Chapter 11 — Exercises
Fifty-five problems on the $S_N1$ mechanism. Mechanism drawings expected wherever a structure or arrow is asked. ∗ marks problems with worked solutions in the appendix.
Section A — Mechanism drawing
11.1∗ Draw the full $S_N1$ mechanism (both steps, both transition states, the carbocation intermediate) for $(CH_3)_3CBr + H_2O$ at 50 °C.
11.2 Draw the mechanism for $(CH_3)_3CCl$ in methanol at 60 °C. Identify all bonds broken and formed.
11.3 Draw the mechanism for the solvolysis of 2-bromo-2-methylbutane in ethanol/water mixture. Predict the major product.
11.4 (moderate) Draw the carbocation intermediate of $S_N1$ on 1-bromo-1-methylcyclohexane. Include the geometry of the cation (planar, sp²) and the empty $p$ orbital. Show how the nucleophile can attack from either face.
11.5 (challenge) Draw the mechanism for $S_N1$ where the substrate is an allyl halide (e.g., 3-chloro-2-methyl-2-butene). Show how the allylic cation is resonance-stabilized.
Section B — Kinetics
11.6∗ For $(CH_3)_3CBr$ in 80% aqueous ethanol, the rate constant is $k = 0.012\, s^{-1}$ at 25 °C. Compute the rate when $[(CH_3)_3CBr] = 0.05\, M$. (Note units — $S_N1$ is first-order, so $k$ has units of $s^{-1}$, not $M^{-1}s^{-1}$.)
11.7 Suppose you double the substrate concentration in problem 11.6. What happens to the rate?
11.8 Suppose you double the water concentration in 11.6 (e.g., by changing solvent composition). What happens to the rate? Why is the answer different from problem 11.7?
11.9 (moderate) A reaction is found to be first-order in substrate and first-order in nucleophile. Is this consistent with $S_N1$? With $S_N2$?
11.10 (moderate) A reaction shows mixed kinetics — partly 1st order, partly 2nd order. Propose an explanation.
11.11 (challenge) Adding $LiClO_4$ to the solvent at 0.1 M increases the rate of a substitution reaction by a factor of 5. Adding it has almost no effect on a different reaction (~1.2× change). What does this tell you about the two reactions?
Section C — Stereochemistry
11.12∗ Predict the stereochemistry of the product of $(R)$-3-bromo-3-methylhexane in methanol at 60 °C.
11.13 $(R)$-2-bromobutane is dissolved in 95% aqueous methanol (a poor solvent for $S_N2$ but reasonable for $S_N1$). The product is the alcohol. What enantiomeric ratio do you expect?
11.14 (moderate) Why do most $S_N1$ reactions show a small inversion bias (e.g., 60:40 inversion:retention) rather than a true 50:50 racemate? What is the ion-pair effect?
11.15 (moderate) A racemic substrate is observed to give 95% one enantiomer and 5% the other in a substitution. Is this consistent with $S_N1$? With $S_N2$? Explain.
11.16 (challenge) Design an experiment using a chiral substrate to distinguish $S_N1$ from $S_N2$. What do you measure?
Section D — Substrate effects and carbocation stability
11.17∗ Rank the following carbocations from most to least stable: $CH_3^+$, $CH_3CH_2^+$, $(CH_3)_2CH^+$, $(CH_3)_3C^+$, $C_6H_5CH_2^+$, $CH_2=CHCH_2^+$.
11.18 Why is methyl cation so unstable that it cannot form in solution? How does this affect $S_N1$ reactivity of methyl halides?
11.19 Why is $(CH_3)_3C^+$ (the t-butyl cation) more stable than $(CH_3)_2CH^+$? Use hyperconjugation in your explanation.
11.20 (moderate) Why is benzyl cation $(C_6H_5CH_2^+)$ stabilized by resonance even though benzyl is a primary cation? Draw the resonance structures.
11.21 (moderate) Allyl cation $(CH_2=CHCH_2^+)$ has equivalent positive charge on the two end carbons by resonance. Predict the products if a nucleophile attacks the cation. What if both attack positions are accessible?
11.22 (challenge) The cation $(CH_3)_3C^+$ has a $pK_a$ of approximately −5 (for the conjugate acid $(CH_3)_3CH$). Methyl cation has $pK_a$ around −33. What does the difference mean for the relative stability of these cations?
11.23 (challenge) A trityl cation $(C(C_6H_5)_3^+)$ is so stable that it can be isolated as a salt with a non-nucleophilic counterion (like $BF_4^-$). What stabilizing factors make it so stable? How does this contrast with simple alkyl cations?
Section E — Solvent and conditions
11.24∗ Explain why $(CH_3)_3CBr$ solvolyzes ~10⁵ times faster in water than in DMSO.
11.25 Rank the following solvents by their ability to support $S_N1$ (best first): hexane, methanol, water, DMSO, ethanol, t-butanol.
11.26 (moderate) A reaction in 70% acetone/30% water gives an $S_N1$ product. The same substrate in 99% acetone/1% water gives no reaction. Why?
11.27 (moderate) Why does the solvent choice for $S_N1$ work opposite to the solvent choice for $S_N2$?
11.28 (challenge) The Grunwald-Winstein equation $\log(k/k_0) = mY$ correlates rate with solvent ionizing power $Y$. What does the slope $m$ tell you about the mechanism?
Section F — Carbocation rearrangements
11.29∗ $(CH_3)_2CHCH_2Cl$ (isobutyl chloride) is treated with methanol at 50 °C. Predict the major product. Show the rearrangement step in your mechanism.
11.30 $CH_3CH_2CH(Br)CH_2CH_3$ (3-bromopentane) is treated with water. Predict the products with and without rearrangement.
11.31 A neopentyl tosylate ($(CH_3)_3CCH_2-OTs$) gives, upon solvolysis in methanol, a tertiary methyl ether instead of the expected primary methyl ether. Draw the rearrangement.
11.32 (moderate) Why are 1,2-hydride shifts and 1,2-methyl shifts more common than 1,3-shifts? (Consider the geometry.)
11.33 (moderate) Predict whether each substrate will rearrange during $S_N1$: (a) (CH₃)₃CCH₂Cl (b) (CH₃)₂CHCH₂Cl (c) (CH₃)₃CCl (d) (CH₃)₂CHCl
11.34 (challenge) Pinacol rearrangement: a 1,2-diol with a tertiary OH and a different secondary or primary OH undergoes a remarkable rearrangement to a ketone. Draw the mechanism, focusing on the carbocation rearrangement step.
Section G — Distinguishing SN1 from SN2
11.35∗ A student observes the following experimental results for an unknown reaction: - The rate is first-order in substrate and zero-order in nucleophile. - The product is racemic. - Adding LiClO₄ to the solution increases the rate. - The substrate is tertiary.
Identify the mechanism. Justify with each observation.
11.36 A different reaction shows: - Second-order kinetics. - 100% inverted product. - Reaction works only with primary or secondary halides. - Polar aprotic solvent dramatically accelerates.
Identify the mechanism.
11.37 (challenge) A reaction shows mostly racemization but with some inversion bias (~60:40), and the rate is ~85% first-order and ~15% second-order at moderate [Nu]. Propose a model.
11.38 (challenge) Design a single experiment that would unambiguously distinguish $S_N1$ from $S_N2$ for a given 2° substrate.
Section H — Common SN1 reactions
11.39∗ Explain how the Lucas test (HCl/ZnCl₂) distinguishes between primary, secondary, and tertiary alcohols. Draw the relevant mechanism.
11.40 Predict the product of $(CH_3)_3COH + HBr$. Draw the mechanism.
11.41 Predict the product of solvolysis of $(R)$-2-bromobutane in 80% aqueous methanol.
11.42 (moderate) Friedel-Crafts alkylation: $(CH_3)_3CCl + AlCl_3 + benzene$. Identify the intermediate cation and the mechanism.
11.43 (moderate) A medicinal chemistry route requires conversion of a tertiary alcohol to a tertiary alkyl chloride. Outline the synthesis.
Section I — Biological SN1 (oxocarbenium chemistry)
11.44 Glucose's anomeric carbon (C1) can lose its hydroxyl (with proton catalysis) to form an oxocarbenium ion. Draw this step. Why is the cation more stable than a typical secondary cation?
11.45 (moderate) Glycoside formation in biology proceeds through an $S_N1$-like mechanism with an oxocarbenium intermediate. Describe how an enzyme might accelerate this.
11.46 (challenge) In cholesterol biosynthesis (Chapter 34), squalene is cyclized through a series of carbocation rearrangements. Draw a simplified version of the cation cascade for one ring closure.
Section J — Cumulative
11.47∗ A substrate has an unknown class. Solvolysis in 80% aqueous methanol gives clean racemic product with first-order kinetics. The rate doubles when $LiClO_4$ is added. What class is the substrate?
11.48 Predict whether $(R)$-2-bromooctane will undergo $S_N1$ or $S_N2$ in: (a) water at 80 °C (b) DMSO at 25 °C (c) ethanol at 60 °C (d) methanol with NaCN at 25 °C
11.49 A mechanism question: why does a tertiary alkyl halide give an acid by hydrolysis with hot KOH (rather than just $S_N2$ to give an alcohol)?
11.50 (challenge) Combining Chapters 3 (acid-base), 5 (kinetics), and 11 ($S_N1$): design a protocol that distinguishes between $S_N1$ and $S_N2$ on a substrate of unknown class.
Section K — Synthesis and design
11.51 (moderate) Design a synthesis of $(CH_3)_3C-OCH_3$ from a starting material containing a $C-Br$ bond and methanol. Use $S_N1$.
11.52 (challenge) A pharma chemist needs to install a $-CN$ group on a tertiary carbon. They cannot use $S_N2$ (not a tertiary substrate substrate). What approach would they use? (Hint: consider $S_N1$ in mostly aqueous solution.)
11.53 (challenge) Why is it difficult to do clean $S_N1$ on a substrate where the cation might rearrange to a more stable cation? Propose how you would suppress rearrangement.
Section L — Conceptual
11.54 What does the Hammond postulate predict about the position of the TS₁ (the slow step's TS) in $S_N1$? How does this compare to TS₂?
11.55 (challenge) Why is "ion pair" rather than "free cation" a better description of the $S_N1$ intermediate in moderately polar solvents? What does this teach about real chemistry vs. textbook mechanism?
Preview of Chapter 12
Chapter 12 covers $E2$ and $E1$ — the elimination counterparts of $S_N2$ and $S_N1$. They share the same overall families (concerted vs. two-step via cation). $E1$ shares the same first step as $S_N1$. The competition between substitution and elimination is what Chapter 13 will resolve.