Methacrolein Dimethylhydrazone

[66064-57-1]  · C6H12N2  · Methacrolein Dimethylhydrazone  · (MW 112.174)

(electron-rich 1-azadiene reacting with electron-poor alkenes to yield Diels-Alder adducts1-5)

Physical Data: bp 40-42 °C/20 mmHg.

Solubility: sol most organic solvents.

Preparative Methods: conveniently prepared either by the direct treatment of N,N-Dimethylhydrazine with Methacrolein or by a Hoffmann cleavage of the pyrazolinium iodide also obtained from methacrolein (eq 1).1-5 These methods have been successfully applied to the preparation of various a,b-unsaturated hydrazones (Table 1).

Handling, Storage, and Precautions: the compound darkens when kept at rt; however, it can be kept for long periods in the refrigerator without decomposition.

Diels-Alder Reactions.

Methacrolein dimethylhydrazone reacts as an electron-rich diene in Diels-Alder reactions with alkenes bearing electron-withdrawing groups (eqs 2 and 3).1,5

The diene is moderately reactive and best results are obtained with more reactive dienophiles (eqs 4 and 5).1,6,7

Dimethyl maleate was isomerized to the more stable dimethyl fumarate under these conditions and, therefore, both dienophiles yielded the trans adducts. Reductive cleavage of the N-N bond was readily effected by Zinc-Acetic Acid to yield substituted piperidines.

Pyridines could not be obtained by reacting a,b-unsaturated hydrazones with alkynic dienophiles.6 However, they were readily obtained by reaction of methacrolein dimethylhydrazone with alkenic dienophiles bearing a nucleofugal group (eq 6)3 or with an allenic dienophile (eq 7).5

Methacrolein dimethylhydrazone and related 1-azadienes have been extensively used for the preparation of aza- and diazaanthraquinone derivatives.1,8 The cycloaddition reaction is highly regioselective (eqs 8 and 9).

Only few examples of intramolecular cycloadditions involving a,b-unsaturated hydrazones have been described.9

Asymmetric Cycloadditions.

Only one example of a reaction of methacrolein dimethylhydrazone with a chiral dienophile has been reported (eq 10).10

Also it has been recently shown that the replacement of the dimethylamino group by a chiral pyrrolidine gives a 1-azadiene which cycloadds to cyclic dienophiles with high facial selectivities (eq 11).11 However, this diene did not react with dimethyl fumarate or acrylic derivatives.

1. Serckx-Poncin, B.; Hesbain-Frisque, A.-M.; Ghosez, L. TL 1982, 3261.
2. (a) Ioffe, B. V.; Zelemin, K. V. DOK 1964, 154, 864 (CA 1964, 60, 12 002a). (b) Gillis, B. T.; La Montagne, M. P. JOC 1968, 33, 762. (c) Gol'din, G. S.; Balabina, T. A.; Ushakova, A. N.; Shor, G. S. ZOR 1969, 5, 1321. (d) Duhamel, C. L.; Valnot, C. Y. CR(C) 1978, 286, 47.
3. (a) Waldner, A. HCA 1988, 71, 486. (b) Waldner, A. SC 1989, 19, 2371.
4. (a) Ioffe, B. V.; Zelenin K. N. DOK 1961, 141, 1369. (CA 1962, 56, 14 038). (b) Ioffe, B. V.; Zelenin, K. N. ZOB 1963, 33, 3589 (CA 1964, 60, 8016).
5. Tamura, Y.; Tsugoshi, T.; Nakajima, Y.; Kita, Y. SC 1984, 930.
6. Ghosez, L.; Serckx-Poncin, B.; Rivera, M.; Bayard, P.; Sainte, F.; Demoulin, A.; Frisque-Hesbain, A.-M.; Mockel, A.; Munoz, L.; Bernard-Henriet, C. JHC 1985, 22, Suppl. Issue; Lectures in Heterocyclic Chemistry 8.
7. Waldner, A. HCA 1989, 72, 1435.
8. (a) Potts, K. T.; Battarcharjee, D.; Walsh, E. B. CC 1984, 114. (b) Potts, K. T.; Walsh, E. B.; Battarcharjee, D. JOC 1987, 52, 2285. (c) Chigr, M.; Fillion, H.; Rougny, A. TL 1988, 29, 5913. (d) Gesto, C.; de la Cuesta, E.; Avendaño, C. T 1989, 45, 4477. (e) Nebois, N.; Barret, R.; Fillion, H. TL 1990, 31, 2569. (f) Valderrama, J. A.; Pessoa-Mahana, H.; Topia, R. JHC 1992, 29, 1177. See also (g) Nebois, P.; Fillion, H. TL 1991, 32, 1307. (h) Nebois, P.; Fillion, H.; Benamene, L. T 1993, 49, 9767. (i) Echavarren, A. M. JOC 1990, 55, 4255.
9. (a) Dolle, R. E.; Armstrong, W. P.; Shaw, A. N.; Novelli, R. TL 1988, 29, 6349. (b) Allcock, S. J.; Gilchrist, T. L.; Shuttleworth, S. J. T 1991, 47, 10053.
10. Waldner, A. TL 1989, 30, 3061.
11. Beaudegnies, R.; Ghosez, L. TA 1994, 5, 557.

Léon Ghosez

Université Catholique de Louvain, Louvain-la-Neuve, Belgium

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