One-pot aerobic oxidative sulfonamidation of aromatic thiols with ammonia by a dual-functional β-MnO2 nanocatalyst

Eri Hayashi , Yui Yamaguchi , Yusuke Kita , Keigo Kamata * and Michikazu Hara *
Laboratory for Materials and Structures, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan. E-mail:;

Received 4th December 2019 , Accepted 22nd January 2020

First published on 22nd January 2020

High-surface-area β-MnO2 (β-MnO2-HS) nanoparticles could act as effective heterogeneous catalysts for the one-pot oxidative sulfonamidation of various aromatic and heteroaromatic thiols to the corresponding sulfonamides using molecular oxygen (O2) and ammonia (NH3) as respective oxygen and nitrogen sources, without the need for any additives.

Sulfonamide derivatives are an important class of organic compounds because they are widely used as medicines, plasticizers for fiber-reinforced composite materials, and intermediates for dyes.1 Various sulfur and/or nitrogen sources have been employed for the synthesis of sulfonamides, and the nucleophilic substitution of sulfonyl chloride with amines,2 three-component aminosulfonylation of aromatic compounds, the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) adduct, and amines,3 the oxidative coupling of organosulfur compounds with amines,4 and Chan-Lam coupling5 have been developed (Scheme 1 and Tables S1 and S2, ESI). Among them, the catalytic oxidative sulfonamidation of thiols has attracted much attention because of the ease of availability and the cost-effectiveness of the starting materials;6 however, most of these systems are homogeneous and have difficulties in terms of catalyst/product separation and the reuse of the catalysts. In addition, significant amounts of additives and/or specific oxidants are typically required to generate sulfonyl chloride intermediates.6b,c There is only one report on heterogeneously catalyzed and reusable oxidative sulfonamidation from thiols by Amberlite® IRA-400 (OH), although the use of POCl3 and H2O2 is required.6a
image file: c9cc09411c-s1.tif
Scheme 1 Various synthetic methods for the production of sulfonamides.

Oxidation of organic substrates into useful oxygenated products with molecular oxygen (O2) as the sole oxidant is an important reaction due to the high contents of active oxygen species and the lack of byproduct formation.7,8 In particular, the dual nature of redox and acid sites on solids sometimes enhances the catalytic performance through their cooperative action.9 During the course of our investigation on crystalline metal oxides as aerobic oxidation catalysts,10–13 the high catalytic activity of high-surface-area β-MnO2 (β-MnO2-HS) has been revealed by experimental and computational studies on the polymorph dependence of a MnO2 catalyst on the aerobic oxidation of biomass-derived 5-hydroxymethyl furfural (HMF).13 However, the catalytic application of β-MnO2-HS to other liquid-phase oxidation reactions, including the oxidative sulfonamidation of thiols, has not been investigated to date. Here, we report that β-MnO2-HS can act as a reusable dual-functional solid catalyst for the one-pot synthesis of sulfonamides from aromatic and heteroaromatic thiols, O2, and ammonia (NH3), without the production of environmentally and economically unacceptable byproducts. This study provides the first example of a heterogeneous catalyst for the oxidative sulfonamidation of thiols using only O2 without the need for any additives.

First, the one-pot oxidative sulfonamidation of benzenethiol (1a) with 28% aqueous NH3 (5 equivalents with respect to 1a) in various solvents catalyzed by β-MnO2-HS at 90 °C for 8 h was examined using O2 (1 MPa) as the sole oxidant (Table 1). The main products were benzenesulfonamide (2a), diphenyl disulfide (3a), and S-phenyl benzenethiosulfonate (4a). Among the solvents tested, N,N-dimethylformamide (DMF) was the most effective and the yields of 2a, 3a, and 4a were 73%, 9%, and 1%, respectively. The sulfonamidation also proceeded in other polar solvents, such as N,N-dimethylacetamide, ethanol, and acetonitrile, to give 2a in moderate yields. The reaction proceeds more efficiently in mixed solvents of DMF/water (Table S3, ESI) and the yield of 2a could be increased to 90% by using DMF/water (3/2, v/v), although the reaction in only water, in which 1a is not soluble, gave no formation of 2a. The yield of 2a using NH3 methanol solution was much lower than that using NH3 aqueous solution. Therefore, the presence of DMF and water might increase the solubility of both 1a and NH3, likely improving the catalytic performance. Furthermore, the yield of 2a reached 99% when the reaction time was 12 h. Aromatic and aliphatic solvents such as o-dichlorobenzene, toluene, and n-octane were not effective for the present sulfonamidation.

Table 1 Effect of solvents on the oxidative sulfonamidation of 1a to 2aa

image file: c9cc09411c-u1.tif

Entry Solvent Yield (%)
2a 3a 4a
a Reaction conditions: β-MnO2-HS (0.1 g), 1a (1 mmol), solvent (1 mL), 28% aqueous NH3 (5 mmol), pO2 (1 MPa), 90 °C, 8 h. Conversion and yield were determined by GC analysis. In all reactions, conversions of 1a were ≥99%. Yield (%) = product (mol)/initial 1a (mol) × 100. b 7 M NH3 in methanol (5 mmol) was used instead of 28% aqueous NH3. c Reaction time was 12 h.
1 DMF 73 9 1
2b DMF 36 44 1
3 N,N-Dimethylacetamide 47 25 2
4 Ethanol 55 28 2
5 Acetonitrile 18 73 1
6 o-Dichlorobenzene Trace 97
7 Toluene 1 95
8 n-Octane 2 92
9 Water 1 97
10 DMF/water (3/2, v/v) 90 1 Trace
11c DMF/water (3/2, v/v) 99

The effect of metal oxide catalysts on the oxidative sulfonamidation of 1a in DMF/water (3/2, v/v) was investigated next (Table S4, ESI). In the absence of a catalyst, only 3a was obtained in 72% yield without the formation of 2a and 4a. β-MnO2-HS was the most effective catalyst among those tested, and the yield of 2a (90%) was much higher than that using β-MnO2 (33%) synthesized by a typical hydrothermal method. The reaction of 1a with β-MnO2-HS under Ar (1 MPa) gave only 3a in 99% yield, which indicates that the presence of O2 is essential for the formation of 2a.14 Other manganese oxides including α-, γ-, δ-, ε-, and λ-MnO2 exhibited lower yields of 2a than β-MnO2-HS, which is in good agreement with the results for the polymorph dependence of MnO2 on the aerobic oxidation of HMF.13 Other Fe-, Co-, Ni-, and Cu-containing metal oxides, the catalyst precursor of MnSO4, and perovskite oxides such as BaFeO3−δ11a and BaRuO312 gave 3a (44–97%) as the main product.

After the one-pot sulfonamidation reaction of 1a with β-MnO2-HS was completed, the used β-MnO2-HS catalyst could be recovered from the reaction mixture by simple filtration. Negligible leaching of Mn species into the filtrate was confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis (0.02% with respect to fresh β-MnO2-HS). The recovered catalyst could be reused three times without significant changes in the activity and selectivity (Fig. 1(a)). In addition, there was no significant difference in the X-ray powder diffraction (XRD) patterns of the fresh and recovered β-MnO2-HS catalysts (Fig. S1, ESI). These results ruled out that leached manganese species contributed to the catalysis, and confirmed that the nature of the observed catalysis was heterogeneous.

image file: c9cc09411c-f1.tif
Fig. 1 (a) Catalyst recycling and (b) time course for the oxidative sulfonamidation of 1a to 2a with β-MnO2-HS. The reaction conditions of (a) and (b) were the same as those of Table 2 and entry 11 in Table 1, respectively.

The present β-MnO2-HS-catayzed system could be applied to the one-pot oxidative sulfonamidation of various aromatic and heteroaromatic thiols using O2 and NH3 (Table 2). Benzenethiols with both electron-donating and weakly electron-withdrawing p-substituents were converted to the corresponding sulfonamides (2b2c and 2e2g). On the other hand, p-nitrobenzenethiol (1i) with a strong electron-withdrawing group required larger catalyst loading to obtain a high yield of 2i (58%); therefore, the reaction rates are affected by the electronic features of the substituents on the aromatic rings. o-Toluenethiol was also efficiently converted to the sulfonamide 2d in 83% yield, although a longer reaction time (40 h) was required than that with p-toluenethiol (1c), which is likely due to steric effects. In the case of p-cyanobenzenethiol, the selectivity to the corresponding sulfonamide decreased due to the hydration reaction of the nitrile group. 2-Naphthalenethiol also gave the corresponding sulfonamide 2j. Not only aromatic, but also heteroaromatic thiols (2-thiophenethiol and 2-pyridinethiol), could be converted to the corresponding sulfonamides without influence on the heteroaromatic rings. For the reactions of alkyl thiols (cyclohexanethiol and 1-octanethiol) with NH3 or 1a with other amines (aniline, n-butylamine, and morphorine), the corresponding sulfonamides could not be obtained whereas the disulfides and/or oxygenates of amines were formed. The present system was applicable to a larger-scale one-pot oxidative sulfonamidation of 1c (20 mmol scale) and 3.05 g of the analytically pure 2c, which has been utilized as an industrially important plasticizer for fiber-reinforced composite materials,1 could be isolated (eqn (1)).

image file: c9cc09411c-u2.tif(1)

Table 2 Oxidative sulfonamidation of 1 to 2 with β-MnO2-HSa
a Reaction conditions: β-MnO2-HS (0.1 g), thiols (1 mmol), DMF/water (0.6/0.4 mL), 28% aqueous NH3 (5 mmol), pO2 (1 MPa), 90 °C, 20 h. In all reactions, conversions of 1 were ≥99%. Values in parentheses are isolated yields. Yield (%) = product (mol)/initial substrate (mol) × 100. b Reaction time was 40 h. c DMF (1 mL). NH3 gas was used instead of aqueous NH3. d β-MnO2-HS (0.15 g).
image file: c9cc09411c-u3.tif

In most systems employed for the oxidative sulfonamidation of thiols, it has been proposed that the formation of sulfonyl halide intermediates is necessary to facilitate the nucleophilic attack of the N atom to the S atom; therefore, significant amounts of activated oxidants and chloride additives are typically required.6a–c On the other hand, the present system based on β-MnO2-HS was effective for the one-pot aerobic sulfonamidation without the need for any additives. Firstly, the time course for the oxidative sulfonamidation of 1a with O2 catalyzed by β-MnO2-HS was investigated to elucidate a possible reaction mechanism (Fig. 1(b)). The conversion of 1a into 3a was completed within 0.5 h, and the desired product 2a, was gradually formed with a decrease in the yield of 3a. In addition, a small amount of 4a (≤1% yield) was detected by gas chromatography (GC) analysis during the reaction.[thin space (1/6-em)]15 To verify 3a and 4a as possible intermediates, the reactions of 3a and 4a as starting materials were performed under standard conditions. In each case, the corresponding sulfonamide was obtained in 74–88% yields, and the formation rate of 2a from 4a was faster than that from 3a (Schemes S1(a) and (b), ESI). Therefore, it is possible that the oxidation of 3a into oxygenated intermediates such as 4a proceeds, followed by the rapid reaction of 4a with NH3 into 2a and 1a.

Density functional theory (DFT) calculations were performed to confirm the possible reaction pathways for the formation of 2a from 1a, O2, and NH3 (Fig. 2, Fig. S2 and Table S5, ESI). The oxidation of thiol 1a to disulfide 3a and that of 3a to 4a with O2 were calculated to be exothermic by 173 and 175 kJ mol−1, respectively. The calculated energy changes for the formation of S–N bonds by the reactions of 3a and 4a with NH3 were +49 and −1 kJ mol−1, respectively; therefore, the nucleophilic attack of NH3 on S atoms of oxygenated products such as 4a was thermodynamically favorable in comparison with non-oxygenated thiol 3a.§ The S–S bond distances of 3a and 4a increased in the order of 3a (2.08 Å) < 4a (2.18 Å), which suggests that the oxidation of sulfur atoms weakens the S–S bonds and facilitates the nucleophilic attack of NH3 on the S atoms of 4a. These calculation results are in good agreement with the faster formation rate of 2a from 4a than that from 3a.

image file: c9cc09411c-f2.tif
Fig. 2 Computational free energy diagrams for the aerobic oxidation of 1a into 2a. Energies are shown in kJ mol−1. 6a is benzenesulfenamide.

On the basis of these results, it is possible that the sulfonamidation of 1a with O2 and NH3 proceeds as follows (Scheme 2). First, the oxidative dimerization of 1a over β-MnO2-HS proceeds to give the disulfide 3a. Although 3a was obtained even without catalysts (72% for 8 h, entry 25 in Table S4, ESI), the presence of β-MnO2-HS significantly enhanced the formation of 3a (99% for 0.5 h, in Fig. 1(b)). Next, 3a is oxidized to 4a with O2 over β-MnO2-HS, and this step is considered to be the rate-determining step. Finally, the nucleophilic attack of the nitrogen atom in NH3 on the sulfur atom of 4a occurs on the β-MnO2-HS surface to give the corresponding sulfonamide 2a and 1a. The formation of 2a was hardly observed for the reaction of 4a under the same reaction conditions but without β-MnO2-HS, whereas 2a was obtained in 74% yield only in the presence of β-MnO2-HS (Schemes S2(b) and (c), ESI), which indicates that β-MnO2-HS facilitates the nucleophilic substitution of 4a with NH3. On the basis of the infrared (IR) spectroscopy for β-MnO2-HS with adsorbed pyridine (Fig. S3 and S4, ESI), β-MnO2-HS showed bands around 1445 cm−1, which were assignable to the adsorption of pyridine on Lewis acid sites,16 and the amount of Lewis acid sites was 163 μmol g−1. In addition, the red-shift of the original SO2 antisymmetric stretching mode of 4a (from 1149 cm−1 to 1127 cm−1)17 most likely indicates the interaction of 4a with Lewis acid sites on the β-MnO2-HS surface, which would facilitate the nucleophilic attack of NH3 on 4a. Therefore, the strong oxidizing ability and Lewis acidity of β-MnO2-HS is essential to the aerobic oxidation of 1a to 4a and the nucleophilic substitution of 4a with NH3, respectively, and such dual-functionality of β-MnO2-HS results in highly efficient one-pot aerobic sulfonamidation from thiols, O2, and NH3.

image file: c9cc09411c-s2.tif
Scheme 2 Proposed reaction mechanism for the one-pot aerobic sulfonamidation of 1a to 2a with β-MnO2-HS.

In conclusion, β-MnO2-HS could heterogeneously catalyze the aerobic oxidative sulfonamidation of various aromatic and heteroaromatic thiols without the need for any additives. The present system was reusable and could be applied to the large-scale sulfonamidation of p-toluenethiol to give the industrially important sulfonamide.

This work was supported in part by Grants-in-Aid (18H01786) for JSPS Scientific Research from MEXT of Japan, JACI The 7th Research Award for New Chemistry and Technology 2018, and the “Creation of Life Innovative Materials for Interdisciplinary and International Researcher Development” programs of MEXT.

Conflicts of interest

There are no conflicts to declare.

Notes and references

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Electronic supplementary information (ESI) available. See DOI: 10.1039/c9cc09411c
The formation of 4a was hardly observed for the oxidation of 3a without NH3 under the conditions of entry 9 in Table 1, which indicates that the presence of NH3 likely plays an important role in the oxidation of 3a into 4a.15
§ While S-phenyl benzenethiosulfinate (5a) formed by the monooxygenation of 3a was not directly observed, 5a can be also a possible intermediate in the same way as 4a because of the following calculation results: (i) the oxidation of 3a to 4a was calculated to be 72 kJ mol−1, (ii) the calculated energy change for the formation of a S–N bond by the reactions of 5a with NH3 was 25 kJ mol−1 and lower than that (49 kJ mol−1) of 3a, and (iii) the S–S bond distance of 5a (2.23 Å) was longer than that (2.08 Å) of 3a.
In this case, no band due to pyridinium ions bonded to the Brønsted acid sites was observed around 1540 cm−1.

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