7. Substitution Reactions

Predict the product of the reaction

Predict the product of the reaction

Predict the product of the substitution reactions, paying attention to the stereochemical outcome.

(b) <IMAGE>

(•••) 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?

<IMAGE>

Predict the product of the following substitution reactions, making sure to note whether a rearrangement should occur.

(a) <IMAGE>

(••) Predict the product of the following substitution reactions, paying close attention to the stereochemical outcome of the reactions.

(f) <IMAGE>

(•••) Give a mechanism for the following substitution and elimination reactions.

(c) <IMAGE>

Would the following nucleophiles be more likely to participate in an Sₙ1 or Sₙ2 reaction?

(c) <IMAGE>

For each solvent, indicate the most likely substitution reaction to take place.

(a) <IMAGE>

For each solvent, indicate the most likely substitution reaction to take place.

(e) <IMAGE>

Would you expect the following conditions to favor Sₙ1 or Sₙ2?

(b) <IMAGE>

Predict the product of the following substitution reactions, making sure to note whether a rearrangement should occur.

(b) <IMAGE>

Predict the product of the following substitution reactions, making sure to note whether a rearrangement should occur.

(d) <IMAGE>

(•) Suggest a mechanism for the following substitution reactions.

(c) <IMAGE>

(•) Suggest a mechanism for the following substitution reactions.

(d) <IMAGE>

(••) Predict the product of the following substitution reactions, paying close attention to the stereochemical outcome of the reactions.

(e) <IMAGE>

Would the following nucleophiles be more likely to participate in an Sₙ1 or Sₙ2 reaction?

(a) <IMAGE>

Would the following nucleophiles be more likely to participate in an Sₙ1 or Sₙ2 reaction?

(f) <IMAGE>

For each solvent, indicate the most likely substitution reaction to take place.

(g) <IMAGE>

(••) Predict the product of the following substitution reactions, paying close attention to the stereochemical outcome of the reactions.

(b) <IMAGE>

(••) Predict the product of the following substitution reactions, paying close attention to the stereochemical outcome of the reactions.

(c) <IMAGE>

Would the following nucleophiles be more likely to participate in an Sₙ1 or Sₙ2 reaction?

(e) <IMAGE>

Fill in the squares in the following chemical equations:

a. <IMAGE>

b. <IMAGE>

Fill in the squares in the following chemical equations:

c. <IMAGE>

d. <IMAGE>

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

Draw the substitution products for each of the following reactions. If the ­products can exist as stereoisomers, show which stereoisomers are formed:

a. (3S, 4S)-3-bromo-4-methylhexane + CH3O-

b. (3S, 4R)-3-bromo-4-methylhexane + CH3O-

Draw the substitution products for each of the following reactions. If the ­products can exist as stereoisomers, show which stereoisomers are formed:

a. (3R, 4R)-3-bromo-4-methylhexane + CH3O-

b. (3R, 4S)-3-bromo-4-methylhexane + CH3O-

a. Propose a mechanism for the following reaction.

<IMAGE>

Draw the substitution and elimination products.

a. <IMAGE>

b. <IMAGE>

What nucleophiles would form the following compounds as a result of reacting with 1-iodobutane?

a. <IMAGE>

b. <IMAGE>

What nucleophiles would form the following compounds as a result of reacting with 1-iodobutane?

e. <IMAGE>

f. <IMAGE>

Aldolase shows no activity if it is incubated with iodoacetic acid before fructose-1,6-bisphosphate is added to the reaction mixture. What causes this loss of activity?

Predict the major products of the following substitutions.

a. ethyl bromide CH3CH2Br + potassium tert-butoxide (CH3)3CO- K+ —>

Predict the major products of the following substitutions.

f. 1-chloropentane + KF 18-crown-6 CH3CN —>

Chlorocyclohexane reacts with sodium cyanide (NaCN) in ethanol to give cyanocyclohexane. 

The rate of formation of cyanocyclohexane increases when a small amount of sodium iodide is added to the solution. 

Explain this acceleration in the rate.

Draw perspective structures or Fischer projections for the substitution products of the following reactions.

(b) <IMAGE> + NaOH water/acetone—> 

Optically active 2-bromobutane undergoes racemization on treatment with a solution of KBr. 

a. Give a mechanism for this racemization.

In contrast, optically active butan-2-ol does not racemize on treatment with a solution of KOH. 

b. Explain why a ­reaction like that in part (a) does not occur.

For each reaction, give the expected substitution product, and predict whether the ­mechanism will be predominantly first order (SN1) or second order (SN2).

Hint: The strength of the nucleophile (or base) usually determines the order of the reaction. Strong nucleophiles encourage bimolecular, second-order reactions, and weak nucleophiles more commonly react by unimolecular, first-order mechanisms. Also, SN2 is unlikely with 3° halides, and SN1 is unlikely with 1° halides unless they are resonance-stabilized.

c. 1-iodo-1-methylcyclohexane + ethanol

The following reaction takes place under second-order conditions (strong nucleophile), yet the structure of the product shows rearrangement.

Also, the rate of this reaction is several thousand times faster than the rate of substitution of ­hydroxide ion on 2-chlorobutane under similar conditions.

Propose a mechanism to explain the enhanced rate and ­rearrangement observed in this unusual reaction. (“Et” is the abbreviation for ethyl.)

<IMAGE> -OH—> <IMAGE> + Cl-

Using the given starting material, any necessary inorganic reagents and catalysts, and any carbon-containing compounds with no more than three carbons,

indicate how each of the following compounds can be prepared:

a. <IMAGE>

For each reaction, give the expected substitution product, and predict whether the ­mechanism will be predominantly first order (SN₁) or second order (SN₂).

a. 2-chloro-2-methylbutane + CH₃COOH

b. isobutylbromide + sodium methoxide

Show how you might use SN2 reactions to convert 1-chlorobutane into the following compounds.

a. butan-1-ol

Show how you might use SN2 reactions to convert 1-chlorobutane into the following compounds.

b. 1-fluorobutane

A solution of pure (S)-2-iodobutane

([α] = +15.90° ) in acetone is allowed to react with radioactive iodide, 131I-, until 1.0% of the iodobutane contains radioactive iodine.

The specific rotation of this recovered iodobutane is found to be +15.58°.

b. What does this result suggest about the mechanism of the reaction of 2-iodobutane with iodide ion?

Show how you would convert (in one or two steps) 1-phenylpropane to the three products shown below.

In each case, explain what unwanted reactions might produce undesirable impurities in the product.

1-phenylpropane <IMAGE>


(c) 2-phenylbutanenitrile <IMAGE>

Using cyclohexane as one of your starting materials, show how you would synthesize the following compounds.

(c) <IMAGE>

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.

<IMAGE>

Which reaction in each of the following pairs takes place more rapidly? (EtOH is ethyl alcohol; Et2O is diethyl ether.)

d. CH3Br+HO−→DMSO CH3OH+Br−

   CH3Br+HO−→EtOH CH3OH+Br−

e. CH3Br+NH3→Et2O CH3N+H3+Br−

  CH3Br+NH3→EtOH CH3N+H3+Br−

Under which of the following reaction conditions will (R)-1-chloro-1-phenylethane form the most (R)-1-phenyl-1-ethanol: in water or in 1.0 M HO−?

Draw the substitution products for each of the following reactions; if the products can exist as stereoisomers, show what stereoisomers are obtained:

e. 1-bromo-2-butene+CH3O−

f. 1-bromo-2-butene+CH3OH

(••) LOOKING BACK When (R)-(1-bromoethyl)benzene is treated with sodium cyanide, a single enantiomer is produced. However, upon treatment of the same molecule with water, a mixture of two enantiomers is obtained. (a) Explain these results. (b) Why is only partial racemization sometimes observed?

<IMAGE>

Order the following molecules on the basis of their nucleophilic strength using the pKₐ values of their conjugate acids.

<IMAGE> <IMAGE> <IMAGE> <IMAGE>

Suggest a reagent to carry out each of the following conversions to an alcohol.

(c) <IMAGE>

(••) Predict the product(s) of the following reactions.

(f) <IMAGE>

(••) Predict the product(s) of the following reactions.

(g) <IMAGE>

(••••) When trans-4-bromocyclohexanol is treated with base, an intramolecular substitution reaction occurs to give a cyclic ether. This product does not form when cis-4-bromocyclohexanol is reacted under the same conditions. Explain these observations.

<IMAGE> <IMAGE>

Which of the following reactions take place more rapidly when the concentration of the nucleophile is increased?

<IMAGE>

<IMAGE>

<IMAGE>

Even with an excess of cyanide, only one equivalent will react with the following dibromoalkane. To which carbon will the cyanide add? Predict the product and explain your choice.

<IMAGE>

(••••) Suggest a mechanism for the following reactions.

(a) Substitution :

<IMAGE>

(••) Predict the product(s) that would result when molecules (a)–(p) are allowed to react under the following conditions: (i) SOCl₂ ; (ii) PBr₃ ; (iii) SOCl₂ , NEt₃ (iv) 1. TsCl, Et₃N 2. NaCN; (v) 1. TsCl, Et₃N 2. NaOt-Bu (vi) H₂SO₄ (vii) HCl; (viii) HBr; (ix) PCC; (x) H₂CrO₄ , H₂O (xi) HOCl, H₂O (xii) HIO₄ If no reaction occurs, write 'no reaction.'

(o) <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.'

(o) <IMAGE>

(••) Predict the product(s) that would result when molecules (a)–(p) are allowed to react under the following conditions: (i) SOCl₂ ; (ii) PBr₃. If no reaction occurs, write 'no reaction.'

(k) <IMAGE>

Explain how 1-butanol can be converted into the following compounds:

a. <IMAGE>

Explain how 1-butanol can be converted into the following compounds:

b. <IMAGE>

cis-4-Bromocyclohexanol and trans-4-bromocyclohexanol form the same elimination product but a different substitution product when they react with HO−.

<IMAGE>

b. Explain, by showing the mechanisms, why different substitution products are obtained.

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.

Provide an arrow-pushing mechanism that rationalizes the outcome of the reaction shown.

<IMAGE>

Provide a mechanism for the following Sₙ1 reactions that feature a rearrangement.

(b) <IMAGE>

Suggest a mechanism for the following substitution reactions.

(c) <IMAGE>

(••) Predict the product(s) that would result when molecules (a)–(p) are allowed to react under the following conditions: (vii) HCl; (viii) HBr; If no reaction occurs, write 'no reaction.'

(o) <IMAGE>

(••) Predict the product(s) that would result when molecules (a)–(p) are allowed to react under the following conditions:(vii) HCl; (viii) HBr If no reaction occurs, write 'no reaction.'

(k) <IMAGE>

What stereoisomers does the following reaction form?

<IMAGE>

When tert-butyl bromide is heated with an equal amount of ethanol in an inert solvent, one of the products is ethyl tert-butyl ether.

a. What happens to the reaction rate if the concentration of ethanol is doubled?

Explain the difference in reactivity between 

CH3O+H2 and CH3OH in a nucleophilic substitution reaction. (The pKa of H3O+ is −1.7.)