (m, 1H), 7.81–7.76 (m, 2H), 7.58–7.53
(m, 2H), 7.52–7.45 (m, 2H), 7.33 (t, J ¼ 7.9 Hz, 1H); 13C NMR (125
MHz, CDCl3): d 146.99, 136.92, 132.27, 131.36, 130.51, 129.86,
128.99, 128.83, 124.42, 123.04, 120.58, 118.12; HRMS (ESI): m/z
calcd for C14H11BrN3 [M + H]+ 300.0136, found 300.0141.
58 mg (25%) of 4s was obtained as a white solid; Rf ¼ 0.360
(ethyl acetate/n-hexane, 1 : 1); mp. 132–133 ꢀC (lit. 128–130
ꢀC);25b 1H NMR (500 MHz, CDCl3): d 7.81 (t, J ¼ 7.2 Hz, 2H), 7.68
(s, 1H), 7.43–7.34 (m, 5H), 7.35–7.27 (m, 3H), 5.56 (t, J ¼ 6.1 Hz,
2H); 13C NMR (125 MHz, CDCl3): d 148.15, 134.69, 130.47,
129.16, 128.82, 128.79, 128.22, 128.08, 125.76, 119.69, 54.47;
HRMS (ESI): m/z calcd for C15H14N3 [M + H]+ 236.1188, found
236.1197.
1-Phenyl-4-(3-(triuoromethyl)phenyl)-1H-1,2,3-triazole (4y)
161 mg (56%) of 4y was obtained as white solid; Rf ¼ 0.519 (ethyl
acetate/n-hexane, 1 : 1); mp. 223–225 ꢀC; 1H NMR (500 MHz,
DMSO): d 9.39 (s, 1H), 8.25–8.10 (m, 2H), 8.02–7.91 (m, 2H), 7.80
(d, J ¼ 8.1 Hz, 2H), 7.71–7.57 (m, 2H), 7.50 (ddt, J ¼ 11.5, 10.4,
5.2 Hz, 1H); 13C NMR (125 MHz, DMSO): d 146.41, 135.88 (q, J ¼
286.7 Hz), 130.47, 129.43, 128.97, 126.51 (q, J ¼ 3.3 Hz), 126.42,
126.36; 126.28, 125.80, 121.48, 120.62; HRMS (ESI): m/z calcd for
8-(4-Phenyl-1H-1,2,3-triazol-1-yl)quinoline (4t)
176 mg (65%) of 4t was obtained as a yellow solid; Rf ¼ 0.230
(ethyl acetate/n-hexane, 1 : 1); mp. 120–123 ꢀC (lit. 115–117
1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 9.06 (d, J ¼ 43.6 Hz, 2H),
C
15H11F3N3 [M + H]+ 290.0905, found 290.0909.
8.35 (d, J ¼ 46.8 Hz, 2H), 7.98 (d, J ¼ 22.4 Hz, 3H), 7.73 (s, 1H),
7.47 (t, J ¼ 46.1 Hz, 4H); 13C NMR (125 MHz, CDCl3): d 150.86,
147.31, 140.30, 136.54, 133.93, 130.89, 129.18, 128.81, 128.05,
126.49, 125.98, 124.51, 123.65, 122.03; HRMS (ESI): m/z calcd for
4-(1-Phenyl-1H-1,2,3-triazol-4-yl)phenol (4z)
165 mg (70%) of 4z was obtained as a pale white solid; Rf ¼
17H13N4 [M + H]+ 273.1140, found 273.1139.
1
ꢀ
C
0.137 (ethyl acetate/n-hexane, 1 : 1); mp. 194–196 C; H NMR
(500 MHz, DMSO): d 9.62 (s, 1H), 9.24 (s, 1H), 7.97 (d, J ¼ 7.8 Hz,
2H), 7.64 (t, J ¼ 7.6 Hz, 2H), 7.52 (t, J ¼ 7.2 Hz, 1H), 7.41 (s, 1H),
7.37 (d, J ¼ 7.4 Hz, 1H), 7.29 (t, J ¼ 7.7 Hz, 1H), 6.80 (d, J ¼
7.3 Hz, 1H); 13C NMR (125 MHz, DMSO): d 158.32, 147.92,
137.16, 131.94, 130.49, 130.38, 129.14, 120.48, 119.99, 116.67,
115.77, 112.63; HRMS (ESI): m/z calcd for C14H12N3O [M + H]+
238.0980, found 238.0987.
4-(4-Fluorophenyl)-1-phenyl-1H-1,2,3-triazole (4u)
162 mg (68%) of 4u was obtained as white solid; Rf ¼ 0.466
(ethyl acetate/n-hexane, 1 : 1); mp. 205–207 ꢀC (lit. 198–200
1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 8.15 (s, 1H), 7.91–7.87 (m,
2H), 7.81–7.77 (m, 2H), 7.58–7.53 (m, 2H), 7.50–7.43 (m, 1H),
7.19–7.13 (m, 2H); 13C NMR (125 MHz, CDCl3): d 162.91 (d, J ¼
255.5 Hz), 147.53, 137.01, 129.86, 129.01, 127.72 (d, J ¼ 8.2 Hz);
126.35 (d, J ¼ 3.0 Hz), 120.61, 117.57, 115.99 (d, J ¼ 21.8 Hz)
HRMS (ESI): m/z calcd for C14H11FN3 [M + H]+ 240.0937, found
240.0943.
4-(4-Methoxyphenyl)-1-phenyl-1H-1,2,3-triazole (4aa)
205 mg (82%) of 4aa was obtained as a white solid; Rf ¼ 0.206
(ethyl acetate/n-hexane, 1 : 1); mp. 137–139 C (lit. 142–143);23a
ꢀ
1H NMR (500 MHz, CDCl3): d 8.10 (s, 1H), 7.83 (d, J ¼ 8.5 Hz,
2H), 7.77 (d, J ¼ 7.9 Hz, 2H), 7.52 (t, J ¼ 7.7 Hz, 2H), 7.43 (t, J ¼
7.4 Hz, 1H), 6.98 (d, J ¼ 8.4 Hz, 2H), 3.84 (s, 3H); 13C NMR (125
MHz, CDCl3): d 159.86, 148.28, 137.14, 129.78, 128.70, 127.24,
122.91, 120.44, 116.95, 114.38, 55.47; HRMS: m/z calcd for
4-(4-Chlorophenyl)-1-phenyl-1H-1,2,3-triazole (4v)
173 mg (68%) of 4v was obtained as a white solid; Rf ¼ 0.820
(ethyl acetate/n-hexane, 1 : 1); mp. 209–211 ꢀC (lit. 207–209
1
ꢀC)23a; H NMR (500 MHz, DMSO): d 9.37 (d, J ¼ 11.2 Hz, 1H),
C
15H14N3O [M + H]+ 252.1137, found 252.1106.
8.03–7.91 (m, 4H), 7.65 (t, J ¼ 7.8 Hz, 2H), 7.59 (d, J ¼ 8.4 Hz,
2H), 7.54 (t, J ¼ 7.4 Hz, 1H); 13C NMR (125 MHz, DMSO):
d 146.71, 137.02, 133.21, 130.44, 129.66, 129.57, 129.31, 127.51,
1-Phenyl-4-(p-tolyl)-1H-1,2,3-triazole (4ab)
120.54, 120.50; HRMS (ESI): m/z calcd for C14H11ClN3 [M + H]+ 190 mg (81%) of 4ab was obtained as a white solid; Rf ¼ 0.551
256.0642, found 256.0645.
(ethyl acetate/n-hexane, 1 : 1); mp. 148–150 ꢀC (lit. 152–154
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1
ꢀC)23a; H NMR (500 MHz, CDCl3): d 8.08 (s, 1H), 7.85–7.66 (m, 127.16, 123.16, 122.23, 117.11, 114.81, 114.35, 55.65, 55.35;
4H), 7.54–7.42 (m, 2H), 7.38 (t, J ¼ 7.2 Hz, 1H), 7.20 (d, J ¼ HRMS (ESI): m/z calcd for C16H16N3O2 [M + H]+ 282.1243, found
5.6 Hz, 2H), 2.33 (s, 3H); 13C NMR (125 MHz, CDCl3): d 148.48, 282.1255.
138.41, 137.12, 129.84, 129.68, 128.78, 127.33, 125.92, 120.65,
117.83, 21.46; HRMS (ESI): m/z calcd for C15H14N3 [M + H]+
236.1188, found 236.1184.
Conflicts of interest
There are no conicts to declare.
4-(4-Ethylphenyl)-1-phenyl-1H-1,2,3-triazole (4ac)
Acknowledgements
206 mg (83%) of 4ac was obtained as a white solid; Rf ¼ 0.866
(ethyl acetate/n-hexane, 1 : 1); mp. 123–125 C (128–130 C)23a
;
ꢀ
ꢀ
G. S. M and K. D. is thankful to the Department of Pharma-
ceuticals, the Ministry of Chemicals and Fertilizers Govt. of
India, New Delhi for the award of a Research Fellowships.
1H NMR (500 MHz, CDCl3): d 8.16 (s, 1H), 7.90–7.74 (m, 4H),
7.61–7.50 (m, 2H), 7.48–7.43 (m, 1H), 7.30 (d, J ¼ 8.3 Hz, 2H),
2.70 (q, J ¼ 7.6 Hz, 2H), 1.28 (t, J ¼ 7.6 Hz, 3H); 13C NMR (125
MHz, CDCl3): d 148.51, 144.72, 137.12, 129.78, 128.72, 128.45,
127.65, 125.88, 120.51, 117.32, 28.64, 15.52; HRMS (ESI): m/z
calcd for C16H16N3 [M + H]+ 250.1344, found 250.1353.
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2H), 7.20–7.10 (m, 2H), 7.09–6.97 (m, 2H), 3.88 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 162.63 (d, J ¼ 239.0 Hz), 159.92, 147.38,
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