Organic Chemistry

Section 12.9 Crown Ethers 463

3-D Molecule:

[18]-Crown-6

with potassium ion

Donald J. Cram (1919–2001)was

born in Vermont. He received a B.S.

from Rollins College, an M.S. from

the University of Nebraska, and a

Ph.D. from Harvard University.

He was a professor of chemistry at

the University of California,

Los Angeles, and was an avid surfer.

The ability of a host to bind only certain guests is an example of molecular

recognition. Molecular recognition explains how enzymes recognize their substrates,

how antibodies recognize antigens, how drugs recognize receptors, and many other

biochemical processes. Only recently have chemists been able to design and synthe-

size organic molecules that exhibit molecular recognition, although the specificity of

these synthetic compounds for their guests is generally less highly developed than the

specificity exhibited by biological molecules.

A remarkable property of crown ethers is that they allow inorganic salts to be

dissolved in nonpolar organic solvents, thus permitting many reactions to be carried

out in nonpolar solvents that otherwise would not be able to take place. For example,

the reaction of 1-bromohexane with acetate ion poses a problem because potassi-

um acetate is an ionic compound that is soluble only in water, whereas the alkyl halide

is insoluble in water. In addition, acetate ion is an extremely poor nucleophile.

Potassium acetate can be dissolved in a nonpolar solvent such as benzene if

[18]-crown-6 is added to the solution. The crown ether binds potassium in its cavity, and

the nonpolar crown ether–potassium complex dissolves in benzene, along with the ac-

etate ion, to maintain electrical neutrality. The crown ether is acting as a phase-transfer

catalyst—it is bringing a reactant into the phase where it is needed. Because acetate is

not solvated in the nonpolar solvent, it is a much better nucleophile than it would be in a

SN 2

[12]-crown-4 [15]-crown-5 [18]-crown-6

CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 Br ++CH 3 CO− Br−

O

CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 OCCH 3

O

[18]-crown-6

soluble only in a

nonpolar sovent

soluble only

in water

AN IONOPHOROUS ANTIBIOTIC

An antibiotic is a compound that interferes with

the growth of microorganisms. Nonactin is a

naturally occurring antibiotic that owes its biological activity to

its ability to disrupt the carefully maintained electrolyte balance

between the inside and outside of a cell. To achieve the gradient

between potassium and sodium ions inside and outside the cell

that is required for normal cell function, potassium ions are

pumped in and sodium ions are pumped out. Nonactin disrupts

this gradient by acting like a crown ether. Nonactin’s diameter

is such that it specifically binds potassium ions. The eight

oxygens that point into the cavity and interact with are

highlighted in the structure shown here. The outside of nonactin

is nonpolar, so it can easily transport K+ions out of the cell

K+

through the nonpolar cell membrane. The decreased concentra-

tion of within the cell causes the bacterium to die. Nonactin

is an example of an ionophorousantibiotic. An ionophoreis a

compound that transports metal ions by binding them tightly.

O

O O O

O O

O

O

O

OO

nonactin

O

K+

BRUI12-437_480r3 27-03-2003 11:51 AM Page 463