Why are alcohols nucleophiles

Getting alcohols to act as nucleophiles is a little like trying to get pandas to mate in a zoo. It only happens if the female electrophile is incredibly horny.

As for hydroxyl groups as leaving groups, forget it. The hydroxy HO- and alkoxy RO - groups are both fairly strong bases, and therefore poor leaving groups. The bottom line here is that the hydroxyl groups of R—OH are not particularly reactive nucleophiles or electrophiles, as themselves. While I am currently unaware of progress on the panda aphrodisiac front, I can tell you that it is actually quite straightforward to make alcohols more reactive.

Leaving group ability and nucleophilicity. The leaving group is now H 2 O — a weak base and a great leaving group. The oxonium ion is much better set up to participate in reactions such as the SN1 and E1, as well as more rarely the S N 2 and E2. Since a protonated alcohol has a better leaving group, this also makes it a much better electrophile as well. However, if we remove a proton by adding a base we then get an alkoxide ion RO- which has much higher electron density, and is a much better nucleophile as well as being a strong base.

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The functional group of the alcohols is the hydroxyl group, —OH. Unlike the alkyl halides, this group has two reactive covalent bonds, the C—O bond and the O—H bond. The electronegativity of oxygen is substantially greater than that of carbon and hydrogen. Consequently, the covalent bonds of this functional group are polarized so that oxygen is electron rich and both carbon and hydrogen are electrophilic, as shown in the drawing on the right.

Indeed, the dipolar nature of the O—H bond is such that alcohols are much stronger acids than alkanes by roughly 10 30 times , and nearly that much stronger than ethers oxygen substituted alkanes that do not have an O—H group. The most reactive site in an alcohol molecule is the hydroxyl group, despite the fact that the O—H bond strength is significantly greater than that of the C—C, C—H and C—O bonds, demonstrating again the difference between thermodynamic and chemical stability.

For a discussion of how acidity is influenced by molecular structure Click Here. Electrophilic Substitution at Oxygen. Because of its enhanced acidity, the hydrogen atom on the hydroxyl group is rather easily replaced by other substituents. A simple example is the facile reaction of simple alcohols with sodium and sodium hydride , as described in the first equation below.

Another such substitution reaction is the isotopic exchange that occurs on mixing an alcohol with deuterium oxide heavy water.

This exchange, which is catalyzed by acid or base, is very fast under normal conditions, since it is difficult to avoid traces of such catalysts in most experimental systems.

The mechanism by which many substitution reactions of this kind take place is straightforward. The oxygen atom of an alcohol is nucleophilic and is therefore prone to attack by electrophiles. The resulting "onium" intermediate then loses a proton to a base, giving the substitution product. If a strong electrophile is not present, the nucleophilicity of the oxygen may be enhanced by conversion to its conjugate base an alkoxide.

This powerful nucleophile then attacks the weak electrophile. These two variations of the substitution mechanism are illustrated in the following diagram. Alkyl substitution of the hydroxyl group leads to ethers. This reaction provides examples of both strong electrophilic substitution first equation below , and weak electrophilic substitution second equation. One of the most important substitution reactions at oxygen is ester formation resulting from the reaction of alcohols with electrophilic derivatives of carboxylic and sulfonic acids.

The following illustration displays the general formulas of these reagents and their ester products, in which the R'—O— group represents the alcohol moiety. The electrophilic atom in the acid chlorides and anhydrides is colored red. Examples of specific esterification reactions may be selected from the menu below the diagram, and will be displayed in the same space.

Hydroxyl Group Substitution. Using the chemical behavior of alkyl halides as a reference, we are encouraged to look for analogous substitution and elimination reactions of alcohols. The chief difference, of course, is a change in the leaving anion from halide to hydroxide. Since oxygen is slightly more electronegative than chlorine 3. Despite this promising background evidence, alcohols do not undergo the same S N 2 reactions commonly observed with alkyl halides.

For example, the rapid S N 2 reaction of 1-bromobutane with sodium cyanide, shown below, has no parallel when 1-butanol is treated with sodium cyanide. In fact ethyl alcohol is often used as a solvent for alkyl halide substitution reactions such as this. The key factor here is the stability of the leaving anion bromide vs. We know that HBr is a much stronger acid than water by more than 18 powers of ten , and this difference will be reflected in reactions that generate their conjugate bases.

The weaker base, bromide anion, is more stable and its release in a substitution or elimination reaction will be much more favorable than that of hydroxide ion, a stronger and less stable base. Clearly, an obvious step toward improving the reactivity of alcohols in S N 2 reactions would be to modify the —OH functional group in a way that improves its stability as a leaving anion.

The only problem with this strategy is that many nucleophiles, including cyanide, are deactivated by protonation in strong acid, effectively removing the nucleophilic co-reactant needed for the substitution. The strong acids HCl, HBr and HI are not subject to this difficulty because their conjugate bases are good nucleophiles and are even weaker bases than alcohols.