7. Substitution Reactions

Predict the product of the following reaction.

Predict the product of the following reaction:

Will the following Sₙ2 reaction proceed more rapidly in DMSO or H₂O?

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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?

The following reaction, though run under standard solvolysis conditions, occurs via an Sₙ2 reaction. Why?

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(•••) Crown ethers are able to solvate cations based on their size. Specifically, 15-crown-5 forms stable complexes with sodium. How would the addition of a crown ether change the rate of an Sₙ2 reaction?

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The S_N2 reaction is the concerted, backside displacement of a good leaving group by a nucleophile [see Chapter 12]. Why do nucleophiles attack from the back in S_N2 reactions?

(••) For each pair, choose the haloalkane that would react most quickly in an Sₙ2 reaction.

(a) <IMAGE> vs. <IMAGE>

(••) Predict the product(s) that would result when molecules (a)–(p) are allowed to react under the following conditions: (iii) SOCl₂ , NEt₃ (iv) 1. TsCl, Et₃N 2. NaCN; If no reaction occurs, write 'no reaction.'

(f) <IMAGE>

Practice your electron-pushing skills by drawing a mechanism for the following Sₙ2 reactions.

(c) <IMAGE>

(•) For each pair, choose the nucleophile that would react most quickly in an Sₙ2 reaction (assume H₂O is the solvent).

(c) <IMAGE> vs. <IMAGE>

(••) For each pair, choose the haloalkane that would react most quickly in an Sₙ2 reaction.

(c) <IMAGE> vs. <IMAGE>

In which solvent—ethanol or diethyl ether—would the equilibrium for the following SN2 reaction lie farther to the right?

<IMAGE>

How will the rate of each of the following SN2 reactions change if it is carried out in a more polar solvent?

b. <IMAGE>

How will the rate of each of the following SN2 reactions change if it is carried out in a more polar solvent?

c. CH3CH2I+NH3→CH3CH2N+H3 I−

Show all the products, including their configurations, that are obtained from the above reaction.

You were told in [SECTION 7.11] that is best to use a methyl halide or a primary alkyl halide for the reaction of an acetylide ion with an alkyl halide. Explain why this is so.

Would you expect acetate ion (CH₃CO₂⁻) to be a better nucleophile in an S_N2 reaction with an alkyl halide carried out in methanol or in dimethyl sulfoxide?

Draw a perspective structure or a Fischer projection for the products of the following SN2 reactions.

e. <IMAGE> + NaOCH3 CH3OH—>

Draw a perspective structure or a Fischer projection for the products of the following SN2 reactions.

f. <IMAGE> + NH3 excess

Predict the compound in each pair that will undergo the SN2 reaction faster.

(c) <IMAGE> or <IMAGE>

(d) <IMAGE> or <IMAGE>

For each pair of compounds, state which compound is the better SN2 substrate.

c. 2-bromobutane or isopropyl bromide

d. 1-chloro-2,2-dimethylbutane or 2-chlorobutane

e. 1-iodobutane or 2-iodopropane

Triethyloxonium tetrafluoroborate, (CH3CH2)3O+ BF4-, is a solid with melting point 91–92 °C.

Show how this reagent can transfer an ethyl group to a nucleophile (Nuc:−) in an SN2 reaction.

What is the leaving group?

Why might this reagent be preferred to using an ethyl halide?

(Consult [TABLE 6-2] <IMAGE>)

b. Explain why a much better yield of primary amine is obtained from the reaction of an alkyl halide with azide ion

(-N3), followed by catalytic hydrogenation. (Hint: An alkyl azide is not nucleophilic.)

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Consider the reaction of 1-bromobutane with a large excess of ammonia (NH3).

b. Draw the reactants, the transition state, and the products. Note that the initial product is the salt of an amine (RNH3+ Br−), which is deprotonated by the excess ammonia to give the amine.

Draw a perspective structure or a Fischer projection for the products of the following SN₂ reactions.

a. trans-1-bromo-3-methylcyclopentane + KOH

b. (R)-2-bromopentane + KCN

Draw a perspective structure or a Fischer projection for the products of the following SN2 reactions.

c. <IMAGE> + NaI acetone—>

d. <IMAGE> + NaSH

Predict the major products of the following reactions.

(d) the tosylate of cyclohexylmethanol + excess NH₃

(e) n-butyl tosylate + sodium acetylide, <IMAGE>

Rank the following compounds in decreasing order of their reactivity toward the SN2 reaction with sodium ethoxide (Na^{+ -}OCH2CH3) in ethanol.

Methyl chloride

Tert-butyl iodide 

Neopentyl bromide

Isopropyl bromide

Methyl iodide

Ethyl chloride

When (±)−2,3−dibromobutane reacts with potassium hydroxide, some of the products are (2S,3R)-3-bromobutan-2-ol and its enantiomer and trans-2-bromobut-2-ene.

Why is no cis-2-bromobut-2-ene formed?

3 bromobutan-2-ol <IMAGE> <IMAGE>

trans-2-bromobut-2-ene <IMAGE>

a. Which reacts faster in an SN2 reaction?

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a. Explain why the alkyl halide shown here reacts much more rapidly with guanine than does a primary alkyl halide (such as pentyl chloride).

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Which of the following Sₙ2 reactions should proceed at a faster rate? Justify your answer on a reaction coordinate diagram.

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vs.

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