Unit1 Worked Examples

PROBLEM 6 — SOLVED
Draw the products obtained from the SN2 reaction of

a. 2-bromobutane and methoxide ion. c. (S)-3-chlorohexane and hydroxide ion.
b. (R)-2-bromobutane and methoxide ion. d. 3-iodopentane and hydroxide ion.
Solution to 6 a.
The product is 2-methoxybutane. Because the reaction is an SN2 reaction, we know that the configuration of the
product is inverted relative to the configuration of the reactant. The configuration of the reactant is not specified,
however, so we cannot specify the configuration of the product. In other words, because we also do not know if the
reactant is R or S or a mixture of the two, we also do not know if the product is R or S or a mixture of the two.
Organic Chemistry: 8th Edition, Global Edition © 2017 Pearson Education, Ltd.
Paula Yurkanis Bruice
Draw the substitution product formed when cis-1-bromo-4-methylcyclohexane and hydroxide ion undergo an SN2
reaction.
Solution
Only the trans product is formed in this SN2 reaction because the carbon bonded to the leaving group is attacked by
the nucleophile on its back side.
Rank the following species from best nucleophile to poorest nucleophile in an aqueous solution:
Solution
Let’s first divide the nucleophiles into groups. There is one nucleophile with a negatively charged sulfur, three with
negatively charged oxygens, and one with a neutral oxygen. We know that in the polar aqueous solvent, the compound
with the negatively charged sulfur is the best nucleophile because sulfur is larger than oxygen. We also know that the
poorest nucleophile is the one with the neutral oxygen. To complete the problem, we need to rank the three
nucleophiles with negatively charged oxygens, which we can do by looking at the pKa values of their conjugate acids.
A carboxylic acid is a stronger acid than phenol, which is a stronger acid than water (Section 8.9). Because water is
the weakest acid, its conjugate base is the strongest base and the best nucleophile. Thus, the relative
nucleophilicities are:
What product is obtained when ethylamine reacts with excess methyl iodide in a basic solution of potassium
carbonate?
Solution
Ethylamine and methyl iodide undergo an SN2 reaction. The product of the reaction is a secondary amine that is
predominantly in its basic (neutral) form because the pH of the basic solution is greater than the pKa of the protonated
amine (Section 2.9). The secondary amine can undergo an SN2 reaction with another equivalent of methyl iodide,
forming a tertiary amine. The tertiary amine can react with methyl iodide in yet another SN2 reaction. The final
product of the reaction is a quaternary ammonium iodide.
The reaction of an amine with sufficient methyl iodide to convert the amine into a quaternary ammonium iodide is
called exhaustive methylation.
PROBLEM-SOLVING STRATEGY
Predicting Whether a Nucleophilic Substitution Reaction Will Be an SN1 Reaction or an SN2 Reaction and
Determining the Product(s) of the Substitution Reaction
Draw the configuration(s) of the substitution product(s) that are formed from the reactions of the following
compounds with the indicated nucleophile:
a. Because the reactant is a secondary alkyl halide, we know it is an SN2 reaction. Therefore, the product has the
inverted configuration relative to the configuration of the reactant.
b. Because the reactant is a tertiary alkyl halide, we know it is an SN1 reaction. Therefore, there are two
substitution products, one with the retained configuration and one with the inverted configuration relative to the
configuration of the reactant.
PROBLEM-SOLVING STRATEGY (CONTINUED)
c. Because the reactant is a tertiary alkyl halide, we know it is an SN1 reaction. The product does not have an
asymmetric center, so it does not have stereoisomers. Therefore, only one product is formed.
d. Because the reactant is a secondary alkyl halide, we know it is an SN2 reaction. Therefore, the configuration of
the product is inverted relative to the configuration of the reactant. But because the configuration of the reactant
is not indicated, we do not know the configuration of the product.
Proposing a Mechanism
Propose a mechanism for the following reaction:
When we see that one of the reactants is an acid, we know we should start by protonating the other reactant. We need
to protonate it at the position that allows the most stable carbocation to be formed. Therefore, we protonate the CH2
group because that forms a tertiary doubly-allylic carbocation with a positive charge that is shared by three carbons as
a result of electron delocalization. A 1,2-methyl shift results in a carbocation with the desired carbon skeleton. Loss of
a proton forms the final product.
The rate law for the reaction of HO- with tert-butyl bromide to form an elimination product in 75% ethanol/ 25% water
at 30 °C is the sum of the rate laws for the E2 and E1 reactions. What percentage of the reaction takes place by an E2
pathway when [HO–] = 5.0 M? (k2 = 7.1 × 10–5, and k1 = 1.5 × 10–5)
rate = rate law for the E2 reaction + rate law for the E1 reaction
rate = k2 [tert-butyl bromide][HO–] + k1 [tert-butyl bromide]
Solution
Determining the Major Product of an E2 Reaction
What is the major product formed when the following compounds undergo an E2 reaction?
a.
The alkyl halide in part a has two hydrogens on the β-carbon from which a hydrogen is removed in the elimination
reaction. Therefore, both the E and Z isomers are formed, but the E isomer is the major product.
The alkyl halide in part b has only one hydrogen on the β-carbon from which a hydrogen is removed, so there is only
one elimination product. First, we need to determine the configuration of the two asymmetric centers. Next, we need to
draw the perspective formula showing only the H and Br that are eliminated and putting them on bonds drawn in the
plane of the paper. Because we know the configurations of the asymmetric centers, we can add the other groups. When
H and Br are eliminated, the two groups bonded to solid wedges are on the same side of the double bond in the product.
What is the major product formed when the following compound undergoes an E1 reaction?
Solution
First, we need to consider the regiochemistry of the reaction: the major product is 3,4-dimethyl-3-hexene because it is
the most stable of the three possible alkene products.
Next, we need to consider the stereochemistry of the reaction: the major product has two stereoisomers, and more
(E)-3,4-dimethyl-3-hexene is formed because it is more stable than (Z)-3,4-dimethyl-3-hexene.
Predicting Relative Reactivities
Which compound would you expect to be more reactive in an SN1 reaction?
When asked to determine the relative reactivities of two compounds, we need to compare the G ‡ values of their
rate-determining steps. The faster-reacting compound will have the smaller G‡ value—that is, the smaller difference
between its free energy and the free energy of its rate-determining transition state.
Both alkyl halides have approximately the same stability, so the difference in their reaction rates is due primarily to
the difference in the stabilities of the transition states of their rate-determining steps. The rate-determining step is
carbocation formation. This is an endothermic reaction, so the transition state resembles the carbocation more than it
resembles the reactant (Section 6.3). Therefore, the compound that forms the more stable carbocation is the one that
reacts more rapidly.
Unlike the carbocation formed by the alkyl halide on the left (which does not have delocalized electrons), the
carbocation formed by the alkyl halide on the right is stabilized by electron delocalization. Thus, the alkyl halide on the
right undergoes as SN1 reaction more rapidly.
Describe how a double bond can be converted to a triple bond. For example, how can 2-butene be converted to
2-butyne?
Solution
Because we know that a vinylic halide can be converted to an alkyne, the question becomes, how can an alkene be
converted to a vinylic halide? The vinylic halide can be obtained by adding Br2 to the alkene followed by an E2
reaction. –NH2 is used for the E2 reaction so the two successive E2 reactions can be carried out simply by adding
excess – NH2 to the vicinal dibromide.
Predicting Whether SN2/E2 or SN1/E1 Reactions Occur
Draw the substitution and elimination products that are formed from the reactions of the following compounds with the
indicated nucleophile:
Solution to a.
The reactant is a secondary benzylic halide, so it can undergo SN2/E2 and SN1/E1 reactions. Because a good
nucleophile is employed, we know that SN2 and E2 reactions occur. The substitution product has a configuration that is
inverted relative to that of the reactant. Stereoisomers are not possible for the elimination product.
PROBLEM-SOLVING STRATEGY (CONTINUED)
Solution to b.
The reactant is a secondary benzylic halide so it can undergo SN2/E2 and SN1/E1 reactions. Because a poor nucleophile
is employed, we know that SN1 and E1 reactions occur. Therefore, two substitution products are formed, one with the
retained configuration and one with the inverted configuration, relative to the configuration of the reactant.
Most of the pKa values given in this text were determined in water. How would the pKa values of carboxylic acids,
+ +
alcohols, ammonium ions (RNH3), phenol, and an anilinium ion (C6H5NH3) change if they were determined in a
solvent less polar than water?
Solution
A pKa is the negative logarithm of an equilibrium constant, Ka (Section 2.2). Because we are determining how
decreasing the polarity of a solvent affects an equilibrium constant, we must look at how decreasing the polarity of
the solvent affects the stability of the reactants and products (Section 5.6).
Carboxylic acids, alcohols, and phenol are neutral in their acidic forms (HB) and charged in their basic forms (B–). A
polar solvent stabilizes B– and H+ more than it stabilizes HB, thereby increasing Ka. Therefore, Ka is larger (a
stronger acid) in water than in a less polar solvent, so the Ka values of carboxylic acids, alcohols, and phenol are
smaller (they are weaker acids) and, therefore, their pKa values are larger in a less polar solvent.
Ammonium ions and an anilinium ion are charged in their acidic forms (HB+) and neutral in their basic forms (B). A
polar solvent stabilizes HB+ and H+ more than it stabilizes B. Because HB+ is stabilized slightly more than H+, Ka is
smaller (a weaker acid) in water than in a less polar solvent, so the pKa values of ammonium ions and an anilinium
ion are smaller (they are stronger acids) in a less polar solvent.
Investigating How Stereochemistry Affects Reactivity
Which of the following compounds forms an epoxide as a result of reacting with sodium hydride (NaH)?
Hydride ion removes a proton from the OH group, forming a good nucleophile that can react with the secondary alkyl
halide in an intramolecular SN2 reaction to form an epoxide. An SN2 reaction requires back-side attack. Only when the
alkoxide ion and Br are on opposite sides of the cyclohexane ring is the alkoxide ion able to attack the back side of the
carbon that is attached to Br. Therefore, only the trans isomer is able to form an epoxide.

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PROBLEM 6 — SOLVED

Draw the products obtained from the SN2 reaction of

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