Attack of cyanide on aldehydes and ketones

Cyanohydrins from the attack of cyanide on aldehydes and ketones... 

The last nucleophile of this chapter, sodium bisulfite, NaHSC, adds to aldehydes and some ketones to give what is usually known as a bisulfite addition compound. The reaction occurs by nucleophilic attack of a lone pair on the carbonyl group, just like the attack of cyanide. This leaves a positively charged sulfur atom but a simple proton transfer leads to the product. 

Addition of HCN to aldehydes or ketones gives a cyanohydrin (Figure 14.13). However, HCN is not a sufficiently strong acid (p/Cj, = 9.1) to protonate the carbonyl group to make it into a better electrophile. The dissociation of HCN gives an insufficient concentration of cyanide effectively to attack the carbonyl group. So it is necessary to catalyze the process with potassium cyanide (KCN), which is fully dissociated. The process is reversible, and the position of the equilibrium is dependent on both steric and electronic factors. 

Aromatic aldehydes generally do not produce cyanohydrins on reaction with hydrogen cyanide, but undergo the benzoin condensation (Scheme 6.12). The initial product from nucleophilic attack by cyanide ion is depro-tonated to form a resonance-stabilized carbanion, which attacks a second molecule of the aldehyde. Elimination of HCN leads to an a-hydroxy ketone, benzoin (2-hydroxy-1,2-diphenylethanone). The benzoin condensation is catalysed specifically by cyanide ion, which assists in both the formation and stabilization of the carbanion. The reaction is limited to aromatic aldehydes, since the aryl ring also stabilizes the anion. 

The Michael-type addition, a nucleophilic addition of an anion to the carbon-carbon double bond of an a,(3-unsaturated ketone, aldehyde, nitrile, nitro, sulphonyl, or carboxylic acid derivative, provides a powerful tool for carbon-carbon bond formation. The reaction is most successful with relatively nonbasic ( soft ) nucleophiles such as thiols, cyanide, primary and secondary amines, and P-dicarbonyl compounds. There is often a competition between direct attack on the carbonyl carbon (1,2-addition) and conjugate addition (1,4-addition) when the substrate is an a,(3-unsaturated carbonyl compound. 

The conjugate base of hydrogen cyanide is the cyanide ion ( C=Ns). Cyanide ion is a strong base and a strong nucleophile. It attacks ketones and aldehydes to give addition products called t anohydrins. The mechanism is a base-catalyzed nucleophilic addition attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate. 

In this section, we will focus primarily on nucleophilic additions to carbonyl groups. The carbonyl substrate may be an aldehyde or ketone, as well as various carboxylic acid derivatives such acid halides and esters. Among the variety of nucleophiles that can participate in these reactions are hydride, hydroxide, alkoxide, and a variety of carbon-based nucleophiles. For carbonyl substrates, attack by a nucleophile typically results in an opening up of the C-O ar-bond, leading to a tetrahedral intermediate, as shown below for the addition of cyanide to a ketone in the presence of water. 

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