(Rated as: excellent)
Taken from Arch. Pharm. 1963, p. 656 :
Clemmensen reduction of o-vanillin gives 40% yield of 2-hydroxy-3-methoxytoluene according to Ber. D. Chem. Gesell. 49 (1916) p. 1488
6.9 gr (0.05 mol) 2-hydroxy-3-methoxytoluene, obtained from Clemmensen reduction of o-vanillin, was dissolved with 3 gr (0.053 mol) KOH in 16 ml water, and 4.3 gr (0.05 mol) 35% formaldehyde solution was added and the mixture was stirred at 40-50° for 4 hours. The green colour of the mixture became an intensive violet. After cooling the mixture was slightly acidified with 1% HCl and extracted with ether. The solvent was evaporated and the resulting oil recrystallised from EtOAc. This was purified by means of column chromatography with a silica gel column and chloroform as the eluting solvent. Next to tars and a bit of unchanged precursor there was obtained 10% 3,3'-dimethoxy-4,4'-dihydroxy-5,5'-dimet
5.5 gr 3-methoxy-4-hydroxy-5-methylbenzyl alcohol was dissolved in methanol and treated with an ethereal diazomethane solution. After work-up the phenol-free yellow oil was distilled at the Kugelrohr (120-125°/1mm), yield 5 gr (84%).
5 gr 3,4-dimethoxy-5-methyl-benzyl alcohol was dissolved in 40 ml anhydrous ether and placed in an ice-bath. The mixture was saturated with dry HCl-gas. After evaporation of the solvent there remained an colourless oil, which was distilled at the Kugelrohr (105-110°/3mm), yield 5 gr (91%)
5 gr 3,4-dimethoxy-5-methyl-benzyl chloride was dissolved in 5 gr DMF and heated with stirring to 70-75°, and a solution of 1.5 gr NaCN, 4 drops of water and 5 gr DMF was added dropwise. The mixture was left stirring for 3 hours at 70-75°, solvent was evaporated and the resulting oil was distilled at the Kugelrohr (115°/1mm). Yield 3.3 gr (70%).
To a suspension of 1.6 gr (0.04 mol) LiAlH4 in 50 ml anhydrous ether was gently added with good stirring a solution of 5.2 gr (0.04 mol) anhydrous AlCl3 in 60 ml anhydrous ether, followed by the dropwise addition of 3.8 gr (0.02 mol) 3,4-dimethoxy-5-methyl-benzyl cyanide. There was a vigorous reaction and a white solid precipitated. The mixture was stirred for an additional hour at RT. After work-up 3.0 gr (77%) of a brown oil was obtained, this was made into the HCl salt and recrystallised from MeOH and ether, mp. 208°
Does anyone have any data on possible activity?
That is a really nice thing, i hope i will have the luck to eat some meta-desoxy mescaline one day....