Mandelic nitrile

Mandelic Nitrile.—Freshly distilled benzaldehyde (15 g.) is stirred with a glass rod in a cylinder with about 50 c.c. of a concentrated solution of sodium bisulphite until a paste of the addition compound /H... 

In the synthesis of mandelic nitrile described above asymmetry ... 

This reaction is of especial interest, since the addition of a new carbon atom is brought about. Concerning the value of this reaction for the synthesis of a-oxyacids, see Mandelic Nitrile, page 279. 

Example Mandelic Add from Benzaldehyde1 (a) Mandelic Nitrile... 

R)-Oxynitrilase C-C-bond formation with CN and benzaldehyde Mandelic nitrile 2400 7000 ... 

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. 

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]. 

Mateo, C., Chmura, A., Rustler, S. et al. (2006) Synthesis of enantiomerically pure (S)-mandelic acid using an oxynitrilase-nitrilase bienzymatic cascade a nitrilase surprisingly shows nitrile hydratase activity. Tetrahedron Asymmetry, 17, 320-323. 

Hydrolysis of the Nitrile.—The nitrile, mixed in a porcelain basin with four times its volume of concentrated hydrochloric acid, is heated on the water bath until an abundant separation of crystals begins to take place on the surface of the liquid. The reaction mixture is then allowed to stand over night in a cool place, and the crystals which have been deposited, after being rubbed with a little water, are separated at the filter pump and washed with water (not too much). A further quantity of the acid is obtained from the filtrate by extraction with ether. The crude mandelic acid is pressed on a porous plate, dried, and purified by crystallisation from benzene. Melting point 118°. Yield about 10-15 g. 

There are a few data in the literature to suggest that the hydrolysis of aliphatic nitriles occurs in mammals, but only as a minor or even undetectable pathway in competition with oxidative denitrilation. For example, benzyl cyanide (11.80, Fig. 11.12) undergoes cytochrome P450 catalyzed hydroxy-lation to mandelonitrile (11.81), from which cyanide and benzaldehyde are produced, the latter being oxidized to benzoic acid (11.83) [118]. However, a careful metabolic study of mandelonitrile has shown that, in the rat, this pathway accounts for ca. 90% and not 100% of the dose [122], Only ca. 10% of orally administered benzyl cyanide was converted to mandelic acid (11.82, Fig. 11.12) by hydrolysis of the CN group. 

The dimethylaminooxazolidone derivative thozalinone (40-3) is described as an antidepressant. The synthesis of this agent again uses a cyanamide, provided in this case as a preformed reagent. Thus, reaction of alkoxide from ethyl mandelate (40-1) with A,A-dimethylcyanamide leads to the amidine (40-2) by addition to the nitrile. Internal displacement of the ester ethoxide group closes the ring to an oxazo-lidinone, forming the product (40-3) [42]. 

See for a discussion of asymmetric transformation of a-amino nitriles with mandelic acid Hassan,... 

Hydrolysing nitriles howto make the almond extract, mandelic acid... 

From these results we concluded that the preferred biocatalysts for the selective hydrolysis of la, lb and Ic into the (R)-acids are, respectively, NIT-104, NIT-106 and NIT-104, although the hydrolysis of lb and Ic is rather less enantioselective than would be desirable. Thus, in a preparative experiment, NIT-104 converted la (0.1 M starting concentration) into (R)-mandelic acid (98% conversion, 98% ee), attesting that under the prevailing conditions the racemisation of the nitrile is fast... 

The cyanohydrin synthesis of a-hydroxy acids is very often carried out without isolation or purification of the cyanohydrins. The various techniques for the preparation of the cyanohydrins are discussed elsewhere (method 390). Hydrolysis to the a-hydroxy acids is usually effected by heating with concentrated hydrochloric acid. Excellent directions are given for mandelic acid (52% over-all from benzaldehyde), a-methyl-a-hydroxybutyric acid (65% from methyl ethyl ketone), and eighteen dialkyl- and alkylphenyl-glycolic acids (60-80%). Sodium hydroxide solution is used in the preparation of /S-hydroxypropionic acid from the /S-hydroxy nitrile (80%). ... 

Mandellic Acid.—Mandellic acid is phenyl glycolic acid, CeHs— CH(OH)—COOH, phenyl hydroxy acetic acid. This constitution is proven by its synthesis from benzaldehyde by condensation with hydrogen cyanide and the hydrolysis of the resulting nitrile. 

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