Alkylation of silver cyanides

Silver(I) isocyanide complexes have been known for a long time and they were usually prepared by alkylation of silver cyanide.226 More recent reports include the study of steric effects of ligands... 

Methyl isocyanide has been prepared chiefly by minor modifications of the original method of Gautier,3 which is the alkylation of silver cyanide by an alkyl halide. 

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... 

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. 

Reaction CXXXTV. Action of Silver Cyanide on Alkyl Halides. 

Tautomerism.—Here as in many other instances which we shall mention we have a condition of change in the molecule so that at one time and toward certain reagents one formula is true, while at another time and toward other reagents another formula is the correct representation, This phenomenon which is not the same as isomerism is known as tautomerism. It is probable that the different products formed by the action of silver cyanide and potassium cyanide on alkyl halides (p. 68) is to be explained by tautomerism. 

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). ... 

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

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. 

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... 

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. ... 

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). 

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

Treatment of a-halo ethers with metallic cyanides such as cuprous, mercuric, or silver cyanides gives the corresponding cyano ethers the alkali cyanides are without effect. Very little of the corresponding isonitriles are encountered despite the fact that these compounds often result from the interaction of heavy-metal cyanides and alkyl halides. Generally, cuprous cyanide, the most commonly used reagent, is suspended in dry anhydrous ether or dry benzene and treated with the halo ether under gentle reflux (55-80%). 

The next class of substitution products of the saturated hydrocarbons which we shall study are those formed from the alkyl halides by the action of potassium cyanide or silver cyanide. 

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. 

Iso-nitriles, Carbylamines.— The alkyl cyanides because of tlieir relations to acids are known as acid nitriles methyl cyanide by hydrolysis yields acetic acid and it is thus known also as acetic nitrile. The iso-cyanides being isomeric with the nitriles are also termed isonitriles. Another name is sometimes used because of. their amine relationship, viz., carbyl-amine methyl iso-cyanide, CH3—NC, being methyl carbylamine. The lower alkyl-iso-cyanides are liquids with a very strong disagreeable odor. They are readily hydrolized by water but form salts with hydrochloric acid and also with silver cyanide. 

When hydrolized they yield alkyl amines in which the alkyl radical is linked to nitrogen and they may be made, as previously stated (p. 72), from the iso-cyanides through the dichloride by means of silver oxide. 

Nitro Substitution Products.—Nitric acid is HO—NO2 and nitrous acid is HO—NO. If these are reduced ammonia is the result. When the silver salt of nitrous acid acts upon an alkyl halide a reaction occurs similar to that of potassium cyanide upon the alkyl halides. 

Now while isomerism exists in the alkyl cyanogen compounds there is no isomerism in the case of either hydrocyanic acid, potassium cyanide or silver cyanide. Each of these compounds is known in only one form. 

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