Cyanides, metal, reaction with alkyl halides

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). 

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. 

Both potassium and sodium cyanide react with alkyl halides to give excellent yields of the nitrile in the solvent DMSO. When the reaction is done in refluxing alcohol or when certain other metal cyan-ides are used, an isomeric product (see 4) is often observed called an isonitrile (isocyanide). Isonitriles were first reported... 

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 ... 

Substitution reactions of cyanide with secondary alkyl halides are often accompanied by the formation of elimination products in variable amounts (Cook et al., 1974). The same holds for reactions of metal acetate complexes of crown ethers (Liotta et al., 1974). 

Alkyl halides undergo Sn2 reactions with a variety of nucleophiles, e.g. metal hydroxides (NaOH or KOH), metal alkoxides (NaOR or KOR) or metal cyanides (NaCN or KCN), to produce alcohols, ethers or nitriles, respectively. They react with metal amides (NaNH2) or NH3, 1° amines and 2° amines to give 1°, 2° or 3° amines, respectively. Alkyl halides react with metal acetylides (R C=CNa), metal azides (NaN3) and metal carboxylate (R C02Na) to produce internal alkynes, azides and esters, respectively. Most of these transformations are limited to primary alkyl halides (see Section 5.5.2). Higher alkyl halides tend to react via elimination. 

We have already learnt that alkyl halides react with alcohols and metal hydroxide (NaOH or KOH) to give ethers and alcohols, respectively. Depending on the alkyl halides and the reaction conditions, both S l and Sn2 reactions can occur. Alkyl halides undergo a variety of transformation through Sn2 reactions with a wide range of nucleophiles (alkoxides, cyanides, acetylides, alkynides, amides and carboxylates) to produce other functional groups. 

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 ... 

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

Four oxidation states of palladium are encountered in organometallic chemistry see Palladium Inorganic Coordination Chemistry) In order of importance, they are Pd , Pd , Pd, and Pd . With the reduction of palladium from Pd to Pd , the metal changes its reactivity from electrophile to nucleophile. However, unlike main group nucleophiles such as thiolates or cyanide, Pd complexes react with both alkyl halides and aryl or vinyl halides. Reactions of Pd complexes with these latter sp halides generate new Pd aryl or vinyl bonds through the process of oxidative addition. 

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. ... 

When potassium cyanide is heated with an alkyl halide, a reaction takes place that is analogous to many with which the student is familiar. The metal and the halogen unite to form a salt, and the radicals to form an organic compound —... 

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. 

The alkylation of a-cyano anions [49,50] and metal cyanides [49] with organic halides has been among the most popular methods for the preparation of nitriles. Some years ago. Brown et al. [51, 52] showed that the reaction of tri-alkylboranes with chloroacetonitrile gave the corresponding nitriles in good yields. Their results suggest that the alkylation of haloacetonitriles with orga-nometallic compounds would provide an alternative route for the preparation of nitriles by carbon-carbon bond formation. However, no related examples have been reported. 

Monomers with electron-rich double bonds produce one-to-one copolymers with monomers having electron-poor double bonds in reaction systems that also contain certain Lewis acids. These latter are halides or alkyl halides of nontransition metal elements, including AlCb, ZnCh, SnCL, BF3, AI(CH2CH3)Cl2, alkyl boron halides, and other compounds. The acceptor monomer generally has a cyano or carbonyl group conjugated to a vinyl double bond. Examples are acrylic and methacrylic acids and their esters, acrylonitrile, vinyl ketones, maleic anydride, fumaric esters, vinylidene cyanide, sulfur dioxide, and carbon monoxide. The variety of donor molecules is large and includes various olefins, styrene, isoprene, vinyl halides and esters, vinylidene halides, and allyl monomers [30]. 

Alkylthiocyanates have been prepared in higji yield by reaction of alkali metal thiocyanates with various primary and secondary alkyl halides under phase transfer conditions. Quaternary alkylammonium salts [12—14], crown ethers [15], cryptates [16], and tertiary amines [14] have all proved effective phase transfer catalysts for this reaction (Eq. 13.7 and Table 13.4). The mechanism of the thiocyanate displacement is probably similar to that of the cyanide displacement reaction (see Sect. 7.2). 

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