SYNTHESIS OF RESOLUTION OF (±)-OCTAN-2-OL*

• Heat a mixture of 65g (0.5 mol) of dry octan-2-ol (b.p. 178-180°C), 74g (0. 5 mol) of pure phthalic anhydride (1) and 40g of dry pyridine (CAUTION) on a water bath for 1 hour, and allow to cool. 

• Dissolve the resulting viscous mass in an equal volume of acetone. 

• Add slowly, preferably with stirring, 55 ml of concentrated hydrochloric acid diluted with an approximately equal volume of crushed ice: if an oil separates before all the hydrochloric acid has been added, introduce more acetone to render the mixture homogeneous. 

• Add ice-water until the oil is completely precipitated; this usually sets to a hard mass within 1-2 hours. 

• If the resulting mass is semi-solid or pasty (2), transfer it to a large flask and pass steam through it until the octan-2-one is removed, i.e. until the steam distillate is clear; pour the contents of the flask while still warm into a beaker. 

• The (±)-2-octyl hydrogen phthalate solidifies on cooling. 

• Filter the octyl hydrogen phthalate at the pump, wash it with water, grind it thoroughly in a mortar with water, filter again and dry in the air. 

• The crude material is quite satisfactory for the subsequent resolution (3). 

• Introduce 197g (0.5 mol) of anhydrous brucine (CAUTION: poisonous) or 215g of the air-dried dihydrate (4) into a warm solution of 139g of (±)-2-octyl hydrogen phthalate in 300 ml of acetone and warm the mixture under reflux on a water bath until the solution is clear. 

• Upon cooling, the brucine salt [(+)-A, (—)-B] separates as a crystalline solid. 

• Filter this off on a sintered glass funnel, press it well to remove mother-liquor and wash it in the funnel with 123 ml of acetone. 

• Set the combined filtrate and washings (W) aside. 

• Cover the crystals with acetone and add, slowly and with stirring, a slight excess (to Congo red) of dilute hydrochloric acid (1:1 by volume; about 60 ml); if the solution becomes turbid before the introduction of the acid is complete, add more acetone to produce a clear liquid. 

• Add ice-water until the precipitation of the active 2-octyl hydrogen phthalate [crude (+)-A] is complete; filter (5), wash with cold water and dry in the air. 

• The yield is about half that of the (±)-ester originally taken (6). 

• Concentrate the combined filtrate and washings (W) to about half the original volume, and pour it into slightly more than the calculated amount of dilute hydrochloric acid (use a mixture of 30 ml of concentrated hydrochloric acid and 30 ml of ice-water); then add about 300 ml of water. 

• Collect the active 2-octyl hydrogen phthalate (crude(—)-A) as above (5). 

• The weight of the air-dried ester is about half that of the (±)-ester originally used (7). 

• Crystallise the two lots of crude active 2-octyl hydrogen phthalates separately twice from 90 per cent acetic acid; use 2g of acetic acid to each gram of solid. 

• The recrystallised esters, if optically pure (8), will melt sharply at 75 °C; if the melting points are below 75 °C, further recrystallisation is necessary. 

• The yields of optically pure products, m.p. 75 °C, are 48g and 49g respectively. To obtain optically pure (+)- and (—)-octan-2-ol, steam distil the respective esters with 30 per cent sodium hydroxide solution; use the proportions 1 mol of ester to 2 mols of sodium hydroxide. 

• Separate the alcohols from the steam distillate, dry over anhydrous potassium carbonate and distil under diminished pressure. 

• Both samples boil at 86 °C/20 mmHg (9) and have the following rotations:

• The yields from the 2-octyl hydrogen phthalates are almost quantitative.

Notes to keep in mind:

1. If the presence of phthalic acid is suspected, it may be readily removed by mixing with cold chloroform; phthalic anhydride dissolves readily, but the acid is insoluble.

2. This is due to octan-2-one in the original octan-2-ol; it is most easily separated by steam distillation as described.

3. The inactive 2-octyl hydrogen phthalate may be recrystallised from light petroleum, b.p. 60-80 °C, or from glacial acetic acid, and then melts at 55 °C. If the octan-2-ol is pure, the yield of pure material is almost quantitative.

4. Commercial brucine is usually the tetrahydrate C₂₃H₂₆O₄N₂, 4H₂O; upon air drying, this loses two molecules of water of crystallisation and passes into the dihydrate.

5. The filtrates from the decomposition of the brucine salts with dilute hydrochloride acid should be carefully preserved. The brucine is recovered by the addition of an excess of dilute ammonia solution (1:4); if the solution becomes turbid before all the ammonia solution is added, introduce a little ethanol until the solution becomes clear. After several hours in an open beaker, filter off the brucine, wash it well with cold water and dry it in the air.

6. The rotation in absolute ethanol is about [𝜶]ᴅ +44°, [𝜶]₅₄₆₁ +47°.

7. The rotation in absolute ethanol is about [𝜶]ᴅ -44°,  [𝜶]₅₄₆₁ -47°.

8. The optically pure esters have rotations in ethanol of [𝜶]ᴅ —48.4°, [𝜶]₅₄₆₁ —58.5°, and [𝜶]ᴅ +48.4°, [𝜶]₅₄₆₁ +58.5° respectively. A preliminary check of the optical purity is, however, more simply made by a m.p. determination; the rotation is determined, if desired, when the m.p. is 75 °C.

9. The boiling point under atmospheric pressure is 179 °C.