Cyanide → Benzo[b]thiophene-3-acetonitrile

Participants

Reaction Steps

The synthesis of ibogaine analogs 7a-c is outlined in FIG. 2, wherein the benzo[b]thiophene is chloromethylated to yield 1, then reacted with cyanide ion to yield 3-cyanomethylbenzothiophene (2), which is reduced with LiAlH4 /AlCl3 to yield the corresponding primary amine 3. The latter was acetylated with acetic anhydride and the resulting amide was reduced with borane-tetrahydrofuran to yield 5. Refluxing of the 5 with a preselected styrene oxide in EtOH and subsequent cyclization of the corresponding secondary alcohol provided the compounds 7a, (R=H) 7b (R=NO2) and 7c (R=Br). The compounds were characterized by 1H NMR and purity was determined by combustion analysis. Cyclization was associated with a 0.1δ upfield shift in the methine proton signal. The hydrochlorides were prepared by passing HCl gas through a solution of the corresponding free bases in EtOH.

Provenance & Evidence