An unusual triazole synthesis from aurones

Article abstract of DOI:10.1055/s-0040-1708019

Attempts to prepare azido-substituted aurones via a copper-catalyzed azidation failed to afford the desired product, but instead resulted in an unusual triazole formation reaction. Further efforts noted that copper was not required for this reaction, but simply thermal treatment with sodium azide in a polar aprotic solvent. A wide range of substitution patterns were tolerated in this reaction to afford the interesting salicyl-substituted triazoles in modest to excellent yield. While the mechanism is not yet clear, a simple elimination/cyclization pathway seems unlikely given the failure of the reaction on the corresponding thioaurones, which feature an even better thiol leaving group. Regardless, the potential utility of these easily accessible, multifunctional compounds should engender further interest and applications.

Full text of DOI:10.1055/s-0040-1708019

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–J
paper
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A. Kafle et al.
Paper
Synthesis
An Unusual Triazole Synthesis from Aurones
Arjun Kaflea
Shrijiana Bhattaraia
Scott T. Handy*a,b
a Molecular Biosciences Program, Middle Tennessee State University,
Murfreesboro, TN 37132, United States
b Department of Chemistry, Middle Tennessee State University,
Murfreesboro, TN 37132, United States
Scott.Handy@mtsu.edu
Received: 09.01.2020
Accepted after revision: 30.03.2020
Published online: 20.04.2020
While it is true that there are many commercially avail-
able aldehydes as well as a number of commercially avail-
able benzofuranones, we were interested in potentially
combining our recently reported azidation/click reaction of
aryl halides to further diversify and functionalize halogen
containing aurones.3 In this way, even greater structural di-
versity could be accessed without the need to synthesize a
new aldehyde for each new aurone.
In addition, this same azidation chemistry in the ab-
sence of an alkyne should afford the unknown 4-azido-
aurone. This compound or similar azidoaurones are expect-
ed to be suitable substrates for photoaffinity labeling via
nitrene generation and thus find application in studies to
better understand the interaction of these compound with
biological systems.4
DOI: 10.1055/s-0040-1708019; Art ID: ss-2020-m0018-op
Abstract Attempts to prepare azido-substituted aurones via a copper-
catalyzed azidation failed to afford the desired product, but instead re-
sulted in an unusual triazole formation reaction. Further efforts noted
that copper was not required for this reaction, but simply thermal treat-
ment with sodium azide in a polar aprotic solvent. A wide range of sub-
stitution patterns were tolerated in this reaction to afford the interest-
ing salicyl-substituted triazoles in modest to excellent yield. While the
mechanism is not yet clear, a simple elimination/cyclization pathway
seems unlikely given the failure of the reaction on the corresponding
thioaurones, which feature an even better thiol leaving group. Regard-
less, the potential utility of these easily accessible, multifunctional com-
pounds should engender further interest and applications.
Key words aurones, triazoles, cycloaddition, metal-free, polar aprotic
With these twin goals in mind, iodoaurone 1 was select-
ed as a substrate for an in situ azidation/click reaction. Ini-
tial attempts did result in consumption of the iodoaurone,
but failed to afford any of the anticipated triazole 2 (Scheme
2). In an effort to understand the failure of this transforma-
tion, iodoaurone 1 was simply subjected to our standard
azidation conditions but without the alkyne [sodium azide,
catalytic copper(I) iodide and N,N′-dimethylethylenedi-
amine in choline chloride/glycerol (CC/G)]. Again, this con-
sumed the starting material, but failed to afford any azide 3.
Further variations in solvent, catalyst, and temperature
likewise only resulted in conversion to a new unknown
product that did not contain an azide, but featured most of
the anticipated spectral features of an aurone with the ex-
ception of the very characteristic enone -proton.
Aurones are an interesting minor sub-family of the fla-
vonoid family of natural products.1 Although known for
some time, they have received comparatively little interest
until fairly recently. Even this current interest has been fair-
ly limited in terms of its diversity. In part, this situation is
the result of most efforts being determined by the synthetic
approach employed to access the aurone framework. In vir-
tually all cases, this approach is the Knoevenagel-type con-
densation of a benzofuranone with an aromatic aldehyde2
(Scheme 1).
O
O
Ar
O
H
Ar
After several other failed attempts, new attempts were
made to react cyanoaurone 5a with sodium azide to form
the corresponding tetrazole 4 (Scheme 3). Again, the reac-
tion failed to afford the anticipated tetrazole but did result
in consumption of the starting material and the formation
of a new polar product that showed considerable similarity
O
O
aurone
benzofuranone
Scheme 1 Condensation route to aurones
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A. Kafle et al.
Paper
Synthesis
Table 1 Reaction Conditions Study
Ph
N
N
I
CN
Ph
H
N
N
NaN3, CuI
N
N
O
O
O
NaN3 (2 equiv)
MeHN
NHMe
O
DMSO
CC/G, 60 °C
O
OH
120 °C, 80 min
O
2
5
5a
CN
1
O
N3
Entry
Condition modification
Time
80 min
Yield (%)a
1
2
3
4
5
6
7
8
9
CuSO4, 140 °C
none
100 (75)
100 (83)
100 (ND)
100 (ND)
100 (88)
NR
O
via
30 min
6 h
O
80 °C
3
100 °C
3 h
Scheme 2 Azidation/click attempt
DMF, 105 °C
1,4-dioxane, 105 °C
THF, 65 °C
20 min
15 h
24 h
15 h
12 h
to that obtained from the reactions with iodoaurone 1. This
product could be isolated as a solid that could be crystal-
lized to afford crystals suitable for X-ray diffraction analy-
sis5 (Scheme 3). This analysis confirmed that the product
was indeed not a tetrazole, but actually the triazole 5.
NR
EtOH (95%), 105 °C
glacial AcOH, 120 °C
75 (ND)
NR
a Conversion yields by 1H NMR analysis (values in parentheses are isolated
yields). ND = Not determined; NR = no reaction.
H
N
N
N
dioxane) were not effective, while a protic solvent (EtOH)
was slower, but did afford the product in a reduced yield.
While the results in Table 1 might appear to indicate
that DMF was the best solvent, further examples did not
demonstrate this to be a consistent result. Further, one ma-
jor challenge with this chemistry was product isolation. The
triazole products are quite polar and frequently do not af-
ford good recovery following chromatography. DMSO could
be removed much more readily from the reactions than
DMF and was used in all subsequent examples.
N
CN
O
4
O
NaN3 (2 equiv)
anticipated
O
H
N
CuSO4•7H2O
(10 mol%)
DMSO
N
N
O
O
5a
120 °C, 80 min
OH
In examining the scope of the reaction, variations of the
aryl group proved to be well tolerated (Scheme 4). While
the isolated yields varied from near 50% to just under 90%,
there was no clear trend. Electron-withdrawing groups af-
forded high yields, as did methyl ethers. Most halogens
were similarly efficient. Curiously, free hydroxyl groups and
alkyl groups tended to afford the lowest yields. In the case
of free hydroxyl groups, this is likely due to their highly po-
lar nature, making isolation and purification difficult. It is
worth noting that NMR analysis of the crude reaction mix-
tures showed clean conversion to product, with only small
amounts (<10%) of starting material or unidentified by-
products as well as residual solvent. Further, mass balance
was near quantitative, demonstrating that the yield chal-
lenge is clearly in the purification step. Two heteroaromat-
ics that were explored afforded similar yields.
5
CN
actual
Scheme 3 New triazole formation
With this structural confirmation, reexamination of the
products from the reaction with iodoaurone 1 proved to
have similarly afforded these unusual triazole products.
Further optimization of this transformation was conducted
using cyanoaurone 5a (Table 1).
Using sodium azide in DMSO without any catalyst also
afforded the triazole product 5. Further attempts at optimi-
zation of this transformation noted that polar aprotic sol-
vents were good for this reaction, affording modest to good
yields of the triazole after short reaction times at moderate
temperature (120 °C). Decreasing the temperature resulted
in slower conversion to the triazole, with the reaction at
100 °C requiring 3 hours and one at 80 °C requiring 6 hours.
Further reduction in temperature resulted in a very slug-
gish and unclean reaction. Less polar solvents (THF and 1,4-
In probing the utility of the reaction with respect to the
benzofuranone portion, it proved to be equally general
(Scheme 5). Halogens were tolerated at all positions as were
methyl groups at all 3 positions that were tested. Yields
ranged from 55–81%.
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A. Kafle et al.
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Synthesis
H
R
O
N
N
N
NaN3 (1.5 equiv)
R
DMSO
120 °C, 30 min
O
OH
O
5a–31a
5–31
H
H
H
N
N
N
N
N
N
N
N
N
CN
O
O
O
OH
OH
OH
5
NO2
6, 74%
7, 73%
CN
5, 83%
H
N
H
H
N
N
N
N
N
N
N
N
OMe
OMe
OMe
O
O
O
OH
8, 89%
OH
OH
10
O2N
MeO
10, 78%
9, 83%
H
H
H
N
H
N
N
N
N
N
N
N
N
N
N
N
OMe
OMe
O
O
O
O
OH
OH
OH
14, 90%
OH
Cl
MeO
13, 80%
MeO
Cl
11, 86%
12, 70%
H
N
N
H
N
H
H
N
N
N
N
N
N
N
N
N
Cl
Cl
I
O
O
O
O
OH
15, 94%
OH
17, 63%
OH
16, 61%
OH
18, 88%
I
Cl
H
N
H
H
N
N
H
N
N
N
N
N
N
N
N
N
CF3
CF3
O
O
O
O
OH
22, 50%
OH
OH
21, 72%
OH
OH
CF3
20, 73%
19, 89%
H
H
H
H
N
N
N
N
N
N
N
N
N
N
N
N
OMe
OH
Me
O
O
O
O
OH
OH
OH
OH
23, 43%
25, 57%
24, 58%
26, 50%
H
N
H
N
H
H
N
N
N
N
N
N
N
N
N
N
O
O
O
O
S
OH
OH
OH
29, 61%
OH
Ph
N
Ph
30, 73%
Ph
28, 57%
27, 50%
H
N
N
N
S
O
OH
31, 48%
Scheme 4 Aurone variations
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A. Kafle et al.
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Synthesis
quence, or an elimination to an intermediate ynone fol-
lowed by cycloaddition is occurring. Considering that
ynones are known to readily undergo reaction with sodium
azide to afford triazoles, elimination/cycloaddition would
appear to be the simplest mechanistic explanation.7 Unfor-
tunately, attempts to observe a ynone intermediate have
not been successful and reactions under the same reaction
conditions using thioaurone 47a afforded only recovered
starting material even though it would be expected that
elimination of the better thiol leaving group would be more
facile and thus afford better yields of the triazole product
(Scheme 6). Additionally, attempts to induce elimination
using DBU in DMSO at temperatures up to 120 °C for up to
12 hours have resulted only in recovery of the starting au-
rone, as has thermal treatment of the aurone in the absence
of sodium azide.
H
N
N
N
NaN3
(1.5 equiv)
7
Ar
O
R
R
Ar
DMSO
120 °C, 30 min
O
4
O
OH
55–81%
H
H
N
H
N
N
N
N
N
N
N
N
Cl
Ar
Ar
Ar
Cl
O
O
O
Cl
OH
OH
OH
32, 83%
33, 60%
34, 82%
Ar = 4-NCC6H4
Ar = 4-NCC6H4
Ar = 4-NCC6H4
H
N
H
N
H
N
N
N
N
N
N
N
Cl
Br
Ar
Ar
Ar
O
O
O
Br
OH
OH
OH
35, 58%
36, 56%
37, 74%
Ar = 4-NCC6H4
Ar = 4-NCC6H4
Ar = 4-NCC6H4
CN
H
N
H
N
H
N
H
N
N
N
N
N
N
N
N
N
F
Me
NaN3
S
Ar
Ar
Ar
O
DMSO
120 °C, 30 min
O
O
O
SH
O
CN
OH
OH
Me
OH
47a
38, 81%
39, 59%
40, 62%
Ar = 4-NCC6H4
Ar = 3-MeOC6H4
Ar = 3-MeOC6H4
Scheme 6 Thioaurone attempt
H
N
H
H
N
N
N
N
O
N
N
Ar
N
N
Me
Me
From the literature, the closest transformation was re-
ported a number of years ago by Bognar and co-workers on
the conversion of dibromochalcones with sodium azide in
DMF into a number of different compounds including a tri-
azole.8 Even in this case, the mechanism is unclear, and a
number of possible pathways are proposed. Ring openings
of aurones using methyl isocyanoacetate have been report-
ed recently by Shao and co-workers for which a more com-
plicated cyclization/ring opening pathway has been pro-
posed.9 However, this reaction also requires a base catalyst
and proceeds best in protic solvents, unlike our conversion
to triazoles. Msadek and co-workers have reported the ring-
opening synthesis of pyrazoles from aurones by reaction
with aryldiazomethanes under mild thermal conditions.
They propose that this reaction occurs via cycloaddition fol-
lowed by elimination to afford the aromatic pyrazole, but
no mechanistic evidence is provided.10 As a result, the
mechanism for this transformation to triazoles is far from
clear at present.
In conclusion, we have observed an unusual ring-open-
ing triazole formation by the reaction of aurones with sodi-
um azide. The product triazoles feature two clear sites for
alkylation chemistry as well as great opportunity for modi-
fication at many sites in the ring system. Given this poten-
tial and their ease of access, it is anticipated that they could
prove to be new, unexplored scaffolds for further develop-
ment.
Ar
Ar
Me
O
O
OH
OH
Me
OH
41, 71%
42, 72%
43, 60%
Ar = 3-MeOC6H4
Ar = 3-O2NC6H4
Ar = 3-O2NC6H4
H
N
H
N
H
N
N
N
N
N
N
N
Me
Me
Ar
Me
Ar
O
Ar
Me
O
O
Cl
OH
OH
OH
44, 68%
45, 64%
46, 55%
Ar = 3-O2NC6H4
Ar = 4-MeC6H4
Ar = 4-MeC6H4
Scheme 5 Benzofuranone variations
Additional peaks observed, which were particularly evi-
dent in the 13C NMR of some triazoles, suggested the pres-
ence of tautomeric mixtures that depend on the concentra-
tion and type of solvent used. Tautomerism has been re-
ported as a common phenomenon in 1,2,3-triazoles,6 which
in our case, was further evidenced in the crystal structures
of triazoles 5 and 10 which feature the N2 and N1 tautom-
ers respectively (Figure S1).5 This tautomerization is evi-
dent from the hybridization and bond lengths indicated in
the crystal structures and the inferred location of hydrogen
atoms.
With respect to the reaction mechanism, it is unclear at
this point whether some form of Michael addition/elimina-
tion/cyclization sequence, a cycloaddition/elimination se-
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Synthesis
All the reactions were done under an air atmosphere. 1H and 13C NMR
of all the compounds were recorded on JEOL AS (500 and 300 MHz)
NMR instrument and chemical shifts were recorded in ppm. All the
chemical shifts were recorded taking CDCl3 or DMSO, or acetone as a
standard reference.11 Standard abbreviations are used for multiplici-
ties. Cary 630 FT-IR (Agilent Technologies) was used to collect IR spec-
tra. All mass spectra were acquired on a Waters Synapt HDMS QToF
with Ion Mobility. All extracts were concentrated under reduced pres-
sure using a Büchi Rotary Evaporator. During purification and identi-
fication of compounds, TLC was performed on silica gel coated TLC
plates and monitored by short wavelength (254 nm) UV light. Prod-
ucts were purified by silica gel column chromatography. ACS grade
reagents were employed during the experiments.
(2-Hydroxyphenyl)[5-(4-nitrophenyl)-2H-1,2,3-triazol-4-yl]meth-
anone (7)
From aurone 7a (80 mg, 0.30 mmol); eluent: 40% EtOAc/hexane;
yield: 68 mg (73%); yellow solid; mp 200–202 °C.
IR (neat): 3471, 2903, 1596, 1467, 1438, 1207, 1162, 1149, 1041, 929,
834, 754 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 8.34 (d, J = 9.0 Hz, 2 H), 8.26 (dd,
J = 8.0, 1.5 Hz, 1 H), 8.10 (d, J = 9.0 Hz, 2 H), 7.63 (ddd, J = 8.5, 7.5, 1.5
Hz, 1 H), 7.04 (d, J = 8.5 Hz, 1 H), 6.99 (ddd, J = 8.5, 7.5, 1.0 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.4, 164.3, 149.0, 138.2,
136.8, 134.9, 130.6, 130.5, 124.4, 120.5, 119.9, 118.8 (peaks for anoth-
er tautomer were also observed).
HRMS (EI): m/z [M + H] calcd for C15H11N4O4: 311.0780; found:
311.0781.
The synthesis and characterization of starting aurones are described
in the Supporting Information.
(2-Hydroxyphenyl)[5-(3-nitrophenyl)-2H-1,2,3-triazol-4-yl]meth-
Triazoles; General Procedure
anone (8)
In a 3-dram glass vial, aurone (1 equiv) and NaN3 (1.5 equiv) were
combined and dissolved in regular DMSO (1.5 mL). The reaction mix-
ture was then stirred for 30 min at 120 °C in a sand bath. The mixture
immediately changed its color to dark brown. The reaction was moni-
tored by TLC. After 30 min, the mixture was transferred to a 50 mL
centrifuge tube, diluted with distilled H2O, and extracted several
times with EtOAc. To remove residual DMSO, the organic fraction was
then washed with distilled H2O followed by brine. The organic frac-
tion was concentrated in vacuo and the crude material was further
purified by flash column chromatography using mixtures of hexane
and EtOAc (20–50% EtOAc/hexane) to obtain the desired triazole.
From aurone 8a (101.5 mg, 0.38 mmol); eluent: 50% EtOAc/hexane;
yield: 105 mg (89%); yellow solid; mp 157–158 °C.
IR (neat): 3110, 2903, 1628, 1534, 1482, 1350, 1253, 1153, 1100, 925,
817, 747 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 8.72 (br s, 1 H), 8.32 (t, J = 7.5 Hz,
2 H), 8.27 (d, J = 8.5 Hz, 1 H), 7.79 (t, J = 8.0 Hz, 1 H), 7.62 (t, J = 8.0 Hz,
1 H), 7.04 (d, J = 8.5 Hz, 1 H), 6.99 (t, J = 7.5 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.2, 164.3, 149.2, 138.1,
134.9, 132.2, 130.7, 124.6, 124.4, 124.2, 124.0, 120.5, 119.9, 118.8
(peaks for another tautomer were also observed).
HRMS (EI): m/z [M + H] calcd for C15H11N4O4: 311.0780; found:
4-[5-(2-Hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzonitrile (5)
311.0783.
From aurone 5a (215 mg, 0.87 mmol), no chromatographic separation
was needed; yield: 241 mg (83%); yellow solid; mp 162–164 °C.
[5-(3,5-Dimethoxyphenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
nyl)methanone (9)
IR (neat): 3160, 2997, 2924, 2238, 1737, 1628, 1469, 1432, 1264,
1233, 1153, 991, 920, 747 cm–1
.
From aurone 9a (107.3 mg, 0.38 mmol); eluent: 50% EtOAc/hexane;
yield: 103 mg (83%); waxy solid; mp 79–82 °C.
1H NMR (500 MHz, acetone-d6):  = 8.29–8.20 (m, 1 H), 8.02 (d, J = 8.5
Hz, 2 H), 7.88 (d, J = 8.5 Hz, 2 H), 7.62 (ddd, J = 8.5, 7.5, 1.5 Hz, 1 H),
7.04 (dd, J = 8.5, 0.9 Hz, 1 H), 6.98 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.4, 164.3, 138.1, 135.5,
134.9, 133.1, 133.0, 130.2, 130.1, 120.5, 119.9, 119.0, 118.8, 113.4
(peaks for another tautomer were also observed).
IR (neat): 3478, 3070, 2905, 2838, 1600, 1596, 1469, 1439, 1289,
1248, 1151, 1069, 752, 678 cm–1
.
1H NMR (500 MHz, CDCl3):  = 11.99 (s, 1 H), 7.99 (d, J = 6.0 Hz, 1 H),
7.49 (t, J = 7.5 Hz, 1 H), 7.02 (d, J = 8.5 Hz, 1 H), 6.85 (d, J = 7.5 Hz, 1 H),
6.82 (s, 2 H), 6.49 (d, J = 2.5 Hz, 1 H), 3.74 (s, 6 H).
13C{1H} NMR (125 MHz, CDCl3):  = 192.4, 163.6, 160.9, 137.4, 133.8,
119.6, 119.3, 118.3, 106.7, 102.1, 55.6.
HRMS (EI): m/z calcd [M + H] for C16H11N4O2: 291.0882; found:
291.0885.
HRMS (EI): m/z [M + H] calcd for C17H16N3O4: 326.1141; found:
3-[5-(2-Hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzonitrile (6)
326.1138.
From aurone 6a (94 mg, 0.38 mmol); eluent: 40% EtOAc/hexane;
yield: 82 mg (74%); yellow solid; mp 159–161 °C.
(2-Hydroxyphenyl)[5-(3-methoxyphenyl)-2H-1,2,3-triazol-4-
yl]methanone (10)
IR (neat): 3306, 3073, 2924, 2231, 1628, 1600, 1475, 1315, 1145,
1119, 924, 760, 732 cm–1
.
From aurone 10a (96 mg, 0.38 mmol); eluent: 50% EtOAc/hexane;
yield: 96 mg (78%); yellow solid; mp 94–96 °C.
1H NMR (500 MHz, acetone-d6):  = 8.31 (d, J = 7.5 Hz, 1 H), 8.24 (s, 1
H), 8.13 (dd, J = 8.0, 1.5 Hz, 1 H), 7.88–7.85 (m, 1 H), 7.70 (dd, J = 10.0,
6.0 Hz, 1 H), 7.61 (ddd, J = 10.0, 6.0, 1.5 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1
H), 6.98 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H).
IR (neat): 3078, 2959, 2907, 1628, 1598, 1585, 1484, 1441, 1225,
1150, 1033, 1009, 752 cm–1
.
1H NMR (500 MHz, CDCl3):  = 12.03 (s, 1 H), 8.05 (d, J = 5.0 Hz, 1 H),
7.51 (ddd, J = 8.5, 3.0, 1.5 Hz, 1 H), 7.31 (t, J = 8.0 Hz, 1 H), 7.27 (over-
lapped with residual CHCl3 in the solvent, 1 H) 7.23 (d, J = 7.6 Hz, 1 H),
7.04 (d, J = 8.5 Hz, 1 H), 6.96 (d, J = 8.1 Hz, 1 H), 6.87 (t, J = 8.0 Hz, 1 H),
3.79 (s, 3 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.1, 164.3, 138.0, 134.9,
133.9, 133.4, 132.2, 132.9, 132.5, 131.8, 130.6, 120.5, 119.9, 118.9,
118.7, 113.4 (peaks for another tautomer were also observed).
HRMS (EI): m/z [M + H] calcd for C16H11N4O2: 291.0882; found:
291.0879.
13C{1H} NMR (125 MHz, CDCl3):  = 192.3, 163.5, 159.6, 140.7, 137.3,
133.8, 129.9, 128.6, 121.0, 119.5, 119.3, 118.3, 115.8, 114.1, 55.4.
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A. Kafle et al.
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Synthesis
HRMS (EI): m/z [M + H] calcd for C16H14N4O3: 296.1035; found:
296.1038.
13C{1H} NMR (75 MHz, CDCl3):  = 191.9, 163.6, 141.1, 137.6, 134.8,
133.7, 129.9, 128.7, 126.9, 119.4, 118.5 (peaks for another tautomer
were also observed).
[5-(2,4-Dimethoxyphenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
HRMS (EI): m/z [M + H] calcd for C15H11ClN3O2: 300.0540; found:
nyl)methanone (11)
300.0541.
From aurone 11a (107.3 mg, 0.38 mmol); eluent: 50% EtOAc/hexane;
yield: 96 mg (86%); yellow solid; mp 194–195 °C.
[5-(2-Chlorophenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
nyl)methanone (15)
IR (neat): 3237, 1624, 1581, 1499, 1458, 1441, 1210, 1032, 925, 819,
756 cm–1
.
From aurone 15a (97.5 mg, 0.38 mmol); eluent: 40% EtOAc/hexane;
yield: 107 mg (94%); yellow solid; mp 102–105 °C.
1H NMR (300 MHz, DMSO-d6):  = 11.55 (s, 1 H), 7.8 (br s, 1 H), 7.46
(dd, J = 18.6, 7.5 Hz, 2 H), 6.95 (d, J = 8.1 Hz, 1 H), 6.86 (t, J = 7.5 Hz, 1
H), 6.62 (dd, J = 8.5, 2.1 Hz, 1 H), 6.53 (s, 1 H), 3.79 (s, 3 H), 3.43 (s, 3
H).
13C{1H} NMR (75 MHz, acetone-d6):  = 194.5, 164.1, 163.3, 158.3,
137.4, 134.6, 131.8, 120.6, 119.7, 118.5, 106.4, 99.2, 55.8, 55.3.
IR (neat): 3460, 3091, 2812, 1601, 1473, 1452, 1249, 1153, 1037, 992,
752 cm–1
.
1H NMR (500 MHz, CDCl3):  = 11.91 (s, 1 H), 8.36 (br s, 1 H), 7.56–
7.54 (m, 1 H), 7.51 (d, J = 7.0 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 7.44–
7.38 (m, 2 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.93 (t, J = 7.5 Hz, 1 H).
HRMS (EI): m/z [M + H] calcd for C17H16N3O4: 326.1141; found:
13C{1H} NMR (125 MHz, CDCl3):  = 191.1, 163.6, 137.2, 133.5, 133.4,
326.1143.
131.5, 131.1, 130.1, 127.2, 119.3, 119.1, 118.3.
HRMS (EI): m/z [M + H] calcd for C15H11ClN3O2: 300.0540; found:
300.0538.
(2-Hydroxyphenyl)[5-(3,4,5-trimethoxyphenyl)-2H-1,2,3-triazol-
4-yl]methanone (12)
From aurone 12a (62.5 mg, 0.20 mmol); eluent: 50% EtOAc/hexane;
[5-(2,4-Dichlorophenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
yield: 50 mg (70%); yellow solid; mp 211–213 °C.
nyl)methanone (16)
IR (neat): 2957, 2928, 1631, 1596, 1482, 1441, 1248, 1132, 983, 935,
From aurone 16a (128 mg, 0.44 mmol); eluent: 30% EtOAc/hexane;
yield: 90 mg (61%); yellow waxy solid; mp 62–64 °C.
760 cm–1
.
1H NMR (500 MHz, DMSO-d6):  = 7.77 (s, 1 H), 7.52–7.42 (m, 1 H),
IR (neat): 3132, 2909, 1626, 1601, 1447, 1248, 1151, 922, 618 cm–1
.
7.10 (s, 2 H), 6.93 (m, 2 H), 3.77 (m, 6 H), 3.69 (m, 3 H).
13C{1H} NMR (125 MHz, DMSO-d6):  = 190.7, 159.3, 152.7, 138.3,
134.9, 131.9, 123.5, 118.9, 117.2, 106.1, 60.1, 55.9.
1H NMR (500 MHz, CDCl3):  = 11.88 (s, 1 H), 8.35 (br s, 1 H), 7.56–
7.52 (m, 1 H), 7.51–7.49 (m, 2 H), 7.39 (dd, J = 8.0, 2.0 Hz, 1 H), 7.04 (d,
J = 8.5 Hz, 1 H), 6.94 (t, J = 7.5 Hz, 1 H).
HRMS (EI): m/z [M + H] calcd for C18H18N3O5: 356.1247; found:
13C{1H} NMR (125 MHz, CDCl3):  = 190.8, 163.7, 137.3, 136.5, 134.2,
356.1246.
133.4, 132.3, 129.9, 127.6, 119.3, 119.0, 118.4.
HRMS (EI): m/z [M + H] calcd for C15H10Cl2N3O2: 334.0150; found:
334.0151.
[5-(4-Chlorophenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
nyl)methanone (13)
From aurone 13a (97.5 mg, 0.38 mmol); eluent: 40% EtOAc/hexane;
(2-Hydroxyphenyl)[5-(4-iodophenyl)-2H-1,2,3-triazol-4-yl]meth-
yield: 91 mg (80%); yellow solid; mp 147–149 °C.
anone (17)
IR (neat): 3150, 2913, 2825 (br), 1626, 1596, 1443, 1259, 1318, 1259,
From aurone 17a (250.7 mg, 0.72 mmol); eluent: 30% EtOAc/hexane;
yield: 177 mg (63%); yellow solid; mp 161–163 °C.
1222, 1154, 1099, 924, 791 cm–1
.
1H NMR (300 MHz, acetone-d6):  = 12.03 (br s, 1 H), 8.28 (d, J = 9.0
Hz, 1 H), 7.82 (d, J = 8.4 Hz, 2 H), 7.59 (ddd, J = 8.5, 4.5, 0.7 Hz, 1 H),
7.49 (d, J = 8.4 Hz, 2 H), 7.03 (d, J = 8.4 Hz, 1 H), 6.96 (dd, J = 7.2 Hz, 1
H).
13C{1H} NMR (75 MHz, acetone-d6):  = 193.5, 164.3, 137.9, 135.6,
134.9, 131.1, 130.9, 129.4, 129.3, 120.5, 119.8, 118.7 (peaks for anoth-
er tautomer were also observed).
IR (neat): 3132, 2909, 1626, 1601, 1447, 1248, 1151, 922, 618 cm–1
.
1H NMR (500 MHz, CDCl3):  = 11.98 (s, 1 H), 8.08 (br s, 1 H), 7.78 (d,
J = 8.5 Hz, 1 H), 7.55 (ddd, J = 8.5, 7.5, 1.5 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1
H), 7.26 (s, 1 H), 7.06 (dd, J = 8.5, 1.0 Hz, 1 H), 6.91 (t, J = 8.0 Hz, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 192.1, 163.58, 138.0, 137.6, 133.7,
130.3, 119.5, 119.4, 118.6, 96.5.
HRMS (EI): m/z [M + H] calcd for C15H11IN3O2: 391.9896; found:
391.9896.
HRMS (EI): m/z [M + H] calcd for C15H11ClN3O2: 300.0540; found:
300.0545.
(2-Hydroxyphenyl)[5-(3-iodophenyl)-2H-1,2,3-triazol-4-yl]meth-
anone (18)
[5-(3-Chlorophenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
nyl)methanone (14)
From aurone 18a (212.4 mg, 0.61 mmol); eluent: 30% EtOAc/hexane;
yield: 209 mg (88%); waxy solid; mp 60–61 °C.
From aurone 14a (97.5 mg, 0.38 mmol); eluent: 30% EtOAc/hexane;
yield: 103 mg (90%); waxy solid; mp 67–69 °C.
IR (neat): 2887, 3060 (br), 2920, 1628, 1443, 1257, 1218, 1153, 1009,
IR (neat): 3161 (br), 2920, 1626, 1598, 1445, 1255, 1153, 925, 754,
924, 752 cm–1
.
680 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 8.27 (d, J = 8.0 Hz, 1 H), 8.21 (t, J =
1.5 Hz, 1 H), 7.83 (t, J = 7.5 Hz, 2 H), 7.62 (t, J = 8.0 Hz, 1 H), 7.29 (t, J =
8.0 Hz, 1 H), 7.04 (d, J = 8.0 Hz, 1 H), 6.98 (t, J = 7.5 Hz, 1 H).
1H NMR (300 MHz, CDCl3):  = 11.98 (s, 1 H), 8.04 (d, J = 8.0 Hz, 1 H),
7.73 (d, J = 1.5 Hz, 1 H), 7.57–7.49 (m, 2 H), 7.40–7.29 (m, 1 H), 7.05
(d, J = 8.5 Hz, 1 H), 6.87 (t, J = 7.6 Hz, 1 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Kafle et al.
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Synthesis
13C{1H} NMR (125 MHz, CDCl3):  = 209.5, 192.1, 163.6, 145.5, 141.1,
IR (neat): 3131, 2961, 1615, 1592, 1434, 1223, 922, 748 cm–1
.
138.5, 137.3, 133.8, 130.2, 128.0, 119.5, 119.3, 118.4, 94.3.
1H NMR (500 MHz, acetone-d6):  = 8.26 (d, J = 6.0 Hz, 1 H), 7.65 (d, J =
8.5 Hz, 2 H), 7.56–7.50 (m, 1 H), 6.98 (d, J = 8.5 Hz, 1 H), 6.92–6.87 (m,
3 H) (peaks for another tautomer were also observed).
HRMS (EI): m/z [M + H] calcd for C15H11IN3O2: 391.9896; found:
391.9898.
13C{1H} NMR (125 MHz, acetone-d6):  = 193.8, 164.3, 159.5, 137.6,
135.0, 131.0, 130.8, 120.7, 119.7, 118.6, 116.3, 116.0 (peaks for anoth-
er tautomer were also observed).
(2-Hydroxyphenyl){5-[4-(trifluoromethyl)phenyl]-2H-1,2,3-tri-
azol-4-yl}methanone (19)
From aurone 19a (98.7 mg, 0.34 mmol), no chromatographic separa-
tion was needed; yield: 101 mg (89%); yellow solid; mp 127–129 °C.
HRMS (EI): m/z [M + H] calcd for C15H11N3O3: 282.0878; found:
282.0875.
IR (neat): 3226, 2828, 1626, 1607, 1479, 1450, 1432, 1322, 1158,
1110, 920, 845 cm–1
.
[5-(4-Hydroxy-3-methoxyphenyl)-2H-1,2,3-triazol-4-yl](2-hy-
1H NMR (500 MHz, CDCl3):  = 11.96 (s, 1 H), 8.07 (d, J = 8.0 Hz, 1 H),
7.88 (d, J = 8.0 Hz, 2 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.56 (ddd, J = 8.5, 7.5,
1.5 Hz, 1 H), 7.08 (d, J = 8.5 Hz, 1 H), 6.92 (t, J = 8.0 Hz, 1 H).
droxyphenyl)methanone (23)
From aurone 23a (110 mg, 0.41 mmol); eluent: 50% EtOAc/hexane;
yield: 55 mg (43%); yellow solid; mp 186–187 °C.
13C{1H} NMR (75 MHz, CDCl3):  = 192.1, 163.7, 146.2, 141.3, 137.8,
133.6, 131.8 (q, 2JC,F = 30 Hz), 129.1, 127.4 (q, 1JC,F = 240 Hz), 125.7 (q,
3JC,F = 4.5 Hz), 119.5, 119.4, 118.6 (peaks for another tautomer were
also observed).
IR (neat): 3181, 2939, 1628, 1594, 1486, 1445, 1214, 927, 789 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 12.08 (s, 1 H), 8.26 (s, 1 H), 7.60
(ddd, J = 8.5, 7.5, 1.5 Hz, 1 H), 7.46 (d, J = 1.5 Hz, 1 H), 7.30 (dd, J = 8.0,
2.0 Hz, 1 H), 7.02 (d, J = 8.5 Hz, 1 H), 6.96 (t, J = 8.0 Hz, 1 H), 6.92 (d, J =
8.5 Hz, 1 H), 3.87 (s, 3 H) (peaks for another tautomer were also ob-
served).
HRMS (EI): m/z [M + H] calcd for C16H11F3N3O2: 334.0803; found:
334.0800.
13C{1H} NMR (125 MHz, acetone-d6):  = 194.0, 164.3, 148.9, 148.3,
137.7, 135.1, 122.9, 120.9, 119.8, 118.7, 116.0, 113.1, 56.3 (peaks for
other tautomers were also observed).
(2-Hydroxyphenyl){5-[3-(trifluoromethyl)phenyl]-2H-1,2,3-tri-
azol-4-yl}methanone (20)
From aurone 20a (119 mg, 0.41 mmol); eluent: 30% EtOAc/hexane;
yield: 99 mg (73%); mp 113–115 °C.
HRMS (EI): m/z [M + H] calcd for C16H14N3O4: 312.0984; found:
312.0981.
IR (neat): 3226, 2828, 1626, 1607, 1479, 1432, 1322, 1110, 920, 758
cm–1
.
(2-Hydroxyphenyl)[5-(m-tolyl)-2H-1,2,3-triazol-4-yl]methanone
1H NMR (301 MHz, CDCl3):  = 11.97 (s, 1 H), 8.07 (d, J = 9.0 Hz, 2 H),
7.91 (d, J = 7.5 Hz, 1 H), 7.69 (d, J = 7.4 Hz, 1 H), 7.54 (t, J = 7.8 Hz, 2 H),
7.06 (d, J = 8.4 Hz, 1 H), 6.89 (t, J = 7.7 Hz, 1 H).
(24)
From aurone 24a (45 mg, 0.19 mmol); eluent: 30% EtOAc/hexane;
yield: 31 mg (58%); waxy solid.
13C{1H} NMR (125 MHz, CDCl3):  = 191.9, 163.6, 141.1, 137.7, 133.6,
IR (neat): 3134, 2918, 1626, 1445, 1309, 1257, 1151, 925, 754 cm–1
.
2
3
132.1, 131.2 (q, JC,F = 32.5 Hz), 129.3, 129.1, 126.4 (q, JC,F = 2.5 Hz),
1H NMR (500 MHz, CDCl3):  = 12.05 (s, 1 H), 8.11 (d, J = 8.0 Hz, 1 H),
7.53–7.46 (m, 2 H), 7.43 (d, J = 8.0 Hz, 1 H), 7.28 (t, J = 7.5 Hz, 1 H),
7.23 (d, J = 7.5 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.86 (t, J = 7.5 Hz, 1 H),
2.34 (s, 3 H).
125.6 (q, 3JC,F = 3.75 Hz), 123.8 (q, 1JC,F = 270 Hz), 119.4, 119.3, 118.3.
HRMS (EI): m/z [M + H] calcd for C16H11F3N3O2: 334.0803; found:
334.0801.
13C{1H} NMR (125 MHz, CDCl3):  = 192.3, 163.7, 141.1, 138.7, 137.3,
133.9, 130.8, 129.3, 128.8, 127.6, 125.9, 119.7, 119.3, 118.4, 77.4, 77.2,
76.9, 21.5.
(2-Hydroxyphenyl){5-[2-(trifluoromethyl)phenyl]-2H-1,2,3-tri-
azol-4-yl}methanone (21)
From aurone 21a (41 mg, 0.14 mmol); eluent: 30% EtOAc/hexane;
yield: 36 mg (72%); yellow solid; mp 147–150 °C.
HRMS (EI): m/z [M + H] calcd for C16H14N3O2: 280.1086; found:
280.1084.
IR (neat): 3084, 2855, 1629, 1574, 1439, 1328, 1253, 1076, 973,
758 cm–1
.
{5-[4-(tert-Butyl)phenyl]-2H-1,2,3-triazol-4-yl}(2-hydroxyphe-
1H NMR (500 MHz, CDCl3):  = 11.90 (s, 1 H), 8.48 (d, J = 7.5 Hz, 1 H),
7.77 (d, J = 7.5 Hz, 1 H), 7.61 (td, J = 15.0, 7.3 Hz, 2 H), 7.53–7.46 (m, 2
H), 6.99 (d, J = 8.0 Hz, 1 H), 6.93 (t, J = 7.5 Hz, 1 H).
nyl)methanone (25)
From aurone 25a (142 mg, 0.51 mmol); eluent: 20% EtOAc/hexane;
yield: 93 mg (57%); yellow solid; mp 138–139 °C.
13C{1H} NMR (125 MHz, CDCl3):  = 190.3, 163.6, 143.3, 137.1, 133.61,
132.3, 131.8, 129.9, 129.3 (q, 2JC,F = 30 Hz), 127.5, 126.5 (q, 3JC,F = 5 Hz),
123.7 (q, 1JC,F = 272.5 Hz), 120.4, 119.3, 118.3.
IR (neat): 3272, 2969, 1628, 1452, 1328, 1205, 998, 922, 756 cm–1
.
1H NMR (500 MHz, CDCl3):  = 12.07 (s, 1 H), 8.14 (s, 1 H), 7.63 (d,
J = 8.2 Hz, 2 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 2 H), 7.04 (d,
J = 8.5 Hz, 1 H), 6.86 (t, J = 7.6 Hz, 1 H), 1.32 (s, 9 H) (COSY, HMQC,
HMBC data are provided in the Supporting Information).
HRMS (EI): m/z [M + H] calcd for C16H11F3N3O2: 334.0803; found:
334.0804.
13C{1H} NMR (125 MHz, CDCl3):  = 192.3, 163.7, 153.4, 137.2, 133.9,
128.4, 125.9, 119.7, 119.3, 118.4, 34.9, 31.3.
(2-Hydroxyphenyl)[5-(4-hydroxyphenyl)-2H-1,2,3-triazol-4-
yl]methanone (22)
HRMS (EI): m/z [M + H] calcd for C19H20N3O2: 322.1555; found:
322.1556.
From aurone 22a (100 mg, 0.42 mmol); eluent: 50% EtOAc/hexane;
yield: 59 mg (50%); yellow solid; mp 130–132 °C.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Kafle et al.
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Synthesis
[5-(4-Butylphenyl)-2H-1,2,3-triazol-4-yl](2-hydroxyphenyl)meth-
anone (26)
13C{1H} NMR (125 MHz, CDCl3):  = 206.8, 192.3, 163.7, 142.7, 140.9,
140.0, 137.4, 133.9, 129.1, 129.0, 127.9, 127.5, 127.2, 119.6, 119.3,
118.4.
From aurone 26a (147.5 mg, 0.53 mmol); eluent: 20% EtOAc/hexane;
yield: 85 mg (50%); brown oil.
HRMS (EI): m/z [M + H] calcd for C21H16N3O2: 342.1242; found:
IR (neat): 3105, 2928, 1628, 1469, 1253, 1151, 922, 756 cm–1
.
342.1238.
1H NMR (500 MHz, CDCl3):  = 12.08 (s, 1 H), 8.16 (s, 1 H), 7.62 (d, J =
8.0 Hz, 2 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.26 (d, J = 0.7 Hz, 2 H), 7.05 (d, J =
8.5 Hz, 1 H), 6.90 (t, J = 7.5 Hz, 1 H), 2.65 (t, J = 7.5 Hz, 2 H), 1.62 (dt, J =
13.0, 7.5 Hz, 2 H), 1.37 (dq, J = 14.5, 7.5 Hz, 2 H), 0.93 (t, J = 7.5 Hz,
3 H).
(2-Hydroxyphenyl)[5-(thiophen-3-yl)-2H-1,2,3-triazol-4-yl]meth-
anone (30)
From aurone 30a (89 mg, 0.39 mmol); eluent: 20% EtOAc/hexane;
yield: 77 mg (73%); yellow solid; mp 125–126 °C.
13C{1H} NMR (125 MHz, CDCl3):  = 192.4, 163.6, 145.2, 140.7, 137.2,
133.9, 128.9, 128.6, 119.7, 119.2, 118.3, 35.6, 33.4, 22.5, 14.0.
IR (neat): 2883, 2922, 1628, 1600, 1445, 1309, 1255, 1108, 931, 732
cm–1
.
1H NMR (500 MHz, CDCl3):  = 12.11 (s, 1 H), 8.17 (d, J = 8.0 Hz, 1 H),
8.07 (d, J = 2.0 Hz, 1 H), 7.52 (dd, J = 12.0, 6.0 Hz, 2 H), 7.38 (dd, J = 5.0,
3.0 Hz, 1 H), 7.05 (d, J = 8.0 Hz, 1 H), 6.89 (t, J = 7.5 Hz, 1 H).
HRMS (EI): m/z [M + H] calcd for C19H20N3O2: 322.1555; found:
322.1554.
(2-Hydroxyphenyl)[5-(4-isopropylphenyl)-2H-1,2,3-triazol-4-
13C{1H} NMR (125 MHz, CDCl3):  = 192.0, 163.7, 140.8, 137.3, 133.9,
yl]methanone (27)
127.6, 127.3, 126.6, 119.7, 119.3, 118.5.
From aurone 27a (129.5 mg, 0.49 mmol); eluent: 20% EtOAc/hexane;
HRMS (EI): m/z [M + H] calcd for C13H10N3O2S: 272.0493; found:
yield: 75 mg (50%); yellow solid; mp 125–126 °C.
272.0491.
IR (neat): 3250, 2961, 1618, 1488, 1452, 1244, 1210, 1162, 998, 924,
761 cm–1
.
(2-Hydroxyphenyl)[5-(thiophen-2-yl)-2H-1,2,3-triazol-4-yl]meth-
anone (31)
1H NMR (500 MHz, CDCl3):  = 12.06 (s, 1 H), 8.12 (d, J = 7.5 Hz, 1 H),
7.59 (d, J = 8.0 Hz, 2 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.25 (d, J = 2.0 Hz, 1 H),
7.24 (d, J = 1.0 Hz, 1 H), 7.03 (d, J = 8.5 Hz, 1 H), 6.84 (t, J = 7.5 Hz, 1 H),
3.12–2.81 (m, 1 H), 1.24 (d, J = 7.0 Hz, 6 H).
From aurone 31a (105 mg, 0.46 mmol); eluent: 30% EtOAc/hexane;
yield: 60 mg (48%); yellow solid; mp 131–132 °C.
IR (neat): 3080, 2928, 1626, 1596, 1467, 1443, 1255, 1161, 985, 912,
752 cm–1
.
13C{1H} NMR (125 MHz, CDCl3):  = 192.3, 163.7, 151.1, 140.8, 137.2,
1H NMR (500 MHz, CDCl3):  = 8.18 (d, J = 7.5 Hz, 1 H), 7.80 (dd, J = 4.0,
1.0 Hz, 1 H), 7.54 (ddd, J = 8.5, 7.5, 1.5 Hz, 1 H), 7.45 (dd, J = 5.0, 1.0 Hz,
1 H), 7.12 (dd, J = 5.0, 3.5 Hz, 1 H), 7.08–7.05 (dd, J = 8.5, 1.0 Hz, 1 H),
6.92 (t, J = 7.5 Hz, 1 H).
133.9, 128.7, 127.1, 119.7, 119.2, 118.4, 34.1, 23.8.
HRMS (EI): m/z [M + H] calcd for C18H18N3O2: 308.1399; found:
308.1401.
{5-[4-(Diphenylamino)phenyl]-2H-1,2,3-triazol-4-yl}(2-hydroxy-
13C{1H} NMR (125 MHz, CDCl3):  = 191.7, 163.8, 140.5, 137.3, 133.8,
phenyl)methanone (28)
129.5, 128.4, 127.9, 119.7, 119.3, 118.5.
From aurone 28a (210 mg, 0.54 mmol); eluent: 30% EtOAc/hexane;
HRMS (EI): m/z [M + H] calcd for C13H10N3O2S: 272.0493; found:
yield: 133 mg (57%); orange solid; mp 88–90 °C.
272.0490.
IR (neat): 3159, 2922, 1600, 1590, 1486, 1447, 1253, 1151, 920, 821,
754, 696 cm–1
.
4-[5-(3-Chloro-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
nitrile (32)
1H NMR (500 MHz, CDCl3):  = 12.07 (s, 1 H), 8.13 (s, 1 H), 7.55 (dd, J =
8.5, 2.0 Hz, 2 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.26 (t, J = 7.0 Hz, 4 H), 7.10
(d, J = 8.0 Hz, 4 H), 7.06 (t, J = 7.5 Hz, 2 H), 7.04–6.99 (m, 3 H), 6.81 (t,
J = 7.0 Hz, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 192.4, 163.7, 149.6, 147.0, 137.2,
133.9, 129.6, 125.5, 124.1, 121.7, 119.7, 119.2, 118.4.
From aurone 32a (113 mg, 0.40 mmol); eluent: 50% EtOAc/hexane;
yield: 108 mg (83%); yellow solid; mp 182–183 °C.
IR (neat): 3170, 2922, 2231, 1624, 1430, 1261, 1143, 951, 737 cm–1
1H NMR (300 MHz, acetone-d6):  = 8.33 (dd, J = 8.1, 1.5 Hz, 1 H), 8.05
(d, J = 8.7 Hz, 2 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.76 (dd, J = 7.9, 1.5 Hz, 1
H), 7.03 (t, J = 8.0 Hz, 1 H).
.
HRMS (EI): m/z [M + H] calcd for C27H21N4O2: 433.1664; found:
13C{1H} NMR (125 MHz, acetone-d6):  = 192.9, 170.9, 159.7, 148.1,
142.1, 141.6, 137.7, 135.4, 134.6, 133.7, 133.1, 133.0, 130.3, 130.2,
122.8, 121.6, 120.2, 118.9, 113.5, 113.3 (tautomers).
433.1665.
[5-([1,1′-Biphenyl]-4-yl)-2H-1,2,3-triazol-4-yl](2-hydroxyphe-
nyl)methanone (29)
HRMS (EI): m/z [M + H] calcd for C16H10ClN4O2: 325.0492; found:
From aurone 29a (137 mg, 0.46 mmol); eluent: 20% EtOAc/hexane;
325.0493.
yield: 94 mg (61%); yellow solid; mp 165–166 °C.
IR (neat): 3071, 2920, 1628, 1596, 1475, 1445, 1259, 1223, 1156, 924,
4-[5-(4-Chloro-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
nitrile (33)
735 cm–1
.
1H NMR (500 MHz, CDCl3):  = 12.06 (s, 1 H), 8.15 (d, J = 6.5 Hz, 1 H),
7.78 (d, J = 8.5 Hz, 2 H), 7.65 (d, J = 8.5 Hz, 2 H), 7.61–7.59 (m, 2 H),
7.54–7.50 (m, 1 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.38 (ddd, J = 7.5, 4.0, 1.5
Hz, 1 H), 7.05 (dd, J = 8.0, 1.0 Hz, 1 H), 6.90–6.87 (m, 1 H).
From aurone 33a (113 mg, 0.40 mmol); eluent: 50% EtOAc/hexane;
yield: 78 mg (60%); yellow solid; mp 200–201 °C.
IR (neat): 3203, 2922, 2237, 1596, 1469, 1292, 1128, 935, 782 cm–1
.
1H NMR (300 MHz, acetone-d6):  = 8.37 (d, J = 8.7 Hz, 1 H), 8.03 (d, J =
8.7 Hz, 2 H), 7.88 (d, J = 8.7 Hz, 2 H), 7.09 (d, J = 2.1 Hz, 1 H), 7.03 (dd,
J = 8.7, 2.1 Hz, 1 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Synthesis
13C{1H} NMR (75 MHz, acetone-d6):  = 192.25, 164.91, 143.09,
138.15, 136.38, 134.69, 133.12, 133.05, 130.40, 130.29, 130.23,
120.45, 119.96, 119.36, 119.02, 118.57, 113.56 (tautomers).
HRMS (EI): m/z [M + H], calcd for C16H10BrN4O2: 368.9987; found:
368.9984.
4-[5-(5-Fluoro-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
HRMS (EI): m/z [M + H] calcd for C16H10ClN4O2: 325.0492; found:
nitrile (38)
325.0495.
From aurone 38a (106 mg, 0.40 mmol); no chromatographic separa-
tion was needed; yield: 100 mg (81%); yellow solid; mp 220–223 °C.
4-[5-(5-Chloro-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
nitrile (34)
IR (neat): 3153, 2995, 2922, 2240, 1611, 1469, 1430, 1244, 1141, 991,
From aurone 34a (113 mg, 0.40 mmol); eluent: 50% EtOAc/hexane;
789 cm–1
.
yield: 106 mg (82%); yellow solid; mp 212–214 °C.
1H NMR (500 MHz, acetone-d6):  = 8.16 (dd, J = 10.0, 3.5 Hz, 1 H),
8.04 (d, J = 8.0 Hz, 2 H), 7.89 (d, J = 8.0 Hz, 2 H), 7.47–7.43 (m, 1 H),
7.06 (dd, J = 9.0, 4.5 Hz, 1 H).
IR (neat): 3155, 2995, 2922, 2237, 1737, 1628, 1467, 1257, 1158, 937,
827, 737 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 8.42 (d, J = 2.0 Hz, 1 H), 8.05 (d, J =
8.5 Hz, 2 H), 7.90 (d, J = 8.5 Hz, 2 H), 7.62 (dd, J = 9.0, 2.5 Hz, 1 H), 7.08
(d, J = 8.5 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 191.8, 160.6, 155.6 (d, 1JC,F
235 Hz), 148.3, 141.7, 135.5, 134.7, 133.1, 125.3 (d, JC,F = 25 Hz),
120.3 (d, 3JC,F = 7.5 Hz), 120.1 (d, 3JC,F = 7.5 Hz), 119.4 (d, 2JC,F = 25 Hz),
119.0, 113.6, 113.3.
=
2
13C{1H} NMR (125 MHz, acetone-d6):  = 190.9, 161.9, 141.4, 136.6,
133.9, 132.9, 132.3, 129.7, 129.6, 123.3, 120.6, 119.9, 118.2, 112.8.
HRMS (EI): m/z [M + H] calcd for C16H10FN4O2: 309.0788; found:
309.0791.
HRMS (EI): m/z [M + H] calcd for C16H10ClN4O2: 325.0492; found:
325.0490.
(2-Hydroxy-5-methylphenyl)[5-(3-methoxyphenyl)-2H-1,2,3-tri-
azol-4-yl]methanone (39)
4-[5-(2-Chloro-6-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
From aurone 39a (77 mg, 0.29 mmol); eluent: 50% EtOAc/hexane;
nitrile (35)
yield: 55 mg (59%); yellow solid; mp 119–121 °C.
From aurone 35a (113 mg, 0.40 mmol); eluent: 50% EtOAc/hexane;
yield: 75 mg (58%); yellow solid; mp 177–179 °C.
IR (neat): 3177, 2924, 2235, 1672, 1588, 1287, 1140, 905, 780 cm–1
1H NMR (300 MHz, acetone-d6):  = 8.23 (d, J = 8.0 Hz, 1 H), 7.92 (d, J =
6.9 Hz, 1 H), 7.29 (t, J = 8.1 Hz, 1 H), 6.96 (dd, J = 13.2, 8.2 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 187.2, 155.7, 145.5, 134.1,
132.2, 131.3, 130.8, 129.7, 129.6, 127.9, 120.3, 118.3 114.6, 112.2
(tautomers).
IR (neat): 3466, 3347, 2667, 1605, 1585, 1477, 1261, 1033, 955, 830,
795 cm–1
.
.
1H NMR (500 MHz, CDCl3):  = 11.85 (s, 1 H), 7.77 (s, 1 H), 7.32 (t, J =
8.0 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 1 H), 6.97–6.91 (m, 2 H), 3.80 (s, 3 H),
2.21 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 161.7, 159.8, 138.6, 133.3, 130.0,
128.5, 121.0, 119.3, 118.2, 115.8, 114.0, 55.5, 20.6.
HRMS (EI): m/z [M + H] calcd for C17H16N3O3: 310.1191; found:
310.1187.
HRMS (EI): m/z [M + H] calcd for C16H10ClN4O2: 325.0492; found:
325.0494.
(2-Hydroxy-3-methylphenyl)[5-(3-methoxyphenyl)-2H-1,2,3-tri-
azol-4-yl]methanone (40)
4-[5-(3-Bromo-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
nitrile (36)
From aurone 40a (133 mg, 0.50 mmol); eluent: 30% EtOAc/hexane;
yield: 96 mg (62%); yellow solid; mp 77–80 °C.
From aurone 36a (130 mg, 0.40 mmol); eluent: 50% EtOAc/hexane;
yield: 83 mg (56%); yellow solid; mp 217–218 °C.
IR (neat): 3470, 2890, 1605, 1425, 1259, 1041, 849, 756 cm–1
.
IR (neat): 3287, 2231, 1622, 1564, 1426, 1330, 1223, 1138, 996,
765 cm–1
.
1H NMR (500 MHz, CDCl3):  = 12.30 (s, 1 H), 7.82 (d, J = 6.0 Hz, 1 H),
7.38 (d, J = 7.5 Hz, 1 H), 7.31 (t, J = 8.0 Hz, 1 H), 7.28 (s, 1 H), 7.23 (d, J =
7.6 Hz, 1 H), 6.96 (dd, J = 8.3, 2.5 Hz, 1 H), 6.77 (t, J = 8.0 Hz, 1 H), 3.80
(s, 3 H), 2.30 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 192.8, 162.1, 159.8, 138.2, 131.4,
129.9, 127.4, 120.9, 118.9, 118.6, 115.8, 113.9, 55.5, 15.7.
1H NMR (500 MHz, acetone-d6):  = 8.38 (dd, J = 8.0, 1.4 Hz, 1 H), 8.04
(d, J = 8.0 Hz, 2 H), 7.93–7.86 (m, 3 H), 6.97 (t, J = 8.0 Hz, 1 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 206.3, 192.9, 160.5, 148.1,
142.0, 141.5, 140.9, 135.4, 134.5, 133.1, 133.1, 130.4, 130.3, 121.5,
120.8, 118.9, 113.5, 113.3, 111.9 (tautomers).
HRMS (EI): m/z [M + H] calcd for C17H16N3O3: 310.1191; found:
310.1189.
HRMS (EI): m/z [M + H] calcd for C16H10BrN4O2: 368.9987; found:
368.9989.
(2-Hydroxy-4,5-dimethylphenyl)[5-(3-methoxyphenyl)-2H-1,2,3-
triazol-4-yl]methanone (41)
4-[5-(5-Bromo-2-hydroxybenzoyl)-2H-1,2,3-triazol-4-yl]benzo-
nitrile (37)
From aurone 41a (118 mg, 0.38 mmol); eluent: 50% EtOAc/hexane;
yield: 87 mg (71%); waxy solid; mp 75–78 °C.
From aurone 37a (98 mg, 0.30 mmol), no chromatographic separation
was needed; yield: 82 mg (74%); yellow solid; mp 240–243 °C.
IR (neat): 3458, 2920, 1639, 1579, 1451, 1264, 1246, 1030, 901,
IR (neat): 3162, 2922, 2238, 1626, 1467, 1231, 1158, 991, 726 cm–1
.
700 cm–1
.
1H NMR (300 MHz, acetone-d6):  = 8.55 (s, 1 H), 8.05 (d, J = 8.2 Hz, 2
H), 7.89 (d, J = 7.9 Hz, 2 H), 7.72 (d, J = 8.9 Hz, 1 H), 7.01 (d, J = 8.9 Hz,
1 H).
1H NMR (500 MHz, CDCl3):  = 11.91 (s, 1 H), 7.68 (s, 1 H), 7.32–7.25
(m, 2 H, 7.22 (d, J = 7.4 Hz, 1 H), 6.94 (dd, J = 5.8, 4.7 Hz, 1 H), 6.83 (s, 1
H), 3.78 (s, 3 H), 2.25 (s, 3 H), 2.09 (s, 3 H).
13C{1H}NMR (75 MHz, acetone-d6):  = 191.6, 163.1, 140.2, 136.7,
133.0, 130.5, 121.9, 121.10, 119.03, 113.52, 110.94.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Kafle et al.
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Synthesis
13C{1H} NMR (125 MHz, CDCl3):  = 191.9, 162.1, 159.8, 148.5, 141.1,
133.6, 129.9, 127.8, 120.9, 118.9, 117.6, 115.8, 113.9, 55.5, 20.8, 18.9.
13C{1H} NMR (125 MHz, CDCl3):  = 191.7, 162.0, 148.2, 140.0, 133.7,
129.5, 128.5, 127.7, 126.5, 118.8, 117.6, 21.5, 20.7, 18.8 (tautomeric
peaks observed).
HRMS (EI): m/z [M + H] calcd for C18H18N3O3: 324.1348; found:
324.1350.
HRMS (EI): m/z [M + H] calcd for C18H18N3O2: 308.1399; found:
308.1401.
(2-Hydroxy-3-methylphenyl)[5-(3-nitrophenyl)-2H-1,2,3-triazol-
4-yl]methanone (42)
(3-Chloro-2-hydroxyphenyl)[5-(p-tolyl)-2H-1,2,3-triazol-4-
yl]methanone (46)
From aurone 42a (120 mg, 0.43 mmol); eluent: 30% EtOAc/hexane,
yield: 101 mg (72%); yellow solid; mp 170–171 °C.
From aurone 46a (97 mg, 0.36 mmol); eluent: 20% EtOAc/hexane;
yield: 63 mg (55%); yellow solid; mp 107–109 °C.
IR (neat): 2998, 1624, 1598, 1430, 1264, 1147, 1007, 955, 737 cm–1
.
IR (neat): 3200, 2922, 1605, 1540, 1426, 1356, 1268, 1074, 968,
737 cm–1
.
1H NMR (500 MHz, acetone-d6):  = 8.72–8.70 (m, 1 H), 8.35–8.30 (m,
1 H), 8.26 (d, J = 7.5 Hz, 1 H), 8.12 (t, J = 7.0 Hz, 1 H), 7.80 (t, J = 8.0 Hz,
1 H), 7.51 (d, J = 7.5 Hz, 1 H), 6.89 (t, J = 8.0 Hz, 1 H).
1H NMR (500 MHz, CDCl3):  = 12.63 (s, 1 H), 8.22 (s, 1 H), 7.63 (dd, J =
8.0, 1.5 Hz, 1 H), 7.57 (d, J = 8.0 Hz, 1 H), 7.26 (dd, J = 8.5, 0.5 Hz, 1 H),
6.88 (t, J = 8.0 Hz, 1 H), 2.41 (s, 2 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.7, 162.9, 149.2, 138.9,
135.1, 132.7, 132.3, 130.8, 130.7, 127.7, 124.6, 124.4, 124.1, 123.9,
119.7, 119.4, 15.5.
13C{1H} NMR (125 MHz, CDCl3):  = 191.7, 159.2, 140.7, 137.0, 132.49,
129.7, 128.6, 122.8, 120.5, 119.3, 21.6.
HRMS (EI): m/z [M + H] calcd for C16H13ClN3O2: 314.0696; found:
HRMS (EI): m/z [M + H] calcd for C16H13N4O4: 325.0937; found:
314.0700.
325.0941.
(2-Hydroxy-5-methylphenyl)[5-(3-nitrophenyl)-2H-1,2,3-triazol-
4-yl]methanone (43)
Funding Information
Financial support for the acquisition of the diffractometer by National
Science Foundation is acknowledged (MRI program, grant ID
From aurone 43a (130 mg, 0.46 mmol); eluent: 30% EtOAc/hexane;
yield: 90 mg (60%); yellow solid; mp 152–153 °C.
1626549).
N
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o
n
a
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c
i
e
n
c
e
F
o
u
n
d
ati
o
n
(1
6
2
6
5
4
9)
IR (neat): 3276, 2920, 1631, 1592, 1469, 1255, 1100, 955, 730 cm–1
.
1H NMR (500 MHz, CDCl3):  = 11.77 (s, 1 H), 8.69 (t, J = 2.0 Hz, 1 H),
8.30–8.27 (m, 1 H), 8.12–8.09 (m, 1 H), 7.85 (s, 1 H), 7.62 (t, J = 8.0 Hz,
1 H), 7.38 (dd, J = 8.5, 2.0 Hz, 1 H), 6.99 (d, J = 8.5 Hz, 1 H), 2.27 (s, 3 H).
13C{1H} NMR (125 MHz, acetone-d6):  = 193.1, 162.3, 149.1, 139.1,
135.6, 134.5, 134.4, 132.2, 130.7, 130.62, 128.95, 124.49, 124.06,
120.16, 118.57, 20.41 (tautomeric mixture).
Acknowledgment
The authors acknowledge support from Middle Tennessee State Uni-
versity and Dr. Jakub Wojciechowski for the crystal structure.
HRMS (EI): m/z [M + H], calcd for C16H13N4O4: 325.0937; found:
325.0936.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1708019.
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(2-Hydroxy-4,5-dimethylphenyl)[5-(3-nitrophenyl)-2H-1,2,3-tri-
azol-4-yl]methanone (44)
From aurone 44a (121 mg, 0.41 mmol); eluent: 40% EtOAc/hexane;
yield: 92 mg (68%); yellow solid; mp 155–157 °C.
References
IR (neat): 3330, 3185, 1639, 1534, 1352, 1268, 991, 735 cm–1
.
(1) Popava, A. V.; Bondarenko, S. P.; Frasinyuk, M. S. J. Heterocycl.
Chem. 1019, 55, 285.
1H NMR (500 MHz, CDCl3):  = 11.84 (s, 1 H), 8.68 (s, 1 H), 8.26 (d, J =
8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.75 (s, 1 H), 7.60 (t, J = 8.0 Hz, 1
H), 2.28 (s, 3 H), 2.15 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 191.2, 162.3, 149.0, 148.4, 134.7,
133.3, 130.9, 129.7, 128.0, 124.1, 123.8, 119.1, 117.4, 20.8, 19.0.
(2) Kumar, G. G.; Vinod, K. Res. J. Chem. Environ. 2014, 18, 73.
(3) Kafle, A.; Handy, S. T. Tetrahedron 2017, 73, 7024.
(4) Wilson, R. M.; Voskresenska, V. In Nitrenium Ions and Related
Species in Photoaffinity Labeling, Wiley Series on Reactive Inter-
mediate in Chemistry and Biology, Vol. 6; Falvey, D. E.;
Gudmundsdottir, A. D., Ed.; Wiley: Hoboken, 2013, 77–115.
(5) CCDC 1832154 and 1832153 contain the supplementary crys-
tallographic data for compound 5 and 10, respectively. The data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/getstructures.
(6) Albert, A.; Taylor, P. J. J. Chem. Soc., Perkin Trans. 2 1989, 1903.
(7) Li, J.; Zhang, Y.; Wang, D.; Wang, W.; Gao, T.; Wang, L.; Li, J.;
Huang, G.; Chen, B. Synlett 2010, 1617.
(8) Patonay, T.; Bognar, R.; Litkei, G. Tetrahedron 1984, 40, 2555.
(9) Wang, Z-P.; He, Y.; Saho, P-L. Org. Biomol. Chem. 2018, 16, 5422.
(10) Haouas, A.; Hamadi, N. B.; Nsira, A.; Msadek, M. J. Chem. Res.
2013, 435.
(11) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997, 62,
7512.
HRMS (EI): m/z [M + H] calcd for C17H15N4O4: 339.1093; found:
339.1089.
(2-Hydroxy-4,5-dimethylphenyl)[5-(p-tolyl)-2H-1,2,3-triazol-4-
yl]methanone (45)
From aurone 45a (80 mg, 0.30 mmol); eluent: 30% EtOAc/hexane;
yield: 59 mg (64%); yellow solid; mp 129–132 °C.
IR (neat): 3209, 2918, 1631, 1603, 1467, 1432, 1266, 1186, 897,
799 cm–1
.
1H NMR (500 MHz, CDCl3):  = 11.96 (s, 1 H), 7.78 (s, 1 H), 7.51 (d, J =
8.0 Hz, 2 H), 7.14 (d, J = 8.0 Hz, 2 H), 6.80 (s, 1 H), 2.33 (s, 3 H), 2.23 (s,
3 H), 2.05 (s, 3 H) (tautomeric peaks observed).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J