Ethyl Diethoxyacetate

(R = Et)

[6065-82-3]  · C8H16O4  · Ethyl Diethoxyacetate  · (MW 176.24) (R = Me)

[89-91-8]  · C5H10O4  · Methyl Dimethoxyacetate  · (MW 134.15)

(lithium derivatives act as nucleophiles;1-9 useful reagents for synthesis of heterocyclic compounds1,3,10)

Alternate Name: ethyl glyoxylate diethyl acetal.

Physical Data: R = Et, bp 86-88 °C/16 mmHg; d 0.985 g cm-3. R = Me, bp 67 °C/18 mmHg; d 1.096 g cm-3.

Handling, Storage, and Precautions: these liquid compounds are moisture sensitive. They should be stored at low temperature.

Reaction of Lithium Derivatives.

A key step in a high yield total synthesis of (±)-4-isoavenaciolide is the conjugate addition of the lithium derivative of ethyl diethoxyacetate to a butenolide (eq 1).1 Conjugate addition also occurs with 3-methoxy-2-cyclohexenone2 and phenyl vinyl sulfoxide (eq 2).3 However, reactions with a,b-enones mainly give the 1,2-addition products in many cases; exclusive conjugate addition is observed in the case of a 16-methylene-17-oxo steroid for steric reasons.4 Obviously reactions with saturated ketones give the expected 1,2-adducts.5,6

Alkylation with alkyl halides gives acetals of a-keto esters (eq 3).7,8 The same reaction with 7-iodoheptanoic acid gives an intermediate for prostaglandins synthesis.9

Synthesis of Heterocyclic Compounds.

Alkyl dialkoxyacetates are widely used in heterocyclic chemistry.1,3,10 For instance, reaction of a lithium derivative with an a-iminocarbonyl compound gives the carbonyl addition product, precursor of 4-benzoyl-b-lactams (eq 4).10a

Substitution of a methoxy group of the acetal function of methyl dimethoxyacetate by a bromine using Triphenylphosphine Dibromide leads to an interesting reagent for synthesis of tetrahydroisoquinolines.10b Synthesis of 1H-1,2,4-triazole-3,5-dicarbaldehyde occurs according to eq 5.10c

Reactions with Nucleophiles.

Tertiary alcohols are obtained by reactions with Ethynylmagnesium Bromide10d and with Trimethylsilylmethylmagnesium Chloride and Cerium(III) Chloride.5 These alcohols are intermediates in syntheses of tin heterocycles10d and of 2-methylene-3-trimethylsilylpropionaldehyde (eq 6),5 respectively. An organodimagnesium compound leads to the cyclic product (eq 7).11

Ester10f,12 or ketone10e enolates are also effective as nucleophiles in Claisen reactions. A similar result is obtained from dimsylsodium (eq 8).13 However, ammonia gives an amide which leads to an interesting intermediate for synthesis of a polyheterocyclic antibiotic.10g

Preparation of Thioacetals.

Thioacetals are obtained by reaction with thiols10i or dithiols14 which leads to a convenient synthesis of a-keto esters (eq 9).14

Reaction of Ylides.

Reaction with phosphonium ylides leads to other ylides which react with aldehydes and yield a,b-unsaturated carbonyl compounds (eq 10).15

Formation of the Deacetalization Product.

Reactions with glyoxylic acid monohydrate lead to mixtures of hemiacetal and of alkyl glyoxylate hydrate. Dehydrations provide ethyl or methyl glyoxylate in a convenient way.16

Related Reagents.

1,2-Diethoxy-1,2-bis(trimethylsilyloxy)ethylene; Ethyl 3,3-Diethoxypropanoate; Glyoxylic Acid Diethyl Dithioacetal; Methyl Glyoxylate.

1. Damon, R. E.; Schlessinger, R. H. TL 1975, 4551.
2. Flores-Parra, A.; Khuong-Huu, F. T 1986, 42, 5925 (CA 1987, 107, 197 884y).
3. Stevens, R. V.; Polniaszek, R. P. T 1983, 39, 743.
4. Neef, G.; Eder, U. TL 1977, 2825.
5. Lee, T. V.; Channon, J. A.; Cregg, C.; Porter, J. R.; Roden, F. S.; Yeoh, H. T.-L. T 1989, 45, 5877.
6. Coldham, I.; Warren, S. JCS(P1) 1992, 2303.
7. Huet, F.; Pellet, M.; Conia, J. M. S 1979, 33.
8. Cameron, A. G.; Hewson, A. T.; Osammor, M. I. TL 1984, 25, 2267.
9. Cameron, A. G.; Hewson, A. T.; Wadworth, A. H. JCS(P1) 1984, 2337.
10. Examples: (a) Alcaide, B.; Rodriguez-Lopez, J.; Monge, A.; Pérez-Garcia, V. T 1990, 46, 6799. (b) Cheung, G. K.; Earle, M. J.; Fairhurst, R. A.; Heaney, H.; Shumaibar, K. F.; Eyley, S. C.; Ince, F. SL 1991, 721. (c) De Mendoza, J.; Ontaria, J. M.; Ortega, M. C.; Torres, T. S 1992, 398. (d) Mäerkl, G.; Kneidl, F. AG(E) 1974, 13, 667. (e) Pehr, H.; Manninger, G.; Severin, T. Carbohydr. Res. 1978, 64, 1 (CA 1978, 89, 197 825q). (f) Taylor, E. C.; Dumas, D. J. JOC 1980, 45, 2485. (g) Inami, K.; Shiba, T. BCJ 1985, 58, 352. (h) Schregenberger, C.; Seebach, D. LA 1986, 2081 (CA 1987, 106, 49 829y). (i) Amat, M.; Linares, A.; Bosh, J. JOC 1990, 55, 6299.
11. Canonne, P.; Belley, M.; Fytas, G.; Plamondon, J. CJC 1988, 66, 168 (CA 1988, 109, 169 887z).
12. Bisagni, E.; Marquet, J. P.; André-Louisfert, J. BSF(2) 1968, 637 (CA 1968, 69, 59 024p).
13. Balsevitch, J. CJC 1983, 61, 1053.
14. Eliel, E. L.; Hartmann, A. A. JOC 1972, 37, 505.
15. Le Corre, M. BSF(2) 1974, 1951 (CA 1975, 82, 140 260c). Le Corre, M. BSF(2) 1974, 2005 (CA 1975, 83, 9090a).
16. Hook, J. M. SC 1984, 14, 83.

François Huet

University of Le Mans, France

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