Nucleophilic Substitution by Cyanide

Suggest reagents for each of the following transformations, which may require more than one step  

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Nucleophilic substitution by cyanide ion (Sections 8.1, 8.13) Cyanide ion is a good nucleophile and reacts with alkyl halides to give nitriles. The reaction is of the S m2 type and is limited to primary and secondary alkyl halides. Tertiary alkyl halides undergo elimination aryl and vinyl halides do not react. 

SAMPLE SOLUTION (a) Bromobenzene is an aryl halide and is unreactive toward nucleophilic substitution by cyanide ion. The route QHsBr C6H5CN C6HSC02H fails because the first step fails. The route proceeding through the Grignard reagent is perfectly satisfactory and appears as an experiment in a number of introductory organic chemistry laboratory texts. 

Benzyl cyanide is the product of nucleophilic substitution by cyanide ion on benzyl bromide or benzyl chloride. The benzyl halides are prepared by free-radical halogenation of the toluene side chain. 

Selenium.—Much of the work on selenium chemistry has come from the same laboratory that has investigated the cyanide substitutions at the polythionates. A study of nucleophilic substitution by cyanide ion at the dicyanides of sulphur and selenium in acetonitrile leads (in excess cyanide) to the di-iminosuccinonitrile dianion, [(CN)J . ... 

Section 19 12 Nitnles which can be prepared from primary and secondary alkyl halides by nucleophilic substitution with cyanide ion can be converted to car boxyhc acids by hydrolysis... 

Mescaline a hallucinogenic amine obtained from the peyote cactus has been synthesized in two steps from 3 4 5 trimethoxybenzyl bromide The first step is nucleophilic substitution by sodium cyanide The second step is a lithium aluminum hydnde reduction What is the structure of mescaline" ... 

Because nitriles can be prepaied from alkyl halides by nucleophilic substitution with cyanide ion, the overall process RX RC=N RCH2NH2 leads to primary fflnines that have one more carbon atom than the starting alkyl halide. 

Of the halogens, the fluoro-substituent is a favourite in photosubstitution (c/. Section 2). It shows a curious selectivity in that as a rule it is not easily substituted by cyanide ion, a nucleophile that functions so well with other leaving groups. 

Although the hydroxy group is a relatively poor leaving group, its base-catalyzed nucleophilic substitution by the mechanism shown in Scheme 69 accounts not only for the hydrogenolysis of the 3-hydroxymethylindoles, but also for their SN reactions with ethoxide ions, cyanide ions and with piperidine. Nucleophilic substitution on 2-hydroxymethyl-pyrroles is generally precluded by the faster formation of the bis(2-pyrrolyl)methanes, but the synthesis of 2-cyano-2-(2,5-dimethyl-3-pyrroIyl) propanes from 2,5-dimethylpyrrole, propanone and potassium cyanide probably results from an SN reaction of the cyanide ion upon the initially formed 3-pyrrolylcarbinol (81USP4248784). The formation of (294)... 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

Prunza [14], however, has proposed an ionic copper complex wltich is suitable for direct nucleophilic substitution by the cyanide ion (Equation (14)). 

Nucleophilic substitution by halide, cyanide, carbon nucleophiles, such as enamines, and acetate (by reaction with acetic anhydride), with concomitant loss of the oxide function, occur smoothly in all three systems, though the site of introduction of the nucleophile is not always that predicted by analogy with pyridine chemistry (a to the AT-oxide), as illustrated by two of the examples below. 

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