Mechanochemical sulfonation of aromatic compounds using NaHSO 4 ·H 2 O/P 2 O 5

Abstract

A series of aromatic sulfonic acids is synthesized by subjecting arenes and NaHSO₄·H₂O to high-speed ball milling in the presence of P₂O₅. It is suggested the aromatic sulfonation occurs via in situ generated H₂SO₄ to give aromatic sulfonic acids. In some cases, formation of diaryl sulfones was observed.

Introduction

The sulfonation of aromatic compounds is of significant importance in both industry and academia.^1–3 Traditional methods for the synthesis of aromatic sulfonic acids involve the sulfonylation of aromatic compounds with sulfonating agents such as concentrated sulfuric acid, ⁴ trifluoroacetic acid–sulfuric acid, ⁵ sulfur trioxide in dichloromethane, ⁶ silica–sulfuric acid, ⁷ the sulfur trioxide–dioxane complex, ⁸ oleum, ⁹ sulfur trioxide in nitrobenzene, ¹⁰ and 1,3-disulfo-1H-imidazol-3-ium chloride in aqueous media. ¹¹ Other alternative methods include the sulfonation of Grignard and lithium reagents, ¹² the Vilsmeier–Haack reaction in acetonitrile, ¹³ destructive oxidation of aryl thioglycolate esters, ¹⁴ and oxidation of thiols and disulfides using HOF·MeCN. ¹⁵ Despite their usefulness, these methods have limitations such as the requirements of harsh reaction conditions, prefunctionalized starting materials, high temperatures, expensive catalysts, and toxic solvents. Hence, the development of a general, facile, and efficient synthetic protocols to prepare sulfonic acid is still highly desirable.

Along with the rapid development of green chemistry, mechanochemical organic synthesis has attracted increasing attention from organic chemists.^16–22 As a green alternative to traditional solution-based synthetic approaches, mechanochemical organic synthesis exhibits many advantages over its liquid-phase counterpart in terms of higher product yields, better selectivity, shorter reaction times, simple work-up procedures, elimination of harmful organic solvents, and so on. During our exploration of high-speed ball milling (HSBM) reactions,^23–29 we recently found that arenes could be converted into diarylsulfones using 3CdSO₄·xH₂O/P₂O₅ as the sulfonating reagent, and noted that aromatic sulfonic acids were formed as by-products during the reaction. ²⁹ We speculated that a higher yield of the aromatic sulfonic acid could be achieved by optimizing the HSBM conditions. We report herein the facile synthesis of aromatic sulfonic acids via the reaction of arenes and NaHSO₄·H₂O under HSBM conditions.

Results and discussion

Following our previous work on the synthesis of diarylsulfones, biphenyl was chosen as the standard substrate and the molar ratio of the biphenyl substrate, sulfate salt, and P₂O₅ was fixed at 1:3.5:11. The reactions were conducted in a standard 2.5-mL screw-capped milling beaker and milled with one stainless steel ball of 6.0 mm diameter in a high-energy vibrational MM400 mixer mill at a frequency of 28 Hz for 5 h at room temperature. A variety of different sulfate salts were tested under HSBM condition (Table 1, entries 1–7). It was found that CaSO₄·0.5H₂O, CdSO₄·H₂O, NiSO₄·6H₂O, MgSO₄·7H₂O, and Co₂(SO₄)₃·7H₂O were all ineffective in producing [1,1’-biphenyl]-4-sulfonic acid (2a) (Table 1, entries 3–7). However, anhydrous NaHSO₄ afforded 2a in 28% yield (Table 1, entry 1), while NaHSO₄·H₂O was more suitable and produced 2a in 35% yield (Table 1, entry 2). Taking NaHSO₄·H₂O, the HSBM reaction conditions were further optimized by adjusting the molar ratio of NaHSO₄·H₂O and P₂O₅ in relation to biphenyl (Table 1, entries 8–14). When the molar ratio of biphenyl, NaHSO₄·H₂O, and P₂O₅ was 1:5:11, a 39% yield of 2a was obtained (Table 1, entry 11). However, remarkably sticky substances were found at the bottom of beaker after completion of the reaction, suggesting that an excess loading of the reactant in the milling beaker resulted in insufficient grinding by the ball. So, we reduced the amount of the reactant to half and tested the reaction by varying the molar ratio of biphenyl, NaHSO₄·H₂O, and P₂O₅ (Table 1, entries 15–18). To our delight, when 0.05 mmol of biphenyl was used and the molar ratio of biphenyl, NaHSO₄·H₂O, and P₂O₅ was kept as 1:5:11, a 55% yield of 2a was obtained (Table 1, entry 15). Thus, NaHSO₄·H₂O, biphenyl (0.05 mmol), and a molar ratio of arene/NaHSO₄·H₂O/P₂O₅ of 1:5:11 were selected for the HSBM reaction in further studies.

Table 1.

Optimization of the reaction conditions. ^a

Entry	Sulfate	Molar ratio b	Yield (%) c
			2a	3a
1	NaHSO4	1:3.5:11	28	25
2	NaHSO4·H2O	1:3.5:11	35	30
3	CaSO4·0.5H2O	1:3.5:11	10	9
4	CdSO4·H2O	1:3.5:11	5	12
5	NiSO4·6H2O	1:3.5:11	6	4
6	MgSO4·7H2O	1:3.5:11	5	5
7	Co2(SO4)3·7H2O	1:3.5:11	7	6
8	NaHSO4·H2O	1:2:11	32	30
9	NaHSO4·H2O	1:4:11	36	33
10	NaHSO4·H2O	1:4.5:11	38	31
11	NaHSO4·H2O	1:5:11	39	23
12	NaHSO4·H2O	1:5.5:11	32	28
13	NaHSO4·H2O	1:6:11	14	16
14	NaHSO4·H2O	1:7:11	3	4
15 d	NaHSO4·H2O	1:5:11	55	23
16 d	NaHSO4·H2O	1:5:14	46	37
17 d	NaHSO4·H2O	1:5:16	38	39
18 d	NaHSO4·H2O	1:5:20	33	41

a

Reaction conditions: biphenyl (0.1 mmol), reaction frequency (28 Hz), 5 h.

b

Molar ratio of biphenyl/sulfate/P₂O₅.

c

Yields were determined by ¹H NMR.

d

Biphenyl (0.05 mmol) was used.The bold values indicate the optimized HSBM reaction condition.

As for organic mechanochemical reactions, the mechanochemistry process parameters usually have a strong influence on the outcomes.^30–37 So, the influence of the ratios between the milling ball and the milling materials, as well as a study of the combined assessment of the grinding time and vibration frequency were carried out. To investigate the influence of the ratios between the milling ball and the milling materials, stainless steel balls of different sizes were selected for this HSBM reaction (Figure 1(a) and Table S1 in the Supporting Information). When the weight ratio between the milling ball and the milling materials was 4.45 (the diameter of the ball is 6.0 mm), the best yield of 55% of 2a was obtained. The combined influence of the grinding time and vibration frequency was also investigated by varying the time and vibration frequency. When the vibration frequency was set as 20 Hz, the yield of 2a increased from 4% to 9% when the time was prolonged from 2 to 5 h. However, when the vibration frequency was set as 28 Hz, the yield increased sharply from 23% to 61% when the time was extended from 2 to 3 h. This implies that a high vibration frequency is more favorable for this HSBM reaction (Figure 1(b) and Table S2 in the Supporting Information). Combined with the results of the ratios between the milling ball and the milling materials, the best HSBM conditions involve grinding for 3 h at a vibration frequency of 28 Hz, with a weight ratio of 4.45 between the milling ball and the milling materials.

Figure 1.

Optimization of the mechanochemical parameters. (a) Influence of the weight ratio of the milling ball and milling materials. (b) Influence of the time and frequency.

With optimized reaction conditions in hand, we next extended the methodology to various substituted arenes. The results are summarized in Table 2. Arenes with only one activating substituent all gave a sulfonic acid as the major product (Table 2, entries 2–4). Toluene gave a 55% yield of 4-methylbenzenesulfonic acid (2b) and 37% of the corresponding diarylsulfone 3b (Table 2, entry 2). Ethylbenzene gave a 57% yield 4-ethylbenzenesulfonic acid (2c) and diarylsulfone 3c, while anisole gave 4-methoxybenzenesulfonic acid (2d) and 30% diarylsulfones 3d in 62% and 30% yields, respectively (Table 2, entries 3 and 4). All the mono-substituted arenes mainly afforded the para-substituted sulfonic acid isomer, implying that the regioselectivity was determined by steric hindrance effects. This result is similar to Hajipour’s work employing silica sulfuric acid as the sulfonating reagent in solution chemistry. ⁷ The formation of diarylsulfones 3 may be explained by interactions between the sulfonic acid and unreacted arenes through electrophilic substitution reaction. ²⁹ Arenes with one weakly deactivating substituent, such as fluorobenzene (1e), chlorobenzene (1f), and bromobenzene (1g), also gave similar results, indicating that halogen groups on the aromatic ring did not affect the efficiency of this reaction (Table 2, entries 5–7). However, arenes bearing one strongly deactivating substituent, such as nitrobenzene, benzenesulfonic acid, and benzoic acid, all failed to give the corresponding acids, with only unreacted starting materials being recovered.

Table 2.

Preparation of sulfonic acids 2 via the mechanochemical reaction. ^a

Entry	Substrate		Conversion	Sulfonic acid	Yield		Sulfone	Yield
1		1a	100%		2a	61% (61%)		3a	27% (27%)
2		1b	100%		2b	55% (55%)		3b	37% (37%)
3		1c	100%		2c	57% (57%)		3c	32% (32%)
4		1d	100%		2d	62% (62%)		3d	30% (30%)
5		1e	100%		2e	59% (59%)		3e	31% (31%)
6		1f	100%		2f	55% (55%)		3f	40% (40%)
7		1g	100%		2g	60% (60%)		3g	34% (34%)
8		1h	100%		2h	58% (58%)		3h	32% (32%)
9		1i	100%		2i	64% (64%)		3i	25% (25%)
10		1j	100%		2j	50% (50%)		3j	27% (27%)
11		1k	52%		2k	52% (100%)
12		1l	50%		2l	49% (100%)
13		1m	60%		2m	60% (100%)
14		1n	100%		2n	71% (71%)		3n	21% (21%)
15		1o	100%		2o	77% (77%)		3o	12% (12%)
16 b		1a	100%		2a	58% (58%)		3a	37% (37%)

a

Reaction conditions: 1 (0.05 mmol), reaction frequency (28 ), 3 h. Molar ratio (arenes/NaHSO₄·H₂O/P₂O₅) = 1:5:11. Isolated yield by combining 10 reactions of 0.05 mmol. The numbers in brackets are the yields based on the reacted arenes.

b

Biphenyl (1.0 mmol) was used and reaction was carried using a polytetrafluoroethylene milling ball.

Arenes bearing multiple alkyl groups, such as o-, m-, and p-dimethylbenzene (1h, 1i, and 1j), afforded only one regioisomer (2h, 2i, and 2j) as the major product in 58%, 64%, and 50% yields, respectively (Table 2, entries 8–10). Disubstituted benzenes bearing both an activating group and a deactivating group on the aromatic ring, for example, 4-nitrotoluene (1k), 4-methylbenzoic acid (1l), and 4-methoxybenzoic acid (1m), reacted smoothly to give 2k, 2l, and 2m in 52%, 49%, and 60% yields, respectively (Table 2, entries 11–13). To our surprise, the only identifiable products in the resulting mixtures were the corresponding sulfonic acids and some unreacted starting material, while no diarylsulfones were observed. Apparently, the arenes were all converted into the corresponding sulfonic acids in 100% yields. These results may be due to the fact that the strong electron-withdrawing effect of the nitro and carboxylic groups reduced the reactivity of the aromatic rings of 1k–m, thus preventing their further electrophilic substitution reaction with the resulting sulfonic acid 2k–m to afford diarylsulfones. This implies that an electrophilic substitution process may be involved in the formation of 3.

Naphthalene (1n) was sulfonated mainly at the 1-position to afford naphthalene-1-sulfonic acid (2n) in 71% yield (Table 2, entry 14), similar to the conventional sulfonation of naphthalene with sulfuric acid at low temperature, thus indicating this reaction is under kinetically controlled conditions. ³⁸ In addition, aromatic heterocyclic thiophene (1o) was converted into thiophene-2-sulfonic acid (2o) in 77% yield (Table 2, entry 15), implying that heterocyclic sulfonic acids could also be prepared by this method.

In order to investigate the applicability of our protocol on a larger scale, the sulfonation of a larger quantity of biphenyl (1 mmol) was performed in a polytetrafluoroethylene milling vessel at the same molar ratio as described above (Table 2, entry 16). As shown, our sulfonation reaction also worked well and [1,1’-biphenyl]-4-sulfonic acid was obtained in 58% yield.

Compared with our previous work, when 3CdSO₄·xH₂O/P₂O₅ was chosen as the sulfonating reagent under the same HSBM conditions, toluene (1b), ethylbenzene (1c), and anisole (1d) provided the corresponding diarylsulfones in excellent yields (89%–95%), and fluorobenzene (1e), chlorobenzene (1f), bromobenzene (1g) as well as m-dimethylbenzene (1i) provided the expected diarylsulfones in good yields (62%–75%). ²⁹ It becomes clear that the sulfating reagent NaHSO₄·H₂O/P₂O₅ mainly converts arenes into the corresponding sulfonic acids, while the CdSO₄·xH₂O/P₂O₅ system favors the formation of sulfones, indicating that the use of different sulfates as sulfating reagents leads to different major products and selectivities, which may be due to the subtle regulatory effects of the metal cation.

It is interesting to note that the sulfonic acid was afforded along with diarylsulfones in this work, which is in contrast to our previous work, wherein the desired diarylsulfones were obtained along with sulfonic acids. ²⁹ It appears that diarylsulfones can be converted into the corresponding sulfonic acids under HSBM conditions. In order to gain a deeper insight into our sulfonation reaction, we investigated the possibility of the decomposition of diarylsulfones, using 4,4’-sulfonyldibiphenyl (3a) as a standard. The reaction of a mixture of 3a, NaHSO₄·H₂O, and P₂O₅ (according to the molar ratio indicated in Table 3) was conducted in a stainless milling beaker (2.5 mL) for 5 h at 28 Hz, and the progress was analyzed by ¹H NMR. Although diarylsulfone 3a is decomposed to sulfonic acids 2a, it could not be converted into 2a completely; this being despite several efforts such as varying the molar ratio (Table 3, entries 1–8). This is likely because of a reversible conversion between diarylsulfones and sulfonic acids, similar to that observed in solution chemistry.^39,40

Table 3.

Optimization of the conversion of diarylsulfone 3a into sulfonic acid 2a. ^a

Entry	Molar ratio b	Yield (%) c
1	1:1:3	20
2	1:2:4	26
3	1:2:5	28
4	1:2:7	37
5	1:3:7	18
6	1:2:9	46
7	1:2:11	39
8	1:3.5:11	21
9	1:5:11	16
10	1:7:11	7

a

Reaction conditions: 3a (0.1 mmol), reaction frequency (28 Hz), 5 h.

b

Molar ratio of 3a/sulfate/P₂O₅.

c

Yields were determined by ¹H NMR.

Currently, it is not easy to monitor the mechanism of an organic mechanochemical reaction. In connection with our previous work, we have proposed a plausible mechanism to demonstrate the sulfonation of aromatic compounds with a sulfate salt under HSBM condition (Scheme 1). First, the sulfate reacts with P₂O₅ to produce H₂SO₄. Subsequently, the aromatic compound 1 is sulfonated by the in situ generated H₂SO₄ to give aromatic sulfonic acid 2, which can further undergo electrophilic substitution with the unconverted starting aromatic compound 1 to afford sulfone 3. Next, sulfone 3 can decompose to give sulfonic acid 2, resulting in a reversible reaction between the sulfonic acid and the sulfonate. The in situ generated water was absorbed by excess P₂O₅ produces phosphoric acid. This process consumes water from the reaction medium, thereby driving the HSBM reaction forward.

Scheme 1.

A plausible reaction mechanism.

Conclusion

In summary, we have shown that the combination of NaHSO₄·H₂O and P₂O₅ can successfully convert aromatic compounds into sulfonic acids in moderate yields under HSBM conditions. The method is facile, eco-friendly, operationally simple, and can be performed safely on large scale. We propose that the in situ generated H₂SO₄ from the reaction of the sulfate and P₂O₅ participates in the aromatic sulfonation to afford the aromatic sulfonic acid.

Experimental

General

All chemicals and reagents were purchased from Sigma-Aldrich (Billerica, MA, USA), Alfa Aesar (Ward Hill, MA, USA), or TCI (Tokyo, Japan), and were used without further purification. The reactions were conducted in a stainless milling beaker (2.5 mL) using a stainless milling ball or in a polytetrafluoroethylene milling beaker (35 mL) using a polytetrafluoroethylene milling ball (ø = 19.05 mm) in an MM400 mixer ball mill (Retsch GmbH, Germany). Column chromatography was performed using 100–200 mesh silica gel purchased from the Qingdao Haiyang Chemical Co., Ltd. Appropriate solvent systems for chromatography were selected according to TLC analysis using UV light (254 nm) to visualize the reaction components. NMR spectra were recorded on Bruker AV 400 spectrometer at 400 MHz (¹H NMR) and at 101 MHz (¹³C NMR). TMS was used as the internal standard. The peak patterns are designated as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet-doublet; dt, doublet-triplets; m, multiplet. Coupling constants, J, are reported in Hz. The product was dissolved in an appropriate deuterium reagent with 3.5 μL of dibromomethane as a reference. An APEX II (Bruker Inc.) mass spectrometer was used for HRMS analysis.

General procedure of compounds 2 and 3

A mixture of arene (1) (0.05 mmol), NaHSO₄·H₂O (0.25 mmol), and P₂O₅ (0.55 mmol) was added to a stainless milling beaker (2.5 mL), along with a stainless milling ball (ø = 6.00 mm). The beaker was sealed and placed in the mixer mill. The reaction was performed at 28 Hz for 3 h. The reaction mixture was extracted with a mixed solvent of chloroform and ethyl acetate (chloroform:ethyl acetate = 2:3) (3 × 5 mL). The organic extracts from 10 such reactions were put together and the mixture was filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel to afford of product 2 and product 3. Product 3 was eluted first because of its low polarity in all cases, while product 2 was elute latterly.

[1,1’-Biphenyl]-4-sulfonic acid (2a)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:2) in 61% yield (71.37 mg); white solid; m.p. 138–141 °C (lit. ²⁹ 134–136 °C); ¹H NMR (400 MHz, D₂O): δ 7.88 (d, J = 8.5 Hz, 2H), 7.78 (d, J = 8.6 Hz, 2H), 7.72 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.4 Hz, 2H), 7.46 (t, J = 7.3 Hz, 1H); ¹³C NMR (101 MHz, D₂O): δ 143.59, 141.21, 139.36, 129.15, 128.34, 127.38, 127.17, 126.01; HRMS (ESI): m/z [M − H]⁻ calcd for C₁₂H₉O₃S: 233.0278; found: 233.0274.

4,4’-Sulfonyldi-1,1’-biphenyl (3a)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 75:1) in 27% yield (21.28 mg); white solid; m.p. 213–214 °C (lit. ²⁹ 213–216 °C); ¹H NMR (400 MHz, CDCl₃): δ 8.05 (d, J = 8.4 Hz, 4H), 7.72 (d, J = 8.5 Hz, 4H), 7.57 (d, J = 7.0 Hz, 4H), 7.50-7.35 (m, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 146.33, 140.45, 139.37, 129.26, 128.71, 128.32, 128.19, 127.55; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₄H₁₉O₂S: 371.1100; found: 371.1103.

4-Methylbenzenesulfonic acid (2b)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 2:3) in 55% yield (47.57 mg); white crystalline solid; m.p. 104–106 °C (lit. ⁴¹ 99–102 °C); ¹H NMR (400 MHz, D₂O): δ 7.67 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 2.37 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 176.61, 129.39, 125.32, 100.00, 20.33; HRMS (ESI): m/z [M − H]⁻ calcd for C₇H₇O₃S: 171.0121; found: 171.0124.

4,4’-Sulfonylbis(methylbenzene) (3b)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 65:1) in 37% yield (22.75 mg); white solid; m.p. 156–158 °C (lit. ²⁹ 155–158 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.73 (d, J = 8.3 Hz, 4H), 7.16 (d, J = 8.1 Hz, 4H), 2.24 (s, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 143.73, 138.82, 129.65, 127.22, 21.21; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₄O₂SNa: 269.0607; found: 269.0605.

4-Ethylbenzenesulfonic acid (2c)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 5:6) in 57% yield (55.82 mg); brown crystalline solid; m.p. 109–111 °C; ¹H NMR (400 MHz, D₂O): δ 7.33 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.3 Hz, 2H), 2.19 (q, J = 7.6 Hz, 2H), 0.73 (t, J = 7.6 Hz, 3H); ¹³C NMR (101 MHz, D₂O): δ 148.28, 139.42, 128.04, 125.22, 27.84, 14.39; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₉O₃S: 185.0278; found: 185.0275.

4,4’-Sulfonylbis(ethylbenzene) (3c)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 120:1) in 28% yield (19.25 mg); white solid; m.p. 92–95 °C (lit. ²⁹ 93–95 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.76 (d, J = 8.2 Hz, 4H), 7.18 (d, J = 8.1 Hz, 4H), 2.51 (q, J = 7.6 Hz, 4H), 1.05 (t, J = 7.7 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 149.84, 138.92, 128.43, 127.37, 28.41, 14.76; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈O₂SNa: 297.0920; found: 297.0919.

4-Methoxybenzenesulfonic acid (2d)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:1) in 62% yield (58.65 mg); brown crystalline solid; m.p. 83–85 °C (lit. ⁴¹ 88–90 °C); ¹H NMR (400 MHz, D₂O): δ 7.56 (d, J = 8.9 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 3.64 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 161.01, 134.71, 127.21, 113.98, 55.38; HRMS (ESI): m/z [M − H]⁻ calcd for C₇H₇O₄S: 187.0071; found: 187.0070.

4,4’-Sulfonylbis(methoxybenzene) (3d)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 100:1) in 31% yield (20.89 mg); white solid; m.p. 125–127 °C (lit. ²⁹ 124–126 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.81 (d, J = 8.9 Hz, 4H), 6.91 (d, J = 8.9 Hz, 4H), 3.78 (s, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 163.13, 133.96, 129.43, 114.49, 55.67; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₅O₄S: 279.0686; found: 279.0683.

4-Fluorobenzenesulfonic acid (2e)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:3) in 59% yield (51.79 mg); brown solid; m.p. 89–92 °C (lit. ⁴² 87 °C); ¹H NMR (400 MHz, D₂O): δ 7.92-7.75 (m, 2H), 7.24 (t, J = 8.9 Hz, 2H); ¹³C NMR (101 MHz, D₂O): δ 163.86 (d, J = 248.9 Hz), 138.56, 127.88 (d, J = 8.9 Hz), 115.67 (d, J = 22.6 Hz); HRMS (ESI): m/z [M − H]⁻ calcd for C₆H₄O₃FS: 174.9871; found: 174.9878.

4,4’-Sulfonylbis(fluorobenzene) (3e)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 65:1) in 31% yield (19.71 mg); white solid; m.p. 99–102 °C (lit. ²⁹ 96–98 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.94 (dd, J = 8.9, 5.0 Hz, 4H), 7.18 (t, J = 8.6 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 165.50 (d, J = 256.2 Hz), 137.72, 130.42 (d, J = 9.6 Hz), 116.75 (d, J = 22.7 Hz); HRMS (ESI): m/z [M + H]⁺ calcd for C₁₂H₉O₂F₂S: 255.0286; found: 255.0289.

4-Chlorobenzenesulfonic acid (2f)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 2:3) in 52% yield (49.96 mg); yellow solid; m.p. 87–91 °C (lit. ⁴¹ 85–87 °C); ¹H NMR (400 MHz, D₂O): δ 7.72 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 8.7 Hz, 2H); ¹³C NMR (101 MHz, D₂O): δ 140.92, 136.95, 128.99, 127.02; HRMS (ESI): m/z [M − H]⁻ calcd for C₆H₄O₃ClS: 190.9575; found: 190.9578.

4,4’-Sulfonylbis(chlorobenzene) (3f)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 85:1) in 40% yield (29.04 mg); white solid; m.p. 145–148 °C (lit. ²⁹ 145–148 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.67 (d, J = 10.8 Hz, 4H), 7.28 (d, J = 8.6 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 140.34, 139.85, 129.82, 129.29; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₂H₈O₂Cl₂SNa: 308.9514; found: 308.9511.

4-Bromobenzenesulfonic acid (2g)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:2) in 60% yield (70.75 mg); yellow solid; m.p. 91–94 °C (lit. ⁴³ 88–90 °C); ¹H NMR (400 MHz, D₂O): δ 7.72 (d, J = 9.0 Hz, 2H), 7.70 (d, J = 9.2 Hz, 2H); ¹³C NMR (101 MHz, D₂O): δ 141.44, 132.04, 127.20, 125.40; HRMS (ESI): m/z [M − H]⁻ calcd for C₆H₄O₃BrS: 234.9070; found: 234.9072.

4,4’-Sulfonylbis(bromobenzene) (3g)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 50:1) in 34% yield (31.71 mg); white solid; m.p. 161–164 °C (lit. ²⁹ 161–165 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.78 (d, J = 8.6 Hz, 4H), 7.64 (d, J = 8.6 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 140.36, 132.95, 129.37, 128.94; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₂H₈O₂Br₂SNa: 396.8504; found: 396.8501.

3,4-Dimethylbenzenesulfonic acid (2h)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:3) in 58% yield (53.77 mg); white solid; m.p. 85–88 °C (lit. ⁴¹ 81–83 °C); ¹H NMR (400 MHz, D₂O): δ 7.34 (s, 1H), 7.28 (d, J = 7.9 Hz, 1H), 7.07 (d, J = 7.9 Hz, 1H), 2.06 (d, J = 4.1 Hz, 6H); ¹³C NMR (101 MHz, D₂O): δ 142.06, 137.61, 135.78, 132.40, 126.61, 126.08, 20.03, 19.26; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₉O₃S: 185.0278; found: 185.0277.

4,4’-Sulfonylbis(1,2-dimethylbenzene) (3h)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 65:1) in 32% yield (21.92 mg); white solid; m.p. 157–159 °C (lit. ²⁹ 159–161 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.70-7.61 (m, 4H), 7.19 (d, J = 7.9 Hz, 2H), 2.23 (d, J = 5.4 Hz, 12H); ¹³C NMR (101 MHz, CDCl₃): δ 142.55, 139.26, 137.87, 130.27, 128.19, 124.92, 19.73, 19.65; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉O₂S: 275.1100; found: 275.1102.

2,4-Dimethylbenzenesulfonic acid (2i)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 5:9) in 64% yield (59.56 mg); white solid; m.p. 65–68 °C (lit. ⁴¹ 61–63 °C); ¹H NMR (400 MHz, D₂O): δ 7.71 (d, J = 8.0 Hz, 1H), 7.19 (s, 1H), 7.13 (d, J = 7.9 Hz, 1H), 2.54 (s, 3H), 2.31 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 142.39, 137.75, 136.06, 132.59, 126.83, 126.28, 20.18, 19.35; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₉O₃S: 185.0278; found: 185.0273.

4,4’-Sulfonylbis(1,3-dimethylbenzene) (3i)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 76:1) in 25% yield (17.14 mg); white solid; m.p. 117–121 °C (lit. ⁴⁴ 122–125 °C); ¹H NMR (400 MHz, CDCl₃): δ 8.03 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.1 Hz, 2H), 6.98 (s, 2H), 2.31 (s, 6H), 2.26 (s, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 144.04, 137.45, 136.27, 133.24, 129.89, 126.63, 21.35, 19.86; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉O₂S: 275.1100; found: 275.1106.

2,5-Dimethylbenzenesulfonic acid (2j)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:2) in 50% yield (46.53 mg); white solid; m.p. 95–98 °C (lit. ⁴¹ 89–91 °C); ¹H NMR (400 MHz, D₂O): δ 7.57 (s, 1H), 7.19-7.09 (m, 2H), 2.44 (s, 3H), 2.21 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 140.27, 136.03, 132.83, 132.00, 131.95, 127.03, 19.91, 18.97; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₉O₃S: 185.0278; found: 185.0279.

2,2’-Sulfonylbis(1,4-dimethylbenzene) (3j)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 55:1) in 27% yield (18.52 mg); white solid; m.p. 167–169 °C (lit. ⁴⁴ 163–165 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.99 (s, 2H), 7.27 (d, J = 7.6 Hz, 2H), 7.09 (d, J = 7.7 Hz, 2H), 2.40 (s, 6H), 2.26 (s, 6H); ¹³C NMR (101 MHz, CDCl₃): δ 138.71, 136.12, 134.63, 134.27, 132.65, 129.90, 21.07, 19.64; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈O₂SNa: 297.0920; found: 297.0922.

2-Methyl-5-nitrobenzenesulfonic acid (2k)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:4) in 47% yield (50.98 mg); yellow solid; m.p. 137–139 °C (lit. ⁴⁵ 132–133 °C); ¹H NMR (400 MHz, D₂O): δ 8.25 (s, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 2.38 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 144.91, 144.56, 141.83, 133.01, 125.45, 121.77, 19.61; HRMS (ESI): m/z [M − H]⁻ calcd for C₇H₆O₅NS: 215.9972; found: 215.9978.

4-Methyl-3-sulfobenzoic acid (2l)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:3) in 49% yield (53.17 mg); yellow solid; m.p. 262–265 °C; ¹H NMR (600 MHz, MeOD): δ 8.04 (s, 1H), 7.98 (q, J = 8.4 Hz, 2H), 2.57 (s, 3H); ¹³C NMR (101 MHz, MeOD): δ 166.33, 151.99, 134.39, 133.57, 132.84, 127.93, 124.04, 18.35; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₇O₅S: 215.0019; found: 215.0015.

4-Methoxy-3-sulfobenzoic acid (2m)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:4) in 50% yield (63.76 mg); yellow solid; m.p. 256–257 °C (lit. ⁴⁶ 250–251 °C); ¹H NMR (400 MHz, D₂O): δ 7.39 (s, 1H), 7.03 (d, J = 8.7 Hz, 1H), 6.19 (d, J = 8.8 Hz, 1H), 3.07 (s, 3H); ¹³C NMR (101 MHz, D₂O): δ 166.80, 159.63, 134.29, 129.39, 129.05, 120.65, 111.78, 55.62; HRMS (ESI): m/z [M − H]⁻ calcd for C₈H₇O₆S: 230.9969; found: 230.9965.

Naphthalene-1-sulfonic acid (2n)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:3) in 71% yield (73.84 mg); yellow solid; m.p. 80–85 °C (lit. ⁴¹ 79–81 °C); ¹H NMR (400 MHz, D₂O): δ 7.91 (d, J = 5.2 Hz, 1H), 7.44 (q, J = 8.6 Hz, 2H), 7.41-7.35 (m, 1H), 7.91 (s, 1H), 7.12-6.98 (m, 2H); ¹³C NMR (101 MHz, D₂O): δ 141.15, 135.46, 130.72, 130.36, 129.64, 129.25, 127.20, 123.47; HRMS (ESI): m/z [M − H]⁻ calcd for C₁₀H₇O₃S: 207.0126; found: 207.0121.

1,1’-Sulfonyldinaphthalene (3n)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 75:1) in 21% yield (33.39 mg); white solid; m.p. 144–146 °C (lit. ⁴⁷ 143–146 °C); ¹H NMR (400 MHz, CDCl₃): δ 8.34 (d, J = 4.4 Hz, 2H), 7.98-7.82 (m, 8H), 7.55 (dd, J = 6.5, 2.6 Hz, 4H); ¹³C NMR (101 MHz, CDCl₃): δ 141.62, 134.27, 132.55, 128.63, 128.48, 127.69, 127.53, 126.91, 125.44, 122.76; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₄O₂SNa: 341.0601; found: 341.0607.

Thiophene-2-sulfonic acid (2o)

Isolated by silica gel column chromatography (dichloromethane/ethyl acetate = 1:4) in 77% yield (63.03 mg); yellow solid; m.p. 72–75 °C (lit. ⁴⁸ 71–72 °C); ¹H NMR (400 MHz, D₂O): δ 7.38 (d, J = 6.3 Hz, 1H), 7.26 (d, J = 3.7 Hz, 1H), 6.92-6.84 (m, 1H); ¹³C NMR (101 MHz, D₂O): δ 129.39, 128.72, 128.26, 126.76; HRMS (ESI): m/z [M − H]⁻ calcd for C₄H₃O₃S₂: 162.9529; found: 162.9526.

2,2’-Sulfonyldithiophene (3o)

Isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 86:1) in 12% yield (6.89 mg); white solid; m.p. 127–129 °C (lit. ²⁹ 123–125 °C); ¹H NMR (400 MHz, CDCl₃): δ 7.72 (d, J = 3.8 Hz, 2H), 7.65 (d, J = 5.0 Hz, 2H), 7.10-7.05 (m, 2H); ¹³C NMR (101 MHz, CDCl₃): δ 133.95, 133.47, 131.08, 127.91; HRMS (ESI): m/z [M + Na]⁺ calcd for C₈H₆O₂S₃Na: 252.9422; found: 252.9420.

Supplemental Material

sj-docx-1-chl-10.1177_17475198211032571 – Supplemental material for Mechanochemical sulfonation of aromatic compounds using NaHSO4·H2O/P2O5

Supplemental material, sj-docx-1-chl-10.1177_17475198211032571 for Mechanochemical sulfonation of aromatic compounds using NaHSO4·H2O/P2O5 by Lu-Lu Zuo, Shuai Qin, Pu Zhang, Yu-Jun Qin and Zhi-Xin Guo in Journal of Chemical Research