SYNTHESIS OF 3-METHYLBUTAN-2-OL (secondary alcohol from an aldehyde)

• Prepare a solution of isopropylmagnesium bromide from 37.5 g (1.54 mol) of magnesium turnings and 185 g (142 ml, 1.50 mol) of isopropyl bromide in 200 ml of anhydrous ether; use a 1-litre flask, and follow the broad experimental details given in the Cognate Preparations. 

• Cool the resulting Grignard reagent to — 10 to — 5 °C in a freezing mixture of crushed ice and anhydrous calcium chloride. 

• Remove the separa­tory funnel and re-attach to the flask via a two-necked adapter to allow the introduction of a thermometer for monitoring the reaction temperature. 

• Add a solution of 67 g (83.5 ml, 1.53 mol) of freshly distilled acetaldehyde (b.p. 20.5-21 °C) in 90 ml of anhydrous ether over a period of 30 minutes. 

• Do not allow the temperature to rise above — 5 °C. 

• When all the acetaldehyde has been added, pour the reaction product upon 700 g of crushed ice; any excess of magnesium should remain in the flask. 

• Dissolve the basic magnesium bromide by the addition of 350 ml of 15 per cent sulphuric acid. 

• Separate the ethereal solution and extract the aqueous layer with four 50 ml portions of ether. 

• Dry the combined ethereal solutions over 8 g of anhydrous potassium carbonate (or the equivalent quantity of anhydrous calcium sulphate), and fractionally distil through an all-glass Dufton (or other efficient fractionating) column. 

• Collect the 3-methylbutan-2-ol at 110-111.5 °C. 

• The yield is 70 g (52%). The '³C-n.m.r. absorption (CDC1₃, TMS) occur at 6 18.2 (Me₂), 19.9 (C₁), 35.2 (C₃) 72.5 (C₂).

Cognate preparation: Nonan-5-ol (secondary alcohol from ethyl formate)

• Prepare a solution of butylmagnesium bromide from 12.2 g (0.50 mol) of magnesium turnings, 69 g (54 ml, 0.50 mol) of butyl bromide and 250 ml of dry ether in a 1-litre flask. 

• Cool the flask containing the resulting Grignard reagent in an ice bath. 

• Place a solution of 18.5 g (20 ml, 0.25 mol) of pure ethyl formate (Expt 5.143) in 40 ml of anhydrous ether in the separatory funnel. 

• Stir the solution of the Grignard reagent and run in the ethyl formate solution at such a rate that the ether refluxes gently (10-15 minutes). 

• Remove the ice bath and continue the stirring for 10 minutes.

• Place 35 ml of water in the separatory funnel and run it into the vigorously stirred reaction at such a rate that rapid refluxing occurs. 

• Follow this by a cold solution of 15.5 ml of concentrated sulphuric acid in 135 ml of water. 

• Two practically clear layers will now be present in the flask. Decant as much as possible of the ethereal layer (A) into a 500-m1 round-bottomed flask.

• Transfer the remainder, including the aqueous layer, into a separatory funnel: wash the residual solid with two 10 ml portions of ether and combine these washings with the liquid in the separatory funnel. 

• Separate the ethereal por­tion and combine it with (A). 

• Distil off the ether through an efficient fraction­ating column until the temperature of the vapour rises to about 50 °C. 

• The residual crude nonanol contains a little of the corresponding formic ester. Remove the latter by refluxing for 3 hours with 25 ml of 15 per cent aqueous potassium hydroxide, and then isolate the purified nonanol by steam distilla­tion (volume of distillate about 500 m1). 

• Separate the upper layer of the secondary alcohol, dry it over anhydrous potassium carbonate or anhydrous calcium sulphate, and distil from a flask carrying a Claisen still-head under reduced pressure. 

• Collect the pure nonan-5-ol at 97-98 °C/20 mmHg; the yield is 30 g (83%). 

• The boiling point under atmospheric pressure is 195 °C.