Cyanide as nucleophile

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... 

A second factor that can tip the balance m favor of substitution is weak basicity of the nucleophile Nucleophiles that are less basic than hydroxide react with both pri mary and secondary alkyl halides to give the product of nucleophilic substitution m high yield To illustrate cyanide ion is much less basic than hydroxide and reacts with 2 chlorooctane to give the corresponding alkyl cyanide as the major product... 

What product would you expect from a nucleophilic substitution reaction of (R)-l-bromo-l-phenylethane with cyanide ion, C=N, as nucleophile Show the stereochemistry of both reactant and product, assuming that inversion of configuration occurs. 

Rate constants for the substitution reactions of square-planar dithio-phosphates and dithiocarbonate complexes of Ni(II), Pd(II), and Pt(II), with ethylenediamine and cyanide ion as nucleophiles, have been measured in methanol. The results were compared with those obtained in previous investigations, and interpreted in terms of the stabilities of 5-coordinate species that are formed prior to substitution (377). 

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

The reaction of difunctional nucleophiles with alkyl isocyanides under the influence of silver cyanide as catalyst has been described in an earlier section on imidazoles an example of the use of this simple approach in an oxazoline synthesis is shown in Scheme 107.169... 

It is well known that oxidation of carbamates leads to the formation of N-acyliminium ions via dissociation of the C-H bond a. to nitrogen. The electrochemical,4 metal-catalyzed,5 and chemical methods6 have been reported in the literature to accomplish this transformation. The transformation serves as a useful tool for organic synthesis, although only compounds of high oxidation potentials such as methanol and cyanide ion can be used as nucleophile. It... 

Again, a hnear relationship of and [CNS] i shows a bimolecular reaction between the excited triplet state of 1 and the nucleophile to take place. The triplet lifetime of la is 4.7 X 10 s in water and 1.2xl0 8s in aqueous 10 2M solutions of potassium cyanide as determined from quenching studies The nitro group in 7 a is likewise replaced photochemically by methoxide and cyanate ions. 

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

Nucleophilic Substitution. The copper catalysed replacement of halogen adjacent to the azo link by other nucleophiles is a commercial manufacturing process. Important blue disperse dyes, e.g. Cl Disperse Blue 165 and related dyes, are made by displacement of the bromo derivatives by cyanide, as shown in Figure 2.10. 

Examples of nonasymmetric organocatalysts that were introduced in the 1950s include analogs of thiamine reported by Breslow in 1957 as an alternative to cyanide as a catalyst for the benzoin condensation [8]. Asymmetric versions of these thiazolium catalysts were used in organocatalytic benzoin condensations by Sheehan and Hunneman in 1966 [9]. In another important development, in 1969 the nucleophilic catalyst 4-(dimethylamino)pyridine (DMAP), which is now widely used for difficult esterifications, was reported by Steglich [10]. 

The preparation of amides by the addition of hydrogen cyanide or alkyl nitriles to alkenes in the presence of acids, known as the Ritter reaction, has been reviewed.229-232 The reaction may be considered simplistically as nucleophilic attack of a nitrile on a carbocation formed by the protonation of an alkene. Subsequent hydrolysis of the nitrilium intermediate gives the amide product (equation 164). The overall result is addition of a molecule of H—NHCOR to a C—C double bond. 

Once cyclopentyl bromide has been prepared, it is converted to cyclopentyl cyanide by nucleophilic substitution, as shown in part (a). 

The use of acetylides as nucleophiles is a particularly important example of nucleophilic substitution because it results in a new carbon-carbon bond. Thus, larger organic molecules can be assembled from smaller ones using this method. The same is true for cyanide ion as a nucleophile (part b). 

The regiospecific nucleophilic displacement of 1,2-cyclic sulfamidates 130 with methyl thioglycolate or a-amino esters 130 can be accompanied by lactamization (thermal, base mediated, or cyanide catalyzed) to give thiomorpho-lin-3-ones and piperazin-2-ones 131 (Scheme 19) <20030L811>. If malonate esters, phosphonate-stabilized esters, or aryl-substituted enolates were used as nucleophiles in this reaction, trisubstituted pyrrolidines were obtained in high yield <2004OL4727>. 

Alkyllithium compounds and alkali cyanides, mercaptides, and alkoxides,322,323 etc. have been used as nucleophilic reagents in reactions with the enamine salts. Nitrile groups can be removed by reduction or by treatment with acids. Treatment of cotarnine (100)... 

These are O-, S- and iVnucleophiles. Halide ions are not able to react as nucleophiles with carbonyl compounds, but a pseudohahdethat is, the cyanide ion, is. The addition of the cyanide ion to aldehydes and ketones displays considerable analogies with the addition reactions of ()-, S- and N nucleophiles and this is why Section 9.1 addresses these cyanide additions. 

The HOMO of the nucleophile will depend on what the nucleophile is, and we will meet examples in which it is an sp or sp3 orbital containing a lone pair, or a B-H or metal-carbon o orbital. We shall shortly discuss cyanide as the nucleophile cyanide s HOMO is an sp orbital on carbon. 

---