Organic Chemistry

368 CHAPTER 10 Substitution Reactions of Alkyl Halides

The Nucleophile

When we talk about atoms or molecules that have lone-pair electrons, sometimes we

call them bases and sometimes we call them nucleophiles. What is the difference be-

tween a base and a nucleophile?

Basicityis a measure of how well a compound (a base) shares its lone pair with a

proton. The stronger the base, the better it shares its electrons. Basicity is measured by

an equilibrium constant(the acid dissociation constant, ) that indicates the tenden-

cy of the conjugate acid of the base to lose a proton (Section 1.17).

Nucleophilicityis a measure of how readily a compound (a nucleophile) is able to

attack an electron-deficient atom. Nucleophilicity is measured by a rate constant(k).

In the case of an reaction, nucleophilicity is a measure of how readily the nucle-

ophile attacks an hybridized carbon bonded to a leaving group.

When comparing molecules with the same attacking atom,there is a direct relation-

ship between basicity and nucleophilicity: Stronger bases are better nucleophiles. For

example, a species with a negative charge is a stronger base anda better nucleophile

than a species with the same attacking atom that is neutral. Thus is a stronger

base and a better nucleophile than

stronger base, weaker base,

better nucleophile poorer nucleophile

When comparing molecules with attacking atoms of approximately the same size,

the stronger bases are again the better nucleophiles. The atoms across the second row of

the periodic table have approximately the same size. If hydrogens are attached to the

second-row elements, the resulting compounds have the following relative acidities

(Section 1.18):

Consequently, the conjugate bases have the following relative base strengths and

nucleophilicities:

Note that the amide anion is the strongest base, as well as the best nucleophile.

When comparing molecules with attacking atoms that are very different in size,an-

other factor comes into play—the polarizability of the atom. Because the electrons are

farther away in the larger atom, they are not held as tightly and can, therefore, move

more freely toward a positive charge. As a result, the electrons are able to overlap from

farther away with the orbital of carbon, as shown in Figure 10.5. This results in a

greater degree of bonding in the transition state, making it more stable. Whether the

greater polarizability of the larger atoms makes up for their decreased basicity depends

on the conditions under which the reaction is carried out.

relative base strengths and relative nucleophilicities

strongest −NH 2 > HO− > F−

base

best nucleophile

relative acid strengths

weakest NH 3 < H 2 O < HF

acid

HO-

CH 3 O-

• NH
  2
  CH 3 CH 2 NH-

7

7

7

7

H 2 O

CH 3 OH

NH 3

CH 3 CH 2 NH 2

H 2 O.

HO-

sp^3

SN 2

Ka