Cyanohydrin reaction

Molecular modeling studies revealed a similar binding mode for (5)-2-nitro-1 -phenylethanol in the catalytic center of ///)HNL as was determined experimentally for (5)-mandelonitrile, preserving all mechanistically important polar interactions with active-site residues. This implies that the mechanism for the cyanohydrin reaction applies to the nitroaldol reaction as well. 

The extension of the salt-acid,27 phenylhydrazide,28 and amide rules29 to the derivatives of the 2-(hydroxymethyl) sugars by Schmidt and Weber-Molster30 indicated that the configuration of C2 in hamamelonic acid is the same as that of D-ribonic acid. Finally, the d-ribo configuration of the sugar was established by the synthesis of hamamelonic acid and its C2 epimer from D-ery/ftro-pentulose31 by the cyanohydrin reaction of Fischer and Kiliani. 

The best results for the asymmetric cyanohydrination reactions are obtained through biocatalysis, using the readily available enzyme oxynitrilase. This provides cyanohydrins from a number of substances with over 98% ee.146... 

This example (the cyanohydrin reaction) appears to me to provide a simple solution for the natural asymmetric synthesis. The formation of the sugar, as the plant physiologists assume, occurs in the chlorophyll grain, which itself is composed of optically active substances.. . . The prepared sugar is released and later on used by the plant, as is known, for the preparation of other organic components. Their asymmetry is thus explainedfrom the nature of the building material. Of course, they also provide material for new chlorophyll... 

Thus tartaric acid can be be synthesized from glyceraldehyde via cyanohydrin reaction. 

For the reaction-based sensing of anions, the most considerable success has been reached in cyanide sensing, basically due to the necessity for assessing this toxic species and because it can be easily addressed in water due to its high nucleophi-licity. For instance, the coumarin derivative 50 shows a dramatic fluorescence increase after cyanide-induced cyanohydrin reaction (Fig. 19), no response to... 

The hydroxynitrile lyase (HNL)-catalysed cyanohydrin reaction is a useful method to synthesize enantiopure a-hydroxy nitriles and the corresponding a-hydroxy acids. However, small ketones, such as 2-butanone, are converted with low selectivities, due to the poor discrimination between methyl and ethyl. ... 

The benzaldehydes (23-27) were chosen in order to attain similar reactivities in the cyanohydrin reactions, and thus securing sufficiently unbiased, isoenergetic dynamic systems. The rates of the individual reactions of these benzaldehydes were further investigated by H-NMR, indicahng the establishment of individual aldehyde-cyanohydrin equilibria within 30 minutes. Under these conditions, the complete dynamic cyanohydrin system generated from cyanide and benzaldehydes (23-27) then reached... 

The next milestone in the realm of enantioselective organocatalysis was reached by Inoue and coworkers, who elegantly modernized the cyanohydrin reaction, first outlined by Bredig and Fiske in 1912. In these studies, a cyclic histidine-containing dipeptide (4) catalyzed the HCN addition to aromatic aldehydes with high enantioselectivities (97% ee) [Eq. (11.4)] a result that effectively paved the way for the field of peptide-catalyzed nucleophilic addition to aldehydes and imines ... 

The enzyme-catalyzed cyanohydrin reaction offers new and interesting perspectives for the synthesis of different kinds of chiral cyanohydrins, because over the next few years the continuous development of new genetically modified oxynitrilases will be without any doubt of great utility for the preparation of pharmaceuticals. 

H. Kiliani, as Fischer always emphatically acknowledged, discovered and developed the method of building up the aldose series by the cyanohydrin reaction to give nitriles from the nitrile, the next higher aldonic acid could then be prepared. In 1890, A. Wohl, working in Fischer s Berlin laboratory, elaborated the dehydration of an aldose oxime to the nitrile, from which the next lower aldose could be prepared by loss of hydrocyanic acid. Fischer exploited the possibilities of sugar extension and degradation afforded by the use of these two important methods. 

Natural D-mannose is the aldehyde of natural D-mannitol, and is transformed by the action of bromine water into D-mannonic acid, which was isolated as its phenylhydrazide. The acid was regenerated from the phenyl-hydrazide and isolated as its crystalline lactone. Kiliani hod obtained the enantiomorph of this lactone on applying the cyanohydrin reaction to natural L-arabinose. A mixture of both lactones formed a racemate. Then, by taking recourse to his newly discovered reduction of the lactones to the aldoses, a reaction which Fischer designated the most significant in the... 

In 1894, Fischer wrote "It will probably be possible to obtain all riiem-bers of the sugar group by a combination of the cyanohydrin reaction with the reduction of lactones, as soon as we have succeeded in finding the two optically active forms of glyceraldchyde. All observations agree with the isomerisms foreseen by Van t Hoff, above all the disappearance of isomers if the molecule becomes constitutionally symmetric. This includes the transformation of different stereoisomers into one and the same substance if one of several asymmetric centers is abolished." An example of this is... 

By means of the cyanohydrin reaction, higher sugars of the heptose. octosc, and nonosc types have been prepared. A monosaccharide such as an aldohexosc may be converted into the next lower monosaccharide, such as an aldopeniosc. by oxidation to the acid, which corresponds to the aldohexose. then treating the calcium salt solution of this acid with a solution or ferrous acetate plus hydrogen peroxide. Carbon dioxide is evolved and aldopentose formed. 

Exercise 16-10 One possible way of carrying out the cyanohydrin reaction would be to dispense with hydrogen cyanide and just use the carbonyl compound and sodium cyanide. Would the equilibrium constant for cyanohydrin formation be more... 

Four mechanisms have been advanced for the prebiotic formation of amino acids. The first involves a cyanohydrin (reaction 2) and a related route (reaction 3) can be invoked to account for the presence of hydroxy acids. These particular reactions have been studied in considerable detail both kinetically and in terms of thermodynamic quantities.347 An alternative route (4) involves the hydrolysis of a-aminonitriles, which are themselves formed directly in anhydrous CH4/NH3 mixtures.344 Cyanoacetylene, formed in CH4/N2 irradiations,349 yields significant amounts of asparagine and aspartic acids (reaction 5). Finally, a number of workers336,350"354 have proposed that HCN oligomers, especially the trimer aminoacetonitrile and the tetramer diaminomaleonitrile, could have been important precursors for amino acid synthesis. Reaction mixtures involving such species have yielded up to 12 amino acids. Table 11 indicates the range of amino acids produced in these kinds of sparking syntheses. Of some interest is the fact that close parallels between these kinds of experiments and amino acid contents of carbonaceous chondrite meteorites exist.331,355,356... 

Ishizu et al.29H found that D-xylose and D-fructose react with aqueous calcium hydroxide to produce 13 lactonizable saccharinic and other acids. These were identified after separation by cellulose column and gas-liquid chromatography, and the Cs-saccharinic acids, 2-C-methyl-D-threonic acid (117) and 2-C-methyl-D-erythronic acid (118), were among those isolated. These authors299 later reported that L-sorbose reacts similarly, to generate 14 lactones, including the 2-C-methyl-L-xr/o o-l,4-lactone and 2-C-methyl-L-lyxono-1,4-lactone, which were also prepared from 1-deoxy-L-threo-pentulose via the cyanohydrin reaction. 

Catalytic ring opening of epoxides and aziridines was also observed (Eq. 27). The acetone cyanohydrine reaction provided j8-hydroxy nitrile and / -amino nitriles, with the lanthanide isopropoxides exhibiting a higher reactivity than Et3N [233]. 

To prepare dynamic cyanohydrin systems under mild conditions, a range of aldehyde compounds and cyanide sources was evaluated. As a result, benzaldehydes 23A-E were selected due to their diverse substitution patterns and their inability to generate any side reactions. Even though there are many cyanide sources, acetone cyanohydrin 24 was chosen as cyanide source in presence of triethylamine base, resulting in smooth cyanide release. Dynamic cyanohydrin systems (CDS-3) were thus generated from one equivalent of each benzaldehyde 23A-E and acetone cyanohydrin 24 in chloroform- at room temperature (Scheme 10). One equivalent of triethylamine was added to accelerate the reversible cyanohydrin reactions and this amount was satisfactory to force the dynamic system to reach equilibrium even at low temperature. 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

It was pointed out that N-methyl-L-glucosaminic acid nitrile was only the second nitrile in the sugar series to be isolated in the cyanohydrin reaction and that extension of the general procedure by which it was prepared should result in the isolation of other members. The nitrile of N-methyl-L-glucosaminic acid showed the same unusual mutarotation as does that of the lower-melting form of D-gluconic acid nitrile. Wolfrom and Thompson have noted that N-methyl-L-glucosaminic acid nitrile hydrochloride was a much more stable compound than the free base. 

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