The opportunity to try the tryptamine/formaldehyde/NaBH4 DMT synthesis has presented itself. The procedure is (from Lego, 5/29/03):
A solution of 35% formaldehyde (35 mL, 416 mmol) in MeOH (35 mL) and a solution of NaBH4 (5 g, 132 mmol) in H2O (70 mL) were added dropwise, simultaneously, at 15°C to a well-stirred solution of tryptamine (4.166 g, 26 mmol) in MeOH (150 mL). The mixture was stirred at 15°C for 0.5 h, 2N aqueous HCl was cautiously added to bring the pH to 3, and the resulting mixture was stirred for 10 min. Then, the pH was adjusted to 6.5-7 with saturated aqueous NaHCO3, MeOH was evaporated, and H2O (50 mL) was added. The mixture was washed with EtOAc (2x150 mL), basified with K2CO3, and extracted with EtOAc (2x130 mL). The organic extracts were dried, filtered, and concentrated to give DMT.
There are a series of concerns with this, however. First, formaldehyde reacts with methanol, and the only available formaldehyde is in water solution. So the procedure will be attempted with 37% formaldehyde in water, rather than methanol. The second concern is with the NaBH4 in water. NaBH4 reacts explosively with water, so how can a solution of 5 g in 70 mL be safely made? Instead of making a water solution, an IPA solution is being considered. Would there be an undesirable difference between the two solvents? The last question concerns the statement 'The mixture was washed with EtOAc (2x150 mL), basified with K2CO3, and extracted with EtOAc (2x130 mL).' The pKa DMT is something like 8.86, so to what extent is the basification with K2CO3 taken? pH 9, 10, 11? Also, should concentration of the organic extracts be conducted with rotovap?
These two modifications, if valid, don't really change the reaction extensively. Using water/formaldehyde and NaBH4/IPA would be essentially the same, upon mixing with the tryptamine/MeOH, as MeOH/formaldehyde and NaBH4/H2O, the only difference being presence of IPA.
Some comments on these ideas would be welcomed. Especially before the procedure is eXecuted, circa 1 week from the present.