SYNTHESIS OF 4-OXODECANOIC ACID

3-Carboxydec-3-enoic acid. (Heptylidenesuccinic acid.) Potassium t-butoxide. 

• Prepare a solution of potassium t-butoxide in t-butyl alcohol using the following procedure. 

• Equip a two-necked, round-bottomed 1-litre flask with a reflux condenser and a pressure-equalising dropping funnel. 

• Attach to the top of the condenser a nitrogen inlet system with nitrogen escape valve and place the flask in a magnetic stirrer-heating mantle unit. 

• Flush the flask with a stream of dry nitrogen, charge the flask with 375 ml of dry t-butanol and add 19.6g (0.5 mol) of potassium. 

• Heat the mixture under reflux until the potassium completely dissolves (c. 4 hours). 

• To the cooled solution add a mixture of 122g (0.7 mol) of diethyl succinate and 63g (0.5 mol) of heptanal over half an hour; the reaction is exothermic. 

• Finally heat the mixture under reflux for 1 hour. 

• Rearrange the condenser for distillation and remove the t-butyl alcohol by vacuum distillation using a water pump. 

• Acidify the residue with dilute hydrochloric acid and extract with three 200 ml portions of ether. 

• Extract the acidic compounds from the ethereal solution by shaking with 50 ml portions of saturated sodium hydrogen carbonate solution until no more carbon dioxide is evolved. 

• Acidify the combined aqueous solutions by the careful addition of concentrated hydrochloric acid. 

• Extract the 3-ethoxycarbonyldec-3-enoic acid which separates as an oil with ether, dry the ethereal extract over magnesium sulphate and evaporate the ether solution on a rotary evaporator. 

• Saponify the crude half ester by heating it under reflux for 1 hour with 400 ml of 10 per cent sodium hydroxide solution. 

• Cool the solution, acidify with concentrated hydrochloric acid and filter the precipitated acid with suction. 

• Dissolve the crude acid in the minimum volume of ether (about 200 ml are required) and add the solution to an equal volume of light petroleum (b.p. 60-80 °C). 

• Filter the precipitate with suction and recrystallise from benzene. 

• The yield of 3-carboxydec-3-enoic acid, m.p. 128-130 °C, 37.3 g (31.6%). The infrared spectrum shows absorptions at 3500-2300 cm⁻¹ (O — H stretch of carboxylic acid), 1700 cm⁻¹ (C=O) and 1640 cm⁻¹ (C=C).

3-Carboxy-3,4-dibromodecanoic acid:

• This reaction should be carried out in a fume cupboard. 

• Place 5.3g (0.025 mol) of 3-carboxydec-3-enoic acid, 6.0g (0.038 mol) of bromine and 60 ml of carbon tetrachloride in a 100 ml round-bottomed flask equipped with a magnetic stirrer and reflux condenser. 

• Irradiate the stirred mixture with a 100- watt lamp for 6 hours; the dibromide forms and precipitates out during this period. 

• Filter the product with suction and wash thoroughly with hexane. 

• The yield of 3-carboxy-3,4-dibromodecanoic acid is 7.9g (85%). The acid can be recrystallised from toluene, m.p. 142-143 °C. The infrared spectrum shows absorptions at 3400-2400 cm⁻¹ (O — H stretch of CO₂H) and 1730 cm⁻¹ (C=O).

4-Oxodecanoic acid:

• Dissolve 4.0g of 3-carboxy-3,4-dibromodecanoic acid in 60 ml of 2M sodium hydroxide solution and heat the solution at 80-90 °C for 2 hours. 

• Cool to room temperature and acidify with dilute sulphuric acid; carbon dioxide is evolved and a white precipitate is formed. 

• Filter the precipitated keto acid from the cold solution and recrystallise from light petroleum (b.p. 40-60 °C). 

• 4-Oxodecanoic acid, m.p. 68-69 °C, is obtained; the yield is 1.6g (80%). The infrared spectrum shows absorptions at 3400-2400 cm⁻¹ (OH stretch of CO₂H) and 1700 cm⁻¹ (C=0).

• If the dibromo acid is treated with alkali under milder conditions, for example with 1 m sodium hydroxide solution at 20-25 °C for 0.5 hour, the intermediate y-hexylaconic acid (m.p. 123-125 °C) can be isolated after acidification. 

• The infrared spectrum shows absorptions at 3110 cm⁻¹ (C — H stretch, alkene), 1715 and 1745 cm⁻¹ (C=O stretch of carboxylic acid and lactone) and 1630 cm (C=C stretch).

Notes to keep in mind:

1. Great care must be taken in the handling of potassium.