Question

Naturally occurring compounds called cyanogenic glycosides, such as lotaustralin, release hydrogen cyanide, HCN, when treated with aqueous acid. The reaction occurs by hydrolysis of the acetal linkage to form a cyanohydrin, which then expels HCN and gives a carbonyl compound. (a) Show the mechanism of the acetal hydrolysis and the structure of the cyanohydrin that results. (b) Propose a mechanism for the loss of HCN, and show the structure of the carbonyl compound that forms.

Short answer

Acetal hydrolysis forms a cyanohydrin, which loses HCN to form a carbonyl compound.

Step-by-step solution

Understanding Acetal Hydrolysis

The first step in this reaction is the hydrolysis of the acetal group in the cyanogenic glycoside. Acetal hydrolysis typically involves protonation of one of the ether linkages by the aqueous acid, which increases its susceptibility to nucleophilic attack by water, eventually resulting in the formation of a hemiacetal.

Formation of the Hemiacetal

Upon protonation, one of the ether oxygen atoms becomes more electrophilic, allowing water to attack and form a tetrahedral intermediate. This intermediate then collapses, releasing an alcohol and forming a hemiacetal.

Formation of the Cyanohydrin

The hemiacetal further reacts to yield a cyanohydrin. In the context of a cyanogenic glycoside, the hemiacetal collapses to form the cyanohydrin, which contains an alcohol group and a nitrile group attached to the same carbon.

Proposed Mechanism for HCN Loss

The cyanohydrin is not very stable and can readily lose a molecule of HCN. This occurs when a base abstracts a proton, making the hydroxyl group a good leaving group. As the hydroxyl group leaves, a double bond forms between the hydroxyl-bearing carbon and the cyanide carbon, resulting in the expulsion of HCN and formation of a carbonyl compound.

Structure of the Carbonyl Compound

After the loss of HCN, the cyanohydrin converts into a carbonyl compound. The resulting structure is typically either an aldehyde or a ketone, depending on the original structure of the cyanogenic glycoside.

Key concepts

Cyanogenic Glycosides

Cyanogenic glycosides are natural plant compounds that contain sugar molecules linked to a moiety capable of releasing cyanide. These compounds are found in many plants like apricots, cassava, and almonds, as a means of defense against herbivores. When these plants are damaged, enzymes break the glycosidic bond, releasing a sugar and a cyanohydrin. The cyanohydrin can further decompose to produce hydrogen cyanide (HCN). These compounds can be toxic if ingested in large amounts, as the HCN competes with oxygen in the body, inhibiting cellular respiration.

In chemistry, studying cyanogenic glycosides provides insight into the mechanisms of natural detoxification processes. Understanding these processes helps in developing methods for food processing and pharmaceutical applications that mitigate cyanide exposure.

Cyanohydrin Formation

Cyanohydrins form when a carbonyl compound reacts with hydrogen cyanide (HCN). In the case of cyanogenic glycosides, hydrolysis of the acetal linkage in the sugar part of the molecule initiates the process. This hydrolysis leads to protonation of the ether oxygen making it more susceptible to nucleophilic attack.
Once hydrolysis starts, a carbonyl group is temporarily reverted into a hemiacetal and then into a cyanohydrin. A cyanohydrin contains a nitrile (CN) group and a hydroxyl (OH) group attached to the same carbon atom. This intermediate is crucial because it sets the stage for the next step, where HCN will eventually be expelled, resulting in a stable carbonyl compound.

Carbonyl Compound Formation

The transformation from a cyanohydrin to a carbonyl compound involves the loss of a hydrogen cyanide molecule. This process can occur when a base or possibly another catalyst abstracts a proton, prompting the hydroxyl group to leave.
As the –OH group departs, a double bond forms between the carbon that originally held the hydroxyl group and the adjacent carbon, effectively creating a carbonyl group. Carbonyl compounds, like aldehydes and ketones, are stable and occur widely in organic chemistry. This step is crucial in biochemical pathways, as the carbonyl group serves as a key functionality that can further participate in a variety of chemical reactions.

Hydrogen Cyanide Release

Hydrogen cyanide release during the breakdown of cyanogenic glycosides is a key process. The release happens when the relatively unstable cyanohydrin structure decomposes. The expulsion of HCN is facilitated by the loss of a hydroxyl group, driven by either an enzymatic action or a chemical catalyst like a base.

Once HCN is released, its potential toxicity becomes evident. Ingestion or inhalation of HCN can cause serious harm due to its ability to inhibit critical cellular enzymes like cytochrome c oxidase. This inhibition disrupts cellular respiration and can be life-threatening. Understanding the chemical release of HCN is essential for comprehending its risk and for the development of methods to neutralize or safely handle this compound in food products and other biological contexts.