Chapter 8

Write Lewis structures for each of the following reagents and classify them as either electrophilic, nucleophilic, both, or neither by evaluating whether they will react appreciably with hydroxide ion, \(\mathrm{HO}^{\ominus}\), or hydronium ion, \(\mathrm{H}_{3} \mathrm{O}^{\oplus}\). Write equations for each of the reactions involved. a. \(\mathrm{NH}_{3}\) b. \(\mathrm{NH}_{2}^{-}\) c. \(\mathrm{Na}^{\oplus}\) d. \(\mathrm{Cl}^{\ominus}\) e. \(\mathrm{Cl}_{2}\) f. \(\mathrm{CH}_{4}\) g. CN h. \(\mathrm{CH}_{3} \mathrm{OH}\) i. \(\mathrm{CH}_{3} \mathrm{O} \mathrm{H}_{2}\) j. \(\mathrm{BF}_{4}^{-}\) k. \(\mathrm{HBr}\) l. \(\mathrm{HC} \equiv \mathrm{C}:^{\ominus}\) \(\mathrm{m}\). : \(\mathrm{CH}_{2}\) n. \(\mathrm{FSO}_{3} \mathrm{H}\) o. \(\mathrm{SO}_{3}\)

Ethyl chloride \((0.1 \mathrm{M})\) reacts with potassium iodide \((0.1 \mathrm{M})\) in 2 -propanone (acetone) solution at \(60^{\circ}\) to form ethyl iodide and potassium chloride at a rate \((v)\) of \(5.44 \times 10^{-7} \mathrm{~mol} \mathrm{~L}^{-1} \mathrm{~s}^{-1}\). a. If the reaction proceeded by an \(S_{N} 2\) mechanism, what is the value of \(k\) (in proper units) and what would be the rate of the reaction in moles per liter per sec at \(0.01\) M concentrations of both reactants? Show your method of calculation. b. Suppose the rate were proportional to the square of the potassium iodide concentration and the first power of the ethyl chloride concentration. What would be the rate with \(0.01\) M reactants? c. It one starts with solutions initially \(0.1 \mathrm{M}\) in both reactants, the rate of formation of ethyl iodide initially is \(5.44 \times 10^{-7} \mathrm{~mol} \mathrm{~L}^{-1} \mathrm{~s}^{-1}\), but falls as the reaction proceeds and the reactants are used up. Plot the rate of formation of ethyl iodide against the concentration of ethyl chloride as the reaction proceeds (remembering that one molecule of ethyl chloride consumes one molecule of potassium iodide). Assume that the rate of reaction is proportional to the first power of the ethyl chloride concentration; and to (1) the zeroth power, (2) the first power, and (3) the second power of the potassium iodide concentration. d. What kind of experimental data would one need to determine whether the rate of the reaction of ethyl chloride with potassium iodide is first order in each reactant or second order in ethyl chloride and zero order in potassium iodide?

The rate of solvolysis of tert-butyl chloride in aqueous solution is unaffected by having sodium azide, \(\stackrel{\oplus}{\mathrm{Na}} \stackrel{\mathrm{N}}=\mathrm{N}=\mathrm{N}\), in the solution, yet the products include both 2 -azido-2-methylpropane, 1 , and tert-butyl alcohol: Show how this information can be used to determine whether an \(S_{\mathrm{N}} 1\) or an \(S_{\mathrm{N}} 2\) mechanism occurs in the solvolysis of tertbutyl chloride in aqueous solution.

What inference as to reaction mechanism might you make from the observation that the rate of hydrolysis of a certain alkyl chloride in aqueous 2-propanone is retarded by having a moderate concentration of lithium chloride in the solution?

When either of the enantiomers of 1 -deuterio-1-bromobutane is heated with bromide ion in 2 -propanone, it undergoes an \(S_{\mathrm{N}} 2\) reaction that results in a slow loss of its optical activity. If radioactive bromide ion \(\left(\mathrm{Br}^{*} \ominus\right)\) is present in the solution, radioactive 1 -deuterio-1-bromobutane is formed by the same \(S_{N} 2\) mechanism in accord with the following equation: $$ \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHDBr}+\mathrm{Br}^{* \ominus} \stackrel{2 \text { -propanone }}{\longrightarrow} \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHDBr}^{*}+\mathrm{Br}^{\ominus} $$ Within experimental error, the time required to lose \(10 \%\) of the optical activity is just equal to the time required to have \(5 \%\) of the \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHDBr}\) molecules converted to \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHDBr}^{*}\) with radioactive bromide ion. Explain what we can conclude from these results as to the degree to which the \(S_{N} 2\) reaction produces inversion of configuration of the primary carbon of 1 -deuterio-1-bromobutane.

In the reaction of 1 -phenylethanol with concentrated \(\mathrm{HCl}\), 1 -phenylethyl chloride is formed: If the alcohol originally has the \(D\) configuration, what configuration would the resulting chloride have if formed (a) by the \(S_{\mathrm{N}} 2\) mechanism and (b) by the \(S_{\mathrm{N}} 1\) mechanism?

Select the compounds from the following list that would be expected to hydrolyze more rapidly than phenylmethyl (benzyl) chloride by the \(S_{N} 1\) mechanism: a. 2 -phenylmethyl chloride b. diphenylmethyl chloride c. 1 -phenylmethyl chloride d. (chloromethyl)cyclohexane e. 1 -chloro-4-methylbenzene

Explain the following observations: a. The tertiary chloride, apocamphyl chloride, is unreactive in either \(S_{N} 1\) or \(S_{N} 2\) reactions. For example, no reaction occurs when its solution in aqueous ethanol containing \(30 \%\) potassium hydroxide is refluxed for 20 hours. CC1(C)CCCCC1(C)C chlonide b. Chloromethyl alkyl (or aryl) ethers, \(\mathrm{ROCH}_{2} \mathrm{Cl}\), are very reactive in \(S_{\mathrm{N}} 1\) solvolysis reactions. Compared to chloromethane, the rate of hydrolysis of chloromethyl phenyl ether is about \(10^{14}\). Also, the rate of hydrolysis is retarded significantly by lithium chloride.

Account for the following observations: a. tert-Alkyl fluorides are unreactive in \(S_{\mathrm{N}} 1\) solvolysis reactions unless a strong acid is present. b. \(D-1\) -Phenylethyl chloride dissolved in aqueous 2 -propanone containing mercuric chloride loses much of its optical activity before undergoing hydrolysis to give racemic 1 -phenylethanol. c. 1-Bromobutane can be prepared by heating 1 -butanol with a mixture of sodium bromide and sulfuric acid. The reaction fails, however, if the sulfuric acid is omitted. d. Benzenoxide (phenoxide) ion, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{O}^{\ominus}\), is a better leaving group than ethoxide, \(\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{O}^{\ominus}\).

Methyl ethers of the type \(\mathrm{R}-\mathrm{O}-\mathrm{CH}_{3}\) cannot be prepared by the reaction of the alcohol \(\mathrm{ROH}\) with \(\mathrm{CH}_{3} \mathrm{I}\), but if \(\mathrm{Ag}_{2} \mathrm{O}\) is present the following reaction occurs under mild conditions: $$ 2 \mathrm{R} \mathrm{OH}+\mathrm{Ag}_{2} \mathrm{O}+2 \mathrm{CH}_{3} \mathrm{I} \rightarrow 2 \mathrm{ROCH}_{3}+2 \mathrm{AgI}+\mathrm{H}_{2} \mathrm{O} $$ Explain how \(\mathrm{Ag}_{2} \mathrm{O}\) promotes this reaction.

Explain each of the following observations: a. Methyl sulfide \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{~S}\) reacts with \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{COCH}_{2} \mathrm{Cl}\) in benzene to give the sulfonium salt, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{COCH}_{2} \mathrm{~S}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{Cl}^{\ominus}\), which precipitates as it is formed. Attempts to recrystallize the product from ethanol result in formation of methyl sulfide and \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{COCH}_{2} \mathrm{Cl}\). b. \(S_{N} 2\) displacements of alkyl chlorides by OH often are catalyzed by iodide ion, \(\mathrm{RCl}+\mathrm{i} \mathrm{O} \mathrm{H} \stackrel{\mathrm{I}^{\ominus}}{\longrightarrow} \mathrm{ROH}+\mathrm{Cl}^{\ominus}\) and may result in a product with less than \(100 \%\) of inverted configuration at the carbon carrying the chlorine. c. \(^{*}\) Tris(trifluoromethyl)amine, \(\left(\mathrm{CF}_{3}\right)_{3} \mathrm{~N}\), is completely nonnucleophilic, whereas trimethylamine is a good nucleophile.

Classify the following solvents according to effectiveness for solvation of (i) cations and (ii) anions: a. 2 -propanone, \(\mathrm{CH}_{3} \mathrm{COCH}_{3}\) b. tetrachloromethane, \(\mathrm{CCl}_{4}\) c. anhydrous hydrogen fluoride, HF d. trichloromethane, \(\mathrm{CHCl}_{3}\) e. trimethylamine, \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{~N}\) f. trimethylamine oxide, \(\left(\mathrm{CH}_{3}\right)_{3} \stackrel{\oplus}{\mathrm{N}}-\stackrel{\ominus}{\mathrm{O}}\)

Would you expect the \(S_{\mathrm{N}} 2\) reaction of sodium cyanide with methyl bromide to be faster, slower, or about the same with \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{~S}=\mathrm{O}\) or ethanol as solvent? Explain.

An alternative mechanism for \(E 2\) elimination is the following: $$ \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{Cl}+\mathrm{OH}^{\ominus} \stackrel{\text { fast }}{\rightleftharpoons} \ominus: \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Cl}+\mathrm{H}_{2} \mathrm{O} \stackrel{\text { slow }}{\longrightarrow} \mathrm{CH}_{2}=\mathrm{CH}_{2}+\mathrm{Cl}^{\ominus} $$ a. Would this mechanism lead to overall second-order kinetics with respect to the concentrations of \(\mathrm{OH}^{\ominus}\) and ethyl chloride? Explain. b. This mechanism as written has been excluded for several halides by carrying out the reaction in deuterated solvents such as \(\mathrm{D}_{2} \mathrm{O}\) and \(\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{OD}\). Explain how such experiments could be relevant to the reaction mechanism.

Write equations and mechanisms for all the products that might reasonably be expected from the reaction of 2 chlorobutane with a solution of potassium hydroxide in ethanol.

a. Why is potassium tert-butoxide, \(\stackrel{\oplus}{\mathrm{K}} \mathrm{O} \mathrm{C}\left(\mathrm{CH}_{3}\right)_{3}\), an excellent base for promoting elimination reactions of alkyl halides, whereas ethylamine, \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{NH}_{2}\), is relatively poor for the same purpose? b. Potassium tert-butoxide is many powers of ten more effective a reagent for achieving \(E 2\) eliminations in methylsulfinylmethane (dimethyl sulfoxide) than in tert-butyl alcohol. Explain.

The reaction of tert-butyl chloride with water is accelerated strongly by sodium hydroxide. How would the ratio of elimination to substitution products be affected thereby? Explain.

Predict the products of the following reactions: a. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CBr}\left(\mathrm{CH}_{3}\right) \mathrm{CH}_{2} \mathrm{CH}_{3} \underset{S_{\mathrm{N}} 1, E 1}{\stackrel{\mathrm{H}_{2} \mathrm{O}}{\longrightarrow}}\) b. \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCH}\left(\mathrm{CH}_{3}\right) \mathrm{Cl} \underset{S_{\mathrm{N} 1, E 1}}{\stackrel{\mathrm{H}_{2} \mathrm{O}}{\longrightarrow}}\)

Nitriles, RCN, can be prepared by \(S_{\mathrm{N}} 2\) displacement of alkyl derivatives, \(\mathrm{RX}\), by using sodium or potassium cyanide: $$ \mathrm{RX}+\mathrm{NaCN} \rightarrow \mathrm{RCN}+\mathrm{NaX} $$ a. Which of the following solvents would be most suitable for this reaction: water, 2 -propanone, ethanol, benzene, \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{~S}=\mathrm{O}\), or pentane? Give reasons for your choice. b. Which of the six isomeric monobromoderivatives of 1 -methylcyclohexane would you expect to react most rapidly with sodium cyanide? Why? c. If you wished to make 2 -phenylethanenitrile, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CN}\), which of the following phenylmethyl compounds, \(\mathrm{RCH}_{2} \mathrm{X}\), would you select to convert to the nitrile? \(\mathrm{X}=-\mathrm{F},-\mathrm{OH},-\mathrm{OCOCH}_{3},-\mathrm{H},-\mathrm{NH}_{2},-\mathrm{O}_{3} \mathrm{SCH}_{3}\), \(-\mathrm{SO}_{3}-\mathrm{CH}_{3} .\) Why?

Give a plausible explanation for each of the following observations: a. Aqueous sodium chloride will not convert tert-butyl alcohol to tert-butyl chloride but concentrated hydrochloric acid will. b. Better yields are obtained in the synthesis of isopropyl methyl ether starting with methyl iodide rather than sodium methoxide: $$ \begin{array}{l} \mathrm{CH}_{3} \mathrm{I}+\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHO}^{\ominus} \mathrm{Na}^{\oplus} \rightarrow\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHOCH}_{3}+\mathrm{Na}^{\oplus} \mathrm{I}^{\ominus} \\\ \left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHI}+\mathrm{CH}_{3} \mathrm{O}^{\ominus} \mathrm{Na}^{\oplus} \rightarrow\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHOCH}_{3}+\mathrm{Na}^{\oplus} \mathrm{I}^{\ominus} \end{array} $$ c. The following reaction proceeds only if an equivalent amount of silver fluoroborate, \(\mathrm{Ag}^{\oplus} \mathrm{BF}_{4} \ominus\), is added to the reaction mixture: d. 1 -Bromo- 2 -butene reacts with water to give a mixture of 2 -buten- 1 -ol, 3 -buten-2-ol, and some 1,3 -butadiene.

Which compound in the following pairs would react faster under the reaction conditions? Draw the structures of the major products expected. a. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Br}\) or \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{C}\left(\mathrm{CH}_{3}\right)(\mathrm{Br}) \mathrm{CH}_{3}\) in ethanol-water solution. b. Same as in Part a, but with potassium iodide in acetone. c. Same as in Part a, but with potassium hydroxide in ethanol. d. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{~N}\left(\mathrm{CH}_{3}\right)_{3} \mathrm{BF}_{4}\) or \(\mathrm{CH}_{3} \mathrm{CH}_{2} \stackrel{\oplus}{\mathrm{N}}\left(\mathrm{CH}_{3}\right)_{3} \stackrel{\ominus}{\mathrm{O} \mathrm{CH}_{3}}\) on heating in methanol solution.

The \(S_{N} 1\) reactions of many RX derivatives that form moderately stable carbocations are substantially retarded by adding \(\mathrm{X}^{\ominus}\) ions. However, such retardation is diminished, at given \(\mathrm{X}^{\ominus}\) concentrations, by adding another nucleophile such as \(\mathrm{N}_{3} \ominus\). Explain.

Which compound in each of the following pairs would you expect to react more readily with (A) potassium iodide in 2 -propanone, (B) concentrated sodium hydroxide in ethanol, and (C) silver nitrate in aqueous ethanol? Write equations for all the reactions involved and give your reasoning with respect to the predicted orders of reactivity. a. methyl chloride and isobutyl chloride with \(\mathrm{A}, \mathrm{B}\), and \(\mathrm{C}\) b. methyl chloride and tert-butyl chloride with \(\mathrm{A}, \mathrm{B}\), and \(\mathrm{C}\) c. tert-butyl chloride and 1 -fluoro-2-chloro-2-methylpropane with \(\mathrm{B}\) and \(\mathrm{C}\) d. 1 -chloro-2-butene and 4 -chloro-1-butene with \(\mathrm{A}, \mathrm{B}\), and \(\mathrm{C}\)