Alkyl cyanides reactions

The large rate enhancements observed for bimolecular nucleophilic substitutions m polai aprotic solvents are used to advantage m synthetic applications An example can be seen m the preparation of alkyl cyanides (mtiiles) by the reaction of sodium cyanide with alkyl halides... 

Hydrocarbon Gngnard reagents give the alkyl cyanides, whereas perfluo-rinated Grignard reagents produce the sulfides This reaction is useful for the preparation of alkyl perfluoroalkyl sulfides to the exclusion of di and polysulfides, which are produced by other methods... 

Acetonitrile.—The various reactions by which the nitriles or alkyl cyanides are obtained have already been mentioned m one or other of the previous notes, but they may be recapitulated. 

A common method for the preparation of alkyl cyanide 2 is the treatment of corresponding alkyl halides 1 with cyanide. The corresponding reaction with aromatic substrates is called the Rosenmund-von-Braun reaction. 

Silver cyanide, reaction with alkyl halides in synthesis of iso-cyamdes, 46, 77... 

Niobium, tris(diethyldilhiocarbamato)oxy-stereochemistry, 1,82 structure, 1, 83 Niobium, tris(oxa ato)oxy-stereochcmistry, 1, 82 Niobium, tris(phcnylcncdirhio)-structure, 1, 63 Niobium alanate, 3, 685 Niobium complexes alkyl alkoxy reactions, 2, 358 amides, 2,164 properties, 2, 168 synthesis, 2, 165 applications, 6,1014 carbamicacid, 2, 450 clusters, 3, 672,673,675 hexamethylbenzene ligands, 3, 669 cyanides synthesis, 2, 9 p-dinitrogen, 3, 418 fluoro... 

Vinylic copper reagents react with CICN to give vinyl cyanides, though BrCN and ICN give the vinylic halide instead." Vinylic cyanides have also been prepared by the reaction between vinylic lithium compounds and phenyl cyanate PhOCN." Alkyl cyanides (RCN) have been prepared, in varying yields, by treatment of sodium trialkylcyanoborates with NaCN and lead tetraacetate." Vinyl bromides reacted with KCN, in the presence of a nickel complex and zinc metal to give the vinyl nitrile. Vinyl triflates react with LiCN, in the presence of a palladium catalyst, to give the vinyl nitrile." ... 

B. From Cyano-compounds and Phosphorus(v) Halides.—Continued reports of the reactions of alkyl cyanides with phosphorus pentachloride appear. With dicyanides the formation of phosphazenes occurs via a series of intermediates whose stability varies with the nature of X ... 

The alkyl halides react with cyanide to produce alkyl cyanides. But this reaction has rarely been employed to obtain the increased length of the chain because of the long reaction times and poor yields. However, the use of DMSO as a solvent has simplified the procedure and improved the yields for the conversion of primary and secondary alkyl chlorides into cyanides, without any rearrangement. 

Silicon tetraisothiocyanate, reaction with 2,6-dimethylaniline to yield 2,6-diraethylphenyl thiourea, 46, 70 Silver cyanide, reaction with alkyl halides in synthesis of isocyanides, 46, 77... 

Addition of an alkyl nucleophile leads, due to the loss of one double bond, to a decrease of electron affinity and a concomitant negative shift of the reduction potential of about 100 to 150 mV per lost double bond. One possibility to compensate for this negative shift is the introduction of an electron-withdrawing substituent such as cyanide. Reaction of liCN or NaCN with Cjq at room temperature generates the monoadduct anion that can be quenched with various electrophiles [6]. 

The synthesis of zolpidem began with an alkylation/condensation reaction of amino-pyridine 5 and bromide 6 to give imidazopyridine 7 (Scheme 15.1). Mannich-type reaction with formaldehyde and dimethylamine provided 8. Treatment of 8 with methyliodide to form the quaternary salt 9, followed by reaction with sodium cyanide, gave 10. Acidic hydrolysis followed by reaction of the resultant acid 11 with carbonyldiimidazole (GDI) and dimethylamine afforded zolpidem (1) in 46% overall yield (George et al., 1991 Rossey and Long, 1988). 

This method has been reviewed recently (78RCR975). Alkyl cyanides are difficult to trimerize, needing both very high pressures and temperatures (Table 14). It is one of the few organic reactions which requires pressures above 1000 atm. In contrast to other nitriles, the alkyl cyanides will not trimerize in acid conditions thus in the presence of hydrogen chloride, alkyl cyanides form N-substituted amidines (73BCJ292). 

In this context it is interesting to note that benzonitrile, Ph—C=N, trimerizes to a triazine on a Raney nickel surface. It was assumed that Jt-bonded nitriles were involved in the reaction mechanism.10 This reaction resembles the well-known template synthesis of phthalocyanine complexes from phthalodinitrile. Formation of linear polymers [—C(R)—N—] occurs on heating aryl or alkyl cyanides with metal halides.11... 

Since alkyl cyanides are readily available from the interaction of alkyl halides with sodium or potassium cyanide in aqueous alcoholic solution (Expts 5.157 and 5.158), their hydrolysis to carboxylic acids is a valuable synthetic method. Aqueous alkaline or acidic conditions may be used. The reaction proceeds via the intermediate formation of an amide. Experimental conditions may be selected to interrupt the hydrolysis at the amide stage (Expt 6.167). 

Reaction conditions which are particularly applicable to aromatic nitriles involve the use of an aqueous solution of sodium hydroxide containing hydrogen peroxide, but alkyl cyanides do not always give good results the method is illustrated by the preparation of toluamide (Expt 6.167). 

An ab initio study of the. S N2 and E2 mechanisms has been performed for the reaction between the cyanide ion and ethyl chloride in dimethyl sulfoxide solution.5 Theoretical calculations have predicted a free energy barrier for nitrile formation of 24.1 kcal mol-1, close to the experimental value of 22.6 kcal mol-1 (Scheme 3). It has also been predicted that the isonitrile formation is less favorable by 4.7 kcal mol-1, while the elimination mechanism is less favorable by more than 10 kcal mol-1. These results indicated that isonitrile formation and bimolecular elimination are not significant side-reactions for primary alkyl chloride reactions. 

Alkyl halides react with nucleophiles, reagents that can supply an electron pair to form a covalent bond, to give a product in which the nucleophile takes the place of the halogen. Table 6.1 gives fifteen examples of such nucleophilic substitution reactions, which can be used to convert alkyl halides to alcohols, ethers, esters, amines, thiols, alkyl cyanides, or acetylenes. 

Walton, R. A. The Reactions of Metal Halides with Alkyl Cyanides. Quart. Rev. 19, 126 (1965). 

In a variation of the Gatterman reaction an alkyl cyanide RCN is used in place of HCN as a useful way of preparing ketones from reactive aromatic species that do not react well under Friedel-Crafts conditions. The electrophile involved is effectively R—C NH+, although, perhaps, the imino chloride, R(C NH)C1, the analogue of an acyl chloride, RCOCl, is also involved. As in the Gatterman reaction, the imine is an intermediate. 

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