Solution: Explain how the following changes would affect the

What product is formed when 1-bromopropane reacts with each of the following nucleophiles? a. \(\mathrm{HO}^{-}\) b. \({ }^{-} \mathrm{NH}_{2}\) c. \(\mathrm{CH}_{3} \mathrm{SH}\) d. \(\mathrm{HS}^{-}\) e. \(\mathrm{CH}_{3} \mathrm{O}^{-}\) f. \(\mathrm{CH}_{3} \mathrm{NH}_{2}\)

Which member of each pair is a better nucleophile in methanol?

Which member in each pair in Problem 34 is a better leaving group?

What nucleophiles would react with 1-iodobutane to prepare the following compounds?

Explain how the following changes would affect the rate of the reaction of 1-bromobutane with methoxide ion in DMF. a. The concentration of both the alkyl halide and the nucleophile are tripled. b. The solvent is changed to ethanol. c. The nucleophile is changed to ethanol. d. The alkyl halide is changed to 1-chlorobutane. e. The alkyl halide is changed to 2-bromobutane.

Explain how the following changes would affect the rate of the reaction of 2-bromo-2- methylbutane with methanol: a. The alkyl halide is changed to 2-chloro-2-methylbutane. b. The alkyl halide is changed to 2-chloro-3-methylbutane

Starting with cyclohexene, how could the following compounds be prepared? a. methoxycyclohexane b. cyclohexylmethylamine c. dicyclohexyl ether

Rank the following species in order from best nucleophile to poorest nucleophile.

The p Ka of acetic acid in water is 4.76. What effect would a decrease in the polarity of the solvent have on the p Ka ? Why?

a. Identify the substitution products that form when 2-bromo-2-methylpropane is dissolved in a mixture of 80% ethanol and 20% water. b. Explain why the same products are obtained when 2- chloro-2-methylpropane is dissolved in a mixture of 80% ethanol and 20% water.

Draw the substitution products for each of the following reactions; if the products can exist as stereoisomers, show what stereoisomers are obtained: a. ( R )-2-bromopentane + CH 3 O d. allyl chloride + CH 3 OH b. ( R )-3-bromo-3-methylheptane + CH 3 OH e. 1-bromo-2-butene + CH 3 O c. benzyl chloride + CH 3 CH 2 OH f. 1-bromo-2-butene + CH 3 OH

Draw the products obtained from the solvolysis of each of the following compounds in ethanol:

Would you expect methoxide ion to be a better nucleophile if it were dissolved in CH 3 OH or if it were dissolved in DMSO? Why? 48. Which reaction in each of the following pairs will take place more

Which reaction in each of the following pairs will take place more rapidly?

Alkylbenzyldimethyl ammonium chloride is a leave-on skin antiseptic used to treat such things as cuts and cold sores. It is also the antiseptic in many hand sanitizers. It is actually a mixture of compounds that differ in the number of carbons (any even number between 8 and 18) in the alkyl group. Show three different sets of reagents (each set composed of an alkyl chloride and an amine) that can be used to synthesize the alkylbenzyldimethyl ammonium chloride shown here.

Fill in the blanks in the following chemical equations:

In Section 9.9 , we saw that S -adenosylmethionine (SAM) methylates the nitrogen atom of noradrenaline to form adrenaline, a more potent hormone. If SAM methylates an OH group attached to the benzene ring instead, it completely destroys noradrenalines activity. Show the mechanism for the methylation of the OH group by SAM.

tert -Butyl chloride undergoes solvolysis in both acetic acid and formic acid. Solvolysis occurs 5000 times faster in one of these two solvents than in the other. In which solvent is solvolysis faster? Explain your answer. ( Hint: See Table 9.5 .)

What substitution products are obtained when each of the following compounds is added to a solution of sodium acetate in acetic acid? a. 2-chloro-2-methyl-3-hexene b. 3-bromo-1-methylcyclohexene

Show how each of the following compounds can be synthesized from the given starting materials:

In which solventethanol or diethyl etherwould the equilibrium for the following S N 2 reaction lie farther to the right?

The rate of the reaction of methyl iodide with quinuclidine was measured in nitrobenzene, and then the rate of the reaction of methyl iodide with triethylamine was measured in the same solvent. The concentration of the reagents was the same in both experiments. a. Which reaction had the larger rate constant? b. The same experiment was done using isopropyl iodide instead of methyl iodide. Which reaction had the larger rate constant? c. Which alkyl halide has the larger kquinuclidine/ktriethylamine ratio?

Two bromoethers are obtained from the reaction of the following alkyl dihalide with methanol. Draw the structures of the ethers.

The rate constant of an intramolecular reaction depends on the size of the ring ( n ) that is formed. Explain the relative rates of formation of the cyclic secondary ammonium ions.

Draw the substitution products for each of the following reactions, assuming that all the reactions are carried out under S N 2 conditions. If the products can exist as stereoisomers, show what stereoisomers are formed:

a. Draw the product of each of the following reactions: b. Give two sets of reactants (each set including an alkyl halide and a nucleophile) that could be used to synthesize the following alkyne: c. Give two sets of reactants (each set including an alkyl halide and a nucleophile) that could be used to synthesize the following ether:

Propose a mechanism for the following reaction:

Explain why tetrahydrofuran can solvate a positively charged species better than diethyl ether can.

The reaction of an alkyl chloride with potassium iodide is generally carried out in acetone to maximize the amount of alkyl iodide that is formed. Why does the solvent increase the yield of alkyl iodide? ( Hint: Potassium iodide is soluble in acetone, but potassium chloride is not.)

a. Propose a mechanism for the following reaction. b. Explain why two products are formed. c. Explain why methanol substitutes for only one of the bromines

Chlordane, like DDT, is an organohalide that was used as an insecticide for crops such as corn and citrus and for lawns. In 1983, it was banned for all uses except against termites, and in 1988 it was banned for use against termites as well. Chlordane can be synthesized from two reactants in one step. One of the reactants is hexachlorocyclopentadiene. What is the other reactant? ( Hint : See Section 8.19 .)

When equivalent amounts of methyl bromide and sodium iodide are dissolved in methanol, the concentration of iodide ion quickly decreases and then slowly returns to its original concentration. Account for this observation.

Explain why the following alkyl halide does not undergo a substitution reaction, regardless of the conditions under which the reaction is run.

The reaction of chloromethane with hydroxide ion at \(30 \ ^\circ C\) has a \(\Delta G^\circ\) value of -21.7 kcal/mol . What is the equilibrium constant for the reaction?

Problem 1P Draw the structure of DDE.

Problem 2P Methoxychlor is an insecticide that was intended to take DDT’s place because it is not as soluble in fatty tissues and is more readily biodegradable. It, too, can accumulate in the environment, however, so its use was also banned—in 2002 in the European Union and in 2003 in the United States. Why is methoxychlor less soluble in fatty tissues than DDT?

Problem 3P How would the rate of the reaction between bromomethane and hydroxide ion be affected if the following changes in concentration are made? a. The concentration of the alkyl halide is not changed and the concentration of the nucleophile is tripled. b. The concentration of the alkyl halide is cut in half and the concentration of the nucleophile is not changed. c. The concentration of the alkyl halide is cut in half and the concentration of the nucleophile is doubled.

Does increasing the energy barrier for an \(S_{N}2\) reaction increase or decrease the magnitude of the rate constant for the reaction?

Problem 5P Arrange the following alkyl bromides in order of decreasing reactivity in an SN2 reac­tion: l-bromo-2-methylbutane, l-bromo-3-methylbutane, 2-bromo-2-methylbutane, and 1-bromopcntane.

Problem 6P 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

Draw the substitution products that will be formed from the following \(S_{N}2\) reactions: a. cis-1-bromo-4-methylcyclohexane and hydroxide ion b. trans-1-iodo-4-ethylcyclohexane and methoxide ion c. cis-1-chloro-3-methylcyclobutane and ethoxide ion

Problem 9P Indicate whether each of the following solvents is protic or aprotic: a. chloroform (CHCl3) b. diethyl ether c. acetic acid d. hexane

Which alkyl halide would you expect to be more reactive in an \(\mathrm{S}_\mathrm{N}2\) reaction with a given nucleophile? In each case, you can assume that both alkyl halides have the same stability.

Problem 10P a. Which is a stronger base, RO- or RS-? b. Which is a better nucleophile in an aqueous solution? c. Which is a better nucleophile in DMSO?

Problem 11P Which is a better nucleophile? a. Br - or Cl - in H2O b. Br - or Cl - in DMSO c. CH3O - or CH3OH in H2O d. CH3O - or CH3OH in DMSO e. HO - or -NH2 in H2O f. HO - or -NH2 in DMSO g. I - or Br - in H2O h. I - or Br - in DMSO

Which reaction in each of the following pairs occurs faster:

What is the product of the reaction of bromoethane with each of the following nucleophiles? a. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{O}^{-}\) b. \(\mathrm{CH}_{3} \mathrm{C} \equiv \mathrm{C}^{-}\) c. \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{N}\) d. \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{S}^{-}\)

a. Explain why the reaction of an alkyl halide with ammonia gives a low yield of primary amine. b. Explain why a much better yield of primary amine is obtained from the reaction of analkylhalide with azide ion (\(^-\text{N}_3\)), followed by catalytic hydrogenation. (Hint: An alkyl azide is not nucleophilic.) Equation Transcription: -N3 Text Transcription: -N3

Problem 17P Draw the stereoisomers that will be formed from the following SN1 reactions: a. 3-bromo-3-methylpentane and methanol b. 3-chloro-3-methylhexane and methanol

Problem 18P Arrange the following alkyl halides in order from most reactive to least reactive in an SN1 reaction: 2-bromo-2-methylpentane, 2-chloro-2-methylpentane, 3-chloropentane, and 2-iodo-2-methylpentane.

Which alkyl halide would you expect to be more reactive in an \(\mathrm{S}_\mathrm{N}1\) solvolysis reaction? Equation Transcription: SN1 Text Transcription: S_N 1

Which alkyl halide would you expect to be more reactive in an \(\mathrm{S}_\mathrm{N}1\) reaction? In each case, you can assume that both alkyl halides have the same stability. Equation Transcription: SN1 Text Transcription: S_N 1

For the pairs of alkyl halides in \(\text{Problem} \ 20\), which would be more reactive in an \(\mathrm{S}_\mathrm{N}2\) reaction? Equation Transcription: Problem 20 SN2 Text Transcription: Problem 20 S_N 2

Problem 22P Two substitution products result from the reaction of 3-chloro-3-methyl-1-butene with sodium acetate (CH3COO-Na+) in acetic acid under conditions that favor an SN1 reaction. Identify the products.

Draw the products obtained from each of the following reactions and show their configurations a. under conditions that favor an \(\mathrm{S}_\mathrm{N}2\) reaction. b. under conditions that favor an \(\mathrm{S}_\mathrm{N}1\) reaction. Equation Transcription: SN2 SN1 Text Transcription: S_N 2 S_N 1

Draw the configuration(s) of the substitution product(s) that will be formed from the reactions of the following compounds with the indicated nucleophile:

Which of the following reactions will go faster if the concentration of the nucleophile is increased?

Problem 26P Amines are good nucleophiles, even though they are neutral molecules. How would the rate of an SN2 reaction between an amine and an alkyl halide be affected if the polarity of the solvent is increased?

How will the rate of each of the following \(\mathrm{S}_\mathrm{N}2\) reactions change if it is carried out in a more polar solvent? Equation Transcription: SN2 Text Transcription: S_N 2

Which reaction in each of the following pairs will take place more rapidly?

Problem 30P Would you expect acetate ion (CH3CO2-) to be a better nucleophile in an SN2 reaction with an alkyl halide carried out in methanol or in dimethyl sulfoxide?

Problem 31P Under which of the following reaction conditions would (R)-1-chloro-1-phenylethane form the most (R)-1-phenyl-1-ethanol: HO- in 50% water and 50% ethanol or HO- in 100% ethanol?

After a proton is removed from the \(\mathrm{OH}\) group, which compound in each pair would form a cyclic ether more rapidly? Equation Transcription: OH Text Transcription: OH

Draw the products of the following reactions:

Propose a mechanism for the following reaction:

Problem 35P What product is formed when 1-bromopropane reacts with each of the following nucleophiles? a. HO- c. CH 3SH e. CH3O- b. -NH2 d. HS- f. CH3NH2

Problem 36P Which member of each pair is a better nucleophile in methanol? a. H2O or HO- c. H2O or H2S e. I- or Br- b. NH3 or H2O d. HO- or HS- f. Cl- or Br-

Problem 37P Which member in each pair in Problem 36 is a better leaving group? 36. Which member of each pair is a better nucleophile in methanol? a. H2O or HO- c. H2O or H2S e. I- or Br- b. NH3 or H2O d. HO- or HS- f. Cl- or Br-

What nucleophiles would react with \(1-\text{iodobutane}\) to prepare the following compounds? Equation Transcription: 1-iodobutane Text Transcription: 1-iodobutane

Problem 39P Explain how the following changes would affect the rate of the reaction of 1-bromobutane with methoxide ion in DMF. a. The concentration of both the alkyl halide and the nucleophile are tripled. b. The solvent is changed to ethanol. c. The nucleophile is changed to ethanol. d. The alkyl halide is changed to 1-chlorobutane. e. The alkyl halide is changed to 2-bromobutane.

Problem 40P Explain how the following changes would affect the rate of the reaction of 2-bromo-2-methylbutane with methanol: a. The alkyl halide is changed to 2-chloro-2-methylbutane. b. The alkyl halide is changed to 2-chloro-3-methylbutane.

Starting with cyclohexene, how could the following compounds be prepared? a. methoxycyclohexane b. cyclohexylmethylamine c. dicyclohexyl ether

Rank the following species in order from best nucleophile to poorest nucleophile.

Problem 43P The pKa of acetic acid in water is 4.76. What effect would a decrease in the polarity of the solvent have on the pKa? Why?

a. Identify the three products that are formed when 2-bromo-2-methylpropane is dissolved in a mixture of 80% ethanol and 20% water. b. Explain why the same products are obtained when 2-chloro-2-methylpropane is dissolved in a mixture of 80% ethanol and 20% water.

Draw the substitution products for each of the following reactions; if the products can exist as stereoisomers, show what stereoisomers are obtained: a. (R)-2-bromopentane + \(\mathrm{CH}_{3} \mathrm{O}^{-}\) b. (R)-3-bromo-3-methylheptane + \(\mathrm{CH}_{3} \mathrm{OH}\) c. benzyl chloride + \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OH}\) d. allyl chloride + \(\mathrm{CH}_{3} \mathrm{OH}\) e. 1-bromo-2-butene + \(\mathrm{CH}_{3} \mathrm{O}^{-}\) f. 1-bromo-2-butene + \(\mathrm{CH}_{3} \mathrm{OH}\)

Draw the products obtained from the solvolysis of each of the following compounds in ethanol:

Problem 47P Would you expect methoxide ion to be a better nucleophile if it were dissolved in CH3OH or in DMSO? Why?

Which reaction in each of the following pairs will take place more rapidly?

Problem 49P Alkylbenzyldimethyl ammonium chloride is a leave-on skin antiseptic used to treat such things as cuts and cold sores. It is also the antiseptic in many hand sanitizers. It is actually a mixture of compounds that differ in the number of carbons (any even number between 8 and 18) in the alkyl group. Show three different sets of reagents (each set composed of an alkyl chloride and an amine) that can be used to synthesize the alkylbenzyldimethyl ammonium chloride shown here.

Fill in the blanks in the following chemical equations:

In \(\text{Section} \ 9.9\), we saw that \(\mathrm{S}-\text{adenosylmethionine}\) (\(\mathrm{SAM}\)) methylates the nitrogen atom of noradrenaline to form adrenaline, a more potent hormone. If \(\mathrm{SAM}\) methylates an \(\mathrm{OH}\) group attached to the benzene ring instead, it completely destroys noradrenaline’s activity. Show the mechanism for the methylation of the \(\mathrm{OH}\) group by \(\mathrm{SAM}\). Equation Transcription: Section 9.9 S-adenosylmethionine (SAM) OH Text Transcription: Section 9.9 S-adenosylmethionine (SAM) OH

tert-Butyl chloride undergoes solvolysis in both acetic acid and formic acid. Solvolysis occurs \(5000\) times faster in one of these two solvents than in the other. In which solvent is solvolysis faster? Explain your answer. (Hint: See \(\text{Table} \ 9.5\)) Equation Transcription: 5000 Table 9.5 Text Transcription: 5000 Table 9.5

Problem 53P What substitution products are obtained when each of the following compounds is added to a solution of sodium acetate in acetic acid? a. 2-chloro-2-methyl-3-hexene b. 3-bromo-1-methylcyclohexene

Show how each of the following compounds can be synthesized from the given starting materials:

In which solvent—ethanol or diethyl ether—would the equilibrium for the following \(\mathrm{S}_\mathrm{N}2\) reaction lie farther to the right? Equation Transcription: SN2 Text Transcription: S_N 2

The rate of the reaction of methyl iodide with quinuclidine was measured in nitrobenzene, and then the rate of the reaction of methyl iodide with triethylamine was measured in the same solvent. The concentration of the reagents was the same in both experiments. a. Which reaction had the larger rate constant? b. The same experiment was done using isopropyl iodide instead of methyl iodide. Which reaction had the larger rate constant? c. Which alkyl halide has the larger \(\mathrm{K}_{\text {quiauclidine }} / \mathrm{K}_{\text {tciethylacine }}\) ratio? Equation Transcription: kquinuclidine/ktriethylamine Text Transcription: k_quinuclidine/k_triethylamine

Two bromoethers are obtained from the reaction of the following alkyl dihalide with methanol. Draw the structures of the ethers.

The rate constant of an intramolecular reaction depends on the size of the ring (\(\mathrm{n}\)) that is formed. Explain the relative rates of formation of the cyclic secondary ammonium ions. Equation Transcription: n Text Transcription: n

Problem 59P Draw the substitution products for each of the following reactions, assuming that all the reactions are carried out under SN2 conditions. If the products can exist as stereoisomers, show what stereoisomers are formed: a. (3S,4S)-3-bromo-4-methylhexane + CH3O- c. (3R,4R)-3-bromo-4-methylhexane + CH3O- b. (3S,4R)-3-bromo-4-methylhexane + CH3O- d. (3R,4S)-3-bromo-4-methylhexane + CH3O-

1. Draw the product of each of the following reactions: 2. Give two sets of reactants (each set including an alkyl halide and a nucleophile) that could be used to synthesize the following alkyne: 3. Give two sets of reactants (each set including an alkyl halide and a nucleophile) that could be used to synthesize the following ether:

Propose a mechanism for the following reaction:

Explain why tetrahydrofuran can solvate a positively charged species better than diethyl ether can.

Problem 63P The reaction of an alkyl chloride with potassium iodide is generally carried out in acetone to maximize the amount of alkyl iodide that is formed. Why does the solvent increase the yield of alkyl iodide? (Hint: Potassium iodide is soluble in acetone, but potassium chloride is not.)

1. Propose a mechanism for the following reaction. 2. Explain why two products are formed. 3. Explain why methanol substitutes for only one of the bromines.

Chlordane, like \(\mathrm{DDT}\), is an organohalide that was used as an insecticide for crops such as corn and citrus and for lawns. In \(1983\), it was banned for all uses except against termites, and in \(1988\) it was banned for use against termites as well. Chlordane can be synthesized from two reactants in one step. One of the reactants is hexachlorocyclopentadiene. What is the other reactant? (Hint : See \(\text{Section} \ 8.19\)) Equation Transcription: DDT 1983 1988 Section 8.19 Text Transcription: DDT 1983 1988 Section 8.19

Problem 66P When equivalent amounts of methyl bromide and sodium iodide are dissolved in methanol, the concentration of iodide ion quickly decreases and then slowly returns to its original concentration. Account for this observation.

Explain why the following alkyl halide does not undergo a substitution reaction, regardless of the conditions under which the reaction is run.

Problem 68P The reaction of chloromethane with hydroxide ion at 30 oC has a ?Go value of -21.7 kcal/mol. What is the equilibrium constant for the reaction?