Silver cyanide, reaction with alkyl

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

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... 

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). 

When an alkyl halide is treated with silver cyanide, reaction takes place in the usual way a silver halide and an organic compound are formed. The product, however, is not an alkyl cyanide, as is the case when potassium cyanide is used, but an isomeric compound. The substances prepared from silver cyanide are called isocyanides, isonitriles, or carbylamines. The last name is given to them on account of the fact that they unite with acids and thus resemble the amines. The addition-products do not, however, resemble salts in their chemical properties. When hydrogen chloride is passed into an ethereal solution of methyl isocyanide, a compound of the formula 2CH3NC.3HCI is formed, which is decomposed when brought into contact with water. 

With alkali cyanides, a reaction via a SN2-mechanism takes place the alkyl halide is attacked by cyanide with the more nucleophilic carbon center rather than the nitrogen center, and the alkylnitrile is formed. In contrast, with silver cyanide the reaction proceeds by a SnI-mechanism, and an isonitrile is formed, since the carbenium intermediate reacts preferentially with the more electronegative center of the cyanide—i.e. the nitrogen (Kornblum s rule, HSAB concept). ... 

Imidazolines are also formed in silver cyanide-catalyzed cyclization of alkyl isocyanides with aliphatic diamines (Scheme 103).169 This simple synthesis can be applied in a general way with difunctional nucleophiles and has been used to prepare benzimidazoles, oxazoles, thiazoles, and oxazines.169 It is suggested that transient carbene complexes are formed in these reactions (cf. 87 in Scheme 103) but further work is required to ascertain the mechanism and scope of these processes. 

The scope of the silver cyanide-catalyzed reaction of difunctional nucleophiles with alkyl isocyanides has been described in the earlier section on imidazoles an example of the use of this simple approach in benzimidazole synthesis is illustrated in Scheme 105.169... 

As esters the alkyl halides are hydrolysed by alkalis to alcohols and salts of halogen acids. They are converted by nascent hydrogen into hydrocarbons, by ammonia into amines, by alkoxides into ethers, by alkali hydrogen sulphides into mercaptans, by potassium cyanide into nitriles, and by sodium acetate into acetic esters. (Formulate these reactions.) The alkyl halides are practically insoluble in water but are, on the other hand, miscible with organic solvents. As a consequence of the great affinity of iodine for silver, the alkyl iodides are almost instantaneously decomposed by aqueous-alcoholic silver nitrate solution, and so yield silver iodide and alcohol. The important method of Ziesel for the quantitative determination of alkyl groups combined in the form of ethers, depends on this property (cf. p. 80). 

Aromatic isocyanides can also be prepared conveniently by the dehydration of the corresponding formamides by phosphorus oxychloride, but much better results are obtained if the reaction is done in the presence of potassium fer/-butoxide rather than pyridine.6 Neither method of dehydrating formamides has yet been used to prepare methyl or ethyl isocyanide because their low boiling points make them difficult to isolate from the reaction mixture hence, until a suitable dehydration procedure is worked out, they are best made by reaction of the corresponding alkyl iodide with silver cyanide. ... 

Reactions at o -Position. Many studies have been concerned with the reactions of alkyl halides with cyanide in the presence of various metal ions, and with the direct alkylation of cyanide complexes. The classic synthesis of isonitriles was accomplished by the use of silver cyanide, whereas the corresponding reaction of organic halogen compounds with alkali cyanides yields nitriles (Equations 40 and 41) (34,36). 

Reaction XLVm. (a) Action of Alkali Cyanides on Alkyl and Acyl Halides. (Bl., [2], 50, 214.)—This reaction is capable of very wide application, all the simple alkyl halogen compounds, the acyl halides, and the halogen fatty acids come within its scope. The nitriles so formed yield acids by hydrolysis, so it is frequently the first step in the synthesis of an acid—the preparation and hydrolysis of the nitrile are often combined. The preparations of malonic, succinic, tricarballylic and other acids (Preparations 60, 61, 62) illustrate this. The extension of this reaction to acyl halides is important, and should be referred to, as should the interaction of silver cyanide, and alkyl iodides, to give isonitriles. Mercuric and silver cyanides, it may be noted, give with acyl chlorides and bromides better yields of normal acyl nitriles than do the alkali cyanides. 

Figure 5-59. The reaction of alkylating agents with potassium cyanide gives nitriles, whilst the reaction with silver cyanide gives isonitriles.

Action of Alkyl Halides and Silver Cyanide.—The compounds formed by the reaction of alkyl halides with metal cyanides exhibit a new and peculiar case of somerism. When silver cyanide, instead of potassium cyanide, acts upon an alkyl halide there is formed a compound of the same composition as methyl cyanide, viz., C2H3N, but with distinctly different properties, i.e.y an isomeric compound. It is known therefore as methyl iso-cyanide. The explanation of the isomerism of these two compounds is furnished by the character of the products which they yield when decomposed with water. We have proven that in methyl cyanide the methyl carbon atom is linked to the cyanogen carbon atom. 

To obtain isocyanides Gautier heated silver cyanide with 0.5-1.0 equivalent of alkyl iodide for several hours on a steam-bath for low-boiling alkyl iodides a pressure vessel is used. The mixture should not become brown in this reaction. The isocyanide is precipitated as a complex with silver cyanide, which, after removal of the excess of alkyl iodide by distillation, is decomposed by addition of a concentrated solution of potassium cyanide. The isocyanide can then be isolated by distillation. 

The alkylation reaction involving silver cyanide is utilized for the preparation of alkyl isocyanides, because the initially formed isocyanide complex decomposes with RNC evolution while heated with KCN ... 

There are exceptions to this rule, however, particularly when the electrons on the carbon of cyanide are tied up in a covalent bond. Both silver cyanide (AgCN) and cuprous cyanide (CuCN) have bonds between the metal and carbon (Ag-C or Cu-C) that have significant covalent character. The Ag and Cu ions are not charge dense, and they prefer to coordinate to atoms that are also not dense in charge (the C end of cyanide). If the metal-carbon bond in M-CN is covalent, the electrons on carbon are shared and less available for donation, which makes carbon less nucleophilic. In both AgCN and CuCN, the nitrogen atom is more nucleophilic and reaction with an alkyl halide R-X leads to a molecule called an isocyanide (or isonitrile, R-+N=C ). Isocyanides and the reaction of such compounds are not discussed in this hook. 

Thus the electrophiles which attack cyanide ion on nitrogen will be the harder ones, and the ones which attack on carbon will be the softer ones. This fits with the reactions illustrated above. As already seen (pp. 38-39) alkyl halides in simple Sn2 reaction are soft electrophiles thus it is appropriate for cyanide to react from the soft end of the ion (32). When a silver ion is present (other Lewis acids like zinc and mercuric ion behave similarly), the halide ion is assisted in leaving the carbon atom, and in the transition state there is now a greater development of charge on the carbon atom undergoing substitution (33). Car-bonium ions are hard electrophiles, and therefore it is again appropriate that on this occasion cyanide ion should react from the harder end of the ion. 

---