[107-46-0]  · C6H18OSi2  · Hexamethyldisiloxane  · (MW 162.42)

(silylating agent for carboxylic acids1,2 and alcohols;3 used in preparation of aroyl chlorides;4 precursor for a variety of trimethylsilyl derivatives5)

Alternate Names: bis(trimethylsilyl) ether; bis(trimethylsilyl) oxide.

Physical Data: mp -59 °C; bp 101 °C/760 mmHg; d 0.764 g cm-3.

Solubility: sol organic solvents such as toluene, chloroform.

Form Supplied in: colorless liquid; available in NMR (99.5%+) and technical (98 or 99%) grade; available in research and commercial quantities.

Analysis of Reagent Purity: 1H NMR 0.49 ppm; 13C NMR 1.94 ppm (in CDCl3).

Handling, Storage, and Precautions: skin irritant. Incompatible with strong acids, strong bases, and oxidizing agents. Use in a fume hood.

Silylation of Carboxylic Acids.

Alkanoic and aromatic carboxylic acids can be readily silylated with hexamethyldisiloxane.1 The reaction is carried out under acid catalysis (usually sulfuric acid) and azeotropic removal of water (eq 1). The rate of reaction is strongly influenced by the acidity of the carboxylic acid and increases with increased acidity. This method avoids the use of an amine and thus simplifies isolation of the product because it does not have to be separated from an amine hydrochloride. A limitation is the need for a solvent which allows for azeotropic removal of water.

An alternate silylation procedure employs Zinc Chloride as the catalyst and uses the carboxylic acid anhydride as starting material for the preparation of the silyl ester (eq 2).2 A limited number of examples (benzoic and acetic anhydrides) of this reaction have been published. Distillation is the preferred method for isolation of the product.

Silylation of Alcohols.

Pyridinium p-Toluenesulfonate can be used as the catalyst in the silylation of primary and secondary alcohols and phenols (eq 3).3 Even alcohols sensitive to acid-catalyzed rearrangements can be successfully silylated under these conditions. Continuous removal of the water generated during the reaction is necessary and is achieved via the use of a Soxhlet extractor filled with 4Å molecular sieves.

A special case for the preparation of a phenyl silyl ether involves ultrasound irradiation of benzenediazonium fluoroborate in the presence of hexamethyldisiloxane.6

Preparation of Aroyl Chlorides.

Substituted benzylidene chlorides (trichloromethylarenes) can be converted to the corresponding substituted benzoyl chlorides (aroyl chlorides) with hexamethyldisiloxane in the presence of a catalytic amount of Iron(III) Chloride (eq 4).4 These mild reaction conditions offer a distinct advantage over procedures which employ inorganic oxides and high temperatures to achieve the transformation.7

Preparation of Other Trimethylsilyl Derivatives.

Hexamethyldisiloxane has been used as an inexpensive starting material for the preparation of numerous synthetically useful trimethylsilyl derivatives. Examples include Fluorotrimethylsilane,5a,b Bromotrimethylsilane,5c and Iodotrimethylsilane,5d,e as well as polyphosphoric acid trimethylsilyl ester (PPSE).5f

Related Reagents.

N,O-Bis(trimethylsilyl)acetamide; N,N-Bis(trimethylsilyl)urea; Chlorotrimethylsilane; Hexamethyldisilazane; N-(Trimethylsilyl)imidazole.

1. Matsumoto, H.; Hoshino, Y.; Nakabayashi, J.; Nakano, T.; Nagai, Y. CL 1980, 1475.
2. Valade, M. J. CR 1958, 246, 952.
3. Pinnick, H. W.; Bal, B. S.; Lajis, N. H. TL 1978, 4261.
4. Nakano, T.; Ohkawa, K.; Matsumoto, H.; Nagai, Y. CC 1977, 808.
5. (a) Schmidt, M.; Schmidbaur, H. CB 1961, 94, 2446. (b) Pray, B. O.; Sommer, L. H.; Goldberg, G. M.; Kerr, G. T.; Di Giorgio, P. A.; Whitmore, F. C. JACS 1948, 70, 433. (c) Aizpurua, J. M.; Palomo, C. NJC 1984, 8, 51. (d) Jung, M. E.; Lyster, M. A. OSC 1988, 6, 353. (e) Voronkov, M. G.; Turkin, Y. A.; Mirskov, R. G.; Kuzimina, E. E.; Rakhlin, V. I. ZOB 1989, 59, 2641 (CA 1990, 112, 118 935t). (f) Yamamoto, K.; Watanabe, H. CL 1982, 1225.
6. Olah, G. A.; Wu, A. S 1991, 204.
7. (a) Schreyer, R. C. JACS 1958, 80, 3483. (b) Rondestvedt, C. S., Jr. JOC 1976, 41, 3569, 3574, 3577.

Joerg Pfeifer

Eli Lilly and Company, Lafayette, IN, USA

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