Introduction
In this blog, we have spent a lot of time discussing aspects of substitution reactions, for example, the rates of the reactions, the mechanisms of the reactions, and the stereochemistry of the products. In doing so, however, we have neglected other key classes of reactions in organic chemistry, that is, addition and elimination reactions.
As such, we will begin to devote more of our time to addition reactions (an earlier post listed some addition compounds), and much less time on substitution reactions. After we explain addition reactions, we will then move on to elimination reactions. So, without further ado, let us begin our introduction into the chemistry of addition reactions.
We have noted in a previous post that addition reactions are of a large scope. In the series on addition compounds, we discussed host-guest chemistry, cryptands, and other similar addition reactions. However, in this post, and many of the subsequent ones, we will be focussing specifically on addition to multiple bonds.
Addition to multiple bonds is the class of addition reactions that is taught most commonly in organic chemistry, given that key chemistry is unlocked by the reactivity of multiple bonds. In this article, we will first be studying the mechanisms of addition reactions (of which there are a considerable amount, unfortunately, just like substitution reactions), followed by discussions of substrate reactivity in the next article.
The mechanisms of addition reactions include: electrophilic addition, nucleophilic addition, free radical addition, pericyclic addition (or similar reactions, as we will touch on later) and addition to conjugated dienes. Finally, there is also another mechanism which we will consider a variation of the first three mechanisms, and it will not be discussed separately.
Electrophilic Addition
This mechanism of addition reactions is a two-step mechanism. It is very similar to nucleophilic addition. In the first step of electrophilic addition, the electrophile, a positively-charged species, attacks the multiple bond. The multiple bond donates a pair of π electrons to the electrophile, forming a bond to it, and breaking a π bond simultaneously in the process. The intermediate formed from this first step is shown in Fig. 1.
Fig. 1: Step 1 of the electrophilic addition mechanism.
In the second step of the mechanism, a nucleophile attacks the positively-charged carbocation (formed after attack by the electrophile on the adjacent carbon). Of course, the nucleophile carries uses its pair of electrons to form a bond with the carbocation, thus resolving the positive charge and resulting in an neutral 1,2-addition product (i.e. adjacent carbons are substituted). This second step is shown in Fig. 2.
Fig. 2: Step 2 of the electrophilic addition mechanism.
The second step may vary because it is possible for some atoms to form bonds to both carbons instead of just one (in the intermediate between the steps). While this bridging atom still carries a charge, it can form bonds between the two carbon atoms, providing greater stabilization. Subsequent attack by the nucleophile breaks the ‘extra’ bond and forms the 1,2-addition product. This reaction may be considered SN2.
Since this alternative mechanism follows the SN2 reaction, it should be expected that the stereochemistry of the products would be the same. This means that only anti addition products can result from such an alternative mechanism (i.e. the products add to opposite sides of the multiple bond, due to ‘backside attack’).
As for the typical electrophilic addition mechanism, it should be nonstereospecific, considering that we only look at the mechanism itself and not any other factors involved. In reality, it is likely that some factor will interfere with the stereochemistry and cause a larger proportion of one stereoisomer to be produced over the other. Examples of these factors include the formation of ion pairs or even ‘partial bonds’ between the electrophile (which is bonded to the carbon atom) and the adjacent carbon atom.
Nucleophilic Addition
Having learnt about the mechanisms of electrophilic addition, we will move on to discuss nucleophilic addition. In fact, the two mechanisms (and even the next one, free radical addition), are highly similar, in that the general mechanism is the same, but the order of attack is different, and reversed specifically in the case of nucleophilic addition as compared to electrophilic addition.
In the first step of the nucleophilic addition mechanism, a nucleophile (instead of an electrophile) attacks the multiple bond using its pair of electrons to form a bond to a carbon atom. This breaks the π bond between the carbon atoms, with the π electrons going to the adjacent carbon atom and giving it a negative charge.
In the second step of this mechanism, an electrophile approaches the negatively-charged, nucleophilic site, and attacks it. The result is that a bond is formed using the additional π electrons, between the electrophile and the carbon atom. This results in the 1,2-addition product that is similar to that of electrophilic addition.
Side reactions are known to occur in some cases, given that nucleophilic attack occurs in the first step. This first step bears similarities to nucleophilic substitution, and if the carbon atom being attacked possesses a leaving group, it is possible for this leaving group to depart upon attack by the nucleophile. This is known as nucleophilic vinylic substitution.
What about the stereochemistry of nucleophilic addition products? As we should expect, they are similar to that of the stereochemistry of electrophilic addition products, because their mechanisms are so similar. Addition to cyclic double bonds are likely to be stereospecific, while addition to triple bonds is generally nonstereospecific, and this applies to both nucleophilic and electrophilic addition.
Free Radical Addition
Even free radical addition possesses similarities to nucleophilic and electrophilic addition. For this reason we will no longer be illustrating their mechanisms, because it is only the point charges which change. Free radical addition is different from free radical substitution, which we have already discussed.
Instead of point charges, free radicals are involved, and this means that in the first step (there are still two steps), there is an attack on the double bond by a radical. There are a few ways to produce the radical. Firstly, spontaneous homolytic cleavage of some molecules will form radicals without any other reaction conditions. Molecules such as peroxides can spontaneously cleave to produce hydroxy or alkoxy radicals. Alternatively molecules can cleave after being exposed to heat or light.
In the first step, the radical attacks one of the carbons forming the multiple bond. The π bond will then homolytically cleave and one of the π electrons is used to form a bond with the radical, while the other π electron goes to the adjacent carbon, forming another radical. This may be considered a propagation step as a new radical is produced, even though no abstraction is involved, as would be typical of free radical substitutions.
Then, in the second step, the radical is resolved. Typically, and this also applies for free radical substitution reactions, there are two ways to resolve the radical, which is by the abstraction of another atom (from a stable molecule) or by a termination step (from a radical). Usually, it is the former that is more accessible and thus it takes place more often.
It is interesting to note that the intermediate formed in step 1 is also a radical, which means it should be able to perform free radical addition on another multiple bond. This may happen indefinitely, meaning that long carbon chains may result. This is known as free radical polymerization, often forming unwanted side products in similar free radical addition reactions.
The reaction can also occur intramolecularly for 1,5 or 1,6-dienes, as a ring-closing reaction. Only these reactants may be used because otherwise there would be considerable strain within the ring. For example, in a 1,6-diene, a radical attacks one of the double bonds first, forming another radical. This radical then attacks the other double bond in the molecule, forming a bond to it, and this closes the ring.
As we may suspect, free radical additions are usually not stereospecific because of their high reactivities. Rarely will there be factors which are able to result in the predominance of one of the stereoisomers over another. In some cases, the same bridged intermediate (i.e. in the alternative mechanism), known as a bridged free radical, may form, causing an SN2-type reaction to occur, resulting in stereospecific products.
Pericyclic Addition
In pericyclic addition, an unusual one-step reaction occurs instead of the usual two-step we have observed for nucleophilic, electrophilic, and free radical addition. This has some implications, one of which is that both carbons forming the double bond are attacked simultaneously. The mechanism does not necessarily have to be pericyclic, but this is common especially when both attacking atoms (of the multiple bond) are on the same molecule.
When both attacking atoms are on the same molecule, a ringed compound should result, and syn addition should take place. Anti addition typically does not occur because the attacking atoms have to be close to each other, given that they are on the same molecule. The mechanism of pericyclic addition is not within the scope of this article, but a six-membered transition state can be involved.
One example of a pericyclic reaction is the Diels-Alder reaction, which involves the reaction between a diene and a dienophile. The resulting compound is a six-membered ring.
Conjugated Addition
We have briefly touched on 1,5 and 1,6-dienes previously, but never on 1,3-dienes or other similar conjugated dienes. Being conjugated means that double bonds are adjacent to to each other. In these cases two products may be obtained, which is 1,2 or 1,4-addition. This means that the attacking reagents either add to the 1 and 2 carbons or add to the 1 and 4 carbons.
Why is it possible for two products to be formed? When electrophilic attack occurs at the 1 position (or also at the 4 position), the adjacent carbon will become a carbocation. Relative to the untouched double bond, it is an allylic carbocation. This means that resonance can occur to delocalize the carbocation over the 2 and 4 positions (Fig. 3), leaving two possible positions for later attack in step 2 by the nucleophile.
Fig. 3: Resonance over 2 and 4-carbons.
Attack at the 2-position results in 1,2-addition, while attack at the 4-position results in 1,4-addition. Since this is the case, it appears that the products should be produced in equal proportions; however, this is not always the case. It is possible for one of the products to be favored over another by factors such as the formation of ion pairs.
Addition to Cyclopropanes
Strictly, this is not considered addition to multiple bonds, because cyclopropanes do not possess π electrons. However, the bonding between two adjacent carbons in a molecule of cyclopropane is rather similar to that of a double bond, just that one of the bonds is extended by one carbon. This feature gives cyclopropanes reactivity akin to double bonds themselves, allowing them to participate in some addition reactions.
For example, it is possible for cyclopropanes to react with reagents such as hydrogen bromide, forming 1-bromopropane. We note that the reaction is also a ring-opening reaction, because the addition reaction breaks one π bond. In the case of cyclopropane, one of the single bonds is broken and the ring is opened. The mechanism for this reaction, however, is unclear, as evidence so far seems to have proved inconclusive.