[4704-77-2]  · C3H7BrO2  · 3-Bromo-1,2-propanediol  · (MW 154.99)

(carbonyl protecting group which can be cleaved under neutral conditions2)

Physical Data: bp 92-94 °C/1.5 mmHg; d 1.769 g cm-3.

Form Supplied in: widely available as 95% or 98% pure; viscous colorless liquid.

Preparative Method: prepared according to the procedure of Winstein and Goodman.4 Epibromohydrin (1) is treated with a catalytic amount of p-toluenesulfonic acid in H2O at refluxing temperature for 7 h (eq 1). Distillation of the final product gives a 65% yield of the desired diol (2).

Handling, Storage, and Precautions: harmful liquid and fumes (CO, CO2, HBr); incompatible with strong oxidizing agents; corrosive; irritant; use in fume hood only; refrigerate.3

Synthetic Utility.

The transformation of aldehydes and ketones to cyclic acetals is a commonly used method for the protection of the carbonyl functional group. The cleavage of these acetal protecting groups is usually accomplished with acidic media, rendering acid incompatible functional groups unsuitable for schemes employing such deprotection steps. The development of 3-bromo-1,2-propanediol as a protecting group for carbonyls stemmed from the need for a protecting group which could be removed under neutral conditions in high yields. 4-t-Butylcyclohexanone (3) in the presence of bromoglycol (2) and catalytic p-Toluenesulfonic Acid in refluxing benzene gives 98% of acetal (4) (eq 2). Deprotection of the bromomethylethylene acetal (4) is accomplished by treating it with Zinc dust in refluxing methanol for 12 h to afford 89% of 4-t-butylcyclohexanone (3) (eq 2).2

Under acidic conditions, a,b-saturated ketones can be selectively protected in the presence of their a,b-unsaturated counterparts. For example, exposure of enedione (5) to 3-bromo-1,2-propanediol and p-toluenesulfonic acid in refluxing benzene gives a mixture of isomeric acetals (6a and 6b) and the monoprotected compound (7). Treatment of this mixture with p-toluenesulfonic acid and acetone gives pure (7) in 74% overall yield (eq 3).5

Formation of this acetal has also been used to shift the double bond of an a,b-unsaturated enone. For example, treatment of enone (8) with 3-bromo-1,2-propanediol under standard conditions gives a mixture of acetals (9 and 10) (eq 4). The mixture of isomers can be deprotected without separation with zinc in refluxing methanol for 18 h. Enone (11) is isolated in 37% yield after chromatographic separation of the alkenic isomers.6

Stability of the Acetal.

The bromomethylethylene acetal moiety is stable to a variety of reagents that react with carbonyl groups. For example, treatment of acetal (4) with m-Chloroperbenzoic Acid, Ammonia, Sodium Borohydride, Methyllithium, or Chromium(VI) Oxide gives a quantitative recovery of the starting material.2 On the other hand, while there are many hydroxy, amino, and carbonyl protecting groups that are stable to the reductive conditions employed to remove this protecting group,2,7 the b-halo ethers (12 and 13) are incompatible with such conditions.

1. (a) Meskens, F. A. J. S 1981, 501. (b) Showler, A. J.; Darley, P. A. CRV 1967, 67, 427.
2. Corey, E. J.; Ruden, R. A. JOC 1973, 38, 834.
3. Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, 1988; Vol. 1, p 572B.
4. Winstein, S.; Goodman, L. JACS 1954, 76, 4368.
5. Liu, H-J.; Dieck-Abularach, T. H 1987, 25, 245.
6. Yamakawa, K.; Tominaga, T.; Nishitani, K. TL 1975, 4137.
7. Greene, T.; Wuts, P. G. M. In Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991.

Michael A. Walters & Hélène R. Arcand

Dartmouth College, Hanover, NH, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.