Alkyl Chlorides to Nitriles in DMSO

Chain extension by means of the reaction of alkyl halides with cyanide is frequently alluded to but rarely employed, mainly because of the long reaction times and poor yields usually encountered. The use of DMSO as a solvent has greatly simplified the procedures and improved the yields of many ionic reactions, and the conversion of alkyl chlorides to nitriles is a good example. 

DMSO is dried over calcium hydride and distilled, bp 64°/4 mm, before use. Sodium cyanide is dried at 110° for 12 hours and stored in a tightly stoppered bottle. 

Primary Chlorides Dry sodium cyanide (30 g, 0.61 mole) is added to 150 ml of dimethyl sulfoxide in a flask fitted with a stirrer, reflux condenser, dropping funnel, and thermometer. The thick slurry is heated on a steam bath to 90° and the steam bath is then removed. The halide (0.5 mole of monochloride or 0.25 mole of dichloride) is slowly added to the stirred mixture, causing the temperature to increase immediately. The rate of addition should be adjusted so that the temperature of the reaction does not go above about 160°. After all the halide is added (about 10 minutes) the mixture is stirred for 10 minutes more, or until the temperature drops below 50°. In the preparation of mononitriles, the reaction mixture is then poured into water, and the product is extracted with chloroform or ether. The extract is washed several times with saturated sodium chloride solution then dried over calcium chloride, and the product is distilled. 

With dinitriles a slightly different procedure is necessary due to their water solubility. After the reaction has cooled, 150 ml of chloroform is added to the flask, and this mixture is then poured into saturated salt solution. Enough water is added to dissolve precipitated salt and the chloroform layer is separated. The aqueous layer is extracted once with chloroform. The combined extracts are then washed twice with salt solution, dried, and distilled. 

Secondary Chlorides With a low-boiling chloride such as 2-chlorobutane, a stirred slurry of 30 g (0.61 mole) of sodium cyanide in 150 ml of dimethyl sulfoxide is heated to 90° with a heating mantle, and 0.5 mole of the chloride is slowly added over a period of 30 minutes. The temperature of the refluxing reaction mixture slowly increases as nitrile is formed. Refluxing continues as the temperature slowly rises to 150° after 3 hours reaction time. The flask is then cooled and the reaction mixture is worked up in the same way as for the primary nitriles. With 2-chlorooctane, the sodium cyanide-dimethyl sulfoxide slurry is heated to 130° and 0.5 mole of the chloride added. The reaction mixture is maintained at 135-145° for 1 hour, then cooled, and the product is isolated as above. Examples are given in Table 16.1. 

---