Nucleophilic Substitution Reactions
Nucleophilic substitution reactions are a general class of reactions that commonly occur with organic molecules. The general reaction is:
R-L + Nuc- ® R-Nuc + L-
where R-L is the organic reactant, Nuc is the nucleophile, and L is the leaving group.
SN2 Reactions
Examination of the kinetics of nucleophilic substitution reactions indicates that there are two basic types of reactions. Unhindered alkyl compounds typically obey the mixed, second order rate law shown below. Because of this, these reactions are referred to as SN2 reactions (Substitution, Nucleophilic, 2nd order).
Rate = k [R-L]1 [Nuc]1
These reactions are believed to occur by a concerted mechanism, where the nucleophile attacks the "backside" of the carbon center at the same time the carbon-leaving group bond is being broken. The transition state involves a five-coordinate carbon, which is ideally assumed to be trigonal bipyramidal. The three unaffected groups and the reaction site (carbon) lie approximately in a plane with the nucleophile and leaving groups above and below this plane.
Examination of the above mechanism indicates that these reactions should proceed with inversion at the carbon center. If an optically pure starting material is used and SN2 attack occurs at a stereocenter, the stereochemical label (R or S) will almost always change. (The obvious exception to this is when the leaving group and the nucleophile do not have the same "priority" based on the standard Cahn-Prelog-Ingold rules. However, this occurs only rarely.)
The five-coordinate transition state is much more crowded around the reactive center than either the reactant or product. The presence of bulky groups around this center has a detrimental effect on the rate of these reactions. In general, the rate of SN2 reactions obey the following trend:
Methyl > 1° > 2° > 3°
The rate of SN2 reactions at tertiary carbon centers is too slow to contribute any significant amount of product. To further illustrate that steric hinderance is the primary reason for the slowing of these reactions, the kinetics of SN2 reactions of neopentyl halides ( (CH3)3CCH2X) have been examined. Even though the reactive site is a primary alkyl halide, these reactions proceed at a negligible rate due to the size of the R group.
Below is a simple animation illustrating the mechanism for the SN2 reaction:
CH3Cl + F- ® CH3F + Cl-
SN1 Reactions
Tertiary alkyl halides are known to undergo nucleophilic substitution reactions. Examination of the kinetics of these types of reactions yielded the following first order rate law:
Rate = k [R-L]1 [Nuc]0 = k [R-L]1
The mechanism for these reactions is somewhat more complicated. The first step is the slow (rate-determining) step, and involves breaking the carbon-leaving group bond to yield a carbocation. This carbocation intermediate is very reactive and can form significant amounts of product in a fast reaction step even when poor nucleophiles are used. The carbocation is electron deficient (it has a formal charge of +1, and its Lewis structure has too few electrons to obey the octet rule). Alkyl groups are much better at stabilizing this ion than hydrogen atoms. Thus, tertiary carbocations are much more stable than primary or secondary carbocations, and are the only type of compound that routinely undergo SN1 reactions.
The carbocation intermediate is also symmetric. The nucleophile can attack on either side of the plane. If an optically pure reactant undergoes an SN1 reaction, a racemic mixture is produced.
Below is a simple animation illustrating the mechanism for the SN1 reaction:
(CH3)3CCl + F- ® (CH3)3CF + Cl-
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One of the more important features to note in this animation is the planar carbocation intermediate. Once the halide ion has left, the (CH3)3C+ ion is approximately planar.