Diethyl Ethoxymagnesiomalonate1

[35227-78-2]  · C9H16MgO5  · Diethyl Ethoxymagnesiomalonate  · (MW 228.53)

(synthesis of acyl malonates1 or methyl ketones2)

Preparative Methods: prepared from Diethyl Malonate, Magnesium, ethanol, and a catalytic amount of CCl4, as described in several procedures.1,2a

Handling, Storage, and Precautions: typically prepared and used immediately as a solution in solvents such as ether or benzene. The reagent is moisture sensitive; best yields are obtained when the reagent is used under anhydrous conditions.

Use in Synthesis.

Diethyl ethoxymagnesiomalonate (1) can be acylated with many activated carboxylic acid derivatives and alkyl chloroformates. It is soluble in aprotic solvents such as ether and benzene, and undergoes exclusive C-acylation.3 A number of acylmalonates have been prepared from (1) including tris(ethoxycarbonyl)methane,1a diethyl benzoylmalonate,1b diethyl phenylacetylmalonate,1c and diethyl cyclopropylmalonate.1d

Several hydroxycoumarin analogs have been prepared by the addition of (1) to salicylic acid derivatives (eq 1).4 A similar protocol has been utilized in the preparation of hydroxybutenolides.5

Methyl ketones can be conveniently obtained from the acylmalonate intermediate following a more vigorous hydrolysis (eq 2).2b Substituted acetophenones have also been prepared in this manner.2

Methanetricarboxylic esters are generally prepared by the reaction of (1) with an alkyl chloroformate.6 Thus Triethyl Methanetricarboxylate is obtained in high yield from (1) and Ethyl Chloroformate (eq 3).1a

The magnesium enolate of diethyl malonate can also be generated and acylated with acid chlorides under milder conditions in a single step. Complexation of the malonate with MgCl2 increases the acidity to a degree such that tertiary amines can be employed for deprotonation.7 A number of acylmalonates can be conveniently prepared (eq 4), with optimal yields obtained using Triethylamine (2 equiv).

Other workers have extended this procedure to an efficient preparation of methyl ketones following bis-dealkoxycarbonylation of the intermediate acylmalonate.8 The Michael addition of diethyl malonate to a,b-unsaturated ketones and aldehydes under these conditions has also been examined (eq 5).9 Magnesium Oxide is also an effective base for the acylation of diethyl malonate, generating acyl malonates in moderate yields.10

Related Reagents.

Bis(trimethylsilyl) Malonate; Diethyl Malonate; Ethyl 3,3-Diethoxyacrylate; Ethyl Trimethylsilyl Malonate; Magnesium Ethyl Malonate; Magnesium Methoxide; Malonic Acid; Triethyl Methanetricarboxylate.

1. (a) Lund, H.; Voigt, A. OSC 1943, 2, 594. (b) Price, J. A.; Tarbell, D. S. OSC 1963, 4, 285. (c) Meyer, K.; Bloch, H. S. OSC 1955, 3, 637. (d) Hormi, O. OS 1987, 66, 173.
2. (a) Reynolds, G. A.; Hauser, C. R. OSC 1963, 4, 708. (b) Ghatak, U. R.; Sanyal, B.; Ghosh, S.; Sarkar, M.; Raju, M. S.; Wenkert, E. JOC 1980, 45, 1081. (c) Chatterjea, J. N.; Sahai, R.; Swaroopa, B. B.; Bhakta, C.; Jha, H. C.; Zilliken, F. CB 1980, 113, 3656. (d) Kruger, G.; Keck, J.; Noll, K.; Pieper, H. AF 1984, 34, 1612. (e) Dasgupta, R.; Kanjilal, P. R.; Patra, S. K.; Sarkar, M.; Ghatak, U. R. T 1985, 41, 5619. (f) McKinnon, D. M.; Abouzeid, A. JHC 1991, 28, 347. (g) Singh, B. JHC 1991, 28, 881.
3. For a review of methods used to control C vs. O-acylation, see: Black, T. H. OPP 1989, 21, 179.
4. Obaseki, A. O.; Steffen, J. E.; Porter, W. R. JHC 1985, 22, 529.
5. Hormi, O. E. O.; Peltonen, C.; Heikkila, L. JOC 1990, 55, 2513.
6. For a review of the synthesis and reactions of methanetricarboxylic esters, see: Newkome, G. R.; Baker, G. R. OPP 1986, 18, 117.
7. Rathke, M. W.; Cowan, P. J. JOC 1985, 50, 2622.
8. (a) Kuo, D. L. T 1992, 48, 9233. (b) Yamazaki, T.; Matoba, K.; Itooka, T.; Chintani, M.; Momose, T.; Muraoka, O. CPB 1987, 35, 3453.
9. Prasad, C. S. N.; Adapa, S. R. IJC(B) 1991, 30B, 347.
10. Skarzewski, J. T 1989, 45, 4593.

Gary L. Bolton

Parke-Davis/Warner-Lambert Company, Ann Arbor, MI, USA

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