| Prilezhaev reaction | |
|---|---|
| Named after | Nikolai Alexandrovich Prilezhaev (also spelled Nikolaj Alexandrovich Prileschajew, Russian: Николай Александрович Прилежаев) |
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | prilezhaev-reaction |
| RSC ontology ID | RXNO:0000405 |
ThePrilezhaev reaction, also known as thePrileschajew reaction orPrilezhaev epoxidation, is thechemical reaction of analkene with aperoxy acid to formepoxides.[1] It is named afterNikolai Prilezhaev, who first reported this reaction in 1909.[2] A widely usedperoxy acid for this reaction ismeta-chloroperoxybenzoic acid (m-CPBA), due to its stability and good solubility in most organic solvents.[1][3] The reaction is performed in inert solvents (C6H14,C6H6,CH2Cl2,CHCl3,CCl4) between -10 and 60 °C with the yield of 60-80%.
An illustrative example is the epoxidation oftrans-2-butene withm-CPBA to givetrans-2,3-epoxybutane:[4]
The oxygen atom that adds across the double bond of the alkene is taken from the peroxy acid, generating a molecule of the correspondingcarboxylic acid as a byproduct. The reaction is highly stereospecific in the sense that the double bond stereochemistry is generally transferred to the relative configuration of the epoxide with essentially perfect fidelity, so that atrans-olefin leads to the stereoselective formation of thetrans-2,3-substituted epoxide only, as illustrated by the example above, while acis-olefin would only give thecis-epoxide. This stereochemical outcome is a consequence of the accepted mechanism, discussed below.
In general, the Prilezhaev reaction epoxidizes the most substituted double bond.[1]
The reaction proceeds through what is commonly known as the "butterfly mechanism", first proposed by Bartlett, wherein the peracid is intramolecularly hydrogen-bonded at the transition state.[5] Although there are frontier orbital interactions in both directions, the peracid is generally viewed as theelectrophile and the alkene as thenucleophile. In support of this notion, more electron-rich alkenes undergo epoxidation at a faster rate. For example, the relative rates of epoxidation increase upon methyl substitution of the alkene (the methyl groups increase the electron density of the double bond byhyperconjugation): ethylene (1, no methyl groups), propene (24, one methyl group),cis-2-butene (500, two methyl groups), 2-methyl-2-butene (6500, three methyl groups), 2,3-dimethyl-2-butene (>6500, four methyl groups).
The reaction is believed to be concerted, with atransition state that is synchronous or nearly so.[6] The "butterfly mechanism" takes place via a transition state geometry in which the plane of the peracid bisects that of the alkene, with the O–O bond aligned perpendicular to it. This conformation allows the key frontier orbital interactions to occur. The primary interaction of the occupied πC=C orbital (HOMO) and the low-lying unoccupied σ*O-O orbital (LUMO). This interaction accounts for the observed overall nucleophilic character and electrophilic character of the alkene and peracid, respectively. There is also a secondary interaction between a lone pair orbital perpendicular to the plane of the peracid, nO(p) (HOMO) and the unoccupied π*C=C orbital (LUMO).[7][8] Using the approach of Anslyn and Dougherty (2006, p. 556), the mechanism can be represented as follows:[9]
There is a very large dependence of the reaction rate on the choice of solvent.[10]