[24057-28-1] · C12H13NO3S · Pyridinium p-Toluenesulfonate · (MW 251.33)
(used as an acid catalyst for the protection and deprotection of alcohols and acetals)
Alternate Name: PPTS.
Solubility: sol benzene, toluene, dichloromethane, chloroform, ethanol, and acetone.
Form Supplied in: white, moisture-sensitive crystalline solid.
Handling, Storage, and Precautions: the title reagent is moisture sensitive, requiring storage under nitrogen in a desiccator over a suitable drying agent. Stored in this manner, the reagent has an excellent shelf life. Irritant; handle with gloves.
PPTS (1) is a weakly acidic salt frequently used in catalytic quantity for the protection of alcohols as tetrahydropyranyl (eq 1)1 and trimethylsilyl ethers (eq 2).3
PPTS is particularly favored for use with acid-sensitive functionalities such as allylic alcohols, epoxides, and acetals. N-Tosyl-L-norephedrine has been converted to its oxazolidine using a catalytic amount of (1) (25 mol%) and Triethyl Orthoformate (eq 3).3
p-Methoxyphenol has been protected as its THP ether (80% yield) using 4 equiv of (1).4 All these reactions are run in dry aprotic solvent (benzene, toluene, or dichloromethane) and water formed during the course of the reaction is removed by azeotropic distillation or by 4 Å molecular sieves. Yields are good to excellent.
A catalytic quantity of (1) (30 mol %) in ethanol selectively cleaves t-butyldimethylsilyl ethers in the presence of t-butyldiphenylsilyl ethers (eq 4).5
PPTS is an excellent catalyst for the preparation of 1,3-dioxolane acetals from ketones and ethanediol (90-95% yield).6 The weak acidic nature of (1) makes it ideal for acid-sensitive compounds.
The reaction is carried out using 10-30 mol % of (1) in refluxing benzene, accompanied by the azeotropic removal of water (Dean-Stark apparatus). Similar conditions have been used for the preparation of acetals using (R,R)-hydrobenzoin and a tricyclic benzaldehyde derivative.7
PPTS is a versatile catalyst for the deprotection of acid-sensitive acetal protecting groups. For example, 10-30 mol % of (1) efficiently cleaves tetrahydropyran ethers (THP) (eq 6),1 1,3-dioxolanes (eq 7),6 methoxymethyl ethers (MOM), and methoxyethoxymethyl ethers (MEM) (eq 8).8
PPTS catalyzes the isomerization of allenyl ethers to 1-alkyl-2-methoxybutadienes. Freshly prepared crude allenyl ethers are treated with (1) (1 mol %) in dichloromethane at room temperature (eq 9).9
PPTS converts 5-acetoxy-4,5-dihydrofurans to the corresponding furans (eq 10).10 The reaction is carried out in refluxing toluene for 3-6 h. Yields are poor to modest.
Reaction of a-sulfinylhydrazones with alcohols in the presence of (1) (10-30 mol %) results in a-oxy substituted hydrazines (eq 11).11
Adam A. Galan
Parke Davis Pharmaceutical Research Division, Ann Arbor, MI, USA