SYNTHESIS OF ETHYL 3-PHENYL-3-HYDROXYPROPANOATE

• It is essential that all the apparatus and the reagents be scrupulously dry for successful results (compare Grignard reaction). 

• Equip a 500-ml three-necked flask with a 250-ml separatory funnel, a mechanical stirrer and a double surface condenser; insert calcium chloride guard-tubes in the funnel and condenser. 

• Place 40g (0.61 mol) of zinc dust (previously dried at 100 °C) in the flask, and a solution of 83.5g (55.5 ml, 0.5 mol) of ethyl bromoacetate (1) and 65 g (62 ml, 0.615 mol) of purified benzaldehyde in 80 ml of sodium-dried benzene and 20 ml of sodium-dried ether in the separatory funnel. 

• Add about 10 ml of the solution to the zinc and warm the flask gently until the reaction starts. 

• When the reaction has commenced, but not before, stir the mixture and add the remainder of the solution at such a rate that moderate refluxing occurs (about 1 hour). 

• Reflux the reaction mixture on a water bath for a further 30 minutes. 

• Cool the flask in an ice bath, and add 200 ml of cold 10 per cent sulphuric acid with vigorous stirring. 

• Transfer to a separatory funnel, remove the aqueous layer, wash the benzene layer twice with 50 ml portions of 5 per cent sulphuric acid, once with 25 ml of 10 per cent sodium carbonate solution and finally with two 25 ml portions of water. 

• Extract the combined solutions with 100 ml of ether, and dry the combined benzene and ether solution with 5g of anhydrous calcium sulphate. 

• Filter from the desiccant, remove the solvent by distillation under atmospheric pressure and distil the residue under reduced pressure. 

• Collect the ethyl 3-phenyl-3-hydroxypropanoate at 152-154 °C/12mmHg. The yield is 60g (62%).

Notes to keep in mind:

1. Great care must be exercised in handling ethyl bromoacetate. Keep a 10 per cent aqueous ammonia solution available to react with any bromo-ester which may be spilled.

Cognate preparation: Ethyl 1'-hydroxycyclohexylacetate

• Place 65g (1 mol) of clean dry zinc dust and a few crystals of iodine in a 2.5-litre three-necked flask, equipped with an efficient reflux condenser with drying tube, a mechanical stirrer and a dropping funnel. 

• Prepare a mixture of 400 ml of sodium-dried benzene and 350 ml of sodium-dried toluene with 167g (111 ml, 1 mol) of ethyl bromoacetate and 98g (103.5 ml, 1 mol) of pure dried and redistilled cyclohexanone. 

• Transfer 150 ml of this mixture to the flask, start the stirrer and heat the flask in a boiling water bath. 

• A vigorous reaction soon sets in. Add the remainder of the mixture through the dropping funnel at such a rate that gentle refluxing is maintained. 

• Continue the stirring for an additional 2 hours: practically all the zinc dissolves. 

• Cool the mixture, add sufficient 10 per cent sulphuric acid with stirring to dissolve all the zinc hydroxide. 

• Separate the benzene-toluene layer, dry it with anhydrous sodium sulphate, remove the solvent using a rotary evaporator and distil the residue under reduced pressure. 

• Collect ethyl 1'-hydroxycyclohexylacetate at 86-89 °C/2 mmHg. The yield is 125g(67%).