Organic Chemistry I For Dummies, 2nd Edition (2014)

Appendix B. Working Reaction Mechanisms

IN THIS APPENDIX

Defining mechanism problems

Seeing the do’s and don’ts of mechanism problems

Distinguishing mechanism from synthesis questions

Seeing common mistakes in drawing mechanisms

Organic chemists want to know what reagents convert one kind of molecule or functional group into another. But they also want to know how reactions happen. They want to know what exactly happened when they scooped different chemicals into a flask that converted the starting materials into the product. If organic chemists know how a reaction happens, they can more easily optimize reaction conditions (the solvent, temperature, acidity, reagent amounts, and so on) that allow the reaction to proceed most efficiently. The mechanism of a reaction shows how a reaction takes place.

By understanding the mechanism of a reaction, chemists also get a better understanding of how reactions work, and they’re better informed about when a new reaction is likely to succeed or fail. A reaction mechanism is the detailed stepwise process that uses arrows to show how electrons moved during a reaction. A complete mechanism includes all the bond-making and -breaking steps that convert the starting material into product, and shows any intermediate species formed along the way.

The Two Unspoken Mechanism Types

From a very pragmatic standpoint, in organic chemistry you see two unspoken classes of reaction mechanisms — those reaction mechanisms that you can figure out on your own, and those that you simply have to learn. If you’re taking a typical class in introductory organic chemistry, you’ll likely see an abundance of both types. The bromination reaction of alkenes (see Chapter 10), for example, is a reaction mechanism that you simply have to learn. You’d have a very hard time figuring out on your own that the reaction mechanism involves a three-membered bromonium ion intermediate. The existence of this intermediate may even have come as a surprise to the researchers who discovered the mechanism!

Because you simply have to commit these kinds of mechanisms to memory, I can’t do much to help you to learn them, except to show you the mechanisms when discussing the reactions in this book, and to give you tips on how to draw mechanisms using arrow-pushing. Where I can help you is in understanding the mechanisms that you can work out on your own, and in arming you with general principles for reactions whose mechanisms are not found in the text.

I think that one reason students have problems with mechanism problems is that they don’t see this distinction between mechanisms that they need to learn — which are often impossible to figure out independently — and mechanisms that they need to be able to work on their own. Many look, for example, at the bromination reaction and, knowing that they have to be able to work out mechanisms for themselves, pour ashes on their heads and rend their garments and think, “I could never figure that out on my own!” They then become discouraged about the whole business, even though bromination is not a mechanism that students are expected to be able to deduce on their own.

Still, even if this distinction is understood, most students find these work-it-yourself mechanism problems quite challenging. These problems are challenging for two reasons:

· Unlike the mechanisms you need to commit to memory, memorization is useless and impossible with the kinds of mechanism problems you’re supposed to be able to work out on your own.

· Professors think that asking students to draw the mechanisms for reactions they’ve never seen before is perfectly reasonable.

The trick for working mechanism problems is to understand the general principles of arrow pushing (see Chapter 3), and to get lots of practice (lots and lots of practice!). I detail some of the general principles here, and give you some tips on good mechanism-writing habits. I also show you some common pitfalls to avoid when writing mechanisms.

Do’s and Don’ts for Working Mechanisms

Knowing what not to do in a mechanism problem is almost as important as knowing what to do. So, here’s a list of do’s and don’ts for writing mechanisms:

· Don’t confuse mechanism problems with multistep synthesis problems. This is a common mistake. Mechanism problems give you all the reagents that you need to convert the starting material into the product. So, don’t supply additional reagents on your own.

· Do use all the reagents given in a mechanism problem. Mechanism problems don’t include any extraneous reagents that are not used in a mechanism, so your reaction mechanism must account for the use of all the reagents.

· Don’t confuse solvents and base scavengers with reagents. Be able to recognize typical solvents that will generally not come into play in a mechanism — solvents such as THF, DMF, DMSO, CHCl₃, CH₂Cl₂, and so on. If you recognize these solvents, you won’t try to incorporate the solvent into the mechanism (although it’s sometimes acceptable to use the solvent for proton transfers, particularly alcohol solvents and water). Also, base scavengers (like pyridine and triethylamine) are sometimes added to neutralize any acid formed in the reaction, but often they don’t have much bearing on the mechanism itself.

· Do get in the habit of drawing out all the atoms at the reaction centers. Drawing out full Lewis structures rather than line-bond structures for at least the portions of the molecule that change makes losing or misplacing atoms or charges less likely. Drawing out atoms becomes particularly important when charges are involved in a mechanism, because spotting which atoms have charge is much easier when all the atoms are explicitly drawn out.

· Don’t try to do two things at once in a mechanism. Take the mechanism one step at a time. That’s not to say that there won’t be more than one arrow in a given step (there often will be), but don’t try to do two steps at once. Don’t protonate an alcohol and kick off water to make a carbocation in the same step, for example. Make these separate steps.

· Do draw out all resonance structures for intermediates. Although drawing the resonance structures of reactive intermediates may not be required by your professor, doing so is good practice. For example, when writing the mechanism for the electrophilic aromatic substitution reaction (see Chapter 16), draw out all the resonance structures for the cationic intermediate.

· Do look where you’re going. If you want to go from Tallahassee to Tacoma, you don’t just get in your car, drive in any direction, and hope you’ll eventually get there. In other words, even though a step you’ve proposed looks like it could conceivably happen, make sure that step will get you headed in the right direction toward the product. Ask yourself what bonds must be broken and what bonds must be formed in order to take the starting material into the product. Keep the answers to these questions in the back of your mind while you work the mechanism so you can keep track of where you’re going.

· Don’t overanalyze why you wouldn’t get a different product than the one indicated. You’re given the product, so you don’t need to worry too much about why the indicated product is formed rather than another. Often minor products in a reaction are shown to be the product because the professor wants you to figure out how the reaction made these minor products. Asking questions of why things happen is a sign of an excellent student, but getting too bogged down on why you form one product over another in a shown mechanism may not yield much. As a general principle, draw the mechanism first, and ask questions later.

· Do ignore spectator ions. You often see ionic reagents that include potassium (K), sodium (Na), or lithium (Li) as parts of the reagent. It’s often a good idea to cross off these spectator ions so you don’t get tempted to include them in the mechanism. For example, if the reagent is NaOH, cross off the sodium and make the reagent OH–. That way you won’t be tempted to include the spectator sodium (Na) cation in the mechanism.

· Do ask yourself if all your proposed steps and intermediates are reasonable. Do you always show minuses attacking pluses (and never, ever, vice versa)? If you’re in acidic conditions, did you make sure that you didn’t form any strongly basic negatively charged intermediates? If you’re under basic conditions, did you make sure that you didn’t form any strongly acidic positively charged intermediates? Did you make sure to never draw a pentavalent carbon (a carbon with five bonds) or break any of the rules of valence? Do all the charges balance? Ask yourself these kinds of questions after you propose a mechanism.

· Do be able to work the different types of mechanisms (discussed in the following section). After working many problems, you’ll spot mechanism patterns and you’ll begin to notice that some mechanisms are similar to each other.

Types of Mechanisms

After working many problems, you notice that patterns in working mechanisms emerge for different kinds of reaction mechanisms. The most common different kinds of mechanisms are shown in the following list:

· Thermal mechanisms: These are mechanisms with no reagents. These mechanisms are seen mostly in the second semester of organic chemistry, but the Diels–Alder reaction is an example of this mechanism (see Chapter 14).

· Nucleophile-electrophile mechanisms: These are probably the most common types of mechanisms. If you can do nucleophile-electrophile mechanisms, you have understood a big part of organic chemistry. These mechanisms involve nucleophiles (nucleus lovers) attackingelectrophiles (electron lovers). Typically, some species with a lone pair of electrons (a nucleophile) attacks an electron-deficient carbon (an electrophile).

· Acid-base mechanisms: These mechanisms are identifiable by seeing a strong acid (like HCl or H₂SO₄) or a strong base (like NaNH₂) as the reagent. With acid mechanisms, you typically don’t want to form any species that have net negative charges (with the exception of an acid’s conjugate base, which is usually negatively charged), and with base mechanisms, you don’t want to form any species that have net positive charges. Typically, the first step in acid mechanisms is protonation, while in a base mechanism the first step is deprotonation.

· Carbocation mechanisms: These mechanisms take place generally under acidic conditions. (You typically won’t see net positive charges — like the positive charge on a carbocation — under basic conditions.) Watch out for carbocation rearrangements in these mechanisms (like alkyl or hydrogen shifts). If an intermediate has a net negative charge and is highly basic, you probably did something wrong (you’re probably missing a proton transfer step).

· Anion mechanisms: These mechanisms are found mostly in carbonyl reactions (ketones, aldehydes, and so on), and they usually take place under basic conditions. You don’t see these reactions very often in the first semester of organic chemistry.

· Free-radical mechanisms: These are somewhat less common than the other types of mechanisms, but they do pop up occasionally. When you see light (hν), or peroxide (ROOR), think free-radical mechanisms. You see radical mechanisms in the bromination of alkanes using light and bromine, for example (Chapter 8). When working free-radical mechanisms, use half-headed arrows rather than full-headed arrows to show the movement of only one electron. Drawing out all initiation, propagation, and termination steps is standard practice for many free-radical reactions.

Of course, some of these kinds of mechanisms overlap each other. For example, often in acid mechanisms you make cations, and often in base mechanisms, you generate anions. Determining the kind of mechanism can help you organize your thoughts when tackling problems.