This is the second in a series of posts answering some frequently asked questions about the third edition of Joel Karty’s Organic Chemistry: Principles and Mechanisms. You can see the first post in the series here. This section covers questions from interchapter C through the end of the book. If you have any unanswered questions please ask them in the comments below.
Why are the orbital pictures of the common elementary steps presented in Interchapter C?
There are two main reasons. One is to allow instructors to tailor the teaching of frontier molecular orbital theory to their own students. With the orbital pictures of the common elementary steps presented in an interchapter, an instructor can teach as much or as little as they see fit, without having to worry about main topics later in the book relying on material that was skipped.
The second reason is to show frontier molecular orbital theory more holistically. In other textbooks, the HOMO-LUMO interactions are shown only for a few elementary steps, such as SN2 and nucleophilic addition. Moreover, those pictures tend to be tied to specific functional groups, isolated from orbital pictures of other elementary steps. My textbook, by contrast, presents the frontier molecular orbital picture of all ten common elementary steps together in Interchapter C, including E2 steps and carbocation rearrangements. Thus, students can see how frontier molecular orbital theory is applied in similar ways to different elementary steps, and they can come away with a better appreciation of the power of frontier molecular orbital theory.
Why are multistep mechanisms introduced in the context of SN1 and E1 reactions in Chapter 8?
Once the 10 common elementary steps have been covered in Chapter 7, any of a variety of multistep mechanisms can be introduced. My textbook proceeds to introduce SN1 and E1 reactions as the first multistep mechanisms. With these reactions, we can teach students how stereochemistry and reaction kinetics are used to justify a proposed mechanism. We can also teach students how to reasonably incorporate proton transfer and carbocation rearrangements into fundamental mechanisms. Other multistep mechanisms, such as additions to alkenes or additions to carbonyl compounds, do not lend themselves to teaching all of these ideas.
Why are nucleophilic substitution and elimination reactions introduced before electrophilic addition reactions or nucleophilic addition reactions?
Nucleophilic substitution and elimination reactions are relatively self-contained, and their mechanisms remain simple throughout their discussion. These reactions, furthermore, do not require students to wrestle with thermodynamic control versus kinetic control. By contrast, electrophilic addition reactions and nucleophilic addition reactions begin rather straightforwardly, but they both ramp up in complexity quite quickly. Consider electrophilic addition reactions to alkenes and alkynes, where some textbooks introduce electrophilic addition reactions. The addition of a Brønsted acid is a simple two-step mechanism, with no leaving groups. Soon after, however, reactions that proceed through a bromonium ion intermediate are introduced, where the opening of the ring occurs with SN2-type stereospecificity and with regiochemistry governed by steric hindrance and charge stability reminiscent of carbocations. The mechanisms rapidly become complex, too, particularly with oxidative cleavage reactions and hydroboration-oxidation reactions. Similarly, nucleophilic addition reaction mechanisms start out rather simple, but they become complex rather quickly, too. Acetal formation, for example, is a 7-step mechanism. Moreover, both electrophilic addition and nucleophilic addition reactions tend to include the competition between 1,2-addition and 1,4-addition, which requires students to wrestle with thermodynamic versus kinetic control.
Why are strategies for multistep synthesis introduced in Chapters 10 and 11, and not earlier?
The main reason is to prevent students from memorizing reactions. In other textbooks, expectations for students to solve multistep syntheses begin earlier, when students are still at the outset of learning mechanisms. Student focus is shifted away from mechanisms and onto net reactions, and when this is done too early, students fail to develop sufficient skills with or true buy-in for mechanisms. It is then quite challenging to get students back on the path of learning mechanisms when the next reactions are introduced; students instead tend to stick with memorizing reactions.
With strategies for multistep mechanisms in my book delayed a few chapters, until Chapters 10 and 11, students have a few more chapters to develop their skills in mechanisms, and more importantly, to see how mechanisms simplify organic chemistry. Thus, students develop a firm buy-in for mechanisms. So, when we later return to learning more reactions, it is much easier for students to transition back to focusing on mechanisms instead of memorization.
Delaying the introduction of strategies for multistep synthesis a few chapters does not mean that students’ skills in solving multistep syntheses are compromised. Quite the contrary, a better mastery of mechanisms helps students master synthesis problems, particularly because understanding mechanisms helps students more successfully choose the right reactions to accomplish desired transformations. Literature supports this idea. What it means instead is that we instructors simply need to slightly delay the expectations we place on students to solve complex synthesis problems. But with that slight delay, we can ultimately place high levels of expectations for synthesis on students, even higher than with other textbooks.
Why are the nucleophilic substitution & elimination that are useful for synthesis introduced in two chapters (Chapters 10 and 11) instead of one?
The answer is scaffolding. The introduction of strategies for multistep synthesis places new and significant demands on students, especially on the ways that they must think about reactions and what they accomplish. With these ramped-up demands on students, it is important to keep the synthesis problems simple at the outset. Chapter 10 keeps those synthesis problems simple by dealing only with syntheses that keep the carbon structure unchanged; solving these synthesis problems thus requires only functional group transformations, the topic of Chapter 10. Then, the demands are ramped up even more in Chapter 11, where the syntheses require changes to the carbon structure. Chapter 11 therefore deals with reactions that form carbon-carbon bonds, and it also introduces retrosynthetic analysis as a tool for students to mentally disconnect those carbon-carbon bonds as they think backward.
Why is mass spectrometry (Chapter 15) introduced before IR, UV-vis, and NMR spectroscopy?
The main reason is because of what a mass spectrum affords us, which is a molecular formula. Chapters 16 and 17 introduce spectroscopy, and solving the structure of a molecule from IR, UV-vis, or NMR spectra rely on having a molecular formula at our disposal. That said, you can teach Chapters 15-17 in any order you see fit. If Chapter 15 is delayed until after Chapter 16 or 17, you will just need to avoid assigning end-of-chapter Integrated Problems in Chapter 16 or 17 that rely on interpreting information from a mass spectrum.
Can the structure determination chapters (Chapters 15-17) be moved earlier?
Yes, and in fact some users of my textbook already do this. It works because Chapters 15-17 are self-contained. In some textbooks organized according to functional group, introductory aspects of spectroscopy are presented in a self-contained chapter or two, but important aspects tied to certain functional groups are reserved for separate chapters on those functional groups. In my textbook, those aspects that are tied to certain functional groups are also included in the self-contained structure determination chapters.
If you move Chapters 15-17 earlier, I recommend not moving them any earlier than Chapter 4, because Chapters 4 deals with conformers and constitutional isomers—concepts that students should have under their belts when solving spectroscopy problems. Additionally, if you move those chapters earlier, you might also consider moving Chapter 14 earlier, which deals with conjugation and aromaticity. Understanding conjugation and aromaticity is not absolutely critical to solving spectroscopy problems, but it can help.
Why are nucleophilic addition reactions presented in two chapters (Chapters 18 and 19)? Similarly, why are nucleophilic addition-elimination reactions presented in two separate chapters (Chapters 22 and 23)?
The answer is scaffolding. In Chapters 18 and 22, the reactions that are taught are ones in which a reagent that is added is already strongly nucleophilic. Thus, the mechanism for the nucleophilic addition or nucleophilic addition-elimination reaction is kept rather short and simple. As such, we can maintain focus and emphasis on just the fundamental mechanism throughout Chapters 18 and 22. Then, in Chapters 19 and 23, we ramp up the complexity of the mechanisms when the reagents that are added are only weakly nucleophilic or non-nucleophilic. Complexity is introduced when the reaction is acid- or base-catalyzed, and when the number of steps in the mechanism is substantially greater.
Why are a carbon reactions not presented in their own chapter?
In other textbooks, a carbon reactions are presented in their own chapter, typically after short chapters on nucleophilic addition and nucleophilic addition-elimination reactions of carbonyl compounds (ketones/aldehydes, and carboxylic acids and their derivatives). My book instead distributes a carbon reactions over four chapters, in the context of the mechanisms that are actually taking place: a-halogenation and a-alkylation reactions are presented in Chapters 10 and 11 because they have SN2 mechanisms; aldol addition reactions are introduced in Chapter 19 because they have base-catalyzed nucleophilic addition mechanisms; and Claisen condensation reactions are introduced in Chapter 23 because they have irreversible base-promoted nucleophilic addition-elimination mechanisms.
When other textbooks present a carbon reactions late in their own chapter, it puts these reactions on a pedestal, in which case students will have the unfortunate tendency of treating these reactions as somehow being different than other ones they have encountered. I say this is unfortunate because, if students see reactions sharing the same mechanism as being different, mechanisms will fail to simplify organic chemistry for these students. By contrast, in my textbook, by introducing each type of a carbon reaction alongside other reactions that share the same mechanism, it reinforces the power of mechanisms to simplify organic chemistry. As one user of my textbook said: For the first time, my students actually ‘got’ aldol reactions.
Why are the reactions that form organometallic reagents presented in Chapter 20?
In my textbook, Section 11.2 is the first time students see the use of an organometallic reagent in a new organic reactions, in the context of opening epoxide rings with Grignard or alkyllithium reagents. Why not introduce how to synthesize those organometallic reagents concurrently, instead of waiting until Section 20.6? After all, making a Grignard reagent or an alkyllithium reagent from an alkyl halide is really simple, at least on paper! The answer is to prevent the learning curve for solving multistep synthesis problems from becoming too steep. Chapter 11 is the tail end of students being introduced to basic strategies for solving multistep synthesis problems, and students will already be challenged with syntheses that call for changes to the carbon structure. By allowing students to use organometallic reagents as starting materials, one variable for these synthesis problems is removed. And for many students, that one variable could be the difference between the synthesis problem being straightforward or not, especially at a time when multistep synthesis problems are still a new challenge.
That having been said, you can easily move the organometallic reagent formation reactions in Section 20.6 earlier as you see fit. You can teach those reactions alongside the epoxide-opening reactions in Section 11.2, or when students see these reagents again in the context of Grignard/alkyllithium reactions involving ketones and aldehydes in Section 18.4.
Why are the Diels-Alder, syn dihydroxylation, and oxidative cleavage reactions introduced in their own chapter (Chapter 26) instead of alongside electrophilic addition reactions (Chapters 12 and 13)?
The main reason is that a key step in these reactions is different from the elementary steps introduced in Chapter 7. The 10 elementary steps in Chapter 7 are used to construct the mechanisms for all reactions introduced in my textbook through Chapter 25. Then, the Diels-Alder, syn dihydroxylation, and oxidative cleavage reactions in Chapter 26 invoke [4+2] cycloaddition steps. More than simply having different curved arrow notation from the elementary steps in Chapter 7, this new elementary step also carries with it specific new rules for stereochemistry and regiochemistry, which bring additional challenges.
The second reason applies principally to oxidative cleavage reactions. These reactions depend on students having experience with conditions that are oxidative or reductive, and the different outcomes of each. Notably, in the oxidative cleavage reaction with KMnO4 or in an ozonolysis reaction with oxidative workup, students need to know how an initial aldehyde that is produced would be oxidized to a carboxylic acid, whereas ketones are left alone. Students don’t gain a feel for these oxidations of aldehydes (and the lack of oxidation of ketones) until Chapter 20.
In some other textbooks that are organized by functional group, the reactions that I introduce in Chapter 26 are instead introduced in an alkene chapter. The stereochemistry and regiochemistry rules for Diels-Alder reactions are a tall order for a lot of students, to the point of becoming overwhelming. Moreover, that would place oxidative cleavage reactions before the treatment of the oxidation of ketones/aldehydes. The danger is that this essentially asks students to memorize such outcomes, rather than relying on any intuition they might otherwise gain from previous chapters.
Why are radical reactions presented at the end of the book (Chapter 27)?
First and foremost, it is because radical reactions proceed by mechanisms that are different from most mechanisms that students encounter in undergraduate organic chemistry. The curved arrow notation for these radical mechanisms is different, and some radical reactions are also distinguished by proceeding through chain reaction mechanisms. By delaying radical reactions until the end (Chapter 27), it allows us to build a complete story of reactions proceeding through closed-shell mechanisms, without chain-reaction mechanisms, before changing gears quite dramatically. The benefit from this kind of continued focus is that it reinforces a student’s buy-in for mechanisms simplifying organic chemistry. If instead we have a dramatic change in gears much earlier in the course, like we see in other textbooks, it can substantially take away from a student’s trust about the simplifying nature of mechanisms.
The second main reason is that delaying radical reactions to the end reduces student mistakes, particularly when it comes to curved arrows. When students learn single-barbed curved arrow notation alongside double-barbed curved arrow notation, as in other textbooks, they too often end up using the two types of curved arrows interchangeably. By contrast, when students first encounter single-barbed curved arrow notation in Chapter 27 in my textbook, they have no opportunity for mistakenly using single-barbed curved arrow notation in the first 26 chapters.
-Joel Karty, Elon University
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