SYNTHESIS OF HEXAN-2-ONE (Butyl methyl ketone)

• Fit a 2-litre three-necked flask with an efficient double surface condenser and a separatory funnel; close the central neck with a stopper. 

• The apparatus must be perfectly dry. 

• Place 34.5 g (1.5 mol) of clean sodium cut into small pieces in the flask and clamp the flask by the wide central neck. 

• Measure out 1 litre of super-dry ethanol, and place about 500 ml in the separatory funnel; insert calcium chloride guard-tubes at the top of the condenser and the separatory funnel respectively. 

• Place a large bowl beneath the flask and have a large wet towel in readiness to control the vigour of the subsequent reaction. 

• Run in about 200 ml of the absolute ethanol on to the sodium (1); a vigorous reaction takes place. If the ethanol refluxes violently in the condenser, cool the flask by wrapping it in the wet towel and also, if necessary, run a stream of cold water over it. 

• As soon as the reaction moderates somewhat, introduce more alcohol to maintain rapid, but controllable, refluxing. 

• In this manner most of the sodium reacts rapidly and the time required to produce the solution of sodium ethoxide is considerably reduced. 

• Finally add the remainder of the ethanol and reflux the mixture on a water bath until the sodium has reacted completely. 

• Remove the stopper in the central neck and introduce a sealed mechanical stirrer. 

• Add 195 g (190 ml, 1.5 mol) of pure ethyl acetoacetate, stir the solution and heat to gentle boiling, then run in 205 g (1 51 ml, 1.66 mol) of propyl bromide over a period of about 60 minutes. 

• Continue the refluxing and stirring until a sample of the solution is neutral to moist litmus paper (6-10 hours); the reaction is then complete. 

• Cool the mixture and decant the solution from the sodium bromide; wash the salt with two 20 ml portions of absolute ethanol and add the washings to the main solution. 

• Distil off the ethanol, which contains a slight excess of propyl bromide, through a short fractionating column from a water bath. 

• The residue (A) of crude ethyl propylacetoacetate may be used directly in the preparation of hexan-2-one. 

• If the fairly pure ester is required, distil the crude product under diminished pressure and collect the fraction boiling at 109-113°C/27mmHg (183 g, 71%) (B).

• To prepare hexan-2-one add the crude ester (/I) or the redistilled ethyl propylacetoacetate (B) to 1500 ml of a 5 per cent solution of sodium hydroxide contained in a 4-litre flask equipped with a mechanical stirrer. 

• Continue the stirring at room temperature for 4 hours; by this time the mono-substituted acetoacetic ester is completely hydrolysed and passes into solution. 

• Transfer the mixture to a large separatory funnel, allow to stand and remove the small quantity of unsaponified material which separates as an upper oily layer. 

• Place the aqueous solution of sodium propylacetoacetate in a 3-litre two-necked flask fitted with a small separatory funnel and a wide bent delivery tube connected to a condenser set for downward distillation. 

• Add 150 ml of 50 per cent by weight sulphuric acid (d. 1.40) slowly through he separatory funnel with shaking; a vigorous evolution of carbon dioxide occurs. 

• When the latter has subsided, heat the reaction mixture slowly to the boiling point and distil slowly until the total volume is reduced by about one-half; by this time all the hexan-2-one should have passed over. 

• The distillate contains the ketone, ethanol and small quantities of acetic and valeric acids. 

• Add small portions of solid sodium hydroxide to the distillate until it is alkaline and redistil the solution until 80-90 per cent has been collected; discard the residue. 

• Separate the ketone layer from the water, and redistil the latter until about one-third of the material has passed over. 

• Remove the ketone after salting out any dissolved ketone with potassium carbonate (2). 

• Wash the combined ketone fractions four times with one-third the volume of 35-40 per cent calcium chloride solution in order to remove the alcohol. 

• Dry over 15 g of anhydrous calcium chloride; it is best to shake in a separatory funnel with 1- 2g of the anhydrous calcium chloride, remove the saturated solution of calcium chloride as formed, and then allow to stand over 10 g of calcium chloride in a dry flask. 

• Filter and distil. 

• Collect the hexan-2-one at 126-128 °C. The yield is 71 g (67%).

Notes to keep in mind:

1.  The addition of the ethanol to the sodium, although attended by a very vigorous reaction which must be carefully controlled, is preferable to the reverse procedure of adding the sodium in small pieces to the ethanol. The latter method is longer and has the further disadvantage that it necessitates frequent handling and exposure to the air of small pieces of sodium.

2.  A more complete recovery of the ketone from the aqueous solution may be obtained by repeated distillation of the aqueous layer until no appreciable amount of ketone is found in the distillate. The procedure outlined is, however, quite satisfactory.

Cognate preparation: Heptan-2-one

• Use 34.5 g (1.5 mol) of sodium, 1 litre of super-dry absolute ethanol, 195 g (1.5 mol) of redistilled ethyl acetoacetate and 225 g (177 ml, 1.63 mol) of dry Butyl Bromide. This yields 280 g of crude or 200 g (72%) of pure ethyl butylacetoacetate, b.p. 1 1 2-1 1 6 °C/ 16mmHg. Upon hydrolysis 105g (80%) of heptan-2-one, b.p. 149-151 °C, are isolated.