Writing Mechanisms in Organic Chemistry

Copyright Linda M. Sweeting 1998. You may use these notes but you may NOT download them for use at another site, nor may you charge for access to them.

A. Introduction and Basic Principles

Chemists have a passion to understand why and how reactions occur because they want to be able to predict what reactions will occur when faced with new compounds. In organic chemistry, one of the first things that was noted was that certain groups of atoms nearly always react the same way - we now call them functional groups.

The reactivity of functional groups can be readily understood by examining their polarity, which of course depends on the electronegativity of the atoms. For example, the carbonyl groups are somewhat negative at the electronegative oxygen and thus somewhat positive at the carbon. Polarity is indicated by a d+ or d- to tell people that the electrons are not shared equally, but the atoms in a carbonyl do not have a formal charge.

Once you understand the polarity of the organic molecule and the nature of any other reagents, you can make a good guess - a hypothesis - about how the molecule will react. The carbon end of this group is d+ and thus react with electron donors - bases or reducing agents. The oxygen end of the group is d- and thus will react with electron acceptors - acids or oxidizing agents.

B. What Is a Mechanism?

To really understand how a reaction takes place you need to do some experiments which will unravel the steps; the kinds of experiments that have been found to work well, and how they are interpreted, are described briefly in "Determination of Mechanisms".

Once these experiments have been done, we may know certain things about a reaction, for example, that it is acid-catalyzed. We may then do some additional experiments - perhaps spectroscopic - to determine what position on the molecule is protonated by the acid (alas, two of the common functional groups, OH and C=O, have similar basicities). Examining all the reagents that could affect the rate gives us the composition of the reacting "activated complex" at the transition state. Then we sit down with a piece of paper and a pencil and propose a theory for how the reaction occurs, showing the transformation of starting material into products as a series of discreet steps, each of which produces a distinct intermediate compound or ion, called an "intermediate". This theory is called the mechanism. Like all theories, it is subject to modification or complete revamping when new experiments show that the currently accepted mechanism is incorrect or incomplete.

The mechanism explicitly shows every intermediate compound (neutral or ionic) that we have evidence for; if we have no evidence for any such "intermediates", then we propose a transition state or activated complex structure.

C. What is an Intermediate?

The easiest way to understand the difference between a transition state and an intermediate is to use what is commonly called a reaction (energy) diagram, like the one below. For a simple reaction like the S_N1 reaction of 2-chloro-2-methylpropane with iodide, we know that the rate-determining step is breaking the C-Cl bond, i.e. ionization to form a carbocation. Thus we could make a graph of the change in energy as a function of C ... Cl distance (at least for the first part of the reaction). The only energy values that are actually measurable are the energies of the transition state and the carbocation relative to the halide, but we assume the energy changes smoothly. The energy of the 2-chloro-2-methylpropane with its bond partially broken is actually higher than the energy of the carbocation and it is this highest energy state that is the transition state. Any stretching or shrinking of the C...Cl distance from that transition state is downhill in energy, and, just like a ball, it rolls to the bottom of that energy "hill". The transition state has essentially no lifetime - it is a fleeting arrangement that happens to have the highest energy.

The carbocation, once it is made, is stabilized by solvation, and can move closer or farther from the chloride without being destroyed, so it lasts for a little while before reacting with the iodide, i.e., it has a lifetime. The finite lifetime, created by the small energy "hills" around it, is what makes the carbocation an intermediate and not a transition state.

In many reactions, lots of distances are changing simultaneously, for example, in the E2 reaction, 3 bonds are made and broken at once. Even in the ionization of 2-chloro-2-methylpropane, several things are happening in addition to the stretching of the C...Cl distance: the methyl groups are moving away from each other and the carbon is changing its hybridization from sp³ to sp²as it becomes positively charged. Thus, most of the reaction (energy) diagrams we make are rather vague about the x-axis, calling it "reaction coordinate" rather than labeling it with any particular distance. We are essentially making a plot of a molecular roller-coaster ride by omitting all the twists and turns and plotting only the ups and downs.

D. Writing Mechanisms with Intermediates

When you write a mechanism, you do not have to include the reaction (energy) diagram, just the steps showing all the intermediates. Here are the conventions for writing a particular mechanism:

Show all intermediates that you know about as separate sequential drawings (part E gives tips for figuring out what might come next).
Link all intermediates by straight arrows, double if you know the step is reversible and single if you know it is not. Each set of arrows followed by a new structure is a step.
Show one change in bonding for each step (e.g. for E1: ionization, removal of proton), unless you know that more than one bond is changed in a given step (e.g. E2).
If there are steps that you have little evidence about because they are after the rate determining step, use analogies to other known reactions to fill in the blanks (e.g. loss of a proton after an acid-catalyzed reaction)
If necessary, add an intermediate to the set you know about, again using analogies to other known reactions, to ensure that only one bond-making / bond-breaking occurs for each step.
If there are no known intermediates, sketch the transition state and label it as such (see F).

Here is an annotated example using the dehydration of an alcohol:

Equilibrium 1: reaction is acid-catalyzed; spectroscopy shows the conjugate acid of the alcohol, intermediate 1, is formed very fast - proton transfers are almost never rate-determining steps for other reactions.
Equilibrium 2: the rate determining step (acid and alcohol concentrations affect the rate). Evidence for a carbocation, intermediate 2? With all alcohols, some substitution is observed, more if the acid is something like HBr, whose conjugate base is nucleophilic; with some alcohols, rearrangement occurs. Both of these observations are consistent with carbocation formation (and not with concerted, carbanion or radical reactions)
Equilibrium 3: This reaction cannot be readily observed under these reaction conditions since it is after the rate-determining step. However, we observe separately that alkenes dissolve in concentrated sulfuric acid, and thus must undergo an acid-base reaction themselves (protonation) to form soluble ions, which must be carbocations.

Note that this whole reaction is reversible, and in fact, alkenes can be hydrated to form alcohols. How would you change the conditions to produce alcohol as the major product from this equilibrium?

E. Understanding and Predicting Mechanisms

To help us understand how and why these steps occur, we add one important detail to the outline of a mechanism above: we show how the electrons are used. For the bonds to break and form, electrons must change their affiliation: unshared become shared, shared with one atom become shared with another.

We illustrate this dynamic process with a curved arrow for each electron pair which

starts in the middle of the original location of the electron pair,
ends at the middle of the final location of the electron pair, as shown below, and
uses the electrons at a negative or d- site for binding to positive or d+ site.

To avoid confusion, arrows may never be used to show the motion of molecules or ions.

Note that this convention for drawing mechanisms is a shorthand. What is "really" happening is that atoms are rehybridizing and otherwise reorganizing orbitals to adjust to new bonding patterns. The arrows show what electron reorganization has to occur to convert the structure with the arrows into the next one in the sequence of steps in the mechanism, i.e. the structure after the arrow. Our shorthand does not automatically show stereochemistry - we have to arrange the molecule so that we convey that information too.

These arrows are powerful tools to help clarify our thinking about mechanism. They give us a formalism to show how bonds are broken and made during a reaction which allows us to predict reactions that might occur in new compounds with new reagents. They are very useful for keeping track of what does happen - if you use the arrows, they will help you remember the mechanism without memorizing a sequence of structures. Some instructors require that they be included in the mechanism that you write. Learn to use them and it will make your life easier.

The curved arrow notation is also very good at showing the effect of resonance stabilization on a reaction - the arrow notation is also used to illustrate the relationship between contributors to a resonance hybrid. If your drawings include contributors to a resonance hybrid, enclose all the sketches of the same molecule in square brackets (the standard connection is a double-headed arrow, but you can omit that) to let people know that the sequence of structures is a set of drawings of one molecule. See the tips by Liina Ladon for further help.

F. Mechanisms without Intermediates

If experiments indicate that no intermediates exist, that the reagents are converted to products in one step, the reaction is said to be "concerted". Such reactions are even called "no mechanism" reactions. Many of them are stereospecific (e.g. E2 and S_N2), and we know from the rate law what ingredients go into the transition state, so we do know a lot about how they happen. We do in fact know the mechanism - it is just short. To tell people what we know, we try to make a sketch of the transition state. There are two ways to do this: with curved arrows or with dotted lines (the dotted lines are a simplified version of a molecular orbital picture). The E2 reaction is shown below in both notations. Be sure your transition state is in parentheses to indicate its instability and labeled as such. The character traditionally used for transition state does not exist for html, so I have tried to generate it with the drawing program.

For more examples of concerted and step-wise reactions, see the essay by Drs. Ryzhkov and Wingrove on the S_N1, S_N2, E1 and E2 reactions.