2,4,6-Collidinium p-Toluenesulfonate

[59229-09-3]  · C15H19NO3S  · 2,4,6-Collidinium p-Toluenesulfonate  · (MW 293.39)

(acid catalyst in acetalization,1,2 transacetalization,7 macrolactonization,8 and conversion of enynones to phenols9)

Physical Data: mp 130-132 °C.

Solubility: sol benzene, toluene, dichloromethane, chloroform, ethanol, acetone.

Form Supplied in: white, moisture-sensitive, crystalline solid. Commercially available.

Preparative Method: can be prepared by the slow addition of p-Toluenesulfonic Acid in methanol to a rapidly stirred solution of 2,4,6-Collidine in diethyl ether, at 20 °C. Cooling to 0 °C results in crystallization of the title reagent.

Purification: recrystallization from acetone.

Handling, Storage, and Precautions: store in desiccator under nitrogen. Very good shelf life at room temperature when kept dry. Irritant; handle with gloves.

Acid-Catalyzed Selective Acetalization.

Collidinium p-toluenesulfonate (1) is a weakly acidic salt that catalyzes selective acetalization of a,b-unsaturated ketones in the presence of saturated ketones (eq 1). Using Ethylene Glycol in the presence of (1) results in the isomerization of the enone double bond and acetalization of the carbonyl.1

A recent improvement uses (1) to form a mixture of acetal isomers (eq 2) which undergo isomerization in the presence of (1) to give the thermodynamically more stable acetal (eq 3).2

The title reagent has been used in the acetalization of a steroidal ketone with ethylene glycol in the presence of an acid sensitive epoxide functionality (eq 4).3

Acetalization of ketones (e.g. cyclohexanone) with the optically active diols (2) (eq 5)4 and (3) (eq 6)5 has been achieved using (1) in refluxing benzene, accompanied by the azeotropic removal of water. Use of toluene reduces the reaction time with no loss of yield.6

Transacetalization of Dioxolane Protecting Groups.

A stoichiometric amount of (1) in refluxing acetone-water (120 h) leads to the deprotection of an acetal (eq 7), maintaining the integrity of an acid-sensitive TBS ether and the oxetane ring (84% yield).7

Acid-Catalyzed Macrolactonization.

The title reagent effects the intramolecular macrolactonization of hydroxy triamides, resulting in 8- and 10-membered lactones (eq 8).8 The reaction is achieved by the syringe pump addition of a triamide solution in benzene to a refluxing solution of (1) under high dilution.

Acid-Catalyzed Cyclization of Enynones to Phenols.

The title reagent catalyzes the cyclization of enynones to phenols (eq 9).9 The reaction is carried out at 250 °C to give yields of 30-89%.

1. Nitz, T. J.; Paquette, L. A. TL 1984, 25, 3047.
2. Smith, A. B., III; Leenay, T. L. JACS 1989, 111, 5761.
3. Bischofberger, N.; Walker, K. A. M. JOC 1985, 50, 3604.
4. Sugimara, T.; Yoshikawa, M.; Futagawaja, T.; Tai, T. T 1990, 46, 5955.
5. Sugimara, T.; Futagawa, T.; Yoshikawa, M.; Tai, A. TL 1989, 30, 3807.
6. Underiner, T. L.; Paquette, L. A. JOC 1992, 57, 5438.
7. Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.; Danishefsky, S. J. JOC 1992, 57, 3274.
8. Wasserman, H. H.; DeSimone, R. W.; Ho, W.-B.; McCarthy, K. E.; Prowse, K. S.; Spada, A. P. TL 1992, 33, 7207.
9. Jacobi, P. A.; Kravitz, J. I. TL 1988, 29, 6873.

Adam A. Galan

Geron Corporation, Menlo Park, CA, USA

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