'One-flask' synthesis to 3,5-disubstituted 1,2,4-triazoles from aldehydes with hydrazonoyl hydrochlorides via 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/j.tet.2011.05.003

A new 'one-flask' synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to synthesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cycloaddition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this 'one-flask' 1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine under basic condition. Furthermore, this newly developed methodology can be applied to various aldehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes. Crown Copyright

Full text of DOI:10.1016/j.tet.2011.05.003

Tetrahedron 67 (2011) 5339e5345
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
‘One-flask’ synthesis to 3,5-disubstituted 1,2,4-triazoles from aldehydes with
hydrazonoyl hydrochlorides via 1,3-dipolar cycloaddition
,
,
Wen-Che Tseng a, Li-Ya Wang b, Tian-Shung Wu b c, Fung Fuh Wong a
*
a Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC
b The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC
c School of Pharmacy, China Medical University, No. Hsueh-91, Shih Rd., Taichung 40402, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A new ‘one-flask’ synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to syn-
thesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cyclo-
addition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes
with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this ‘one-flask’
1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine
under basic condition. Furthermore, this newly developed methodology can be applied to various al-
dehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes.
Crown Copyright Ó 2011 Published by Elsevier Ltd. All rights reserved.
Received 10 February 2011
Received in revised form 22 April 2011
Accepted 3 May 2011
Available online 14 May 2011
Keywords:
1,2,4-Triazoles
Aldehydes
Hydrazonoes
Nitrilimine
1,3-Dipolar cycloaddition
1. Introduction
converted to their oxime derivatives by means of hydroxylamine
hydrochloride and are widely applied in the organic sysnthesis.20
Nitrilimine cycloadditions to ethylenic or ethylynic dipolar-
ophiles are of great interest due to their potential application on the
synthesis of variously bioactive 5-substituted-4,5-dihydrpyrazole
heterocyclic derivatives.1 Triazoles are also an important class of
heterocyclic compounds, which is responsible for the biological
activity of many pharmaceutically active compounds showing the
antifungal,2,3 antimicrobial,4 antiviral,5 anti-inflammatory,6 anti-
asthmatic,7 antiproliferative,8,9 hypotonic activities,10 antibacterial,
antifungal, and antihelmintic activities.11 More recently, triazole-
based agonists or antagonists targeting different receptors
were described,12,13 especially molecules based on the 3,4,5-
trisubstituted 1,2,4-triazole scaffold.14e18 Herein, we provided an
efficient methodology for the conversion of a series of aldehydes to
3,5-disubstituted 1,2,4-triazoles by use of hydrazonoyl hydrochlo-
rides and hydroxylamine hydrate in the presence of triethylamine
as a catalyst through the 1,3-dipolar cycloaddition mechanism.
It is well known that in situ generation of nitrilimines from
hydrazonoyl chlorides19 occurs in homogeneous aqueous system
by base treatment. Hydrazonoyl chlorides were thus considered as
the precursor for niritimines in aqueous base catalytic 1,3-dipolar
cycloaddition.1b On the other hand, aldehydes were effectively
Hydrazonoyl chlorides and aldehydes were accordingly concerned
as the masked agents for niritimines and oximes, respectively. In this
paper, we reported a new 1,3-dipolar cycloaddition reaction for the
synthesis 3,5-disubstituted 1,2,4-triazoles by reacting aldehydes
with hydrazonoyl hydrochlorides using hydroxylamine hydrochlo-
ride as a transferring agent and triethylamine as a base catalyst. The
newly developed method can be applicable to aliphatic, cyclic ali-
phatic, aromatic and heterocyclic aldehyde substrates to provide
products in moderate to excellent yields.
2. Result and discussion
Aldehydes 1e12 are the commercially available materials. Var-
ious anilines were first converted to its corresponding diazonium
salt by treatment with NaNO2/HCl,19 and then this intermediate
was reacted with methyl 2-chloroacetoacetate to give hydrazonoyl
chloride compounds 13e20.19 In the newly developed method, we
treated a toluene solution of aldehydes 1e12 with 1.0 equiv of hy-
droxylamine hydrochloride with excess amount of triethylamine at
room temperature for 0.5 h. When the aldehydes 1e12 were
completely consumed and converted to the oxime intermediates,20
then hydrazonoyl chloride 13e20 was added into the reaction
mixture in the presence of excess amount of triethylamine and the
solution was heated to reflux for 1e2 h. After the 1,3-dipolar
* Corresponding author. Tel.: þ886 4 220 53366x5603; fax: þ886 4 220 78083;
e-mail
addresses:
ffwong@mail.cmu.edu.tw,
wongfungfuh@yahoo.com.tw
(F.F. Wong).
0040-4020/$ e see front matter Crown Copyright Ó 2011 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.003

5340
W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
cycloaddition reaction was completed, the filtration, concentration,
and purification with silica gel column chromatography were per-
formed. The desired 3,5-disubstituted 1,2,4-triazole products
21e44 were isolated often in solid form (see Scheme 1).
that various substituents on the phenyl ring of the hydrazonoyl
hydrochlorides were suitable for this newly developed method.
Fluorine-21 and trifluoromethane-containing22 compounds are
well known to play an important role in bio- and agrochemical
field. For example, replacement of hydrogen atoms by fluorine or
trifluoromethane in pheromones has been shown to produce a va-
riety of effects on the insect response. We thus turned our attention
to synthesize a series of fluorine- or trifluoromethane-containing
3,5-disubstituted 1,2,4-triazole derivatives. p-Trifluoromethyl-
phenylchlorohydrazone 17 and p-fluorophenylchlorohydrazone 20
were selected as the 1,3-dipole reactants for further evolution. On
the other hand, due to the considerable substituent effect of the
dipolarphile property on this 1,3-dipolar cycloaddition, we in-
vestigated p-fluorophenylchlorohydrazone 20 with variously
substituted aldehydes 2e7 in the advanced priority model, in-
cluding ethyl, i-propyl, n-butyl, cyclopropyl, cyclopentyl, and
cyclohexyl substituted groups. When the normal 1,3-dipolar cy-
cloaddition was performed, the corresponding fluorine-containing
desired products 29e34 were successfully obtained in excellent
yields (86e91%, see the entries 1e6 in Table 2 and Chart 2). The
substituent effect of aliphatic and cyclic aliphatic aldehydes almost
unchanged the reaction results.
X
O
1. NH2OH.HCl, toluene
N
R
N
X
2.
R
H
Cl
N
N
CO2Me
NH CO2Me
21-44
1-12
13-20
NEt3, toluene, at reflux, 1-2 h
Scheme 1.
To investigate the reactivity of hydrazonoyl hydrochlorides
13e20 with various substituents on the phenyl ring, acetaldehyde 1
was used as the model dipolarophile substrates. Acetaldehyde 1 was
allowed to react with various aromatic hydrazonoyl hydrochlorides
13e20 bearing various substituents including F, Cl, Br, CF3, and OMe
at ortho or meta or para position to the nitrilimine group. The 1,3-
dipolar cycloaddition smoothly proceeded to give the correspond-
ing 3,5-disubstituted 1,2,4-triazole products 21e28 in good yields
(53e91%, see the entries 1e8 in Table 1 and Chart 1). For compound
26 possessing the electron-donating p-methoxyl functionality in
nitrilimine, the unreacted starting material was recovered from the
reaction mixture as well as the less satisfactory result (53%, see the
entry 6 of Table 1). Compounds 21e28 were fully characterized by
spectroscopic methods. Served as an example, compound 21 pos-
sessed two characteristic peaks at 153.62 and 154.03 ppm, which
represented the 13C in triazole ring. The IR absorptions of 21 showed
peaks at 1740 cmꢀ1 for the stretching of the eC]O(OMe) carbonyl
group. The assignment data of the corresponding product 21 was
consistent with the literature data.3 Results in Table 1 demonstrated
Table 2
The results of synthesis of 1,2,4-triazole derivatives from various of aldehydes with
hydrazonoyl hydrochlorides 17 or 20
Aldehydes
Hydrazones
Entry
1,2,4-Triazoles Yield
(%)
O
X
Cl
R
H
N
NH CO2Me
R
No.
X
No.
Table 1
1
2
3
4
5
6
7
8
Ethyl
i-Propyl
n-Butyl
Cyclopropyl
Cyclopentyl
Cyclohexyl
3-Furyl
3-Thienyl
2-pyrrolyl
Phenyl
2-Naphthyl
Cyclopentyl
Cyclohexyl
3-Furyl
3-Thienyl
2-Pyrrolyl
2
3
4
5
6
7
8
9
10
11
12
6
7
8
p-F
p-F
p-F
p-F
p-F
p-F
p-F
p-F
p-F
p-F
p-F
p-CF3
p-CF3
p-CF3
p-CF3
p-CF3
20
20
20
20
20
20
20
20
20
20
20
17
17
17
17
17
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
91
90
89
91
88
86
62
57
41
33
28
94
91
64
62
51
Synthesis of 1,2,4-triazole derivatives using acetaldehyde (1) with various hydra-
zonoyl hydrochlorides
Aldehydes
Hydrazones
Entry
1,2,4-Triazoles
Yield
(%)
O
X
Cl
9
R
H
N
10
11
12
13
14
15
16
NH CO2Me
R
No.
X
No.
9
10
1
2
3
4
5
6
7
8
Methyl
Methyl
Methyl
Methyl
Methyl
Methyl
Methyl
Methyl
1
1
1
1
1
1
1
1
H
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
88
87
86
85
87
53
86
91
o-CF3
m-Br
m-CF3
p-CF3
p-OMe
p-Cl
This newly synthetic strategy was applied to p-fluorophenyl-
chlorohydrazone 20 with the heterocyclic aldehydes 8e10, in-
volving furan-3-carbaldehyde 8, thiophene-3-carbaldehyde 9, and
1H-pyrrole-3-carbaldehyde 10. The moderate yields were also
p-F
X
X
CF3
N
N
N
N
Me
Me
Me
N
Me
N
N
N
N
N
N
N
CO2Me
CO2Me
CO2Me
CO2Me
21
22
23. X = Br
24. X = CF3
25. X = CF3, 26. X = OMe
27. X = Cl, 28. X = F
Chart 1.

W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
5341
F
F
X
X
N
N
N
N
R
N
N
N
N
N
N
N
N
CO2Me
CO2Me
CO2Me
CO2Me
29. R = Et
32
33. X = F
34. X = F
40. X = CF3
41. X = CF3
30. R =
31. R =
i
n
-Pr
-Bu
X
X
X
F
N
N
N
N
N
O
S
R
N
N
N
N
H
N
N
N
N
CO2Me
CO2Me
CO2Me
CO2Me
38. R = Ph
39. R = 2-Naphthyl
35. X = F
42. X = CF3
36. X = F
43. X = CF3
37. X = F
44. X = CF3
Chart 2.
achieved in 41e62% yields (see the entries 7e9 in Table 2 and Chart
2). When benzaldehyde 11 and 2-naphthaldehyde 12 were reacted
with p-fluorophenylchlorohydrazone 20 under the same reaction
condition, the less satisfactory yielding results were observed (33%
and 28% yields, respectively, see the entries 10e11 in Table 2). Based
on the simple FMO theory, nitrilimines are used as 1,3-dipoles. The
dipoles LUMO and oxime hydrochlorides dipolarophile HOMO
interaction has been suggested to be the interaction term in 1,3-
dipolar cycloaddition.19,20 Whatever, the electron-rich dipolar-
ophile of aromatic or heterocyclic aldehydes 8e12 would decrease
both the frontier molecular orbital (FMO) energy barrier of the two
reactants. Since, the dissatisfied isolated yields were provided in
aromatic and heterocyclic reactants.
to p-trifluoromethylphenylchlorohydrazone 17 with a series of
cyclic aliphatic and heterocyclic aldehyde diplarophiles including
cyclopentanecarboxaldehyde 6, cyclohexanecarboxaldehyde 7, fu-
ran-3-carbaldehyde 8, thiophene-3-carbaldehyde 9, 1H-pyrrole-3-
carbaldehyde 10. The same consistent tendency was achieved, the
excellent isolated yields (91% and 94%) were obtained in cyclic al-
iphatic aldehydes 6 and 7, and the moderate to excellent yields
were observed in heterocyclic aldehydes (51e64%, see the entry
14e16 of Table 2). The results also indicated the electron-rich al-
dehyde dipolarophiles, such as aromatic and heterocyclic alde-
hydes were un-favored for the 1,3-dipolar cycloaddition reaction.
Consequently, we proposed the plausible mechanism for the
effective 1,3-dipolar cycloaddition for the synthesis of 3,5-
disubstituted 1,2,4-triazoles (see Scheme 2). Acetaldehyde 1 was
reacted with 1.0 equiv of hydroxylamine hydrochloride in toluene
For the further demonstration of the substituent effect on the
aldehyde dipolarophile reactants, we employed the above strategy
O
1. NH2OH.HCl, toluene
2. Cl
N
Ph
N
Me
H
N
N
CO2Me
NH CO2Me, NEt3
21
1
13
H2O
NH2OH.HCl
NEt3
dehydroxylation
NEt3.HCl
CO2Me
OH2+Cl-
H
N
N
N
Me
N
+
N
B:
H
Me
N
CO2Me
H2O
46
45
47
Scheme 2.

5342
W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
at reflux to generate oxime hydrochloride intermediate 45. Treat-
ment of hydrazonoyl hydrochloride 13 with excess amount of
triethylamine resulted in situ generation of nitrilimine specie 46.
The requisite 1,3-dipolar cycloadduct dihydrotriazole 47 was
formed by treating dipolarophile oxime 45 with 1,3-dipole nitrili-
mine 46. When the subsequent dehydroxylation condensation was
completed, the corresponding 3,5-disubstituted 1,2,4-triazole
product 21 was obtained in good yield (88%, see Scheme 2).
4.2.1. 1-Phenyl-3-methoxycarbonyl-5-methyl-1,2,4-triazole
(21). Yellow solid; mp 107e108 ꢂC; 1H NMR (CDCl3, 200 MHz)
d
2.47 (s, 3H, CH3), 3.90 (s, 3H, CH3), 7.35e7.46 (m, 5H, ArH); 13C
NMR (CDCl3, 50 MHz)
d
13.12, 52.67, 124.79 (2ꢁ CH), 129.49 (2ꢁ
CH), 129.51, 136.63, 153.62, 154.03, 160.27; IR (diffuse reflectance)
2955 (m), 1740 (s, C]O), 1597 (m), 1481 (m), 1431 (m), 1223 (s,
CeO), 1145 (m), 1018 (m), 822 (m,), 772 (m) cmꢀ1; MS (ESI) m/z: 217
(Mþþ1); Anal. Calcd for C11H11N3O2; C: 60.82; H: 5.10; N: 19.34.
Found: C: 60.85; H: 5.07; N: 19.30.
3. Conclusion
4.2.2. 1-(2-Trifluorophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (22). Yellow solid; mp 83e84 ꢂC; 1H NMR (CDCl3,
In conclusion, we have developed a new ‘one-flask’ 1,3-dipolar
cycloaddition method to prepare a series of 3,5-disubstituted
1,2,4-triazole compounds by reacting various aldehydes with
hydrazonoyl hydrochlorides in the presence of hydroxylamine hy-
drochloride as a functionality transferring reagent and triethyl-
amine as a basic catalyst. This new methodology can be widely
applied to aliphatic, cyclic aliphatic, aromatic, and heterocyclic al-
dehyde substrates and the corresponding 1,2,4-triazoles were
obtained in moderate to excellent yields.
200 MHz)
d
2.27 (s, 3H, CH3), 3.91 (s, 3H, CH3), 7.33e7.37 (m, 1H,
12.14,
ArH), 7.64e7.81 (m, 3H, ArH); 13C NMR (CDCl3, 50 MHz)
d
52.70, 119.64, 125.09, 127.58, 127.66, 128.22, 129.78, 131.27, 133.24,
133.93, 153.98, 156.12, 160.10; IR (diffuse reflectance) 2955 (m),
1740 (s, C]O), 1605 (m), 1516 (m), 1458 (m), 1396 (m), 1319 (m),
1223 (m), 1138 (m), 779 (m) cmꢀ1; MS (ESI) m/z: 285 (Mþþ1). Anal.
Calcd for C12H10F3N3O2; C: 50.53; H: 3.53; N: 14.73. Found: C:
50.57; H: 3.50; N: 14.70.
4.2.3. 1-(3-Bromophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (23). Yellow solid; mp 119e120 ꢂC; 1H NMR (CDCl3,
4. Experimental section
4.1. General
200 MHz)
d
2.54 (s, 3H, CH3), 3.95 (s, 3H, CH3), 7.35e7.38 (m, 2H,
13.28,
ArH), 7.55e7.64 (m, 2H, ArH); 13C NMR (CDCl3, 50 MHz)
d
52.84, 123.04, 123.20, 129.97, 130.75, 132.70, 137.66, 153.90, 154.14,
160.10; IR (diffuse reflectance) 3095 (m), 1740 (s, C]O), 1585 (m),
1470 (m), 1431 (m), 1219 (m), 1146 (m), 826 (m), 791 (m), 737 (m),
676 (m) cmꢀ1; MS (ESI) m/z: 295 (Mþþ1). Anal. Calcd for
C11H10BrN3O2; C: 44.62; H: 3.40; N: 14.19. Found: C: 44.58; H: 3.38;
N: 14.21.
All chemicals were reagent grade and used as purchased. All
reactions were carried out under argon or nitrogen atmosphere
and monitored by TLC. Flash column chromatography was carried
out on silica gel (230e400 mesh). Analytical thin-layer chroma-
tography (TLC) was performed on precoated plates (silica gel 60 F-
254) purchased from Merck Inc. Mixtures of ethyl acetate and
hexanes were used as eluants. Infrared (IR) spectra were mea-
sured on a Bomem Michelson Series FT-IR spectrometer. The
wavenumbers reported are referenced to the polystyrene ab-
sorption at 1601 cmꢀ1. Absorption intensities are recorded by the
following abbreviations: s, strong; m, medium; w, weak. Proton
NMR spectra were obtained on a Bruker (200 MHz or 400 MHz)
spectrometer by use of CDCl3 as solvent. Carbon-13 NMR spectra
were obtained on a Bruker (75 MHz or 100 MHz) spectrometer by
used of CDCl3 as solvent. Carbon-13 chemical shifts are referenced
4.2.4. 1-(3-Trifluorophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (24). Yellow solid; mp 58e59 ꢂC; 1H NMR (CDCl3,
200 MHz)
d
2.54 (s, 3H, CH3), 3.94 (s, 3H, CH3), 7.62e7.73 (m, 4H,
13.23, 52.81, 120.39, 121.83,
ArH); 13C NMR (CDCl3, 50 MHz)
d
121.89, 125.81, 126.25, 127.84, 130.32, 131.29, 131.95, 132.62, 133.28,
137.13,154.06,154.21,160.02; IR (diffuse reflectance) 2955 (m),1740
(s, C]O),1600 (m),1450 (m),1389 (m),1327 (m),1065 (m), 899 (m),
806 (m), 694 (m) cmꢀ1; MS (ESI) m/z: 285 (Mþþ1). Anal. Calcd for
C12H10F3N3O2; C: 50.53; H: 3.53; N: 14.73. Found: C: 50.56; H: 3.50;
N: 14.69.
to the center of the CDCl3 triplet (d 77.0 ppm). Multiplicities are
recorded by the following abbreviations: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet; J, coupling constant (Hz). ESI-MS
spectra were obtained from an Applied Biosystems API 300 mass
spectrometer. High-resolution mass spectra were obtained by
means of a JEOL JMS-HX110 mass spectrometer. Elemental anal-
yses were carried out on a Heraeus CHNeO RAPID element
analyzer.
4.2.5. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (25). Light yellow solid; mp 117e118 ꢂC; 1H NMR (CDCl3,
200 MHz)
d 2.54 (s, 3H, CH3), 3.91 (s, 3H, CH3), 7.59 (d, 2H,
J¼8.62 Hz, ArH), 7.72 (d, 2H, J¼8.62 Hz, ArH); 13C NMR (CDCl3,
50 MHz)
d 13.34, 52.77, 102.62, 124.91, 126.04, 126.73, 126.80,
130.44, 131.13, 131.79, 132.45, 139.43, 154.06, 154.18, 160.00; IR
(diffuse reflectance) 2959 (m), 1740 (s, C]O), 1616 (m), 1527 (m),
1477 (m), 1454 (m), 1015 (m), 860 (m), 741 (m) cmꢀ1; MS (ESI) m/z:
285 (Mþþ1). Anal. Calcd for C12H10F3N3O2; C: 50.53; H: 3.53; N:
14.73. Found: C: 50.55; H: 3.51; N: 14.75.
4.2. Standard procedure of one flask synthesis of 3,5-
disubstituted 1,2,4-triazoles (19e44)
A solution of aldehyde derivatives (1e12, 1.0 mmol, 1.0 equiv)
and hydroxylamine hydrochloride (1.0 mmol, 1.0 equiv) was stirred
at room temperature in toluene solution (6 mL) for 0.5 h. Then
triethylamine (2.0 mmol, 2.0 equiv) and various of hydrazonoyl
hydrochlorides (13e20, 1.0 mmol, 1.0 equiv) were added into the
reaction mixture and heated to reflux within 1e2 h. When the re-
action was completed, the reaction mixture was concentrated,
added to water (10 mL), and extracted with CH2Cl2 (3ꢁ30 mL). The
organic extracts were washed with saturated NaHCO3, dried over
MgSO4, filtered, and concentrated under reduced pressure. The
residue solution was purified by column chromatography on silica
gel to give the corresponding 3,5-disubstituted 1,2,4-Triazole
products (21e44) in 28e91% yields.
4.2.6. 1-(4-Methoxyphenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (26). 1H NMR (CDCl3, 200 MHz)
d
2.49 (s, 3H, CH3), 3.84 (s,
3H, CH3), 3.98 (s, 3H, CH3), 6.96e7.00 (m, 2H, ArH), 7.32e7.37 (m,
2H, ArH); 13C NMR (CDCl3, 50 MHz)
d
12.88, 52.58, 55.53,114.49 (2ꢁ
CH), 126.24 (2ꢁ CH), 129.40, 153.26, 154.10, 160.20, 160.26; IR
(diffuse reflectance) 2928 (m), 1740 (s, C]O), 1516 (m), 1481 (m),
1400 (m),1261 (m),1219 (m), 1146 (m), 737 (m) cmꢀ1; MS (ESI) m/z:
247 (Mþþ1). Anal. Calcd for C13H13Cl N4O2; C: 53.34; H: 4.48; N:
19.14. Found: C: 53.35; H: 4.50; N: 19.13.
4.2.7. 1-(4-Chlorophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (27). Yellow solid; mp 118e119 ꢂC; 1H NMR (CDCl3,

W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
5343
200 MHz)
d
2.50 (s, 3H, CH3), 3.93 (s, 3H, CH3), 7.34e7.46 (m, 4H,
50 MHz)
d
25.62 (2ꢁ CH2), 32.81 (2ꢁ CH2), 36.20, 52.67, 116.27,
ArH); 13C NMR (CDCl3, 50 MHz)
d
13.18, 52.77, 126.02 (2ꢁ CH),
116.73, 127.60, 127.78, 132.81, 153.75, 160.38, 162.26, 165.38; IR
(diffuse reflectance) 2958 (m), 1740 (s, C]O), 1512 (m), 1477 (m),
1412 (m), 1219 (m), 1134 (m), 1015 (m), 849 (m) cmꢀ1; MS (ESI) m/z:
288 (Mþþ1). Anal. Calcd for C15H16FN3O2; C: 62.27; H: 5.57; N:
14.52. Found: C: 62.30; H: 5.56; N: 14.49.
129.75 (2ꢁ CH), 135.13, 135.58, 153.83, 154.08, 160.13; IR (diffuse
reflectance) 2955 (m), 1740 (s, C]O), 1500 (m), 1477 (m), 1400 (m),
1223 (m), 1146 (s), 1096 (s), 1011 (s), 841 (m) cmꢀ1; MS (ESI) m/z:
251 (Mþþ1). Anal. Calcd for C11H10ClN3O2; C: 52.50; H: 4.01; N:
16.70. Found: C: 52.48; H: 4.03; N: 16.74.
4.2.14. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-
4.2.8. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-methyl-1,2,4-
triazole (34). 1H NMR (CDCl3, 200 MHz)
d 1.09e1.27 (m, 4H,
CyclohexyleH), 1.60e1.78 (m, 6H, CyclohexyleH), 2.60e2.75 (m,
1H, CyclohexyleH), 3.93 (s, 3H, CH3), 7.13e7.22 (m, 2H, ArH),
triazole (28). Yellow solid; mp 169e170 ꢂC; 1H NMR (CDCl3,
200 MHz)
d
2.47 (s, 3H, CH3), 3.92 (s, 3H, CH3), 7.10e7.18 (m, 2H,
13.02,
ArH), 7.36e7.43 (m, 2H, ArH); 13C NMR (CDCl3, 50 MHz)
d
7.32e7.41 (m, 2H, ArH); 13C NMR (CDCl3, 50 MHz)
d
25.17, 25.66 (2ꢁ
52.73, 116.35, 116.82, 126.81, 126.99, 132.75, 153.71, 154.15, 160.17,
160.29, 165.28; IR (diffuse reflectance) 2963 (m), 1739 (s, C]O),
1516 (m), 1474 (m), 1427 (m), 1219 (m), 1150 (m), 845 (m), 810 (m),
671 (m) cmꢀ1; MS (ESI) m/z: 235 (Mþþ1). Anal. Calcd for
C11H10FN3O2; C: 56.17; H: 4.29; N: 17.86. Found: C: 56.14; H: 4.27;
N: 17.87.
CH2), 31.30 (2ꢁ CH2), 35.36, 52.63, 116.33, 116.79, 127.53, 127.71,
132.65, 153.79, 160.33, 162.16, 165.37; IR (diffuse reflectance) 2940
(m), 1740 (s, C]O), 1605 (m), 1512 (m), 1447 (m), 1412 (m), 1366
(m), 1018 (m), 737 (m) cmꢀ1; MS (ESI) m/z: 303 (Mþþ1). Anal. Calcd
for C16H18FN3O2; C: 63.35; H: 5.98; N: 13.85. Found: C: 63.38; H:
6.01; N: 13.84.
4.2.9. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-ethyl-1,2,4-triazole
4.2.15. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-(3-furyl)-1,2,4-
(29). Light yellow solid; mp 102e103 ꢂC; 1H NMR (CDCl3,
triazole (35). Yellow solid; mp 145e146 ꢂC; 1H NMR (CDCl3,
200 MHz)
3.93 (s, 3H, CH3), 7.12e7.21 (m, 2H, ArH), 7.37e7.44 (m, 2H, ArH);
13C NMR (CDCl3, 50 MHz)
11.85, 19.97, 52.63, 116.27, 116.73, 127.11,
d
1.27 (t, 3H, J¼7.54 Hz, CH3), 2.77 (q, 2H, J¼7.54 Hz, CH2),
200 MHz)
ArH), 7.32e7.33 (m, 1H, ArH), 7.37e7.44 (m, 2H, ArH), 7.49 (s, 1H,
ArH); 13C NMR (CDCl3, 50 MHz)
52.87, 109.34, 113.53, 116.60,
d 3.94 (s, 3H, CH3), 6.39 (s, 1H, ArH), 7.12e7.20 (m, 2H,
d
d
127.29, 132.59, 153.67, 159.02, 160.20, 165.25; IR (diffuse re-
flectance) 2986 (m), 1740 (s, C]O), 1520 (m), 1373 (m), 1204 (m),
1018 (m), 964 (m), 853 (m), 607 (m) cmꢀ1; MS (ESI) m/z: 249
(Mþþ1). Anal. Calcd for C12H12FN3O2; C: 57.90; H: 4.87; N: 16.86.
Found: C: 57.87; H: 4.89; N: 16.88.
117.06, 128.25, 128.42, 133.13, 143.52, 143.75, 150.37, 154.38, 160.13,
160.81, 165.81; IR (diffuse reflectance) 2954 (m), 1740 (s, C]O),
1609 (m),1520 (m),1470 (m),1408 (m),1200 (m), 810 (m) cmꢀ1; MS
(ESI) m/z: 287 (Mþþ1). Anal. Calcd for C14H10F N3O3; C: 58.54; H:
3.51; N: 14.63. Found: C: 58.56; H: 3.48; N: 14.64.
4.2.10. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-isopropyl-1,2,4-
4.2.16. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-(3-thienyl)-1,2,4-
triazole (30). 1H NMR (CDCl3, 200 MHz)
d
1.27 (s, 3H, CH3), 1.31 (s,
3H, CH3), 2.94e3.15 (m, 1H, CH), 3.95 (s, 3H, CH3), 7.13e7.21 (m, 2H,
ArH), 7.34e7.41 (m, 2H, ArH); 13C NMR (CDCl3, 50 MHz)
triazole (36). Yellow solid; mp 148e149 ꢂC; 1H NMR (CDCl3,
200 MHz)
ArH), 7.36e7.43 (m, 2H, ArH), 7.48 (dd, 1H, J¼1.23 Hz, J¼2.92 Hz
ArH); 13C NMR (CDCl3, 50 MHz)
52.99, 116.60, 117.06, 126.66,
d 3.97 (s, 3H, CH3), 3.95 (s, 3H, CH3), 7.10e7.27 (m, 4H,
d
21.36 (2ꢁ
CH3), 25.99, 52.79, 116.39, 116.85, 127.66, 127.83, 132.73, 153.90,
160.40, 163.14, 165.50; IR (diffuse reflectance) 2974 (m), 1740 (s, C]
O), 1512 (m), 1481 (m), 1369 (m), 1227 (m), 1126 (m), 1015 (mw),
849 (m), 606 (m) cmꢀ1; MS (ESI) m/z: 263 (Mþþ1). Anal. Calcd for
C13H14FN3O2; C: 59.31; H: 5.29; N: 15.94. Found: C: 59.35; H: 5.32;
N: 15.92.
d
127.20, 128.11, 128.30 (2ꢁ CH), 133.49, 152.07, 154.17, 160.26, 160.68,
165.68; IR (diffuse reflectance) 2954 (m), 1740 (s, C]O), 1566 (m),
1512 (s), 1474 (m), 1223 (m), 849 (m), 806 (m), 733 (m), 617 (m)
cmꢀ1; MS (ESI) m/z: 303 (Mþþ1). Anal. Calcd for C14H10FN3O2S; C:
55.44; H: 3.32; N: 13.85. Found: C: 55.41; H: 3.29; N: 13.89.
4.2.11. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-n-butyl-1,2,4-
4.2.17. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-(2-pyrrolyl)-1,2,4-
triazole (31). 1H NMR (CDCl3, 200 MHz)
d
0.73 (t, 3H, J¼8.62 Hz,
triazole (37). Yellow solid; mp 226e227 ꢂC; 1H NMR (CDCl3,
CH3), 1.10e1.29 (m, 2H, CH2), 1.54e1.69 (m, 2H, CH2), 2.63e2.71 (m,
2H, CH2), 3.89 (s, 3H, CH3), 7.05e7.17 (m, 2H, ArH), 7.28e7.36 (m,
200 MHz)
1H, ArH), 6.89e6.93 (m, 1H, ArH), 7.18e7.28 (m, 2H, ArH), 7.46e7.52
(m, 2H, ArH), 9.76 (br, 1H, NH); 13C NMR (CDCl3, 50 MHz)
53.01,
d 3.98 (s, 3H, CH3), 5.78e5.81 (m, 1H, ArH), 6.06e6.11 (m,
2H, ArH); 13C NMR (CDCl3, 50 MHz)
d
13.42, 22.12, 165.33; IR (dif-
d
fuse reflectance) 2959 (m), 1740 (s, C]O), 1512 (m), 1223 (m), 1142
(m), 1015 (w), 849 (m), 613 (w) cmꢀ1; MS (ESI) m/z: 263 (Mþþ1),
248 (11), 194 (32), 109 (100). Anal. Calcd for C14H16FN3O2; C: 60.64;
H: 5.82; N: 15.15. Found: C: 60.62; H: 5.85; N: 15.11.
110.42, 111.41, 116.63, 117.09, 118.11, 121.95, 128.67, 128.85, 133.40,
150.31, 153.69, 160.36, 160.90, 165.90; IR (diffuse reflectance) 3399
(br, NH), 1740 (s, C]O), 1593 (m), 1512 (m), 1481 (m), 1211 (m), 1180
(m), 814 (m), 737 (m) cmꢀ1; MS (ESI) m/z: 286 (Mþþ1). Anal. Calcd
for C14H11FN4O2; C: 58.74; H: 3.87; N: 19.57. Found: C: 58.76; H:
3.89; N: 19.60.
4.2.12. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-cyclopropyl-1,2,4-
triazole (32). Yellow solid; mp 113e114 ꢂC; 1H NMR (CDCl3,
200 MHz)
1.79e1.92 (m, 1H, CH), 3.93 (s, 3H, CH3), 7.13e7.22 (m, 2H, ArH),
7.49e7.59 (m, 2H, ArH); 13C NMR (CDCl3, 50 MHz)
CH2), 52.78, 116.28, 116.74, 127.09, 127.27, 132.82, 153.59, 159.72,
160.26, 165.23; IR (diffuse reflectance) 2954 (m), 1740 (s, C]O),
1601 (m), 1523 (m), 1203 (m), 1130 (m), 1022 (m), 957 (m), 517 (m)
cmꢀ1; MS (ESI) m/z: 261 (Mþþ1). Anal. Calcd for C13H12FN3O2; C:
59.77; H: 4.63; N: 16.08. Found: C: 59.75; H: 4.65; N: 16.04.
d
1.01e1.11 (m, 2H, CH2), 1.24e1.32 (m, 2H, CH2),
4.2.18. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-phenyl-1,2,4-
triazole (38). Yellow solid; mp 166e167 ꢂC; 1H NMR (CDCl3,
d
7.44, 9.86 (2ꢁ
200 MHz)
d
4.00 (s, 3H, CH3), 7.03e7.12 (m, 2H, ArH), 7.25e7.48 (m,
52.90, 116.36, 116.83, 126.47,
7H, ArH); 13C NMR (CDCl3, 50 MHz)
d
127.43, 127.61, 128.68 (2ꢁ CH), 129.03 (2ꢁ CH), 130.74, 133.62,
154.26, 155.70, 160.23, 165.27; IR (diffuse reflectance) 2954 (m),
1740 (s, C]O), 1601 (m), 1513 (m), 1396 (m), 1223 (m), 1022 (m),
849 (m), 729 (m), 698 (m) cmꢀ1; MS (ESI) m/z: 297 (Mþþ1). Anal.
Calcd for C16H12FN3O2; C: 64.64; H: 4.07; N: 14.13. Found: C: 64.60;
H: 4.10; N: 14.15.
4.2.13. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-cyclopentyl-1,2,4-
triazole (33). 1H NMR (CDCl3, 200 MHz)
d 1.52e1.58 (m, 2H, CH2),
1.72e1.97 (m, 6H, CH2), 2.89e3.06 (m, 1H, CH), 3.93 (s, 3H, CH3),
4.2.19. 1-(4-Fluorophenyl)-3-methoxycarbonyl-5-(2-naphthyl)-
7.13e7.21 (m, 2H, ArH), 7.35e7.42 (m, 2H, ArH); 13C NMR (CDCl3,
1,2,4-triazole (39). Yellow solid; mp 139e140 ꢂC; 1H NMR (CDCl3,

5344
W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
200 MHz)
d
4.03 (s, 3H, CH3), 7.06e7.14 (m, 2H, ArH), 7.36e7.53 (m,
126.08, 126.97 (2ꢁ CH), 132.09, 132.75, 140.31, 150.17, 154.00,
160.18; IR (diffuse reflectance) 1740 (s, C]O), 1605 (m), 1493 (m),
1385 (m),1327 (s),1227 (m),1126 (m),1065 (m) cmꢀ1; MS (ESI) m/z:
336 (Mþþ1). Anal. Calcd for C15H11F3N4O2; C: 53.58; H: 3.30; N:
16.66. Found: C: 53.61; H: 3.31; N: 16.63.
5H, ArH), 7.73e7.81 (m, 3H, ArH), 8.14 (s, 1H, ArH); 13C NMR (CDCl3,
50 MHz)
d 53.01, 116.44, 116.90, 123.68, 125.04, 127.04, 127.50,
127.68, 127.77, 127.93, 128.48, 128.70, 129.87, 132.65, 133.77, 133.89,
154.40, 155.81, 160.31, 165.33; IR (diffuse reflectance) 2955 (m),
1740 (s, C]O), 1454 (m), 1396 (m), 1229 (m), 1157 (m), 849 (m), 818
(m), 756 (m) cmꢀ1; MS (ESI) m/z: 347 (Mþþ1). Anal. Calcd for
C20H14FN3O2; C: 69.16; H: 4.06; N: 12.10. Found: C: 69.19; H: 4.17;
N: 12.12.
Acknowledgements
We are grateful to the China Medical University (CMU99-COL-
11) and the National Science Council of Republic of China for fi-
nancial support (NSC-99-2320-B-039-014-MY3). This study is
supported in part by Taiwan Department of Health Clinical Trial and
Research Center of Excellence (DOH100-TD-B-111-004). This study
is supported in part by Taiwan Department of Health Clinical Trial
and Research Center of Excellence (DOH100-TD-B-111-004).
4.2.20. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-cyclopentyl-
1,2,4-triazole (40). Yellow solid; mp 75e76 ꢂC; 1H NMR (CDCl3,
200 MHz)
d 1.52e1.63 (m, 2H, CH2), 1.79e2.00 (m, 6H, CH2),
2.99e3.16 (m, 1H, CH), 3.94 (s, 3H, CH3) 7.54e7.58 (d, 2H, J¼8.52 Hz,
ArH), 7.73e7.78 (d, 2H, J¼8.52 Hz, ArH); 13C NMR (CDCl3, 50 MHz)
d
25.69 (2ꢁ CH2), 33.06 (2ꢁ CH2), 36.36, 52.89, 115.24, 120.65,
125.92 (2ꢁ CH), 126.73, 126.78, 130.73, 131.39, 132.05, 132.72,
139.56, 154.20, 160.31, 162.38; IR (diffuse reflectance) 2936 (m),
1739 (s, C]O), 1616 (m), 1327 (m), 1223 (m), 1065 (m), 1015 (m),
852 (s), 737 (m) cmꢀ1; MS (ESI) m/z: 339 (Mþþ1). Anal. Calcd for
C16H16F3N3O2; C: 56.64; H: 4.75; N: 12.38. Found: C: 56.62; H: 4.74;
N: 12.35.
Supplementary data
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.05.003.
References and notes
4.2.21. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-
triazole (41). Light yellow solid; mp 67e68 ꢂC; 1H NMR (CDCl3,
1. (a) Giorgio Molteni, G.; Alessandro Pontib, A.; Orlandi, M. New J. Chem. 2002, 26,
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d 1.22e1.33 (m, 4H, CyclohexyleH), 1.67e1.82 (m, 6H,
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ArH); 13C NMR (CDCl3, 50 MHz)
d 25.17, 25.7, 29.61, 31.48, 35.58,
52.83, 115.22, 120.65, 125.84, 126.78, 126.85, 130.76, 131.43, 132.08,
132.74, 139.50, 145.25, 160.26, 162.25; IR (diffuse reflectance) 2959
(m), 1739 (s, C]O), 1616 (m), 1483 (m), 1412 (m), 1227 (m), 1107
(m), 1015 (m), 852 (s) cmꢀ1; MS (ESI) m/z: 353 (Mþþ1). Anal. Calcd
for C17H18F3N3O2; C: 57.79; H: 5.13; N: 11.89. Found: C: 58.77; H:
5.15; N: 11.88.
4.2.22. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-(3-furyl)-1,2,4-
triazole (42). Yellow solid; mp 155e156 ꢂC; 1H NMR (CDCl3,
7. Naito, Y.; Akahoshi, F.; Takeda, S.; Okada, T.; Kajii, M.; Nishimura, H.; Sugiura,
M.; Fukaya, C.; Kagitani, Y. J. Med. Chem. 1996, 39, 3019e3029.
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Milligan, D. L.; Malikzay, A.; Fleming, J.; Gerlak, J.; Deevi, D.; Doody, J. F.; Chiang,
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200 MHz)
d
4.00 (s, 3H, CH3), 6.39 (s, 1H, ArH), 7.39e7.41 (m, 1H,
53.13,
ArH), 7.60e7.81 (m, 5H, ArH); 13C NMR (CDCl3, 50 MHz)
d
109.35, 113.28, 120.58, 122.13, 126.00, 126.47, 126.90, 126.96, 131.42,
132.08, 132.74, 133.40, 139.84, 143.88, 144.04, 144.31, 146.21, 150.21,
154.78, 160.09; IR (diffuse reflectance) 1743 (s, C]O), 1620 (m),
1535 (m), 1415 (m), 1327 (s), 1168 (m), 1123 (s), 1065(m), 845(s),
9. Saha, A. K.; Liu, L.; Simoneaux, R.; DeCorte, B.; Meyer, C.; Skrzat, S.; Breslin, H. J.;
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Brighton Crop Prot. Conf. Pests. Dis. 1990, 2, 407e417; Ammermann, E.; Loecher,
F.; Lorenz, G.; Janseen, B.; Karbach, S.; Meyer, N. Chem. Abstr. 1991, 114, 223404h;
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2005, 15, 3555e3559.
13. Jagerovic, N.; Hemandez-Folgado, L.; Alkorta, I.; Goya, P.; Martin, M. I.; Dannert,
M. T.; Alsasua, A.; Frigola, J.; Cuberes, M. R.; Dordal, A.; Holenz, J. Eur. J. Med.
Chem. 2006, 41, 114e120.
14. Alanine, A.; Anselm, L.; Steward, L.; Thomi, S.; Vifian, W.; Groaning, M. D. Bi-
oorg. Med. Chem. Lett. 2004, 14, 817e821.
15. Dumaĭtre, B.; Dodic, N. J. Med. Chem. 1996, 39, 1635e1644.
16. Yeung, K.-S.; Farkas, M. E.; Kadow, J. F.; Meanwell, N. A. Tetrahedron Lett. 2005,
46, 3429e3432.
17. Liu, C.; Iwanowicz, J. Tetrahedron Lett. 2003, 44, 1409e1411.
18. Abdel-Megeed, A. M.; Abdel-Rahman, H. M.; Alkaramany, G.-E. S.; El-Gendy, M.
A. Eur. J. Med. Chem. 2009, 44, 117e123.
19. (a) Pfefferkorn, J. A.; Choi, C.; Larsen, S. D.; Auerbach, B.; Hutchings, R.; Park, W.;
Askew, V.; Dillon, L.; Hanselman, J. C.; Lin, Z.; Lu, G. H.; Robertson, A.; Sekerke,
C.; Harris, cM. S.; Pavlovsky, A.; Bainbridge, G.; Caspers, N.; Kowala, M.; Tait, B.
D. J. Med. Chem. 2008, 51, 31e45; (b) Silvestri, R.; Cascio, M. G.; Regina, G. L.;
Piscitelli, F.; Lavecchia, A.; Brizzi, A.; Pasquini, S.; Botta, M.; Novellino, E.; Marzo,
V. D.; Corelli, F. J. Med. Chem. 2008, 51, 1560e1576; (c) Pinto, D. J. P.; Orwat, M. J.;
Koch, S.; Rossi, K. A.; Alexander, R. S.; Smallwood, A.; Wong, P. C.; Rendina, A. R.;
741(m) cmꢀ1
;
MS (ESI) m/z: 337 (Mþþ1). Anal. Calcd for
C15H10F3N3O3; C: 53.42; H: 2.99; N: 12.46. Found: C: 53.46; H: 3.01;
N: 12.45.
4.2.23. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-(3-thienyl)-
1,2,4-triazole (43). Yellow solid; mp 85e86 ꢂC; 1H NMR (CDCl3,
200 MHz)
d
4.00 (s, 3H, CH3), 7.10 (dd, 1H, J¼1.26, 4.24 Hz ArH), 7.30
(dd, 1H, J¼2.98, 5.10 Hz ArH), 7.55e7.59 (m, 3H, ArH), 7.72e7.76 (d,
2H, J¼8.44 Hz, ArH); 13C NMR (CDCl3, 50 MHz)
d 53.03, 114.44,
119.54, 120.62, 126.23 (2ꢁ CH), 126.81, 126.88, 127.00, 127.09,
128.71, 131.73, 132.39, 140.18, 151.99, 154.57, 160.11; IR (diffuse re-
flectance) 3121 (m), 1740 (s, C]O), 1616 (m), 1566 (m), 1481 (m),
1443 (m), 1327 (s), 1227 (m), 1145 (s), 1065 (s) cmꢀ1; MS (ESI) m/z:
353 (Mþþ1). Anal. Calcd for C15H10F3N3O2S; C: 50.99; H: 2.85; N:
11.89. Found: C: 51.02; H: 2.84; N: 11.92.
4.2.24. 1-(4-Trifluorophenyl)-3-methoxycarbonyl-5-(2-pyrrolyl)-
1,2,4-triazole (44). Brown solid; mp 201e202 ꢂC; 1H NMR (CDCl3,
200 MHz) d 3.97 (s, 3H, CH3), 5.78e5.81 (m, 1H, ArH), 6.06e6.11 (m,
1H, ArH), 6.90e6.94 (m,1H, ArH), 7.65e7.69 (d, 2H, J¼8.44 Hz, ArH),
7.78e7.82 (d, 2H, J¼8.44 Hz, ArH), 9.92 (br, 1H, NH); 13C NMR
(CDCl3, 50 MHz)
d 52.99, 110.47, 111.74, 117.68, 120.65, 122.39,

W.-C. Tseng et al. / Tetrahedron 67 (2011) 5339e5345
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