Alcohols

ALCOHOLS

The alcohol functional group is a very important functional group in organic chemistry. Not only do many important compounds and pharmaceuticals contain the alcohol group, but the alcohol group can be prepared from many other groups and converted to many functional groups. Thus alcohols occupy a central position in functional group manipulations. In addition, most of the tradi-tional methods for the preparation of alcohols are still among the most useful methods.

Alcohols are at a fairly low oxidation level compared to other oxygen-containing functional groups and consequently are readily prepared by reduction. Large numbers of reductive methods have been reported for the preparation of alcohols. Carboxylic acids and esters react vigorously with lithium aluminum hydride (LAH) to produce primary alcohols. Carboxylic acids, but not esters, are also reduced easily by borane, which is the only reducing agent that reacts faster with carboxylic acids than with esters or other acid derivatives.

Its unique reactivity comes from the fact that borane first forms a Lewis acid – base complex with the acid and then a boron – carboxylate intermediate which increases the reactivity of the boron hydride and delivers the hydride by an intramolecular reaction. As such it provides a selective way to reduce acids and produce alcohols in the presence of most other functional groups.

Aldehydes and ketones are conveniently reduced by sodium borohydride, which is much milder than LAH and does not require aprotic conditions (an alcohol is often the preferred reaction solvent). Aldehydes give primary alcohols while ketones give secondary alcohols.

Alcohols and olefins are at the same oxidation level and are interconvertible without a change in oxidation level. Addition of water across an olefinic dou-ble bond is thus a common method for the preparation of alcohols. However, simple acid-catalyzed addition of water is often the least desirable alternative. Instead methods are used which permit much greater regiochemical control and are milder. For example, the preferred way to produce the Markovnikov alcohol from an olefin is to use hydroxymercuration for the addition step followed by reductive removal of mercury with NaBH₄. In this process mercury serves as a surrogate for the proton during the addition step and is replaced by hydrogen in the reduction. The advantage is that the mercuric electrophile forms a bridged or partially bridged intermediate that is stabilized and hence gives higher yields and cleaner product mixtures because rearrangements are suppressed. Other nucle-ophiles such as alcohols, acids, and hydrogen peroxide can also be employed as the cation trap.

Hydroboration is widely employed to obtain an anti-Markovnikov alcohol from an olefin. Addition of diborane to the double bond produces an organoborane intermediate. Three equivalents of the olefin are needed to consume the BH₃ and a trialkylborane is produced. Reaction with basic H₂O₂ converts the carbon – boron bond to a carbon oxygen bond. This process is effective and widely used.

The initial addition step occurs in a concerted fashion so that the hydrogen and boron are added to the same side of the planar double bond. Furthermore, the cleavage of the carbon – boron bond occurs with retention of configuration. These features can be used advantageously to prepare stereochemically pure alcohols.