Cyanide, reaction with aldehydes, bisulfite

Cyanohydrins can be formed by the acid- or base-catalyzed reaction of hydrogen cyanide with an aldehyde or ketone, the displacement of bisulfite ion by cyanide ion on the bisulfite addition compounds of aldehydes and... 

The reversibility of the reaction makes bisulfite compounds useful intermediates in the synthesis of oilier adducts from aldehydes and ketones. For example, one practical method for making cyanohydrins involves bisulfite compounds. The famous practical book Vogel3 suggests reacting acetone first with sodium bisulfite and then with sodium cyanide to give a good yield (70%) of the cyanohydrin. 

Aromatic aldehydes react with sodium hydrogen sulfite to yield bisulfite compounds. Further reaction with sodium cyanide forms the hydroxynitrile (cyanohydrin), which can sometimes be formed directly from the aldehyde by reaction with hydrogen cyanide (Scheme 6.11). 

Rather than direct reaction with an aldehyde or ketone, the bisulfite addition product is often treated with cyanide. The addition is nucleophilic and the actual nucleophile is CN, so the reaction rate is increased by the addition of base. " " This was demonstrated by Lap worth in 1903, and consequently this was one of the first organic mechanisms to be known. This method is especially useful for aromatic aldehydes, since it avoids competition from the benzoin condensation. If desired, it is possible to hydrolyze the cyanohydrin in situ to the corresponding a-hydroxy acid. This reaction is important in the Kiliani-Fischer method of extending the carbon chain of a sugar. 

In the Bucherer-Strecker synthesis, hydrogen [ C] cyanide is reacted with the bisulfite adduct of an aldehyde (Hayes et al. 1978 Casey et al. 1981 Barrio et al. 1982) to produce neutral amino acids labeled in the carboxylic position. Labeled aromatic aldehydes have also been applied in the Bucherer-Strecker synthesis (HaUdin and Langstrom 1984b) as well as in condensation reactions with oxazolones (Halldin and Langstrom 1984c, d, 1986) for labeling in the a- or the P-positions, respectively. 

Although there are a number of syntheses of pantothenic acid, that of Folkers et al. is among the earliest. As shown in Scheme 12.108, a clean synthesis of a-hydroxy-P,P-dimethyl-Y-butyrolactone was needed. First, 2-methylpropanal (isobutyraldehyde) underwent an aldol condensation with formaldehyde (formalin, H2C=0) to produce a,a-dimethyl-P-hydroxypropanal. Then, the bisulfite adduct of this aldehyde underwent reaction with potassium cyanide (KCN) and the separated cyanohydrin was hydrolyzed with concentrated hydrochloric acid (HCI), and the product was carefully made basic. The racemic a-hydroxy-P,P-dimethyl-y-butyrolactone was separated, while the lactone underwent ring opening in the... 

In a 4-I. wide-mouthed glass jar, fitted with a mechanical stirrer, is placed a solution of 150 g. (3 moles) of sodium cyanide (Note i) in 500 cc. of water and 318 g. (3 moles) of u.s.P. benz-aldehyde. The stirrer is started and 850 cc. of a saturated solution of sodium bisulfite (Note 2) is added to the mixture, slowly at first and then in a thm stream. The time of addition is ten to fifteen minutes. During the addition of the first half of this solution, 900 g. of cracked ice is added to the reaction mixture, a handful at a time. The layer of mandelonitrile which appears during the addition of the sulfite solution is separated from the water in a separatory funnel. The water is extracted once with about 150 cc. of benzene, the benzene is evaporated, and the residual mandelonitrile is added to the main portion. 

The Strecker reaction has been performed on the aldehyde 182 prepared from L-cysteine [86] (Scheme 28). The imine was formed in situ by treatment with benzylamine, then TMS cyanide was added to afford prevalently in almost quantitative yield the syn-diamine 183, which is the precursor of (-l-)-biotin 184. The syn selectivity was largely affected by the solvent, toluene being the solvent of choice. Since the aldehyde 182 is chemically and configurationally unstable, a preferred protocol for the synthesis of 183 involved the prehminary formation of the water-soluble bisulfite adduct 185 and the subsequent treatment with sodium cyanide. Although in this case the syn selectivity was lower, both diastereomers could be transformed to (-l-)-biotin. 

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