From metal cyanides alkylation

Alkylation of Alkali Metal Cyanides by Alkyl Halides Activated in the a-Posi-tion by a Double Bond. When a mixture consisting of 4 to 8 moles of an alkyl halide activated in the apposition by a double bond is heated with 1 mole of alkali metal ferrocyanide, several alkylation products of the ferrocyanide anion can be isolated from the reaction mixture (12). The relative proportions of the tetra-, penta-, and hexaalkylated complexes can be varied by varying the alkyl halide to ferrocyanide ratio and the time of reaction. When potassium ferrocyanide is alkylated with benzyl bromide at a ratio of 4 alkyl halides to ferrocyanide anion, short reaction times favor the tetraalkylated complex an 8 to 1 ratio and long reaction times favor the hexaalkylated complex of the alkylating agents tested benzyl bromide provided the fastest alkylation ... 

In the reaction of butyllithium or lithium di-isopropylaminc with the Mannich bases derived from hydrogen cyanide, phosphine oxides, and phosphorous esters, as well as from phenols, jhc metal atom is prevalently bound to the CH2—N moiety (313 in big. 119, route b). This intermediate is then allowed to react with halides, epoxides, and other alkylating reagents in order to link an alkyl group to methylene. Under proper conditions, aldehydes, ketones and enamines can be prepared by this method. 

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 transformation of alkyl halides into alkanenitriles with cyanide ions has frequently been carried out in protic solvents such as methanol or ethanol, sometimes with the addition of water or acetone, and often at elevated temperatures. Under these conditions reaction rates decrease in the order iodides, bromides, chlorides, as would be expected. Accordingly iodide ions have a catalytic effect and increase reaction rates. The use of anhydrous ethylene glycol or di- and poly-ethylene glycols and their corresponding ethers allows the use of higher temperatures, which means better solubility of the alkali metal cyanides. There is probably additional help from the extensive solvation of the countercations by some of these hydroxy polyethers. While for primary halides yields for nitriles range up to 90% (Table 1), they drop sharply with secondary and tertiary halides. ... 

Table 8.1. Preparation of isonitriles from alkyl halides and metal cyanides.

As can be seen from the structures shown, A,jV-dimethyl-0-(methylsulfonyl)hydroxylainine (1) aminates alkyl Grignard compounds (to give 3) and aryl Grignard compounds (to give 4) with moderate yields. The same is true for benzylic anion type carbon atoms (5-9). Compounds (10) and (11) are formed from the corresponding malonates, while (12)-(16) are derived from (es-ter)enolates, although with aryl-stabilized anionic carbon atoms. Metalated cyanides lead to (17)-(19). 

Reaction with Alkynes. The silyl cuprate reacts with alkynes by syn stereospecific metallo-metallation (eq 3). Provided that the cuprate is derived from copper cyanide, the regioselectivity with terminal alkynes is highly in favor of the isomer with the sUyl group on the terminus. The intermediate vinyl cuprate (3) reacts with many substrates, familiar in carbon-based cuprate chemistry, to give overall syn addition of a silyl group and an electrophile to the alkyne. A curious feature of this reaction is that the intermediate (3), although uncharacterized, has the stoichiometry of a mixed silicon-carbon cuprate, and yet it transfers the carbon-based group to most substrates, in contrast to the behavior of mixed silyl alkyl cuprates. 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

Of the synthetic reactions of the alkyl halides that with potassium cyanide, which enabled H. Kolbe to synthesise acetic acid from a methane derivative, has already been mentioned (cf. the preparations on pp. 137 and 254). Of the simpler syntheses that of Wiirtz may be mentioned here. Metallic sodium removes the halogen from two molecules and the two radicles combine. Thus, in the simplest case, ethane is formed from methyl bromide ... 

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... 

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). 

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