Cyanohydrin table

Nitriles contain the —C=N functional group We have already discussed the two mam procedures by which they are prepared namely the nucleophilic substitution of alkyl halides by cyanide and the conversion of aldehydes and ketones to cyanohydrins Table 20 6 reviews aspects of these reactions Neither of the reactions m Table 20 6 is suitable for aryl nitriles (ArC=N) these compounds are readily prepared by a reaction to be dis cussed m Chapter 22... 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

The two established Hnls, those from L. usitatissimum and P. amygdalus, have found biocatalytic applications for the production of (i )-cyanohydrins. The former of these Hnls is the least widely applied, the natural substrates being acetone cyanohydrin or (i )-2-butanone cyanohydrin (Table 1) [28]. Although an improved procedure for the purification of this enzyme has been reported [27] it is still only available in limited quantities (from 100 g of seedlings approximately 350 U of enzyme are obtained). It was found that this enzyme transforms a range of aliphatic aldehyde and ketone substrates [27], the latter of which included five-membered cyclic (e.g. 2-methylcyclopentanone) and chlorinated ketone substrates. In contrast, attempts to transform substituted cyclohexanones and 3-methylcyclopentanone failed and it was even found that benzaldehyde deactivated the enzyme. 

These results suggest that the concentration of cyanide ions must be very low, even less than the solubility of NaCN in anhydrous ethanol (0.1%). In fact by saturating ethanol with NaCN at 50°C and then adding the catalyst, the reaction occurred to a limited extent. Analogous conclusions can be drawn from the results of reactions carried out with acetone cyanohydrin (Table IV). 

Most of the aforementioned hydroxynitrile lyases are able to catalyze the addition of HCN to ketones to furnish (R)- or (S)-ketone cyanohydrins (Table 10.3). Using PflHnL as catalyst, alkyl methyl ketones gave moderate yields and high optical purities, whereas with alkyl ethyl ketones the)fields and optical purities were lower [39,42]. The substrate scope has been extended to methyl phenyl ketones, cyclic, bicyclic, heterocyclic, as well as silicon-containing compounds [16]. Concerning (S)-ketone cyanohydrins, excellent results were achieved with aliphatic and aromatic ketones, for example, acetophenone cyanohydrin, using (S)-HbHnL (40% conversion, 99% ee.. Table 10.3) or (S)-MeHnL (87% conversion, 98% ee... 

World consumption data by end use in 1987 are shown in Table 8 (39). Solvent appHcations account for the largest use of acetone worldwide, followed by production of acetone cyanohydrin for conversion to methacrylates. Aldol chemicals are derivatives of acetone used mainly as solvents (40). 

Selected physical properties of various methacrylate esters, amides, and derivatives are given in Tables 1—4. Tables 3 and 4 describe more commercially available methacrylic acid derivatives. A2eotrope data for MMA are shown in Table 5 (8). The solubiUty of MMA in water at 25°C is 1.5%. Water solubiUty of longer alkyl methacrylates ranges from slight to insoluble. Some functionalized esters such as 2-dimethylaniinoethyl methacrylate are miscible and/or hydrolyze. The solubiUty of 2-hydroxypropyl methacrylate in water at 25°C is 13%. Vapor—Hquid equiUbrium (VLE) data have been pubHshed on methanol, methyl methacrylate, and methacrylic acid pairs (9), as have solubiUty data for this ternary system (10). VLE data are also available for methyl methacrylate, methacrylic acid, methyl a-hydroxyisobutyrate, methanol, and water, which are the critical components obtained in the commercially important acetone cyanohydrin route to methyl methacrylate (11). 

A cyanohydrin is an organic compound that contains both a cyanide and a hydroxy group on an aUphatic section of the molecule. Cyanohydrias are usually a-hydroxy nitriles which are the products of base-cataly2ed addition of hydrogen cyanide to the carbonyl group of aldehydes and ketones. The lUPAC name for cyanohydrias is based on the a-hydroxy nitrile name. Common names of cyanohydrias are derived from the aldehyde or ketoae from which they are formed (Table 1). 

Cyanohydrins are usually colorless to straw yellow Hquids with an objectionable odor akin to that of hydrogen cyanide. The lower molecular-weight cyanohydrins can be distilled under reduced pressure provided the cyanohydrin is kept at a slightly acidic pH. Table 2 Hsts physical properties of some common cyanohydrins. 

Table 3. Equilibrium Constants for Formation of Cyanohydrins from Hydrogen Cyanide Plus Carbonyl Compounds ...

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Table 10. Synthesis of Cyanohydrins by Oxynitrilase-Catalyzed Transacylation...

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

The cyanohydrin of methyl perfluoroheptyl ketone was synthesized by a two-step process addition of sodium bisulfite and subsequent treatment with sodium cyanide. When the ketone was reacted with sodium cyanide, cyclic addition products were obtained, instead of the product of cyanohydrin formation. This result was attributed to the solubility characteristic of a long perfluoroalkyl group, which makes the compound less soluble in water and polar organic solvents [54] (equation 40) (Table 14). 

Table 1. ( )-Cyanohydrins by Enzymatic Formation from Aldehydes and Hydrocyanic Acid 14,15...

The enzyme-catalyzed stereoselective synthesis of (/ )- and (S )-cyanohydrins allows a simple access to compounds which can be easily transformed into the corresponding a-hydroxy-car-boxylic acids (see Table 2)20,21,23, a-hydroxyaldehydes26 or acyloins27, without racemization. 

A general method for preparing (/ )-cyanohydrins, derived from ketones, is the (/ )-oxyni-trilase-catalyzed addition of hydrocyanic acid to ketones in an organic solvent30. The (R)-cyanohydrins are obtained with good chemical yields and in high optical purity (Table 3)30. 

Table 3. (R)-Cyanohydrins by Enzymatic Formation from Ketones and Hydrocvamic Acid as well as (7 )-a-Hydroxy-a-methyl Carboxylic Acids by Hydrolysis...

By simply hydrolyzing the easily accessible 2-hydroxy-2-methylalkanenitriles with concentrated acid, 2-hydroxy-2-methylalkanoic acids are obtained without measurable racemization (Table 3). The reaction sequence from the starting ketone to the carboxylic acid can be carried out in one pot without isolation of the cyanohydrin. The enantiomeric excesses of the (/ )-cyanohydrins and the (ft)-2-hydroxyalkanoic acids are determined from the ( + )-(/T)-Mosher ester derivatives and as methyl alkanoates by capillary GC, respectively. The most efficient catalysis by (R)-oxynitrilase is observed for the reaction of hydrocyanic acid with 2-alkanoncs. 3-Alkanoncs are also substrates for (ft)-oxynitrilase, to give the corresponding (/ )-cyanohydrins32. 

In Table 2, the properties and characteristics of the five HNLs presently applied in the enzyme-catalyzed large-scale preparation of chiral cyanohydrins are summarized. ... 

Substituted 1-hydroxy cyclohexane-1-carboxyhc acids, which could be prepared from the corresponding cyanohydrins by acid hydrolysis as described above, are important as pharmaceuticals and plant-protective agents. Although the compounds derived from 2- and 3-cyclohexanones have two stereogenic centers, stereoselective syntheses of these interesting products have been published only very recently. " Completely unexpected are the results of HNL-catalyzed additions to 4-substituted cyclohexanones, which do not possess a prochiral center. The (R)-PaHNL-catalyzed addition affords almost exclusively fran -isomers, whereas with (5 )-MeHNL cA-addition is favored (Table 4). ... 

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