MCAT Organic Chemistry Review
5.2 Reactions of Alcohols
The main reactions that we will see on the MCAT for alcohols include oxidation, preparation of mesylates and tosylates, and protection of carbonyls by alcohols.
Oxidation of alcohols can produce several products. Primary alcohols can be oxidized to aldehydes, but only by pyridinium chlorochromate (PCC), a mild anhydrous oxidant, as shown in Figure 5.6. This reactant stops after the primary alcohol has been converted to an aldehyde because PCC lacks the water necessary to hydrate the otherwise easily hydrated aldehyde. With other oxidizing agents, aldehydes are rapidly hydrated to form geminal diols (1,1-diols), which can be easily oxidized to carboxylic acids.
Figure 5.6. Oxidation of a Primary Alcohol to an Aldehyde by Pyridinium Chlorochromate (PCC)
Secondary alcohols can be oxidized to ketones by PCC or any stronger oxidizing agent. Tertiary alcohols cannot be oxidized because they are already as oxidized as they can be.
The oxidation of primary alcohols with a strong oxidizing agent like chromium(VI) will produce a carboxylic acid. In the process, chromium(VI) is reduced to chromium(III). Common examples of chromium-containing oxidizing agents include sodium and potassium dichromate salts (Na2Cr2O7 and K2Cr2O7). As with other strong oxidizing agents, these will fully oxidize primary alcohols to carboxylic acids, and secondary alcohols to ketones. An example is shown in Figure 5.7.
Figure 5.7. Oxidation of a Secondary Alcohol to a Ketone by a Dichromate Salt
Alcohols are readily oxidized to carboxylic acids by any oxidizing agent other than PCC (which will only oxidize primary alcohols to aldehydes).
Finally, an even stronger chromium-containing oxidizing agent is chromium trioxide, CrO3. When dissolved with dilute sulfuric acid in acetone, this is called the Jones oxidation, as shown in Figure 5.8. As expected, this reaction oxidizes primary alcohols to carboxylic acids and secondary alcohols to ketones.
Figure 5.8. Jones Oxidation A primary alcohol is oxidized to a carboxylic acid by CrO3.
MESYLATES AND TOSYLATES
The hydroxyl groups of alcohols are fairly poor leaving groups for nucleophilic substitution reactions. However, they can be reacted to form much better leaving groups called mesylates and tosylates. A mesylate is a compound containing the functional group –SO3CH3, derived frommethanesulfonic acid; its anionic form is shown in Figure 5.9.
Figure 5.9. Structure of the Mesylate Anion
Mesylates are prepared using methylsulfonyl chloride and an alcohol in the presence of a base.
Tosylates contain the functional group –SO3C6H4CH3, derived from toluenesulfonic acid. These compounds are produced by reaction of alcohols with p-toluenesulfonyl chloride, forming esters of toluenesulfonic acid. A tosylate is shown in Figure 5.10.
Figure 5.10. Structure of a Tosylate
In addition to making hydroxyl groups of alcohols into better leaving groups for nucleophilic substitution reactions, mesyl and tosyl groups can also serve as protecting groups when we do not want alcohols to react. These groups are protective in that they will not react with many of the other reagents that would attack alcohols, especially oxidizing agents. Thus, reacting an alcohol to form a mesylate or tosylate is sometimes performed before multistep reactions in which the desired products do not derive from the alcohol.
Alcohols can also be used as protecting groups for other functional groups. For example, aldehydes and ketones can be reacted with two equivalents of alcohol or a diol (dialcohol), forming acetals (primary carbons with two –OR groups and a hydrogen atom) or ketals (secondary carbons with two –OR groups). Carbonyls are very reactive with strong reducing agents like lithium aluminum hydride (LiAlH4). Acetals and ketals, on the other hand, do not react with LiAlH4. The acetal or ketal functionality thereby protects the aldehyde or ketone from reaction. After reducing other functionalities in the molecule, the acetal or ketal can be reverted back to a carbonyl with aqueous acid, a step called deprotection. These reactions are shown in Figure 5.11.
Figure 5.11. Protection of a Ketone by Ketal Formation Using a Dialcohol
MCAT Concept Check 5.2:
Before you move on, assess your understanding of the material with these questions.
1. What will happen to primary and secondary alcohols, respectively, in the presence of strong oxidizing agents?
· Primary alcohols:
· Secondary alcohols:
2. How can primary alcohols be oxidized to aldehydes?
3. What is the purpose of a mesylate or tosylate?
4. How can aldehydes or ketones be protected using alcohols?