Hydroxynitrile (Cyanohydrin): The Sweet and Toxic World of Cyanide Addition
Understanding the Carbonyl Group and Nucleophilic Attack
To understand how a cyanohydrin forms, we first need to look at the starting materials. Aldehydes and ketones are organic molecules that contain a carbonyl group, which is a carbon atom double-bonded to an oxygen atom ($C=O$). This group is very important because it is reactive. The oxygen atom is more electronegative than the carbon atom, meaning it pulls the shared electrons in the double bond closer to itself. This creates a partial positive charge ($\delta+$) on the carbon atom and a partial negative charge ($\delta-$) on the oxygen atom.
A nucleophile is a "nucleus-loving" species that is attracted to positively charged centers. It has a lone pair of electrons or a negative charge that it can donate to form a new bond. In the case of cyanohydrin formation, the nucleophile is the cyanide ion ($CN^-$), which comes from hydrogen cyanide (HCN). The partially positive carbon of the carbonyl group is a perfect target for the cyanide ion's attack.
The Step-by-Step Mechanism of Cyanohydrin Formation
The formation of a cyanohydrin is a classic two-step nucleophilic addition reaction. Let's break it down using acetaldehyde ($CH_3CHO$) as our example aldehyde.
The cyanide ion ($CN^-$) uses its lone pair of electrons to attack the electrophilic, partially positive carbon of the carbonyl group. This breaks the $pi$ bond of the $C=O$ group, and its electrons move entirely to the oxygen atom. This step creates a new carbon-carbon bond and a negatively charged oxygen atom (an alkoxide ion).
The unstable, negatively charged alkoxide ion immediately grabs a proton ($H^+$) from the surrounding environment (often from the HCN molecule itself or from water). This step converts the alkoxide ion into a stable hydroxyl group (-OH).
The final product is 2-hydroxypropanenitrile, the cyanohydrin of acetaldehyde: $CH_3CH(OH)CN$.
The general reaction can be summarized with the following equation, where R and R' can be hydrogen atoms (for an aldehyde) or carbon chains (for aldehydes or ketones):
$R-(C=O)-R' + HCN \longrightarrow R-C(OH)(CN)-R'$
Comparing Aldehydes and Ketones in Cyanohydrin Formation
Not all carbonyl compounds react with HCN with the same ease. There is a clear difference in reactivity between aldehydes and ketones. Aldehydes are generally much more reactive than ketones in nucleophilic addition reactions. The table below compares the two.
| Feature | Aldehydes | Ketones |
|---|---|---|
| General Formula | $R-CHO$ | $R-COR'$ |
| Steric Hindrance | Low. One small H atom and one R group. | High. Two larger R groups block the approach. |
| Electronic Effects | More positive carbonyl carbon, more electrophilic. | Two electron-donating R groups make the carbon less positive. |
| Reactivity with HCN | High. Most aldehydes form cyanohydrins readily. | Low. Only a few ketones (like acetone) form stable cyanohydrins. |
| Example Product | $CH_3CH(OH)CN$ (from acetaldehyde) | $(CH_3)_2C(OH)CN$ (from acetone) |
From Bitter Almonds to Plastics: Real-World Applications
The cyanohydrin reaction is not just a laboratory curiosity; it has significant practical importance. One of the most famous natural cyanohydrins is amygdalin, found in the seeds of apples, apricots, and bitter almonds. When these seeds are crushed, an enzyme breaks down amygdalin, releasing benzaldehyde (which gives the characteristic almond smell), glucose, and the highly toxic HCN. This is why consuming large quantities of these seeds is dangerous.
In industry, the most important application is in the synthesis of methyl methacrylate (MMA)1, the key monomer for making poly(methyl methacrylate) (PMMA)2, a transparent plastic known by trade names like Plexiglas and Lucite. The process often starts with acetone cyanohydrin.
Industrial Synthesis of Methyl Methacrylate:
- Acetone reacts with HCN to form acetone cyanohydrin: $(CH_3)_2C=O + HCN \longrightarrow (CH_3)_2C(OH)CN$
- Acetone cyanohydrin is then treated with concentrated sulfuric acid and methanol, undergoing dehydration and esterification to form methyl methacrylate.
Another major use is in the production of alpha-hydroxy acids, which are valuable in the pharmaceutical and cosmetic industries. For example, the cyanohydrin of formaldehyde can be hydrolyzed to produce glycolic acid, a common ingredient in skin care products.
Safety First: Handling Hydrogen Cyanide
It is crucial to address the dangers associated with hydrogen cyanide. HCN is an extremely toxic and volatile liquid. Its vapor can be fatal if inhaled. Because of this, directly using HCN gas in laboratories or industrial settings is very risky. To overcome this, chemists have developed safer alternatives. A common method is to use an alkali metal cyanide (like sodium cyanide, NaCN) and a strong acid (like sulfuric acid, $H_2SO_4$). The acid protonates the cyanide salt in situ (in the reaction mixture) to generate HCN slowly and safely right where it is needed.
Important Questions
The cyanide ion ($CN^-$) is an excellent nucleophile for two main reasons. First, it has a full negative charge, which makes it strongly attracted to positively charged centers. Second, carbon is the atom that donates the electron pair, and because carbon is less electronegative than atoms like oxygen or nitrogen, it holds onto its electrons less tightly, making it more willing to share them and form a new bond.
Yes, cyanohydrin formation is an equilibrium reaction. This means the reaction can go backwards, breaking the cyanohydrin back into the original aldehyde/ketone and HCN. In a basic solution, cyanohydrins are relatively stable. However, in an acidic solution, the reverse reaction is favored. This property is useful in organic synthesis for protecting aldehyde groups from unwanted reactions.
Hydrolysis is a reaction with water. When a cyanohydrin is hydrolyzed, the nitrile group (-C≡N) is converted into a carboxylic acid group (-COOH). This is a very important transformation because it provides a method to make alpha-hydroxy acids. For example, the cyanohydrin of acetaldehyde, when hydrolyzed, gives lactic acid: $CH_3CH(OH)CN \longrightarrow CH_3CH(OH)COOH$.
Footnote
1 MMA (Methyl Methacrylate): An organic compound with the formula $CH_2=C(CH_3)COOCH_3$. It is a colorless liquid and the monomer used to produce poly(methyl methacrylate).
2 PMMA (Poly(Methyl Methacrylate)): A synthetic polymer derived from methyl methacrylate. It is a transparent thermoplastic, often used as a lightweight or shatter-resistant alternative to glass.
3 Nucleophile: A chemical species that donates an electron pair to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons or at least one pi bond can act as nucleophiles.
4 Carbonyl Group: A functional group composed of a carbon atom double-bonded to an oxygen atom ($C=O$). It is present in aldehydes, ketones, carboxylic acids, esters, and amides.