Ethyl Ethoxymethylenecyanoacetate

(R = Et)5

[94-05-3]  · C8H11NO3  · Ethyl Ethoxymethylenecyanoacetate  · (MW 169.20) (E)

[42466-67-1] (Z)

[42466-69-3] (R = Me)4,5

[13974-74-8]  · C6H7NO3  · Methyl Methoxymethylenecyanoacetate  · (MW 141.14) (E)

[55883-89-1] (Z)


(push-pull alkene;1 N-heterocycle synthesis; 1,3-dipolar cycloaddition;2 1,4-addition-elimination (AdN-E)3)

Physical Data: R = Et, mp 51-53 °C; bp 190-191 °C/30 mmHg; subl. 25 °C/0.02 mmHg. R = Me, mp 88 °C; bp 185 °C/25 mmHg.

Solubility: slightly sol water; sol ethanol, diethyl ether.

Form Supplied in: white solid; widely available.

Preparative Methods: can be prepared from Triethyl Orthoformate, Ethyl Cyanoacetate, and Acetic Anhydride in the presence of Zinc Chloride (catalyst).4

Purification: recrystallization from ethanol and sublimation.

Handling, Storage, and Precautions: use in a fume hood.

Ethyl ethoxymethylenecyanoacetate is a valuable reagent in the synthesis of N-heterocycles. Pyrimidines (eq 1),6 pyridines,7 pyrazoles,8 indolizines,9 quinolizones, and pyridones10 can be obtained. It is also used in the synthesis of pyrones (eq 2).11

The [3 + 2] cycloaddition of ethyl ethoxymethylenecyanoacetate with cyclopropenone acetals2a (see also Diethyl Ethoxymethylenemalonate and Diethyl Ethylidenemalonate), benzonitrilium isopropylide (eq 3)2d or diazo compounds2b,c,12 leads to cyclopentenones, pyrrolines, and pyrazolines, respectively. Benzonitrilium isopropylide is generated in situ from a photoinduced cleavage of the corresponding 2H-azirine (eq 3).

The ethoxy group of ethyl ethoxymethylenecyanoacetate can be substituted by various nucleophiles in an AdN-E mechanism. Malonates,3f enolates,3b,c,g quarternary salts of heterocyclic bases containing an active methylene group,3d amines,3a,e etc. were used as nucleophiles in this reaction.

Related Reagents.

Diethyl Ethoxymethylenemalonate; 3-Ethoxyacrolein; 3-Ethoxyacrylonitrile; Ethoxymethylenemalonitrile; Ethyl Cyanoacetate; Ethyl 3-Ethoxyacrylate; Ethyl Ethoxymethyleneacetoacetate.

1. Reviews on push-pull alkenes: (a) Sandstroem, J. Top. Stereochem. 1983, 14, 83. (b) Rudorf, W. D. Wiss. Z. Martin-Luther-Univ. Halle-Wittenberg Math. Naturwiss. Reihe 1983, 32, 57. (c) Kristen, H.; Peseke, K. Wiss. Z. Wilhelm-Pieck-Univ. Rostock Math. Naturwiss. Reihe 1976, 25, 1123.
2. (a) Tokuyama, H.; Isaka, M.; Nakamura, E. JACS 1992, 114, 5523. (b) Hamaguchi, M.; Nagai, T. CC 1987, 1299. (c) Abdallah, H; Grée, R.; Carrié, R. T 1985, 41, 4339. (d) Stegmann, W.; Gilgen, P.; Heimgartner, H.; Schmid, H. HCA 1976, 59, 1018.
3. (a) Al-Shaar, A. H. M.; Chambers, R. K.; Gilmour, D. W.; Lythgoe, D. J.; McClenaghan, I.; Ramsden, C. A. JCS(P1) 1992, 2789. (b) Mérour, J. Y.; Cossais, F. JHC 1991, 28, 1875. (c) Mérour, J. Y.; Piroëlle, S. JHC 1991, 28, 1869. (d) Kussler, M.; Balli, H. HCA 1987, 70, 1583. (e) Ilavský, D.; Bobošík, V.; Martvon, A. Chem. Pap. 1985, 39, 527. (f) Kakehi, A.; Ito, S.; Wada, B.; Watanabe, K.; Nishimura, K.; Kumagai, A. BCJ 1982, 55, 3590. (g) Baker, S. R.; Crombie, L.; Dove, R. V. JCS(P1) 1981, 165.
4. De Bellemont, G. E. BCF 1901, 25[3], 18.
5. For the geometrical isomers of ethyl ethoxymethylenecyanoacetate, see: Ceder, O.; Stenhede, U. T 1973, 29, 1585.
6. (a) Kampe, K.-D. AG 1982, 94, 543. (b) Nishigaki, S.; Senga, K.; Aida, K.; Takabatake, T.; Yoneda, F. CPB 1970, 18, 1003. (c) Ulbricht, T. L. V.; Okuda, T.; Price, C. C. OSC 1963, 4, 566.
7. (a) Cocco, M. T.; Congiu, C.; Onnis, V.; Maccioni, A. JHC 1991, 28, 797. (b) Cocco, M. T.; Congiu, C.; Maccioni, A. JHC 1990, 27, 1143. (c) Fahmy, S. M.; Mohareb, R. M. S 1985, 1135. (d) Fahmy, S. M.; Abd Allah, S. O.; Mohareb, R. M. S 1984, 976.
8. (a) Plescia, S.; Daidone, G.; Bajardi, M. L. JHC 1982, 19, 685. (b) Elnagdi, M. H.; Hafez, E. A. A.; El-Fahham, H. A.; Kandeel, E. M. JHC 1980, 17, 73.
9. Kakehi, A.; Ito, S.; Yotsuya, T. CPB 1986, 34, 2435.
10. Crombie, L.; Dove, R. V. JCS(P1) 1979, 686.
11. Whitney, J. G.; Lee, K. T. JOC 1973, 38, 2093.
12. The photoinduced rearrangement or thermolysis of pyrazolines is used in the syntheses of cyclopropanes: see Ref. 2b, c.

Lutz F. Tietze & Holger Geissler

Georg-August-Universität zu Göttingen, Germany

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