Aldehydes hydrocyanations

Mandelic Acid.—The reaction furnishes a simple and general method for obtaining hydroxy-acids from aldehydes or ketones by the aid of the cyanhydrin. The formation of the cyanhydrin may be effected in the manner described or by the action of hydrochloric acid on a mixture of the aldehyde or ketone with potassium cyanide, or, as in the case of the sugais, by the use of liquid hydrocyanic acid and a little amme-nia. 

A general property of aldehydes and ketones is that when heated with hydrocyanic acid, additive compounds, termed nitriles or cyanohydrins, are produced, according to the general equations—... 

BerL Ber., abbrev. (Berliner Berichte) Berickte der deutscken chemiachen Gesellscka/t. Berliner-blau, n. Berlin blue, Prussian blue, -blaus ure, /. hydrocyanic acid, -braun, n. Prussian brown, -griin, n. Prussian green, -rot, n. Berlin red (a red lake color), -saure,/. prussic acid, -weiss, n. a kind of white lead. Bernstein, m. amber. — schwarzer —, jet. Bernstein-, amber succinic, succinyl, succino-. -alaun, m. aluminous amber, -aldehyd, n. succinaldehyde. bemateinartig, a. amber-like. 

I.3.7.I.I. (/ )-Oxynitrilase-Catalyzed Addition of Hydrocyanic Acid to Aldehydes... 

Table 1. ( )-Cyanohydrins by Enzymatic Formation from Aldehydes and Hydrocyanic Acid 14,15...

Method B A solution of (/ )-oxynitrilase (150 pL, sec Method A) is dropped onto 2 g of Avicel cellulose [soaked in 20 mL of 0.01 M acetate buffer (pH 5.4) for 1 2 h, filtered off and pressed]. 20 mL of ethyl acetate (saturated with 0.01 M acetate buffer, pi I 5.4) are added, followed by 5 mmol of aldehyde and 250 pL (6.5 mmol) of hydrocyanic acid. After stirring at r.t. (Tabic 1) the mixture is filtered, and the filter cake pressed and washed with ethyl acetate. The combined solutions are dried and concentrated. 

Recently, the enantioselective addition of hydrocyanic acid to aldehydes, analogous to the synthesis of (/ )-cyanohydrins, yielding (.S)-cyanohydrins in very high optical purity, with (S )-oxynitrilase as catalyst, was reported20,21. 

The synthesis of analogous iminoacyl complexes by isonitrile insertion into linear alkyl-zirconocene chlorides is also known. In an overall regiospecific hydrocyanation of alkenes, iminoacyls 21 derived from tBuNC or Me3SiCN (as the Me3SiNC isomer) may be treated with I2 to rapidly generate an imidoyl iodide and subsequently the nitrile 22 (Scheme 3.6) [22], Less hindered iminoacyl complexes (e. g. R = Bu, Cy) may be hydrolyzed to afford aldehydes 23 [23]. 

Remarks on Sections 6 and 7.-—The method here described for the synthesis of cyanohydrins—treatment of the bisulphite compound of the aldehyde with potassium cyanide—cannot be used in all cases. Concentrated solutions of hydrocyanic acid or anhydrous hydrogen cyanide are often used. The general method for the synthesis of a-amino-acids, the nitriles of which are formed by the union of ammonium cyanide with aldehydes or ketones (Strecker), is to be contrasted with that for the synthesis of a-hydroxy acids. For additional amino-acid syntheses see Chap. VII. 2, p. 276. 

Van Langen, L.M., yan Rantwijk, F. and Sheldon, R.A., Enzymatic hydrocyanation of a sterically hindered aldehyde. Optimization of a chemoenzymatic procedure for (R)-2-chloro-mandelic acid. Org. Proc. Res. Dev., 2003, 7, 828-831. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

Table 8. Asymmetric Hydrocyanation of Aldehydes with Cyanotrimethylsilane...

By analogy with the synthesis of a-hydroxy acids one can envisage a one-pot synthesis of a-hydroxy amides from aldehydes via hydrocyanation and in situ NHase-catalyzed hydrolysis to the amide. Since enantioselective NHases are very rare, the enantioselectivity should be derived from HnL-catalyzed hydrocyanation. The second step has been described for the Rhodococcus erythropolis NHase-catalyzed hydration of (R)-mandelonitrile to give the (R)-amide with retention of enantiopurity [43]. 

When an aldehyde is allowed to react with an optically active amine and hydrocyanic acid, one of the two diastereomeric amino nitriles, (124a) or (124b), may be formed in excess. To prepare the chiral amino acids (125a) or (125b), the nitriles (124a) and (124b), respectively, are hydrolyzed with mineral acids, whereupon R is split off. However, this asymmetric synthesis of amino acids has no industrial significance. 

Hydrocyanic acid transforms aldehyde into alanin ... 

By digesting bitter almonds wth water for five or six hours at 8(f-40. The synaptase present acts as afermeut on the amygdalin, converting it into glucose, bensoio aldehyde, and hydrocyanic noidj—... 

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