Aldehyde cyanohydrin

Early preparations of the product from benzil, hydrogen cyanide, and hydrogen chloride (315) and by the action of hydrogen chloride on mandelonitrile (benz-aldehyde cyanohydrin) (316) were formulated by Japp and Knox (317) as 3-hydroxy-2,5-diphenylpyrazine, and a mechanism for the reaction was proposed by Ingham (318). The structure of the product, however, has been refuted by Gallagher et al. (282). 

In a procedure similar to that used by Minovici (316), McCombie and Parry 

A modification of this procedure was introduced by McKenzie and Kelman 

A number of miscellaneous reactions, of which the mechanism is not known but which may involve a-aminocarbonyl compounds, is listed in Table 11.7 (14, 242, 321-328) without further comment. 

TABLE II.7 MISCELLANEOUS SYNTHESIS OF PYRAZINES POSSIBLY VIA a-AMINO 

---

The Fisher oxazole synthesis involves condensation of equimolar amounts of aldehyde cyanohydrins (1) and aromatic aldehydes in dry ether in the presence of dry hydrochloric acid. ... 

The first report on the reaction of D-pseudoephedrine 66 with phosphoryl chloride appeared as early as 1962 [49], More recently it was found that this condensation gave 2-chloro-l,3,2-oxazaphospholidine 2-oxides 67 as a single diastereomer which was subsequently esterified with racemic aldehyde cyanohydrins 68 without racemization at the phosphorus atom. The prepared diastereomeric esters 69 were used as substrates for the asymmetric synthesis of optically active cyanohydrins 72, which involves the intermediate formation of the tertiary esters 70, as shown in Scheme 22 [50],... 

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 double process of cyanation/transcyanation of co-bromoaldehydes and racemic cyanohydrins as a source of HCN is a really interesting process (Scheme 10.25). Thus, using this reaction it is possible to obtain optically active (S)-ketone- and (R)-aldehyde-cyanohydrins in one pot [55], The reaction is carried out in diisopropyl ether using a crude extract of almond containing (R)-oxynitrilase as biocatalyst. The optically active (a-bromocyanohydrins prepared by this method is used as starting materials for the synthesis of valuable compounds such as... 

The use of an optically active RBC12 gave secondary amines of essentially 100% optical purity.363 In other methods, trialkylboranes R3B gave secondary amines RR NH upon treatment with N-chloroamines R NHCl,364 and aryllead triacetates ArPb(OAc)3 give secondary amines ArNHAr when treated with primary aromatic amines Ar NH2 and Cu(OAc)2. s An indirect method for the conversion of aldehydes to N,N-disubstituted amides is based on the conversion of an 0-(trimethylsilyl)aldehyde cyanohydrin 34 to the amine 35.366... 

Acyloins.3 Grignard reagents of the type R1CH2MgX react with the O-tri-methylsilyl ethers of aldehyde cyanohydrins to form products that are hydrolyzed by acids to acyloins in 75-85% yield. 

The original Strecker procedure is the reaction of an aldehyde with ammonia and then with hydrogen cyanide to form the a-amino nitrile. This intermediate may also be obtained by reacting the aldehyde cyanohydrin with ammonia, but a more convenient method is to treat the aldehyde in one step with ammonium chloride and sodium cyanide. The a-amino acid is obtained when the amino nitrile is hydrolysed under either acidic or basic conditions the former are usually preferred. The preparation of a-phenylglycine (R = Ph) from benzalde-hyde is typical of the general procedure (cognate preparation in Ept 5.181). 

Cyanohydrin formation is therefore an equilibrium between starting materials and products, and we can only get good yields if the equilibrium favours the products. The equilibrium is more favourable for aldehyde cyanohydrins than for ketone cyanohydrins, and the reason is die size of the groups attached... 

On the other hand, the aldehyde cyanohydrin has no plane of symmetry the plane of the paper has OH on one side and CN on the other while the plane at right angles to the-paper has H on one side and RCH2 on the other. This compound is completely unsyinmetrical and has two enantiomers. 

An aldehyde cyanohydrin is chiral because it does not have a plane of symmetry. In fact, it cannot have a plane of symmetry, because it contains a tetrahedral carbon atom carrying four different groups OH, CN, RCH2, and H. Such a carbon atom is known as a stereogenic or chiral centre. The product of cyanide and acetone is not chiral it has a plane of symmetry, and no chiral centre because two of the groups on the central carbon atom are the same. 

We saw how the two enantiomers of the aldehyde cyanohydrin arose by attack of cyanide on the two faces of the carbonyl group of the aldehyde. We said that there was nothing to favour one face over the other, so the enantiomers must be formed in equal quantities. A mixture of equal quantities of a pair of enantiomers is called a racemic mixture. 

Reay, PP. and Gonn, E.E. (1974) The purification and properties of a uridine diphosphate glucose aldehyde cyanohydrin (3-glucosyltransferase from sorghum seedlings. Arch. Biochem. Biophys., 249, 5826-30. 

Wurtele, E.S., Thayer, S.S. and Corm, E.E. (1982) Subcellular localization of a UDP-glucose aldehyde cyanohydrin (i-glucosyl transferase in epidermal plastids of Sorghum leaf blades. Plant Physiol, 10,1732-7. 

The simplest aldehyde cyanohydrin, glycolonitrile, has been prepared by a cyanohydrin interchange between formalin and methyl ethyl ketone cyanohydrin. ... 

The preparations of hydroxypyrazines by primary syntheses have been described in Chapter II, and are summarized briefly, together with further data, as follows Section II.IG, from the reaction of a, 3-dicarbonyl compounds with ammonia [282 (cf. 281, 280), 283, 285] with additional information (1042, 1043) Section II.IM, from 1,2-dicarbonyl compounds with a-amino acids (311) Section II.IN, from a-amino acids through piperazine-2,5-diones (93,95,101,282,312,313)with additional data (843) Section 11.10, from aldehyde cyanohydrins ( ) [317-319 (cf. 282)1 and Section II.IP, from o-nitromandelonitrile and ethereal hydrogen cyanide (325). The preparations from a,iJ-dicarbonyl compounds with a,/ -diamino compounds are described in Section 11.2 (60, 80, 358, 359, 361-365b, 365d, 366-375) additional data have also been reported (824, 825, 827,845,846,971, 1044, 1045) and some reaction products have been isolated as the dihydro-pyrazines (340,341,357). 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

The mechanism of the benzoin condensation, as depicted in Scheme 1, suggested that anions derived from a protected aldehyde cyanohydrin should function as nucleophilic acylating reagents. The use of protected cyanohydrins as carbanion equivalents has been studied by Stork and by Hunig and has found wide applicability in chemical synthesis. Such species may serve as either acyl anion equivalents or homoenolate anions. ... 

On the other hand, the aldehyde cyanohydrin has no plane of symmetry the plane of the CN... 

---