17.7 Oxidation of Alcohols

Oxidation Products of Alcohols

Alcohol oxidation converts the $\text{C–OH}$ group into a carbonyl ($\text{C=O}$) group. The product you get depends entirely on the class of alcohol you start with, and which oxidizing agent you choose controls how far the reaction goes.

Oxidation Products by Alcohol Type

Primary alcohols ($RCH_2OH$) can be oxidized in two stages:

• Mild oxidation stops at the aldehyde ($RCHO$). Reagents like PCC (pyridinium chlorochromate) or Swern oxidation conditions are selective enough to halt here.
• Strong oxidation pushes the aldehyde further to a carboxylic acid ($RCOOH$). Reagents like chromic acid ($H_2CrO_4$) or potassium permanganate ($KMnO_4$) will carry the reaction all the way through.

The reason strong oxidants over-oxidize is that the aldehyde intermediate still has a $\text{C–H}$ bond on the carbonyl carbon, making it vulnerable to further oxidation.

Secondary alcohols ($R_2CHOH$) oxidize to ketones ($R_2C=O$). The reaction stops here because the ketone's carbonyl carbon has no hydrogen attached to it, so there's nothing left to oxidize. Chromic acid, PCC, Swern, and Dess-Martin periodinane all work for this conversion.

Tertiary alcohols ($R_3COH$) are resistant to oxidation under normal conditions. The carbon bearing the $\text{–OH}$ has no hydrogen, so the key step of the mechanism (hydride transfer) simply can't occur. Under harsh acidic conditions, tertiary alcohols tend to undergo elimination (dehydration) or substitution instead.

Mechanism of Alcohol Oxidation

At its core, alcohol oxidation involves removing two things from the substrate: a hydrogen from the $\text{O–H}$ bond and a hydrogen (as hydride, $H^-$) from the $\text{C–H}$ bond on the same carbon. This creates the $\text{C=O}$ double bond.

Here's how the general chromate-based mechanism works:

1. The alcohol attacks the chromium center, forming a chromate ester (a $\text{Cr–O}$ bond to the alcohol carbon).
2. A base abstracts the $\text{C–H}$ proton (or hydride is transferred to chromium) in an E2-like elimination step.
3. The $\text{C=O}$ bond forms as chromium is reduced from Cr(VI) to Cr(IV).

Common Oxidizing Agents

A practical tip: PCC works in anhydrous (water-free) $CH_2Cl_2$. The absence of water is exactly why the aldehyde doesn't get further oxidized, since over-oxidation of aldehydes to carboxylic acids by chromium requires the hydrated form of the aldehyde.

Biological Oxidation of Alcohols

Living systems oxidize alcohols using the same fundamental chemistry, but with enzymes and coenzymes instead of chromium reagents.

NAD$^+$ (nicotinamide adenine dinucleotide) and NADP$^+$ serve as the biological oxidizing agents. They accept a hydride ($H^-$) from the substrate, getting reduced to NADH and NADPH respectively.

The enzymatic process works in two stages:

1. Alcohol dehydrogenase (ADH) catalyzes hydride transfer from the alcohol's $\text{C–H}$ bond to NAD$^+$, producing an aldehyde (from a primary alcohol) or a ketone (from a secondary alcohol), plus NADH.
2. Aldehyde dehydrogenase (ALDH) can then oxidize the aldehyde further to a carboxylic acid, again using NAD$^+$ as the hydride acceptor.

This is exactly what happens when your body metabolizes ethanol: ADH converts ethanol to acetaldehyde, then ALDH converts acetaldehyde to acetic acid.

The reduced coenzymes don't go to waste. NADH feeds into the electron transport chain to generate ATP. NADPH provides reducing power for biosynthetic reactions like fatty acid synthesis.

Redox Framework

Alcohol oxidation is a redox reaction: the alcohol is the reducing agent (it loses electrons/hydrogen), and the oxidizing agent (chromium, DMP, or NAD$^+$) is the electron acceptor that gets reduced.

A useful way to track oxidation state in organic molecules: count the number of $\text{C–O}$ bonds. An alcohol has one $\text{C–O}$ bond, an aldehyde or ketone has two (the $\text{C=O}$), and a carboxylic acid has three. Each step up represents an oxidation.