458 CHAPTER 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing CompoundsArene oxides are important intermediates in the biosynthesis of biochemically
important phenols such as tyrosine and serotonin.An arene oxide can react in two different ways. It can react as a typical epoxide,
undergoing attack by a nucleophile to form an addition product (Section 12.7).
Alternatively, it can rearrange to form a phenol, something that epoxides such as
ethylene oxide cannot do.When an arene oxide reacts with a nucleophile, the three-membered ring undergoes
back-side nucleophilic attack, forming an addition product.When an arene oxide undergoes rearrangement, the three-membered epoxide ring
opens, picking up a proton from a species in the solution. Instead of immediately losing
a proton to form phenol, the carbocation forms an enoneas a result of a 1,2-hydride
shift. This is called an NIH shiftbecause it was first observed in a laboratory at the
National Institutes of Health. Removal of a proton from the enone forms phenol.OB+ NIH shiftHB+
H+ H++ HB+H OH OH
HHOHObenzene oxide a carbocation an enone phenol++−OHO HO−O−
H 2 OOHaddition productOHOHaddition productY−rearranged productOHOHYOtyrosine
an amino acidCH 2 CHCOO−
+NH
3HOserotonin
a vasoconstrictorN
HHO CH 2 CH 2 NH 2cytochrome P 450
O 2benzene oxide
an arene oxidebenzeneO3-D Molecule:
Benzene oxidebenzenebenzene oxideBRUI12-437_480r3 27-03-2003 11:51 AM Page 458