Appendix Seven
The alkyl bromides required for THC and the variants through THC-IV are all commercially available. If necessary they can be prepared by the methods described in the references given by Heilbron in the Dictionary of Organic Compounds, Oxford University press.

The sec-alkyl bromides (2-bromo-heptane or 2-bromo-octane) required for THC-V and THC-VI are also commercially available, but not so common as the others. While the chloro- compounds can usually be obtained readily, it is worthwhile from the point of view of yield to prepare the bromo- analogues. The starting materials are readily available 2-heptanol and 2-octanol, and the synthesis is one-step and simple. If necessary the alcohols can be prepared by the method of Cason and Rappoport (Reference 186 - page 323), or (Reference 417).

Example: Preparation of 2-bromo-heptane or 2-bromo-octane. Into a 1 liter Pyrex flask there is placed 1.97 moles (228 grams 2-heptanol or 255 grams 2-octanol) of the required alcohol and it is cooled to -20 deg. C. by means of a cooling bath composed of crushed ice and concentrated hydrochloric acid (dry-ice and acetone mixture can also be used but should be managed to keep the temperature at about -20 rather than the much lower temperature (-70 deg. C.) which the bath itself will attain). To the cold solution there is added with stirring over 2.5 hours dropwise from a dropping funnel 194 grams (0.72 moles) phosphorus tribromide. The temperature must be kept below -10 deg. C. throughout the addition, then is allowed to come slowly to room temperature and stand overnight. The reaction mixture is poured into 400 grams of crushed ice and the organic layer separated, washed with dilute sodium bicarbonate solution, and then distilled under water-pump reduced pressure. The yield of 2-bromo-heptane (b.p. 64-66 deg. C./ 25 mm.) is 88% of theory, or about 307 grams of colorless liquid. About the same yield of 2-bromo-octane can be expected, b.p. ?? deg, C,/ 25 mm. (References 406, 407 and 408)


Appendix Six
Appendix Eight