Ketones cyanohydrins

Cya.nideExcha.nge, Acetone cyanohydrin and methyl isobutyl ketone cyanohydrin [4131 -68-4] dissolved in an organic solvent, such as diethyl ether or methyl isobutyl ketone, undergo cyanide exchange with aqueous cyanide ion to yield a significant cyanide carbon isotope separation. The two-phase system yields cyanohydrin enriched in carbon-13 and aqueous cyanide depleted in carbon-13. Fquilibrium is obtained in seconds. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

Kragl and coworkers investigated using organic-solvent-free systems to overcome the thermodynamic limitations in the synthesis of optically active ketone cyanohydrins. With organic-solvent-free systems under optimized reaction conditions, conversions up to 78% with > 99.0 enantiomeric excess (ee) (S) were obtained. Finally, 5 mL of (S)-acetophenone cyanohydrin with an ee of 98.5% was synthesized using MeHNL [52]. 

Effenberger, F., Hoersch, B., Weingart, F. et al. (1991) Enzyme-catalyzed synthesis or (/ )-ketone-cyanohydrins and their hydrolysis to (R)-a-hydroxy-a-methyl-carboxylic acids. Tetrahedron Letters, 32, 2605-2608. 

Biihler, H., Bayer, A. and Effenberger, F. (2000) Enzyme-catalyzed reactions, part 39. A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5f/)-furanones from (5)-ketone cyanohydrins. Chemistry - A European Journal, 6, 2564—2571. 

Cyanohydrins are starting materials of widespread interest for preparing important compounds such as a-hydroxy acids/esters, a-amino acids, / -amino alcohols, a-hydroxy aldehydes, vicinal diols, and a-hydroxy ketones. Cyanohydrin compounds can be synthesized using various chiral catalysts such as cyclic... 

Procedure 1 General Procedure for the Preparation of Enantioenriched Methyl Ketone Cyanohydrins... 

The preparation of (S)-ketone cyanohydrins has also been achieved in a one-pot procedure, using the PaHnl, by decomposition of the corresponding racemic cyanohydrins followed by stereoselective addition of the HCN that is liberated to m-bromoaldehydes [97]. This tandem reaction process yielded both (S)-ke-tone cyanohydrins (from the decomposition of the racemic cyanohydrin) and (i )-m-bromocyanohydrins (the HCN addition product), the latter being con-... 

We reported a catalytic enantioselective cyanosUylation of ketones that produces chiral tetrasubstituted carbons from a wide range of substrate ketones [Eq. (13.31)]. The catalyst is a titanium complex of a D-glucose-derived ligand 47. It was proposed that the reaction proceeds through a dual activation of substrate ketone by the titanium and TMSCN by the phosphine oxide (51), thus producing (l )-ketone cyanohydrins ... 

Figu re 9.4 Enzymatic transcyanation of -bromoaldehydes and racemic ketone cyanohydrins [53]. 

The Gotor group succeeded in using almond meal for the enantioselective cleavage of ketone cyanohydrins, which served additionally as the cyanide source in the subsequent asymmetric addition of HCN to co-bromoaldehydes in one pot (Figure 9.4) [53]. 

The presence of the aldehyde as cyanide acceptor is essential to achieve the resolution of ketone cyanohydrins with good enantioselectivities. The unreacted (S)-ketone cyanohydrin and the (R)-co-bromoaldehyde cyanohydrin formed could be isolated in moderate to good enantiopurity (50 to 95% and 75 to 92% respectively) [53]. 

We began our synthesis by finding the optimum reaction conditions for the catalytic asymmetric cyanosilylation of ketone 28 (Table 1). Based on previous studies,30 the titanium complex of a D-glucose derived ligand (catalyst 32 or 33) generally gives (/ )-ketone cyanohydrins, which is required for a synthesis of natural fostriecin. 

Cyanohydrin formation is therefore an equilibrium between starting materials and products, and we can only get good yields if the equilibrium favours the products. The equilibrium is more favourable for aldehyde cyanohydrins than for ketone cyanohydrins, and the reason is die size of the groups attached... 

Methyl ethyl ketone cyanohydrin, 20,44 N-Methylformanilide, 20, 11, 66 Methyl- 8-formylpropionate, 21, 88 a-Methylglucoside, 20, 99... 

Hahlbrock, K. and Gonn, E.E. (1970) The biosynthesis of cyanogenic glycosides in higher plants purification and properties of a uridine diphosphate-glucose-ketone cyanohydrin p-glucosyltransferase from Linum usitatissimum (L.). /. Biol. Chem., 245, 917-22. 

Aliphatic hydrazines of the type RiC(CN)NHNHC(CN)Rj are prepared by the interaction of ketone cyanohydrins and hydrazine. These compounds can be oxidized to azonitriles with hypobromous acid in methanol. In a similar manner, ethyl azodicarboxylate, CjH50jCN=NC0jCiHj, is synthesized by the action of hypochlorous acid on ethyl hydrazodicar-boxylate (83%)- ... 

A variety of aldehydes—aliphatic, aromatic, and heterocyclic—have been condensed with hydantoin. Sodium acetate in a mixture of acetic acid and acetic anhydride as well as pyridine containing traces of piperidine serves as condensing agent. Reduction of the double bond is accomplished with phosphorus and hydriodic acid, ammonium sulfide, or stannous chloride, In a more recent modification, the hydantoins are synthesized from aldehyde or ketone cyanohydrins and ammonium... 

The simplest aldehyde cyanohydrin, glycolonitrile, has been prepared by a cyanohydrin interchange between formalin and methyl ethyl ketone cyanohydrin. ... 

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