APPLICATION
TCI Practical Example: Tosylation of Hydroxy Group Using TsCl
Used Chemicals
p-Toluenesulfonyl chloride (= TsCl) [T0272]
Diethylene Glycol Monobenzyl Ether [D3408]
Triethylamine [T0424]
4-Dimethylaminopyridine (= DMAP) [D1450]
Dichloromethane
Procedure
Triethylamine (1.23 mL, 7.64 mmol, 1.5 eq.), DMAP (23.1 mg, 0.19 mmol, 0.04 eq.), and TsCl (1.17 g, 6.11 mmol, 1.2 eq.) were added to a solution of diethylene glycol monobenzyl ether (1.00 g, 5.10 mmol) in dichloromethane (12.1 mL) at room temperature. The reaction mixture was stirred for overnight. The reaction mixture was quenched with 1 mol/L HCl (10 mL) and extracted with dichloromethane (3 x 10 mL). The organic layer washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane = 10:90 – 25:75 on silica gel), giving 1 as a colorless liquid (1.58 g, 89% yield).
Experimenter’s Comments
The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:1, Rf = 0.55).
Analytical Data
Tosylate 1
1H NMR (270 MHz, CDCl3); δ 7.80 (d, J = 8.4 Hz, 2H), 7.39-7.29 (m, 7H), 4.54 (s, 2H), 4.17 (t, J = 4.6 Hz, 2H), 3.70 (brt, J = 4.9 Hz, 2H), 3.62 (m, 2H), 3.56 (m, 2H), 2.43 (s, 3H).
Other Reference
A Synthesis of Acetamidines
J. R. Harjani, C. Liang, and P. G. Jessop, J. Org. Chem. 2011, 76, 1683.
Application
Stereocomplementary Enol Tosylation
Typical Procedure (Enol Tosylation of α-Formyl Esters) Method A: An α-formyl ester (1.00 mmol) in toluene (1 mL) and TsCl (228 mg, 1.20 mmol) in toluene (1 mL) are successively added dropwise to a stirred solution of N-methylimidazole (NMI) (99 mg, 1.20 mmol) and Et3N (121 mg, 1.20 mmol) in toluene (1 mL) at 0－5 °C under an Ar atmosphere, and the mixture is stirred at the same temperature for 1 h. Water is added to the mixture, which is extracted twice with AcOEt. The combined organic phase is washed with brine, dried (Na2SO4), and concentrated. The residue is purified by SiO2 column chromatography (hexane : AcOEt = 25 : 1－5 : 1) to give the desired (E)-enol tosylates. Method B: An α-formyl ester (1.00 mmol) in toluene (1 mL), TsCl (228 mg, 1.20 mmol) in toluene (1 mL), and NMI (99 mg, 1.20 mmol) are successively added dropwise to a stirred suspension of LiOH powder (anhydrous; 29 mg, 1.20 mmol) in toluene (1 mL) at 0－5 °C under an Ar atmosphere, and the mixture is stirred at the same temperature for 1 h. A workup similar to that of method A gives the desired (Z)-enol tosylates.
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