Cyanhydrins

CHjiCH-CN. Volatile liquid b.p. 78"C. Manufactured by the catalytic dehydration of ethylene cyanhydrin, by the addition of hydrogen cyanide to ethyne in the presence of CuCI or the reaction of propene, ammonia and air in the presence of a molybdenum-based catalyst. 

By (he direct addition of hydrogen cyanide to aldehydes and ketones, giving cyanhydrins ... 

Acetone cyanhydrin (a-Hydroxy sobutyronitrile) By this method, the nitrile of an a-hydroxy acid U necessarily obtained. 

To 2 ml. of the ester, add 2--3 drops of a saturated freshly prepared solution of scdium bisulphite. On shaking, a gelatinous precipitate of the bisulphite addition product (D) of the keto form separates, and on standing for 5-10 minutes usually crystallises out. This is a normal reaction of a ketone (see p. 344) hydrogen cyanide adds on similarly to give a cyanhydrin. 

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

Mandelic Acid.—The reaction furnishes a simple and general method for obtaining hydroxy-acids from aldehydes or ketones by the aid of the cyanhydrin. The formation of the cyanhydrin may be effected in the manner described or by the action of hydrochloric acid on a mixture of the aldehyde or ketone with potassium cyanide, or, as in the case of the sugais, by the use of liquid hydrocyanic acid and a little amme-nia. 

Dodge has based a process for the determination of benzaldehyde. A strong (2 5 N) alcoholic potash solution is required for the estimation, which is performed. by allowing a mixture of 10 c.c. of this solution with 1 to 2 grams benzaldehyde to stand at the ordinary temperature for twenty-four hours, after which the unabsorbed pota is titrated back with N/2 hydrochloric acid. A blank test is also made, and from the amount of potash entering into reaction, the percentage of aldehyde can be calculated. The process breaks down in the assay of natural oil of bitter almonds, probably due to the presence of benzaldehyde cyanhydrin. 

Hydroxy-nitrile (Cyanhydrine) werden am besten mit Diboran reduziert z.B.2 ... 

Cyanhydrine konnen auch mit Natriumboranat/Kobalt(II)-chlorid zu den 2-Hydroxy-aminen reduziert werden (s.S. 115). Aus Phenyl-glykolsaure-nitril werden so z.B. 80% d.Th. 2-Amino-l-phenyl-athanol erhalten3,... 

Decomposition by cyanide gives the same products (except that the sugar forms the cyanhydrin) and probably involves coordination of cyanide in the trans position, followed by the elimination of Co(III) and oxygen (as RO ) to give the olefin. For further references and discussion about both these reactions see Chapter 13 of ref. (136). These two methods of decomposition... 

The upper layer which contains, in addition to acrylonitrile, hydrogen cyanide, acrolein, acetonitrile, and small quantities of other impurities, passes to a second reactor (E) where, at a suitable pH, all the acrolein is converted to its cyanohydrin. (Cyanohydrins are sometimes known as cyanhydrins.) The product from the reactor (E) is fed to a cyanohydrin separation column (F), operating at reduced temperature and pressure, in which acrolein cyanohydrin is separated as the bottom product and returned to the ammox-idation reactor (A) where it is quantitatively converted to acrylonitrile and hydrogen cyanide. 

Die a-standige Aminogruppe ist ohne grundsatzliche Bedeutung fiir die Halbhydrierung auch einfache Aldosen lassen sich iiber ihre Cyanhydrine in die um 1 C-Atom reicheren Zucker iiberfuhren. 

ACH (1) [Acetone cyanhydrin] A process for making methyl methacrylate via this intermediate. Acetone reacts with hydrogen cyanide to yield the cyanhydrin. This is then converted to methacrylamide, using concentrated sulfuric acid. Methanolysis of this yields methyl methacrylate. Developed by Rohm GmbH Chemische Fabrik, Germany, and ICI, UK used in 11 countries in 1990. 

Both acrylic acid and methacrylic acid polymerise to give water soluble hard resins. The viscous solutions so formed have been used as emulsifying agents, adhesives and as thickening agents for inks and dyes. Polymers of esters of these acids are of greater commercial importance. Esters can be prepared from cyanhydrins by reaction with an alcohol ... 

Allyl derivatives of a range of cyanhydrins have been obtained from the liquiddiquid two-phase reaction catalysed by Aliquat at 0°C [17]. Yields range from ca. 25% to 45%. 

Acyloxy-l-cyanoalkanes [45, 46], which can be used as precursors for ketones [47], a-hydroxy ketones [48] and 1,4-dicarbonyl compounds [47], are prepared in one pot from the appropriate aldehyde, sodium or potassium cyanide, and the acylating agent under phase-transfer catalytic conditions [47-49]. Attempts to synthesize chiral cyanhydrins using chiral phase-transfer catalysts have been unsuccessful (see Section 12.3). 

Method E (using acetone cyanhydrin) TBA-CN or TBA-OH (11 mmol) in MeCN (10 ml) is added dropwise over 20-30 min to the haloalkane (10 mmol) and Me2C(OH)CN (1.3 g, 15 mmol) in MeCN (20 ml) and the mixture is stirred until TLC analysis indicates the reaction to be complete. The mixture is evaporated and the residue taken up in H20 (10 ml) and Et20 (40 ml). The organic phase is separated, washed with H20 (3x5 ml), dried (MgS04), and evaporated to yield the nitrile. 

Acetone cyanhydrin has been used as a convenient source of cyanide ion for the preparation of alkyl cyanides (6.1.1.E) [21]. Moderate yields (50-77%) have been achieved using tetra-n-butylammonium cyanide or hydroxide as the base. 

Regio-control of the formation of benzoic esters of mixed benzoin derivatives results from the initial formation of the cyanhydrin benzoate (see Chapter 3). Subsequent base-catalysed hydrolysis of the esters produces the mixed benzoins (Scheme 6.20) [66]. 

Aqueous NaOH (50%, 0.2 ml), TEBA-CI (15 mg, 0.06 mmol), and the cyanhydrin benzoate (1 mmol) in PhH (4 ml), are stirred at room temperature under argon for 10 min. The aryl aldehyde (1 mmol) in PhH (4 ml) is then added at 0°C and the mixture is stirred at room temperature for ca. 5 h (monitored by TLC). On completion of the reaction, the organic solution is separated and washed well with H20, dried (MgS04), and evaporated to yield the benzoin benzoate (Table 6.15). 

Attempts to produce chiral cyanhydrins under phase-transfer catalytic conditions (3.3.9) using ephedrinium or cinchoninium catalysts has been singularly unsuccessful [21,22]. Optical purities varying from 0 to 60% have been recorded [22], but verification of the reproducibility of the higher values is needed. Similarly, nucleophilic attack on a carbonyl group by the trichloromethyl anion under phase-transfer catalytic conditions (see Section 7.4) in the presence of benzylquininium chloride produces a chiral product, but only with an enantiomeric excess of 5.7% [23]. The veracity of this observation has also been questioned [24],... 

F]Fluorobenzaldehydes have also been used as starting materials for the preparation of enantiomers of [6- F]fluoronorepinephrine,a myocardial marker [166]. The key step is the formation of a protected F-cyanhydrine which is reduced into an amino alcohol. Deprotection, purification and resolution on a chiral column provide both enantiomers (Scheme 30). 

The mechanism for replacement of a methoxyl group by cyanide in these reactions follows Scheme 6.7. The radical-cation reacts with cyanide ion at the point of highest positive charge density. Oxidation of the radical so formed to the carbon-ium ion is followed by elimination of proton and formaldehyde [79]. The elimination step is analogous to the conversion of cyanhydrins to the carbonyl compound and cyanide ion in basic solution. 

Lubavin, in 1882, stated that glycine was formed by the action of ammonium cyanide upon glyoxal, which probably first breaks down into formaldehyde and then by the cyanhydrin reaction yields glycine —... 

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