Introduction
Throughout all of our posts on substitution reactions, we have sadly not yet managed to cover free radical substitution reactions. Before we start looking at the mechanisms of free radical substitution, let us first understand what these reactions are first. This is what we will be discussing in the introduction.
Free radicals refer to a chemical species with an unpaired electron. Note that there is no difference between the terms ‘radical’ and ‘free radical’, and they are interchangeable. Given that unpaired electrons are present, we would expect that the species be reactive, because it is more stabilizing for a pair of electrons to be present.
However, this is not always true, as there are some atoms that have unpaired electrons (i.e. they are radicals) but yet are relatively stable, so much so that we would not even be aware that they are radicals. Examples of this include, most prominently, molecular oxygen (O2).
It is not clear why molecular oxygen should be a radical because it seems that there are 16 electrons in O2 (which should mean that all electrons are paired, since it is an even number). The explanation for this is that each of the oxygen atoms have one unpaired electron, making it a biradical (two radical atoms). The reason for this is outside the scope of our discussion but this paper is useful.
So, how are radicals formed? In many cases the main way is by homolytic cleavage of a single bond. The homolytic cleavage may be spontaneous for exceedingly weak bonds (such as peroxide bonds), or can be caused by UV light or heat. In either case molecules that have weak bonds (low bond dissociation energies) are preferred, because they do not require much energy to cleave.
It is also possible for radicals to be formed from other radicals, and this occurs in one of the steps of the free radical substitution, which we will discuss later. Finally, the rearrangement of a radical to form a new radical may also be considered.
Free Radical Substitution Reactions
In any free radical substitution reaction, there are at least two steps. These steps form the start and the end of any free radical substitution, and are aptly named the initiation and termination steps. Before we begin discussing these steps, we should note that it is very rare for a reaction to contain only these two steps. More often, there is an in-between step known as the propagation step.
In the initiation step (Fig. 1), radicals are formed. There are a few ways to form radicals, and one of the key methods is to homolytically cleave molecules. This means that a bond between two atoms is split equally between both, such that out of the two electrons which form the bond, one goes to each atom. This will form two radicals.
Fig. 1: Initiation step of free radical substitution.
The final step of every free radical substitution reaction is known as the termination step (Fig. 2). In this step, two radicals will combine, forming a stable product (since all the electrons are now paired). Since UV light or heat is only exposed to the molecules in the initiation step, it is not possible for this stable product to undergo another free radical substitution reaction by homolytic cleavage (although it may still react with radicals).
Fig. 2: Termination step of free radical substitution.
In many free radical substitution reactions, a step is present between the initiation and termination steps. This is known as the propagation step, and as the name suggests, radicals are propagated in this step (i.e. new radicals are created). Radicals are so reactive that they are even able to react with stable molecules, resulting in the formation of another stable molecule and radical.
When a radical reacts with a stable molecule, there will overall be an odd number of molecules, since odd + even is still odd. So, how does the radical react with a molecule? For aliphatics (aromatics react with radicals via a different mechanism that we will explain later), abstraction usually occurs.
In abstraction (Fig. 3), a radical takes away an atom from a stable molecule such that this atom homolytically cleaves. This means that the stable molecule becomes a radical while the other radical atom combines with the original radical to form a separate stable molecule. Thus, this is a propagation step as a new radical is created.
Fig. 3: Abstraction of an atom by a radical.
In certain cases there is no propagation step at all, but this can only occur when the radical is too weak to abstract an atom from a stable molecule to ‘continue’ the chain of reactions, and the only energetically favorable step possible is the termination step (the initiation step only occurs after energy input). This is quite rare. Examples of such radicals are aryl radicals, which are discussed later.
It is relatively easy to distinguish free radical reactions from other types of reactions simply because a radical is highly reactive. In most cases, changing the medium of reaction should not affect the rate of the reaction, because the high reactivity is typically not affected by changes in the medium of reaction. Also, many free radical substitutions are not enantioselective, with some exceptions.
The reaction is also likely to be a free radical reaction if heat and light (which are represented by a high temperature, or hv, respectively), or even promoters such as peroxides (which participate in the propagation step by abstracting stable reactant molecules), are present. Finally, if inhibitors (which should lower the rate of reaction) are demonstrated to slow down a reaction, it may also be proof that the reaction follows a free radical mechanism.
Free Radical Mechanisms
There are three types of free radical mechanisms. These are the SH1, SH2, and the neighboring-group mechanism, which we have already discussed for nucleophilic substitution reactions in this post. Logically we will begin by discussing the more simple SH1 and SH2 mechanisms first, followed by the more difficult neighboring-group mechanism.
Two common ways exist to form aliphatic radicals, as we have noted previously. This is either by homolytic cleavage (which includes spontaneous cleavage as well as heat and light) or abstraction by another radical. These form the different mechanisms.
The ‘SH1’ refers to substitution homolytic unimolecular. Just by the name, we can guess what it refers to. When a radical is produced via homolytic cleavage involving just a single molecule, it is called the SH1 mechanism. There are two ways for this to occur, which is where the cleavage is caused by input of energy from heat or light, or it may also be spontaneous.
There is also the SH2 mechanism, which refers to substitution homolytic bimolecular. As can be easily guessed, this refers to the reaction between 2 reactant molecules to form a new radical. An example of this is the propagation step found in many reactions, where a radical and a stable molecule react to form a new radical.
Finally, there is also the neighboring-group mechanism. After we consider this mechanism, we will be moving on to take a look at the mechanisms of aromatic free radical substitution. In order for the neighboring-group mechanism to take place, there must be a neighboring group present. In a previous post (also linked above) we have listed down several types of neighboring groups, so we will not explain them again.
In the neighboring-group mechanism, the propagation step is catalyzed. For example, if the atom to be abstracted was a hydrogen bonded to a carbon, it should be possible for a neighboring group present on the adjacent carbon to stabilize the product formed after the abstraction. After an abstraction occurs, there would be a radical present on the carbon atom, which is unstable. This makes the abstraction less energetically favorable.
The neighboring group is able to stabilize the radical formed by forming a bond to both the original carbon and its adjacent carbon, moving the unpaired electron away from the carbons and toward itself. Such an intermediate is cyclic and is known as a bridged free radical.
Finally, we will also look at one mechanism for aromatic substrates. Although it is possible for an abstraction to occur, this cannot explain how it is possible for an aryl radical and a benzene ring to react and form a biaryl.
The formation of the biaryl cannot possibly occur through the abstraction mechanism because that would mean that the aryl would have to abstract the phenyl from the hydrogen, which is difficult and highly unlikely. Instead, it is more probable that a separate mechanism is occurring in this case, which we will detail below.
This new mechanism for aromatic free radical substitution is very similar to the electrophilic and nucleophilic aromatic substitution reaction mechanisms, which we have explained here. Attack by the aryl radical results in an unstable intermediate which has the radical delocalized throughout the ring.
This intermediate is relatively stable and there are three ways to resolve it. The first way is direct coupling of two such intermediates to form an interesting quaterphenyl-like (Fig. 5) compound. The second is disproportionation (i.e. an acid-base reaction between two similar intermediates), which would form the biphenyl as well as an aryl with a cyclohexadienyl substituent. Finally it is also possible for abstraction to occur by another radical, forming a biaryl as well as the hydrogenated radical.
Influencing Radical Reactivity
For aliphatics (more specifically hydrocarbons, because they most commonly participate in free radical substitutions), it is more common for a stable product to be formed from the abstraction step than the termination step. This is because while abstraction steps may happen numerous times to a reactant, the termination step may only occur once. As such, we will be focussing our attention on the abstraction step.
In many abstraction steps, we note that only univalent atoms are abstracted. Examples of univalent atoms are hydrogens and halogens. We rarely see tetravalent atoms like carbon being abstracted. Why? The answer lies in steric factors (Fig. 4). Since the univalent atom can only bond to one other atom, it is relatively easy for a radical to approach the atom and abstract it. For tetravalent atoms, they are surrounded by four groups and this makes it more difficult for the radical to approach them.
Fig. 4: Steric factors between atoms.
Preferences also exist within the group of univalent atoms. For alkane hydrogens, tertiary types are preferred, followed by secondary, then primary hydrogens. The reason for this is kinetic as evidenced by the fact that selectivity decreases with increasing temperatures. While stericity is not often a factor when comparisons are made between different hydrogens, it may be so if the radicals are bulky enough. This would make the abstraction of primary hydrogens more favorable (Fig. 5).
Fig. 5: Steric factors between hydrogens.
We have not yet looked at a possible abstraction step for alkenes. Since alkenes are still hydrocarbons, it is still more likely for univalent atoms to be abstracted. For alkenes, though, it is unlikely that a vinylic hydrogen (hydrogen bonded to a sp2-hybridized carbon) will be abstracted.
A separate position of attack is the allylic hydrogen (hydrogen on the carbon adjacent to the double bond). Attack here will be much more likely because of resonance from the double bond that can stabilize the allyl radical. This also explains why benzylic hydrogens may be abstracted.