Tandem oxidative a-tosyloxylation of alcohols/nucleophilic addition of azide/copper-catalyzed 1,3-dipolar cycloaddition

Article abstract of DOI:10.1055/s-0029-1217034

An efficient method is described for the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles (β-keto-1,2,3-triazoles) in good to excellent yields by the successive treatment of secondary alcohols with [hydroxy(tosyloxy)iodo]benzene (Koser's reag

Full text of DOI:10.1055/s-0029-1217034

PAPER
4203
Tandem Oxidative a-Tosyloxylation of Alcohols/Nucleophilic Addition of
Azide/Copper-Catalyzed 1,3-Dipolar Cycloaddition
O
ne-Pot Regio
.
selective Sy
S
b
-K
u
e
to-1, 2,3-tria
r
zoles endra Reddy, B. Sreedhar*
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160921; E-mail: sreedharb@iict.res.in
Received 7 July 2009
driven 1,3-dipolar cycloaddition of organic azides with
alkynes pioneered by Huisgen.4 Recently, Sharpless5 and
Meldal6 groups independently reinvigorated the Huisgen
1,3-dipolar cycloaddition by using a substoichiometric
Abstract: An efficient method is described for the regioselective
synthesis of 1,4-disubstituted 1,2,3-triazoles (b-keto-1,2,3-tria-
zoles) in good to excellent yields by the successive treatment of sec-
ondary alcohols with [hydroxy(tosyloxy)iodo]benzene (Koser’s
reagent, HTIB), sodium azide followed by copper(I) iodide cata- amount of copper(I) metal source. The copper-accelerated
lyzed 1,3-dipolar cycloaddition with terminal alkynes.
1,3-dipolar cycloaddition reaction of alkynes and azides
does not only take place with high yields under mild con-
ditions, but also leads exclusively to the 1,4-regioisomeric
product. Although organic azides are stable against most
reaction conditions, compounds of low molecular weight
or those containing several azides (such as multivalent
scaffolds) tend to be explosive and are difficult to handle.7
Thus, a number of procedures with which to generate the
azide in situ followed by azide–alkyne cycloaddition have
been reported.8 Despite these advances, there is a need to
broaden the scope of one-pot multistep reactions in com-
bination with ‘click chemistry’. As part of our research
program directed towards the synthesis of triazoles under
various reaction conditions,9 recently we have reported
the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
directly from secondary alcohols.10 In the present work,
we report an efficient approach to the one-pot synthesis of
b-ketotriazoles by the successive treatment of secondary
alcohols with [hydroxy(tosyloxy)iodo]benzene (HTIB),
sodium azide followed by copper(I) iodide catalyzed 1,3-
dipolar cycloaddition with terminal alkynes (Scheme 1).
Key words: b-keto-1,2,3-triazoles, 1,3-dipolar cycloaddition, sec-
ondary alcohols, a-tosyloxylation, copper iodide, terminal alkynes
Functionalization of nitrogen heterocycles constitutes a
powerful tool for the synthesis of natural products and
bioactive substances. The rapid assembly of molecular di-
versity is an important goal of synthetic organic chemistry
and one of the key paradigms of modern drug discovery.
One approach to address this challenge involves the de-
velopment of multicomponent reactions (MCRs), in
which three or more reactants are combined together in a
single reaction flask in order to generate a product incor-
porating most of the atoms contained in the starting mate-
rials. In addition to the intrinsic atom economy and
selectivity underlying such reactions, simpler procedures
and equipment, time and energy savings, as well as envi-
ronmental friendliness have all led to a sizable effort to
design and implement MCRs in both academia and indus-
try.1
Our study began with the direct conversion of an alcohol
with HTIB into a tosyloxyketone11 intermediate which,
without isolation, was treated with sodium azide and phe-
nylacetylene, using copper(I) iodide as catalyst to furnish
the 1,3-dipolar cycloaddition product b-keto-1,2,3-tria-
zole in an one-pot operation (Scheme 1). Water plays an
important role in this reaction for (a) quenching of HTIB;
(b) formation of azide nucleophile; and (c) formation of
copper acetylide from copper iodide and acetylene with-
out any amine base.
Cycloaddition reactions involving heteroatoms, such as
1,3-dipolar addition, provide rapid access to an enormous
variety of interesting five- and six-membered heterocy-
cles which have found wide applications in medicinal
chemistry and material science.2 1,4-Disubstituted 1,2,3-
triazoles exhibit a remarkably broad scope of selectivity,
with a wide range of applications across a broad range of
therapeutic areas.3 The most widely used method for the
synthesis of 1,2,3-triazoles has involved the thermally
N
OH
O
N
1. HTIB (2 equiv)
R2
R1
+
N
MeCN, reflux, 30 min
NaN3
+
R2
R1
2. CuI (5 mol%), H2O
80 °C, 4 h
R1 = H, Me, Et
2 = aryl or alkyl
R
Scheme 1
SYNTHESIS 2009, No. 24, pp 4203–4207
x
x.
x
x
.
2
0
0
9
Advanced online publication: 12.10.2009
DOI: 10.1055/s-0029-1217034; Art ID: P09809SS
© Georg Thieme Verlag Stuttgart · New York

4204
P. S. Reddy, B. Sreedhar
PAPER
As exemplified in Table 1, the reaction proceeds smooth- in good yields, whereas the reaction of alcohols bearing
ly to completion and the products were obtained in good electron-donating substituents, such as p-methyl, afforded
yields. The reaction of alcohols bearing electron-rich and the corresponding product in poor yield; there was no re-
electron-poor substituents influence the yield of the prod- action with p-methoxybenzhydrol even after prolonged
uct formed. The reaction of benzhydrol with electron- reaction times (Table 1, entries 1–7).
withdrawing substituents gave the corresponding product
Table 1 Synthesis of Triazoles via the Three-Component Reaction of Various Secondary Alcohols, Alkynes and Sodium Azidea
Entry Alcohol 1
Alkyne 2
Product 3
Yield (%)b
N
N
N
OH
OH
OH
O
O
O
N
N
Ph
Ph
Ph
1
2
3
4
1a
1b
1c
1d
2a
3a
85
N
N
2a
2a
2a
3b
3c
3d
71
75
82
N
N
N
N
OH
OH
O
Ph
Ph
N
Br
Cl
Br
Cl
N
O
N
N
5
6
7
1e
1f
2a
2a
2a
3e
3f
75
17
0
N
N
OH
O
Ph
N
N
OH
O
N
N
Ph
1g
3g
MeO
MeO
N
N
O
8
9
1a
1a
2b
2c
3h
3i
91
79
N
Ph
Ph
N
N
O
O
N
N
N
N
10
11
1a
1a
2d
2e
3j
75
62
Ph
Ph
N
N
N
O
3k
OMe
OMe
Synthesis 2009, No. 24, 4203–4207 © Thieme Stuttgart · New York

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One-Pot Regioselective Synthesis of b-Keto-1,2,3-triazoles
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Table 1 Synthesis of Triazoles via the Three-Component Reaction of Various Secondary Alcohols, Alkynes and Sodium Azidea (continued)
Entry Alcohol 1
Alkyne 2
Product 3
Yield (%)b
70
N
N
N
O
O
O
N
N
3l
12
13
1a
1a
2f
Ph
Ph
Ph
N
N
2j
2k
2l
3m
3n
3o
64
82
75
OH
OH
N
N
N
14
15
1a
1a
N
N
O
N
N
S
Ph
S
a Reaction conditions as exemplified in typical experimental procedure.
b Isolated yield.
Typical Experimental Procedure
In order to extend the scope of the reaction, several termi-
nal alkynes were reacted with the azides of benzhydrol,
which were generated in situ. It was observed that the re-
action with a range of terminal alkynes, such as substitut-
ed phenyl acetylenes as well as aliphatic terminal alkynes,
were equally effective and the resulting triazoles were ob-
tained in good yields (90–60%). Among the terminal
alkynes used in this present study, 4-methyl-, 2,4,5-tri-
methyl- and 4-pentyl-substituted phenyl acetylenes were
found to be more reactive when compared to the 4-meth-
oxy-substituted phenyl acetylenes (entries 8–11). Propar-
gylic alcohol and octyne were also found to be equally
effective as substrates for this reaction (entries 12 and 13).
Among the heterocyclic terminal alkynes investigated, 2-
ethynyl pyridine was found to be more reactive compared
to 3-ethynyl thiophene (entries 14 and 15).
A solution of secondary alcohol (1a; 1 mmol) and HTIB (2 mmol)
in MeCN (3 mL) was stirred at 80 °C for 1–2 h. The turbid reaction
mixture became colorless at the end of reaction. NaN3 (1.5 mmol),
terminal alkyne (1.2 mmol), H2O (2 mL) and CuI (5 mol%) were
then added sequentially. After completion of the reaction (as moni-
tored by TLC), the reaction mixture was filtered through Celite and
the product was extracted with EtOAc (3 × 10 mL). After removing
the solvent under vacuum, the crude product was purified by col-
umn chromatography on silica gel (hexane–EtOAc).
1-Phenyl-2-(4-phenyl[1,2,3]triazol-1-yl)ethanone (3a)
White solid; mp 172–175 °C; Rf = 0.34 (EtOAc–hexane, 30%).
IR (KBr): 3087, 2929, 1700, 1586, 1443, 1223, 982, 761, 688 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.85 (s, 2 H), 7.29–7.42 (m, 3 H),
7.52–7.69 (m, 3 H), 7.84 (d, J = 7.6 Hz, 2 H), 7.91 (s, 1 H), 8.04 (d,
J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 55.4, 121.4, 125.8, 127.3, 128.2,
128.9, 129.2, 132.2,133.9, 194.7.
In conclusion, an efficient method for the synthesis of 1,4-
disubstituted 1,2,3-triazoles from a variety of secondary
alcohols, sodium azide and terminal alkynes has been de-
veloped via a simple one-pot, three-step procedure involv-
ing the oxidative a-tosyloxylation of alcohols, followed
by azidation of the formed a-tosyloxyketones and copper-
catalyzed 1,3-dipolar cycloaddition.
MS (ESI): m/z = 264 [M + H]+.
Anal. Calcd for C16H13N3O: C, 72.99; H, 4.98; N, 15.96. Found: C,
72.58; H, 4.84; N, 15.92.
1-Phenyl-2-(4-phenyl[1,2,3]triazol-1-yl)propan-1-one (3b)
White solid; mp 122–125 °C; Rf = 0.42 (EtOAc–hexane, 40%).
IR (KBr): 3137, 2924, 1694, 1588, 1463, 1218, 1090, 971, 963
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.83 (d, J = 7.3 Hz, 3 H), 6.47 (q,
J = 7.3 Hz, 1 H), 7.26–7.49 (m, 6 H), 7.80 (d, J = 7.8 Hz, 2 H), 7.88
(s, 1 H), 8.01 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 18.4, 59.3, 118.6, 125.9, 128.3,
128.8, 129.5, 129.5, 130.2, 132.1, 192.9.
All chemicals were purchased from Sigma–Aldrich or S.D. Fine
Chemicals, Pvt. Ltd. India and used as received. ACME silica gel
(100–200 mesh) was used for column chromatography and thin-lay-
er chromatography was performed on Merck precoated silica gel
60-F254 plates. All the other chemicals and solvents were obtained
from commercial sources and purified using standard methods.
Melting points were measured in open capillary tubes and are un-
corrected. The IR spectra of all compounds were recorded on a
Perkin–Elmer Spectrum GX FTIR spectrometer using KBr pellet
method. The IR values are reported in reciprocal centimeters (cm–1).
MS (ESI): m/z = 279 [M]2+.
Anal. Calcd for C17H15N3O: C, 73.63; H, 5.45; N, 15.15. Found: C,
73.84; H, 5.60; N, 14.97.
1
The H and 13C NMR spectra were recorded on a Varian Gemini
200 MHz or a Bruker Avance 300 MHz spectrometer. Chemical
shifts (d) are reported in ppm, using TMS (d = 0 ppm) as an internal
standard in CDCl3 or DMSO-d6. ESI mass spectra were recorded on
a Finnigan LCQ Advantagemax spectrometer. EI mass spectra were
recorded on a GC-MS QP2010 Plus (Shimadzu).
1-Phenyl-2-(4-phenyl[1,2,3]triazol-1-yl)butan-1-one (3c)
White solid; mp 114–116 °C; Rf = 0.5 (EtOAc–hexane, 40%).
IR (KBr): 3119, 2963, 1697, 1596, 1383, 1223, 1077, 765 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.99 (t, J = 7.6 Hz, 3 H), 2.07–
2.19 (m, 1 H), 2.23–2.35 (m, 1 H), 6.31 (dd, J = 6.0, 9.8 Hz, 1 H),
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P. S. Reddy, B. Sreedhar
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7.28–7.64 (m, 6 H), 7.82 (d, J = 7.0 Hz, 2 H), 7.99 (s, 1 H), 8.07 (d,
J = 8.3 Hz, 2 H).
1-Phenyl-2-[4-(2,4,5-trimethylphenyl)[1,2,3]triazol-1-yl]etha-
none (3i)
White solid; mp 165–167 °C; Rf = 0.32 (EtOAc–hexane, 30%).
IR (KBr): 2951, 1712, 1447, 1221, 1601, 994, 753 cm–1.
13C NMR (75 MHz, CDCl3): d = 10.4, 26.8, 65.1, 118.8, 125.7,
128.2, 128.8, 129.1, 130.6, 134.4, 194.2.
MS (ESI): m/z = 292 [M + H]+.
1H NMR (300 MHz, CDCl3): d = 2.27 (s, 3 H), 2.28 (s, 3 H), 2.43
(s, 3 H), 5.87 (s, 2 H), 7.00 (s, 1 H), 7.44–7.67 (m, 4 H), 7.76 (s,
1 H), 8.04 (d, J = 7.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 19.1, 19.4, 20.6, 55.3, 123.2, 127.2,
128.1, 129.1, 130.0, 132.2, 132.6, 134.1, 134.2, 134.5, 136.6, 190.3.
Anal. Calcd for C18H17N3O: C, 74.20; H, 5.88; N, 14.42. Found: C,
74.24; H, 5.69; N, 14.57.
1-(4-Bromophenyl)-2-(4-phenyl[1,2,3]triazol-1-yl)ethanone
(3d)
MS (EI): m/z = 305 [M+].
Pale-yellow solid; mp 115–118 °C; Rf = 0.37 (EtOAc–hexane,
Anal. Calcd for C19H19N3O: C, 74.73; H, 6.27; N, 13.76. Found: C,
74.15; H, 5.87; N, 13.82.
30%).
IR (KBr): 3083, 2925, 1696, 1484, 1231, 1078, 762, 691 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.81 (s, 2 H), 7.29–7.44 (m, 3 H),
7.52–7.63 (m, 2 H), 7.71 (s, 1 H), 7.83 (d, J = 7.3 Hz, 2 H), 7.99 (d,
J = 7.8 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 55.3, 121.3, 125.8, 128.3, 128.2,
128.8, 129.6, 129.7, 132.5, 134.7, 136.2, 189.5.
2-{4-(4-Pentylphenyl)[1,2,3]triazol-1-yl}-1-phenylethanone (3j)
White solid; mp 172–175 °C; Rf = 0.39 (EtOAc–hexane, 30%).
IR (KBr): 3086, 2925, 2854, 1704, 1451, 1346, 1221, 981, 756
cm–1.
1H NMR (300 MHz, CDCl3): d = 0.90 (t, J = 6.8 Hz, 3 H), 1.30–
1.39 (m, 4 H), 1.58–1.69 (m, 2 H), 2.62 (t, J = 7.5 Hz, 2 H), 5.83 (s,
2 H), 7.19 (d, J = 7.6 Hz, 2 H), 7.50–7.68 (m, 3 H), 7.73 (d, J = 8.3
Hz, 2 H), 7.86 (s, 1 H), 8.03 (d, J = 7.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 22.5, 31.0, 31.5, 35.7, 55.4,
121.0, 125.7, 127.9, 128.2, 128.8, 129.1, 134.0, 134.5, 143.1, 148.3,
190.3.
MS (ESI): m/z = 343 [M + H]+.
Anal. Calcd for C16H12BrN3O: C, 56.16; H, 3.53; N, 12.28. Found:
C, 56.05; H, 3.62; N, 12.35.
1-(4-Chlorophenyl)-2-(4-phenyl[1,2,3]triazol-1-yl)ethanone
(3e)
White solid; mp 106–109 °C; Rf = 0.35 (EtOAc–hexane, 30%).
IR (KBr): 3122, 2987, 1706, 1456, 1352, 1223, 1076, 765 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.83 (s, 2 H), 7.23–7.59 (m, 7 H),
7.75 (s, 1 H), 7.98 (d, J = 7.8 Hz, 2 H).
MS (ESI): m/z = 333 [M]+.
Anal. Calcd for C21H23N3O: C, 75.65; H, 6.95; N, 12.60. Found: C,
74.92; H, 7.11; N, 12.69.
2-{4-(4-Methoxyphenyl)[1,2,3]triazol-1-yl}-1-phenylethanone
(3k)
White solid; mp 106–109 °C; Rf = 0.33 (EtOAc–hexane, 30%).
13C NMR (75 MHz, CDCl3): d = 55.3, 125.9, 128.3, 129.1, 129.7,
130.6, 134.4, 135.5, 139.4, 190.1.
MS (ESI): m/z = 265 [M + H]+.
IR (KBr): 3093, 1703, 2840, 1498, 1450, 1247, 1220, 1026, 823
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.84 (s, 3 H), 5.85 (s, 2 H), 6.92
(d, J = 8.7 Hz, 2 H), 7.44–7.66 (m, 3 H), 7.74 (s, 1 H), 7.80 (d,
J = 8.0 Hz, 2 H), 8.04 (d, J = 7.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 33.3, 55.4, 114.2, 120.5, 127.1,
127.3, 127.9, 128.2, 129.2, 132.0, 134.6, 140.4, 161.6, 188.1.
Anal. Calcd for C16H12N3O: C, 64.54; H, 4.06; N, 14.11. Found: C,
64.42; H, 4.12; N, 41.14.
2-(4-Phenyl[1,2,3]triazol-1-yl)-1-p-tolylethanone (3f)
White solid; mp 158–160 °C; Rf = 0.27 (EtOAc–hexane, 30%).
IR (KBr): 2832, 1700, 1598, 1385, 1223, 1074, 814 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.40 (s, 3 H), 5.81 (s, 2 H), 7.12
(d, J = 8.0 Hz, 2 H), 7.41–7.69 (m, 5 H), 7.81 (s, 1 H), 7.92 (d,
J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.2, 55.3, 120.2, 125.6, 126.4,
127.9, 128.5, 129.1, 131.4, 134.7, 140.0, 146.9, 190.8.
MS (EI): m/z = 293 [M+].
Anal. Calcd for C17H15N3O2: C, 69.61; H, 5.15; N, 14.33. Found: C,
69.42; H, 5.09; N, 14.51.
2-(4-Hexyl[1,2,3]triazol-1-yl)-1-phenylethanone (3l)
White solid; mp 106–108 °C; Rf = 0.26 (EtOAc–hexane, 30%).
MS (EI): m/z = 277 [M] +.
Anal. Calcd for C17H15N3O: C, 73.63; H, 5.45; N, 15.15. Found: C,
73.51; H, 5.34; N, 15.22.
IR (KBr): 3396, 3062, 2926, 2852, 1594, 1706, 1447, 1220, 1057,
985, 756 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.89 (t, J = 6.6 Hz, 3 H), 1.27–
1.41 (m, 6 H), 1.63–1.77 (m, 2 H), 2.75 (t, J = 7.3 Hz, 2 H), 5.76 (s,
2 H), 7.40 (s, 1 H), 7.48–7.65 (m, 3 H), 8.01 (d, J = 8.03 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 22.5, 25.6, 28.9, 29.2, 31.6,
55.3, 125.1, 128.1, 134.0, 134.4, 190.6.
1-Phenyl-2-(4-p-tolyl[1,2,3]triazol-1-yl)ethanone (3h)
White solid; mp 158–160 °C; Rf = 0.28 (EtOAc–hexane, 30%).
IR (KBr): 2930, 1700, 1448, 1347, 1223, 976, 817 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.39 (s, 3 H), 5.83 (s, 2 H), 7.19
(d, J = 8.1 Hz, 2 H), 7.38–7.73 (m, 5 H), 7.86 (s, 1 H), 8.03 (d,
J = 8.0 Hz, 2 H).
MS (ESI): m/z = 272 [M + H]+.
Anal. Calcd for C16H21N3O: C, 70.82; H, 7.80; N, 15.49. Found: C,
69.98; H, 7.61; N, 15.69.
13C NMR (75 MHz, CDCl3): d = 21.2, 55.3, 125.7, 128.2, 128.8,
129.1, 129.4, 129.8, 134.5, 137.9, 139.1, 190.4.
MS (EI): m/z = 277 [M]+.
2-(4-Hydroxymethyl[1,2,3]triazol-1-yl)-1-phenylethanone (3m)
White solid; mp 115–118 °C; Rf = 0.29 (MeOH–CH2Cl2, 10%).
IR (KBr): 3306, 1690, 1443, 1225, 933, 755 cm–1.
Anal. Calcd for C17H15N3O: C, 73.63; H, 5.45; N, 15.15. Found: C,
73.45; H, 5.31; N, 14.95.
Synthesis 2009, No. 24, 4203–4207 © Thieme Stuttgart · New York

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One-Pot Regioselective Synthesis of b-Keto-1,2,3-triazoles
4207
1H NMR (200 MHz, DMSO-d6): d = 4.67 (d, J = 5.9 Hz, 2 H), 4.85
(t, J = 5.9 Hz, 1 H), 5.96 (s, 2 H), 7.50–7.66 (m, 3 H), 7.77 (s, 1 H),
8.04 (d, J = 8.1 Hz, 2 H).
13C NMR (50 MHz, CDCl3): d = 55.3, 56.7, 123.5, 128.1, 128.2,
129.2, 134.6, 148.0, 190.0.
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MS (ESI): m/z = 218 [M + H]+.
Anal. Calcd for C11H11N3O2: C, 60.82; H, 5.10; N, 19.34. Found: C,
60.30; H, 4.96; N, 19.42.
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(4) For reviews, see: (a) L’Abbe, G. Chem. Rev. 1969, 69, 345.
(b) Lwowski, W. In 1,3-Dipolar Cycloaddition Chemistry;
Padwa, A., Ed.; Wiley: New York, 1984, 559. (c) Sha, C.-
K.; Mohanakrishnan, A. K. In Synthetic Applications of 1,3-
Dipolar Cycloaddition Chemistry Toward Heterocycles and
Natural Products; Padwa, A.; Pearson, W. H., Eds.; Wiley:
New York, 2002, 623.
1-Phenyl-2-(4-pyridin-2-yl[1,2,3]triazol-1-yl)ethanone (3n)
Yellowish green solid; mp 173–175 °C; Rf = 0.35 (EtOAc–hexane,
50%).
IR (KBr): 3065, 2936, 1705, 1593, 1561, 1443, 1350, 1225, 1049,
993, 755 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.88 (s, 2 H), 7.17–7.23 (m, 1 H),
7.51–7.81 (m, 4 H), 8.05 (d, J = 7.5 Hz, 2 H), 8.20 (d, J = 8.0 Hz,
1 H), 8.27 (s, 1 H), 8.54 (d, J = 6.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 55.5, 120.3, 122.8, 123.9, 128.2,
129.1, 134.6, 136.8, 149.4, 189.8.
MS (ESI): m/z = 265 [M + H]+.
Anal. Calcd for C15H12N4O: C, 68.17; H, 4.58; N, 21.20. Found: C,
68.02; H, 4.32; N, 21.44.
1-Phenyl-2-(4-thiophen-3-yl[1,2,3]triazol-1-yl)ethanone (3o)
White solid; mp 167–170 °C; Rf = 0.31 (EtOAc–hexane, 40%).
IR (KBr): 2988, 1703, 1595, 1448, 1321, 1222, 943 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.84 (s, 2 H), 7.21 (d, J = 6.2 Hz,
1 H), 7.32–7.43 (m, 5 H), 7.81 (s, 1 H), 8.03 (d, J = 7.6 Hz, 2 H).
(5) Rostovtsev, H. V.; Green, L. G.; Fokin, V. V.; Sharpless, K.
B. Angew. Chem. Int. Ed. 2002, 41, 2596.
(6) Torne, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057.
13C NMR (75 MHz, CDCl3): d = 54.0, 121.2, 122.9, 125.4, 125.9,
126.9, 128.1, 128.8, 129.2, 134.5, 147.4, 189.9.
(7) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew.
Chem. Int. Ed. 2005, 44, 5188.
(8) (a) Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V.
Org. Lett. 2004, 6, 2853. (b) Feldman, A. K.; Colasson, B.;
Fokin, V. V. Org. Lett. 2004, 6, 3897. (c) Prasad, A.; Wim,
D.; Fokin, V. V.; Eycken, E. V. Org. Lett. 2004, 6, 4223.
(d) Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9, 1.
(e) Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett.
2007, 9, 1809. (f) Tao, C.-Z.; Cui, X.; Li, J.; Liu, A.-X.; Liu,
L.; Guo, Q.-X. Tetrahedron Lett. 2007, 48, 3525.
(9) (a) Sreedhar, B.; Reddy, P. S.; Kumar, N. S. Tetrahedron
Lett. 2006, 47, 3055. (b) Sreedhar, B.; Reddy, P. S. Synth.
Commun. 2007, 37, 805.
MS (EI): m/z = 269 [M]+.
Anal. Calcd for C14H11N3OS: C, 62.43; H, 4.12; N, 15.60; S, 11.91.
Found: C, 62.62; H, 3.98; N, 15.74; S, 11.87.
Acknowledgment
P.S.R. thanks the Council of Scientific and Industrial Research
(CSIR), India, for a Senior Research Fellowship.
(10) Sreedhar, B.; Reddy, P. S.; Krishna, V. R. Tetrahedron Lett.
2007, 48, 5831.
(11) (a) Ueno, M.; Nabana, T.; Togo, H. J. Org. Chem. 2003, 68,
6424. (b) Nicolaou, K. C.; Montagnon, T.; Ulven, T.; Baran,
P. S.; Zhong, Y.-L.; Sarabia, F. J. Am. Chem. Soc. 2002, 124,
5718.
References
(1) For recent reviews, see: (a) Ramon, D. J.; Miguel, Y.
Angew. Chem. Int. Ed. 2005, 44, 1602. (b) Orru, R. V. A.;
de Greef, M. Synthesis 2003, 1471. (c) Ugi, I.; Heck, S.
Comb. Chem. High Throughput Screening 2001, 4, 1.
(d) Weber, L.; Illgen, K.; Almstetter, M. Synlett 1999, 366.
Synthesis 2009, No. 24, 4203–4207 © Thieme Stuttgart · New York