Nitriles from cyanohydrins

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. 

You met a way of making nitriles—from HCN (or NaCN + HC1) plus aldehydes the hydroxynitrile products are known as cyanohydrins. 

A synthesis of nitriles from the cyanohydrins of aromatic aldehydes via the reduction of the corresponding a-halo cyanides has been proposed. As an example, benzaldehyde cyanohydrin is converted by the action of thionyl chloride to phenylchloroacetonitrile (80%). This substance is reduced with zinc in acetic acid to phenylacetonitrile (70%). ... 

Cyclopropylimines are usually generated by reduction of nitriles or condensation of carbonyl compounds with amines. An alternative to this process involves the generation of cyclopropylinunoni-um salts such as (209) at room temperature from cyanohydrin equivalent (208 Scheme 49). ... 

Mechanism 28.1 for the formation of the a-amino nitrile from an aldehyde (the first step in the Strecker synthesis) consists of two parts nucleophilic addition of NH3 to form an imine, followed by addition of cyanide to the C=N bond. Both parts are related to earlier mechanisms involving imines (Section 21.11) and cyanohydrins (Section 21.9). 

The carbanion (1) can be generated independently from cyanohydrins and can be added to the double bond of a,3-unsaturated ketones, esters and nitriles by an irreversible reaction which ultimately leads to y-diketones, 4-oxocarboxylic esters and4-oxonitriles. ... 

Recently, the group of Herrera, Bernardi, and Ricci realized the enantioselective synthesis of protected a-amino nitriles from the corresponding a-amino sulfones 137, which act as effective precursors for the in situ generation of imines, by the use of acetone cyanohydrin (138) as a cyanide source using quinine-derived PTC 136 [64]. The aminonitriles 139 were produced with broad generality in 50-88% ee (Scheme 8.53). However, a similar protocol using KCN and TMSCN resulted in a lower ee value. 

Amines from nitriles s. 1, 53 a-Aminoalcohols from cyanohydrins s. 1, 54 Hydrogenation of the isoquinoline ring s. 2, 839 1,2,3 4-T etrahydroquinoxalines Removal of catalyst poisons s. 4, 65 CN —CH2NH2 [Pg.274]

Hydrolysis of the hydantoins gives the a>amino acids, often in better yield than can be obtained from the -amino nitriles. Among the amino acids that have been prepared from cyanohydrins and hydantoins are methionine,986 lysine,987 988 alanine,989 and phenylalanine.989... 

Glycine from Cyanohydrin. As previously stated, it is not possible to aminate chloroacetic acid without obtaining a mixture of primary and secondary amines. However, amination of cyanohydrin with about 5 moles of anhydrous ammonia, followed by alkaline hydrolsrsis of the nitrile group, gives a practically quantitative yield of glycine. -... 

Aromatic and Vinyl Nitriles. Aromatic haUdes (Br, I) have been converted into nitriles in excellent yields by Pd(Ph3P)4 catalysis in the presence of Sodium Cyanide Alumina,Potassium Cyanide, or Cyanotrimethykilane (eq 24). While the latter two procedures require the use of Arl as substrates, a more extensive range of substituents are tolerated than the alternative method employing ArBr. A Pd(Ph3P)4-catalyzed extrasion of CO from aromatic and heteroaromatic acyl cyanides (readily available from cyanohydrins) at 120 °C provides aryl nitriles in excellent yields (eq 25). ... 

You met a way of making nitriles—from HCN (or NaCN + HCl) plus aldehydes—in Chapter 6 the hydroxynitrile products are known as cyanohydrins. With this in mind, you should be able to suggest a way of making mandelic acid, an extract of almonds, from benzaldehyde. 

A rapid conversion of alcohols to nitriles through chlorides prepared in situ has been published. Good yields of a-acoxy-nitriles can be obtained from cyanohydrins and a,/ -unsatd. aldehydes carrying electron-attracting substituents . 

Due to the high price of trimethylsilyl cyanide, access to alternative cyanation reagents is desirable. In this regard, cyanoformate esters (CNCO2R) have been employed, providing direct access to O-alkojycarbonyl-functionalised cyanohydrins, which are stable and not easily hydrolysed by moisture in air. Moreover, they are useful synthetic intermediates and can be applied in the synthesis of a-amino alcohols and (3-substituted unsaturated nitriles from O-carbonylated allylic cyanohydrins. ... 

Thiolic acid esters from nitriles via thioiminoester hydrochlorides oc-Hydroxythiolic acid esters from cyanohydrins... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

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). 

Acetaldehyde Cyanohydrin. This cyanohydrin, commonly known as lactonitnle, is soluble in water and alcohol, but insoluble in diethyl ether and carbon disulfide. Lactonitnle is used chiefly to manufacture lactic acid and its derivatives, primarily ethyl lactate. Lactonitnle [78-97-7] is manufactured from equimolar amounts of acetaldehyde and hydrogen cyanide containing 1.5% of 20% NaOH at —10 20 ° C. The product is stabili2ed with sulfuric acid (28). Sulfuric acid hydroly2es the nitrile to give a mixture of lactic acid [598-82-3] and ammonium bisulfate. 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

Cyanides are dangerously toxic materials that can cause instantaneous death. They occur in a number of industrial situations but are commonly associated with plating operations, and sludges and baths from such sources. Cyanide is extremely soluble and many cyanide compounds, when mixed with acid, release deadly hydrogen cyanide gas. Cyanide is sometimes formed during the combustion of various nitrile, cyanohydrin, and methacrylate compounds. Cyanides (CN ) are commonly treated by chlorine oxidation to the less toxic cyanate (CNO ) form, then acid hydrolyzed to COj and N. Obviously, care should be taken that the cyanide oxidation is complete prior to acid hydrolysis of the cyanate. 

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