Solvent-dependent oxidations of 5- and 6-azaindoles to trioxopyrrolopyridines and functionalised azaindoles.
A regioselective synthesis of 4,7-dimethoxy 5- and 6-azaindoles 2 has been achieved, based on the appropriate choice of ortho-directing or ortho-repulsing groups in the formylation of a pyridine ring. Studies on the regioselectivity of the formylation step and on the preparation of azidoacrylate intermediates 4 are described in this paper. The reactivity of the 5- and 6-azaindole structures towards BBr3-mediated selective monodemethylation and oxidative demethylation reactions were also investigated. The regioselectivity of the deprotection was confirmed using a chemical approach. Oxidation reactions were then carried out on either dimethoxy- or hydroxymethoxyazaindoles, in different solvents, using [bis(trifluoroacetoxy)iodo]benzene. In acetonitrile-water, trioxopyrrolopyridines 12 were obtained, whereas the formation of functionalised azaindoles 17 was observed in acetonitrile-methanol. The tautomeric structure of the trioxopyrrolopyridines was proved by X-ray diffraction analysis.
Mahiout
Zahia
Z
Laboratoire de Chimie Thérapeutique, Université de Lyon, Lyon, F-69003, France.
Lomberget
Thierry
T
Goncalves
Sylvie
S
Barret
Roland
R
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
C512290:5-azaindole; C504762:6-azaindole; D001372:Aza Compounds; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D012997:Solvents