N2-selective alkylation of NH-1,2,3-triazoles with vinyl ethers: Via gold catalysis

Article abstract of DOI:10.1039/c8ra04790a

A new method was developed to synthesize N²-alkyl-substituted 1,2,3-triazoles via gold catalyzed alkylation of vinyl ethers with mono- and unsubstituted NH-1,2,3-triazoles and benzotriazole. A hydrogen bond between the oxygen atom of the vinyl ethers, activated via the gold catalyst, and the NH-1,2,3-triazoles was supposed to be generated, which selectively gave the N²-alkylation products.

Full text of DOI:10.1039/c8ra04790a

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2
N -selective alkylation of NH-1,2,3-triazoles with
vinyl ethers via gold catalysis†
Cite this: RSC Adv., 2018, 8, 27610
Guoli Luo, Chenyang Sun, Yan Li, Xiaoxiao Li * and Zhigang Zhao*
2
Received 5th June 2018
Accepted 4th July 2018
A new method was developed to synthesize N -alkyl-substituted 1,2,3-triazoles via gold catalyzed
alkylation of vinyl ethers with mono- and unsubstituted NH-1,2,3-triazoles and benzotriazole. A
DOI: 10.1039/c8ra04790a
hydrogen bond between the oxygen atom of the vinyl ethers, activated via the gold catalyst, and the
2
NH-1,2,3-triazoles was supposed to be generated, which selectively gave the N -alkylation products.
rsc.li/rsc-advances
Introduction
Substituted 1,2,3-triazoles are among the most important N-
heterocyclic compounds and display a broad spectrum of
applications in the areas of medicinal chemistry, agrochemi-
1
cals, and materials science. 1,2,3-Triazoles containing hetero-
cyclic compounds serve as intermediates for the synthesis of
2
biologically active compounds. Both thermal and Cu(I)/Ru(II)-
catalyzed condensations of alkynes and azides provide an
1
3
excellent approach to N -substituted triazoles. However, the
2
4,5
synthesis of N -substituted triazoles remains a challenge.
particularly interesting subset of these compounds are N -alkyl-
A
2
1
,2,3-triazoles, which possess a broad spectrum of antiherpetic,
6
antiarrhythmic and antiviral activities. Ideally, the most direct
route to N -alkyl-1,2,3-triazoles involves nucleophilic substitu-
2
2
Scheme 1 N alkylation of NH-1,2,3-triazoles.
tion of alkylating reactants with NH-1,2,3-triazoles, however,
7
a mixture of the isomeric products is oen produced. Recently,
the N -selective alkylation reactions of alkyl halides with 1,2,3-
2
between the oxygen atom of vinyl ethers activated via gold
catalyst with NH-1,2,3-triazoles produces N -alkyl-1,2,3-triazoles
2
triazoles have been achieved by incorporating C-4- and C-5-
substituents on the heteroarenes, of which the synthetic
utility was thus restricted by the substrate's steric requirements.
(Scheme 1b).
2
Another route to the N -alkyl-1,2,3-triazoles, addition of 1-
Results and discussion
sulfonyl-1,2,3-triazoles to olens or vinyl ethers catalyzed by
2
8
TsOH or gold catalyst, was reported by Chen and our group.
Based on our previous results with respect to the N -selective
2
8b
Very recently, Chen and co-workers reported the highly N - gold-catalyzed alkylation of 1-sulfonyl-1,2,3-triazoles,
we
selective alkylation reactions of NH-1,2,3-triazoles with olens began our studies by exploring the reaction between NH-1,2,3-
9
1
mediated by NIS, in which the favored N -type intermolecular triazole (1a) and vinyl ether (2a). The optimization results are
2
hydrogen bonding connection during the transition summarized in Table 1. To our delight, the desired N -alkyl-
state provides the coupling adduct with a high N -selectively 1,2,3-triazole 3a was obtained in 95% yield in the presence of
Scheme 1a). Based on our previous report of gold catalyzed N
alkylation of 1-sulfonyl-1,2,3-triazoles with vinyl ethers, we (DCE) at 80 C, without a N -coupling adduct (Table 1, entry 1).
2
2
(
3 2
Ph PAuCl (5 mol%)/AgNTf (5 mol%) in 1,2-dichloroethane
ꢀ
1
8b
hope to extend this reaction involving the use of NH-1,2,3- In order to optimize the reaction conditions, different silver
triazoles as nucleophiles, in which the hydrogen bond salts were screened, of which Ph PAuCl/AgNTf was found to be
3 2
the best silver combination (Table 1, entries 2 and 3). The
catalyst ligands were then evaluated. The N-heterocyclic car-
bene ligand IPrAuCl showed moderate activity, while the
phosphine ligand JohnphosAuCl was not favored in this trans-
formation, affording 3a in only 30% yield (Table 1, entries 4 and
5). Further solvent optimization identied DCE to be the best
College of Chemistry and Environmental Protection Engineering, Southwest Minzu
University, Chengdu 610041, P. R. China. E-mail: lixiaoxiao.2005@163.com;
zzg63129@163.com
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c8ra04790a
1
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a
Table 1 Condition optimization for the reaction of 1a with 2a
conversion of 3a to 65% (Table 1, entry 11), which indicates that
the excess of vinyl ether probably is necessary due to the high
tendency of vinyl ethers to undergo cationic polymerization
initiated by gold(I). Decreasing the catalyst loading to 2 mol%
led to reduced reaction yield of 72% (Table 1, entry 12). In the
11
control experiments, employing Ph
3 2
PAuCl and AgNTf sepa-
rately gave none of the desired product (Table 1, entries 12 and
b
13) even aer 24 hours.
Entry Cat. (mol%)
Solvent
Time (h) Yield (%)
With the optimized reaction conditions in hand, we exam-
ined the scope of this transformation by synthesizing a series
N -alkyl-1,2,3-triazoles. As shown in Table 2, various NH-1,2,3-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
Ph
Ph
Ph
3
3
3
PAuCl/AgNTf
PAuCl/AgOTf (5)
PAuCl/AgSbF (5)
(5)
JohnphosAuCl/AgNTf
2
(5)
DCE
DCE
DCE
DCE
6
6
6
6
6
6
6
6
95
81
75
79
30
34
24
60
71
69
65
72
NR
NR
2
6
triazoles were explored by using vinyl ether 2a as the reac-
tants. First, various 4-aryl substituted NH-1,2,3-triazoles were
explored. The NH-1,2,3-triazoles containing electron-donating
functional groups, such as methyl, t-butyl, and methoxy, at
the para position of the aromatic ring gave comparably good
IPrAuCl/AgNTf
2
2
(5) DCE
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl/AgNTf
PAuCl (5)
2
2
2
2
2
2
2
(5)
(5)
(5)
(5)
(5)
(5)
(2)
DCM
CHCl
3
CH
3
CN
Toluene
DCE
DCE
DCE
DCE
6
2
c
yields (80–87%) of the desired N -alkyl-1,2,3-triazoles. However,
0
1
2
3
4
22
24
24
24
24
d
4
-halogen phenyl substituted NH-1,2,3-triazoles gave the cor-
responding products in moderate yields, in which the more
electron decient triazole rings reduced their nucleophilicities.
The reaction of 2-thienyl substituted NH-1,2,3-triazoles went
e
e
AgNTf
2
(5)
DCE
a
Unless noted, all reactions were carried out at the 0.1 mmol scale in smoothly, affording 3h in 77% yield. Moreover, 4-alkyl
3
mL solvent with the addition of 5 mol% catalyst (1a/2a ¼ 1/3) at
b c
˚
substituted NH-1,2,3-triazoles 1i and unsubstituted NH-1,2,3-
ꢀ
8
0 C, NR ¼ no reaction. Isolated yield. 100 mg 4 A MS was added.
2
d
e
triazole 1j could also provide the corresponding N -alky-
2
Equiv. 2a was added. No consumption of starting material 1a
was seen aer 24 h.
substituted 1,2,3-triazoles 3i and 3j in moderate yields. Benzo-
triazole 1k was also tested, giving 3k in 89% yield.
We next set out to explore the scope of vinyl ethers 2 in the
presence of 4-phenyl substituted 1,2,3-triazol 1a (Table 3). First,
cyclic vinyl ether 2,3-dihydrofuran 2b worked very well, giving
a,b
Table 2 Variation of the NH-1,2,3-triazoles 1
4b in 74% yield. Next, we investigated the linear vinyl ether's
reactions. We found that mono-substituted and 1,2-disubsti-
tuted linear vinyl ether could be employed in this reaction and
gave the desired products in good yields. Moreover, 1,1-disub-
2
stituted vinyl ether 2j could also provide the desired N -alkyl-
1,2,3-triazole 4j in 77% yield. This reaction was also efficient
with alpha-angelica lactone, giving 4k in 93% yield.
In order to understand the mechanism for the regioselective
2
synthesis of N -alkyl-1,2,3-triazoles, we performed two control
experiments. First, we replaced vinyl ether with 4-tert-butyl-
styrene in the model reaction, no product was obtained. This
may be due to the lower complexation of olen with gold
(
Scheme 2(1)). Then, we performed this reaction in the presence
1
of phenylacetylene, N -vinyl substituted 1,2,3-triazole 7 was
obtained in 70% yield, which was in accordance with our
12
previous report (Scheme 2(2)). The two control experiments
2
suggested that the N -regioselectivity may be induced by the
substrate vinyl ethers in this reaction.
Based on our experimental results and precedents in the
literature, a proposed catalytic cycle for the N -selective alkylation
a
Unless noted, all reactions were carried out at the 0.1 mmol scale in
2
3
8
mL solvent with the addition of 5 mol% catalyst (1/2a ¼ 1/3) at
ꢀ
b
0 C. Isolated yield.
is presented in Scheme 3. Initial complexation of gold could
8a
13
occur via pathway A or B. Pathway A shows a one-step process
involving the nucleophilic attack of the internal nitrogen of the
NH-1,2,3-triazole 1a on Au(I)-coordinated vinyl ether 2a through
the hydrogen bond interaction to form the alkyl gold interme-
reaction medium (Table 1, entries 6–9). The addition of 4 A˚
molecular sieves resulted in a decreased conversion into 3a in
6
gold catalyst poisons contained in molecular sieves. Variation
of the number of equivalents of 2a from 3.0 to 2.0 lowed the
9% yield aer 22 hours (Table 1, entry 10), due to the possible
14
10
diate. This subsequently undergoes protodemetalation giving
2
the N -alkyl-1,2,3-triazole 3a. Pathway B shows a two-step process
invoking a triazole–Au complex, which then activated vinyl ether
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a,b
2
Table 3 Variation of the vinyl ethers 2
and subsequently undergoes N -selective alkylation with the
internal nitrogen of the NH-1,2,3-triazole 1a to give the alkyl gold
1
4
intermediate. This subsequently undergoes protodemetalation
2
giving the N -alkyl-1,2,3-triazole 3a. However, pathway B might be
unfavorable because the N -vinyl substituted 1,2,3-triazole could
2
not be observed in our control experiment (Scheme 2(2)).
Conclusions
2
In summary, we have developed a new method to synthesis N -
alkyl-1,2,3-triazoles through gold catalyzed alkylation of vinyl
ethers with NH-1,2,3-triazoles. The reaction is facile, high
yielding and regioselective. The regioselectivity may be induced
by the hydrogen bond between the oxygen atom of vinyl ethers
with NH-1,2,3-triazole. The potential utilization and extension
of this interesting synthetic methodology are currently
underway.
Experimental
General methods
All reactions were performed using Schlenk-tubes, septa, and
syringes under nitrogen atmosphere. Commercial reagents were
used as supplied or puried by standard techniques where
necessary. Column chromatography was performed using 200–
a
Unless noted, all reactions were carried out at the 0.1 mmol scale in
3
8
mL solvent with the addition of 5 mol% catalyst (1a/2 ¼ 1/3) at
ꢀ
b
0 C. Isolated yield.
300 mesh silica with the proper solvent system according to TLC
analysis using KMnO stain and UV light to visualize the reaction
4
components. Unless otherwise noted, nuclear magnetic reso-
nance spectra were recorded on a Agilent 400 MHz spectrometer
using CDCl
NMR data were reported as follows: chemical shi, multiplicity (s
singlet, d ¼ doublet, t ¼ triplet, m ¼ multiplet and bs ¼ broad
singlet), coupling constant in Hz and integration. Chemical shis
3
with TMS as internal reference at room temperature.
¼
1
3
for C NMR spectra were recorded in parts per million from
tetramethylsilane using the central peak of deuterochloroform
Scheme 2 Control experiments.
(77.0 ppm) as the internal standard. Melting points were deter-
mined on a WRS-1B digital melting point instrument. IR spectra
were obtained on Nicoletisso FTIR using KBr disks. HR-MS
spectral were determined on a Bruker Daltonics Bio TOF mass
spectrometer. NH-1,2,3-triazoles 1a–1m were prepared according
14
to the published methods. Vinyl ethers were obtained
commercially and used without further purication.
General procedure for synthesis of compound 3a
To a Schlenk tube charged with nitrogen was added Ph PAuCl/
3
AgNTf
2
(5 mol%) in dry DCE (3 mL). Aer three minutes, NH-
1,2,3-triazole 1a (0.1 mmol), vinyl ether 2a (0.3 mmol) were
added to the reaction. Then the reaction mixture was stirred at
ꢀ
8
0 C for 6 h until complete consumption of starting material as
monitored by TLC. Concentration of the reaction mixture in
vacuo followed by purication through ash chromatography
2
on silica gel column (hexane/EtOAc ¼ 30/1) afforded N -alkyl-
substituted 1,2,3-triazole 3a.
2
4-Phenyl-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3a).
The spectroscopic data are in accordance with those reported.
Scheme 3 Proposed catalytic cycle for the N -selective alkylation.
8
b
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Yield: 21.8 mg (95%); yellow oil liquid; R
f
¼ 0.20 (hexane– NMR (400 MHz, CDCl
3
): d 7.90 (s, 1H), 7.76 (d, J ¼ 8.3 Hz, 2H), 7.40
ꢁ1 1
EtOAc, 10 : 1). IR (neat): 3475, 2951, 1611, 1391, 1063 cm . H (d, J ¼ 8.2 Hz, 2H), 5.77–5.72 (m, 1H), 4.08 (d, J ¼ 11.8 Hz, 1H), 3.79
NMR (400 MHz, CDCl ): d 7.92 (s, 1H), 7.82 (d, J ¼ 7.7 Hz, 2H), (d, J ¼ 9.9 Hz, 1H), 2.51–2.43 (m, 1H), 2.16–2.09 (m, 2H), 1.77–1.72
3
13
7
1
(
1
1
.42 (t, J ¼ 7.4 Hz, 2H), 7.35 (t, J ¼ 6.9 Hz, 1H), 5.75 (d, J ¼ 8.8 Hz, (m, 2H), 1.69–1.66 (m, 1H). C NMR (100 MHz, CDCl ): d 147.1,
3
H), 4.08 (d, J ¼ 11.3 Hz, 1H), 3.77 (t, J ¼ 10.4 Hz, 1H), 2.52–2.45 134.4, 131.5, 129.0, 128.7, 127.3, 89.2, 67.5, 29.4, 24.8, 21.8.
m, 1H), 2.15–2.10 (m, 2H), 1.74–1.72 (m, 2H), 1.69–1.63 (m,
4-(4-Bromophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-tri-
1
3
H). C NMR (100 MHz, CDCl
3
): d 148.1, 131.5, 130.1, 128.8, azole (3g). The spectroscopic data are in accordance with those
8
b
28.5, 126.1, 89.1, 67.5, 29.4, 24.7, 21.8.
-(Tetrahydro-2H-pyran-2-yl)-4-(p-tolyl)-2H-1,2,3-triazole
3b). The spectroscopic data are in accordance with those EtOAc, 10 : 1). IR (neat): 3470, 2948, 1645, 1387, 1066 cm . H
reported.
2
Yield: 17.7 mg (76%); colorless oil liquid; R
f
¼ 0.20 (hexane–
ꢁ1 1
(
8
b
reported.
NMR (400 MHz, CDCl ): d 7.93 (s, 1H), 7.72 (d, J ¼ 8.4 Hz, 2H),
3
Yield: 19.4 mg (80%); colorless oil liquid; R ¼ 0.20 (hexane– 7.58 (d, J ¼ 8.3 Hz, 2H), 5.79–5.74 (m, 1H), 4.10 (d, J ¼ 11.7 Hz,
f
ꢁ1 1
EtOAc, 10 : 1). IR (neat): 3466, 2955, 1645, 1398, 1070 cm . H 1H), 3.79 (d, J ¼ 9.9 Hz 1H), 2.53–2.45 (m, 1H), 2.18–2.12 (m,
1
3
NMR (400 MHz, CDCl
3
): d 7.89 (s, 1H), 7.71 (d, J ¼ 8.0 Hz, 2H), 2H), 1.78–1.71 (m, 2H), 1.72–1.67 (m, 1H). C NMR (100 MHz,
.23 (d, J ¼ 7.9 Hz, 2H), 5.73 (dd, J ¼ 9.3, 2.4 Hz, 1H), 4.08 (d, J ¼ CDCl ): d 147.1, 131.9, 131.5, 129.1, 127.6, 122.6, 89.2, 67.5,
1.4 Hz, 1H), 3.80–3.73 (m, 1H), 2.54–2.44 (m, 1H), 2.38 (s, 3H), 29.4, 24.8, 21.8.
7
1
2
3
1
3
.17–2.08 (m, 2H), 1.78–1.72 (m, 2H), 1.68–1.62 (m, 1H).
C
2-(Tetrahydro-2H-pyran-2-yl)-4-(thiophen-2-yl)-2H-1,2,3-tri-
NMR (100 MHz, CDCl ): d 148.2, 138.5, 131.4, 129.5, 127.2, azole (3h). The spectroscopic data are in accordance with those
3
8
b
1
25.9, 89.1, 77.3, 29.4, 24.8, 21.9, 21.3.
-(4-(tert-Butyl)phenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-
,2,3-triazole (3c). The spectroscopic data are in accordance EtOAc, 10 : 1). IR (neat): 3470, 2951, 1648, 1392, 1075 cm . H
reported.
4
Yield: 18.1 mg (77%); colorless oil liquid; R ¼ 0.20 (hexane–
f
ꢁ1 1
1
8b
with those reported.
NMR (400 MHz, CDCl
3
): d 7.80 (s, 1H), 7.64 (d, J ¼ 1.4 Hz, 1H),
Yield: 22.8 mg (80%); colorless oil liquid; R
EtOAc, 10 : 1). IR (neat): 3470, 2970, 1644, 1490, 1092 cm . H 1.9 Hz, 1H), 4.06 (d, J ¼ 11.4 Hz, 1H), 3.74 (t, J ¼ 10.6 Hz, 1H),
NMR (400 MHz, CDCl
f
¼ 0.20 (hexane– 7.47 (d, J ¼ 5.0 Hz, 1H), 7.39–7.34 (m, 1H), 5.71 (dd, J ¼ 9.0,
ꢁ1 1
3
): d 7.88 (s, 1H), 7.74 (d, J ¼ 8.4 Hz, 2H), 2.49–2.42 (m, 1H), 2.13–2.06 (m, 2H), 1.74–1.72 (m, 2H), 1.69–
1
3
7
1
2
.44 (d, J ¼ 8.3 Hz, 2H), 5.77–5.70 (m, 1H), 4.06 (d, J ¼ 11.4 Hz, 1.63 (m, 1H). C NMR (100 MHz, CDCl ): d 144.3, 131.7, 131.5,
3
H), 3.76 (t, J ¼ 9.7 Hz, 1H), 2.51–2.43 (m, 1H), 2.14–2.08 (m, 126.4, 126.0, 122.0, 89.1, 67.5, 29.4, 24.8, 21.9.
1
3
H), 1.75–1.71 (m, 2H), 1.67–1.62 (m, 1H), 1.33 (s, 9H). C NMR
4-Butyl-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole
(3i).
(
8
100 MHz, CDCl
3
): d 151.7, 148.1, 131.5, 127.3, 125.9, 125.7, Yield: 15.1 mg (72%); colorless oil liquid; R
9.1, 67.5, 34.7, 31.3, 29.4, 24.8, 21.9. EtOAc, 10 : 1). IR (neat): 3464, 2931, 1658, 1266, 1092 cm . H
-(4-Methoxyphenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3- NMR (400 MHz, CDCl
): d 7.36 (s, 1H), 5.55 (dd, J ¼ 9.5, 1.6 Hz,
triazole (3d). The spectroscopic data are in accordance with 1H), 3.98 (d, J ¼ 11.6 Hz, 1H), 3.65 (t, J ¼ 10.7 Hz, 1H), 2.62 (t, J ¼
f
¼ 0.20 (hexane–
ꢁ1 1
4
3
8b
those reported.
7.8 Hz, 2H), 2.33 (dd, J ¼ 20.2, 9.8 Hz, 1H), 2.00 (t, J ¼ 14.0 Hz,
Yield: 22.6 mg (87%); yellow oil liquid; R ¼ 0.10 (hexane– 2H), 1.68–1.52 (m, 5H), 1.31 (dd, J ¼ 14.9, 7.4 Hz, 2H), 0.86 (t, J ¼
f
ꢁ1
1
13
EtOAc, 10 : 1). IR (neat): 3467, 2954, 1631, 1396, 1058 cm . H 7.3 Hz, 3H). C NMR (100 MHz, CDCl ): d 149.3, 133.2, 88.8,
3
NMR (400 MHz, CDCl ): d 7.83 (s, 1H), 7.73 (d, J ¼ 8.5 Hz, 2H), 67.6, 31.2, 29.4, 25.2, 24.8, 22.3, 22.1, 13.8. HRMS (ESI): m/z [M +
3
+
+
6
1
1
.94 (d, J ¼ 8.7 Hz, 2H), 5.71 (dd, J ¼ 9.5, 2.6 Hz, 1H), 4.06 (d, J ¼ H] calcd for C11
20 3
H N O : 210.1601; found: 210.1599.
1.5 Hz, 1H), 3.83 (s, 3H), 3.74 (t, J ¼ 11.2, 1H), 2.50–2.43 (m,
2-(Tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3j). Yield:
¼ 0.50 (hexane–EtOAc,
H), 2.14–2.07 (m, 2H), 1.75–1.70 (m, 2H), 1.68–1.63 (m, 1H). 9.3 mg (61%); colorless oil liquid; R
f
1
3
ꢁ1
1
C NMR (100 MHz, CDCl
14.2, 89.1, 67.5, 55.3, 29.4, 24.8, 21.9.
-(4-Fluorophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-tri-
3
): d 159.9, 148.0, 131.1, 127.4, 122.8, 10 : 1). IR (neat): 3454, 2954, 1661, 1358, 1095 cm . H NMR
(400 MHz, CDCl
): d 7.68 (s, 2H), 5.73 (d, J ¼ 9.1 Hz, 1H), 4.04 (d,
J ¼ 11.5 Hz, 1H), 3.77–3.71 (m, 1H), 2.48–2.39 (m, 1H), 2.09–2.06
1
3
4
1
3
azole (3e). The spectroscopic data are in accordance with those (m, 2H), 1.73–1.65 (m, 3H). C NMR (100 MHz, CDCl ): d 134.6,
3
+
8
b
reported.
Yield: 13.8 mg (56%); colorless oil liquid; R
EtOAc, 10 : 1). IR (neat): 3477, 2959, 1617, 1397, 1094 cm . H
NMR (400 MHz, CDCl ): d 7.86 (s, 1H), 7.80–7.75 (m, 2H), 7.10 (t, Yield: 18.1 mg (89%); colorless oil liquid; R
88.9, 67.4, 29.4, 24.7, 21.8. HRMS (ESI): m/z [M + H] calcd for
H
+
f
¼ 0.20 (hexane–
C
7
12
N
3
O : 154.0975; found: 154.0968.
ꢁ1 1
2-(Tetrahydro-2H-pyran-2-yl)-2H-benzo[d][1,2,3]triazole (3k).
¼ 0.10 (hexane–
3
f
ꢁ
1 1
J ¼ 8.6 Hz, 2H), 5.72 (dd, J ¼ 9.1, 2.0 Hz, 1H), 4.06 (d, J ¼ 11.4 Hz, EtOAc, 10 : 1). IR (neat): 3467, 2940, 1664, 1274, 1086 cm . H
1
2
H), 3.75 (t, J ¼ 10.7 Hz, 1H), 2.49–2.42 (m, 1H), 2.13–2.07 (m, NMR (400 MHz, CDCl
3
): d 8.07 (d, J ¼ 8.4 Hz, 1H), 7.74 (d, J ¼
1
3
H), 1.74–1.71 (m, 2H), 1.68–1.63 (m, 1H). C NMR (100 MHz, 8.3 Hz, 1H), 7.49 (t, J ¼ 7.6 Hz, 1H), 7.38 (t, J ¼ 7.7 Hz, 1H), 6.04
CDCl ): d 162.9 (d, J ¼ 246.5 Hz), 147.3, 131.3, 127.9 (d, J ¼ 8.2 (dd, J ¼ 8.2, 2.7 Hz, 1H), 3.95 (dd, J ¼ 11.7, 4.6 Hz, 1H), 3.83–3.75
3
Hz), 126.4, 115.8 (d, J ¼ 21.6 Hz), 89.2, 67.5, 29.4, 24.8, 21.9.
-(4-Chlorophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-tri-
azole (3f). The spectroscopic data are in accordance with those 66.8, 29.3, 24.9, 21.6. HRMS (ESI): m/z [M + H] calcd for
(m, 1H), 2.68–2.57 (m, 1H), 2.23–2.19 (m, 1H), 1.90–1.71 (m, 4H)
C NMR (100 MHz, CDCl ): d 127.4, 124.1, 119.9, 111.1, 85.6,
3
1
3
4
+
8
b
+
reported.
Yield: 16.8 mg (64%); yellow oil liquid; R
EtOAc, 10 : 1). IR (neat): 3475, 2971, 1645, 1393, 1093 cm . H spectroscopic data are in accordance with those reported.
C
11
H
14
N
3
O : 204.1131; found: 204.1130.
f
¼ 0.20 (hexane–
ꢁ1 1
4-Phenyl-2-(tetrahydrofuran-2-yl)-2H-1,2,3-triazole (4b). The
8b
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Yield: 15.9 mg (74%); colorless oil liquid; R
EtOAc, 10 : 1). IR (neat): 3474, 2979, 1645, 1381, 1074 cm . H troscopic data are in accordance with those reported.
f
¼ 0.20 (hexane–
2-(1-Ethoxypropyl)-4-phenyl-2H-1,2,3-triazole (4h). The spec-
ꢁ
1
1
8b
NMR (400 MHz, CDCl ): d 7.97 (s, 1H), 7.89 (d, J ¼ 7.4 Hz, 2H),
Yield: 17.1 mg (74%); colorless oil liquid; R ¼ 0.50 (hexane–
3
f
ꢁ1 1
7
2
7
1
1
.52 (t, J ¼ 7.6 Hz, 2H), 7.45 (t, J ¼ 7.3 Hz, 1H), 6.43 (dd, J ¼ 6.7, EtOAc, 10 : 1). IR (neat): 3465, 2963, 1650, 1381, 1107 cm . H
.3 Hz, 1H), 4.30 (dd, J ¼ 14.1, 7.6 Hz, 1H), 4.16 (dd, J ¼ 14.0, NMR (400 MHz, CDCl ): d 7.90 (s, 1H), 7.82 (d, J ¼ 7.1 Hz, 2H), 7.42
3
.7 Hz, 1H), 2.83–2.76 (m, 1H), 2.59–2.48 (m, 2H), 2.25–2.16 (m, (t, J ¼ 7.4 Hz, 2H), 7.34 (t, J ¼ 7.4 Hz, 1H), 5.52 (t, J ¼ 6.7 Hz, 1H),
1
3
H). C NMR (100 MHz, CDCl
3
): d 148.0, 131.4, 130.3, 128.8, 3.57–3.50 (m, 1H), 3.43–3.36 (m, 1H), 2.21 (p, J ¼ 7.4 Hz, 2H), 1.15
13
28.5, 126.0, 92.3, 69.6, 31.4, 24.5.
(t, J ¼ 7.0 Hz, 3H), 0.88 (t, J ¼ 7.5 Hz, 3H). C NMR (100 MHz,
2
-(1-Ethoxyethyl)-4-phenyl-2H-1,2,3-triazole (4c). The spec- CDCl ): d 147.9, 131.3, 130.3, 128.8, 128.5, 126.0, 94.5, 64.7, 28.0,
3
8b
troscopic data are in accordance with those reported.
Yield: 19.5 mg (90%); colorless oil liquid; R ¼ 0.40 (hexane–
14.7, 9.0.
f
2-(1-Ethoxybutyl)-4-phenyl-2H-1,2,3-triazole (4i). The spec-
ꢁ1
1
8b
EtOAc, 10 : 1). IR (neat): 3466, 3001, 1650, 1357, 1125 cm . H troscopic data are in accordance with those reported.
NMR (400 MHz, CDCl
3
): d 8.07 (s, 1H), 7.98 (d, J ¼ 7.1 Hz, 2H),
Yield: 21.6 mg (88%); colorless oil liquid; R ¼ 0.50 (hexane–
ꢁ1 1
f
7
1
3
1
.59 (t, J ¼ 7.4 Hz, 2H), 7.51 (t, J ¼ 7.4 Hz, 1H), 5.96 (q, J ¼ 6.0 Hz, EtOAc, 10 : 1). IR (neat): 3469, 2962, 1647, 1381, 1112 cm . H
H), 3.75–3.68 (m, 1H), 3.58–3.50 (m, 1H), 2.00 (d, J ¼ 6.0 Hz, NMR (400 MHz, CDCl ): d 7.89 (s, 1H), 7.81 (d, J ¼ 7.2 Hz, 2H),
3
1
3
H), 1.32 (t, J ¼ 7.0 Hz, 3H). C NMR (100 MHz, CDCl
3
): d 147.8, 7.42 (t, J ¼ 7.4 Hz, 2H), 7.34 (t, J ¼ 7.3 Hz, 1H), 5.60 (t, J ¼ 6.7 Hz,
1H), 3.57–3.49 (m, 1H), 3.43–3.35 (m, 1H), 2.19–2.147 (m, 2H),
31.3, 130.3, 128.8, 128.5, 126.0, 89.5, 64.6, 20.9, 14.7.
2
-(1-Isopropoxyethyl)-4-phenyl-2H-1,2,3-triazole (4d). The 1.45–1.35 (m, 1H), 1.28–1.21 (m, 1H), 1.15 (t, J ¼ 7.0 Hz, 3H),
8b
13
spectroscopic data are in accordance with those reported.
0.93 (t, J ¼ 7.4 Hz, 3H). C NMR (100 MHz, CDCl ): d 147.8,
3
Yield: 20.3 mg (88%); colorless oil liquid; R ¼ 0.50 (hexane– 131.3, 130.3, 128.8, 128.5, 126.0, 93.0, 64.7, 36.7, 18.0, 14.7, 13.5.
f
ꢁ
1 1
EtOAc, 10 : 1). IR (neat): 3473, 2972, 1649, 1375, 1118 cm . H
2-(2-Ethoxypropan-2-yl)-4-phenyl-2H-1,2,3-triazole (4j). Yield:
NMR (400 MHz, CDCl
3
): d 8.02 (s, 1H), 7.95 (d, J ¼ 7.1 Hz, 2H), 16.7 mg (77%); colorless oil liquid; R ¼ 0.30 (hexane–EtOAc,
f
ꢁ
1 1
7
1
3
1
.55 (t, J ¼ 7.5 Hz, 2H), 7.47 (t, J ¼ 7.4 Hz, 1H), 6.03 (q, J ¼ 6.0 Hz, 10 : 1). IR (neat): 3442, 2940, 1661, 1384, 1072 cm . H NMR
H), 3.87–3.77 (m, 1H), 1.94 (d, J ¼ 6.0 Hz, 3H), 1.36 (d, J ¼ 6.1 Hz, (400 MHz, CDCl ): d 7.92 (s, 1H), 7.84 (d, J ¼ 7.2 Hz, 2H), 7.44 (t,
3
1
3
H), 1.07 (d, J ¼ 6.2 Hz, 3H). C NMR (100 MHz, CDCl ): d 147.7, J ¼ 7.5 Hz, 2H), 7.37 (d, J ¼ 7.4 Hz, 1H), 3.10 (s, 3H), 1.98 (s, 6H).
3
13
31.2, 130.3, 128.8, 128.5, 126.0, 87.4, 70.4, 22.7, 21.4, 21.3.
3
C NMR (100 MHz, CDCl ): d 147.5, 131.0, 128.8, 128.4, 126.0,
+
+
2-(1-Butoxyethyl)-4-phenyl-2H-1,2,3-triazole (4e). The spec- 93.0, 50.8, 25.7. HRMS (ESI): m/z [M + H] calcd for C H N O :
1
2
16 3
8b
troscopic data are in accordance with those reported.
Yield: 19.4 mg (79%); colorless oil liquid; R
¼ 0.50 (hexane–
EtOAc, 10 : 1). IR (neat): 3475, 2956, 1634, 1381, 1129 cm . H 2(3H)-one (4k). The spectroscopic data are in accordance with
218.1288; found: 218.1289.
f
5-Methyl-5-(4-phenyl-2H-1,2,3-triazol-2-yl)dihydrofuran-
ꢁ1 1
8b
NMR (400 MHz, CDCl
3
): d 7.89 (s, 1H), 7.81 (d, J ¼ 7.1 Hz, 2H), those reported.
7
1
1
0
1
.42 (t, J ¼ 7.4 Hz, 2H), 7.34 (t, J ¼ 7.3 Hz, 1H), 5.77 (q, J ¼ 6.0 Hz,
Yield: 22.6 mg (93%); yellow oil liquid; R ¼ 0.20 (hexane–
f
ꢁ1 1
H), 3.49 (dt, J ¼ 9.2, 6.7 Hz, 1H), 3.31 (dt, J ¼ 9.4, 6.6 Hz, 1H), EtOAc, 10 : 1). IR (neat): 3465, 2978, 1740, 1635, 1380 cm . H
.82 (d, J ¼ 6.0 Hz, 3H), 1.53–1.45 (m, 2H), 1.33–1.24 (m, 2H), NMR (400 MHz, DMSO): d 8.43 (s, 1H), 7.87 (d, J ¼ 7.2 Hz, 2H),
1
3
.83 (t, J ¼ 7.4 Hz, 3H). C NMR (100 MHz, CDCl ): d 147.8, 7.46 (t, J ¼ 7.4 Hz, 2H), 7.39 (t, J ¼ 7.3 Hz, 1H), 3.09–2.96 (m, 2H),
3
1
3
31.2, 130.3, 128.8, 128.5, 126.0, 89.7, 68.9, 31.2, 20.8, 19.1, 13.7. 2.84–2.75 (m, 1H), 2.68–2.60 (m, 1H), 2.14 (s, 3H). C NMR (100
2
-(1-Isobutoxyethyl)-4-phenyl-2H-1,2,3-triazole (4f). The MHz, DMSO): d 176.0, 148.4, 133.2, 129.8, 129.5, 129.4, 126.4,
8b
spectroscopic data are in accordance with those reported.
Yield: 19.6 mg (80%); colorless oil liquid; R
¼ 0.50 (hexane–
97.9, 33.7, 29.2, 25.1.
f
4-Phenyl-1-(1-phenylvinyl)-1H-1,2,3-triazole (7). The spectro-
ꢁ1
1
12
EtOAc, 10 : 1). IR (neat): 3468, 2959, 1648, 1381, 1126 cm . H scopic data are in accordance with those reported.
NMR (400 MHz, CDCl
3
): d 7.89 (s, 1H), 7.81 (d, J ¼ 7.1 Hz, 2H),
.42 (t, J ¼ 7.4 Hz, 2H), 7.34 (t, J ¼ 7.4 Hz, 1H), 5.76 (q, J ¼ 6.0 Hz, EtOAc, 10 : 1). IR (neat): 3038, 2934, 1496, 1459, 756 cm . H
H), 3.26 (dd, J ¼ 9.2, 6.9 Hz, 1H), 3.08 (dd, J ¼ 9.2, 6.6 Hz, 1H), NMR (400 MHz, CDCl ): d 7.99–7.97 (m, 2H), 7.93 (s, 1H), 7.60–
Yield: 17.2 mg (70%); yellow oil liquid; R ¼ 0.20 (hexane–
f
ꢁ1 1
7
1
1
¼
3
1
3
.82 (d, J ¼ 6.0 Hz, 3H), 1.78 (dd, J ¼ 13.4, 6.7 Hz, 1H), 0.85 (d, J 7.45 (m, 8H), 6.00 (d, J ¼ 1.0 Hz, 1H), 5.69 (d, J ¼ 0.9 Hz, 1H).
C
1
3
6.7 Hz, 3H), 0.80 (d, J ¼ 6.7 Hz, 3H). C NMR (100 MHz, NMR (100 MHz, CDCl ): d 147.6, 143.0, 134.6, 130.2, 129.9,
3
CDCl
3
): d 147.7, 131.2, 130.4, 128.8, 128.5, 126.0, 89.9, 75.8, 128.9, 128.8, 128.3, 127.4, 125.8, 119.8, 109.4.
2
8.2, 20.8, 19.2, 19.1.
-(1-(Cyclohexyloxy)ethyl)-4-phenyl-2H-1,2,3-triazole
The spectroscopic data are in accordance with those reported.
2
(4g).
Conflicts of interest
8
b
Yield: 19.3 mg (71%); colorless oil liquid; R ¼ 0.50 (hexane– There are no conicts to declare.
f
ꢁ
1 1
EtOAc, 10 : 1). IR (neat): 3465, 2948, 1644, 1383, 1102 cm . H
NMR (400 MHz, CDCl ): d 7.88 (s, 1H), 7.81 (d, J ¼ 7.1 Hz, 2H),
3
Acknowledgements
7
1
1
1
1
.42 (t, J ¼ 7.4 Hz, 2H), 7.34 (t, J ¼ 7.4 Hz, 1H), 5.93 (q, J ¼ 6.0 Hz,
H), 3.40–3.34 (m, 1H), 2.00–1.98 (m, 1H), 1.80 (d, J ¼ 6.0 Hz, 3H), This work was nancially supported by the Project of Science
.71–1.70 (m, 1H), 1.63–1.56 (m, 1H), 1.48–1.33 (m, 3H), 1.23– and Technology Department of Sichuan Province (No.
1
3
.10 (m, 4H). C NMR (100 MHz, CDCl
3
): d 147.7, 131.1, 130.4, 2018JY0319) and the Fundamental Research Funds of Central
28.8, 128.5, 126.0, 87.2, 76.2, 32.7, 31.4, 25.5, 24.0, 23.9, 21.4.
Universities, Southwest Minzu University (2018NZD05).
27614 | RSC Adv., 2018, 8, 27610–27615
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This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 27610–27615 | 27615