This is an old story, almost forgotten. After reading some reviews on sulfur chemistry, SWIM became convinced that by reacting the N
-phthalimido derivative of 2,5-DMA with MeSCH2
Cl in nitromethane in the presence of a Lewis acid (SWIM chose ZnCl2
for the 1st try), it is possible to obtain DOMTM-NPhth. Incidentally, SWIM had some chloromethyl methyl sulfide (MTM-Cl) and 2,5-DMA-NPhth.DOMTM-NPhth
Indeed, when freshly distilled (awful stench!) MTM-Cl (4.5 eq.) was added to the solution of 2,5-DMA-NPhth and ZnCl2
(1eq.) in nitromethane at rt, HCl began to evolve, and after 1/2 h at rt the reaction was stopped by adding PhMe and aq. NaHCO3
to the mixture. The organic layer was separated and the aqueous layer was extracted several times with PhMe to remove the traces of the product trapped in the suspension of Zn carbonate. The combined extracts were dried by filtering through a pad of the mixture of silica gel with Na2
and evaporated. After column chromatography (gradient elution, hexane - benzene 2:3 v/v --> EtOAc - benzene 1:3 v/v) and crystallization (probably EtOAc-hexane or CHCl3
-MeOH, no notes were kept), approx. 50% yield of the product was obtained.
was identical to that of the starting compound in several eluents tested. However, specially prepared TLC plates could be used to follow the course of the reaction. A solution of AgNO3
in a minimum volume of water was diluted with MeOH to achieve 3 g/100 ml concentration. TLC silica plates (glass) were impregnated with this solution for 1/2 h, and the excess of it was removed using a filter paper. After drying in a vacuum, the plates were kept protected from light. On such plates, the Rf
s of the compounds containing divalent sulfur (mercaptans, sulfides or thioacetals) are considerably lower than on common TLC plates, while the Rf
s of the compounds which cannot form stable complexes with silver remain largely unaffected.DOMTM hydrochloride
Then DOMTM-NPhth was dissolved in hot 95% EtOH. Hydrazine monohydrate (1/10 by volume) was added, and the mixture was refluxed under argon for 3h. After evaporation, the residue was distributed between PhMe (which don't extract hydrazine) and 10% aq. Na2
(which dissolves phthaloyl hydrazide), the organic layer was separated, and the aqueous layer was extracted with PhMe several times. The combined extracts were evaporated, and the residue was purified by a/b extraction. Crystalline hydrochloride was obtained in high yield (details forgotten).
SWIM dared to biotest the compound only up to 1 mg level. At this dosage, there was slight tinnitus, emotional instability, and an unpleasant feeling in the stomach. So, by these rather doubtful results SWIM can suggest that the substance doesn't have the potency of DOB or DOEt (which SWIM found definitely active at this level).DOMTM --> DOMTM-NHAc --> DOM-NHAc
The next idea was to convert DOMTM to DOM by desulfurization on Raney nickel. SWIM realized that with an unprotected amine, there might be formation of complexes with nickel, and possibly oxidative deamination or formation of secondary amines. To avoid these potential difficulties, the amino group was acetylated with Ac2
N. The acetamide was a crystalline solid, individual by TLC. After desulfurization (3 h refluxing in EtOH with large excess of Raney Ni), no remarkable change in Rf
was observed. Again, AgNO3
-impregnated silica plates had to be used to follow the course of the reaction. The spots were visualized by spraying with 1:1 v/v aq. H2
and heating on a hotplate.
The product was crystalline, too.The hydrolysis of DOM-NHAc (failed attempt)
The attempt to hydrolyse the acetamido group by refluxing the amide in 20% aq. HCl was completely unsuccessful. The reaction is extremely slow. After perhaps 24 h refluxing and subsequent evaporating the mixture, some amide still remained unchanged. It is insoluble in water, and was removed by filtration. After the aq. solution of the supposed DOM hydrochloride had been made basic, a violet coloration began to evolve. SWIM ended up with some 30 mg of very dark hydrochloride crystals (from 120 mg of the amide).
A bunch of methylthiomethylation references will be posted soon.