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The role of epoxides as a synthetically useful class of compounds has been widely established (1, 2), and epoxide chemistry is presented in all modern undergraduate organic textbooks. However, neither their reactions nor their preparation are common subjects of undergraduate organic laboratory experiments.(1) This paper describes an operationally straightforward, two-step epoxide synthesis that can be presented to students in the form of two mechanistic "puzzles" that probe the stereoselectivity of two important reactions: halohydrin formation from alkenes and epoxide formation via intramolecular Williamson ether synthesis. It complements the increasing number of puzzle-oriented undergraduate experiments combining synthesis and mechanistic discovery that continue to appear in this Journal (4).
Alkenes are the most common starting material for the preparation of epoxides, Treatment of an alkene with aqueous N-bromosuccinimide (NBS) affords a bromohydrin (1) that, upon treatment with base, eliminates HBr to form an epoxide (2) via intramolecular nucleophilic substitution (eq 1). (All equations omitted)
The first question posed to the student asks whether or not the bromohydrin formation is stereoselective. In the present experiment, trans-stilbene (3) is treated with NBS and H sub 2 O in dimethyl sulfoxide (DMSO) (eq 2) to afford one of two possible diastereomers:
* (+/-)-erythro-2-bromo-1,2-diphenylethanol (4), mp 83-84degC (5)
* (+/-)-threo-2-bromo-1,2-diphenylethanol (5), mp 51-52degC (6)(eq 2)
Because the melting point ranges for the two possible diastereomeric products are separated by 30degC, only a melting-point determination is needed to establish that the product is the erythro bromohydrin (4). (Analogously, the threo bromohydrin (5) can be prepared from cis-stilbene (6)).
The second question asks whether the nucleophilic displacement of bromide that occurs when 4 is treated with base proceeds with inversion of configuration, to afford (+/-)-trans-stilbene oxide (6) (mp 65-67degC), or with retention of configuration, to afford (+/-)-cis-stilbene oxide (7) (mp 38-40degC) (eq 3). Again, the diastereospecificity of the reaction can be established simply by determining the melting-point range of the product.
Experimental Procedure
* Caution: Students should be required to wear gloves when working with either NBS or DMSO because both are skin irritants.
This experiment was carried out by 62 students enrolled in the first-semester organic chemistry laboratory course at Fordham University. A single 4-h lab period was scheduled for the synthesis and isolation of the crude bromohydrin, and the crystallization was...