SYNTHESIS OF 2-CHLOROHEXANOYL CHLORIDE

• Hexanoic acid (11.6g, 0.1 mol) and thionyl chloride (28.8ml, 0.4mol) are placed in a 250-ml flask equipped with a magnetic stirrer bar and a condenser with a drying tube. 

• The reaction mixture is stirred and heated in a 70 °C oil bath. 

• After 0.5 hour, a portion of the reaction mixture is submitted to p.m.r measurement, which shows the disappearance of the triplet at 𝛅2.40 (-CH₂·CO₂H) and the emergence of a new triplet at 𝛅2.87 (-CH₂COCl). 

• The flask is removed from the oil bath and cooled to room temperature. 

• To the reaction mixture are added successively finely powdered N-chlorosuccinimide (26.7g, 0.2 mol), thionyl chloride (20 ml) and concentrated hydrochloric acid (7 drops). 

• The flask is then returned to the oil bath, the temperature of which is raised to 85 °C. 

• The actual temperature of the reaction mixture is 70 °C. 

• After 1.25 hours, the reaction is over, as indicated by the disappearance of the triplet at 𝛅2.87 and the emergence of two doublets at 4.77-4.55(-CHC1ᐧCOC1). 

• The solvent is removed under reduced pressure and the solid (succinimide) is collected and washed with tetrachloromethane. 

• The filtrate is fractionally distilled to give 14.7g (87%) of product, b.p. 174-176 °C/760 mmHg; n 1.4458; i.r. (neat) 1787 vs, 1721 cm⁻¹ (shoulder); p.m.r. spectrum (neat, TMS) 𝛅4.51 (d of d, 1H, J = 5.5 and 6 Hz, —CHClᐧCOCl); m/z 170, 168 (M), 135, 133 (M - CI), 41 (base peak, CH=C=0).

Conversion into 2-chlorohexanamide

• The foregoing compound (0.8g, 4.7 mol) is dissolved in anhydrous ether (10 ml) and held at 10 °C while bubbling dry ammonia into the stirred solution until there is a basic reaction to pH paper (10 minutes). 

• Ether is evaporated, and the white precipitate (0.7g, quantitative yield) is washed with ice-cold water, then sublimed at 30 °C/ 0.05 mmHg; m.p. 56-57 °C.

Cognate preparations: 2-Bromohexanoyl chloride and 2-bromohexanoic acid

• A mixture of hexanoic acid (11. 6g, 0.1 mol), tetrachloromethane (10ml) and thionyl chloride (28.8 ml, 0.4 mol) is stirred at 65 °C for 0.5 hour. 

• N-Bromo-succinimide (21.4g, 0.12 mol), etrachloromethane (50 ml) and 48 per cent hydrobromic acid (7 drops) are added to the mixture. 

• The flask is heated at 70 °C for 10 minutes, then at 85 °C for 1.5 hours. 

• After work-up and fractional distillation in vacuo, 2-bromohexanoyl chloride is obtained as a clear, slightly yellow oil (17.1g, 80%), b.p. 44-47 °C/ 1.5 mmHg. 

• Hydrolysis to the acid is achieved by treating its acetone solution (92 ml) with 115 ml of a saturated sodium hydrogen carbonate solution (c. 115mmol) at 10°C. 

• After acidification with concentrated hydrochloric acid, extraction with chloroform, and drying over magnesium sulphate, the solvent is removed in vacuo to give a colourless liquid [9.36 g, 99.5% yield, 96% pure by g.l.c. (SE-30 column)]. 

• Fractional distillation gives 7.76 g (83%) of 2-bromohexanoic acid, b.p. 64-66°C/0.075mmHg, which is homogeneous by g.l.c.

2-Iodohexanoyl chloride

• Hexanoic acid (11.6g, 0.1 mol), resublimed iodine (15.23g, 0.12g-atom) and thionyl chloride (40 ml, 0.55 mol) are placed in a round-bottomed flask equipped as previously. 

• The mixture is stirred and the heating bath adjusted to 130 °C. 

• When the reflux is steady, the actual temperature of the reaction mixture is 85 °C. 

• The reaction was complete after 1.5 hours, as indicated by p.m.r. measurement which was performed and analysed in the same way as with previous experiments. 

• Thionyl chloride is evaporated under reduced pressure; excess iodine is filtered and washed with tetrachloromethane. 

• The filtrate is shaken with concentrated sodium thiosulphate solution to remove the remaining iodine. 

• The organic layer is separated and dried over magnesium sulphate. 

• After solvent evaporation, the product is distilled to yield 21g (80%) of 2-idohexanoyl chloride, b.p. 62-63°C/0.5mmHg;nᴅ²¹ 1.5179.