Chapter 14

a. Methyl iodide can be prepared from potassium iodide and dimethyl sulfate. Why is dimethyl sulfate preferable to methanol in reaction with potassium iodide? b. 1-Bromobutane can be prepared from 1-butanol and sodium bromide in concentrated sulfuric acid. What is the function of the sulfuric acid? c. Some people like to put salt in their beer. Assess the possibility of \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{Cl}\) poisoning from the reaction of \(\mathrm{NaCl}\) with the ethanol in beer. Give your reasoning. d. Both isopropyl bromide and tert-butyl bromide react with sodium ethoxide in ethanol. Which bromide would give the most alkene? Which bromide would give the most alkene on solvolysis in \(60 \%\) aqueous ethanol? Of the two reagents, sodium ethoxide in ethanol or \(60 \%\) aqueous ethanol, which would give the most alkene with each bromide? Give your reasoning.

In the presence of only traces of ionizing agents, either pure 1 -chloro-2-butene or 3 -chloro-1-butene is converted slowly to a 50-50 equilibrium mixture of the two chlorides. Explain.

a. Write the initiation and propagation steps involved in the radical bromination of methylbenzene (toluene) with bromine. Write the low-energy valence-bond structures of the intermediate phenylmethyl radical. b. Calculate \(\Delta H^{0}\) for the following reactions of the radical, using the \(\mathrm{C}-\mathrm{Br}\) bond strength of \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{Br}(55 \mathrm{kcal})\), and any other necessary bond energies. Assume that stabilization arising from electron delocalization is 38 kcal for a phenyl group (Section \(6-5 \mathrm{~A}\) ) and \(5 \mathrm{kcal}\) for the triene structure 3 . What can you conclude from these calculations about the stability of 3 and the likelihood of its formation in this kind of bromination?

Would you expect the behavior of 3-chloropropyne to more nearly resemble 1 -chloropropane or \(3-\)chloropropane in nucleophilic displacement reactions? Give your reasoning.

Arrange the following halides in order of expected increasing reactivity towards (a) sodium iodide in acetone and (b) silver nitrate in ethanol. Indicate your reasoning. $$ \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Cl}, \mathrm{C}_{5} \mathrm{H}_{5} \mathrm{C} \equiv \mathrm{CCl}, \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{C} \equiv \mathrm{CCH}_{2} \mathrm{Cl}, \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}=\mathrm{CHCl} $$

Write a reasonable mechanism for the formation of phenylethanoic acid on heating phenylbromoethyne with potassium hydroxide in aqueous alcohol: $$ \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{C} \equiv \mathrm{CBr} \stackrel{\mathrm{H}_{2} \mathrm{O}-\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{OH}}{\mathrm{KOH}} \stackrel{\mathrm{H}^{\oplus}}{\longrightarrow} \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H} $$

Would you expect 4-bromonitrobenzene or (4-bromophenyl)-trimethylammonium chloride to be more reactive in bimolecular replacement of bromine by ethoxide ion?

Would you expect 4-chloromethoxybenzene and 4-chlorotrifluoromethylbenzene to be more, or less, reactive than chlorobenzene toward methoxide ion? Explain.

Whereas the order of reactivity of alkyl halides toward a given nucleophile is \(\mathrm{I}>\mathrm{Br}>\mathrm{Cl} \gg \mathrm{F}\), the reverse order of reactivity frequently is observed with aryl halides \((\mathrm{F} \gg \mathrm{Cl} \cong \mathrm{Br} \cong \mathrm{I})\). What does this signify regarding the relative rates of the addition and elimination steps (Equations 14-3 and 14-4) in this kind of aromatic substitution?

The reactions of several 1-substituted 2,4-dinitrobenzenes with piperidine (azacyclohexane), Equation \(14-5\), proceed at nearly the same rate, independent of the nature of \(\mathrm{X}\). Rationalize this observation in terms of a mechanism of nucleophilic aromatic substitution.

In the hydrolysis of chlorobenzene-1- \({ }^{14} \mathrm{C}\) with \(4 \mathrm{M}\) aqueous sodium hydroxide at \(340^{\circ}\), the products are \(58 \%\) benzenol-1- \({ }^{14} \mathrm{C}\) and \(42 \%\) benzenol-2- \({ }^{14} \mathrm{C}\). Calculate the percentage of reaction proceeding (a) by an elimination-addition mechanism, and (b) by direct nucleophilic displacement. Would you expect the amount of direct displacement to increase, or decrease, if the reaction were carried out (a) at \(240^{\circ}\) and (b) with lower concentrations of sodium hydroxide? Give you reasoning.

Both 2,4-D and 2,4,5-T are herbicides that have been used for weed control and as defoliating agents in jungle warfare. Apart from the arguments for or against the use of chemicals for such purposes, there have been reports of serious dermatitis among the industrial workers who produce these substances. The cause finally was traced to \(2,3,7,8\) -tetrachlorodibenzo-p-dioxin (TCDD), which is produced as an impurity in the manufacture of 2,4,5-T. This substance (TCDD) is very toxic. In addition to the dermatitis in produces, it is a potent teratogen (induces birth abnormalities). The lethal does is less than \(10^{-6} \mathrm{~g}\) for guinea pigs. Its presence in 2,4,5-T can be eliminated, but the conditions by which it is formed are pertinent to our present discussion. The production of 2,4,5-T involves the substitution of one chlorine of 1,2,4,5-tetrachlorobenzene with hydroxide ion to give 12. This is followed by a second displacement reaction, this time on chloroethanoate by the sodium salt of 12 : If the temperature of the first step exceeds \(160^{\circ}\), then two molecules of 12 react in a double nucleophilic displacement to give TCDD. a. Write reasonable mechanisms for the steps by which two molecules of 12 are converted to TCDD. b. Would you expect TCDD to be formed in the preparation of 2,4-D from 1,2,4-trichlorobenzene? Explain.

Write the structures of the products of the following equations: a. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{MgBr}+\left(\mathrm{CH}_{3}\right)_{2} \mathrm{SO}_{4} \rightarrow\) b. \(\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{MgBr}+\mathrm{CH}_{3} \mathrm{C} \equiv \mathrm{C}-\mathrm{CH}_{2} \mathrm{Br} \rightarrow\) c. \(\mathrm{CH}_{2}=\mathrm{CH}-\mathrm{CH}_{2} \mathrm{Li}+\mathrm{CH}_{2}=\mathrm{CH}-\mathrm{CH}_{2} \mathrm{Cl} \rightarrow\) d. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{MgBr}+\mathrm{ClCH}_{2} \mathrm{OCH}_{3} \rightarrow\) e. \(\mathrm{C}_{4} \mathrm{H}_{9} \mathrm{Na}+\mathrm{C}_{4} \mathrm{H}_{9} \mathrm{Br} \rightarrow\)

Addition of Grignard reagents, \(\mathrm{RMgX}\), to diethyl carbonate, \(\mathrm{O}=\mathrm{C}\left(\mathrm{OC}_{2} \mathrm{H}_{5}\right)_{2}\), gives tertiary alcohols, \(\mathrm{R}_{3} \mathrm{COH}\), on hydrolysis. Write the steps involved in this reaction.

Write structures for the addition, enolization, and reduction products possible for the following reactions: a. \(\mathrm{CH}_{3} \mathrm{COCH}_{3}+\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CMgX}\) b. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{COC}_{6} \mathrm{H}_{5}+\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgX}\) c. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}=\mathrm{CHCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}+\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{MgX}\)

Grignard reagents, such as \(\mathrm{CH}_{3} \mathrm{MgI}\), often add to the triple bond of nitriles, \(\mathrm{RC} \equiv \mathrm{N}\), to give adducts that, on hydrolysis, yield ketones, \(\mathrm{RCOCH}_{3}\). Show the possible steps involved.

Predict the products expected from the reactions of the following compounds: Grignard reagent to \(\mathrm{CH}_{2}=\mathrm{CH}-\mathrm{COCH}_{3}\) ? Give your reasoning.

In the reaction of \(14-38 e\), when the aqueous acid is mixed with 2 -methyl-2-butanol, the mixture is initially homogenous, but it soon separates into two phases. Explain why two phases appear. On separation of the phases using a separatory funnel, which layer (upper or lower) would contain the organic product? If you were unsure, how could you quickly find out?

Suppose one could hydrolyze pure cis-1-chloro-2-butene exclusively by (a) the \(S_{\mathrm{N}} 1\) mechanism or (b) the \(S_{\mathrm{N}} 2\) mechanism. Would you expect the 2 -butenol formed in each case to be the cis isomer, the trans isomer, or a mixture?

Explain why 2-chloropyridine is more reactive than 3-chloropyridine in nucleophilic substitution reactions.

Explain why 2-chloropyridine reacts with potassium amide \(\left(\mathrm{KNH}_{2}\right)\) in liquid ammonia solution at \(-33^{\circ}\) to give 2 -aminopyridine, whereas 3 -chloropyridine under the same conditions gives a mixture of \(65 \% 4\) -amino- and \(35 \%\) 3aminopyridine.

Explain why the substitution reactions of the following halonaphthalenes give about the same ratio of 1 - and 2- naphthyl products independently of the halogen substituent and the nucleophilic reagent. Show the steps involved.

Nucleophilic displacement of the halogen of 3,5-dimethyl-4-nitrobromobenzene is much slower than with the corresponding compound lacking the methyl groups. Give a reasonable explanation of this observation. (Construction of molecular models will help.)

Methylmagnesium halides have been employed as analytical reagents for the determination of the number of acidic hydrogens in a molecule (the Zerewitinoff determination). The method involves measuring the amount of methane produced from a given weight of compound (such as \(\mathrm{RH}\), with an acidic hydrogen) by the following reaction: $$ \mathrm{CH}_{3} \mathrm{MgI}+\mathrm{RH} \rightarrow \mathrm{CH}_{4}+\mathrm{RMgI} $$ Excess methylmagnesium iodide and \(0.1776 \mathrm{~g}\) of Compound A (formula \(\mathrm{C}_{4} \mathrm{H}_{10} \mathrm{O}_{3}\) ) react to give \(84.1 \mathrm{~mL}\) of methane collected over mercury at \(740 \mathrm{~mm}\) and \(25^{\circ}\). How many acidic hydrogens does Compound A possess per molecule? Suggest a possible structure on the basis that spectral data indicate (a) there is no \(\mathrm{C}=\mathrm{O}\) group in the molecule and (b) \(\mathbf{A}\) is achiral.

From the nature of the carbon-metal bonds in organometallic compounds, predict the products of the following reactions. Give your reasoning. a. \(\mathrm{CH}_{3} \mathrm{MgCl}+\mathrm{ICl}\) b. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{Li}+\mathrm{CH}_{3} \mathrm{OH}\) c. \(\mathrm{CH}_{3} \mathrm{Li}+\mathrm{HC} \equiv \mathrm{CH}\) d. \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{Li}+\mathrm{CuI}\)

The following experimental observations have been reported: 1\. tert-Butyl chloride was added to lithium metal in dry ether at \(35^{\circ}\). A vigorous reaction ensued with evolution of hydrocarbon gases. After all the lithium metal was consumed, the mixture was poured onto dry ice. The only acidic product that could be isolated (small yield) was 4,4-dimethylpentanoic acid. 2\. tert-Butyl chloride was added to lithium metal in dry ether at \(-40^{\circ}\). After all the lithium had reacted, the mixture was carbonated and gave a good yield of 2,2-dimethylpropanoic acid. 3\. tert-Butyl chloride was added to lithium metal in dry ether at \(-40^{\circ} .\) After all the lithium was consumed, ethene was bubbled through the mixture at \(-40^{\circ}\) until no further reaction occurred. Carbonation of this mixture gave a good yield of 4,4-dimethylpentanoic acid. a. Give a reasonably detailed analysis of the results obtained and show as best you can the mechanisms involved in each reaction. b. Would similar behavior be expected with methyl chloride? Explain. c. Would you expect that a substantial amount of 6,6-dimethylheptanoic acid would be found in Observation 3? Explain.

Predict the products of each of the following Grignard reactions before and after hydrolysis. Give reasoning or analogies for each. a. \(\mathrm{CH}_{3} \mathrm{MgI}+\mathrm{HCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5} \rightarrow\) b. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}(\mathrm{MgBr}) \mathrm{CH}_{3}+2,4\) -dimethyl-3-pentanone \(\rightarrow\) c. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}+\mathrm{CS}_{2} \rightarrow\) d. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}+\mathrm{NH}_{3} \rightarrow\)

Each of the following equations represents a "possible" but not actually feasible Grignard synthesis. Consider each equation and determine why it will not proceed satisfactorily as written. Give your reasoning and show what the actual product will be. a. \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CMgBr}+\left[\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}\right]_{2} \mathrm{C}=\mathrm{O} \rightarrow \rightarrow\left(\mathrm{CH}_{3}\right)_{3} \mathrm{C}\left[\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CH}\right]_{2} \mathrm{COH}\) b. \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCH}_{2} \mathrm{MgBr}+\left[\left(\mathrm{CH}_{3}\right)_{3} \mathrm{C}\right]_{2} \mathrm{C}=\mathrm{O} \rightarrow \rightarrow\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCH}_{2}\left[\left(\mathrm{CH}_{3}\right)_{3} \mathrm{C}\right]_{2} \mathrm{COH}\) ?. \(\mathrm{CH}_{3} \mathrm{MgI}+\mathrm{CH}_{3}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{COCl} \rightarrow \rightarrow \mathrm{CH}_{3}\left(\mathrm{CH}_{3}\right)_{2} \mathrm{COCH}_{3}\) d. \(\mathrm{CH}_{3} \mathrm{MgI}+\mathrm{CH}_{3} \mathrm{CCH}=\mathrm{N}-\mathrm{CH}_{3} \rightarrow \rightarrow \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{~N}\left(\mathrm{CH}_{3}\right)_{2}\) e. \(\mathrm{BrCH}_{2} \mathrm{CH}_{2} \mathrm{O}_{2} \mathrm{CCH}_{3} \underset{\left(\mathrm{CH}_{2} \mathrm{H}_{5}\right)_{2} \mathrm{O}}{\stackrel{\mathrm{Mg}}{\longrightarrow}}\) Grignard reagent \(\stackrel{\mathrm{CH}_{2} \mathrm{O}}{\longrightarrow} \rightarrow \mathrm{HOCH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{O}_{2} \mathrm{CCH}_{3}\) f. \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{MgCl}+\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{Br} \rightarrow \mathrm{CH}_{2}=\mathrm{CH}\left(\mathrm{CH}_{2}\right)_{2} \mathrm{CH}_{3}\)

The rate of addition of dimethylmagnesium to excess diphenylmethanone (benzophenone) in diethyl ether initially is cleanly second order, that is, first order in ketone and first order in \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{Mg}\). As the reaction proceeds, the rate no longer follows a strictly second-order rate overall. Suggest how the apparent specific rate could change as the reaction proceeds.

Compound X, of formula \(\mathrm{C}_{3} \mathrm{H}_{5} \mathrm{Br}_{3}\), with methyllithium formed bromocyclopropane and 3-bromopropene. The NMR spectrum of \(\mathrm{X}\) showed a one-proton triplet at \(5.9 \mathrm{ppm}\), a two-proton triplet at \(3.55 \mathrm{ppm}\), and a complex resonance centered at \(2.5\) ppm downfield from TMS. What is the structure of \(X\) ? Account for the products observed in its reaction with methyllithium.