Mandelonitrile

U8 C, (-l-)-or (-)- m.p. 133X. Occurs combined in the glucoside amygdalin. Prepared by hydrolysis of mandelonitrile (ben-zaldehyde cyanohydrin). It is administered in large doses in the treatment of urinary infections. 

Mandelic acid. This preparation is an example of the synthesis of an a-hydroxy acid by the cyanohydrin method. To avoid the use of the very volatile and extremely poisonous hquid hydrogen cyanide, the cyanohydrin (mandelonitrile) is prepared by treatment of the so um bisulphite addition compound of benzaldehj de (not isolated) with sodium cyanide ... 

It is important to mix the mandelonitrile with hydrochloric acid immediately it has been separated from the water. Standing results in rapid conversion to the acetal of benzaldehyde and mandelonitrile C(H,CH[OCH(CN)C H,] and/or the iso-nitrile the yield of mandelic acid will, in consequence, be reduced. 

Carbonyl Group Reactions. Mandelonitrile [532-28-5] is formed by the addition of hydrogen cyanide to the carbonyl double bond. 

Benzaldehyde Cyanohydrin. This cyanohydrin, also known as mandelonitrile [532-28-5] is a yellow, oily Hquid, insoluble in water, but soluble in alcohol and diethyl ether. Mandelonitrile is a component of the glycoside amygdalin [29883-15-6] a precursor of laetdle [1332-94-7] found in the leaves and seeds on most Prunus species (plum, peach, apricot, etc). In 1832, mandelonitrile was the first cyanohydrin to be synthesized. 

It is commercially prepared from benzaldehyde and hydrogen cyanide. Mandelonitrile is used by certain insects (tiger beedes, an African millipede) as a defense duid (38). After expelling the duid an enzyme catalyzes the conversion of mandelonitrile to benzaldehyde and HCN, which is usually fatal to the insect s enemy. 

The reactions of the benzenesulfonyl ester of mandelonitrile (177) provide another illustration of the masked bielectrophile approach. On reaction with a primary thioamide the 4-aminothiazole (178) was obtained and this is a convenient route to these derivatives. With a thiourea, the thiazoline (179) was the initial product, and this on treatment with water gave the thiazolidin-4-one (180) (61JOC2715). 

In a 4-I. wide-mouthed glass jar, fitted with a mechanical stirrer, is placed a solution of 150 g. (3 moles) of sodium cyanide (Note i) in 500 cc. of water and 318 g. (3 moles) of u.s.P. benz-aldehyde. The stirrer is started and 850 cc. of a saturated solution of sodium bisulfite (Note 2) is added to the mixture, slowly at first and then in a thm stream. The time of addition is ten to fifteen minutes. During the addition of the first half of this solution, 900 g. of cracked ice is added to the reaction mixture, a handful at a time. The layer of mandelonitrile which appears during the addition of the sulfite solution is separated from the water in a separatory funnel. The water is extracted once with about 150 cc. of benzene, the benzene is evaporated, and the residual mandelonitrile is added to the main portion. 

The mandelonitrile should be mixed with hydrochloric acid as soon as it is separated from the water. Wood and Lilley (7. Ghent. Soc. 127, 95 (1925)) have found that it undergoes rapid rearrangement to the isonitrilc. Hence if it is allowed to stand long before the hydrolysis, the yield of mandelic acid is reduced. 

Mandelic acid is best prepared by the hydrolysis of mandeloni-trile with hydrochloric acid. The mandelonitrile has been prepared from amygdalin, by the action of hydrocyanic acid on benzaldehyde, and by the action of sodium or potassium cyanide on the sodium bisulfite addition product of benzaldehyde. ... 

Ingham proposed the following sequence to explain the formation of oxazole products following his study of the reaction of benzaldehyde with mandelonitrile and hydrogen chloride. In the event, addition of hydrogen chloride to the cyanide is the first step providing the intermediate iminochloride 5 (Ari = Ph), which upon reaction with benzaldehyde affords oxazole 2 (Ari, Ar2 = Ph) via intermediate 6 (Ari, Ar2 = Ph). 

As early as 1908, Rosenthaler found in the ferment mixture of emulsin a u-oxynitrilase , which directed the addition of hydrocyanic acid (hydrogen cyanide) to benzaldehyde asymmetrically to give x-hydroxybenzeneacetonitrilc (mandelonitrile)9. This result was confirmed1 °, however, it was not until 1963 that Pfeil ct al. first isolated and characterized the enzyme (R)-oxyni-trilase [EC 4.1.2.101 from bitter almonds (Prunus amygdalus)1 12. The yellow-colored enzyme contains a flavin-adenine dinucleotide (FAD)11 and loses its activity by splitting off this prosthet-... 

Jones and Enzie (76) reported that mandelonitrile at 10 3M completely inhibited the growth of pea sections but did not establish whether the inhibition was produced by mandelonitrile per se or by its breakdown products, hydrogen cyanide and/or benzaldehyde. 

The addition of HCN to aldehydes or ketones produces cyanohydrins (a-hydroxy nitriles). Cyanohydrins racemize under basic conditions through reversible loss of FiCN as illustrated in Figure 6.30. Enantiopure a-hydroxy acids can be obtained via the DKR of racemic cyanohydrins in the presence of an enantioselective nitriletransforming enzyme [86-88]. Many nitrile hydratases are metalloenzymes sensitive to cyanide and a nitrilase is usually used in this biotransformation. The DKR of mandelonitrile has been extended to an industrial process for the manufacture of (R)-mandelic acid [89]. 

Mandelonitrile glycosides (cyanoglycosides) e.g. amygdalin, pninasin, taxiphyllin, vicianin... 

Note The colors of the chromatogram zones produced by the mandelonitrile glycosides change with time Those of the D-isomers turn steel blue within an hour, while the 1 isomers turn reddish-brown during this time. It is possible to distinguish between D-and L-forms on the basis of these typical color differences and color changes. Both isomeric forms have a dark brown color after about 24 hours. 

The detection limits for mandelonitrile glycosides are 3 to 5 pg substance per chromatogram zone. 

Layh N, A Stolz, S Eorster, E Effenberger, H-J Knackmuss (1992) Enantioselective hydrolysis of O-acetyl-mandelonitrile to O-acetylmandelic acid by bacterial nitrilases. Arch Microbiol 158 405-411. 

A small quantity of mandelonitrile may be obtained by extracting the aqueous layer with 25 ml. of benzene, evaporating the benzene, and adding the residue to the main portion. This extraction is hardly worth while except for large scale preparations. 

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