SYNTHESIS OF HEXANOIC ACID

Diethyl butylmalonate

• Prepare a solution of sodium ethoxide from 34.5g (1.5 mol) of clean sodium and 1 litre of super-dry ethanol(1) in a 2-litre three-necked flask following the experimental conditions given for ethyl propylacetoacetate. 

• When the sodium ethoxide solution, which is vigorously stirred, has cooled to about 50 °C, add 247.5 g (234.5 ml, 1.55 mol) of redistilled diethyl malonate slowly through the separatory funnel; to the resulting clear solution introduce gradually (60-90 minutes) 205.5g (161.5 ml, 1.5 mol) of redistilled butyl bromide.

• Reaction occurs almost immediately and much heat is evolved; if the reaction becomes violent, cool the flask by directing a stream of cold water over it. 

• Reflux the reaction mixture on a water bath until it is neutral to moist litmus (about 2 hours). 

• Remove as much of the ethanol as possible by distillation under reduced pressure (rotary evaporator) on a water bath. 

• Cool the contents of the flask to about 20 °C, add 600 ml of water and shake well. 

• Separate the upper layer of crude ester, dry it with anhydrous sodium sulphate and distil under reduced pressure. 

• A low boiling point fraction passes over first, followed by diethyl butylmalonate at 130-135 °C/20mmHg. The yield is 285g (88%). 

• The distillation may also be conducted under normal pressure; the b.p. of the ester is 235-240 °C.

Hexanoic acid 

• Into a 2-litre three-necked flask, fitted with a separatory funnel, a mechanical stirrer and a reflux condenser, place a hot solution of 200 g of potassium hydroxide in 200 ml of water. 

• Stir the solution and add slowly 200 g (0.925 mol) of diethyl butylmalonate. 

• A vigorous reaction occurs and the solution refluxes. 

• When all the ester has been added, boil the solution gently for 2-3 hours, i.e. until hydrolysis is complete: a test portion should dissolve completely in water. 

• Dilute with 200 ml of water and distil off 200 ml of liquid in order to ensure the complete removal of the alcohol formed in the hydrolysis (2). 

• To the cold residue in the flask add a cold solution of 320g (174 ml) of concentrated sulphuric acid in 450 ml of water: add the acid slowly with stirring in order to prevent excessive foaming. 

• The solution becomes hot. 

• Reflux the mixture for 3-4 hours and allow to cool. 

• Separate the upper layer of the organic acid and extract the aqueous portion with four 150 ml portions of ether (3). 

• Combine the acid layer with the ether extracts, wash it with 25 ml of water and dry with anhydrous sodium sulphate. 

• Distil off the ether (rotary evaporator), transfer the residue to a flask fitted with a short fractionating column (the latter should be well lagged and, preferably, electrically heated) and distil the product from an air bath. 

• Collect the hexanoic acid at 200-206 °C. The yield is 80 g (75%). 

• Record the i.r. spectrum and compare it. If desired, the distillation may be conducted under reduced pressure. 

• The boiling points under various pressures are 99°C/10mmHg and 111°C/20 mmHg; a 3 °C fraction should be collected.

Notes to keep in mind:

1.  With commercial absolute ethanol, the yield is reduced to about 225 g.

2.  It is essential to remove the alcohol completely, otherwise some ethyl hexanoate, b.p. 168°C, is formed which will contaminate the final product.

3.  Better results are obtained if a continuous extraction apparatus (e.g. Fig. 2.92) is employed.

Cognate preparations: Diethyl propylmalonate

• Use 34.5 g (1.5 mol) of sodium and 345 g (440 ml) of super-dry ethanol, 240g (227.5 ml, 1.5 mol) of diethyl malonate and 185 g (136.5 ml, 1.5 mol) of propyl bromide. The yield of diethyl propylmalonate, b.p. 21 8-225 °C, mainly 219.5-221.5 °C, is 220g (72.5%).

Pentanoic acid (valeric acid)

• Convert the diethyl propylmalonate into valeric acid, b.p. 183-185 °C, following the procedure described for hexanoic acid. The yield is 75 per cent of theory.

3-Phenylpropanoic acid (hydrocinnamic acid)

• Use 1 1.5 g (0.5 mol) of sodium and 250 ml of dry ethanol, 80 g (75 ml, 0.49 mol) of diethyl malonate and 64g (58 ml, 0.51 mol) of redistilled benzyl chloride. 

• Follow the alkylation procedure described above and isolate the crude diethyl benzylmalonate. 

• Hydrolyse the latter with a solution of 75g of potassium hydroxide in 75 ml of water and isolate the resulting crude 3-phenylpropanoic acid as described previously, using 1 80 ml of 5 m sulphuric acid in the acidification stage. 

• Purify the product by distillation under reduced pressure, collecting the fraction of b.p. 164-172 °C/25 mmHg which solidifies at room temperature. 

• Recrystallise from light petroleum, b.p. 40-60 °C (or from water containing a little hydrochloric acid), to obtain 20 g (27%) of 3-phenylpropanoic acid of m.p. 47- 48 °C.

Nonanoic acid (pelargonic acid)

• Equip a 1 -litre three-necked flask with a reflux condenser, a sealed stirrer unit and a thermometer. 

• Place 23 g (1 mol) of sodium, cut in small pieces, in the flask, and add 500 ml of anhydrous butan-1-ol (1) in two or three portions: for the preparation of a solution of sodium ethoxide. 

• When the sodium has reacted completely, allow the solution to cool to 70-80 °C and add 160 g (152 ml, 1 mol) of redistilled diethyl malonate rapidly and with stirring. 

• Heat the solution to 80-90 °C, replace the thermometer with a dropping funnel and add 182.5 g (160ml, 1.02 mol) of 1-bromoheptane slowly at first until precipitation of sodium bromide commences, and subsequently at such a rate that the butanol refluxes gently. 

• Reflux the mixture until it is neutral to moist litmus (about 1 hour). 

• Transfer the entire reaction mixture, including the precipitated sodium bromide and the small volume of water used to rinse the reaction flask, to a 3-litre flask. 

• Add a solution of 140 g of potassium hydroxide in an equal quantity of water slowly and with shaking. 

• Attach a reflux condenser to the flask, introduce a few fragments of porous porcelain and heat the mixture cautiously, with occasional shaking, until refluxing commences. 

• Heat to gentle refluxing until hydrolysis is complete (about 5 hours, i.e. until a test portion is completely miscible with excess of water). 

• Immediately equip the flask for steam distillation and steam distil the mixture until no more butanol passes over. 

• Treat the residue cautiously with 270 ml of concentrated hydrochloric acid while shaking gently, and reflux the mixture for 1 hour; if sodium chloride separates as a solid cake, take care during the heating that the flask does not crack. 

• When cold, transfer the mixture to a separatory funnel and remove the oil to a 750-ml round-bottomed flask.

• Heat it under an air-cooled reflux condenser in an oil bath at 180°C until the evolution of carbon dioxide ceases (about 2 hours). 

• Decant the oil into a Claisen flask with fractionating side-arm (the latter should be well lagged) and distil under reduced pressure. 

• Collect the pelargonic acid at 1 40-1 42 °C/1 2 mmHg. The yield is 1 1 5 g (73%). 

Notes to keep in mind: 

1.  This is conveniently prepared by drying commercial butan-1-ol with anhydrous potassium carbonate or anhydrous calcium sulphate, distilling through a column and collecting the fraction, b.p. 117-118 °C.