SN1 and SN2 reactions In 1935,
Edward D. Hughes and
Sir Christopher Ingold studied nucleophilic substitution reactions of
alkyl halides and related compounds. They proposed that there were two main mechanisms at work, both of them competing with each other. The two main mechanisms were the
SN1 reaction and the
SN2 reaction, where
S stands for substitution,
N stands for nucleophilic, and the number represents the
kinetic order of the reaction. In the SN2 reaction, the addition of the nucleophile and the elimination of leaving group take place simultaneously (i.e. a
concerted reaction). SN2 occurs when the central carbon atom is easily accessible to the nucleophile. In SN2 reactions, there are a few conditions that affect the rate of the reaction. First of all, the 2 in SN2 implies that there are two concentrations of substances that affect the rate of reaction: substrate (Sub) and nucleophile. The rate equation for this reaction would be Rate=k[Sub][Nuc]. For a SN2 reaction, an
aprotic solvent is best, such as acetone, DMF, or DMSO. Aprotic solvents do not add protons (H+ ions) into solution; if protons were present in SN2 reactions, they would react with the nucleophile and severely limit the reaction rate. Since this reaction occurs in one step,
steric effects drive the reaction speed. In the intermediate step, the nucleophile is 185 degrees from the leaving group and the stereochemistry is inverted as the nucleophile bonds to make the product. Also, because the intermediate is partially bonded to the nucleophile and leaving group, there is no time for the substrate to rearrange itself: the nucleophile will bond to the same carbon that the leaving group was attached to. A final factor that affects reaction rate is nucleophilicity; the nucleophile must attack an atom other than a hydrogen. By contrast the SN1 reaction involves two steps. SN1 reactions tend to be important when the central carbon atom of the substrate is surrounded by bulky groups, both because such groups interfere sterically with the SN2 reaction (discussed above) and because a highly substituted carbon forms a stable
carbocation. Like SN2 reactions, there are quite a few factors that affect the reaction rate of SN1 reactions. Instead of having two concentrations that affect the reaction rate, there is only one, substrate. The rate equation for this would be Rate=k[Sub]. Since the rate of a reaction is only determined by its slowest step, the rate at which the leaving group "leaves" determines the speed of the reaction. This means that the better the leaving group, the faster the reaction rate. A general rule for what makes a good leaving group is the weaker the conjugate base, the better the leaving group. In this case, halogens are going to be the best leaving groups, while compounds such as amines, hydrogen, and alkanes are going to be quite poor leaving groups. As SN2 reactions were affected by sterics, SN1 reactions are determined by bulky groups attached to the carbocation. Since there is an intermediate that actually contains a positive charge, bulky groups attached are going to help stabilize the charge on the carbocation through resonance and distribution of charge. In this case, tertiary carbocation will react faster than a secondary which will react much faster than a primary. It is also due to this carbocation intermediate that the product does not have to have inversion. The nucleophile can attack from the top or the bottom and therefore create a racemic product. It is important to use a protic solvent, water and alcohols, since an aprotic solvent could attack the intermediate and cause unwanted product. It does not matter if the hydrogens from the protic solvent react with the nucleophile since the nucleophile is not involved in the rate determining step.
Borderline mechanism An example of a substitution reaction taking place by a so-called
borderline mechanism as originally studied by Hughes and Ingold is the reaction of
1-phenylethyl chloride with
sodium methoxide in methanol. : The
reaction rate is found to the sum of S1 and S2 components with 61% (3,5 M, 70 °C) taking place by the latter.
Other mechanisms Besides S1 and S2, other mechanisms are known, although they are less common. The
Si mechanism is observed in reactions of
thionyl chloride with
alcohols, and it is similar to S1 except that the nucleophile is delivered from the same side as the leaving group. Nucleophilic substitutions can be accompanied by an
allylic rearrangement as seen in reactions such as the
Ferrier rearrangement. This type of mechanism is called an S1' or S2' reaction (depending on the kinetics). With
allylic halides or sulphonates, for example, the nucleophile may attack at the γ unsaturated carbon in place of the carbon bearing the leaving group. This may be seen in the reaction of 1-chloro-2-butene with
sodium hydroxide to give a mixture of 2-buten-1-ol and 1-buten-3-ol: :CH3CH=CH-CH2-Cl -> CH3CH=CH-CH2-OH + CH3CH(OH)-CH=CH2 == Unsaturated carbon centres ==