Preparation of 2-sulfonyl-1,2,3-triazoles by base-promoted 1,2-rearrangement of a sulfonyl group

Article abstract of DOI:10.3987/COM-09-S(S)44

1,2-Rearrangement of a sulfonyl group occurs on treatment of 1-sulfonyl-1,2,3-triazoles with a catalytic amount of 4-dimethylaminopyridine (DMAP) in acetonitrile to give an equilibrium mixture of 1-sulfonyl- and 2-sulfonyl derivatives, with considerable predominance of the latter. Subsequent acidic treatment of the mixture caused selective hydrolysis of the 1-sulfonyl derivative, which led to the isolation of the 2-sulfonyl-1,2,3-triazole in good total yield in a pure form.

Full text of DOI:10.3987/COM-09-S(S)44

HETEROCYCLES, Vol. 80, No. 1, 2010
177
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 177 - 181. © The Japan Institute of Heterocyclic Chemistry
Received, 28th June, 2009, Accepted, 10th August, 2009, Published online, 11th August, 2009
DOI: 10.3987/COM-09-S(S)44
PREPARATION OF 2-SULFONYL-1,2,3-TRIAZOLES BY
BASE-PROMOTED 1,2-REARRANGEMENT OF A SULFONYL GROUP
Motoshi Yamauchi, Tomoya Miura, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University,
Katsura, Kyoto 615-8510, Japan. E-mail: murakami@sbchem.kyoto-u.ac.jp
Dedicated to Professor Akira Suzuki on the occasion of his 80th birthday
Abstract – 1,2-Rearrangement of a sulfonyl group occurs on treatment of
1-sulfonyl-1,2,3-triazoles with a catalytic amount of 4-dimethylaminopyridine
(DMAP) in acetonitrile to give an equilibrium mixture of 1-sulfonyl- and
2-sulfonyl derivatives, with considerable predominance of the latter. Subsequent
acidic treatment of the mixture caused selective hydrolysis of the 1-sulfonyl
derivative, which led to the isolation of the 2-sulfonyl-1,2,3-triazole in good total
yield in a pure form.
1,2,3-Triazoles are five-membered ring heterocycles containing three nitrogen atoms of mixed hybridized
forms in array, and substituted 1,2,3-triazoles constitute an important class of heterocyclic compounds of
a variety of utilities, the area of which covers from pharmaceutical chemistry to materials science.1 The
synthesis of C,N-disubstituted 1,2,3-triazoles often suffers from a regiochemical issue. Thus, it has been
the subject of particular interest in current heterocyclic chemistry to prepare them in a desired
regiochemical form.2 The 1,3-dipolar cycloaddition reaction of alkyl (or aryl) azide with terminal alkynes
is one of the most reliable procedures for the synthesis of C,N-disubstituted 1,2,3-triazoles. Either 1,4- or
1,5-disubstituted 1,2,3-triazoles could be regioselectively prepared by the use of copper3 or ruthenium4
catalysts, respectively (Figure 1).
N
2N
N
1
N
1
N
N
N
N
N
5
4
4
2,4-disubstituted
1,4-disubstituted
1,5-disubstituted
Figure 1. Spacial display of substituent in C,N-disubstituted 1,2,3-triazoles.

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HETEROCYCLES, Vol. 80, No. 1, 2010
However, methods for the synthesis of 2,4-disubstituted 1,2,3-triazoles remain relatively undeveloped.5,6
A substitution reaction of 4-substituted 1,2,3-triazoles with electrophiles often produces a mixture of
regioisomers, i.e., 1,4-disubstituted and 2,4-disubstituted 1,2,3-triazoles.7 Higher electron density is
allocated on the N1 nitrogen atom, which reacts better with an electrophile giving 1,4-disubstituted
1,2,3-triazoles under conditions of kinetic control.8 On the other hand, 2,4-disubstituted 1,2,3-triazoles
experience less steric hindrance than 1,4-disubstituted 1,2,3-triazoles, and therefore, the
thermodynamically more stable 2,4-disubstituted 1,2,3-triazoles predominate under conditions of
equilibrium control.9 The thermodynamic preference for 2,4-disubstituted 1,2,3-triazoles was exploited by
Fokin and co-workers in the regioselective synthesis of 4-substituted 2-hydroxymethyl-1,2,3-triazoles by
a copper-catalyzed cycloaddition reaction of a terminal alkyne with sodium azide in the presence of
formaldehyde.10 During the course of our study on the nickel-catalyzed denitrogenative reaction of
4-substituted 1-sulfonyl-1,2,3-triazoles,11 we found that the sulfonyl group underwent rearrangement
from the N1 position to the N2 position to give 4-substituted 2-sulfonyl-1,2,3-triazoles,12 which is the
subject of the present communication.
4-Phenyl-1-tosyl-1,2,3-triazole (1a) could be readily prepared according to the literature procedure of the
copper-catalyzed azide/alkyne cycloaddition.13 The 1,2,3-triazole 1a thus obtained was treated with a
catalytic amount of 4-dimethylaminopyridine (DMAP, 10 mol%) in MeCN at room temperature for 12 h.
An extractive work-up afforded a regioisomeric mixture of 4-phenyl-2-tosyl-1,2,3-triazole (2a) and 1a
(2a:1a = 88:12), suggesting that the sulfonyl group migrated from the N1 position to the N2 position
(Table 1, entry 1).14
Table 1. Synthesis of 2-sulfonyl-1,2,3-triazoles.a
R1
O S O
N
R1
O
O
S
R1 10 mol% DMAP
N
O
S
N
N
N
N
N
N
N
O
MeCN, rt, 12–48 h
AcOH/H2O, 60 °C, 3–12 h
R2
R2
R2
1
2
N2+N1
Yieldc
Yieldc
85:15 2f 75%
R1
R2
R1
1f 4-MeC6H4 4-CF3C6H4
R2
N2:N1b
N2:N1b
2
Entry
Entry
1
2
1
1
2
3
4
5
1a
1b
1c
4-MeC6H4
4-FC6H4
Ph
Ph
88:12
2a
82%
6
7
1g 4-MeC6H4 4-MeOC6H4
1h 4-MeC6H4 2-Naphthyl
92:8
92:8
2g 86%
2h 78%
91:9
2b
2c
86%
4-MeOC6H4 Ph
87:13
73%d
8
1i 4-MeC6H4 1-Cyclohexenyl 89:11 2i 76%d
1j 4-MeC6H4 n-Hex
90:10 2j 78%e
9
1d 2-Naphthyl Ph
1e n-Bu Ph
88:12
86:14
2d
2e
80%
72%
10
a Reaction conducted on a 0.5 mmol scale. b Determined by 1H NMR analysis. c Isolated yield. d 20 mol%
e
of DMAP was used. The reaction was carried out with 50 mol% of DMAP at 60 °C, and then the
isomeric mixture was heated at 70 °C.

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179
Unfortunately, the regioisomeric mixture failed to be separated with flash column chromatography on
silica gel. However, when the isomeric mixture was heated at 60 °C in AcOH/H2O (10/1), the N1 sulfonyl
group of 1a was selectively hydrolyzed in preference to the N2 sulfonyl group of 2a. Subsequent
chromatographic isolation readily afforded analytically pure 2a in 82% overall yield.15 The structure of 2a
was unambiguously confirmed by X-ray crystallographic analysis.
In order to gain a mechanistic insight, the isolated 2a was subjected to the identical reaction conditions
for the rearrangement [DMAP (10 mol%), acetonitrile, room temperature, 12 h] (eq 1). A regioisomeric
mixture of 2a and 1a was again formed with the former predominating by 90:10. This result indicated that
the sulfonyl group rearrangement was reversible under the reaction conditions and that 2a was the
thermodynamically more stable isomer. We presume that an N-sulfonyl(p-dimethylaminopyridinium) ion
intermediate is involved in the rearrangement process as the intermediate. A computational study at the
B3LYP/6-31G* level also suggested that 2a was more stable than 1a by 0.39 kcal/mol.16
Tol
O S O
N
Tol
O S O
N
O
Tol
N
10 mol% DMAP
MeCN, rt, 12 h
S
O
N
N
(1)
+
N
N
N
N
Ph
90:10
Ph
Ph
1a
2a
2a
We examined the rearrangement reaction of 4-phenyl-1,2,3-triazoles 1b–1e having various sulfonyl
groups (R1) at the N1 position. Substituted benzenesulfonyl groups as well as a naphthalenesulfonyl
group rearranged from the N1 position to the N2 position (Table 1, entries 2–4). Even a butanesulfonyl
group successfully participated in the reaction (Table 1, entry 5). Variation of the substituent (R2) at the
C4 position was also examined. Aryl-and alkenyl-substituted substrates 1f–1i worked well to afford the
corresponding products 2f–2i in yields ranging from 75% to 86% (Table 1, entries 6–9). The reaction of
alkyl-substituted triazole 1j required more forcing conditions to afford the product 2j in 78% yield (Table
1, entry 10).
In summary, we have found a new base-promoted pathway starting from readily accessible 4-substituted
1-sulfonyl-1,2,3-triazoles leading to 4-substituted 2-sulfonyl-1,2,3-triazoles.
ACKNOWLEDGEMENTS
This work was supported in part by MEXT (Grant-in-Aid for Challenging Exploratory Research No.
21655033), the Mitsubishi Chemical Corporation Fund, the Sumitomo Foundation. T.M. acknowledges a
financial support by Astellas Award in Synthetic Organic Chemistry, Japan. M.Y. acknowledges a
financial support by the Global COE Program "Integrated Materials Science" (No. B-09).

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HETEROCYCLES, Vol. 80, No. 1, 2010
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1
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