SYNTHESIS OF GLUTARIC ACID (Pentanedioic acid)

• In a 2-litre round-bottomed flask, equipped with a double surface condenser, place 60g (0.64 mol) of pentanedinitrile and 900 g of 50 per cent sulphuric acid (by weight). 

• Reflux the mixture for 10 hours and allow to cool. Saturate the solution with ammonium sulphate and extract with four 150 ml portions of ether; dry the ethereal extracts with anhydrous sodium sulphate. 

• Distil off the ether on a water bath; the residual glutaric acid (69g, 82%) crystallises on cooling and has m.p. 97-97.5 °C. 

• Upon recrystallisation from chloroform, or benzene, the m.p. is 97.5-98 °C.

Cognate preparations: Suberic acid (octanedioic acid)

• Heat a mixture of octanedinitrile with 15 times its weight of 50 per cent sulphuric acid by weight under reflux for 10 hours. 

• The acid crystallises out on cooling. Filter off the suberic acid upon a sintered glass funnel, and recrystallise it from acetone: m.p. 141-142 °C. The yield is 90 per cent of the theoretical.

Pimelic acid (heptanedioic acid)

• Heat a mixture of 18 g (0.148 mol) of heptanedinitrile and 250g of 50 per cent sulphuric acid by weight in a 750-ml round-bottomed flask under reflux for 9 hours. 

• Most of the pimelic acid separates from the cold reaction mixture. 

• Filter off the crystalline acid upon a sintered glass funnel. Saturate the filtrate with ammonium sulphate and extract it with three 50 ml portions of ether. 

• Dissolve the residue on the filter (which is slightly discoloured, but is fairly pure pimelic acid) in the combined ethereal extracts, dry with anhydrous sodium sulphate and remove the ether by distillation. 

• Recrystallise the residual solid acid from benzene containing 5 per cent of ether. The yield of pure pimelic acid, m.p. 105-106 °C, is 22g (93%).

Phenylacetic acid

• Into a 500-ml round-bottomed flask, provided with a reflux condenser, place 100 ml of water, 100 ml of concentrated sulphuric acid and 100 ml of glacial acetic acid: add 100g (98 ml, 0.85 mol) of benzyl cyanide. 

• Heat under reflux for 45-60 minutes; hydrolysis is then complete. 

• Pour the mixture into 2-3 volumes of water with stirring. 

• Filter the crude acid at the pump. 

• Melt the crude material under water, and wash it two or three times with small volumes of hot water; the acid solidifies on cooling. 

• Test a small portion for the presence of phenylacetamide (m.p. 155°C) by dissolving in sodium carbonate solution. 

• If a clear solution results, phenylacetamide is absent; if the solution is not clear, shake the whole of the crude product with excess of sodium carbonate solution, filter and precipitate the phenylacetic acid from the clear filtrate by the addition of dilute sulphuric acid. 

• Filter off the phenylacetic acid and recrystallise it from hot water or, better, light petroleum (b.p. 40-60 °C). The yield of pure acid, 77 °C, is 50g (43%). 

• Small quantities of acid may be recovered from the mother-liquors by extraction with ether, but this is rarely worth while. 

• Alternatively the acid may be purified by distillation under reduced pressure, b.p. 140-1 50 °C/20mmHg. The ¹³C-n.m.r. spectrum.

p-Nitrophenylacetic acid

• Prepare a dilute solution of sulphuric acid by adding 150 ml of concentrated sulphuric acid cautiously to 140 ml of water. 

• Place 50g (0.31 mol) of p-nitrobenzyl cyanide in a 500-ml round-bottomed flask, pour in about two-thirds of the sulphuric acid and shake well until all the solid is moistened with the acid. 

• Wash down any nitrile adhering to the walls of the flask into the liquid with the remainder of the acid. 

• Attach a reflux condenser to the flask and boil under reflux for 15 minutes. 

• Dilute the rather dark reaction mixture with an equal volume of cold water and cool to °C. 

• Filter with suction, and wash several times with ice-water. 

• Dissolve the solid in 800 ml of boiling water (add decolourising carbon, if necessary) and filter rapidly through a hot-water funnel supporting a fluted filter paper. 

• If any solid remains on the filter, dissolve it in the minimum volume of boiling water and filter into the main filtrate. 

• Collect the pale yellow needles of p-nitrophenylacetic acid which separate on cooling, and dry at 100 °C. The yield of acid, m.p. 151-152 °C, is 53g (95%).

Vinylacetic acid (but-3-enoic acid)

• Place 134g (161 ml, 2 mol) of allyl cyanide and 200 ml of concentrated hydrochloric acid in a 1 -litre round-bottomed flask attached to a reflux condenser. 

• Warm the mixture cautiously with a small flame and shake from time to time. After 7-10 minutes, a vigorous reaction sets in and the mixture refluxes; remove the flame and cool the flask, if necessary, in cold water. 

• Ammonium chloride crystallises out. 

• When the reaction subsides, reflux the mixture for 15 minutes. 

• Then add 200 ml of water, cool and separate the upper layer of acid. 

• Extract the aqueous layer with three 100 ml portions of ether. 

• Combine the acid and the ether extracts, and remove the ether under atmospheric pressure in a 250-ml flask fitted with a Claisen still-head and a short fractionating column: continue the heating on a water bath until the temperature of the vapour reaches 70 °C. 

• Allow the apparatus to cool and distil under diminished pressure; collect the fraction (a) distilling up to 71°C/14mmHg and (b) at 72-74 °C/14mmHg (chiefly at 72.5°C/14mmHg). A dark residue (about 10 ml) and some white solid (?crotonic acid) remains in the flask. 

• Fraction (b) weighs 100g (58%) and is analytically pure vinylacetic acid. 

• Fraction (a) weighs about 50g and separates into two layers: remove the water layer, dry the organic phase with anhydrous sodium sulphate and distil under reduced pressure; a further 15g (8.7%) of reasonably pure acid, b.p. 69-70°C/12mmHg, is obtained.