Itaconic Anhydride

[2170-03-8]  · C5H4O3  · Itaconic Anhydride  · (MW 112.09)

(asymmetrical unsaturated anhydride; used as a dienophile5 and in reactions with various nucleophiles9,10)

Physical Data: mp 70-72 °C; bp 114-115 °C/12 mmHg.

Form Supplied in: white solid; widely available.

Preparative Methods: besides its synthesis from citric acid,1 itaconic anhydride (1)2 can also be prepared by chemical dehydration of itaconic acid.3 The thermal isomerization of itaconic anhydride to citraconic anhydride (2) is facile.4

Handling, Storage, and Precautions: moisture sensitive; irritant.

Pericyclic Chemistry.

Diels-Alder chemistry employing (1) as a dienophile is well developed. Cyclopentadiene has been used to protect the exocyclic methylene of (1) with regeneration of the alkene moiety via a retro-Diels-Alder thermolysis.5 By operating at 6.5 kbar for 8-10 d, excellent regioselectivity and face selectivity has been obtained in the reaction of (1) with the chiral diene (3).6 Itaconic anhydride, with its conjugated carbonyl group participating in secondary orbital overlap, undergoes 1,3-dipolar cycloaddition (eq 1) with the nitrone (4) to afford (5).7

Reaction with Nucleophiles.

Because a variety of 2-methylenebutanedioic acids and acid derivatives display useful8 pesticidal, herbicidal, and growth-regulatory activities, much effort has gone into exploring the reaction of the anhydride moiety with nucleophiles. Ring opening of (1) is highly regioselective. Thus (1) reacts with alcohols9 to afford (6a) (with preferred addition at the unconjugated carbonyl). With amines,10 similar regioselectivity affords the corresponding amides (6b). Reaction with hydroxylamine derivatives gives acids (6c), imides, or isoimides depending on conditions.10b Friedel-Crafts acylation of (1)11 yields the ring-opened product (7) involving acylation at the less-substituted carbonyl.

Miscellaneous Chemistry.

Halogenation of (1) yields halomethylmaleic anhydrides (8).12 Asymmetric hydrogenation of (1) has been explored.13 Hydrocobaltation of (1) gives (9).14 Reaction of (1) with thiourea in water or in acetic acid produces a variety of heterocycle products,15 as does the reaction of (1) with enamino esters.16

1. (a) Beilstein's Handbuch der Organischen Chemie; Springer: Berlin; Vol. 17, p 442. (b) Shriner, R. L.; Ford, S. G.; Roll, L. G. OSC 1943, 2, 368.
2. Horii, Z. Jpn. Kokai Tokkyo 2922, 1960 (CA 1960, 54, 24 557h).
3. (a) Kita, Y.; Akai, S.; Ajimura, N.; Yoshigi, M.; Tsugoshi, T.; Yasuda, H.; Tamura, Y. JOC 1986, 51, 4150. (b) Kita, Y.; Akai, M.; Yoshigi, M.; Nakajima, Y.; Yasuda, H.; Tamura, Y. TL 1984, 25, 6027.
4. (a) Shriner, R. L.; Ford, S. G.; Roll, L. J. OSC 1943, 2, 140. (b) Galanti, M. C.; Galanti, A. V. JOC 1982, 47, 1572.
5. Haslouin, J.; Rouessac, F. BSF 1977, 1242.
6. Winterfeldt, E.; Wray, V. CB 1992, 125, 2159.
7. Ali, S. A.; Wazeer, M. I. M.; Ul-Haque, M. T 1990, 46, 7207.
8. (a) McGowan, J. C.; Brian, P. W.; Heniming, H. G. Ann. Appl. Biol. 1948, 35, 25. (b) L. I. R. C. Laboratori Italianidi Ricera Chimica S.p.A. Ital. Patent 621 315, 1961 (CA 1964, 61, 2976). (c) U.S. Rubber Co. Belg. Patent 613 136, 1962 (CA 1963, 58, 4431).
9. (a) Hassall, C. H.; Krohn, A.; Moody, C. J.; Thomas, W. A. JCS(P1) 1984, 155. (b) Carlson, R. M.; Oyler, A. R. TL 1975, 4099. (c) Taylor, J. W.; Sloan, C. P.; Holden, D. A.; Kovacs, G. J.; Loutfy, R. O. CJC 1989, 67, 2142. (d) Bjorkquist, D. W.; Bush, R. D.; Ezra, F. S.; Keough, T. JOC 1986, 51, 3192.
10. (a) Veverka, M.; Kralovicova, E. CCC 1989, 54, 2731. (b) Akiyama, M.; Shimizu, K.; Alba, S.; Banba, F. JCS(P1) 1980, 2122. (c) Takeda, H.; Tachinami, T.; Hosokawa, S.; Aburatani, M.; Inogouchi, K.; Achiwa, K. CPB 1991, 39, 2706.
11. (a) Kameo, K.; Ogawa, K.; Takeshita, K.; Nakaike, S.; Tomisawa, K.; Sota, K. CPB 1988, 36, 2050. (b) Tomisawa, K.; Kameo, K.; Matsunga, T.; Saito, S.; Hosoda, K.; Asami, Y.; Sota, K. CPB 1986, 34, 701.
12. (a) Nokami, J.; Tamaoka, T.; Ogawa, H.; Wakabayashi, S. CL 1986, 541. (b) Tokoroyama, T.; Matsuo, K.; Kubota, T. T 1978, 34, 1907.
13. Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Akutagawa, S.; Takaya, H. TL 1992, 33, 635.
14. Bhandal, H.; Pattenden, G. CC 1988, 1110.
15. Balasubramaniyan, V.; Balasubramanian, P.; Wani, M. J. IJC(B) 1991, 308, 886.
16. Nagasaka, T.; Inoue, H.; Ichimura, M.; Hamaguchi, F. S 1982, 848.

John L. Belletire & R. Jeffery Rauh

The University of Cincinnati, OH, USA

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