Ethyl Pyruvate Diethyl Acetal

(R1 = R2 = Et)

[7476-20-2]  · C9H18O4  · Ethyl Pyruvate Diethyl Acetal  · (MW 190.27) (R1 = R2 = Me)

[10076-48-9]  · C6H12O4  · Methyl Pyruvate Dimethyl Acetal  · (MW 148.18) (R12 = CH2CH2, R2 = Et)

[56624-93-2]  · C7H12O4  · Ethyl Pyruvate Ethylene Acetal  · (MW 160.19)

(reactions with nucleophiles give various a-difunctional products;1-8 useful reagents for synthesis of heterocyclic compounds;8-10 several interesting results are obtained through transacetalizations3,11-13)

Alternate Name: ethyl 2,2-diethoxypropanoate.

Physical Data: R1 = R2 = Et, bp 70-71 °C/10 mmHg; R1 = R2 = Me, bp 58-60 °C/13 mmHg; R12 = CH2CH2, R2 = Et, bp 70-76 °C/8 mmHg.

Preparative Methods: by acetalization of ethyl or methyl pyruvates (ROH, HC(OR)3, HCl or TsOH or H2SO4; HOCH2CH2OH, TsOH, C6H6, Dean Stark).

Handling, Storage, and Precautions: should be stored at low temperature.

Reactions with Nucleophiles.

Reaction with organomagnesium compounds in HMPA leads to enolates of a-dicarbonyl compound monoacetals and then to a-keto acetals by hydrolysis. Therefore reactions require two molar equivalents of organomagnesium compounds (eq 1).1 In several cases, an alcohol from ketone reduction is also formed; therefore the yield of the keto acetal is improved by oxidation of the crude product (eq 2).1 Reduction of ethyl 2,2-diethoxypropanoate followed by oxidation of the resulting alcohol gives pyruvaldehyde diethyl acetal (eq 3).1,2 Reactions with ketone,3 ester,4 and amide5 enolates lead to Claisen condensation products (eq 4).4 The nitromethane dianion (eq 5),6 the lithium derivative of 1,3-dithiane,7 and ammonia8 also give substitution products.

Synthesis of Heterocyclic Compounds.

Several syntheses of heterocyclic compounds using these reagents have been described.8-10 For instance, 1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanone has been prepared from 2,2-diethoxypropanamide (eq 6).8


Claisen rearrangement of the diallyl acetal obtained from methyl 2,2-dimethoxypropanoate gives the g,d-unsaturated-a-keto ester, methyl 2-oxo-5-hexenoate, in good yield (eq 7).11 Its preparation is thus possible on a large scale. The corresponding dibenzyl acetal is prepared by a similar way and leads to the benzyl alcohol elimination product in the presence of P2O5/DMF.12,13 Intramolecular acetalization occurs after reaction of methyl 2,2-dimethoxypropanoate with the 2-methyl-1,3-cyclohexanedione dianion (eq 8).3

Alcohol Elimination.

In many preparative experiments, elimination of alcohol in acidic medium has been encountered.12-15 Such an elimination product led to 2-methoxyacrylic acid (eq 9),15 an intermediate for synthesis of the ergot alkaloids and related structures.

Related Reagents.

Ethyl Diethoxyacetate; Glyoxal Diethyl Acetal; Pyruvaldehyde Diethyl Acetal.

1. Huet, F.; Pellet, M.; Lechevallier, A.; Conia, J. M. JCR(S) 1982, 246; JCR(M) 1982, 2528.
2. Bernard, D.; Doutheau, A.; Gore, J. T 1987, 43, 2721 (CA 1988, 108, 130 669j).
3. Kelly, T. R.; Behforouz, M.; Echavarren, A.; Vaya, J. TL 1983, 24, 2331.
4. Cameron, A. G.; Hewson, A. T.; Osammor, M. I. TL 1984, 25, 2267.
5. Kawashima, Y.; Sato, M.; Hatada, Y.; Goto, J.; Nakashima, Y.; Hatayama, K.; Shibuya, S. CPB 1990, 38, 393.
6. Carr, K.; Greener, N. A.; Mullah, K. B.; Somerville, F. M.; Sutherland, J. K. JCS(P1) 1992, 1975.
7. Cameron, A. G.; Hewson, A. T. JCS(P1) 1983, 2979.
8. La Mattina, J. L.; Mularski, C. J. JOC 1984, 49, 4800.
9. Adachi, J.; Sato, N. JHC 1986, 23, 871.
10. Coppola, G. M.; Damon, R. E. JHC 1990, 27, 815.
11. Berryhill, S. R.; Price, T.; Rosenblum, M. JOC 1983, 48, 158.
12. Esswein, A.; Betz, R.; Schmidt, R. R. HCA 1989, 72, 213.
13. Pallenberg, A. J.; White, J. D. TL 1986, 27, 559.
14. Wenkert, E.; Alonso, M. E.; Buckwalter, B. L.; Sanchez, E. L. JACS 1983, 105, 2021.
15. Bowman, R. E. JCS(P1) 1982, 1897.

François Huet

University of Le Mans, France

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