[126-30-7]  · C5H12O2  · 2,2-Dimethyl-1,3-propanediol  · (MW 104.17)

(protecting group for aldehydes and ketones;9 a ligand used in boron chemistry12)

Physical Data: mp 123-127 °C.1

Solubility: sol H2O, chloroform, benzene; very sol ethyl alcohol, diethyl ether.2

Form Supplied in: white crystals.

Handling, Storage, and Precautions: skin irritant; hygroscopic; store in cool dry place.1

Cyclic Acetals.

2,2-Dimethyl-1,3-propanediol (1) has been used effectively as a protecting group for ketones and aldehydes. The formation of the cyclic acetal can be accomplished in many ways. The most common is to reflux the ketone and diol (1) with a catalytic amount of acid and force the reaction to completion by removing H2O, usually with a Dean-Stark trap (eq 1).3 Other methods involve treating the ketone-diol mixture with Chlorotrimethylsilane (eq 2)4 or Boron Trifluoride Etherate (eq 3).5

The advantages of diol (1) compared to other diols depend on the compound being protected. In the formation of b-halo acetals, for example, reagent (1) was found to be more effective than Ethylene Glycol because of easier separation and a longer shelf life of the product.6 Diol (1) was also considered to be superior to ethylene glycol when Grignard reagents were prepared from b-halo acetals (eq 4).7

In comparing rates of acid hydrolysis of different cyclic acetals formed from a variety of diols, the following order was discovered; 1,3-propanediol >> (1) > ethylene glycol > 2,2-diethyl-1,3-propanediol > 2,2-diisopropyl-1,3-propanediol.8 This has been attributed to the gem-dialkyl effect which serves to stabilize the cyclic acetal. Cleavage of the protecting group formed from diol (1) is easily accomplished via acidic hydrolysis using acids such as H2SO4, HCl, or TsOH.

Reagent (1) has been used in a variety of syntheses where its merits have not been elucidated. The following reactions show some of these transformations (eqs 5-7).9-11

Use as a Boron Ligand.

This diol has been used to complex boron.12 For example, diol (1) was employed to remove the phenylboronic acid template from a Diels-Alder adduct under neutral conditions (eq 8).13

Related Reagents.

3-Bromo-1,2-propanediol; 2,3-Butanediol; Ethylene Glycol; (2R,4R)-2,4-Pentanediol; 1,3-Propanediol.

1. Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, WI, 1988; Vol. 1, p 1411B.
2. CRC Handbook of Data on Organic Compounds, 2nd ed.; Weast, R. C.; Grasselli, J. G.; Eds.; CRC: Boca Raton, FL, 1989; Vol. 6, p 3645.
3. Williams, D. R.; McGill, J. M. JOC 1990, 55, 3457.
4. Honda, Y.; Ori, A.; Tsuchihashi, G.-I. CL 1987, 1259.
5. (a) Gopalakrishnan, G.; Jayaraman, S.; Rajagopalan, K.; Swaminathan, S. S 1983, 797. (b) Brown, E.; Lebreton, J. TL 1986, 27, 2595.
6. Burnell, D. J.; Wu, Y.-J. CJC 1989, 67, 816.
7. Stowell, J. C.; Keith, D. R.; King, B. T. OSC 1990, 7, 59.
8. (a) Newman, M. S.; Harper, R. J., Jr. JACS 1958, 80, 6350. (b) Smith, S. W.; Newman, M. S. JACS 1968, 90, 1249. (c) Smith, S. W.; Newman, M. S. JACS 1968, 90, 1253.
9. (a) Deslongchamps, P.; Cheriyan, U. O.; Lambert, Y.; Mercier, J.-C.; Ruest, L.; Russo, R.; Soucy, P. CJC 1978, 56, 1687. (b) Carceller, E.; Moyano, A.; Serratosa, F.; Font-Altaba, M.; Solans, X. JCS(P1) 1986, 2055.
10. Annunziata, R.; Cinquini, M.; Cozzi, F.; Raimondi, L.; Restelli, A. HCA 1985, 68, 1217.
11. Walkup, R. D.; Obeyesekere, N. U. S 1987, 607.
12. Narasaka, K.; Yamamoto, I. T 1992, 48, 5743.
13. Narasaka, K.; Shimada, S.; Osoda, K.; Iwasawa, N. S 1991, 1171.

Michael A. Walters & John J. Shay

Dartmouth College, Hanover, NH, USA

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