Chemical Properties
Ethyl trimethylsilylacetate is a clear colorless liquid. It is stable to the usual manipulations, and can be stored in glass containers for years without change of physical and spectral properties.
Uses
Ethyl trimethylsilylacetate is used in the synthesis of ethyl-2,2-dibromo-2-(trimethylsilyl)acetate and α,β-unsaturated esters. It was also used to silylate the enolizable aldehydes and ketones.
Uses
(silylating agent; source of an ethyl acetate anion equivalent.Ethyl trimethylsilylacetate is reactive to nucleophiles and readily undergoes desilylation reactions with acid or alkali,ethanol, and bromine.
Preparation
ethyl trimethylsilylacetate synthesis: Available by a Reformatsky reaction from ethyl bromoacetate, and by reaction of trimethylsilylmethylmagnesium chloride with ethyl chloroformate. An alternative approach requires the treatment of ethyl acetate with triphenylmethylsodium followed by chlorotrimethylsilane The use of a nitrogen base with ethyl acetate in THF followed by reaction with chlorotrimethylsilane results in a mixture of C- and O-silylation. The use of HMPA as additive in the reaction medium increases the amount of O-silylation to 90%. Similar methods can be used to prepare analogs.
General Description
Reaction of ethyl trimethylsilylacetate (ETSA) with dilute hydrochloric acid, dilute alkali, anhydrous HCl, anhydrous bromine and absolute ethanol has been reported. ETSA undergoes condensation with aromatic aldehydes in the presence of base catalyst to yield β-trimethylsiloxycarboxylates. Lithium ETSA reacts with ketones to yield α,β-unsaturated esters.
Synthesis
Zinc powder (9.92 g, 152 mmol) and copper(I) chloride (1.50 g, 15.2 mmol) were added to 15 mL of dry benzene under nitrogen protection, stirred and refluxed for 30 min. Subsequently, trimethylchlorosilane (12.8 mL, 101 mmol) and ethyl bromoacetate (12.3 mL, 111 mmol) dissolved in a mixture of 23 mL of anhydrous tetrahydrofuran and 21 mL of anhydrous benzene were slowly added through a dropping funnel, maintaining a mild reflux condition. The titration process took about 1 hour. After dropwise addition, reflux was continued for 1 hour, followed by cooling in an ice bath. Under stirring, 30 mL of 5% aqueous hydrochloric acid solution was added through a dropping funnel in 10 minutes. The liquid layer was separated and the reaction flask was washed with ether. The organic phase was combined and washed sequentially with saturated sodium bicarbonate solution twice, saturated sodium chloride solution twice, then saturated sodium bicarbonate solution twice, and finally saturated sodium chloride solution twice. The combined organic layers were dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the crude product. Purification by reduced pressure distillation (boiling point 93-94 °C, 104 mmHg) gave ethyl 2-(trimethylsilyl)acetate as a pale yellow liquid in 74% yield (12.0 g, 74.9 mmol).1H NMR (CDCl3) δ 4.09 (q, J = 7.1 Hz, 2H), 1.89 (s, 2H), 1.24 (t, J = 7.1 Hz. 3H), 0.12 (s, 9H).
Purification Methods
Purify it by distilling ca 10g of reagent through a 15cm, Vigreux column (p 11) and then redistilling it through a 21cm glass helices-packed column [Hauze & Hauser J Am Chem Soc 75 994 1953]. Alternatively, dissolve it in Et2O, wash with H2O, dilute Na2CO3, dry over Na2CO3, evaporate Et2O, and distil it through a column of 15 theoretical plates. [Gold et al. J Am Chem Soc 70 2874 1948, Beilstein 4 IV 3974.]
References
[1] Chemistry Letters, 2017, vol. 46, # 2, p. 228 - 231
