Preparation of cyanohydrins

In a German patent issued in 1929, Bergs described a synthesis of some 5-substituted hydantoins by treatment of aldehydes or ketones (1) with potassium cyanide, ammonium carbonate, and carbon dioxide under several atmospheres of pressure at 80°C. In 1934, Bucherer et al. isolated a hydantoin derivative as a by-product in their preparation of cyanohydrin from cyclohexanone. They subsequently discovered that hydantoins could also be formed from the reaction of cyanohydrins (e.g. 3) and ammonium carbonate at room temperature or 60-70°C either in water or in benzene. The use of carbon dioxide under pressure was not necessary for the reaction to take place. Bucherer and Lieb later found that the reaction proceeded in 50% aqueous ethanol in excellent yields for ketones and good yields for aldehydes. ... 

Until 1987, the (R)-PaHNL from almonds was the only HNL used as catalyst in the enantioselective preparation of cyanohydrins. Therefore, it was of great interest to get access to HNLs which catalyze the formation of (5 )-cyanohydrins. (5 )-SbHNL [EC 4.1.2.11], isolated from Sorghum bicolor, was the first HNL used for the preparation of (5 )-cyanohydrins. Since the substrate range of SbHNL is limited to aromatic and heteroaromatic aldehydes as substrates, other enzymes with (5 )-cyanoglycosides have been investigated as catalysts for the synthesis of (5 )-cyanohydrins. The (5 )-HNLs from cassava (Manihot esculenta, MeHNL) and from Hevea brasiliensis (HbHNL) proved to be highly promising candidates for the preparation of (5 )-cyanohydrins. Both MeHNL and HbHNL have been overexpressed successfully in Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris. 

This process presents a typical procedure applicable to preparation of cyanohydrins from ketones and aldehydes of low reactivity. l-Cyano-6-methoxy-3,4-dihydronaphthalene is useful as an intermediate for synthesis of polycyclic compounds. 

Addition of hydrogen cyanide to carbonyl compounds preparation of cyanohydrins... 

Preparation of cathylates, 414 Preparation of cholesta-3,5-diene, 331 Preparation of 5 -cholest-2-ene, 343 Preparation of 5a-cholest-3-ene, 347 Preparation of 5a-cholest-6-ene, 354 Preparation of cyanohydrins, 412 Preparation and dehydrohalogenation of a-halo ketals, 301... 

J. D. Elliott, V. M. F. Choi, and W. S. Johnson, Asymmetric synthesis via acetal templates. 5. Reactions with cyanotrimethylsilane. Enantioselective preparation of cyanohydrins and derivatives, J. Org. Chem. 78 2294 (1983). 

An alternative procedure, suitable for the preparation of cyanohydrins which readily form bisulphite complexes, is illustrated by the preparation of mandelic acid described in Expt 5.168 (see also the preparation of acetone cyanohydrin). Here the procedure involves the addition of a saturated solution of sodium metabisulphite to a stirred solution of the carbonyl compound and aqueous sodium cyanide, and when applicable is usually to be preferred to the in situ generation of hydrogen cyanide or the use of the highly poisonous liquid hydrogen cyanide as a reagent. 

Many enzymes are both active and stable in carbon dioxide and have been used to conduct a number of reactions. Several different types of reactions have been examined, including hydrolysis (Lee et al., 1993 Randolph et al., 1985 Zheng and Tsao, 1996), oxidation (Hammond et al., 1985 Randolph et al., 1988), and esterification/transesterification (Kamihira et al., 1987 Nakamura et al., 1986 Rantakyla and Aaltonen, 1994), but there are other types of reactions that would make worthwhile investigations in carbon dioxide. These include preparation of amides, reduction of ketones, preparation of cyanohydrins from aldehydes, aldol reactions, hydroxylation reactions, and Baeyer-Villiger oxidation. 

Trimethylsilyl)benzophenone cyanohydrin has been prepared previously by the addition of trimethylsilyl cyanide to benzophenone using an aluminum chloride catalyst.4 The preparation of cyanohydrin silyl ethers described in the synthesis is based on... 

Enzymatic processes are now being applied to a wide range of pharmaceutical product syntheses (46). Examples are given for the preparation of cyanohydrins, which can then be used to prepare a-hydroxy acids and a-amino acids. 

The preparation of cyanohydrin was described in connection with the synthesis of acrylates (see Section 11.3.2.2). As for dehydration, this can be conducted in the liquid phase, around -200°C, in the presence of a soluble catalyst based on magnesium formate... 

The hard silicon atom forms strong bonds with oxygenated compounds. This property has been exploited in the direct preparation of cyanohydrin trimethyl-silyl ethers (15-17). Strikingly the carbonyl group of p-benzoquinones can be protected by this method (18). 

The preparation of cyanohydrins is an important reaction in organic synthesis because it is used to lengthen the hydrocarbon chain by one C-atom the molecule of 1-cyanopropanol in the scheme above has one carbon atom more than the starting propanal. Some cyanohydrins are natural products, especially the derivatives of benzaldehyde, which are poisonous and used by particular insects for their defense. The toxic activity of these compounds is based on the hydrolysis of cyanohydrins into benzaldehyde and highly toxic HCN. 

Table 7.4. Preparation of cyanohydrin ethers according to equation 7.9...

In Summary Racemic amino acids are made by the amination of 2-bromocarboxylic acids, applications of the Gabriel synthesis of amines, and the Strecker synthesis. The last method proceeds through an imine variation of the preparation of cyanohydrins, followed by hydrolysis. 

A new two-step procedure for the preparation of cyanohydrins from ketones is particularly useful for the synthesis of highly hindered cyanohydrins [equation (38)]. Note that potassium cyanide and trimethylsilyl chloride can be used in place of trimethylsilyl cyanide in the above reaction. ... 

In the case of TMEDA, stereoselection in favor of the syn product (98 2) is enhanced over that achieved with Diiso-propylethylamine (94 6). Along with bases sueh as Triethy-lamine and ethylisopropylamine, TMEDA facilitates the preparation of cyanohydrin trimethylsilyl ethers from aldehydes and Cyanotrimethylsilane. It has been suggested that eoordination by nitrogen induces formation of an active hypervalent cyana-tion intermediate from cyanotrimethylsilane. The conjugate addition of thiols to enones has been successfully catalyzed by using TMEDA in methanol at room temperature, as exemplified by the reaction of 10-mercaptoisobomeol and 4-/-butoxycyclopentenone... 

Scheme 2 Preparation of (/ )-cyanohydrins 2 by (/ )-PaHNL-catalyzed addition of HCN to aldehydes 1.

Table 3 Preparation of (/ )-Cyanohydrins (/ )-2 Using Almond Meal and Acetone Cyanohydrin as HCN Source...

Results of the PaHNL-catalyzed preparation of (/ )-cyanohydrins by applying the experimental variations mentioned above are summarized in Tables 3 and 4. Table 3 shows results where the isolated (/ )-PaHNL is replaced by almond meal and free HCN by acetone cyanohydrin [22a]. 

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