Aldehydes with cyanide ion

The desired hydroxy acid is available from hydrolysis of the corresponding cyanohydrin, which may be prepared by reaction of the appropriate aldehyde with cyanide ion. 

Treatment of a ketone or aldehyde with cyanide ion (" CsN), followed by protonation of the tetrahedral alkoxide ion intermediate, gives a cyanohydrin. Show structure of tlie cyaiiohydriu obtained from acetone. 

Upon treating certain (but not all) aromatic aldehydes or glyoxals (a-keto aldehydes) with cyanide ion (CN ), benzoins (a-hydroxy-ketones or acyloins) are produced in a reaction called the benzoin condensation. The reverse process is called the retro-benzoin condensation, and it is frequently used for the preparation of ketones. The condensation involves the addition of one molecule of aldehyde to the C=0 group of another. One of the aldehydes serves as the donor and the other serves as the acceptor. Some aldehydes can only be donors (e.g. p-dimethylaminobenzaldehyde) or acceptors, so they are not able to self-condense, while other aldehydes (benzaldehyde) can perform both functions and are capable of self-condensation. Certain thiazolium salts can also catalyze the reaction in the presence of a mild base. This version of the benzoin condensation is more synthetically useful than the original procedure because it works with enolizable and non-enolizable aldehydes and asymmetric catalysts may be used. Aliphatic aldehydes can also be used and mixtures of aliphatic and aromatic aldehydes give mixed benzoins. Recently, it was also shown that thiazolium-ion based organic ionic liquids (Oils) promote the benzoin condensation in the presence of small amounts of triethylamine. The stereoselective synthesis of benzoins has been achieved using chiral thiazolium salts as catalysts. 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

Another method involves treatment with an aldehyde and cyanide ion (see 6-49) in a polar aprotic solvent such as DMF or Me2S0.550... 

Notably, as illustrated in Scheme 124, enantiofaces of aldehydes can be differentiated by a chiral rhenium template to result in stereoselective reaction with cyanide ion (297). The rhenium Lewis acid element forms stereoisomeric it complexes with aldehydes, which are convertible via... 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

An anion may be formed from a symmetrical acid anhydride by using the carboxylate anion of the corresponding acid as the base. This anion may then be reacted with an aldehyde, such as benzaldehyde, to yield as the initial product a mixed anhydride. Dehydration and hydrolysis often follow to result in an a, P-un saturated acid. This is the Perkin reaction. In the benzoin condensation, benzaldehyde is treated with cyanide ion to form an anion, which then attacks another benzaldehyde molecule to form, after the elimination of the original cyanide ion, a 2-hydroxyketone. 

The Introduction of the side chain containing carbon atoms 16 to 11 was accomplished as shown In Scheme 2. Selective tosylatlon of 9A followed by displacement with cyanide ion and protection of the 19 alcohol with tert-butyldimethylsilyl (TBS) chloride gave 11. Subsequent reduction with diisobutylaluminum hydride (DIBAL) and hydrolysis gave the aldehyde 12. Wittig reaction of 12 with (carbethoxyethyl i dene) tri phenl ypfiosphorane provided the o,b... 

The H CN (or CN, if the reaction is done under basic conditions) synthon has been mainly used to extend the carbon chain by one carbon. For example, cyanide ion has been used in the synthesis of amino acids labelled in the carboxylate group. This is accomplished using the high pressure-high temperature modification of the Bucherer-Strecker synthesis. In this reaction, bisulphite addition complex of an aldehyde reacts with cyanide ion in the presence of ammonium carbonate to form a hydantoin, which is then converted into the amino acid by basic hydrolysis (equation 61). 

Oxidation and Reduction.—Shinkai and co-workers have developed micellar models for flavin-dependent oxidases, which operate through the trapping of reactive carbanions. Thus 4-chlorobenzoylformic acid reacts with cyanide ion in aqueous solution to give 4,4 -dichlorobenzoin (72%) together with a small quantity of 4-chlorobenzoic acid (2.4%) formed by aerial oxidation of the carbanion. In the presence of a cationic surfactant micelle, the yield of oxidation product is greatly increased and there is a further rate acceleration in the presence of the hydrophobic flavin (34) since the mechanism shown (Scheme 2) is now strongly favoured. This type of reaction path also accounts for the oxidation of aromatic aldehydes in the same reaction system, and molecular oxygen may replace the flavin but with lower efficiency. The oxidation of nitroethane to acetaldehyde is catalysed by a similar combination of hydrophobic flavin and cationic surfactant and does not occur in their absence. 

Reaction of an aldehyde or a ketone with cyanide ion under acidic conditions forms a cyanohydrin (Section 17.6). The mechanism is shown on page 802. 

In the Strecker synthesis, an aldehyde reacts with ammonia to form an imine. An addition reaction with cyanide ion forms an intermediate, which, when hydrolyzed, forms the amino acid (Section 16.19). Compare this reaction with the Kiliani-Fischer synthesis of aldoses in Section 21.7. 

Some imine-forming reactions are shown in Figure 14.30—all of these were part of longer synthetic sequences. Imines undergo many of the same types of addition reactions as aldehydes and ketones. A particularly useful example of this is their reaction with cyanide ion, the Strecker reaction (Figure 14.31). When a carbonyl compound is treated with ammonia and sodium or KCN, the ammonia adds to the carbonyl to give an unstable imine. This is attacked by cyanide to give the a-aminocyanide. Since the cyanide can be hydrolyzed to a carboxylic acid, this constitutes a simple amino acid synthesis. 

In the Strecker synthesis an aldehyde is converted to an a ammo acid with one more carbon atom by a two stage procedure m which an a ammo nitrile is an mterme diate The a ammo nitrile is formed by reaction of the aldehyde with ammonia or an ammonium salt and a source of cyanide ion Hydrolysis of the nitrile group to a car boxylic acid function completes the synthesis... 

Aldehydes by reaction with ammonia and cyanide ion (the Strecker synthesis)... 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

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