Facile synthesis of arylsulfonates from phenol derivatives and sulfonyl chlorides

Abstract

The CO bond of phenol can be activated by reaction with arylsulfonyl chlorides to yield the corresponding arylsulfonates that can be used as electrophilic partners in subsequent reactions. Arylsulfonates can be conveniently synthesized from inexpensive phenol derivatives and sulfonyl chlorides. Moreover, their crystalline nature makes arylsulfonates easier than other electrophiles to purify and store over a long period of time. Although arylsulfonates are inferior to triflates in terms of electrophilicity, triflates are better leaving groups compared to sulfonates; arylsulfonates however have greater economical advantages over triflates. Facile synthesis of different arylsulfonates from various arylsulfonyl chlorides and phenol are reported. What is unique about the synthesis is that very good to excellent yields of arylsulfonates were obtained without the use of column chromatography. A more efficient purification technique was developed based on recrystallization. Using 2,4-dinitrophenyl 4-methylbenzenesulfonate and various amines, initial experiments have shown greater regioselectivity for the S N Ar products.

Comparison of Various Tosylating Reagents for the Synthesis of Mono-2-O-tosyl-β-cyclodextrin

“…Mp 96.1-96.6 °C (Lit. 30 97-98 °C); R f = 0.39 (n-hexane/AcOEt, 4:1). 1 H NMR (600 MHz, CDCl 3 , Figure S5):  = 8.…”

“…3-Nitrophenyl 4-toluenesulfonate was obtained based on a literature procedure. 30 To 3-nitrophenol (421 mg, 3.03 mmol) dissolved in anhydrous CH 2 Cl 2 (2 mL), pyridine (488 μL, 6.06 mmol) was added and the mixture was cooled in an ice bath at 0 °C. A solution of 4-toluenesulfonyl chloride (578 mg, 3.03 mmol) in CH 2 Cl 2 (1 mL) was added dropwise during 1 h. The mixture was stirred at 0 °C for 30 min and then at rt for 2 h. After reaction completion, the mixture was diluted with CH 2 Cl 2 (4 mL).…”

“…4-Nitrophenyl 4-toluenesulfonate was obtained based on a modified literature procedure. 30 To 4-nitrophenol (134.7 mg, 0.97 mmol) dissolved in anhydrous CH 2 Cl 2 (0.9 mL), pyridine (156.0 μL, 1.94 mmol) was added and the mixture was cooled in an ice bath at 0 °C. 4-Toluenesulfonyl chloride (184.6 mg, 0.97 mmol) was added portionwise during 30 min.…”

“…Mp 80.4-81 °C (Lit. 30 79-82 °C); R f = 0.28 (n-hexane/AcOEt, 4:1). 1 H NMR (600 MHz, CDCl 3 , Figure S1):  = 7.90 (dd, 3 J 34 = 8.1 Hz, 4 J 35 = 1.7 Hz, 1 H, H 3 ), 7.77 (m, 2 H, H 8 ), 7.62 (ddd, 3 J 56 = 8.3 Hz, 3 J 45 = 7.5 Hz, 4 J 35 = 1.7 Hz, 1 H, H 5 ), 7.47 (dd, 4 J 46 = 1.3 Hz, 3 J 56 = 8.3 Hz, 1 H, H 6 ), 7.42 (ddd, 3 J 34 = 8.1 Hz, 3 J 45 = 7.5 Hz, 4 J 46 = 1.3 Hz, 1 H, H 4 ), 7.35 (m, 2 H, H 9 ), 2.47 (s, 3 H, H 11 ).…”

“…Mp 108.2-110.8 °C (Lit. 30 109-110 °C); R f = 0.37 (n-hexane/AcOEt, 4:1). 1 H NMR (600 MHz, CDCl 3 , Figure S3):  = 8.14 (dd, 4 J 24 = 1.0 Hz, 3 J 45 = 8.2 Hz, 4 J 46 = 1.2 Hz, 1 H, H 4 ), 7.80 (t, 4 J 24 = 1.0 Hz, 4 J 26 = 1.8 Hz, 1 H, H 2 ), 7.74 (d, 3 J 89 = 8.1 Hz, 2 H, H 8 ), 7.52 (t, 3 J 45 = 3 J 56 = 8.2 Hz, 1 H, H 5 ), 7.43 (dd, 3 J 46 = 1.2 Hz, J 56 = 8.2 Hz, 1 H, H 6 ), 7.36 (d, 3 J 89 = 8.1 Hz, 2 H, H 9 ), 2.47 (s, 3 H, H 11 ).…”