Cyanide ion, as a nucleophile

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

Cyanide ion ( C = N ) The negatively charged carbon atom of cyanide ion IS usually the site of its nucleophilic character Use of cyanide ion as a nucleophile permits the extension of a carbon chain by carbon-carbon bond formation The product is an alkyl cyanide or nitrile... 

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. 

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 use of cyanide ion as a nucleophile in an SN2 reaction (see Section 10.8), followed by hydrolysis of the product nitrile, provides a useful preparation of carboxylic acids that contain one more carbon than the starting compound ... 

A cyanide anion as a nucleophile adds to an aldehyde molecule 1, leading to the anionic species 3. The acidity of the aldehydic proton is increased by the adjacent cyano group therefore the tautomeric carbanion species 4 can be formed and then add to another aldehyde molecule. In subsequent steps the product molecule becomes stabilized through loss of the cyanide ion, thus yielding the benzoin 2 ... 

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. 

An Sn2 displacement constitutes the key operation in which the ester group at C-3 of catharanthine is introduced [62], Thus, a contrapolarizing change of the 11-position from d to a allows the desired reaction to be performed, using cyanide ion as the nucleophile. 

The first such process was realized over one and a half centuries ago with the discovery of the Strecker reaction [10] which has a cyanide ion as the nucleophile, leading to the formation of a-amino nitriles 10 (Scheme 7.2). These highly versatile synthetic intermediates can be hydrolyzed to a-amino acids or can be converted to other molecules [11, 12]. 

The same disconnection 41 can be used for carboxylic acids with CO2 as the electrophile for a Grignard reagent 40. Dry ice (solid CO2) is particularly convenient for these reactions. Switching polarity by FGI to the nitrile 42, the same disconnection now uses cyanide ion as the nucleophile but the same alkyl halide 39 that was used to make the Grignard reagent. Mechanistic considerations should decide between these alternatives. 

At first glance the conversion of bromobenzene to benzenenitrile looks simple—just carry out a nucleophilic substimtion using cyanide ion as the nucleophile. Then we remember that bromobenzene does not undergo either an S l or an 5 2 reaction (Section 6.14A). The conversion can be accomplished, however, though it involves several steps. Oudine possible steps. 

If we use cyanide ion as the nucleophile (entry 14 in Table 6.1), the alkyl halide must have the halogen (Cl, Br, or I) attached to a propyl group. The... 

A related cleavage by alkaline cyanide can be viewed as a nucleophilic displacement of the deoxy-adenosyl anion by cyanide. The end product is dicyanocobalamin, in which the loosely bound nucleotide containing dimethyl benzimidazole is replaced by a second cyanide ion. Methyl and other simple alkyl cobalamins are stable to alkaline cyanide. A number of other cleavage reactions of alkyl cobalamins are known.392 393... 

The distribution of charge in the resonance forms (28)-(31) suggests that nucleophiles may attack at C-2, C-4 or C-6 (or at C-2 or C-4 in 1-benzopyrylium cations, and at C-l, C-3 or C-4a in 2-benzopyrylium ions) but they most commonly add at C-2 for example, attack by cyanide ion gives a 2//-pyran (37) which exists partly or wholly as the acyclic isomer (38). Steric and electronic effects in the reactants probably have a role in determining the course of the reaction of trisubstituted pyrylium salts with nucleophiles. A mixture of both 2H- and 4H-pyrans is sometimes produced, for example, from methoxide ion and 2,4,6-triphenylpyrylium perchlorate (39) no acyclic product was detected in this reaction... 

This reaction is presented in a style with which you will become familiar. The organic starting material is written first and then the reagent over the reaction arrow and the solvent under it. We must decide what happens. NaCN is an ionic solid so the true reagent must be cyanide ion. As it is an anion, it must be the nucleophile and the carbonyl group must be the electrophile. Let us try a mechanism. 

Cyanide ion is a good small nucleophile and displaces tosylate from primary carbon atoms and adds one carbon atom Lo the chain. As the cyanide (nitrile) group can be converted directly to a carboxylic acid or ester (Chapter 14) this sequence is a useful chain extension. 

Radical cations can be formed by irradiation of unsubstituted aromatic hydrocarbons such as naphthalene, and this makes possible the photochemical displacement of hydride ion by a nucleophile such as cyanide (3.10). Oxygen is not necessary for the success of this type of reaction if a good electron-acceptor is present, such as p-dicyanobenzene (3.11), which enhances the initial photoionization and also provides for reaction with the displaced hydrogen. 

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