N-Phenylmaleimide

[941-69-5]  · C10H7NO2  · N-Phenylmaleimide  · (MW 173.18)

(dienophile2,3 and dipolarophile; Michael acceptor; radical acceptor)

Alternate Name: NPM.

Physical Data: mp 89-90 °C; bp 162-163 °C/12 mmHg.

Solubility: insol H2O; sol alcohol, ether, benzene.

Form Supplied in: yellow solid; widely available.

Purification: recrystallizaton from benzene/ligroin or from cyclohexane.

Handling, Storage, and Precautions: irritant.

Cycloadditions.

N-Phenylmaleimide is a common dienophile which reacts with a wide variety of dienes. Its advantages relative to other dienophiles are that it gives products in high yield and the Diels-Alder adducts are not susceptible to hydrolysis or retro-Diels-Alder reactions. High endo selectivity is usually observed in Diels-Alder reactions with NPM. Exceptionally high endo selectivity has been reported with the related N-methylmaleimide (NMM) relative to N-phenylmaleimide in [4 + 2] reactions with isobenzofuran.1 Studies which have examined the effect of a stereogenic center adjacent to the diene on the facial selectivity of a Diels-Alder reaction have frequently employed N-phenylmaleimide as a representative dienophile.2,3 Acyclic and cyclic 1,3-dienes containing an allylic stereogenic center have been examined (eqs 1-3). The bromo derivative of NPM, N-p-bromophenylmaleimide, has been used to obtain crystalline adducts suitable for single crystal X-ray analysis and unambiguous assignment of stereochemistry.2c

N-Phenylmaleimide readily reacts with a variety of 1,3-dipoles including azomethine ylides (eqs 4 and 5),4 carbonyl ylides (eq 6),5 and nitrones (eq 7).6 The carbene generated by the photolysis of the sodium salt of a glyconolactone tosylhydrazone has been trapped by NPM to provide a 9:1 mixture of isomeric cyclopropanes (eq 8).7

Miscellaneous.

Substituted amines add in a Michael fashion to N-phenyl- and N-alkylmaleimides. In this manner, N-alkyldaunorubicin derivatives have been prepared in good yield (eq 9).8 Similarly, Tri-n-butylstannane-Azobisisobutyronitrile radical additions of glycosyl halides and selenides with N-alkylmaleimides provide C-glycosyl compounds (eq 10).9

Related Reagents.

Dimethyl Fumarate.


1. Tobia, D.; Rickborn, B. JOC 1987, 52, 2611.
2. (a) Franck, R. W.; Argade, S.; Subramaiam, C. S.; Frechet, D. M. TL 1985, 26, 3187. (b) Tripathy, R.; Franck, R. W.; Onan, K. D. JACS 1988, 110, 3257. (c) McDougal, P. G.; Rico, J. G.; VanDerveer, D. JOC 1986, 51, 4492. (d) Fleming, I.; Sarkar, A. K.; Doyle, M. J.; Raithby, P. R. JCS(P1) 1989, 2023.
3. (a) Fisher, M. J.; Hehre, W. J.; Kahn, S. D.; Overman, L. E. JACS 1988, 110, 4625. (b) Datta, S. C.; Franck, R. W.; Tripathy, R.; Quigley, G. J.; Huang, L.; Chen, S.; Sihaed, A. JACS 1990, 112, 8472.
4. (a) Padwa, A.; Dent, W. JOC 1987, 52, 235. (b) Padwa, A.; Dent, W., Lefker, B.; Meyers, A. I. OS 1988, 67, 133. (c) Mkairi, A.; Hamelin, J. TL 1987, 28, 1397.
5. Chou, W.-N.; White, J. B. TL 1991, 32, 7637.
6. (a) Hisano, T.; Harano, K.; Matsuoka, T.; Watanabe, S.; Matsuzaki, T. CPB 1989, 37, 907. (b) Burdisso, M.; Gandolfi, R.; Grunanger, P.; Rastelli, A. JOC 1990, 55, 3427.
7. Mangholz, S. E.; Vasella, A. HCA 1991, 74, 2100.
8. Ram, R. N.; Varsha, K. SC 1991, 21, 121.
9. (a) Araki, Y.; Endo, T.; Tanji, M.; Nagasawa, J.; Ishido, Y. TL 1987, 28, 5853. (b) Araki, Y.; Endo, T.; Tanji, M.; Nagasawa, J.; Ishido, Y. TL 1988, 29, 351.

Gary A. Sulikowski & Michelle M. Sulikowski

Texas A & M University, College Station, TX, USA



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