Project 3 Background

Reaction Background

The oxidation of an alcohol to a carbonyl compound is one of the most valuable functional group transformations in organic chemistry. When the substrate is a primary alcohol, it can be difficult to control the oxidation such that the reaction stops at the aldehyde stage instead of proceeding to carboxylic acid oxidation state (Figure 1).

Figure 1. Oxidation of primary alcohols proceeds through the aldehyde oxidation state to the carboxylic acid oxidation state. Specialized reagents are used to stop the oxidation reaction at the aldehyde stage.

Many textbooks describe only “classic” methods for these reactions, but organic chemists have developed a variety to novel reagents and conditions to enable the  direct production of aldehydes from primary alcohols. One such system is the combination of iodobenzene diacetate (IBD) with a catalytic quantity of TEMPO (2,2,2,6-tetramethylpiperidin-1-oxyl).  Although the mechanism of this transformation is complex,  TEMPO is likely the active oxidizing agent while IBD is the stoichiometric oxidant. This means that a molecule of TEMPO will oxidize a molecule of the alcohol. In the process, the TEMPO molecule is reduced and no longer useful as an oxidant. The IBD then re-oxidizes the TEMPO molecule, which can then react with a fresh molecule of alcohol. The IBD molecule is consumed in this process because it is reduced to iodobenzene.  In fact, the mechanism involves several TEMPO-based intermediates as outlined in Figure 2. In Project 3, you will apply the TEMPO/IBD oxidation reaction to a pair of primary alcohols: geraniol and nerol.

Figure 2. In the TEMPO/IBD reaction, TEMPO is initially oxidized to Intermediate A, which reactions directly with the alcohol to generate the aldehyde. The resulting Intermediate B is then re-oxidized by IBD to generate Intermediate A.

Project 3 Context

Citral is natural oil derived from a variety plants, including lemongrass and several citrus fruit peels. The oil exhibits a distinct, pleasant lemon-like odor and is used as lemon-flavor additive in many foods, beverages, and cosmetics. While citral is commonly cited as the compound 3,7-diemtehyl-2,6-octadienal, it is actually a mixture of the E/Z isomers known as geranial and neral (Figure 3).

Figure 3. Citral, a natural oil obtained from lemongrass and other plants, is a mixture of two alkene isomers.

These two aldehydes are very difficult to separate by conventional methods (e.g., column chromatography), so citral is almost always sold and used as the mixture. By contrast, the corresponding alcohols (geraniol and nerol, Figure 4) are separable and readily purchased individually. In order to obtain a pure sample of geranial or neral, you will oxidize the corresponding alcohol under the TEMPO/IBD reaction conditions. At the end of the reaction, you will purify the aldehyde by column chromatography. This step is necessary in order to separate the oily product from the iodobenzene side-product generated during the reaction.

Figure 4. In Project 3, two groups work together to prepare pure samples of geranial and neral using the TEMPO/IBD oxidation system.

Your lab group will oxidize one isomer and team up with another group working with the opposite isomer. Use the general protocol given on the Procedure page to plan your reaction so that your theoretical yield is 0.152 g of the aldehyde. You will examine your combined data to assess your success at obtaining pure samples of geranial and neral.