Organic Chemistry: Intro to Organic 4: Leaving Groups and Nucleophiles

The Leaving Group

The leaving group is a component of every substitution and elimination reaction discussed in this SparkNote. As such, it makes sense to learn the characteristics of a good leaving group.

In any substitution or elimination reaction, electrons from a nucleophile, carbon-hydrogen bond, or the solvent break a carbon-leaving group bond. Here the leaving group is abbreviated as "LG."

As you can see, the leaving group is aptly named; it is the group that leaves.

There is a bit of terminology dealing with the leaving group important to substitution and elimination. The α-carbon is the carbon atom bonded to the leaving group. β-carbons are attached to the α-carbon. The hydrogens attac hed to the β-carbon are called β-hydrogens. This terminology is vitally important for our discussion of substitution and elimination reactions.

Ranking Leaving Groups

Let's define a good leaving group as one that leaves easily. Then the effectiveness of a leaving group increases with the group's energetic stability after it has left. Thus a weak base is a better leaving group than a strong base. Likewise, a m olecule that is neutral after leaving is generally a better leaving group than one that is negatively charged after leaving.

Halides and the tosyl group (-OTs) are examples of commonly used leaving groups. In general, if the group is relatively stable after leaving the molecule with the C-LG bond's electrons, it's a good candidate for a leaving group.

The Nucleophile

The nucleophile is a key part of every substitution reaction. In these reactions, it is the group that "substitutes" for the leaving group. A nucleophile has a lone pair of electrons that makes up the molecule's business end. A polarizable nucleophile contribute more negative charge from its lone pair and has more punch than its non-polarizable fellow. On the same token, good nucleophiles tend to be negatively charged, but can also be neutral.

For nucleophiles that share the same attacking atom, nucleophilicity roughly follows Bronsted basicity.

With data like this, it is tempting to link nucleophilicity directly to Bronsted basicity. This is not correct. Basicity is defined by the equilibrium constant of its reaction with an acid. Nucleophilicity is defined by the rate constant of its substitution reaction. Thus nucleophilicity is a kinetic variable, while basicity is a thermodynamic one. Increased Bronsted basicity does not necessarily correlate to increased nucleophilicity.

The iodide ion is a very good nucleophile that is only a weak base. Iodide is often a better nucleophile than ethoxide, but is a weak enough base to be a good leaving group.

Solvent Effects on Nucleophilicity

Nucleophilicity is solvent dependent. Polar solvents allow nucleophiles to become highly polarized. They increase nucleophilicity. Protic solvents decrease nucleophilicity by hydrogen bonding to the nucleophile's lone pair end. The hydrogen bonds blunt the molecule's nucleophilicity and must be broken before nucleophilic attack can occur. For these reasons, nucleophilicity is greatest in polar, aprotic solvents.