[123-06-8]  · C6H6N2O  · Ethoxymethylenemalonitrile  · (MW 122.13)

(Michael acceptor for addition/elimination reactions;2 synthesis of substituted benzene rings3 and other aromatic heterocycles;4 dipolarophile5)

Alternate Name: EMMN.

Physical Data: mp 64 °C; bp 160 °C/12 mmHg.

Solubility: sol alcohols, THF, DMF, CHCl3, CH2Cl2.

Form Supplied in: colorless crystalline solid; commercially available.

Analysis of Reagent Purity: mp, 1H NMR, 13C NMR, IR.

Preparative Methods: can be synthesized by the condensation of Triethyl Orthoformate and Malononitrile in the presence of Acetic Anhydride.6 Likewise, ethoxy[2H]methylenemalonitrile can be made using DC(OEt)3.7

Purification: by distillation under reduced pressure.

Handling, Storage, and Precautions: is classified as a strong sensitizing agent and should be handled with gloves and goggles in a fume hood. Avoid contact with eyes, skin, and clothes. Also, ethoxymethlenemalonitrile is a combustible liquid with a flash point of 155 °C. It should be stored in a cool, dry place.

Use as a Michael Acceptor.

Ethoxymethylenemalonitrile has been used as a Michael acceptor for a wide variety of nucleophiles such as alcohols,8 amines,9 anilines,2 enamines,10 ester enolates,11 hydrazines,12 imines,13 pyrroles,14 stabilized carbanions,15 thiazoles,16 and thiols17 to name only a few. Usually, the Michael addition is accompanied by b-elimination of the ethoxy group to give substituted methylenemalonitrile derivatives (eq 1). Some highly conjugated dithiolylidenebutenes can be synthesized in this manner (eq 2).18

Treatment of EMMN with 2 equiv of Phenylmagnesium Bromide results in formation of the double Michael addition product (eq 3) following the customary addition/elimination sequence.19

Use in the Synthesis of Aromatic and Heteroaromatic Derivatives.

Since the nitriles themselves offer yet another electrophilic site for reactivity, the addition/elimination adducts are often not isolated but are converted directly to a variety of aromatic (eq 4)3 and heteroaromatic derivatives including pyridones (eq 5),15 pyrimidines (eq 6),20 thiophenes (eq 7),17 pyrazoles (eq 8),21 pyrones (eq 9),22 and heterocyclic annulenes (eq 10).23

Other Uses.

EMMN has also been used in [3 + 2] dipolar cycloadditions (eq 11)5 as well as an iron-mediated five-membered ring annulation (eq 12).24

Related Reagents.

Diethyl Methylenemalonate; 3-Ethoxyacrylonitrile; Ethyl 3-Ethoxyacrylate; Ethyl Ethoxymethyleneacetoacetate; Ethyl Ethoxymethylenecyanoacetate; Malononitrile.

1. Freeman, F. S 1981, 925.
2. Milata, V.; Ilavsky, D.; Goljer, I.; Lesko, J.; Chahinian, M.; Henry-Basch, E. CCC 1990, 55, 1038.
3. Schmidt, H. W. M 1989, 120, 891.
4. Ram, V. J.; Verma, M. JCR(S) 1990, 12, 398.
5. Dietliker, K.; Heimgartner, H. HCA 1983, 66, 262.
6. (a) Jones, R. G. JACS 1952, 74, 4889. For other preparations, see: (b) Ikawa, K.; Takami, F.; Fukui, Y.; Tokuyama, K. TL 1969, 38, 3279. (c) Cottis, S. G.; Tieckelmann, H. JOC 1961, 26, 79.
7. Uray, G.; Celotto, C. J. Labelled Compd. Radiopharm. 1987, 24, 1455.
8. (a) Antus, S.; Boross, F.; Nogradi, M. CC 1977, 333. (b) Andus, S.; Boross, F.; Nogradi, M. LA 1978, 1, 107.
9. Taylor, J. B.; Tully, W. R. JCS(P1) 1976, 1331.
10. Degraw, J. I.; Tagawa, H.; Christie, P. H.; Lawson, J. A.; Brown, E. G.; Kisliuk, R. L.; Gaumont, Y. JHC 1986, 23, 1.
11. Kakehi, A.; Ito, S.; Ohizumi, T.; Ito, M. BCJ 1983, 56, 1219.
12. Asinger, F.; Saus, A.; Baehr-Wirtz, M. LA 1979, 5, 708.
13. Tamura, Y.; Tsunekawa, M.; Miyamoto, T.; Ikeda, M. JOC 1977, 42, 602.
14. Neidlein, R.; Jeromin, G. CB 1982, 115, 714.
15. Reidlinger, G. H.; Junek, H. S 1991, 10, 835.
16. Cedar, O.; Beijer, B. T 1975, 31, 963.
17. Saito, K.; Kambe, S.; Sakurai, A.; Midorikawa, H. S 1982, 12, 1056.
18. Catel, J. M.; Mollier, Y. BSF(2) 1981, 3-4, 113.
19. Gupte, S. D.; Sunthankar, S. V. JOC 1959, 24, 1334.
20. Ram, V. J.; Kushwaha, D. S.; Mishra, L. IJC(B) 1989, 28B, 242.
21. (a) Schmidt, R. R.; Guillard, W.; Heermann, D.; Hoffmann, M. JHC 1983, 20, 1447. (b) Acevedo, O. L.; Krawczyk, S. H.; Townsend, L. B. JOC 1986, 51, 1050.
22. Jaquet, M. C.; Bellassoued-Fargeau, M. C.; Graffe, B.; Maitte, P. JHC 1985, 22, 757.
23. Shaw, J. T.; Kyler, K. S.; Anderson, M. D. JHC 1977, 14, 679.
24. Rosenblum, M.; Waterman, P. S. JOM 1980, 187, 267.

Scott D. Edmondson

The Ohio State University, Columbus, OH, USA

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