Hydrochloric Acid → HCID 15756621, compound

Participants

Reaction Steps

The instability of 2-dimethylamino-4-(3-indolyl)imidazole 5 normally would not be judged very significant on its own. Referring to FIG. 5, unexpectedly, upon exposure of 2-dimethylamino-4-(3-indolyl)imidazole 5.HCl to a methanol solution saturated with ammonia, α-carboline 8 was produced. Autooxidation of 2-dimethylamino-4-(3-indolyl)imidazole 5.HCl took place upon standing in a MeOH solution in air to yield 2-dimethylamino-5-(3-indolyl)imidazol-4-one 4 as a yellow solid which was identical, by spectral comparison of 1H and 13C NMR data, to natural and synthetic material reported in references 6 and 9, respectively. During the course of the reaction, dimer 7 partially precipitated from solution after 1 day as a dark violet solid. Collection and resubjection of dimer 7 to the reaction conditions afforded α-carboline 8. One mechanistic pathway that might account for the above involves the initial oxidative dimerization of 2-dimethylamino-4-(3-indolyl)imidazole 5 to yield dimer 7. Upon standing in a methanol-saturated ammonia solution in air, dimer 7 undergoes an electrocyclization-aromatization event via tautomer 7a. Oxidation of the resulting intermediate 7b to 7c followed by facile aminolysis results in loss of dimethylguanidine and the formation of α-carboline 8. The sequence is remarkably efficient, delivering 8 directly in one pot and good overall yield from 2-dimethylamino-4-(3-indolyl)imidazole 5. Aromatic α-carboline imine 8 was found to be quite stable and required fairly rigorous hydrolysis conditions to yield grossularine-1 1 as a yellow solid. All spectral data of synthetic grossularine-1 1 were in excellent agreement with data reported for the natural product.[1]

Provenance & Evidence