Aldehydes

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Chapter: Organic Chemistry : Functional Group Synthesis

The aldehyde functional group is a very reactive functional group; thus methods to prepare it must be mild and allow the aldehyde group to survive the reaction conditions.


ALDEHYDES

The aldehyde functional group is a very reactive functional group; thus methods to prepare it must be mild and allow the aldehyde group to survive the reaction conditions. Traditional methods for introduction of the aldehyde functional group include


Aldehydes are intermediate in oxidation level, and thus the aldehyde func-tional group can be installed by either reduction of carboxylic acid derivatives or oxidation of alcohols. Aldehydes are rarely installed without a change of oxi-dation level. One difficulty is that they undergo both oxidation and reduction readily. Special methods are required to stop at the aldehyde stage rather than proceeding by further reduction or oxidation.

Reductive methods utilize carboxylic acid derivatives as starting materials, and the trick is to stop the reduction at the aldehyde stage, which is normally more easily reduced than the starting material. While there are a variety of reducing systems known and many employ acid chlorides as precursors, the most effective reduction method for the preparation of aldehydes is the diisobutylaluminum hydride (DIBAH) reduction of either esters or nitriles using a single equivalent of the reducing agent. By using low temperatures, the intermediate anions produced by hydride addition are at the aldehyde oxidation level, but they are resistant to further reduction. Hydrolysis delivers the aldehyde. Care must be taken to maintain low temperature during both the reaction and the hydrolysis.


The oxidation of primary alcohols to aldehydes also suffers from the problem of overoxidation of the aldehyde to a carboxylic acid. Mild methods capable of stopping the oxidation at the aldehyde oxidation level are required if aldehydes are to be obtained. The most common and effective reagent for this purpose is pyridinium chlorochromate (PCC), produced by the reaction of pyridinium hydrochloride with chromium trioxide. This reagent is soluble in dichloromethane and smoothly oxidizes primary alcohols to aldehydes in high yields. Because of the mild, neutral reaction conditions and the use of stoichiometric amounts of oxidant, the aldehyde product is not oxidized further.

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols.


A different oxidative approach toward the preparation of aldehydes uses the ozonolysis of vinyl groups. If a vinyl group is present in a molecule, it can be oxidatively cleaved to an aldehyde by ozonolysis. This process cleaves the carbon – carbon double bond, but it is mild and very successful in many cases.


The formation of aldehydes without a change in oxidation level is not a common synthetic approach because most compounds that can be hydrolyzed to aldehydes without change in the oxidation level are formed from aldehy-des in the first place. Thus acetals can be hydrolyzed rapidly to aldehydes by acidic water, but they are normally prepared from aldehydes. As such this is a very common protection strategy for aldehydes wherein they are first con-verted to an acetal and later hydrolyzed back to the aldehyde when the time is right.



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