Nucleophilic Substitution and Elimination Mechanisms: Comparative Reactivity and Mechanistic Analysis

Assignment 3 (8%)

1. Which reaction in each of the following pairs would you expect to take place more rapidly? Explain your answer briefly.

1. (CH₃)₃CBr + OH^– (CH3)3COH by S_N1

or

2. CH₃(CH₂)₃Br + OH^– CH3(CH2)3OH  by S_N1

1. (CH₃)₃CBr + OH^– (CH3)3COH by S_N2

or

2. CH₃(CH₂)₃Br + OH^– CH3(CH2)3OH by S_N2

i) CH₃Br + C₃H₇OH CH₃ O C₃H₇

or

ii)

CH₃Br +

C₃H₇O- CH₃ O C₃H₇

i)

or

ii)

i)

or

ii)

CH₃CH₂I

CH₃CH₂Cl

CH₃CH₂I

CH₃CH₂I

+  OH^– CH₃CH₂OH

+  OH^– CH₃CH₂OH

+ Br^– CH₃CH₂Br C₂H₅OH

+ Br^– CH₃CH₂Br DMSO

2. The reaction

_{CH Cl + KSCN} DMF (solvent) _{CH3SCN + KCl}

follows second-order kinetics.

  Fill in the missing rates in the following table of experimental data.

Expt #	[CH3Cl]] in mol•L–1	[KSCN] inmol•L–1	Rate in mol•L–1•s–1
1	0.10	0.10	2.0 × 10–8
2	0.20	0.10
3	0.20	0.30

Draw the mechanism for this reaction. Label the nucleophile and the leaving group.

3. The reaction of A with water gives two substitution products, B and C.

H₃C CH₃

H Br

A

H3C OH

H3C

CH3

H CH3

B

H OH

C

(methyl groups trans) (methyl groups cis)

Answer the following questions:

1. Explain why both the cis and trans products are formed by drawing out the mechanism for this reaction.
2. If the reaction in a) is carried out using sodium methoxide, CH₃O–Na+, in methanol, the elimination product 1,4-dimethylcyclohexene,

H3C

CH3

H

is obtained. Draw the mechanism for this elimination reaction.

4. Answer the following questions:

Which reagent in each of the following pairs is more nucleophilic? Briefly explain your answer.

1. (CH ) N^– or (CH ) NH
2. (CH₃)₃B or (CH₃)₃N

Which reagent in each of the following pairs is more nucleophilic in the specified solvent? Briefly explain your answer.

1. OH^– or SH^– in water
2. Br^– or CI^– in DMSO (dimethyl sulphoxide)
3. Br^– or CI^– in alcohol
4. Ethers can often be prepared by the SN₂ reaction of alkoxide ions, RO-, with alkyl halides. Suppose you wanted to prepare cyclohexyl methyl ether. Which of the two possible routes shown below would you choose? Explain.

O

+ CH3I

or

OCH3

I

+ CH3O

6.

Match each of the following substitution reactions with one of the above potential energy diagrams. Briefly explain the reasons for your selections.

a) (CH₃)₃CCl + (C6H5)3P (CH3)3CP+(C6H5)3 Cl-

2. (CH₃)₂CHI + KBr (CH3)2CHBr + KI
3. (CH₃)₃COH + HBr (CH3)3CBr + H2O
4. _{CH3CH2Br +}  ^–OCH₂CH₃ CH3CH2 O  CH2CH3 + Br^–
5. Answer the following questions:

Draw the mechanism of the free radical chlorination of cyclohexane to form 1,2-dichlorocyclohexane. Use single-barbed arrows to show the direction of movement of single electrons. Label all steps (chain-initiating and others).

  Draw the mechanistic step that would account for a trace of

in the products. How would you classify this step?

8. Predict the major organic product(s) for each of the following reactions. If there is no reaction, briefly explain why.

a)

OTs

NaCl DMSO

Br

2. NaOEt

3. _OH NaOEt EtOH

4. KOC(CH₃)₃

5. NaOMe

9. Explain by means of reaction equations how you would synthesize each of the following compounds. Show reaction conditions, reagents, and solvents in your equations.
   1. (CH₃)₂C C(CH₃)₂

2. CH₂SC₂H₅

3. (CH₃)₃C O C₂H₅

OH

d)

OH

Cl

e) _CH3

CH₂

f)

10. 10.

This alkyl halide is inert to backside S_N2 displacement. Give a reason for this experimental fact.

Although the alkyl bromide is tertiary, it is also unreactive to S_N1 substitution. Suggest an explanation for this. (You may find it useful to make a model here.)