Hydroxy halides, alkylation reaction, with alkali

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. ... 

In the alkyl chain hydroxy groups or side chains may be present. The reaction is somewhat different when acyl halides are used. Hydroxymethanediphosphonic acid is prepared by reacting phosgene with an alkali metal, dialkyl phosphite. The reaction is rapid and exothermic. The temperature is controlled between 10 and 20°C. After hydrolysis with HC1, hydroxymethanediphosphonic acid is recovered [91,92]. 

Even in the strong alkali that favors this reaction, very little of the arsenite will be as the trianion nevertheless, there is evidence that it is this form that is responsible for the reaction (104). The insolubility of many alkyl halides in the necessarily aqueous solution of strong alkali is a limitation on this, so ways around must be found. Further, the R group of R—X should not carry a nucleophilic atom on C-4 or C-5, or else it will attack C-l with expulsion of halide and cyclization. This includes a hydroxy group, since it will be in the nucleophilic -0 form in the alkaline conditions. 

---