Reactions of Cyanide Ion

Phase transfer catalysis found one of its earliest applications in cyanide displacement reactions. Starks studied this reaction in some detail and it was due in large part to his work that the concepts of phase transfer were so clearly understood at an early stage [1, 2]. There was, of course, other early interest in cyanide ion and these efforts should not be overlooked. Brandstrom had solubilized cyanide ion by his ion pair extraction technique [3] Solodar had facilitated the benzoin condensation by utilizing tetrabutylammonium cyanide [4] and Durst [5] and Liotta [6] both used crown ethers to phase transfer cyanide ion. A good deal of other work has now been carried out on phase transferred cyanide ion and is the subject of this chapter. 

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Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Since the value of the equilibrium constant for the hydrolysis reaction of cyanide ion is larger than that for the hydrolysis of ammonium ion, the cyanide ion hydrolysis reaction will proceed to a greater extent. The solution of NH4CN(aq) will be basic (alkaline). 

The fate of the PhSO- liberated through either (27b) or (29) varies depending upon reaction conditions. In some cases, as in the reaction of cyanide ion with PhS(0)SPh in a CN-/HCN buffer (Kice and Liu, 1979), it is converted to PhSNu, presumably through protonation to PhSOH and subsequent reaction of the sulfenic acid with additional nucleophile (30). On the... 

Petrzilka, Felix, and Eschenmoser (19) have shown that the reaction of cyanide ion on the ion 219 gave mainly the addition product 40. Similarly, Riedi-ker and Graf (20) observed that the addition of cyanide on the ion 41 gave preferentially 42 which is the result of a stereoelectronically controlled reaction of the most hindered face of the iminium ion. Stereospecific addition of cyanide to enamine 43 via the iminium salt 44 to yield compound 45 has also been reported (21). 

Reaction of cyanide ion with an alkyl halide is often the most convenient route to a nitrile, but in those cases where the corresponding aldehyde or ketone is more readily available than the alkyl halide, the following procedure is very convenient. The carbonyl compound is first converted into its 2,4,6-triisopropyl-benzenesulphonyl hydrazone (1) (Expt 6.42 gives the method for the preparation of the reagent, TBSH), which without isolation is then reacted with potassium cyanide under gentle reflux.169... 

It has been known for many years that the reaction of cyanide ion with alkylating agents shows a dependency on the presence of metal ions. The classic application of this is the formation of nitriles by reaction with potassium cyanide and isonitriles from the reaction with silver cyanide (Fig. 5-59). 

The reaction of cyanide ion with substituted benzhydryl carbenium ions to form nitriles and isocyanides is controlled by the rates of reaction at carbon and nitrogen.124 In slow reactions, far from the diffusion limit, the attack is completely at the cyanide carbon. Very fast reactions, with little or no reaction barrier reacting at the diffusion-controlled limit, occur at both the N and the C of the cyanide ion. XN2 reactions occur almost exclusively at carbon regardless of the substrate or source of the cyanide ion. The HSAB principle cannot predict the products of these reactions. 

By far one of the most important reactions through the S l mechanism is formation of a C—C bond by the reaction of aryl halides with carbanions derived from hydrocarbons, ketones, esters, amides, nitriles and even, with some limitations, from aldehydes. The reactions of cyanide ions and carbonyl complexes of Co and Fe also form a new C—C bond. 

The reaction of cyanide ion with divalent copper should be mentioned, for here cyanide acts in a dual capacity, both as a complexing agent and as a reducing agent if sufficient cyanide is used, part of the cyanide will be oxidized to cyanogen, (CN)2> and the remainder will attach itself to the Cu+ ions formed in the reduction ... 

Other reduction reactions also result in the formation of primary amines. For example, the catalytic reduction of a nitrile forms a primary amine. (Recall that a nitrile can be obtained from the reaction of cyanide ion with an alkyl halide.)... 

In many PTC systems, a third phase can form where reaction occurs and rates are enhanced. This third phase can form in many multiphase systems, and has been termed the omega phase [18]. The first example of an omega phase was discovered in the ITC reaction of cyanide ion on a benzyl halide in the presence of a crown ether as phase transfer catalyst. This liquid-solid PTC system was found to have rates dependent on the amount of water present. It was determined that in the absence of either water or the... 

The Sn2 reaction is a powerful method for inserting functional groups into a carbon skeleton. There are several important synthetic considerations. The poor reactivity of sterically hindered halides dictates that primary or secondary substrates be used. A typical example is the 8 2 reaction of cyanide ion with the primary tosylate unit in 64, which gave nitrile 65 in Mulzer s synthesis of the C1-C12 segment of the antitumor... 

The photochemically induced reaction of cyanide ion with nitroanisoles provides substituted benzonitriles, the nature of the product being governed by the substitution pattern of the starting material [95]. Thus, 4-nitroanisole affords... 

The explanation used for these two experiments suggests that the reaction of cyanide ion with 9 is reversible with an aldehyde or a ketone, so the yield of cyanohydrin is expected to be poor. The acid-catalyzed reaction, however, leads first to an oxocarbenium ion that easily reacts with cyanide. Therefore, the acid-catalyzed reaction gives a good yield of the cyanohydrin. This difference between direct substitution and acid-catalyzed addition is an important key to understanding and controlling reactions with nucleophiles. Note that when cyanide reacts with the carbonyl unit of 9, a new carbon-carbon bond is formed as the carbonyl 7t-bond is broken. 

A mechanism has been proposed for the reaction of cyanide ion with thio-cyanogen, selenocyanogen, sulphur dicyanide, and selenium dicyanide in acetonitrile on the basis of studies using C as a tracer ... 

The reaction of cyanide ion with tetrathionate in acetonitrile occurs with a 2 1 stoicheiometry, and it is proposed that the SOaCN" ion may be formed. This species, or its conjugate acid, has been postulated as an intermediate in the hydrolysis of thiacyanogen and in the sulphur dicyanide-thiosulphate reaction. A study of the analytical determination of microamounts of hexathionate has included some kinetic work on the reaction... 

The reaction of cyanide ions with bromoethane is also an S)y[2 reaction (Figure 20.23). 

A full account has been given of the work by Brimacombe s group (see Vol. 23, p. 9) on the formation of octuronic acid derivatives by catalytic osmylation of a,p-unsaturated esters in the presence of Sharpless chiral ligands, where double asymmetric induction can be used to enhance the Kishi selectivity.66 The trehalose derivative (44) could be homologated to the bis-uronic acid (45) using a carbonyl insertion procedure (Scheme 13), as well as by use of the reaction of cyanide ion on the ditriflate analogous to (44)67... 

Starks [10] examined the reaction of cyanide ion with n-octyl bromide (Eq. 1.7) and found that 1) the reaction occurred in the organic phase 2) the displacement was first order in alkyl halide and first order in catalyst (QX) 3) the rate of reaction... 

As expected for a bimolecular process, the reaction is faster with primary than with secondary halides. Likewise, -octyl methanesulfonate was found to undergo cyanide displacement at a greater rate than did the corresponding bromide. Moreover, elimination competes with substitution in the case of secondary halides elimination was the exclusive process observed in the reaction of cyanide ion with cyclohexyl halides. 

Crown ethers have also been utilized as phase transfer catalysts in solid-liquid phase transfer cyanide displacements. These reactions are generally carried out in methylene chloride or acetonitrile solution with 18-crown-6 as catalyst and solid potassium cyanide as nucleophile source [5, 6]. Small amounts of water are found not to affect the course of the reaction [5], suggesting some hydration of cyanide ion under these conditions. This is not surprising inasmuch as Starks reported that in the liquid-liquid phase transfer process, four to five molecules of water apparently accompanied each nucleophile into nonpolar solution [2]. It seems likely that if water were or could be rigorously excluded, (i.e., naked anions obtained), the reactivity of cyanide would be even higher. Despite the apparent similarity of the solid-liquid and liquid-liquid phase transfer processes, it should be noted that qualitative differences in the relative reactivity of primary alkyl halides (R—Cl vs. R—Br) have been observed for the crown and quaternary ion cases [2, 6]. Specifically, Starks found that for the reaction of cyanide ion with A2-octyl halides, methanesulfonate... 

Finally, it should be noted that the reaction of cyanide ion with 1-bromooctane to yield 1-octyl cyanide has been catalyzed by a quaternary ammonium catalyst bound to a polystyrene resin. The resin constituted one of three phases, the other two being aqueous cyanide reservoir and toluene containing the substrate. The kinetics observed in this three-phase system are strikingly similar to those observed by Starks [11]. 

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