2-Butanone Ethylene Acetal

[126-39-6]  · C6H12O2  · 2-Butanone Ethylene Acetal  · (MW 116.16)

(reagent for production of cyclic acetals by acid-catalyzed transacetalization1)

Alternate Names: 2-methyl-2-ethyldioxolane; MED.

Physical Data: bp 116-117 °C; d 0.929 g cm-3.

Solubility: miscible with organic solvents.

Form Supplied in: colorless liquid.

Handling, Storage, and Precautions: the reagent is a flammable liquid; it is an irritant.


The reagent (MED) has been employed for the syntheses of cyclic acetals from ketones as an alternative to ethylene glycol.1 In the initial report of the reagent, superior selectivity in acetal formation over that observed with Ethylene Glycol was noted.1 MED also has been reported to be superior to the analogous transacetalization reagent prepared from acetone (2,2-dimethyl-1,3-dioxolane).1 The transacetalization reactions appear to be more subject to steric effects than to electronic effects.

Several general methods initially reported1 have been used extensively. In a typical application, MED is employed in large excess, often as the solvent, although cosolvents such as benzene and CH2Cl2 have been employed. In some cases, acetalization reactions have been conducted with excess MED and a small amount of ethylene glycol. In cases where monoacetalization of a di- or polyketone is desired, a stoichiometric amount of MED may be employed, but monoacetalizations of diketones are usually conducted with excess MED. Reactions are generally run at reflux for several hours with p-Toluenesulfonic Acid (TsOH) as the catalyst. Hindered ketones have been acetalized employing MED as solvent at reflux for several days,1 but some transacetalization reactions have been conducted over extended periods at rt.

The selectivity of transacetalizations with MED has been studied. Simple saturated ketones are acetalized more readily than a,b-unsaturated ketones.1 Thus the Wieland-Mischer ketone reacts with MED to give the monoacetal shown in eq 1 in 95% yield with 2% of the diacetal;2 when the reaction was conducted with ethylene glycol, the monoacetal was produced in 78% yield, the diacetal was formed in 10% yield, and 12% of unreacted diketone remained. The enhanced reactivity of MED with simple ketones over that observed with a,b-unsaturated ketones can be used in a chemical separation scheme; for example, reaction of a 1:1 mixture of the saturated and unsaturated ketones shown in eq 2 with 0.5 equiv of MED in benzene at reflux with TsOH catalysis resulted in the acetal of the saturated ketone and unreacted unsaturated ketone as the only products observed.3

Steric and ring strain effects can overwhelm electronic effects in transacetalizations with MED. Thus a mixture of monoacetals was produced from the diketone shown in eq 3,4 and transacetalization of D4-androstene-3,17-dione with MED gave the monoacetal shown in eq 4.1 The double bond migrations shown in these reactions are common for transacetalizations of a,b-unsaturated ketones with MED as they also are in ethylene glycol acetalizations. The product composition reflects the stability of the double bonds; for example, an equilibrium mixture of acetals was obtained from 2-cyclohexenone (eq 5).5 An advantage of MED transacetalization of a,b-unsaturated ketones over direct ethylene glycol acetalization is seen in the 2-cyclohexenone reaction; when the acetalization was conducted with ethylene glycol, the mixture of unsaturated acetals was obtained with the ether product as a minor impurity.5

Monoacetalization of a 1,3-dione proceeds in good yields, as shown in eq 6.6 In this reaction an eightfold excess of MED was used in CH2Cl2 solvent with 10-Camphorsulfonic Acid as the catalyst.

The transacetalization reactions with MED appear to provide kinetic products as demonstrated in the transacetalization of D4-androstene-3,16,17-trione (eq 7).7 Reaction in the presence of excess MED with TsOH catalysis at reflux for 5 min gave monoacetal (1) in 66% yield. Slow distillation of the reaction mixture over 30 min gave (1),(2), and (3) in 7%, 30%, and 13% yields, respectively. Heating the reaction mixture at reflux for 5 h gave triacetal (3) in 43% yield.

1. Dauben, H. J., Jr.; Löken, B.; Ringold, H. J. JACS 1954, 76, 1359.
2. Bosch, M. P.; Camps, F.; Coll, J.; Guerrero, A.; Tatsuoka, T.; Meinwald, J. JOC 1986, 51, 773.
3. Meyer, W. L.; Goodwin, T. E.; Hoff, R. J.; Sigel, C. W. JOC 1977, 42, 2761.
4. Bauduin, G.; Pietrasanta, Y.; Pucci, B. TL 1975, 2889.
5. Hoye, T. R.; Kurth, M. J. TL 1983, 24, 4769.
6. Kametani, T.; Matsumoto, H.; Honda, T. T 1981, 37, 2555.
7. Rosenkrantz, G.; Velasco, M.; Sondheimer, F. JACS 1954, 76, 5024.

Martin Newcomb

Wayne State University, Detroit, MI, USA

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