HETEROCYCLES

Communication | Special issue | Vol. 80, No. 1, 2010, pp. 177-181
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*

Departmene of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, youdai-katsura, Nishikyo, Kyoto 615-8510, Japan

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).

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

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

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).

References

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15. Representative procedure: To an oven-dried, Ar-purged flask was added 1a (151 mg, 0.5 mmol), DMAP (6.5 mg, 0.05 mmol), and MeCN (5 mL). The reaction mixture was stirred at room temperature for 12 h, and then concentrated under reduced pressure. The residue was diluted with EtOAc (30 mL). The organic solution was washed with 1 M HCl (10 mL) and brine (10 mL), dried over Na2SO4, and evaporated. The residue was again dissolved in AcOH (5 mL) and H2O (0.5 mL). The reaction mixture was stirred at 60 °C for 3 h, and then concentrated under reduced pressure. The crude product was purified by flash column chromatography (hexane/EtOAc = 5/1) to yield 2a as a white solid (124 mg, 0.41 mmol, 82%). 2a: IR (KBr): 1391, 1196, 1163, 1086 cm-1; 1H NMR: δ = 2.41 (s, 3H), 7.34 (d, J = 8.7 Hz, 2H), 7.39–7.48 (m, 3H), 7.79–7.86 (m, 2H), 8.00 (d, J = 8.7 Hz, 2H), 8.08 (s, 1H); 13C NMR: δ = 21.7, 126.6, 128.2, 128.6, 128.9, 129.9, 130.1, 132.9, 135.6, 146.6, 151.4; HRMS (FAB+): Calcd for C15H14N3O2S, M+H+ 300.0807. Found m/z 300.0801.
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