Topic 1: Conjugated dienes and allylic cations: resonance

1.1How do you pronounce “diene”?
 
1.2What is conjugation?
 
1.3 What are the two main classes of dienes?
 
1.4 Which type of diene is of particular interest in this chapter?
 
1.5 What the order in energy from lowest to highest be for hexa-1,2-diene, hexa-1,3-diene, and hexa-1,4-diene be? How do you explain that?
 
1.6 Describe the bonding in 1,3-butadiene. How does that influence its conformational options?
 
1.7 What do s-cis and s-trans refer to? Which is more stable?
 
1.8Explain the bonding in the allyl cation. Why would allyl bromide react faster than propyl bromide in an SN2 reaction? Why might it also react using an SN1 mechanism even though technically it is a primary alkyl halide?
 
1.9Why would 1-bromo-3-methyl-2-butene be particularly reactive in SN1 and SN2 reactions?
 
1.101-bromo-2-butene upon heating will dissociate to give an allylic cation and bromide anion. How else could one generate this same cation using a different starting material and other conditions?
 

Topic 2: Addition of HX to 1,3-dienes: kinetic vs thermodynamic control

2.1 What is Markovnikov‘s Rule? Under what experimental conditions is it relevant?
 
2.2 Why is Markovnikov‘s Rule related to reactions of dienes?
 
2.3 What are “1,2” and “1,4” addition?
 
2.4 Why don‘t we ever consider “1,3”, “2,1”, “2,3”, or “3,1” addition?
 
2.5It is safe to say that the 1,2-addition product is always favored at low temperature. Despite what you might read, it is NOT safe to say anything general about the 1,4-addition product. It is often found that it is favored at high temperature, but in some cases it is never favored under any conditions. How can that be? Can you find an example where the 1,2-addition product is favored at both low and high temperature? [HINT: Explore the reaction with different isomers of dimethylpentadiene.]
 
2.6What is the difference between thermodynamic stability and kinetic stability?
 
2.7 Which of kinetic control and thermodynamic control specifically relates to activation energy?
 
2.8 Which of kinetic control and thermodynamic control specifically relates to ground-state energy?
 
2.9 Based on your understanding of the Boltzmann distribution, why does low temperature favor the kinetic product, at least initially?
 
2.10 How does reversibility fit into this discussion?
 
2.11 If I claimed that even low temperature favors the formation of the thermodynamic product, because all reactions proceed toward equilibrium, how would you help me argue that case? How would you counter it?
 
2.12 What does raising the temperature actually do in all chemical reactions? Think Boltzmann.
 

Topic 3: The Diels-Alder reaction, Part I: concerted [4 + 2] cycloaddition

3.1 Who were Diels and Alder? They‘re long dead, it turns out. When did they do this work? Did they know each other? Were they friends? competitors?
 
3.2 Does “Diels” rhyme with “deals” or “dials”? How do you know?
 
3.3 What exactly is the Diels-Alder reaction? Use a source beyond your book to be sure you have the best definition.
 
3.4 What is a concerted reaction? And why is that especially good for selectivity?
 
3.5 Why is the Diels-Alder reaction still one of the most powerful, most reliable, most used reactions in synthetic organic chemistry, even after all these years?
 
3.6 What is an intramolecular Diels-Alder reaction?
 
3.7 What is a hetero Diels-Alder reaction?+I292
 

Topic 4: The Diels-Alder reaction, Part II: stereo- and regio-selectivity

4.1 The Diels-Alder reaction is both stereoselective and regioselective. Explain the origins of this selectivity
 
4.1 How many different isomeric outcomes are possible in the Diels-Alder addition of the following two compounds? Find pairwise relationships among them that are enantiomeric, diastereomeric, or neither (that is, the two are regioisomers, not stereoisomers).

 
4.2 The Diels-Alder reaction, like the SN2 reaction or catalytic hydrogenation, is also stereospecific. What is it about all these mechanisms that raise them to the special level of being stereospecific, not just stereoselective?
 
4.3 How does your book define “endo” and “exo”?
 
4.4 Can you define endo addition without any reference to a “bridge” position? That is, how would you generalize the idea in the book to real cases, where the diene is not a 1,3-cyclopentadiene?
 
4.5How do the terms “electron withdrawing group” and “electron donating group” fit into this discussion?
 
4.6What is “partial charge”? And how does that fit into this conversation?
 
4.7The Diels-Alder reaction is concerted, but that does not mean all bonds are being formed to the same extent at all times. In order to explain the very high regioselectivity of the Diels-Alder reaction, which bond is probably most formed first?
 
4.8 What is an asymmetric Diels-Alder reaction? Why might that be of particular practical use?
 

Topic 5: Benzene

5.1What is a Kekulé structure?
 
5.2How do we pronounce Kekulé?
 
5.3What does a double-headed arrow mean, and why don‘t we just use two arrows, one going to the right, and one going to the left, to describe resonance contributors?
 
5.4Why is it incorrect to every say that one resonance contributor is “more stable” than another resonance contributor?
 
5.5Draw three valid Lewis structures that are consistent with the formula C6H6, but can be ruled out based on experimental evidence?
 
5.6One of Prof. Hanson‘s pet peeves is that people should never ever use curved arrows to show resonance. Why do you think this bothers him so much?
 
5.7After reading the IUPAC Rule 93.35, comment on whether it is ever appropriate to refer to or ask for the IUPAC name for a compound. That is, why do the authors of this preamble write, To force the naming of all compounds into the Procrustean bed of one set of rules would not serve the needs of general communication?
 
5.8What are the IUPAC-preferred names that do not have “benzene” in them of three monosubstituted benzenes?
 
5.9What do ortho, meta, and para refer to? When (and only when) are they useful in names? When might their use be appropriate outside of actually naming compounds?
 
5.10What is the difference in meaning between phenol, phenyl, and benzyl?
 

Topic 6: Aromaticity, the Hückel (4n + 2) rule, and molecular orbital theory

6.1What is a chemical “species”? (How is that different than a “compound”?)
 
6.2Read the IUPAC Gold Book definition of the Hückle rule . What are the key elements a structure has to have to be said to “obey” the Hückel (4n + 2) rule (and thus likely represent an “aromatic” species)?
 
6.3When do you count electrons in lone pairs on oxygen or nitrogen when those atoms are in rings being considered as possibly aromatic?
 
6.4Why can we read “anti-aromatic” as “hypothetical only — never going to happen.”
 
6.5What is the significance of the terms atomic orbital, MO, HOMO, LUMO, σ (sigma), π (pi), ѱ (psi), bonding, nonbonding, antibonding, and degenerate in the context of aromaticity?
 
6.6The essential success of Hückel‘s simple mathematical analysis was that in aromatic systems there tends to be a deep π orbital below pairs of degenerate orbitals. How does that lead to the 4n + 2 rule?
 
6.7What does “antiaromatic” look like on an MO diagram?
 

Topic 7: Electrophilic aromatic substitution

7.1What is the mechanism of electrophilic aromatic substitution? [Note that when writing mechanisms, it is never necessary to draw more than one resonance contributor. You can do that if you want (as long as you add […] around them), but it is not necessary. Your author does not show these brackets, but you must if you decide to show all resonance contributors.]
 
7.2How many steps are involved in an electrophilic aromatic substitution, ignoring production of the electrophile?
 
7.3Which is the faster reaction — The addition of the electrophile, or the loss of H+?
 
7.4Are the conditions for electrophilic aromatic substitution acidic or basic? Why?
 

Topic 8: Halogenation, nitration, and sulfonation

8.1What is the function of the Lewis acid in these reactions?
 
8.2You know that “H+” does not exist and that it is just an abbreviation. What is it an abbreviation for? [Hint: Most organic reactions are not carried out in water.]
 
8.3If I told you that “Br+” is an abbreviation we can use in an aromatic bromination, what would that be an abbreviation for?
 
8.4Write the mechanism for a bromination reaction using the abbreviations “H+” and “Br+”, using no curvy arrows and only one resonance contributor for the intermediate cation.
 
8.5Why are only Br2 and Cl2 used in aromatic halogenation OF BENZENE, never I22 or F22?
 
8.6Is this a general statement, or is iodination of other aromatic compounds possible? How do you know?
 
8.7What is “E+” in an aromatic nitration? What is the recipe for making it?
 
8.8What is “E+” in an aromatic sulfonation? What is the recipe for making it?
 

Topic 9: Friedel-Crafts alkylation and acylation

9.1What is an “alkyl” group?
 
9.2What is “E+” in a Friedel-Crafts alkylation? (That is, why the quotes?) What is a recipe for making it?
 
9.3What are three other recipes for creating alkyl cations that you learned from last semester?
 
9.4What is a complication of the Friedel-Crafts alkylation that is always a concern when a mechanism involves alkyl cations?
 
9.5(Looking ahead) Alkyl groups on a benzene ring accelerate the F-C alkylation reaction. What is the implication of this, since the product of the F-C alkylation of benzene adds an alkyl group to the benzene ring?
 
9.6What is an “acyl” group?
 
9.7What is “E+” in a Friedel-Crafts acylation? What is a recipe for making it?
 
9.8What problem of the F-C alkylation does F-C acylation solve?
 
9.9(Looking ahead) Adding an acyl group to a benzene ring slows down the F-C acylation reaction. How does this also make F-C acylation more useful than F-C alkylation?
 
9.10What synthetic limitation (bonus?) is introduced by F-C acylation that is not present in F-C alkylation?
 
9.11What does intramolecular mean? What is an example of an intramolecular Friedel-Crafts acylation?
 

Topic 10: Electron-Donating and electron-withdrawing groups

10.1What is the difference between inductive and resonance effects?
 
10.2What is the most electron donating group discussed in this section?
 
10.3What is the most electron withdrawing group discussed in this section?
 
10.4How does the 3D structure of aniline provide strong evidence that for the NH2 group at least, resonance effects win out over inductive effects? (See Wikipedia for aniline, 3D model (JSmol) - Interactive image in the information box on the right.)
 
10.5The 1H nmr signal for benzene comes at δ 7.2. The ortho- and para-hydrogens in anisole appear at δ 6.9. What does this tell you?
 
10.6Why are NO2 and SO3OH such strong electron-withdrawing groups?
 

Topic 11: Electrophilic aromatic substitution of substituted benzenes

11.1Why are electrophilic aromatic substitution reactions accelerated by electron-donating groups already on the benzene ring?
 
11.2How could this cause serious problems specifically for Friedel-Crafts alkylation?
 
11.3How does the same reasoning also lead to the observed preference of electron-donating groups for ortho/para- vs. meta-regioselectivity in electrophilic aromatic substitutions?
 
11.4Why are electrophilic aromatic substitution reactions slowed down by electron-withdrawing groups already on the benzene ring? Explain using the comparison of two reaction coordinate diagrams, including all resonance contributors for the intermediate in each case.)
 
11.5What is the mechanistic explanation for why all meta directors are electron withdrawing?
 
11.6What makes halogens different from all other deactivators in terms of the observed patterns of electrophilic substitution?
 
11.7What makes halogens totally different from other deactivators in terms of electronics?
 
11.8How does your author finesse this issue?
 
11.9What do other authors say about this?
 
11.10What do you think is the best explanation for why halogens slow down electrophilic aromatic substitutions but still direct the incoming electrophile to the ortho and para positions?
 
11.11Why doesn‘t OH also do this? [Hint: The answer to this question has something to do with orbital size.]
 
11.12Why should it not be surprising that aniline cannot be a substrate for any Friedel-Crafts reaction?
 
11.13Why should it be surprising that aniline is an ortho-para director in the case of nitration or sulfonation? [Recall the conditions of the reaction.]
 

Topic 12: Limitations of electrophilic aromatic substitution

12.1Aniline and phenol are too reactive under the standard conditions of halogenation. What happens instead?
 
12.2What is the solution to this problem?
 
12.3Neither Friedel-Crafts alkylation nor Friedel Crafts acylation can be carried out on aromatic systems that already have strong electron-withdrawing groups. (Note that “strong” here excludes halogens.) What is the explanation of this?
 
12.4F-C alkylation and F-C acylation also do not work for aniline. Why is that?
 
12.5(Looking ahead) The solution in cases involving aniline and phenol is to first “tone them down” by treatment with acetyl chloride (Section 22.8), as shown below, where “X” is the benzene ring. See discussion. Why does this solve the problem? What additional potential problem does it raise?



 
12.6What is polyalkylation, and when, specifically, is it a problem?
 
12.7Which group wins if two directing groups already on a benzene ring oppose each other‘s influence?
 

Topic 13: Additional reactions of aromatic compounds

13.1What is nucleophilic aromatic substitution?
 
13.2What sort of substitutents are required for nucleophilic aromatic substitution?
 
13.3What is benzyne? What conditions generate benzyne? What makes it such a reactive intermediate?
 
13.4What is benzylic bromination? When could it be useful in a synthesis?
 
13.5What synthetic problem does benzylic oxidation with KMnO4 solve?
 
13.6What are the Clemmensen and Wolff-Kishner reductions, and what synthetic issue do they solve?
 
13.7Why is the reduction of a nitro group to an amine a particularly useful reaction synthetically?
 
13.8(Looking ahead) The reaction of a Grignard reagent with CO2 is mentioned in Section 20.14. How could that be extremely useful here from a synthetic point of view?
 
112 questions
472 questions for Organic II

472 Questions for Organic II

Dearest Student. This web page is a set of questions I call Detailed Intended Learning Outcomes For Organic Chemistry (Part II). Some time ago I asked myself, "Bob, what do you think are the key questions that you hope students will be able to answer after taking Chemistry 248 at St. Olaf College?" So here you have them. Some are very simple; some require more thought. All are good questions to be thinking about as you read, discuss, and master the practical aspects of organic chemistry. They are discussion starters and review tips. There are no answers here (though there are some clues). The questions are here to help you focus on what's important (to me, at least!) and organize your learning process. The questions are grouped into topics. Bite-size chunks. Take them a few at a time. Don't feast on them all at one sitting!

(preliminary version 2021.01.15 feeback: Bob Hanson)