CH 318M (Majors)

Final Exam

Fall, 2004

Prof. N. L. Bauld





                                                            __________________________________________                                                                              Name (Last, First)















CH 318M (Majors)

Final Exam

Fall, 2004

Prof. N. L. Bauld





                                                            __________________________________________                                                                              Name (Last, First)











Possible Points

Page/Pts/Points Earned




















































I.Mechanisms of Nucleophilic Substitution Reactions


A.  Nucleophilic Substitution Mechanisms


1.   [5 pts] A certain substrate which conforms to the general structure R-L (see below) reacts with a certain nucleophile of generalized structure Nu-‑. The rate of the reaction in this specific case was found to be independent of the concentration of the salt Na+ Nu- which contains the nucleophilic anion. Write the detailed mechanism for this reaction and the mechanistic symbol. Explain why the rate of the reaction is independent of the concentration of the nucleophile.

q      The symbol is SN1.

q      The rate is independent of the concentration of the nucleophile because the nucleophile is not present in the rate-determining step, which is the heterolysis of the R-L bond.


2. [5 pts] Draw a reaction path diagram for the reaction and indicate on this diagram (1)the labels of the coordinate axes  (2) the structures of species which are free energy minima.and (3) the activation free energy for the reaction.




3. [3 pts] Indicate on your reaction path diagram, and by explanation in the space below, the requirements (two) for a given step of a reaction to be rigorously rate-determining.

q      The intermediate must not return to reactants, but always go on to products. This is fulfilled by having the activiation energy for the reversal of the first step be substantially larger than that for the forward second step.

q      The intermediate must not build up substantially in concentration. This is fulfilled by the circumstance that the activation energy for the second step be very small (conversion to the product is very fast).


4. [3 pts] If the rds is partially reversible, is that step still classified as rigorously rate-determining? Why or why not? What would be the appropriate term used to describe this step if it were significantly but only modestly reversible?






5. [6 pts] Employ resonance theory to derive a TS model for the rate-determining step of the reaction, summarize as a DL/PC, and characterize this TS model. Extend your characterization by invoking the Hammond Principle.

q      The TS has carbocation character.

q      Since the step is endothermic, the TS has extensive carbocation character.



6. [5 pts] For the reactions of various R-L, where the nature of R is varied as shown below, but the same mechanism is operative as in the first question (A.1), indicate the expected sequence of rates (1 = fastest). Explain your answer by using the Method of Competing Transition States (i.e., provide a TS model and characterization for each of these R groups).




q      Tertiary carbocation character is the most favorable, followed by secondary, then primary, then methyl as the least favorable.


7. [2 pts]  Is the difference in rates between the various R groups (e.g., tert-butyl and isopropyl) expected to be large or small? Explain, giving two reasons for your answer.

q      Large. First because the difference in stability between a tertiary and a secondary carbocation is large (about 20 kcal/mol).

q      Second, because the TS has extensive carbocation character. A large fraction of the total carbocation stabilizing effect is felt in the TS.

 II. More On Nucleophilic Substitutions



A.   Consider the nucleophilic substitution reaction given in the equation below:



1. [2 pts] Based upon the structure of the alkyl halide involved in this reaction, you should be able to predict the kind of mechanism involved. What is the symbolic mechanistic designation for this reaction?

q      SN2


2. [2] Considering only the number of steps involved in the reaction, what is the appropriate term which applies to a reaction having this number of steps?

q      Concerted


3. [3 pts] Write down the form of the kinetic rate law for this reaction, and define the term “rate constant”.

q      Rate = k [CH3CH2Cl][OH-‑]

q      The rate constant, k, is the rate of the reaction at unit concentrations of all reactants (it represents the intrinsic rate of the reaction).


4.  [6 pts] Provide a complete resonance theoretical treatment (derive) for the rds of this reaction, summarize as a DL/PC structure, characterize the TS, and indicate what kind of structural effect this character is especially sensitive to.


q      The TS has pentacovalent carbon character

q      It is especially sensitive to steric effects.


B. Solvent Effects 

1.    [3 pts] Using the DL/PC model of the TS for the rds of the reaction of chloroethane with the hydroxide anion (IIA. above), provide a prediction of the effect upon the reaction rate of this reaction when the solvent polarity is increased. Be specific, and explain your reasoning.

q      Increased solvent polarity has the effect of modestly (or slightly) slowing down the reaction.

q      This is because the reactant and product side both are anionic, and both will be stabilized by solvation. For this reason the effect upon the rate is small.

q      The rate is decreased because solvation is more effective for smaller ions, and the hydroxide anion is smaller than the TS anion (which contains the hydroxide ion).


C. Stereochemistry of S­N2 Reactions.

1.    [5 pts] S­N2 reactions are known to occur exclusively via a backside (invertive) displacement. Using an appropriate illustration to support your answer, provide an explanation for this powerful preference for inversion over retention (frontside displacement) based upon MO theory (specifically frontier MO theory or HOMO/LUMO theory or Filled Orbital/Vacant Orbital Interactions). Explain why the frontside attack mode would be highly unfavored and why the factor which makes fronside attack unfavorable is not operative for a backside attack.


q      Recall that strong bonding requires two electrons. The interaction between two filled orbitals gives four electrons, which results in no bonding. Therefore the interaction between the filled nucleophile orbital and the BMO corresponding to the C-L sigma bond provides no bonding interaction.

q      But the interaction between the filled nucleophile orbital and the vacant antibonding orbital corresponding to the C-L sigma bond could potentially give rise to bonding. Unfortunately,  positive overlap of the nucleophile with the carbon AO is at least partially or wholly negated by the antibonding interaction between the nucleophile orbital and the orbital on the leaving group, as shown in the diagram.

q      On the other hand the interaction between the filled nucleophile orbital and the antibonding orbital of the C-L bond (shown with sp2 hybridization) can be bonding without the interference of the negative overlap with the leaving group orbital, because the distance between Nu and L is too large for any effective interaction.



2.    [3 pts] Provide another reason for the preference for inversion based upon the shape of the LUMO of the C-L bond. Again, provide an appropriate illustration to support your answer and explain why the LUMO has this shape. 


q      This is because interference between the positive and negative lobes drives electron density away from the antibonding region between the nuclei and more toward the back lobe.

q      For this reason, better overlap with the nucleophile is available from the back lobe on carbon than on its front lobe.



            III.Elimination Reactions; Competition with SN Reactions



A. Mechanism of Elimination Reactions

            1 [7 pts] Use resonance theory to derive a TS model for the elimination reaction shown below, summarize as a DL/PC structure, and characterize the resulting TS model carefully and completely. Your resonance treatment should include all three good resonance structures.



q      The TS has alkene character.

q      It also has some carbanion character at the beta carbon.


2.    [3 pts] Which character of the TS is dominant when chloride ion is the leaving group? What is the proper name which is associated with eliminations of this kind?

q      Alkene Character.

q      Saytzeff or Zaitsev elimination.


3.    [2 pt]  Assuming that this is a concerted reaction, what is the symbolic mechanistic designation for the reaction mechanism?

q      E2


            4. [3 pts] Is this reaction base catalyzed? Why or why not? What is the appropriate term to describe the role of the base in this reaction?

q      No. The base is consumed stoichiometrically in the reaction.

q      Base-promoted.


B. Elimination vs Substitution

1.    [2 pts] In the reaction above between chloroethane and an alkoxide anion, another product can be obtained. Write the structure of that product.


2.    [5 pts] When ethoxide ion (R = Et) is used as the base one of these two possible products is the major one and when tert-butoxide is used as the base (R = tert-butyl) the other is the predominant product. Indicate which base gives which product and explain in detail, with supporting illustrations, the basis for this disparate behaviour.

q      With ethoxide the main product is the SN2 product, because SN2 reactions at primary carbon atoms are fast.

q      With the tert-butoxide ion the main product is ethene. This is partly because this later base is a stronger base (more than 100 fold) than ethoxide.

q      But especially because the the tert-butoxide ion is a somewhat hindered base, which makes the SN2 TS more congested and less favorable.




B. Selectivity in Systems in Which There are Two Non-Equivalent Beta Hydrogens

            1. [5 pts] Provide the structures and names of the products of the following reaction. Designate the alpha and the two distinct beta positions of the reactant and indicate which product arises from the removal of which beta hydrogen, and which product is the major product.



q      The 2-butenes are the major products.



            2. [4 pts] Use the Method of Competing Transition States to compare the TS’s for the reactions leading to these products. Apply the respective characters of these transition states to explain the predominance of the product which is observed to be major.


q      The TS on the left, which leads to 1-butene, has monosubstituted alkene character, while that on the right, which leads to the 2-butenes, has disubstituted alkene character.

q      The 2-butenes are the major products since the more highly substituted alkene character is favored (or alkyl groups stab ilize alkenes and alkene character).



3.    [3 pts] The selectivity in these eliminations is seen to be relatively low, i.e., both products are formed in very substantial amounts. Provide two distinct reasons for this lack of selectivity. One of these reasons should involve an application of the Hammond Principle.

o      Since the reaction “goes” (i.e., it is spontaneous), it is exothermic. Therefore the TS at least somewhat more closely resembles the reactants than the products of this step. The product is the alkene, so the TS has only modest alkene character.

o      The full amount of the difference in stability between a monosubstitued and a disubstituted alkene is only 2.7 kcal/mol, so even if the TS had extensive alkene character, the selectivity would only be moderate.





A.   IUPAC Nomenclature

            1. [3 pts] Provide the correct and complete IUPAC name for the following alcohol. Indicate the numbering system that you are using.

B. Conversion of Alcohols to Ethers

1.    [4 pts] Use Retrosynthetic Analysis to devise two different synthetic routes by which the following ether can be efficiently synthesized,using an alkyl halide and an alcohol as the starting materials. Sketch the synthetic routes.



q      Note to Graders: Give one extra point if the preparation of the alkoxide from the alcohol plus sodium is shown.


2.    [1 pts] What is the appropriate name by which this kind of ether synthesis is commonly known (its inventor)?

q      Williamson Synthesis


3.    [2 pts] What is the mechanistic symbol for the key reaction involved in this ether synthesis? Explain why this particular mechanism is operative.

q      SN2


4.    [2 pts] Describe the limitations of this synthetic method, and indicate specifically what other reaction type can compete with this type of ether synthesis.

q      Only applies to methyl and primary halides.

q      Competition is with E2 elimination, especially for secondary and tertiary halides.

B. pK­a’s of Alcohols.


1.    [3 pts] Explain why the pKa of tert-butyl alcohol is considerably higher than that of primary and secondary alcohols. Provide the specific name of the effect which makes tert-butyl alcohol a weaker acid, as well as a pictorial illustration of the effect.



q      The tert-butoxide anion is less efficiently solvated than an unhindered alkoxide, so the former is less stable. Decreased anion stability engenders decreased acidity.

q      The effect is termed “steric hindrance to solvation”.





A. IUPAC Nomenclature

            1. [3 pts each = 6 pts] Provide correct and complete IUPAC names for the following compounds:

q      a. 2-cyclopropoxybutane (preferred) or cyclopropyl 2-butyl ether (okay)

q      b. cis-3-methoxycyclohexanol


B. “Autoxidation” of Ethers

            1. The overall reaction for the air oxidation of diethyl ether to yield an explosive hydroperoxide product is shown below, following by the detailed mechanism for this reaction.



a.     [3 pts]Indicate the name of the kind of special stabilization the organic radical formed in the first step has and illustrate this by means of an MO energy level diagram.

q      Three electron bonding.




b.    [2 pts] The bond dissociation energy, D, of a peroxidic O-H bond is much less than than of an alcohol or water O-H bond. Provide an explanation for the relative weakness of the peroxide O-H bond. .


q      The peroxy radical also has three electron bonding. The radical site is on oxygen, and the other oxygen supplies the unshared electron pair.


F. Cleavage of Ethers

            1. [4 pts] Although ethers are, relatively speaking, a rather unreactive class of organic compounds, they are effectively cleaved by hydrogen bromide. Write the detailed mechanism for the cleavage of the ether depicted below to form an alkyl bromide and an alcohol. Explain why the ether cleaves in the specific direction that it does cleave.




q      The cleavage could go by an SN1 mechanism as shown, because the tert-butl carbocation is relatively stable, but it could go by an SN2 reaction on the primary carbon to cleave off the ethyl group as ethyl bromide.

q      The cleavage occurs as it does because a unimolecular reaction is inherently faster than a biomolecular reaction.


            2. [2 pts] Explain why HBr is much more effective in cleaving ethers than is HCl. What does this imply about the reactivity of HI? Why?

q      The reaction is generally (except in the case of tertiary ethers) an SN2 reaction, so the stronger the nucleophile the faster the rate.

q      Bromide ion is a much stronger nucleophile than chloride ion (the polarization or soft electron effect).

q      Reaction is even faster with HI.


VI. Epoxides


A. Cleavage of Epoxides in Acidic Media

            1. [5 pts]  Provide a complete resonance theoretical treatment of the conjugate acid of the epoxide of propene (methyloxirane), and summarize as a DL/PC structure. At which carbon is the carbocation character largest? Explain in terms of a simple axiom of resonance theory..



q      Structures B and C show carbocation character on both epoxide carbon atoms, but structure B is of lower energy than structure C, because in B the carbocation center is tertiary and in C it is primary. Therefore B contributes more than C to the resonance hybrid, and there is more carbocation character at the tertiary carbon..


2. [2 pts] Write the structure(s) or the product(s) obtained when this conjugate acid reacts with methanol.


3. [3 pts] If there is any selectivity in this reaction, what type of selectivity is involved. Explain the theoretical basis for the particular kind of selectivity observed here.

q      Regioselectivity

q      The nucleophile tends to react at the position which has the greatest amount of carbocatioin character (positive charge accumulation).

q      Extra 2 points: If it is mentioned that this reaction is strongly exothermic, so the TS resembles the reactant of this step, which is the oxonium ion (which has extensive carbocation character and relatively little product character).

q      Therefore the covalent bond to the nucleophile is weak and long in the TS. Therefore, steric effects are small, and charge effects are large.


5.    [2 pts] In what respect is the site of reactivity of the conjugate acid somewhat surprising?

q      The nucleophile reacts at a tertiary carbon, which is highly hindered, instead of at a much less hindered primary carbon.


VII. Alkynes Synthesis


A. Nomenclature of Alkynes

            1. [ 2 pts] Draw the structure of a non-terminal (internal) alkyne and provide its  correct IUPAC name.. The alkyne must have more than five carbons atoms and one alkyl and one halogen substituent.

q      As just one example.


B. Acidity of Alkynes

            1. [4 pts] Cite the approximate pKa of ethyne (acetylene), and describe its  acidity in comparison to alkenes and alkanes. Your answer should include: (1) the general factor accounting for its differential acidity (2) the specific factor involved (3) an orbital depiction of the conjugate base of ethyne and (4) an explanation of how this factor distinguishes between the acidities of ethene, ethane, and ethyne.


q      The pKa of ethyne is ca. 21.

q      The general factor which accounts for the unusually high acidity of ethyne is anion stability.

q      The specific factor which accounts for anion stability is hybridization. In the ethyne conjugate base, the unshared pair is in an sp AO, which is the lowest energy of the hybrid AO’s. In the case of the conjugate base of ethene, the unshared pair is in an sp2 AO and for ethane an sp3 AO. The order of stability parallels the s content, going from 50% for the alkyne conjugate base, to 25% for the ethane conjugate base.



2. [3 pts] Consider the bond dissociation energies of the C-H bonds shown below. Which C-H bond has the larger D? Explain why.

q      The ethyne C-H bond is stronger, i.e., has the larger D.

q      The C-H bond of ethyne is formed using an sp orbital, whereas that in ethane is formed using an sp3 AO.

q      Since the sp orbital is much lower in energy, the BMO formed from it is also of much lower energy.


            3. [3 pts] Indicate what kind of bond cleavage is occurring in B1 and B2 above, and discuss any differences inf the ease of breaking the ethyne C-H bond by these two different processes.

q      In B1, the bond-breaking is heterolytic, whereas in B2 the bond breaking is hemolytic.

q      The ethyne C-H bond is easier to break heterolytically but harder to break homolytically. This is because in heterolytic dissociation, anion stability effects are dominant over bond dissociation energy effects.


C. Synthesis of Alkynes

            1. [3 pts] Sketch an efficient synthesis of the the alkyne shown below, starting with 1-pentene. [Caution: Be specific and careful in your choice of the nature of the base used and the amount of it]

q      Graders: Do not count off for omitting water from the b. part of the second step.

q      Note that you must start with 1-pentene.

q      You must use sodium amide (at least for one of the elimination steps).

q      You must use 3 moles of NaNH2.


            2. [4 pts]  Show by providing the proper reagents on the scheme below how the latter alkyne (the one made in the immediately preceding question) could be converted to cis-2-hexene and also, independently, trans-2-hexene with high selectivity ( in each case, a single reaction).