TiHKAL #42. 5-MEO-NMT

SYNTHESIS : (from 5-MeO-DMT). To a solution of 0.10 g 5-methoxy-N,N-dimethyl tryptamine (see 5-MeO-DMT) in 5 mL benzene there was added 0.5 g 2,2,2-trichloroethyl chloroformate, and the resulting solution was held at reflux temperature for 2 days. After cooling there was added 5 mL Et2O and the organic phase washed with 2x20 mL 3N HCl followed by 20 mL H2O. The solvent was then removed under vacuum. The residue (N-(2,2,2-trichloroethoxycarbonyl)-N-methyl-5-methoxytryptamine, 0.12 g) was dissolved in 2 mL acetic acid and treated with 0.15 g powdered zinc. After stirring for 4 h at room temperature, the reaction mixture was filtered and the filtrate made basic with 3N NaOH. This was extracted with 3x20 mL Et2O, the extracts pooled, and the solvent removed under vacuum. The residue was purified by preparative TLC, using a n-BuOH / AcOH / H2O (12/3/5) solvent for development. There was thus obtained 0.013 g of 5-methoxy-N-methyltryptamine (5-MeO-NMT) as a solid with a mp of 90-93 °C.

(from 5-MeO-T) A solution of 0.086 g 5-methoxytryptamine (5-MeO-T) in 1 mL dioxane containing 0.5 mL of 2N NaOH was cooled to 0 °C and well-stirred. There was added, at the same time, 0.2 mL benzyl chloroformate and 0.25 mL 4N NaOH. This was allowed to come to room temperature and the stirring was continued for an additional 10 min. There was added concentrated HCl, followed by 10 mL H2O. This mixture was extracted with 3x20 mL Et2O, the extracts pooled, and the solvent removed under vacuum. The crude carbamate was purified by silica-gel column chromatography using n-hexane / CH2Cl2 (1/9) as an eluting solvent. After removal of the chromatographic solvent under vacuum, the residue was dissolved in 10 mL anhydrous THF and added slowly to a ice-cold, well-stirred suspension of 0.178 g LAH in 10 mL anhydrous THF. After being brought to reflux and held there for 4 h, the mixture was cooled and acidified with 1N HCl. The THF was removed under vacuum, and the aqueous residue washed with Et2O. This was then treated with solid NaHCO3 and extracted with 3x50 mL Et2O. The solvent from the combined extract was removed under vacuum, and the residue purified by preparative TLC as described above. There was thus obtained 0.016 g of 5-MeO-NMT with a mp of 88-91 °C.

EXTENSIONS AND COMMENTARY : This base is the botanically and pharmacologically famous 5-MeO-DMT, missing one of its two N-methyl groups. Sort of a nor-5-MeO-DMT. Its human exploration has just been started, but the expected vulnerability of it to metabolic oxidative deamination makes it a good guess that it (as seen with the dimethyl homologue) will only be active parenterally, or when the body's destructive enzymes are held at bay by effective monoamine oxidase inhibition. This base has been found in several Virola species but, as it is always accompanied by 5-MeO-DMT, its contribution to the psychoactivity of the resulting snuff is completely unknown. It has also been found in the skin of the Bufo alvarius at the trivial level of 20-23 micrograms per gram, compared to skin levels of 1.0 to 3.5 mg/g of 5-MeO-DMT.