Ethylene Oxide

[75-21-8]  · C2H4O  · Ethylene Oxide  · (MW 44.05)

(electrophile; 2-hydroxyethyl equivalent)

Alternate Name: oxirane

Physical Data: bp 13.5 °C/746 mmHg; d 0.8824 g cm-3.

Solubility: sol water and most organic solvents.

Form Supplied in: liquid, in 100 mL sealed tubes; gas, in 100 mL cylinders.

Handling, Storage, and Precautions: extremely flammable; vapors can detonate; possible carcinogen; use in a fume hood.

Nucleophilic Opening.

Ethylene oxide and epoxides in general have been the subject of extensive reviews.1 Much of the chemistry involved with ethylene oxide revolves around the opening of the strained ring to form a 2-ethanol substituted moiety. The reagents employed have ranged from carbon nucleophiles, to alcohols and water, to amines.

Reaction with Organolithium Reagents.

The carbon nucleophiles can be classified by the type of organometallic reagent involved in the opening reaction of the epoxide. The reagent of choice for this transformation is an organolithium reagent.2 Treatment of an ester lithium enolate with an excess of ethylene oxide affords a spirolactone (eq 1).2a

A lithio acetylide reacts with ethylene oxide in the presence of Boron Trifluoride Etherate (eq 2).2c While BF3.Et2O has been used to increase the yields of epoxide openings with organolithium reagents,3 the reaction solvent also plays an important role in obtaining high yields of ring-opened material with a lithio acetylide (eq 3).2b While t-Butyllithium readily metalates some epoxides, it only opens ethylene oxide.4

Reaction with Allylpotassium Reagents.

Isoprene has been metalated with Potassium Diisopropylamide (KDA). Employing this nonnucleophilic, strong base lessened polymerization and permitted the reaction of the allylpotassium reagent with ethylene oxide to form the homologated alcohol (eq 4).5

Reaction with Grignard Reagents.

Grignard reagents add with equal facility as organolithium reagents to ethylene oxide (eq 5).6

Reaction with Lithium Dialkylcuprates.

Lithium dialkylcuprates have long been known to react selectively and in high yield with oxiranes.7 A number of more complex, modified cuprate reagents recently have been developed.8 A vinylstannane was treated with the higher-order cuprate derived from Methyllithium and Copper(I) Cyanide and subsequent reaction with ethylene oxide afforded the homologated alcohol in 48% yield. The vinylstannane was also metalated with n-Butyllithium and reaction with 2-thienyl(cyano)copperlithium afforded the mixed higher-order vinyl cuprate that reacted with ethylene oxide in 38% yield. However, the authors found the easiest method for the formation of the homologated alcohol was to produce the mixed cuprate and treat it with ethylene oxide (eq 6).8a

Reaction with Vinylaluminum Reagents.

Vinylaluminum reagents react with ethylene oxide, but lithium alanates react in even higher yield (eq 7).9

Reaction of Ylides.

A new b-oxidobenzyl ylide was formed by reacting lithium diphenylphosphide with ethylene oxide followed by reaction with Benzyl Bromide. The reaction of these ylides with aldehydes afforded (E)-alkenes with good stereoselectivity (eq 8).10 Another ylide formed from ethylene oxide undergoes a Wittig reaction with an aldehyde derived from (R)-limonene. The resulting alkene retains the ethanol moiety derived from ethylene oxide (eq 9).11

Reaction with Amines.

Heteroatom-containing moieties add to ethylene oxide to form 2-substituted ethanol derivatives.1 Amines add in this fashion to form 1,2-ethanolamines.12 For instance, bubbling ethylene oxide through a solution of dimethylethylenediamine in methanol at 35 °C affords the corresponding alcohol (eq 10).13

Reaction with Me3SiI.

By reacting ethylene oxide with Iodotrimethylsilane, a simple derivative is formed that is also useful as a two-carbon synthon in the preparation of pheromone components (eq 11).14

Reaction with Aldehydes.

A very facile method for the formation of acetals under essentially neutral conditions involves the reaction of ethylene oxide with aldehydes in an autoclave at 110-220 °C (eq 12).15

Related Reagents.

1,3-Butadiene Monoxide; Glycidol; Isoprene Epoxide; Propylene Oxide.

1. (a) Smith, J. G. S 1984, 629. (b) Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989; pp 508-520. (c) Bartock, M.; Lang, K. L. In The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups and Their Sulfur Analogs, Part II; Patai, S., Ed.; Wiley: New York, 1980; Chapter 14.
2. (a) King, F. D.; Hadley, M. S.; Joiner, K. T.; Martin, R. T.; Sanger, G. J.; Smith, D. M.; Smith, G. E.; Smith, P.; Turner, D. H.; Watts, E. A. JMC 1993, 36, 683. (b) Viala, J.; Sandri, J. TL 1992, 33, 4897. (c) Kido, F.; Abiko, T.; Kato, M. BCJ 1992, 65, 2471. (d) Girard, S.; Deslongchamps, P. CJC 1992, 70, 1265. (e) Rao, A. V. R.; Sharma, G. V. M.; Bhanu, M. N. TL 1992, 33, 3907. (f) Bartoli, G.; Bosco, M.; Cimarelli, C.; Dalpozzo, R.; Palmieri, G. JCS(P1) 1992, 2095. (g) Krief, A.; Hobe, M. SL 1992, 317. (h) Lattuada, L.; Licandro, E.; Maiorana, S.; Papagni, A.; Zanotti-Geroso, A. SL 1992, 315. (i) Narasaka, K.; Hayashi, Y.; Shimada, S.; Yamada, J. Isr. J. Chem. 1991, 31, 261. (j) Noe, C. R.; Knollmuller, M.; Dungler, K.; Gartner, P. M 1991, 122, 185. (k) Enders, D.; Dahman, W.; Dederichs, E.; Gatzweiler, W.; Weuster, P. S 1990, 1013. (l) Al-Dulayyami, J. R.; Baird, M. S. T 1990, 46, 5703. (m) Jung, M. E.; Miller, S. J. H 1990, 30, 839. (n) Lee, T. V.; Leigh, A. J.; Chapleo, C. B. T 1990, 46, 921.
3. Eis, M. J.; Wrobel, J. E.; Ganem, B. JACS 1984, 106, 3693.
4. Eisch, J. J.; Galle, J. E. JOC 1990, 55, 4835.
5. Klusener, P. A. A.; Tip, L.; Brandsma, L. T 1991, 47, 2041.
6. (a) Sharma, P. K. SC 1993, 23, 389. (b) Dreger, E. E. OSC 1941, 1, 306.
7. Johnson, C. R.; Herr, R. W.; Wieland, D. M. JOC 1973, 38, 4263.
8. (a) Booker-Milburn, K. I.; Heffernan, G. D.; Parsons, P. J. CC 1992, 350. (b) Barbero, A.; Cuadrado, P.; Gonzalez, A. M.; Pulido, F. J.; Fleming, I. JCS(P1) 1991, 2811. (c) Dawson, I. M.; Gregory, J. A.; Herbert, R. B.; Sammes, P. G. JCS(P1) 1988, 2585. (d) Marfat, A.; McGuirk, P. R.; Helquist, P. JOC 1979, 44, 3888. (e) Lipshutz, B. H.; Koerner, M.; Parker, D. A. TL 1987, 28, 945.
9. Warwel, S.; Schmitt, G.; Ahlfaenger, B. S 1975, 632.
10. Boubia, B.; Mann, A.; Bellamy, F. D.; Mioskowski, C. AG(E) 1990, 29, 1454.
11. Becker, D.; Sahali, Y. T 1988, 44, 4541.
12. Alder, R. W.; Mowlam, R. W.; Vachon, D. J.; Weisman, G. R. CC 1992, 507.
13. Pastor, S. D.; Togni, A. HCA 1991, 74, 905.
14. Poleschner, H.; Heydenreich, M.; Martin, D. S 1991, 1231.
15. Nerdel, F.; Buddrus, J.; Scherowsky, G.; Klamann, D.; Fligge, M. LA 1967, 710, 85.

Edward W. Thomas

The Upjohn Company, Kalamazoo, MI, USA

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