Updated: 02/04/1998
Contrary to popular belief, mechanisms were not developed to make the study of reaction processes more difficult. In fact, understanding the processes by which reactions proceed enhances the ability to learn the various reactions. This is in sharp contrast to the general impression that one must have a photographic memory to retain all the reactions presented in a typical organic chemistry course. While having a good memory would be beneficial, it is not absolutely necessary to receive superior grades. This is where understanding the how the reactions proceed plays a key role.
During a one-year, introductory organic chemistry course, students are typically exposed to 200-300 "different" reactions. However, these reactions proceed by one of eleven different processes. By learning these processes, i.e. the mechanisms, one can quickly work a variety of problems. For instance, if the starting material and reagents are provided, the reaction can be classified and the product predicted. Additionally, certain reagents are only useful under certain conditions. Therefore, understanding the mechanisms also assist in learning the reagents. A final advantage involves studying the reaction itself. Many times reactions are conducted in which the desired product doesn't form. Instead, a different product prevails and one must try to explain it's formation. Again, understanding mechanisms will assist the student in these endeavors. It should be stressed at this time that understanding the process and memorizing the process are two different ideals. The ability to memorize every reaction and mechanism does not insure receiving a superior grade in an organic course. In fact, committing every reaction and aspect of the course to memory does not even insure a passing grade. One must be able to APPLY what they have learned (or memorized) to receive a passing grade. This means that students must practice the ideals presented in the lecture by SOLVING problems on their own.
This module will provide a step-by-step approach to solving mechanism problems. In order for this approach, or any approach for that matter, to be successful one must diligently practice it. This means arriving at the answer using only one's knowledge and/or their notes and text. (This doesn't mean reading the answer from the study guide at the point the individual gets stuck.)
For the most part, reactions in an introductory organic chemistry course may be classified under three general headings: radical, polar, and pericyclic processes. These classifications simply determine the electron transfer process that will used.
Radical - These process occur by single-electron transfers. All bonds that form or break do so by tracking individual electrons. As we will see, this is accomplished by using curved arrows that resemble fishhooks. Electron flow always occurs from the source of the electrons (tail of the arrow) to the recipient of the electrons (arrow head). A common way of identifying radical processes by looking at the reagents/conditions for radical initiators. These include peroxides and photochemical sources (hv). If these initiators aren't present, the reaction is probably not a radical reaction.
Polar - This is probably the most common type of reaction. All electron transfers occur by electron pairs. This is illustrated by curved, full-headed arrows. As in radical processes, electron flow always occurs from the source of the electrons (tail of the arrow) to the recipient of the electrons (arrow head). Typically, one looks for ions, polar molecules, molecules with polar bonds, or molecules that have areas that are obviously deficient (e.g., positive charges) or rich (e.g., electron pairs) in electrons.
Pericyclic - These reactions take place by a cyclic redistribution of their bonding electrons. The resulting product contains a ring. When classifying this mechanism, look for a conjugated system (normally a diene) and another alkene.
Substitution - Substitutions occur when one functional group on a molecule is replaced by another functional group. These reactions may be either radical or polar.
Elimination - Eliminations take place by portions of the reactant molecule splitting off to form other species. Typically, one will notice an increase in the number of molecules that are present. These reactions are polar.
Addition - In many respects, the addition reaction is the reverse of the elimination reaction. Basically, another molecule or ion adds to the reactant molecule in some fashion to form the new product. Since this is the opposite of elimination, one will notice a decrease in the number of molecules or atoms that are present. These reactions may be either radical, polar, or pericyclic.
In order to successfully solve a mechanism problem, keep in mind the reaction proceeds as written. The student should not add additional reagents as this changes the problem. These types of problems may be intermolecular processes (between different molecules), intramolecular processes, or even a combination of the two processes. In general, mechanism problems provide a good means of determining how well students understand the material. While "brute force" memorization may work for reactions, mechanism problems can be designed such that simply memorizing the process won't work. Because of this, a systematic means of analyzing the problem is recommended.
Step 1 - Inspect the process and make a general classification. Is it radical, polar, or pericyclic?
Step 2 - Once the overall classification is determined, start looking at the type of process. Is one group replacing another? (Substitution) Remember that hydrogen can be replaced by another species. Is an addition occurring? Is something being eliminated?
Step 3 - At this point the field has been narrowed considerably and a specific mechanism can be proposed. Once the mechanism is identified, proceed with that mechanism until the progression is complete. DO NOT STOP IN THE MIDDLE AND USE A DIFFERENT MECHANISM!!! While multiple reactions are possible on a single molecule, the rules of each mechanism must be observed.
Step 4 - If the correct mechanism has been chosen and applied correctly, the stated product should form in the final step. The following is a list of the specific mechanisms that is covered during the first semester course.
Radical Addition - The starting material is usually either an alkene or alkyne and a radical initiator is present. The reagents are species that are normally classified as electrophiles (HBr, Br2, etc.)
Radical Substitution - A radical initiator is present. Also, the reagent is typically a halogen molecule. The starting material can be any type of molecule. Although, ones that tend to form stable radicals should be given a higher priority. Be certain that due care is given to understanding radical stability.
Electrophilic Addition - The starting material is usually an alkene or alkyne. The reagent is a good electrophile, i.e. something that has an electron deficiency (H+, HBr, HCl, Br2, etc.). Additionally, the reagent is normally a polar species. Be certain to look for an overall dipole moment.
SN2 - The starting material is usually a primary or secondary halide (or other suitable leaving group), the reagent is a species that is electron-rich (nucleophile), and, if given, a polar, aprotic solvent is used. As a further note, keep in mind that poor leaving groups like alcohols may be converted to good leaving groups by using Lewis acids (PCl3, PBr3, etc.) As with substitution reactions, the nucleophile replaces the leaving group.
SN1- The starting is usually a tertiary halide (or other suitable leaving group), the reagent is a species that is electron-rich (nucleophile), and, if given, a polar, protic solvent is used. In a fashion similar to the SN2 reaction, poor leaving groups like alcohols may be converted to good leaving groups by using Bronsted acids (H+) As with substitution reactions, the nucleophile replaces the leaving group.
E2 - The starting material is usually a substituted halide; but, relatively unhindered halides (or compounds containing other good leaving groups) should also be considered. The reagent system is what classifies this reaction. The reagent most commonly used is KOH dissolved in ethyl alcohol (EtOH). In general, when KOH and EtOH are present on the reaction arrow one should strongly consider the E2 process. The process is used to form pi bonds.
E1 - This reaction is not as common as the others. It is commonly a side reaction in an SN1 reaction as the conditions are the same. However, highly substituted alcohols can be made to eliminate by using non-nucleophilc acids such as sulfuric acid or phosphoric acid. The process is used to form pi bonds.
Diels-Alder - For this type of reaction, one should look for a conjugated system (normally a diene) and another alkene as a reagent. Sometimes the delta sign (for added heat) is shown.
When inspecting the reaction, one should consider that every aspect of the reaction may not be shown. For example, SN2 reactions are favored using good nucleophiles, primary halides, and carried out in polar aprotic solvents. However, many times the solvent isn't given, or a polar, protic solvent is used. This is where a good understanding of the process plays a key role. In a situation like this one, keep in mind the majority of the features point toward the SN2 process. Do not allow the missing or unfavorable piece of the puzzle overly influence the classification procedure. Sometimes a "best fit" must be made when deciding on a mechanism.
Another particularly tricky situation occurs when a linear molecule cyclizes. This is where a strong understanding of the process is necessary. There is no difference in the mechanism except that the reaction is intramolecular at some point to effect the ring closure. Proceed with the mechanism to the point where the cyclization occurs. At this time, number the atoms that will become part of the ring (this includes noncarbon atoms). By numbering these atoms, the size of the ring is identified. Next, simply draw a ring of that particular size and number it. Go back to the linear drawing, identify the groups and their numeric position on the chain, and transfer the groups to the same number on the ring.
An initial inspection of the problem yields the following information: it is not a radical reaction due to the absence of initiators; it is not pericyclic due to the absence of a conjugated system. Therefore, it is probably a polar process. In determining the type of reaction, it is apparent that no pi bonds are formed or used. This will rule out additions or eliminations. This leaves only a substitution mechanism. The fact that there is no Br in the final product supports this position. The initial conclusion is that the process is a polar substitution; but, which process is it? Even though no solvent is shown, there are other aspects of the reaction to consider. Halogens are good leaving groups and the Br is attached to a primary carbon. Additionally, alcohols are good nucleophiles. Combining these facts, the logical conclusion to draw is that we have an SN2 reaction. The final consideration is that we need to form a ring which necessitates an intramolecular process. At this point, the nucleophile attacks the carbon containing the leaving group and the leaving group will leave. Before drawing the result of the process, number atom that will be forming the ring as illustrated below. When the five-membered ring of the intermediate is drawn, it is also numbered and the groups that are attached to the chain are transferred. Once the intermediate is drawn, the proton on the oxygen leaves which results in the final product.
For the remaining examples answer the following questions before looking at the answer. The answer key is graduated to assist solving problem as opposed to simply checking the answer should one experience difficulties working the problem. After chapter 5 in the text has been covered, the first three questions may be answered.
Is the reaction a radical, polar, or pericyclic process?
Is the reaction a substitution, elimination, or addition type mechanism?
Does this reaction require a cyclization?
In order to answer the remianing questions, it would helpful to have covered all the processes in class before proceeding. Chapters 6-8 will cover radical and electrophilic additions, as well as, the basics of the two elimination processes. Chapters 10 & 11 will cover all aspects of the two substitution reactions and the two elimination reactions. Finally, chapter 14 will provide the basics of the pericyclic reaction.
What is the specific mechanism for the process?
Are any rearrangements needed?
Show the mechanism.
| General Classification | Specific Type | Cyclization? |
| Specific Mechanism | Rearrangements? | Solution |
| General Classification | Specific Type | Cyclization? |
| Specific Mechanism | Rearrangements? | Solution |
| General Classification | Specific Type | Cyclization? |
| Specific Mechanism | Rearrangements? | Solution |
Additional examples will be placed on this page at a future date.
Reaction Mechanisms - assist in learning reactions and illustrate the advantages and limitations of a proposed step in a synthesis scheme.
Reactions - The student must have a strong knowledge of the reactions covered to that point in the course to successfully propose a synthesis scheme.
Product Prediction - The student should be able to predict the products of reactions given a set of substrates and reagents.
Reagent/Substrate Prediction - The student should be able to derive possible starting materials and reaction conditions to prepare a stated product.
Always keep in mind that more than one correct synthesis scheme may be proposed to arrive at the stated product (Target Molecule). For this reason, it is usually easier to work the problem "backwards." That is to say, work the problem as a series of "reagent/substrate prediction" problems until the stated starting material is used.
Using the reagents of your choosing, show how the following synthesis may be effected.
Step 1 - Inspect the main carbon chain, will you have to add carbons? If yes, what chain extension reactions have you had?
Step 2 - Start with the product and assume you may use any starting material/reagent combination to prepare it. How would you do this?
Step 3 - The alkene becomes your new target molecule. Can you make this from the stated starting material? If yes, do it! Otherwise, propose another substrate/reagent combination. In this case the answer is yes.
Putting all the steps together, the overall scheme is
This routine represents the basic procedure for working synthesis problems. As we progress, more subtle additions will need to be considered. However, the main exercise that will help most in learning this material is practice, Practice, PRACTICE!!!! Don't be afraid to make up your own problems to test yourself or member of your study group.
In all cases, you may use the reagents of your choosing to convert the starting material to the stated product. Please don't use the hint keys unless you are completely stumped. Note: THERE WILL BE NO HINT KEYS ON THE TESTS!!!
| Hint 1 | Hint 2 | Hint 3 |
| Hint 4 | Hint 5 | Answer 1 |
| Hint 1 | Hint 2 | Hint 3 |
| Hint 4 | Answer 2 |
| Hint 1 | Hint 2 | Hint 3 |
| Hint 4 | Answer 3 |
This problem gets its name by the fact that you must fill in the empty spaces of the map of a synthesis scheme with the correct material.
| Hint 1 | Hint 2 |
| Hint 3 | Answer Roadmap |