SYNTHESIS OF HEPTYLAMINE

Heptaldoxime:

• Fit a 1-litre three-necked flask with an efficient mechanical stirrer, a double surface condenser and a thermometer. 

• Place 115g (141ml, 1.25 mol) of heptanal (1) and a solution of 87g of hydroxylamine hydrochloride in 150 ml of water in the flask, and stir the mixture vigorously (2).

• Introduce, from a separatory funnel down the reflux condenser, a solution of 67g (0.63 mol) of anhydrous sodium carbonate in 250 ml of water at such a rate that the temperature of the reaction mixture does not rise above 45 °C. 

• Continue the stirring for 1 hour at room temperature. 

• Separate the upper layer and wash the oil with two 25 ml portions of water; dry with magnesium sulphate. 

• Distil from a flask fitted with a short fractionating column. 

• A small fraction of low boiling point (containing heptanenitrile and heptaldoxime) passes over first, and as soon as the temperature is constant the heptaldoxime is collected (e.g. at 103-107 °C/6mmHg); the temperature of the oil bath is maintained at about 30 °C above the boiling point of the liquid. 

• The yield is about 110g, and the liquid slowly solidifies on cooling and melts at 44-46 °C; it is sufficiently pure for conversion into heptylamine. 

• If required pure, the heptaldoxime may be recrystallised from 60 per cent ethanol (25g of solid to 70 ml of solvent) and then melts at 53-55 °C (the m.p. depends somewhat upon the rate of heating).

Heptylamine:

• In a 3-litre round-bottomed flask, equipped with two large Liebig condensers (34/35 joints) joined in series, place a solution of 64.5g (0.5 mol) of heptaldoxime in 1 litre of super-dry ethanol and heat on a water bath. 

• Immediately the alcohol boils, remove the flask from the water bath and introduce 125g (5.4 mol) of sodium, cut in small pieces, as rapidly as possible through the condenser consistent with keeping the vigorous reaction under control. 

• The last 30g of sodium melts in the hot mixture and may be added very rapidly without appreciable loss of alcohol or of amine. 

• As soon as the sodium has completely dissolved (some warming may be necessary), cool the contents of the flask and dilute with 1250 ml of water. 

• At once equip the flask with a condenser set for downward distillation and arrange for the distillate to be collected in a solution of 75 ml of concentrated hydrochloric acid in 75 ml of water contained in a 3-litre flask. 

• Continue the distillation as long as amine passes over. 

• Towards the end of the reaction considerable frothing sets in; then add a further 750 ml of water to the distillation flask. 

• The total distillate is 2-2.2 litres and contains alcohol, water and some unreacted oxime as well as the amine hydrochloride. 

• Evaporate the solution under reduced pressure using a rotary evaporator; the amine hydrochloride will crystallise out in the flask. 

• Cool the flask, attach a reflux condenser and introduce 250 ml of 40 per cent potassium hydroxide solution. 

• Rotate the flask to wash down the hydrochloride from the sides of the flask, cool the mixture to room temperature and transfer it to a separatory funnel. 

• Run off the lower alkaline layer and add solid potassium hydroxide to the amine in the funnel. 

• Again remove the lower aqueous layer, add more solid potassium hydroxide and repeat the process until no further separation of an aqueous layer occurs. 

• Finally, transfer the amine to a small flask and leave it in contact with potassium hydroxide pellets for 24 hours. 

• Decant the amine into a flask and distil through a well-lagged fractionating column. Collect the heptylamine at 153-157 °C. The yield is 40g (70%).

Notes to keep in mind:

1. The heptanal should be dried and redistilled: b.p. 150-156 °C or 54-59 °C/ 16mmHg.

2. The solution may be rendered homogeneous by the addition of ethanol but the yield appears to be slightly diminished and more high boiling point material is produced.

Cognate preparation: Hexyl methyl ketoxime

• From hexyl methyl ketone (octan-2-one) in 90 per cent yield; b.p. 106-108 °C/12 mmHg.

1-Methylheptylamine:

• Reflux a solution of 50g (0.35 mol) of the oxime in 200 ml of super-dry ethanol on a water bath while adding 75g (3.25 mol) of sodium; introduce more alcohol (about 300 ml) to maintain a vigorous reaction. 

• When all the sodium has passed into solution, cool, dilute with 250 ml of water and distil gently until the b.p. reaches 96 °C; add a further 200 ml of water and repeat the distillation to ensure the complete removal of the alcohol. 

• The amine remains as a layer on the strongly alkaline solution: extract it with ether, dry the ethereal solution with sodium hydroxide or anhydrous calcium sulphate, remove the ether on a water bath, and distil the residue under diminished pressure. 

• Collect the 1-methylheptylamine at 58-59 °C/13 mmHg; the b.p. under atmospheric pressure is 163-164 °C. The yield is 31g (69%).