Synthesis 2022; 54(22): 5110-5118
DOI: 10.1055/a-1870-9282
paper

Bifunctional Ionic Liquid Catalyzed Multicomponent Arylsulfonation of Phenols with Aryl Triazenes and DABSO for the Synthesis of Diaryl Sulfones

Chengzong Tang
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Yonghong Zhang
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Xinlei Zhou
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Bin Wang
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Weiwei Jin
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Yu Xia
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
,
Chenjiang Liu
a   Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
b   College of Future Technology, Xinjiang University, Urumqi 830017, Xinjiang, P. R. of China
› Author Affiliations

This work was supported by the Natural Science Foundation of Xinjiang­ Province (2021D01E10) and the National Natural Science Foundation of China (21861036 and 21961037).
 


Abstract

The bifunctional Lewis acidic ionic liquid (LAIL) catalyzed multicomponent arylsulfonation of phenols with aryl triazenes and DABSO was developed. By using LAILs as redox and Lewis acidic catalysts without any additional promoter or ligand through an N2 extrusion/SO2 insertion sequence, various aryl triazenes were transformed into aryl sulfonyl radicals by coupling with DABSO, and these were then coupled with phenoxy radicals to afford the corresponding diaryl sulfones in good yields. The good functional-group tolerance, gram-scale reaction, and avoidance of the use of SO2 gas further demonstrated the practicality of this arylsulfonation reaction.


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Aryl diazonium salts have been widely used in organic synthesis as aryl precursors and aryl-azo precursors since they were discovered, especially for the efficient construction of C–C and C–heteroatom bonds through Sandmeyer, Pschorr cyclization, Balz−Schiemann, Meerwein arylation, Doyle diazotization, and Kikukawa–Matsuda Pd-catalyzed cross-coupling reactions.[1] However, these versatile building blocks have potential instability and explosive drawbacks during the process of preparation, storage and use, which have greatly impeded their practicality in organic synthesis.[2] Therefore, highly stable and reactive aryl diazonium salt surrogates are in high demand.

In recent years, aryl triazenes have been widely employed as both aryl and aryl diazenyl sources to forge C–C and C–heteroatom bonds under mild conditions.[3] Beside possessing the reactive properties of aryl diazonium salts upon in situ treatment with acid, these robust and diverse reagents have the advantages of superior stability, easy preparation, multiple reaction sites, and prolonged shelf life. Hence, based on these advantages, masked arene diazonium salts were expected to be the best candidates to replace aryl diazonium salts.[3b] [e] [g] [h] However, stoichiometric acid was usually used as a promoter to activate aryl triazenes in the reaction, which greatly reduced the economic viability and practicality of this transformation.[4] Although a few catalytic reactions of aryl triazenes have been reported in recent years,[5] the use of Pd noble metal catalysts and additives allows room for further improvement. Based on continual study on the development of efficient and environmentally friendly diazenylation and arylation reactions with aryl triazenes by using ionic liquids as green promoters, the development of a more economical and practical protocol with aryl triazenes that used a cheap catalyst has been one of our goals.[4a] [b] [f] [h] [r] [s] We envisioned this objective could be achieved through the use of Lewis acidic ionic liquids (LAILs) containing cheap Fe3+ metal as the catalyst to catalyze the reaction of aryl triazenes, by combining the properties of both Lewis acids and ionic liquids. Beside the Lewis acid catalytic activity of these LAILs, their unique physical and chemical properties of non-flammability, non-volatility, and good chemical and thermal stability make this strategy more attractive.[6]

Aryl sulfone compounds are important structural motifs that generally exist in biologically significant molecules and are widely used in clinical treatment as antibacterial and anti-inflammatory drugs (Figure [1]).[7] Accordingly, numerous strategies have been developed for the synthesis of aryl sulfones.[8] In recent developments in this field, the direct insertion of SO2 into organic molecules for the synthesis of aryl sulfones has been extensively studied.[9] Most frequently, DABSO (1,4-diazabicyclo[2.2.2]octane–sulfur dioxide, DABCO . (SO2)2) or inorganic sulfites as sulfur dioxide surrogates have been coupled with aryl diazonium salts to afford aryl sulfones;[10] in particular, the direct C–H bond functionalization of phenols with aryl diazonium salts and DABSO for the synthesis of sulfonated naphthols developed by the Wu group attracted our attention (Scheme [1a]).[10a]

Zoom Image
Figure 1 Representative drugs and biologically active molecules containing diaryl sulfone fragments

However, as mentioned above, the instability of aryl diazonium salts makes this strategy imperfect. On the other hand, Wu and co-workers reported an N2 extrusion/SO2 insertion sequence with aryl triazenes instead of aryl diazonium salts for the synthesis of sulfonamides, although the utilization of gaseous sulfur dioxide limited its applications (Scheme [1b]).[11] Inspired by these important contributions and to address the handling problem and potential safety hazard of using the gaseous sulfur dioxide and aryl diazonium salts, we envisioned that the combination of DABSO and aryl triazenes could be a stable and safe aryl sulfonyl source to obtain diaryl sulfones. Herein, we disclose a LAIL-catalyzed three-component arylsulfonation of phenols with aryl triazenes and DABSO to construct diaryl sulfones in good yields (Scheme [1c]).

Zoom Image
Scheme 1 General approach for the synthesis of aryl sulfones

We began to investigate the reaction by using 2-naphthol (1a), DABSO (2a), and (E)-1-(p-tolyldiazenyl)pyrrolidine (3aa) as our model substrates (Table [1]). Initially, a variety of LAILs were screened (Table [1], entries 1–4), and the results show that LAIL4 can afford the desired product with 74% yield. To our delight, 49% yield was afforded after isolation when the loading of LAIL4 was lowered to 10 mol% (Table [1], entry 5). Encouraged by this result, the dosage of catalyst was further studied (Table [1], entries 5–7). The results demonstrated that 20 mol% of LAIL4 can produce 60% yield (Table [1], entry 6); however, further increase of the dosage of LAIL4 to 30 mol% did not obviously increase the yield (Table [1], entry 7). A variety of solvents, such as DCE, DMSO, EtOH, and water were studied and afforded lower yields than acetonitrile (Table [1], entries 8–11). We then also examined the reaction temperature. Lowering of the temperature did not improve the yield (Table [1], entry 12); however, raising the reaction temperature to 90 °C provided good results (Table [1], entry 13). Finally, to our pleasant surprise, optimized reaction conditions could be obtained through variation of the substrate ratio and upon further decrease of the reaction time to 14 h (Table [1], entry 15). Control experiments showed that air and moisture did not affect this reaction (Table [1], entry 16).

Table 1 Optimization of the Reaction Conditionsa

Entry

LAIL

Solvent

T (°C)

Time (h)

Yieldb (%)

 1

LAIL1 (1 equiv)

MeCN

80

16

55

 2

LAIL2 (1 equiv)

MeCN

80

16

50

 3

LAIL3 (1 equiv)

MeCN

80

16

61

 4

LAIL4 (1 equiv)

MeCN

80

16

74

 5

LAIL4 (0.1 equiv)

MeCN

80

16

49

 6

LAIL4 (0.2 equiv)

MeCN

80

16

60

 7

LAIL4 (0.3 equiv)

MeCN

80

16

62

 8

LAIL4 (0.2 equiv)

DCE

80

16

45

 9

LAIL4 (0.2 equiv)

DMSO

80

16

 9

10

LAIL4 (0.2 equiv)

EtOH

80

16

trace

11

LAIL4 (0.2 equiv)

H2O

80

16

ND

12

LAIL4 (0.2 equiv)

MeCN

70

16

58

13

LAIL4 (0.2 equiv)

MeCN

90

16

70

14c

LAIL4 (0.2 equiv)

MeCN

90

16

82

15c

LAIL4 (0.2 equiv)

MeCN

90

14

89

16c,d

LAIL4 (0.2 equiv)

MeCN

90

14

87

a Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), 3aa (0.2 mmol), and solvent (2.0 mL) in a Schlenk tube under N2 at the indicated temperature for 14–16 h. ND = not detected.

b Yield of isolated product.

c 1a:2a:3aa = 1:1.2:1.5.

d Under air.

After obtaining the initial optimal reaction conditions, we then assessed the masking groups on the 4-methyl-1-phenyltriazene (Table [2]). First, cyclic substitution was screened, and the results show that the ring size exhibited almost no influence on this transformation (3aa, 3ab). In addition to cyclic-group-masked aryl diazonium precursors, acyclic masking groups were compatible with this transformation (3ac3ak). Substrates bearing linear and branched alkyl groups afforded the desired products in good yields (3ac3ag). In addition, a substrate with one cyclohexyl ring on the nitrogen atom reacted smoothly as well (3ah). Notably, diverse reactive groups, such as benzyl (3ai), hydroxy (3aj), and allyl (3ak), were tolerated in this reaction. When the masking group was changed to sp2 substitution, the desired product 4aa was not afforded, probably because of conjugation effects between the π electrons on the phenyl group and the lone electron pair on the nitrogen atom of the aryl triazene, which greatly reduced the reactivity (3al, 3am). Interestingly, a -CH2CH2-linked triazene dimer also produced the corresponding product in 79% yield with a lower substrate loading (3an).

Table 2 Substrate Scope of N-Substituted 4-Methyl Phenyltriazenesa

Substrate

R

Yieldb (%)

Substrate

R

Yieldb (%)

3aa

87

3ab

81

3ac

81

3ad

78

3ae

86

3af

57

3ag

70

3ah

71

3ai

82

3aj

68

3ak

73

3al

trace

3am

ND

3anc

79

a Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), 3aa3am (0.3 mmol), LAIL4 (20 mol%), and MeCN (2 mL) in a Schlenk tube under air at 90 °C for 14 h.

b Yield of isolated product.

c Reaction performed with 3an (0.15 mmol).

We next focused our attention on exploring the scope of the reaction with respect to the aryl triazenes (Scheme [2]). Unsubstituted 1-phenyltriazene produced the target product in 83% yield (4ab). Gratifyingly, when aryl triazenes with electron-donating substituents in the para-position of the benzene ring, such as alkyl, alkoxy, phenoxy, benzyl and phenyl, were treated under the optimized conditions, the transformation proceeded smoothly to provide the required products 4ac4aj in good yields. A halogen-substituted aryl triazene was also tolerated to furnish the desired product 4ak in moderate yield. It is regrettable that the introduction of an electron-withdrawing group (CF3) led to failure produce product 4al. Methyl substituents in the meta- and ortho-positions of the phenyl group appear to have no effect on the reaction (4am, 4ao). It is worth mentioning that the substrate containing a sulfur atom as a methylthio group reacted well to produce 4an; sulfur atoms usually poison metal catalysts. Most importantly, polysubstituted substrates, such as multimethyl- and multimethoxy-substituted aryl triazenes also showed good reactivity (4ap4as). However, the presence of a highly sterically hindered substrate significantly decreased the yield (4at). After systematically investigating the substrate scope of the aryl triazenes, we then extended this protocol to various substituted naphthol and phenol compounds by using 3aa as the model substrate. The results showed that both halogen-substituted naphthols (in 4ba, 4ca) and 2,7-naphthelendiol (in 4da) could be flexibly coupled with the combination of 4-methyl-1-phenyltriazene and DABSO. However, 1-naphthol seems to not be compatible with this transformation; only trace product is detected (4ea). Furthermore, simple phenol was also tolerated, and the required product was furnished in 36% yield after isolation (4fa). However, when polyphenols were employed as substrates, such as hydroquinone and resorcinol, only trace products were detected (4ga, 4ha).

Zoom Image
Scheme 2 Substrate scope of LAIL-catalyzed arylsulfonation reaction. a Reaction conditions: 1 (0.2 mmol), 2a (0.24 mmol), 3 (0.3 mmol), LAIL4 (20 mol%), and MeCN (2 mL) in a Schlenk tube under air at 90 °C for 14 h.

To showcase the utility and applicability of our method, a gram-scale reaction of 2-naphthol (1a), DABSO (2a), and (E)-1-(p-tolyldiazenyl)pyrrolidine (3aa) was carried out under modified reaction conditions. As presented in Scheme [3], 4aa was obtained smoothly in good yield when the reaction time was prolonged to 19 h.

Zoom Image
Scheme 3 Scaling up of 1-tosylnaphthalen-2-ol (4aa) synthesis

To probe the reaction mechanism, several control experiments were carried out. When radical inhibitors, such as TEMPO (2,2,6,6-tetramethyl-piperinedinyloxy), 1,1-diphenylethylene, or BHT (butylated hydroxytoluene), were added to the reaction system, the yield of product 4aa significantly decreased (Table [3]). These results strongly suggest that the LAIL-catalyzed N2 extrusion/SO2 insertion sequence of aryl triazenes proceeds by a radical pathway. To verify the real catalytic intermediate of this reaction, control experiments were carried out. When iron(III) chloride was used as a catalyst independently to replace LAIL4 under the standard conditions, 1-tosylnaphthalen-2-ol (4aa) was observed in 64% yield (Scheme [4a]), which confirmed that FeCl3 acts as an active catalytic species in this reaction. Furthermore, by using NHC-Fe(III) complex as a catalyst under the standard conditions, only trace desired product was obtained; the side product (E)-1-(p-tolyldiazenyl)naphthalen-2-ol (5a) was afforded in 51% yield, indicating that NHC-Fe(III) was not formed as the real catalyst in the reaction process (Scheme [4b]).

Table 3 Radical Capture Experiments

Entry

Radical inhibitor

Dosage

Yield (%)

1

TEMPO

1 equiv

trace

2

BHT

2 equiv

30

3

1,1-diphenylethylene

2 equiv

34

a Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), 3aa (0.3 mmol), LAIL4 (20 mol%), radical inhibitor, and MeCN (2 mL) in a Schlenk tube under air at 90 °C for 14 h.

Zoom Image
Scheme 4 Control experiments

Based on the relevant literature reports[10] [11] and the control experiments, a plausible reaction mechanism is proposed in Scheme [5]. The aryl triazene is activated by LAIL4 to form Lewis acid–base complex A, following which aryl diazonium salt B is produced in situ. Next, aryl sulfonyl radical D is formed by the reaction of intermediate B with DABSO with the release of N2 and formation of complex C. Meanwhile, 2-naphthoxy radical G is generated by the single-electron transfer oxidation of naphthol coupled with the release of secondary amine in the presence of complex E.[12] The reduced Fe2+ ionic liquid F is reoxidized to regenerate LAIL4 by complex C. In addition, 2-naphthoxy radical G can tautomerize to radical H, which couples with aryl sulfonyl radical D to give intermediate I. Finally, target product 4 is obtained by aromatization of I.

Zoom Image
Scheme 5 Plausible mechanism

In summary, we have developed a bifunctional LAIL-catalyzed multicomponent arylsulfonation reaction of phenols with aryl triazenes and DABSO via an N2 extrusion/SO2 insertion sequence. The reaction does not require additional promoter and ligand, and various diaryl sulfones were obtained in good yields. A gram-scale reaction and good substrate tolerance has further demonstrated the potential synthetic utility of this protocol. This approach affords an alternative route for the synthesis of aryl sulfonyl compounds under safer and easier handling conditions.

Unless otherwise noted, all reagents and solvents were purchased from commercial sources (Adamas-beta, Energy Chemical) and used without further purification. 1H and 13C NMR spectra were collected on 400 MHz NMR spectrometers (Varian Inova-400). High-resolution mass spectra (HRMS) were recorded on a Thermo Fisher Scientific QExactive spectrometer. Melting points were recorded on a Büchi (M-560) instrument.


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Synthesis of Aryltriazenes; General Procedure

A solution of aryl amine (20 mmol) in concentrated HCl (4 mL) was cooled in an ice bath while a solution of NaNO2 (20 mmol) in water (5 mL) was added dropwise. The resulting solution of the diazonium salt was stirred in an ice bath for 10 min and then added all at once to a chilled solution of secondary amine (22 mmol) in 1 M KOH (20 mL). The reaction mixture was stirred for 30 min in an ice bath, and the resulting precipitate was isolated by filtration. The damp solid was recrystallized from EtOH or by column chromatography to obtain the desired product.


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Synthesis of LAILs; General Procedure

The ionic liquid was prepared by addition of FeCl3 (0.01 mol) to a solution of 1,3-dialkyl imidazolium chloride (0.01 mol) in EtOH (20 mL). The mixture was then stirred and heated to reflux while the brown ionic liquid was formed. The volatiles were removed and dried under reduced pressure to obtain the desired product.


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Synthesis of NHC-Fe(III) Complex

2,6-Bis(3-methylimidazolium-1-yl)pyridine dibromide were prepared by mixing 1-methylimidazole (106.9 mmol) and 2,6-dibromopyridine (26.7 mmol) in a Schlenk tube and then heating the mixture at 150 °C for 3 h.[13] The off-white solid was collected by filtration, washed with CH2Cl2 (10 mL × 3) and Et2O (10 mL × 3), and dried in vacuo (5.2 g, 81%). The transition-metal complex was prepared by treatment of 2,6-bis(3-methylimidazolium-1-yl)pyridine dibromide (0.46 mmol) and tBuOK (1.5 mmol) in THF solution (3 mL). After 10 min, FeCl3 (0.46 mmol) was added to the mixture and stirred for 1 h, then the resulting chocolate-colored precipitate was collected by filtration. The NHC-Fe(III) complex was obtained after washing with THF (3 × 2 mL) and dried in vacuo (0.12 g, 65%).[14]


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1-Tosylnaphthalen-2-ol (4aa); Typical Procedure for the Synthesis of Diaryl Sulfones

A mixture of LAIL4 (0.04 mmol), 2-naphthol (1a; 0.20 mmol), DABSO (2a; 0.24 mmol), (E)-1-(p-tolyldiazenyl)pyrrolidine (3aa; 0.30 mmol), and MeCN (2 mL) were added to a 10 mL Schlenk tube, and the reaction mixture was stirred at 90 °C for 14 h. When the reaction was complete, the resulting mixture was washed with brine (5 mL) and extracted with EtOAc (3 × 5 mL). The combined organic phases were dried over anhydrous MgSO4 and filtered, and then all volatiles were evaporated under reduced pressure. The resultant residue was purified by silica gel column chromatography (PE/EtOAc = 70:1–50:1, v/v) to afford the desired product 4aa in 87% yield.


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1-Tosylnaphthalen-2-ol (4aa); Gram-Scale Reaction

Ionic liquids LAIL4 (1.2 mmol, 0.06 g), 2-naphthol (6.0 mmol, 0.86 g), DABSO (7.2 mmol, 1.73 g), (E)-1-(p-tolyldiazenyl)pyrrolidine (9.0 mmol, 1.70 g), and MeCN (60 mL) were added to a 100 mL Schlenk flask. The reaction mixture was stirred at 90 °C for 19 h. After completion of the reaction, the resulting mixture was washed with brine (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic phases were dried over anhydrous MgSO4 and filtered, and then all volatiles were evaporated under reduced pressure. The resultant residue was purified by silica gel column chromatography (PE/EtOAc = 70:1–50:1, v/v) to afford the desired product 4aa in 81% yield (1.44 g).


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1-Tosylnaphthalen-2-ol (4aa)

52.1 mg, 87% yield; white solid; mp 130–132 °C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.35 (d, J = 8.7 Hz, 1 H), 7.92 (d, J = 9.1 Hz, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.71 (dd, J = 7.9, 0.7 Hz, 1 H), 7.46 (ddd, J = 8.6, 7.0, 1.4 Hz, 1 H), 7.36–7.30 (m, 1 H), 7.28–7.25 (m, 2 H), 7.18 (d, J = 9.1 Hz, 1 H), 2.36 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.68, 144.57, 139.13, 137.33, 129.81, 129.46, 129.03, 128.71, 128.66, 126.56, 124.27, 122.96, 120.14, 112.11, 21.55.

HRMS (ESI): m/z calcd for C17H13O3S [M – H]: 297.0580; found: 297.0594.


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1-(Phenylsulfonyl)naphthalen-2-ol (4ab)

47.2 mg, 83% yield; orange solid; mp 130–131 °C.

1H NMR (400 MHz, CDCl3): δ = 11.12 (s, 1 H), 8.33 (dd, J = 8.7, 0.6 Hz, 1 H), 8.00–7.90 (m, 3 H), 7.72 (dd, J = 8.1, 0.9 Hz, 1 H), 7.58–7.53 (m, 1 H), 7.50–7.47 (m, 3 H), 7.34 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H), 7.19 (d, J = 9.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 158.91, 142.01, 137.55, 133.53, 129.45, 129.21, 129.07, 128.75, 128.71, 126.47, 124.35, 122.90, 120.13, 111.67.


#

1-((4-Ethylphenyl)sulfonyl)naphthalen-2-ol (4ac)

47.6 mg, 76% yield; red solid; mp 75–77 °C.

1H NMR (400 MHz, CDCl3): δ = 11.16 (s, 1 H), 8.38 (d, J = 8.7 Hz, 1 H), 7.92 (d, J = 9.1 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 7.9 Hz, 1 H), 7.47 (ddd, J = 8.6, 7.0, 1.4 Hz, 1 H), 7.34 (ddd, J = 8.0, 7.1, 1.0 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 2 H), 7.19 (d, J = 9.0 Hz, 1 H), 2.65 (q, J = 7.6 Hz, 2 H), 1.20 (t, J = 7.6 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.63, 150.64, 139.16, 137.34, 129.42, 129.02, 128.66, 126.61, 124.26, 122.94, 120.10, 112.06, 109.39, 28.75, 14.87.

HRMS (ESI): m/z calcd for C18H15O3S [M – H]: 311.0736; found: 311.0751.


#

1-((4-Isopropylphenyl)sulfonyl)naphthalen-2-ol (4ad)

51.4 mg, 79% yield; orange solid; mp 138–140 °C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.38 (d, J = 8.7 Hz, 1 H), 7.93 (d, J = 9.1 Hz, 1 H), 7.88 (d, J = 8.2 Hz, 2 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.51–7.44 (m, 1 H), 7.34 (dd, J = 12.6, 7.9 Hz, 3 H), 7.19 (d, J = 9.0 Hz, 1 H), 2.98–2.85 (m, 1 H), 1.22 (s, 3 H), 1.20 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.66, 155.19, 139.32, 137.32, 129.50, 129.02, 128.70, 128.67, 127.32, 126.65, 124.25, 123.02, 120.13, 112.14, 34.12, 23.45.


#

1-((4-(tert-Butyl)phenyl)sulfonyl)naphthalen-2-ol (4ae)

53.1 mg, 78% yield; orange solid; mp 186–187 °C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.41 (ddd, J = 8.8, 1.6, 0.7 Hz, 1 H), 7.93 (d, J = 9.0 Hz, 1 H), 7.91–7.86 (m, 2 H), 7.73 (dd, J = 8.0, 1.4 Hz, 1 H), 7.51–7.46 (m, 3 H), 7.35 (ddd, J = 8.0, 7.0, 1.1 Hz, 1 H), 7.19 (d, J = 9.0 Hz, 1 H), 1.28 (s, 9 H).

13C NMR (100 MHz, CDCl3): δ = 158.69, 157.48, 138.99, 137.33, 129.55, 129.03, 128.72, 128.70, 126.37, 126.25, 124.26, 123.08, 120.16, 112.16, 35.18, 30.92.


#

1-((4-Methoxyphenyl)sulfonyl)naphthalen-2-ol (4af)

44.8 mg, 71% yield; yellow solid; mp 115–117 °C.

1H NMR (400 MHz, CDCl3): δ = 11.16 (s, 1 H), 8.37 (d, J = 8.7 Hz, 1 H), 7.90 (dd, J = 8.9, 4.5 Hz, 3 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 7.17 (d, J = 9.0 Hz, 1 H), 6.92 (d, J = 8.9 Hz, 2 H), 3.80 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.50, 158.42, 137.19, 133.58, 129.37, 129.04, 128.81, 128.72, 128.63, 124.24, 122.93, 120.14, 114.37, 112.51, 55.60.


#

1-((4-Ethoxyphenyl)sulfonyl)naphthalen-2-ol (4ag)

54.5 mg, 83% yield; yellow solid; mp 128–130 °C.

1H NMR (400 MHz, CDCl3): δ = 11.17 (s, 1 H), 8.38 (d, J = 8.7 Hz, 1 H), 7.94–7.85 (m, 3 H), 7.70 (d, J = 8.1 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.17 (d, J = 9.0 Hz, 1 H), 6.89 (d, J = 8.7 Hz, 2 H), 4.00 (q, J = 7.0 Hz, 2 H), 1.38 (t, J = 7.0 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.93, 158.37, 137.13, 133.26, 129.36, 129.01, 128.76, 128.70, 128.58, 124.21, 122.92, 120.11, 114.73, 112.56, 63.99, 14.45.

HRMS (ESI): m/z calcd for C18H15O4S [M – H]: 327.0686; found: 327.0699.


#

1-((4-Phenoxyphenyl)sulfonyl)naphthalen-2-ol (4ah)

40.0 mg, 56% yield; yellow oil.

1H NMR (400 MHz, CDCl3): δ = 11.11 (s, 1 H), 8.38 (d, J = 8.7 Hz, 1 H), 7.89–7.94 (m, 3 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.49 (t, J = 8.5 Hz 1 H), 7.37 (q, J = 7.6 Hz, 3 H), 7.22 (d, J = 7.6 Hz, 1 H), 7.18 (d, J = 9.1 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H).

13C NMR (100 MHz, CDCl3): δ = 162.36, 158.59, 154.64, 137.37, 135.34, 130.18, 129.42, 129.12, 129.11, 128.88, 128.76, 125.19, 124.33, 122.94, 120.47, 120.18, 117.43, 112.24.

HRMS (ESI): m/z calcd for C22H15O4S [M – H]: 375.0686; found: 375.0698.


#

1-((4-Benzylphenyl)sulfonyl)naphthalen-2-ol (4ai)

53.1 mg, 71% yield; yellow solid; mp 103–105 °C.

1H NMR (400 MHz, CDCl3): δ = 11.14 (s, 1 H), 8.38 (dd, J = 8.7, 0.6 Hz, 1 H), 7.93 (d, J = 9.0 Hz, 1 H), 7.90–7.86 (m, 2 H), 7.75–7.70 (m, 1 H), 7.48 (ddd, J = 8.6, 7.0, 1.4 Hz, 1 H), 7.35 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H), 7.31–7.27 (m, 4 H), 7.23 (dt, J = 5.0, 2.1 Hz, 1 H), 7.19 (d, J = 9.0 Hz, 1 H), 7.14–7.08 (m, 2 H), 3.99 (s, 2 H).

13C NMR (100 MHz, CDCl3): δ = 158.72, 147.54, 139.75, 139.07, 137.40, 129.58, 129.47, 129.04, 128.94, 128.71, 128.67, 126.71, 126.60, 124.29, 122.95, 120.11, 111.96, 41.65.

HRMS (ESI): m/z calcd for C23H17O3S [M – H]: 373.0893; found: 373.0907.


#

1-([1,1′-Biphenyl]-4-ylsulfonyl)naphthalen-2-ol (4aj)

50.2 mg, 70% yield; orange solid; mp 136–138 °C.

1H NMR (400 MHz, CDCl3): δ = 11.16 (s, 1 H), 8.42 (d, J = 8.8 Hz, 1 H), 8.02 (d, J = 7.7 Hz, 2 H), 7.95 (d, J = 9.1 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.67 (d, J = 7.8 Hz, 2 H), 7.53–7.50 (m, 3 H), 7.46–7.34 (m, 4 H), 7.22 (d, J = 9.0 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 158.86, 146.49, 140.51, 138.92, 137.53, 129.49, 129.11, 129.01, 128.80, 128.75, 128.62, 127.81, 127.26, 127.04, 124.37, 122.97, 120.19, 111.92.

HRMS (ESI): m/z calcd for C22H15O3S [M – H]: 359.0736; found: 359.0752.


#

1-((4-Chlorophenyl)sulfonyl)naphthalen-2-ol (4ak)

32.2 mg, 50% yield; yellow solid; mp 111–113 °C.

1H NMR (400 MHz, CDCl3): δ = 11.02 (s, 1 H), 8.29 (d, J = 8.7 Hz, 1 H), 7.95 (d, J = 9.1 Hz, 1 H), 7.89 (d, J = 8.3 Hz, 2 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.36 (t, J = 7.5 Hz, 1 H), 7.19 (d, J = 9.1 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 159.00, 140.49, 140.18, 137.84, 129.57, 129.30, 129.23, 128.96, 128.76, 127.99, 124.52, 122.71, 120.17, 111.31.


#

1-(m-Tolylsulfonyl)naphthalen-2-ol (4am)

43.1 mg, 72% yield; pink solid; mp 128–129 °C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.34 (d, J = 8.7 Hz, 1 H), 7.93 (d, J = 9.1 Hz, 1 H), 7.77–7.71 (m, 3 H), 7.49–7.45 (m, 1 H), 7.40–7.31 (m, 3 H), 7.19 (d, J = 9.0 Hz, 1 H), 2.37 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.84, 141.88, 139.58, 137.44, 134.42, 129.49, 129.04, 129.01, 128.72, 128.69, 126.66, 124.31, 123.67, 122.96, 120.15, 111.80, 21.35.

HRMS (ESI): m/z calcd for C17H14O3SNa [M + Na]+: 321.0561; found: 321.0552.


#

1-((3-(Methylthio)phenyl)sulfonyl)naphthalen-2-ol (4an)

36.0 mg, 54% yield; red solid; mp 119–121°C.

1H NMR (400 MHz, CDCl3): δ = 11.06 (s, 1 H), 8.34 (dd, J = 8.7, 0.7 Hz, 1 H), 7.95 (d, J = 9.0 Hz, 1 H), 7.80 (t, J = 1.7 Hz, 1 H), 7.73 (dd, J = 8.3, 1.0 Hz, 1 H), 7.64 (dt, J = 6.9, 1.9 Hz, 1 H), 7.49 (ddd, J = 8.6, 7.0, 1.4 Hz, 1 H), 7.38–7.33 (m, 3 H), 7.20 (d, J = 9.1 Hz, 1 H), 2.48 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.98, 142.65, 141.27, 137.70, 130.89, 129.42, 129.13, 128.85, 128.72, 124.43, 123.08, 122.86, 122.61, 120.13, 15.37.

HRMS (ESI): m/z calcd for C17H13O3S2 [M – H]: 329.0301; found: 329.0308.


#

1-(o-Tolylsulfonyl)naphthalen-2-ol (4ao)

42.3 mg, 71% yield; red solid; mp 131–133 °C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.32 (dd, J = 7.5, 1.9 Hz, 1 H), 8.11 (d, J = 8.7 Hz, 1 H), 7.95 (d, J = 9.0 Hz, 1 H), 7.74–7.70 (m, 1 H), 7.47–7.42 (m, 2 H), 7.42–7.38 (m, 1 H), 7.34–7.30 (m, 1 H), 7.20 (s, 1 H), 7.18 (s, 1 H), 2.37 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 159.31, 139.98, 137.94, 137.48, 133.63, 132.96, 129.17, 129.01, 128.75, 128.63, 128.55, 126.31, 124.30, 122.86, 120.11, 111.26, 19.07.

HRMS (ESI): m/z calcd for C17H15O3S [M + H]+: 299.0742; found: 299.0732.


#

1-((3,4-Dimethylphenyl)sulfonyl)naphthalen-2-ol (4ap)

50.8 mg, 81% yield; yellow solid; mp 148–149 °C.

1H NMR (400 MHz, CDCl3): δ = 11.18 (s, 1 H), 8.36 (d, J = 8.7 Hz, 1 H), 7.91 (d, J = 9.1 Hz, 1 H), 7.74–7.67 (m, 3 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 7.18 (d, J = 9.0 Hz, 1 H), 2.26 (s, 3 H), 2.25 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.62, 143.38, 139.22, 138.10, 137.24, 130.20, 129.48, 129.00, 128.71, 128.60, 127.16, 124.23, 124.11, 123.01, 120.14, 112.18, 19.93, 19.84.

HRMS (ESI): m/z calcd for C18H17O3S [M + H]+: 313.0898; found: 313.0889.


#

1-((3,5-Dimethylphenyl)sulfonyl)naphthalen-2-ol (4aq)

48.6 mg, 78% yield; yellow solid; mp 148–150 °C.

1H NMR (400 MHz, CDCl3): δ = 11.17 (s, 1 H), 8.35 (d, J = 8.7 Hz, 1 H), 7.93 (d, J = 9.0 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.56 (s, 2 H), 7.48 (t, J = 7.8 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 7.19 (d, J = 9.0 Hz, 1 H), 7.15 (s, 1 H), 2.33 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 158.78, 141.78, 139.31, 137.33, 135.36, 129.54, 129.00, 128.72, 128.62, 124.26, 123.91, 123.02, 120.15, 111.93, 21.21.

HRMS (ESI): m/z calcd for C18H15O3S [M – H]: 311.0736; found: 311.0750.


#

1-((3,4-Dimethoxyphenyl)sulfonyl)naphthalen-2-ol (4ar)

54.4 mg, 79% yield; yellow solid; mp 140–142 °C.

1H NMR (400 MHz, CDCl3): δ = 11.14 (s, 1 H), 8.39 (d, J = 8.7 Hz, 1 H), 7.90 (d, J = 9.0 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.54 (dd, J = 8.5, 2.2 Hz, 1 H), 7.50–7.43 (m, 1 H), 7.41 (d, J = 2.2 Hz, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.17 (d, J = 9.0 Hz, 1 H), 6.86 (d, J = 8.6 Hz, 1 H), 3.88 (s, 3 H), 3.86 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.43, 153.20, 149.13, 137.22, 133.62, 129.38, 129.03, 128.70, 128.57, 124.25, 122.92, 120.77, 120.08, 112.33, 110.57, 108.72, 56.18, 56.10.

HRMS (ESI): m/z calcd for C18H15O5S [M – H]: 343.0635; found: 343.0649.


#

1-((3,4,5-Trimethoxyphenyl)sulfonyl)naphthalen-2-ol (4as)

44.3 mg, 59% yield; orange solid; mp 153–155 °C.

1H NMR (400 MHz, CDCl3): δ = 11.07 (s, 1 H), 8.40 (d, J = 8.7 Hz, 1 H), 7.94 (d, J = 9.0 Hz, 1 H), 7.74 (d, J = 8.1 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.37 (t, J = 7.5 Hz, 1 H), 7.19 (d, J = 9.1 Hz, 1 H), 7.16 (s, 2 H), 3.85 (s, 9 H).

13C NMR (100 MHz, CDCl3): δ = 158.69, 153.38, 142.37, 137.49, 136.59, 129.51, 129.14, 128.79, 128.72, 124.42, 122.98, 120.15, 111.97, 103.92, 60.90, 56.47.

HRMS (ESI): m/z calcd for C19H17O6S [M – H]: 373.0740; found: 373.0753.


#

1-((2,6-Dimethylphenyl)sulfonyl)naphthalen-2-ol (4at)

23.3 mg, 37% yield; yellow solid; mp 139–140 °C.

1H NMR (400 MHz, CDCl3): δ = 11.11 (s, 1 H), 7.93 (d, J = 9.1 Hz, 1 H), 7.76–7.70 (m, 2 H), 7.36–7.27 (m, 3 H), 7.16 (d, J = 9.1 Hz, 1 H), 7.12 (d, J = 7.7 Hz, 2 H), 2.61 (s, 6 H).

13C NMR (100 MHz, CDCl3): δ = 158.17, 139.17, 138.94, 136.91, 132.80, 131.86, 129.25, 128.99, 128.55, 128.33, 124.19, 121.94, 120.15, 114.63, 21.97.

HRMS (ESI): m/z calcd for C18H15O3S [M – H]: 311.0736; found: 311.0751.


#

6-Bromo-1-tosylnaphthalen-2-ol (4ba)

60.1 mg, 80% yield; orange solid; mp 137–139°C.

1H NMR (400 MHz, CDCl3): δ = 11.15 (s, 1 H), 8.30 (d, J = 9.2 Hz, 1 H), 7.90 (s, 1 H), 7.87 (d, J = 8.5 Hz, 3 H), 7.57 (d, J = 9.2 Hz, 1 H), 7.33 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 9.1 Hz, 1 H), 2.42 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 158.70, 144.89, 138.83, 136.15, 131.73, 130.90, 129.99, 129.92, 128.06, 126.53, 124.71, 121.45, 118.15, 112.56, 21.56.


#

7-Bromo-1-tosylnaphthalen-2-ol (4ca)

37.8 mg, 50% yield; clear orange solid; mp 177–178°C.

1H NMR (400 MHz, CDCl3): δ = 11.16 (s, 1 H), 8.57 (d, J = 1.3 Hz, 1 H), 7.88–7.81 (m, 3 H), 7.56 (d, J = 8.6 Hz, 1 H), 7.42 (dd, J = 8.6, 1.8 Hz, 1 H), 7.30 (d, J = 8.5 Hz, 2 H), 7.17 (d, J = 9.0 Hz, 1 H), 2.39 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 159.14, 144.98, 138.77, 136.94, 130.65, 130.34, 129.96, 127.80, 127.19, 126.69, 125.60, 123.60, 120.64, 111.89, 21.58.


#

1-Tosylnaphthalene-2,7-diol (4da)

56.5 mg, 90% yield; orange solid; mp 187–188 °C.

1H NMR (400 MHz, CDCl3): δ = 11.05 (s, 1 H), 7.87–7.79 (m, 4 H), 7.59 (d, J = 8.8 Hz, 1 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.01 (d, J = 9.0 Hz, 1 H), 6.93 (dd, J = 8.7, 2.3 Hz, 1 H), 6.41 (s, 1 H), 2.31 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 159.35, 156.39, 144.73, 138.66, 137.30, 131.23, 131.13, 129.86, 126.49, 123.79, 117.19, 115.61, 110.54, 106.44, 21.51.

HRMS (ESI): m/z calcd for C17H15O4S [M + H]+: 315.0691; found: 315.0689.


#

4-Tosylphenol (4fa)

17.9 mg, 36% yield; orange oil.

1H NMR (400 MHz, CDCl3): δ = 7.81–7.71 (m, 4 H), 7.30–7.25 (m, 2 H), 6.94–6.87 (m, 2 H), 6.60 (br, 1 H), 2.39 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 160.32, 143.94, 139.01, 132.84, 129.87, 127.26, 116.09, 21.52.


#
#

Conflict of Interest

The authors declare no conflict of interest.

Supporting Information


Corresponding Authors

Yonghong Zhang
Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University
Urumqi 830017, Xinjiang
P. R. of China   

Chenjiang Liu
Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University
Urumqi 830017
P. R. China   

Publication History

Received: 21 April 2022

Accepted after revision: 08 June 2022

Accepted Manuscript online:
08 June 2022

Article published online:
26 July 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


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Figure 1 Representative drugs and biologically active molecules containing diaryl sulfone fragments
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Scheme 1 General approach for the synthesis of aryl sulfones
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Scheme 2 Substrate scope of LAIL-catalyzed arylsulfonation reaction. a Reaction conditions: 1 (0.2 mmol), 2a (0.24 mmol), 3 (0.3 mmol), LAIL4 (20 mol%), and MeCN (2 mL) in a Schlenk tube under air at 90 °C for 14 h.
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Scheme 3 Scaling up of 1-tosylnaphthalen-2-ol (4aa) synthesis
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Scheme 4 Control experiments
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Scheme 5 Plausible mechanism