Synthesis and Isolation of Chloro-b-carbolines Obtained by Chlorination of b-Carboline Alkaloids in Solution and in Solid State

A. PONCE, MARIA; I. TARZI, OLGA; ERRA BALSELLS, ROSA

JOURNAL OF HETEROCYCLIC CHEMISTRY

Heterocorporation.

Lugar: Tampa, USA; Año: 2003 vol. 40 p. 419 - 426

0022-152X

 b-Carbolines (1-5) undergo electrophilic aromatic substitution with N-chlorosuccinimide and N-chlorobenzotriazole under different experimental conditions. Although 6-chloro and 8-chloro-nor-harmane (1a and 1b) and 6-chloro and 8-chloro-harmane (2a and 2b) obtained by chlorination with sodium hypochlorite of nor-harmane (1) and harmane (2) were isolated and full characterized recently, other chloroderivatives of nor-harmane and harmane have never been described. The preparation and subsequent isolation, purification and full characterization of the dichloroderivatives 1c and 2c are reported (mp, Rf, 1H nmr, 13C nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the chloroderivatives obtained from harmine (3a-3c), harmol (4a-4b) and 7-acetylharmol (5a-5c). As chlorinating reagent N-chlorosuccinimide and N-chlorobenzotriazole in solution as well as the b-carboline ? N-chlorosuccinimide solid mixture have been used and their uses have been compared. Gc (tR) and gc-ms (m/z) data for other monochloro derivative of nor-harmane (1d) and monochloro- and dichloroderivatives of harmane (2d and 2e-2f), obtained in trace amounts, are also included (Scheme 1 and Table I).  Semiempirical AM1 and PM3 calculations have been performed in order to predict reactivity in terms of the energies of HOMO-LUMO difference and in terms of the charge density of b-carbolines (1-5) and chloro-b-carbolines (1a-1c, 2a-2c, 3a-3c, 4a-4b, and 5a-5c) (Scheme 1). Theoretical and experimental results are discussed briefly.