Dynamic Building Blocks Our current building-block system, which describes molecules as arrangements of static building blocks containing

electrons localized in electron-pair domains (EPDs), is incomplete. We can demonstrate its incompleteness by exploring the relationship between apparent number of EPDs and geometry in greater detail. The table we developed in the last section implies that there is a direct relationship between number of EPDs and geometry: 4 EPDs means tetrahedral, 3 means trigonal planar, and 2 means linear geometry. But crystal structures of a variety of organic compounds have shown that this trend does not hold up under all structural conditions. Certain atoms, like nitrogen within the amide functional group, possess geometries that are inconsistent with their numbers of EPDs in completely neutral, systematically built Lewis structures. Although we would expect nitrogen in the figure below to be tetrahedral, in practice it is trigonal planar.

Figure 1. The empirically observed geometry of amide nitrogens differs from our expectation based on the building-block formalism. How can we enrich our current system to account for inconsistencies like the one seen here? A second difficulty of the static building-block formalism concerns its inability to account for chemical change. Chemical reactions are the result of reorganizations of electrons--using building-block terminology, we might say that chemical reactions occur when building blocks change. Yet, with just the building blocks themselves in hand, we can't make predictions about how they might change into one another. Recognizing that our current system incompletely describes reality, we need to advance our

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understanding by considering the dynamic behavior of building blocks. In this section we'll explore and systematize how electrons within the building blocks can move, both internally (to and from building blocks to which they are directly connected) and externally (to and from building blocks in entirely separate molecules). Like water flowing down a hill, electrons flow from regions of high potential energy to low potential energy, or from sources to sinks. What is "electronic potential energy"? Intuitive ideas that you may already have concerning the energy of charged particles apply to electrons in this context: Negatively charged electrons repel one another, and thus have high potential energy when confined to a small space. Negatively charged electrons closer to the positively charged nucleus have lower potential energy Electrons associated with atoms with high effective nuclear charge have lower potential energy. Remarkably, we can use the Lewis structure of an organic compound as a reasonably reliable "map" of its electronic potential energy. Regions within a molecule where electronic potential energy is high are called electron sources (or electron donors), while regions where electronic potential energy is low are called electron sinks (or electron acceptors). The dynamic behavior of our building blocks can be completely described by the idea that electrons move from electron sources to electron sinks. To illustrate this concept graphically, let's identify the elements of Lewis structures that represent electron sources and sinks, then illustrate how sources and sinks interact within and between molecules. Now is a good time to read and understand the curved-arrow formalism. Electron sources are concentrated regions of electron density in molecules. Being exhaustive, we can say that any pair of electrons (bonds or non-bonding lone pairs) may serve as an electron source. However, more "localized" electrons tend to be better electron donors than less localized electrons with more room to "spread their legs," or less electronelectron repulsion. For this reason, non-bonding lone pairs, which are localized on a single atom (according to our formalism thus far), tend to be the best electron sources. Lone pairs are followed in reactivity by ! bonds (the second and third bonds of double/triple bonds) and " bonds (single

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bonds), respectively. Thinking of a " bond as an electron source is relatively rare, but still very important. In a later section, we will clarify these trends and the labels used in the figures below using molecular orbital theory. For now, it's important just to recognize electron sources within the building blocks. Build your pattern recognition skills now to establish a solid foundation for learning later!

Figure 2. The three classes of electron sources within building blocks. The labels n, !, and " correspond to non-bonding lone pairs, multiple bonds, and single bonds. Electron sinks are a bit more difficult to spot, as they don't correspond to bonds or lone pairs within Lewis structures. An electron sink is an atom or functional group with the ability to gain additional electrons. Using building block terminology, we can identify two ways in which an electron sink might gain electrons. The first involves an increase in total electron count, and only applies to building blocks with fewer than eight total electrons. Carbocations are famous for this type of electronic inheritance. In the figure below, the six-electron carbocation building block becomes an eight-electron, tetrahedral building block after donation from a lone pair associated with bromide anion. Donation from an internal electron source, establishing a new double or triple bond, is also possible. In cases when the electron-accepting building block has six or fewer total electrons, we call the electron sink a ("a" for atomic!).

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Figure 3. Building blocks bearing seven or six total electrons can inherit one or two electrons from an electron source to bring their total electron counts up to eight. These examples illustrate donation from an external (left) and internal (right) electron source. Generalized building blocks for the atom gaining electrons are shown below each structure. The examples above suggest that building blocks bearing fewer than eight electrons tend to be good electron sinks, which is true. However, we would be mistaken to conclude that only electron-deficient building blocks can serve as electron sinks. The vast majority of stable organic compounds are composed of eight-electron building blocks, so in order to explain their reactivity, we need to understand how these atomic fragments may serve as electron acceptors. The key idea here is that electronegative atoms can take up pairs of electrons residing in bonds as localized lone pairs. This is a type of electron acceptance available for eight-electron building blocks. In Figure 4, we can see that moving a bond between two atoms onto a single acceptor atom does not change the total electron count of the acceptor. Now, examine the atom that gave up the electrons in the bond--it bears six total electrons and a positive charge, indicating that it's able to inherit two more electrons. In essence, the electronegative atom pulls electrons toward itself, allowing the other atom in the bond to gain electrons from somewhere else. Because the acceptor atom is electronegative, it's able to bear a negative charge.

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Figure 4. Oxygen as an electron sink in carbonyl compounds. Note that the carbon that gives up electrons ends up with a total electron count of 6, so it's able to accept electrons from a separate donor. Electronegative atoms can inherit electrons from single or multiple bonds. In all of these cases, although we call the electronegative atom the sink per se, the atom to which it's bound is the one that is actually able to gain electrons from a source. The electronegative atom just gains electrons internally. The figure below illustrates the three modes of electron acceptance in which eight-electron building blocks can engage. Please note that the figure below is not meant to feature full building blocks; atoms X and Y may possess additional bonds and lone pairs.

Figure 5. Electronegative atoms Y as electron sinks. The labels "* and !* indicate the nature of the bond whose electrons are given to Y. We're now ready to identify electron sources and sinks in molecules, to predict how electrons may flow within and between them. Within molecules, sinks and sources adjacent to one another can interact. We use curved arrows to represent interactions between sources and sinks within molecules; curved arrows also depict the interconversion of equivalent Lewis structures. In the next section, we'll explore the equivalence of Lewis structures (called resonance) in more detail. Between molecules, electron flow from sources to sinks describes the mechanisms of organic chemical reactions, or chemical change. The distinction between internal electronic

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interactions (resonance) and external electron flow (reactivity) is important, because although both forms of electron movement look similar, the phenomena they represent are fundamentally different. The distinction can be a source of confusion for students and experts alike! Let's now explore at a few examples of resonance and reactivity. Firstly, let's return to the amide functional group that we saw at the beginning of this section. At this point, it should be clear that the amide contains a good electron source (nitrogen's lone pair) next door to a good electron sink (the C=O double bond). The left half of Figure 6 shows curved arrows and resulting Lewis structures for donation from nitrogen and acceptance by the carbonyl oxygen. It's apparent that that these separate, isolated arrows present some problems for the amide. Just drawing electron donation results in a disturbing ten-electron building block in stark violation of the octet rule (no way!). On the other hand, just drawing electron acceptance results in a questionable six-electron carbocation building block (not best). Combining both of these movements into a single, coupled movement of electrons from source to sink produces the best alternative Lewis structure, which includes an octet of electrons on every atom (best).

Figure 6. Internal interactions between an electron source (nitrogen's

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lone pair) and sink (the C=O bond) in the amide functional group. Notice that in the best alternative Lewis structure, we would expect nitrogen to be trigonal planar, not tetrahedral! Pay close attention to the nitrogen atom's building block in the original and best alternative Lewis structures. There seems to be a geometric issue here--the alternative form suggests that the nitrogen should be trigonal planar, but the original Lewis structure suggests that it should be tetrahedral. We saw this issue at the beginning of this section, but we can now see why the observed trigonal planar geometry makes sense: donation of nitrogen's lone pair into the C=O electron sink influences nitrogen's geometry. On your own, try confirming that a trigonal planar geometry at nitrogen brings the lone pair closer to the ! bond relative to a tetrahedral geometry (note that the lone pair sits perpendicular to the trigonal plane). Acylium ions are interesting intermediates in several reactions, most notably Friedel-Crafts acylation of aromatic compounds. The figure below depicts an acylium ion and one of its alternative resonance forms. The adjacent source and sink in this case are two ! bonds: a CC double bond and the CO triple bond. Using the terminology already developed to describe sources and sinks, we can describe the electronic interaction captured here as a !#!* interaction. The source is listed first, before the arrow, and the sink after the arrow.

Figure 7. An alternative Lewis structure for an acylium ion, reflecting a !#!* electronic interaction. Halogen atoms are ubiquitous in organic chemistry, and are famous as electron sinks. The reactivity of alkyl halides in the presence of electron sources provide evidence that halogen atoms tend to be excellent sinks. The SN2 substitution reaction involves the simultaneous donation of a pair of electrons from a source and acceptance of a pair of " bonding electrons

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by a halogen atom. The curved arrows in the figure below portray a reaction mechanism, and are different from the internal arrows in the figures above. While the alternative Lewis structures in the figures above are simplifications of a single, more complex reality, the structures on either side of the single-headed arrow in the figure below are truly unique chemical species. Nonetheless, we can use similar notation to denote the electronic interactions in all three figures. In the figure below, we can describe the curved arrows as representing an n#"* interaction.

Figure 8. Representing chemical change as electron flow in the SN2 substitution reaction. Notice the changes that occur in the building blocks associated with sulfur and bromine as the reaction takes place. Eliminations are a second important class of reactions often observed for alkyl halides. As in substitution reactions, the halogen atom serves as an electron sink in elimination reactions. E2 elimination involves the simultaneous donation of electrons from a " bond and acceptance of electrons by a halogen atom. This electronic interaction is internal, which suggests that chemical change might not be taking place. However, a base is required for the reaction to occur, so an external n#"* interaction also plays a role in the mechanism.

Figure 9. Representing chemical change as electron flow in the E2 elimination reaction. These curved arrows involve a combination of external and internal electronic movements; because of the external component, E2

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elimination is certainly considered chemical change. As you study these examples, keep in mind that our goal is the systematization of organic chemical structure and change. This section has introduced the three electron sources (n, ", !) and three electron sinks (a, "*, !*) of organic chemistry. These sources and sinks form a complete system for describing the structures of even-electron molecules and polar chemical change, and eventually, we will connect the cryptic labels defined in this section to molecular orbital theory. For the time being, recognize our system of dynamic building blocks as a way to classify, categorize, and otherwise organize your knowledge of organic chemistry. You'll be exposed to a vast collection of functional groups and reactions throughout this book, but their similarities (and differences) can be understood in the light of the system developed in this section. I hope to demonstrate this point throughout the remainder of the text. In the next section, we will explore internal electronic interactions in more detail and develop the theory of resonance forms. Like two paintings of the same model, resonance forms are alternative representations of the same physical molecule. Although we already know how to depict the interconversion of resonance forms using internal curved arrows, in the next section we'll develop heuristics for understanding what makes a resonance structure "good" or "bad." Watch The Dynamics of Building Blocks Watch Structural Analogies *** The Curved-arrow Formalism Curved arrows are used both internally, to illustrate the differences between resonance structures, and externally, to depict electron flow during chemical reactions. The distinction is important because while external curved arrows depict real chemical change, internal arrows are just bookkeeping devices that show how resonance forms are related. From this section, it's important to grasp the dynamic behavior of the building blocks (that is, how they can change). The videos in this section will introduce you to a system for describing and labeling different types of electron flow. Just like the building-block formalism, the curved-arrow

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formalism will help you see similarities between different examples of electron flow. In class, we'll focus on understanding resonance theory, identifying and labeling possibilities for electron flow, and recognizing situations in which electron flow is likely. Every curved arrow implies predictable changes in bonding patterns, formal charge, and electron counts. The first video in this series introduces what curved arrows mean in terms of bookkeeping--given a set of reactants and curved arrows, you should be able to draw the resulting products. Watch The Curved-arrow Formalism: Introduction & Definitions The stupendous diversity of organic reaction mechanisms stems from a small set of generalized curved arrows. In this video, we examine the patterns in electron flow that can be found throughout organic reaction mechanisms. Use these patterns to establish mental "shelves" on which you can place related mechanisms. Watch Patterns in Electron Flow Curved arrows are not just an academic curiosity; they're used to drive the formation and testing of hypotheses. Mechanisms are at the center of modern reaction development. In the following video, we look at the case of electrophilic aromatic substitution, and learn how an understanding of the mechanism allows us to predict the relative rates and yields of a series of aromatic starting materials. Watch Curved Arrows as Hypotheses Although curved arrows are often described solely as a bookkeeping device, in most cases they have real, physical meaning. They depict the overlap of a filled molecular orbital in the electron source with an empty molecular orbital in the electron sink. In the final video of this section, we examine localized molecular orbital theory, a framework that allows us to translate curved arrows into three-dimensional orbital interactions. "Bogus" curved arrows, which depict electron flow via impossible orbital interactions, should be avoided at all costs!

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Watch Localized Molecular Orbital Theory *** Electron-donating & -withdrawing Groups Organic chemists often use structural analogies to connect new phenomena with those they've seen in the past. Part of the hypothesisbuilding process involves generating a good guess for the behavior of a new compound based on what one has seen before. However, in many cases, the addition of a new group can have a profound effect on a compound's behavior. Such effects are often transferrable across many different contexts; when this happens, we can attribute the effect to nature of the added group itself. For example, in Figure 10, the dimethylamino group has the effect of increasing the rate of all three of the reactions shown. The nitro group, by contrast, slows all three reactions down.

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Figure 10. Transferrable effects of substituents. Here, adding a dimethylamino group to one of the reactants increases the rate of all three of the reactions shown, while adding a nitro group slows all three reactions down. What's going on here? Let's begin with the dimethylamino group. Within this substituent, we find a lone pair that makes a particularly nice electron source. When the dimethylamino group is attached to a properly aligned building block (usually trigonal planar or linear), nitrogen can donate its lone pair toward the building block, generating a new resonance structure in which the nitrogen atom bears positive charge and an atom in the attached structure bears negative charge (Figure 11). Since this sort of electron flow involves nitrogen as an electron source or donor, the dimethylamino group is called an electron-donating group (EDG). The group donates electron density toward the carbon atoms, which gain significant partial negative charge as a result. Nitrogen is a very active resonance donor, so the resonance forms at the bottom of 11 are significant!

Figure 11. The dimethylamino group is called "electron donating," since it can act as a source toward a good sink (such as a !* sink) to which

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it is directly attached. In other words, it can "donate" electrons to an attached group. In Figure 10, the molecules with variable R groups are all serving as nucleophiles (notice that all the other reacting partners are good electrophiles). Tacking an electron-donating group onto each nucleophile makes it more reactive, because the nucleophilic atom gains partial negative charge from the donating group. This is a generally true principle, so it's worth stating again: Adding an electron-donating group to a nucleophile makes it more reactive. Electron-donating groups provide electron density to their attached structures; thus, if the attached structure is electrophilic (or is acting as an electrophile), the EDG makes the attached structure less reactive. Stated generally, we can say that: Adding an electron-donating group to an electrophile makes it less reactive. Replacing the dimethylamino group with a nitro (NO2) group appears to have the extreme opposite effect: the reactivity of the nucleophile decreases dramatically in all three reactions. As we did for dimethylamino, we can look to structural features of the nitro group to explain these observations (Figure 12). At its attachment point, the nitro group features a very electronegative positive nitrogen atom. Furthermore, that nitrogen is connected to an electronegative oxygen atom by a double bond. The N=O bond is an awesome electron sink, and resonance arrows nicely illustrate how the nitro group can withdraw electron density from attached unsaturated groups. Figure 12 shows the idea for double bonds and benzene rings, but similar resonance structures can be drawn if the attached atom bears a triple bond or anion. Because the nitro group pulls electrons toward itself, it is called an electron-withdrawing group (EWG). Electron-withdrawing groups increase the amount of partial positive charge on nearby atoms--pay close attention to the important resonance forms at

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the bottom of 12.

Figure 12. The nitro group is called "electron withdrawing," since it pulls electron density from electron sources on directly attached atoms. We say the group "withdraws" electrons because resonance structures contain positive charge in the attached group. Logically, tacking an electron-withdrawing group onto a structure makes it a worse nucleophile. In a very real sense, the structure bearing an EWG has less accessible electron density to give to other electrophiles. How do you think an EWG affects the strength of electrophiles? You guessed it--electron-withdrawing groups make electrophiles stronger. Adapting the two general principles above for EWGs, we can conclude the following: Adding an electron-withdrawing group to an electrophile makes it more reactive. Adding an electron-withdrawing group to a nucleophile makes it less reactive. So far, we've looked at specific examples of strong electron-donating and -withdrawing groups. Dimethylamino and nitro are by no means the

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only EDGs and EWGs, however! Examples of a variety of donating and withdrawing groups are shown in Figure 13. What structural similarities do we see among all the donating groups? Most prominently, they all feature at least one lone pair on the atom serving as the attachment point. Returning to the resonance arrows in Figure 11, we can see why all electron-donating groups require a lone pair at this position. They donate electron density from their attachment point, which must bear a good electron source (i.e., a lone pair). A generalized electron-donating group is shown at the top right of Figure 13: all we require is a lone pair on the attachment point X.

Figure 13. Examples of electron-donating and -withdrawing groups, with generalized forms of each (in no particular order!). The dark sphere represents the group to which the EDG/EWG is attached. "R" refers to an arbitrary alkyl group or hydrogen. Examples of electron-withdrawing groups are shown at the bottom of Figure 13. Notice that all of these include a double or triple bond at the attachment point. Furthermore, the far end of the multiple bond is more electronegative than the attachment point. In the ketone, for example, oxygen is more electronegative than carbon. In the cyano group, nitrogen is more electronegative than carbon. We can generalize this idea using the structure at the bottom right of the figure. All electron-withdrawing groups feature a double or triple bond at their attachment point X. The far end of the double bond, Y, is always more electronegative than the near end X. Intuitively, the electronegative Y atom pulls electron density from the

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attachment point X, which in turn pulls electrons from the attached group (represented as a dark sphere in the figure). The structural patterns on the right-hand side of Figure 13 are, arguably, the two most important structural patterns in all of organic chemistry. Recognizing good electron-donating and -withdrawing groups makes drawing analogies between reactions and making predictions much easier. In a sense, we can "clump" all of the electron-donating groups together based on their electronic effects, for example. Think of the electron-donating groups as a set of "interchangeable parts" that may alter the rate or favorability of a chemical reaction without changing the essential electron flow of the reaction. Naturally, we think of electron-withdrawing groups in the same way. Taken together, electron-donating and withdrawing groups differ in a property called electron demand: how much the group "demands" electrons from nearby atoms. Watch Electron-donating and -withdrawing Groups