Organic Chemistry

364 CHAPTER 10 Substitution Reactions of Alkyl Halides

a. Back-side attack

empty σ

antibonding MO

filled σ

bonding MO

b. Front-side attack

an in-phase

(bonding)

interaction

an in-phase

(bonding)

interaction

an out-of-phase

(antibonding)

interaction

*

empty σ

antibonding MO

filled σ

bonding MO

*

Nu C

C

Br

CBr

Nu

Br

CBr

Figure 10.1N
(a) Back-side attack results in a
bonding interaction between the
HOMO (the filled nonbonding
orbital) of the nucleophile and the
LUMO (the empty antibonding
orbital) of (b) Front-side
attack would result in both a
bonding and an antibonding
interaction that would cancel out.

C¬Br.

s*

Molecular orbital theory also explains back-side attack. Recall from Section 8.9

that to form a bond, the LUMO (lowest unoccupied molecular orbital) of one species

must interact with the HOMO (highest occupied molecular orbital) of the other. When

the nucleophile approaches the alkyl halide, the filled nonbonding molecular orbital

(the HOMO) of the nucleophile must interact with the empty antibonding molecu-

lar orbital (the LUMO) associated with the bond. Figure 10.1a shows that

back-side attack involves a bonding interaction between the nucleophile and the larger

lobe of Compare this with what happens when the nucleophile approaches the

front side of the carbon (Figure 10.1b): Both a bonding and an antibonding interaction

occur, and the two cancel each other. Consequently, the best overlap of the interacting

orbitals is achieved through back-side attack. In fact, a nucleophile always approaches

an hybridized carbon from the back side. [We saw back-side attack previously in

the reaction of a bromide ion with a cyclic bromonium ion (Section 5.19).]

sp^3

s*.

C¬Br

s*

A nucleophile always approaches an
hybridized carbon on its back side.

sp^3

Viktor Meyer (1848–1897)was
born in Germany. To prevent him
from becoming an actor, his parents
persuaded him to enter the University
of Heidelberg, where he earned a
Ph.D. in 1867 at the age of 18. He
was a professor of chemistry at the
Universities of Stuttgart and
Heidelberg. He coined the term
“stereochemistry” for the study of
molecular shapes and was the first
to describe the effect of steric
hindrance on a reaction.

How does Hughes and Ingold’s mechanism account for the three observed pieces of

experimental evidence? The mechanism shows the alkyl halide and the nucleophile

coming together in the transition state of the one-step reaction. Therefore, increasing

the concentration of either of them makes their collision more probable. Thus, the re-

action will follow second-order kinetics, exactly as observed.

Because the nucleophile attacks the back side of the carbon that is bonded to the

halogen, bulky substituents attached to this carbon will make it harder for the nucle-

ophile to get to that side and will therefore decrease the rate of the reaction (Figure 10.2).

This explains why substituting methyl groups for the hydrogens in methyl bromide pro-

gressively slows the rate of the substitution reaction (Table 10.1). It is the bulk of the

alkyl groups that is responsible for the difference in reactivity.

Steric effectsare caused by groups occupying a certain volume of space. A steric

effect that decreases reactivity is called steric hindrance. Steric hindrance results

when groups are in the way at the reaction site. Steric hindrance causes alkyl halides to

transition state

HO− HO C Br Br−

δ−δ−

++C Br HO C

‡