Appendix Twelve
Other routes to 5-(alkyl)-resorcinols include proceeding through the 3,5-dinitro-(alkyl)-benzenes and stepwise reduction (Musso; Berichte 98, page 2790, 1965). It is also possible to proceed through the 5-(alkyl)-dihydroresorcinol (Cyclohexanedione-1,3j. See Deorha (Berichte 98, page 1722, 1965), Anker and Cook (J.C.S. page 311, 1945), Shirley (Preparation of Organic Intermediates. page 240, 1951), Boudakian (Chemical abstracts 57, page 16459h), Adams (J.A.C.S. 62, page 2204, 1940), Korte (Liebigs Annalen, 630, page 71, 1960), Mosby (Chemistry and Industry, page 1348, October, 1959). In another preparation 3,5-dimethoxy-benzoic acid has been converted to the benzaldehyde and reacted with an alkyl bromide to give the 3,5-dimethoxy-alkyl benzene (Wenkert; J. Organic Chemistry, 29, pages 437-8, 1964). This route may also be possible using the gallic acid derivative and the resulting 3,4,5-trimethoxy-(alkyl)-benzene can be demethylated in the 4-position with sodium and alcohol, just as when reducing the trimethoxy ketone with these reagents (Asahina Berichte 68B, page 1500, 1935, Asahina Berichte 69B, page 1643, 1936).

Of the above methods, that through the nitro- compound may be of particular value for large-scale preparations (the analogue orcinol, 3,5-dimethoxy-toluene, is prepared commercially by this route. The method through 5-(alkyl)-dihydroresorcinol has also been developed extensively, not only for THC, but also for THC-V. Examination of these references indicates that good results can be obtained by these methods comparable to the route described in detail in this paper. Thus, THC and the variants are available from a wide choice of reactions and raw materials.

For the preparation of 3,4,5-trimethoxy-benzaldehyde garlic acid can be used, through methylation, conversion to benzoyl, chloride, then Rosenmund Reduction (see Huang; J.A.C.S. 70, page 4181, 1948). Or the flavoring agent vanillin can be used (see Pepper; Canadian J. Chem. 31, page 476, 1953: Pearl; J.A.C.S. 74, page 4262, 1952). The required 5-iodo-vanlllin can be prepared by Erdtman (Chem. Abs. 30, page 449, 1936: or in better yield by Thorn; Can. J. Chem. 32, page 385, 1954). '"Gold" paint pigment is a satisfactory copper powder. The pressure reaction is a disadvantage of this method, but it does not require high pressure and the necescary vessel can be constructed from an iron pipe, fitting, one end with a lead-seated cap. Heating is conveniently carried out with an electric wrap-around heating fabric.


Appendix Eleven
References