Biological Oxidation of Alcohols

The example of the reversible oxidation of ethanol (CH3CH2OH) to ethanal (acetaldehyde, CH3CHO) by yeast alcohol dehydrogenase (alcohol NAD oxidore-ductase [EC 1.1.1.1]) is one such (now classical) process and is discussed below. The oxidoreductase uses nicotinamide adenine dinucleotide (NAD ) (oxidized form) as its coenzyme, and it is in the pyridine (azabenzene, C5H5N) ring that the reduction is clearly seen. 

However, in order to demonstrate the specificity of the oxidation, the material on chirality (handedness), discussed earlier (Chapter 4), requires extension. This is because it has been demonstrated that the (chiral) enzyme can distinguish between chemically identical nuclei. 

In some systems, when the reversible enzymatic oxidation occurs with the yeast alcohol dehydrogenase, only the pro-R hydrogen is lost (Equation 8.15). 

The mechanism of chromic acid oxidation is complicated, but can be summarized as a combination of two stages. In the first, the alcohol and chromic acid react to give a chromate ester. 

the chromate ester undergoes a p elimination in which a proton is removed from carbon while the Cr—O bond breaks. 

The second step is slower than the first as evidenced by the observation that (CH3)2CHOH reacts almost seven times faster than (CH3)2CDOH. An H/D kinetic isotope effect this large is consistent with rate-determining carbon-hydrogen bond cleavage (Section 5.17). 

As an alternative to chromium-based oxidants, chemists have developed other reagents for oxidizing alcohols, several of which are based on chlorodimethylsulfonium ion [(CH3)2SC1 ]. Most commonly, chlorodimethylsulfonium ion is generated under the reaction conditions by the reaction of dimethyl sulfoxide with oxalyl chloride. 

The alcohol to be oxidized is then added to the solution of chlorodimethylsulfonium ion, followed by treatment with a weak base such as triethylamine. Primary alcohols yield aldehydes secondary alcohols yield ketones. 

Many biological processes involve oxidation of alcohols to carbonyl compounds or the reverse process, reduction of carbonyl compounds to alcohols. Ethanol, for example, is metabolized in the liver to acetaldehyde. Such processes are catalyzed by enzymes the enzyme that catalyzes the oxidation of ethanol is called alcohol dehydrogenase. 

In addition to enzymes, biological oxidations require substances known as coenzymes. Coenzymes are organic molecules that, in concert with an enzyme, act on a substrate to bring about chemical change. Most of the substances that we call vitamins are coenzymes. The coenzyme contains a functional group that is complementary to a functional group of the substrate the enzyme catalyzes the interaction of these mutually complementary functional groups. If ethanol is oxidized, some other substance must be reduced. This other substance is the oxidized form of the coenzyme nicotinamide adenine dinucleotide (NAD). Chemists and biochemists abbreviate the oxidized form of this 

FIGURE 15.3 Structure of NAD, the oxidized form of the coenzyme nicotinamide adenine dinucleotide. 

According to one mechanistic interpretation, a hydrogen with a pair of electrons is transferred from ethanol to NAD, forming acetaldehyde and converting the positively charged pyridinium ring to a dihydropyridine  

The pyridinium ring of NAD serves as an acceptor of hydride (a proton plus two electrons) in this picture of its role in biological oxidation. 

This synthesis requires nx)re finesse. The aldehyde i s easily over-oxidized to a carboxylic acid, and the double bond reacts with oxidants such as KMn04. Our choices are limited to PCC or the Swem oxidatioa 

Suggest the most appropriate method for each of the following labointoiy syntheses. 

Although it is the least toxic alcohol, ethanol is still a poisonous substance. When someone is suffering from a mild case of ethanol poisoning, we say that he or she is intoxicated. Animals often consume food that has fermented and contains alcohol. Their bodies must detoxify any alcohol in the food to keep it from building up in the blood and poisoning the brain. To detoxify ethanol, the liver produces an enzyme called alcohol dehydrogenase (ADH). 

Alcohol dehydrogenase catalyzes an oxidation the removal of two hydrogen atoms from the alcohol molecule. The oxidizing agent is called nicotinamide adenine dinucleotide (NAD). NAD exists in two forms the oxidized form, called NAD , and the reduced form, called NADH. The following equation shows that ethanol is oxidized to acetaldehyde, and NAD is reduced to NADH. 

A subsequent oxidation, catalyzed by aldehyde dehydrogenase (ALDH), converts acetaldehyde to acetic acid, a normal metabolite. 

---

Oxidation States of Alcohols and Related Functional Groups 467 11-2 Oxidation of Alcohols 469 11-3 Additional Methods for Oxidizing Alcohols 472 11-4 Biological Oxidation of Alcohols 474 11-5 Alcohols as Nucleophiles and Electrophiles Formation ofTosylates 476... 

---