From imidates to vinyl-1,2,4-triazoles: Synthesis, mechanistic aspects and first issues of their reactivity

Article abstract of DOI:10.1016/j.tet.2018.10.050

The reaction of variously substituted acylimidates with hydrazine derivatives represents an efficient and easy to set synthetic entry towards 5-vinyl-1,2,4-triazole derivatives. The construction of the triazole ring allows the installation of variety of s

Full text of DOI:10.1016/j.tet.2018.10.050

Accepted Manuscript
From imidates to vinyl-1,2,4-tiazoles: Synthesis, mechanistic aspects and first issues
of their reactivity
Safa Azzouni, Abderrahmen Abdelli, Anne Gaucher, Youssef Arfaoui, Mohamed Lotfi
Efrit, Damien Prim
PII:
S0040-4020(18)31272-9
https://doi.org/10.1016/j.tet.2018.10.050
TET 29883
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 31 August 2018
Revised Date: 18 October 2018
Accepted Date: 20 October 2018
Please cite this article as: Azzouni S, Abdelli A, Gaucher A, Arfaoui Y, Efrit ML, Prim D, From imidates
to vinyl-1,2,4-tiazoles: Synthesis, mechanistic aspects and first issues of their reactivity, Tetrahedron
(2018), doi: https://doi.org/10.1016/j.tet.2018.10.050.
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ACCEPTED MANUSCRIPT
From imidates to vinyl-1,2,4-tiazoles: synthesis, mechanistic aspects and first issues of their
reactivity.
Safa Azzouni,a,b Abderrahmen Abdelli,b Anne Gaucher,a Youssef Arfaoui,c Mohamed Lotfi Efrit,b
Damien Prima
a ILV, UVSQ, CNRS, University Paris-Saclay,78035 Versailles (France)
b
Laboratory of Heterocyclic and Selective Organic Chemistry, Department of Chemistry, Faculty of
Sciences of Tunis, University of Tunis El Manar, 2092 Tunis (Tunisia).
C
Laboratory of Physical Chemistry of Condensed Materials, Faculty of Sciences of Tunis, University
of Tunis El Manar, 2092 Tunis (Tunisia).
Dedicated to Pr Leon Ghosez in tribute to his strong, lasting and elegant commitment in transmitting a
"way of doing chemistry".
Abstract
The reaction of variously substituted acylimidates with hydrazine derivatives represents an efficient
and easy to set synthetic entry towards 5-vinyl-1,2,4-triazole derivatives. The construction of the
triazole ring allows the installation of variety of substituent combination at the N(1), C(3) and C(5)
positions of the five-membered heterocycle in good to high yields. The method reveals selective
towards 5-vinyl-1,2,4-triazoles avoiding the potential formation of seven- and five-membered side-
products as supported by theoretical calculations and NMR experiments. First lines of Pd-catalyzed
arylation of the vinyl fragment towards 5-styryl-1,2,4-triazoles and Cu-catalyzed arylation at the N(1)
site are finally described.
Key words:
Acylimidates, 1,2,4-triazoles, DFT calculations, Pd-catalyzed arylation
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Introduction
The wide applicability of imidates (also referred as iminoethers) as key intermediates in organic
synthesis is no longer to demonstrate. Professor Léon Ghosez and coworkers have perfectly illustrated
the use of acylimidates as starting material in the preparation of azadienes paving the way towards an
easy and controlled access to six-membered aza heterocycles through Diels-Alder process.1
Acylimidates are useful precursors of α-alkoxyamides, found in insect toxins2 and more recently of
various five-membered heterocycles such as oxadiazoles, diazaphospholes and triazoles.3-8 Among the
latter, 1,2,4-triazole derivatives attracted lasting interest over the past decades.9-11 Indeed, such
aromatic five-membered rings comprise three nitrogen atoms and two carbon atoms which not only set
their reactivity but also originate many of their applications in medicinal, agricultural, chemical and
supramolecular sciences (figure 1).
N- or C-monosubstituted triazoles
Cl
N
N
N
N
N
N
N
N
H2N
N
N
N
NH
N
O
CH3
CH3
O
HN
H3C
N
N
Fungicide
Antimigraine
Anticancer
Herbicide
N-,C-trisubstituted triazoles
N-,C-disubstituted triazoles
O
H2N
N
C2H5
O
P
N
N
NH2
O
N
S
N
O
N
N
N
O
C2H5
N
O
OH
C2H5
O
HO
OH
Antiviral
Cl
Herbicide
Insecticide
Figure 1. Triazoles and applications, selected examples
. Among the different routes to functionalized 1,2,4-triazoles, the use of imidates as key precursors
remains poorly reported but effectively complements the panel of methodological tools available to
the chemist for the selective construction of these heterocycles. As shown in figure 2, imidates are able
to react with amidines or hydrazines to afford variously substituted 1,2,4-triazoles.
Indeed, the condensation of amidines and NH-imidates represented an attractive way towards NH-
triazoles, although hampered by the presence in most cases of small amounts of side products arising
from the self-condensation of the amidine reactant (figure 2a).3-4,8 The use of hydrazines instead of
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amidines allowed to avoid self condensation byproducts (figure 2b). This methodology proved (i)
efficient to install aryl or alkyl groups at both C(4) and N(1) positions and (ii) especially useful to
introduce nitrogen-based fragments at C(5).5-8 Although of interest, the latter method lacks generality.
Owing to the increasing importance of triazoles in emerging domains, the need for developing new
entries towards such heterocycles, using simple workflow, inexpensive reagents, allowing the
controlled installation of new combinations of valuable substituents therefore spreading the molecular
diversity at the triazole core is currently of high interest.
2a) Kalita and Ahamed, ref. 3,4
NH2
alkyl
O
A
B
H
A
H
B
N
N
N
N
NH
A
A
N
N
NH
A = aryl
B = aryl, cyclohexyl
2b) Deng and Efrit ref. 5,8
H
R
N
B
N
N
H2N
C
A
O
N
N
A
C
alkyl
A = aryl, alkyl
B = Nitrogen-based fragment, aryl
C = aryl, alkyl
2c) this work
H
4
N
N
5
N
O
3
H2N
C
A
O
N
1
A
N
2
C
alkyl
A = aryl, alkyl, benzyl
C
H, aryl, functionalized
alkyl groups
=
Figure 2. Construction of triazoles starting from imidates
In this paper we wish to report the preparation of a new series of acryloylimidates, allowing to install
valuable vinyl fragments at the triazole platform (figure 2c). Although, this straightforward and
general approach enables aryl, alkyl and benzyl groups to be incorporated at position C(3). This
method revealed suitable for the preparation of N-H and N-functionalized triazoles. Indeed, aryl, alkyl,
benzoyl groups can easily be installed at the N(1) atom as well as functionalized alkyl groups which
contribute to expand the molecular diversity on the 1,2,4-triazole platform. Alongside to this synthetic
entry to vinyl triazoles, first lines of the Pd-catalyzed arylation of both the vinyl moiety and the N(1)
atom are described.
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Results/Discussion
We first started with the preparation of acryloylimidates 1. To this end iminoethers 2 were reacted
with acryloyl chlorides 3 in the presence of 1.2 eq. of pyridine in anhydrous Et2O (Scheme 1). Four
new acryloylimidates 1a-d bearing a combination of various substituents including Ph, Bn, iPr arising
from the starting imidate and H and Ph resulting from the acryloyl reactant, were isolated in high
yields ranging from 73 to 83%.
Scheme 1. Synthesis of N-acryloylimidates 1.
The next step was the construction of the triazole ring. We began our study by using acryloylimidate
1a as the model starting material. In fact, N-acryloylimidates 3 displays two reactive sites namely
positions 2 and 4 of the α,β-unsaturated amide moiety. Nucleophilic addition may thus generate either
the expected five-membered triazole or the seven-membered ring analogue (scheme 2). Gratifyingly,
reaction with hydrazine at room temperature in MeOH for 2h allowed complete conversion of the
starting imidate and afforded assumed triazole 4 as a unique product in 82% yield.
NH2NH2
N
N
O
NH
Ph
MeOH, 2h,
r.t.
N
Ph OMe
4 82%
1a
O
O
Ph
N
Ph
HN
N
HN
N
NH2
H
not observed
Scheme 2. Synthesis of triazole 4.
The presence of characteristic signal patterns in 1H NMR (at δ: 6.73, 6.20 and 5.61 ppm) that account
for three vinyl fragment protons undoubtedly confirmed the structure of triazole 4. The obtention of
triazole 4 is also in full agreement theoretical DFT calculations. As shown in Figure 3, the DFT
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activation energy calculations for the formation of compounds 4 vs the seven-membered ring show
that the former is 27.2 kJmol-1 more stable than the latter. Transition states TS2 and TS3 that account
for the formation of the N-C bond and subsequent ring formation towards either the five-membered
ring (blue reaction path) or the seven-membered ring (red reaction path) are plausibly the
discriminating step.
Figure 3. Energy profile of compound 4 and seven-membered ring analogue.
We next envisioned the use of substituted hydrazines. In this case, two regioisomeric triazoles might
be generated during the cyclisation process arising from the nucleophilic addition of two different
nitrogen atom lone pairs and further formation of two different C-N bonds. As shown in scheme 3,
both possible regioisomers display a different substitution pattern when the reaction is carried out
using 2-cyanoethylhydrazine as an example. Gratifyingly, only one regioisomer is produced during the
cyclisation process. The regioselectivity of the cyclisation was elucidated thanks to HMBC experiment
(see ESI) allowing the unambiguous assignment of proximal C(5) and the N(1)-functionalized side
chain methylene protons.
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Scheme 3. Selective formation of 1,2,4-triazole 5.
Starting from imidates 1a-d, we were able to construct variously substituted vinyl 1,2,4-triazoles
(figure 4). Indeed, under the aforementioned conditions, hydrazine and phenylhydrazine cleanly afford
the corresponding N-H or N-Ph triazoles 4, 6-9 in high yields. In addition the use of alkylhydrazines
bearing functional groups such as nitrile is also possible. In this case, triazole 5, bearing a cyanoethyl
group at the N(1) position could be isolated in a 74% yield. Thus our method contributed to expand
the molecular diversity and allowed installing new combination of substituents at the 1,2,4-triazole
platform. Most importantly, both N(1)-substituted and N(1)-H heterocycles can be produced with no
significant decrease of the overall yield.
Figure 4. Synthesis of variously substituted vinyl triazoles 4-9.
The selective installation of a valuable vinyl fragment at C(5) position is the characteristic feature of
the construction of triazole from acryloylimidates. We next focused on the installation of aryl groups
at the vinyl moiety. At this stage, we envisioned the preparation of triazole 10 through two
complementary methods. Indeed, as shown in scheme 4, the installation of aryl group may be obtained
from vinyl triazole 8 through Pd-catalyzed arylation or from the acryloylimidate 1d already bearing
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the aryl group at the earliest stage of the sequence. Starting from vinyltriazole 8, the reaction of
bromobenzene in DMF at 110°C using 5% of Pd(OAc)2 as the catalyst and K3PO4 (2eq.) as the base
revealed successful. Although the conversion was incomplete after 24h, leading to a 10:8 ratio of 4 to
1, the expected triazole could be isolated in fair a 62% yield. The complementary route involving the
construction of the triazole heterocycle from acryloylimidate 1d revealed highly competitive. Indeed,
phenylated triazole 10 was isolated in 83% in one step using phenylhydrazine in MeOH for 2h. Both
routes towards arylated products are highly complementary as illustrated in scheme 4. Indeed, when
N-H vinyl triazole 4 was subjected to the aforementioned catalytic conditions, the arylation sequence
failed. No traces of the arylated product could be identified in the crude material. In contrast, it was
possible to selectively obtain target 11 in 83% yield using the ring construction strategy starting from
imidate 1d and hydrazine. The Pd-catalyzed arylation strategy revealed however mandatory to prepare
substituted C(5)-styryl triazoles bearing substituents for whose the corresponding hydrazine precursor
is rather unstable, or poorly commercially available. As an example, triazole 12 bearing a
carboxaldehyde function can be obtained albeit in a modest 18% yield.
Scheme 4. Pathways towards C(5)-aryl-1,2,4-triazole 10-12
The installation of further molecular diversity at N(1) was next examined by mean of two
complementary methods (scheme 5). Similarly, the metal-catalyzed N-functionalisation from triazole 4
was compared to the construction of N-substituted triazoles from N-acryloylimidates 1a. In this
context, the Pd-catalyzed process might afford both C- and N-arylation products. Under the
aforementioned conditions (Pd(OAc)2 (10%), K3PO4 (2eq.), DMF, 110°C) developed for the
successful arylation of N-phenyl triazole 4, no traces of the expected triazole 8 was detected in the
crude material NMR spectra. Again, the use of P-based ligands such as PPh3 or XPhos did not led to
any further conversion. Fortunately, moving from Pd to Cu afforded first lines of reactivity and
selectivity.12 Indeed, CuI in combination with Cs2CO3 (2eq.) as the base, in the presence of
phenanthroline (20%) as the ligand afforded the expected product 8 albeit in a poor 15% conversion
7

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and a poor 11% yield. Under both Pd- and Cu-catalyzed conditions, hypothetical arylation at the vinyl
group could not be observed, leading to a selective arylation process. In this case the triazole ring
construction method compared favourably to the N-arylation process. Indeed, triazole 8 was isolated
in a fair 86% yield starting from imidate 1a and phenylhydrazine.
Construction
of N-arylated
vinyltriazole
Metal-catalyzed
N-arylation
N
N
N
O
N
NH
N
N
Ar
OMe
N
N
N
4
1a
Ph-I, Pd-conditions
0%
H2N NH
86%
4
1a
1a
Ph-I, Cu-conditions
11%
8
Br
N
H2N NH
68%
N
N
Br
13
I
H
H2N N
N
O
N
1a
N
I
51%
O
14
Scheme 5. Pathways towards N(1)-aryl-1,2,4-triazole 8, 13-14. Pd-based conditions: Pd(OAc)2 (10%),
K3PO4 (2eq.), DMF, 110°C with or without P-based ligand (20%). Cu-based conditions: CuI (10%),
Cs2CO3 (2eq.), phenanthroline (20%), DMF, 110°C.
Although targets such as 13 and 14 might effectively be envisioned from improved and selective Cu-
catalysed process or under carbonylative conditions, the poor conversions observed under metal-
catalyzed conditions currently precludes the use of o-dihalobenzene derivatives. In contrast, the ring
construction method appears a favorable pathway by comparison to the arylation process for the
installation at the N(1) site of fragments bearing metal-reactive substituents such as bromide or iodide.
Indeed, triazoles 13 and 14 were obtained in 68 and 51% yields respectively using o-
bromophenylhydrazine and o-iodophenylhydrazide.13
Conclusion
The reaction of easily accessible acryloylimidates with hydrazines represents a useful synthetic entry
towards the selective preparation of 5-vinyl-1,2,4-triazoles derivatives. The method developed allowed
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not only the installation of a valuable vinyl fragment at the C(5) position of the triazole but also of
new combinations of substituents at N(1), C(3) and C(5) positions including aryl, benzyl, benzoyl.
Theoretical calculations as well as NMR experiments have been realized and are in good agreement
with the selectivity observed during the triazole ring construction sequence. Indeed, neither the
potential seven-membered ring nor the isomeric triazole have been observed. First lines of the
reactivity of the vinyl fragments towards 5-styryl-1,2,4-triazoles is described. Comparison of two
routes involving Pd- or Cu-catalyzed arylation and construction of the heterocycles from arylated
starting material is illustrated highlighting the complementarity of both routes. Further studies are
required to expand the scope of the methodology and fully explore the reactivity of the vinyl
fragments under transition-metal catalysis.
Experimental Section
General information
Unless otherwise specified, reagents were obtained from commercial sources and used without further
purification. Solvents were obtained from Fisher Scientific and dried by standard methods. Reactions
were monitored by thin-layer chromatography (TLC) using ALUGRAM®Xtra SIL GUR Silica Gel 60
F254 plates and visualized using UV light (254 nm). Melting points were determined on a Kofler hot-
staged apparatus and were uncorrected. NMR spectra were recorded in CDCl3 as the solvent with
TMS as the internal standard on a Bruker-300 spectrometer. Chemical shifts are reported in ppm (δ)
downfield relative to TMS. Data are reported as follows: chemical shift, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, bs = broad singlet, m = multiplet), coupling constants (Hz), integration.
High resolution mass spectra (HRMS) were performed on a BrukermaXis Q-TOF spectrometer by
electron spray ionization (ESI) operating in positive mode. All the calculations were performed using
the Gaussian 09 program.14 Imidates 2a-c were prepared according to reported procedures.11 The
geometries of all reactants, transition states, intermediates, and products were fully optimized at the
B3LYP,15 levels of theory using the 6-311+G(d,p) basis set. Frequencies were calculated for all
structures to ensure the absence of imaginary frequencies in the minima and for the presence of only
one imaginary frequency (one negative eigenvalue) in the transition states. For all proposed
mechanisms discussed in this study, the transition states were analyzed using the intrinsic reaction
coordinate (IRC) method16 at B3LYP/6-311G+(d,p) to ascertain that each computed transition state
connects with the proper reactants and products.
General procedure for the preparation of imidates (1a-d).
To a well stirred solution of imidate (1 mmol) and pyridine (12 mmol) in anhydrous Et2O (150 mL)
was added dropwise acryloyl chloride (1 mmol) over 10 minutes at 0°C. The reaction mixture was
stirred for 24 h and then the pyridine hydrochloride which formed was filtered. The solvent was
evaporated under vacuum and the residue was distilled to give a colorless liquid. Imidate 1d revealed
unstable even stored at low temperature, decomposes during purification and has thus to be used
immediately after solvent evaporation.
General procedure for the ring construction of 5-vinyl triazole (4-14).
To a solution of N-acryloylimidates (5 mmol) in methanol (10 mL) was added the hydrazine
derivatives (5.2 mmol). The reaction mixture was stirred at room temperature for 3 to 6 h. The
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precipitate thus formed was collected by filtration, washed with diethyl ether (10 mL), dried and
recrystallized from petroleum ether. In the case of phenylated, 2-ethylcyanated and 2-
ethylhydroxylated hydrazines, the reaction mixture was refluxed in methanol for 3 h.
General procedure for the Pd-catalyzed arylation of 5-vinyl triazole.
A 10 mL dram screwed tube equipped with a magnetic stirring bar was charged with 5-vinyl-1,2,4-
triazole (0.17 mmol, 1.0 equiv), the aryl halide (0.17 mmol, 1.0 equiv), and K3PO4 (108 mg, 0.32
mmol, 2.0 equiv) followed by Pd(OAc)2 (1.7 mg, 0.008 mmol) and DMF (1.0 mL) at rt under argon.
The tube was sealed and put into a preheated oil bath at 110 °C for 4 h. The mixture was cooled to rt
and quenched with H2O (20 mL). The layers were separated and the aqueous layer was extracted with
diethyl ether (3×20 mL). The combined organic extracts were dried over MgSO4, filtered and
concentrated in vacuo. The crude product was then purified by preparative tlc [silica gel (H), EtOAc–
PE, 3:7].
General procedure for the Cu-catalyzed arylation of 5-vinyl triazole.
A 10 mL dram screwed tube equipped with a magnetic stirring bar was charged with 5-vinyl-1,2,4-
triazole (0.17 mmol, 1.0 equiv), the aryl halide (0.17 mmol, 1.0 equiv), and Cs2CO3 (110 mg, 0.32
mmol, 2.0 equiv) followed by Cu2O (4.8 mg, 0.034 mmol), 1,10-Phenantroline (6,1 mg, 0.32 mmol)
and DMF (1.0 mL). The tube was sealed and put into a preheated oil bath at 110 °C for 4 h under
argon. The mixture was cooled to rt and quenched with H2O (20 mL). The layers were separated and
the aqueous layer was extracted with diethyl ether (3×20 mL). The combined organic extracts were
dried over MgSO4, filtered and concentrated in vacuo. The crude product was then purified by
preparative tlc [silica gel (H), EtOAc–PE, 3:7].
Methyl N-acryloylbenzimidate (1a):
1
Viscous oil; b.p. 140 °C at 15 mbar, yield: 83%. H NMR (300 MHz, CDCl3) δ 7.67 – 7.55 (m, 2H),
13
7.49 – 7.30 (m, 3H), 6.36 – 5.93 (m, 2H), 5.81 (dd, J = 6.5, 5.1 Hz, 1H), 3.93 (s, 3H). C NMR (75
MHz, CDCl3) δ 176.05, 158.65, 133.43, 132.09, 131.78, 130.50, 129.90, 129.13, 128.56, 128.50,
54.96. HRMS (ESI): m/z calculated for C11H11O2NNa [M+Na]+: 212.0687; found 212.0688.
Methyl N-acryloyl-2-phenylacetimidate (1b):
1
Viscous oil; b.p. 118 °C at 20 mbar, yield: 79%. H NMR (300 MHz, CDCl3) δ 7.24 (m, 5H), 6.45 –
6.02 (m, 2H), 5.85 – 5.56 (m, 1H), 3.73 (s, 3H), 3.65 (s, 2H). 13C NMR (75 MHz, CDCl3) δ 177.35,
163.93, 134.26, 133.64, 129.99, 129.41, 129.10, 128.56, 127.90, 127.10, 54.51, 38.29. HRMS (ESI):
m/z calculated for C12H13O2NNa [M+Na]+: 226.0844; found 226.0841.
Methyl N-acryloylisobutyrimidate (1c):
1
Viscous oil; b.p. 80 °C at 20 mbar, yield: 73%. H NMR (300 MHz, CDCl3) δ 6.46 – 5.94 (m, 2H),
6.11 – 5.63 (m, 1H), 3.74 (s, 3H), 2.70 (m, 1H), 1.15 (dd, 6H). 13C NMR (75 MHz, CDCl3) δ 177.18,
168.29, 134.04, 129.50, 54.16, 32.49, 19.96, 19.75. HRMS (ESI): m/z calculated for C8H13O2NNa
[M+Na]+: 178.0844; found 178.0838.
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3-Phenyl-5-vinyl-1H-1,2,4-triazole (4):
1
White solid; m.p.140 °C, yield: 82%. H-NMR (300 MHz, CDCl3): 6.73 (dd, J = 17.6, 11.1 Hz, 1H),
6.20 (d, J = 17.6 Hz, 1H), 5.61 (d, J = 11.1 Hz, 1H),7,43-7,60 (m,5H, Ar-H), 13C-NMR (75MHz,
CDCl3): 116.8, 122.8, 125.9-131.4, 149.4, 154.3. HRMS (ESI): m/z calculated for C10H10N3 [M+H]+:
172.0875; found 172.0874.
3-(3-benzyl-5-vinyl-1H-1,2,4-triazol-1-yl)propanenitrile (5):
1
White solid, m.p. 148 °C, yield: 74%. H NMR (300 MHz, CDCl3) δ 7.24 (m, J = 13.9, 7.4 Hz, 5H),
6.63 – 6.39 (m, 1H), 6.31 (dd, J = 17.1, 1.2 Hz, 1H), 5.63 (d, J = 10.8 Hz, 1H), 4.18 (t, J = 6.3 Hz,
2H), 4.02 (s, 1H), 2.76 (t, J = 7.3, 4.9 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 163.11, 152.95, 137.80,
128.80, 128.68, 128.55, 128.42, 126.48, 124.26, 119.95, 116.59, 43.10, 34.43, 18.48. HRMS (ESI):
m/z calculated for C13H13N4 [M+H]+: 239.1297; found 239.1293.
3-Benzyl-5-vinyl-1H-1,2,4-triazole (6):
1
Light yellow solid; m.p. 149 °C, yield: 71%. H NMR (300 MHz, CDCl3) δ 7.21 (d, J = 5.7 Hz, 6H),
6.58 (dd, J = 17.6, 11.1 Hz, 1H), 6.10 (d, J = 17.5 Hz, 1H), 5.46 (d, J = 11.0 Hz, 1H), 4.03 (s, 2H). 13C
NMR (75 MHz, CDCl3) δ 158.95, 158.56, 136.34, 128.96, 128.84, 128.76, 128.57, 127.01, 124.89,
120.52, 33.54. HRMS (ESI): m/z calculated for C11H12N3 [M+H]+: 186.1031; found 186.1028.
3-Isopropyl-5-vinyl-1H-1,2,4-triazole (7):
Light pink solid; m.p. 128 °C, yield: 76%. 1H NMR (300 MHz, CDCl3) δ 6.68 (dd, J = 17.7, 11.1 Hz,
1H), 6.17 (d, J = 17.7 Hz, 1H), 5.52 (d, J = 11.2 Hz, 1H), 3.14 (m, 1H), 1.36 (d, J = 7.0 Hz, 8H). 13C
NMR (75 MHz, CDCl3) δ 164.73, 158.88, 125.34, 120.35, 27.30, 21.32, 21.13.HRMS (ESI): m/z
calculated for C7H12N3 [M+H]+: 138.1031; found 138.1029.
1,3-Diphenyl-5-vinyl-1,2,4-triazole (8):
1
Yellow solid; m.p. 99 °C, yield: 86%. H NMR (300 MHz, CDCl3) δ 8.20 (dd, J = 8.0, 1.6 Hz, 2H),
7.66 – 7.27 (m, 8H), 6.57 (dd, J = 15.9, 6.3 Hz, 2H), 5.67 (dd, J = 10.3, 2.2 Hz, 1H . 13C NMR (75
MHz, CDCl3) δ 161.86, 152.92, 137.11, 130.71, 129.47, 129.40, 129.05, 128.69, 128.54, 126.57,
125.35, 123.73, 121.68. HRMS (ESI): m/z calculated for C16H14N3 [M+H]+: 248.1188; found
248.1187.
3-Isopropyl-1-phenyl-5-vinyl-1,2,4-triazole (9):
Yellow solid; m.p. 97 °C, yield: 76%. 1H NMR (300 MHz, CDCl3) δ 7.57 – 7.35 (m, 5H), 6.64 – 6.46
(m, 1H), 6.38 (dd, J = 17.3, 1.6 Hz, 1H), 5.59 (dd, J = 10.8, 1.8 Hz, 1H), 3.14 (m, J = 13.9, 7.0 Hz,
1H), 1.40 (m, J = 6.9, 1.4 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ 169.22, 152.06, 137.21, 129.36,
129.09, 128.75, 125.56, 125.32, 123.09, 121.85, 28.34, 21.69, 21.23. HRMS (ESI): m/z calculated for
C13H16N3 [M+H]+: 214.1344; found 214.1341.
1,3-diphenyl-5-styryl-1,2,4-triazole (10):
Yellow powder, m.p. 132 °C, yield: 78%. 1H NMR (300 MHz, CDCl3) δ 8.22 – 8.07 (m, 2H), 7.82 (d,
J = 16.0 Hz, 1H), 7.52 – 7.17 (m, 13H), 6.82 (d, J = 16.0 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ
162.05, 153.40, 137.93, 137.36, 135.65, 130.86, 129.64, 129.48, 129.34, 129.12, 128.89, 128.65,
127.45, 126.69, 125.50, 111.97. HRMS (ESI): m/z calculated for C22H18N3 [M+H]+: 324.1501 ; found
324.1510
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3-Phenyl-5-styryl-1H-1,2,4-triazole (11):
1
White solid, m.p. 110 °C, Yield: 83%. H NMR (300 MHz, CDCl3) δ 7.99 (dd, J = 6.6, 2.9 Hz, 2H),
7.61 (d, J = 16.3 Hz, 1H), 7.45 – 7.04 (m, 8H), 6.97 (d, J = 16.3 Hz, 1H). 13C NMR (75 MHz, CDCl3)
δ 159.96, 158.18, 135.92, 135.71, 130.05, 128.97, 128.92, 128.81, 128.77, 128.70, 128.44, 128.40,
127.17, 126.61, 126.56, 114.53. HRMS (ESI): m/z calculated for C16H14N3 [M+H]+: 248.1188; found
248.1185.
(E)-2-(2-(1,3-diphenyl-1H-1,2,4-triazol-5-yl)vinyl)benzaldehyde (12):
Yellow powder, m.p. 162 °C, Yield: 18% .1H NMR (300 MHz, CDCl3) δ (major) 10.33 (s, 1H), 8.62
(d, J = 15.8 Hz, 1H), 8.18 (d, J = 6.3 Hz, 2H), 7.83 (d, J = 7.4 Hz, 2H), 7.64 – 7.28 (m, 10H), 6.81 (d,
J = 15.8 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ (major) 91.80, 162.34, 152.84, 138.07, 134.02,
133.89, 133.66, 131.74, 129.69, 129.54, 129.24, 129.15, 128.62, 127.60, 126.71, 126.46, 125.49,
124.71, 117.44, 117.01. HRMS (ESI): m/z calculated for C23H18N3O [M+H]+: 352.1450 ; found
352.1442.
1-(2-bromophenyl)-3-phenyl-5-vinyl-1H-1,2,4-triazole (13)
Yellow powder, m.p 134°C yield: 58%. 1H NMR (300 MHz, CDCl3) δ 8.38 – 8.15 (m, 2H), 7.66 (dd,
J = 7.9, 1.4 Hz, 2H), 7.56 – 7.16 (m, 5H), 6.98 (dd, J = 19.6, 8.0 Hz, 2H), 6.76 (t, J = 7.6 Hz, 1H). 13C
NMR (75 MHz, CDCl3) δ 162.44, 155.87, 142.58, 130.67, 130.59, 130.11, 129.54, 128.80, 128.63,
128.58, 127.88, 127.60, 126.64, 125.07, 124.52, 118.60, 117.12. HRMS (ESI): m/z calculated for
C16H13N3Br [M+H]+: 326.0293 ; found 326.0298.
(2-iodophenyl)(3-phenyl-5-vinyl-1H-1,2,4-triazol-1-yl)methanone (14)
White powder, m.p 159°C yield: 71%. 1H NMR (300 MHz, CDCl3) δ 8.15 – 8.04 (m, 2H), 7.98 (d, J =
7.8 Hz, 1H), 7.62 (dd, J = 17.0, 6.0 Hz, 1H), 7.57 – 7.50 (m, 2H), 7.49 – 7.39 (m, 3H), 7.36 – 7.20 (m,
1H), 6.81 (dd, J = 17.3, 1.4 Hz, 1H), 5.95 (dd, J = 11.0, 1.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ
168.01, 161.96, 157.45, 139.61, 139.29, 132.21, 130.34, 129.87, 129.53, 128.58, 127.73, 127.24,
127.02, 123.42, 95.57. HRMS (ESI): m/z calculated for C17H13N3OI [M+H]+: 402.0103 ; found
402.0105.
Acknowledgments
The authors would like to thank the University of Versailles and the Tunisian Ministry of Higher
Education and Scientific Research for financial support and Dr M A Sanhoury from the Faculty of
Sciences of Tunis for assistance and fruitful discussion of this work.
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