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Recap
In the previous article, the factors affecting the rates of SN1 and SN2 mechanisms were discussed. For SN1 mechanisms, the rate-determining step is the solvolysis, so for less selective substrates, the reaction rate would be first order with respect to the concentration of the substrate.
For more selective substrates, however, they would be affected by the concentration of the substrate and the nucleophile. SN2 mechanisms are much simpler, and only affected by the concentrations of the nucleophile and the substrate.
Knowing which rates are affected by the concentrations of which species in the reaction is very helpful if we want to know which factors can influence the rate of an SN1 or SN2 mechanism. Previously we discussed, incompletely, that the rates of SN1 and SN2 mechanisms were affected by saturation / unsaturation and substitution of the electrophilic carbon. However, given that other factors are also involved, it is relatively incomplete.
Factor: Location
While we do not dispute that the presence of substituents on the electrophilic carbon is important and can greatly influence the rate of a reaction, we note that the location of the carbon on a molecule is also very important; it could be the difference between whether a nucleophilic substitution reaction goes so slowly it is barely observable or whether the reaction proceeds so fast that it is difficult to isolate an intermediate.
First, there are cyclic substrates. Some background information on cyclic aliphatics: simply stated, they are ringed molecules, and for this article we will only be discussing simple, one-ringed cyclic aliphatics, although other types of aliphatics are also possible.
Cyclic aliphatics almost always experience some type of strain; if I can recall correctly, smaller rings experience small-angle strain while larger rings experience large-angle strain. In general, both types of strain can be grouped under the category of ‘angle strain’ in itself. In cycloalkanes, each of the carbons are sp3 hybridized, meaning they assume a tetrahedral geometry and desire 109.5 degree bond angles.
Of the cycloalkanes, only cyclopentane and cyclohexane, with 108 and 120 degree bond angles in planarity, are devoid of such strain. Due to the instability of most cycloalkanes, we might expect that the rate of substitution reactions would be the fastest for the most stable and least strained cycloalkanes; i.e. substituted cyclopentanes or cyclohexanes (Fig. 1).
Fig. 1: Structure of a substituted cyclohexane.
Sadly however, the rate is, counterintuitively, the exact opposite; the more strained the cyclic aliphatic, the faster the rate of a substitution reaction. To understand why, we must know that for most substituted cycloalkanes, ‘normal’ SN reactions do not occur, instead, it is highly likely that a different, concerted mechanism will be followed that also leads to the opening of the ring.
Since the focus of this article is on reaction rates, we will not explain the exact mechanism, but know that the ring-opening will be energetically favorable for a good percentage of molecules, and thus it is likely for many cycloalkanes to follow such a mechanism.
So, what would contribute most to making a ring-opening reaction favorable? Of course, the more strained the ring, the higher its energy and thus the more energetically favorable a ring-opening would be. This is exactly the case for substituted cycloalkanes, of which very small or large cycloalkanes (although cyclopropyls solvolyse quite slowly) would be more strained and thus the ring-opening reaction would proceed at a faster rate. Cyclopentyls and cyclohexyls, in contrast, have relatively slower reaction rates. Electrophilic carbons can thus be influenced by the size of the ring they are on.
A closely related idea to the above is of bridgehead carbons (Fig. 2), which are easier to explain by a picture than by a description. They are relatively similar to the idea of carbon substitution, but in particular, bridgehead carbons cannot react via the SN2 reaction, because of the steric hindrance posed by virtue of their position on the molecule.
In contrast, however, SN1 reactions can and do take place on bridgehead carbons. It should be noted that much research has been carried out in the area of bridgeheads - single and double bonds can act as neighboring groups, delocalizing the charge of the bridgehead carbocation, and forming what is known as a nonclassical carbocation.
There has been much debate on whether these carbocations exist or not, but it seems to have been proven, more or less. Regardless, the single and double bonds may be able to delocalize the charge of the carbocation after solvolysis has occurred, making it stable, and in the same way as resonance, speed up the reaction.
Factor: Nucleophilicity
The nucleophilicity of the nucleophile can also be a factor, but this is only true of SN2 reactions, where the nucleophile is involved in the rate-determining step, and thus the rate can be impacted by the nucleophilicity. There are four general factors that can impact nucleophilicity.
Firstly, the broad, sweeping definition of nucleophiles have allowed many chemical species to be considered nucleophilic - even species without a negative charge, for example, can be considered nucleophilic, as long as a lone (or unshared) pair of electrons is present on the molecule, and that it can be used for attack an electrophilic species (in the same way, an electrophile does not have to possess a positive charge).
In general, a nucleophile will be stronger than its conjugate acid if it possesses a negative charge. Nucleophiles are basic as they have a pair of electrons they can use to attack a proton and form a bond with it. So by the rule stated above, OH- would be stronger than H2O, which is likely to be true.
In the same way to what is stated above, the more basic a molecule, the more nucleophilic it is likely to be. However, a requirement when comparing nucleophiles by this rule is that the attacking atoms must be on the same period in a periodic table.
It is important that we do not confuse nucleophilicity and basicity - nucleophilicity is kinetic while basicity is thermodynamic. As for comparing nucleophiles down a group (or a column on the periodic table), the nucleophilicity increases, yet the basicity decreases - another reason why nucleophilicity is not the same as basicity.
This is especially relevant for the halides, of which F- is the least nucleophilic and I- is the most nucleophilic. The reason for this trend is that molecules get bigger going down a column of the periodic table, making it less likely that the solvent molecules will surround it completely, and increasing the chance that the nucleophile can collide with the electrophile to begin a reaction. There is much strong evidence for the above.