[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.
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.
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
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
Grignard reagents add with equal facility as organolithium reagents to ethylene oxide (eq 5).6
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
Vinylaluminum reagents react with ethylene oxide, but lithium alanates react in even higher yield (eq 7).9
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
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
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
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
Edward W. Thomas
The Upjohn Company, Kalamazoo, MI, USA