Reactions and Reaction Mechanisms

Reaction Mechanism Rules and Patterns

Reaction mechanisms show the mechanistic steps required to convert reactants into products.
A reaction mechanism is the exact step or steps required to convert reactants into products. Mechanisms explain how chemical reactions proceed. Mechanisms consist of individual steps called mechanistic steps. A mechanistic step is a step in a reaction mechanism. The four mechanistic steps are proton transfer, nucleophilic attack, loss of a leaving group, and rearrangement.

Recognizing the Four Main Mechanistic Steps

There are four main steps in mechanisms: proton transfer, nucleophilic attack, loss of leaving group, and rearrangement.

The proton (H+) transfer step is a rapid step, especially when the proton is transferred from an acidic position to a basic position. A solvent is often used to aid proton transfer. Proton transfers involve sigma bonds breaking and sigma bonds forming. Sigma bonds are bonds formed when two orbitals overlap end to end. In the presence of water, a proton will transfer from sulfuric acid to the water molecule, creating the positively charged hydronium ion.

Although acids are defined as proton donors, the mechanism involves the base attacking and removing the hydrogen from the acid. The hydrogen does not attack or move to the base.
A proton transfer is the first step in many mechanisms. In a proton transfer step, a base removes the proton from an acid.
A nucleophilic attack is a step where the nucleophile, which is rich in electrons, will attack an electrophile, which is electron deficient. The lone electron pair of a nucleophile, such as a bromide ion, will attack an electrophilic carbon, forming a new covalent bond. The carbon is electron deficient because it is next to an electronegative oxygen atom. This nucleophilic attack is often paired with another mechanistic step, such as the loss of a leaving group.
A nucleophilic bromide ion attacks a carbon atom to kick off a leaving group.
The loss of leaving group step occurs often but not always with a nucleophilic attack in one mechanistic step. As the nucleophile is attacking an electrophilic atom, the atom has to lose a leaving group to avoid violating the octet rule. In certain reactions, the loss of leaving group can precede the nucleophilic attack. The leaving group is a functional group that is able to leave a compound and usually forms a stable (weak) species. Halogens, such as bromine, chlorine, and iodine, make very good leaving groups, as do hydronium ions, mesylates, tosylates, and triflates. A good leaving group is a group that forms a very stable, weak conjugate base when it leaves. Whether initiated by the nucleophilic attack or on its own, leaving groups will leave the substrate based on their ability to form stable species. The more stable species the leaving group forms, the more likely the leaving group is to leave.
Water will displace the bromine atom in a substitution reaction. Bromine is a leaving group that is used in many substitution and elimination reactions.
The last of the four mechanistic steps is the rearrangement step. Rearrangement steps are very rare compared to the other three steps. Rearrangement steps are often intermediate steps in a mechanism where a positively charged carbocation is formed. Any time a carbocation forms, a rearrangement may occur. A carbocation is a positively charged carbon with three bonds and no lone pairs. Carbocations will always rearrange if they can form a more stable species. Carbocations are classified as primary, secondary, or tertiary based on the number of alkyl groups bonded to the positively charged carbon. Primary carbocations are bonded to one alkyl group and two hydrogens, secondary carbocations are bonded to two alkyl groups and one hydrogen, and tertiary carbocations are bonded to three alkyl groups. Tertiary carbocations are more stable than secondary carbocations, which are more stable than primary carbocations, due to the presence of alkyl groups, which donate electron density to stabilize the carbocation.
Carbocation stability is the main factor in rearrangements. Tertiary carbocations are more stable than secondary carbocations, which are more stable than primary carbocations.

Combining Mechanistic Steps

Mechanisms are combinations of the four main mechanistic steps to show how reactants are converted into products. Many mechanisms are reversible, meaning they can go from reactants to products or from products to reactants.
A reaction takes place in many stages, or steps. Proton transfer, nucleophilic attack, loss of a leaving group, and carbocation rearrangements are intermediate steps in the overall mechanism of a reaction. These steps can occur in any order, and often a mechanism will involve one of these steps repeating multiple times. Many mechanisms have multiple proton transfer steps within the overall mechanism.
The synthesis of pinacolone from pinacol involves multiple steps, including proton transfer steps and a rearrangement from a secondary to a tertiary carbocation.
Many mechanistic steps are reversible and exist in a state of equilibrium. Most elementary steps are reversible, meaning the product or products revert back into the reactants. Reversible steps may be shown with a double-headed arrow or two arrows pointing in opposite directions. In the Haber-Bosch process for production of ammonia from nitrogen gas and hydrogen gas, the reaction is reversible, and conditions need to be adjusted to make this reaction produce ammonia.
N2+3H22NH3Exothermic(Gives out heat energy)\color{#c42126}\begin{aligned}{\rm {N}_2+3{H}}_2\rightarrow2{\rm{NH}}_3\begin{aligned}\;\;&{\text {Exothermic}}\\&(\text{Gives out heat energy})\end{aligned}\end{aligned}
N2+3H22NH3Endothermic(Takes in heat energy)\color{#0047af}\begin{aligned}\rm{N}_2{+}3{H}_2\leftarrow2\rm{NH}_3\;\;\begin{aligned}&{\text {Endothermic}}\\&(\text{Takes in heat energy})\end{aligned}\end{aligned}
N2+3H2EndothermicExothermic2NH3\rm {N}_2{+}3{H}_2\overset{\color{#c42126}\text{Exothermic}}{\underset{\color{#0047af}\text{Endothermic}}{\color{#c42126}\rightleftharpoons}}2{\rm {N}{H}}_3

Summary of the Mechanistic Steps in Organic Reactions

Mechanistic Step Always Used In May Be Used In Arrows Other Notes
Proton transfer Acid-base reactions Addition and elimination 2 arrows:
1st arrow: from lone pair (or bond) of base to hydrogen
2nd arrow: from hydrogen-atom bond to atom (atom is usually carbon, oxygen, nitrogen, or halogen)
Proton transfer steps can occur in any reaction type.
Loss of leaving group Addition and elimination reactions Acid-base reactions 1 arrow: from bond between leaving group and atom (usually carbon) to the leaving group Loss of leaving group often occurs in the same step as nucleophilic attack.
Nucleophilic attack Acid-base, addition, and elimination reactions Used in all ionic reactions 1 arrow: from lone pair of nucleophile to electrophilic atom (usually carbon) Nucleophilic attack often occurs in the same step as loss of leaving group.
Rearrangement None Any reaction where a carbocation forms 1 arrow: from methyl or hydrogen bond to carbocation Rearrangements occur when a carbocation can rearrange to a more stable carbocation.

The table contains a summary of each mechanistic step and what reactions it is always used in or sometimes used in and the reaction arrows associate with each step. Radical reactions have a different set of mechanistic steps than the ones described in this table.