SYNTHESIS OF ISOBUTYRONITRILE (Isopropyl cyanide)

• Equip a 2-litre round-bottomed flask with a simple distillation head carrying a capillary air leak, and attach a double surface condenser fitted with a receiver adapter with vacuum connection and a 100-ml receiver flask. 

• Remove the still-head, wrap some glazed paper around a glass tube and insert it into the flask neck until the lower end enters the bulb of the flask; upon removing the glass tube, the paper roll expands and thus lines the neck of the flask. 

• Weigh out on pieces of glazed paper first 65g (0.75 mol) of 2-methyl-propanamide (isobutyramide) and then, as rapidly as possible because of its extremely hygroscopic character, 114g (0.8 mol) of phosphorus pentoxide (1). 

• Immediately transfer, with the aid of a spatula, the phosphorus pentoxide down the glazed paper cylinder into the flask, then introduce the acid amide similarly, remove the paper, stopper the flask and mix the contents well by gentle shaking (2). 

• Attach the flask to the distillation set-up and heat the flask cautiously with a luminous flame kept in constant motion and applied uniformly over the bottom of the flask. 

• A reaction accompanied by much frothing takes place. 

• After the reaction has subsided, apply the vacuum provided by a water-jet pump carefully and continue heating at such a rate that the isopropyl cyanide distils smoothly. 

• Redistil the product from 10g of phosphorus pentoxide in a flask fitted with a short Vigreux column and heated in an oil bath maintained at 145-155 °C; collect the pure product, b.p. 101-102 °C. The yield is 37g (73%).

Notes to keep in mind:

1. Phosphorus pentoxide must be treated with great care since it produces painful burns if allowed to come in contact with the skin.

2. Wet the papers thoroughly with water before throwing them away, as the residual phosphorus pentoxide may cause them to smoulder.

Cognate preparations: Hexanenitrile (pentyl cyanide)

• (Use of thionyl chloride.) Place 29g (0.25 mol) of hexanamide in a 100-ml flask fitted with a reflux condenser, add 45g (27.5 ml, 0.38 mol) of redistilled thionyl chloride and connect the top of the condenser to a gas absorption device. 

• Boil the mixture gently under reflux for 1 hour. 

• Remove the reflux condenser and arrange it for downward distillation. 

• Distil from an oil bath or an air bath; the excess thionyl chloride passes over below 90 °C. 

• If the residue at this stage is dark and contains some solid matter, add a little anhydrous ether, filter, and remove the ether on a rotatory evaporator. 

• Distil the crude hexanenitrile as a fraction of b.p. 161-163 °C. The yield is 21 g (86%). If the product is slightly turbid, shake it with a little anhydrous calcium sulphate, filter, and redistil.

General procedure for the one-pot conversion of acid chlorides into nitriles

• Heat a mixture of 0.01 mol of the acid chloride and 0.01 2 mol of sulphonamide in 10 ml of sulpholane for 3 hours at 120°C. 

• After cooling, pour the reaction mixture into 75 ml of 1 M sodium hydroxide solution and extract three times with ether-cyclohexane (1:1). 

• Wash the organic layer three times with water to remove traces of sulpholane, dry over anhydrous sodium sulphate and evaporate to give the almost pure product. 

• Distil under reduced pressure or recrystallise as appropriate.