Reaction of aromatic azides with strong acids: formation of fused nitrogen heterocycles and arylamines

Journal of the Brazilian Chemical Society

Universidade Estadual de Campinas, Campinas, Brazil¹  Sorrilha, Ana E.P.M.¹  Rodrigues, J. Augusto R.¹  Carvalho, Marcia de¹ 

关键词: nitrenium ion;    aryl azides;    indoles;    azepines;   

DOI  :  10.1590/S0103-50531999000500012

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

Nitrenium ions are reactive intermediates that have been the subject of much recent attention1. One reason for this is the proposal that arylnitrenium ions are intermediates in the reactions whereby various chemical carcinogens damage DNA2. The target of this reaction appears to be guanine bases in the DNA molecule3. Studies have confirmed that arylnitrenium ions, alleged to be involved in the carcinogenic pathways, do in fact react very rapidly with the critical DNA components4. Moreover, it has become increasingly clear that various ions have microsecond or longer lifetimes in water5. Intramolecular remote functionalization by arylnitrenium ions7 is an useful method for forming six-7a and seven-membered rings7b, lactones7a-c, dihydroxepines7d, dihydrophenanthridines and benzo[c]chromans7e. There are few examples in the literature which describe the intramolecular electrophilic attack by a nitrenium ion upon an ortho-aromatic nucleus. The reaction of boron trichloride with an ortho-aryl and ortho-diazoaryl phenyl azides at room temperature yielded fused azoles via 1,5-cyclization8a,b. Cyclization of 4-azido-3-phenyl-3-phenylpyridazines and 7-azido-6-phenyltetrazolo[1,5-b] by heating with strong acids like methanesulfonic acid gave 5H-pyridazino[4,3-b]indoles and 10H-tetrazolo[1’,5’:1,6]pyridazino[4,3-b]indoles, respectively8c. A remarkable formation of a sixteen-membered ring by an intramolecular electrophilic aromatic substitution involving a nitrenium ion was reported by Abramovitch and coworkers8d. The decomposition of 1-(3-azidobenzyl)-5,6-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline in TFA/TFMSA at -5 °C was observed to afford pronuciferine in 5% yield together with uncyclised amine (16%) [precursor to starting azide] resulting from hydrogen abstraction by the reactive intermediate. Using the same acids, Takeuchi reported that aryl azides undergo intermolecular aromatic N-substitution9a-c. Inter- and intra-molecular aromatic N-substitution by arylnitrenium-aluminium chloride complexes generated from aryl azides in the presence of aluminium chloride was reported by Takeuchi10. Olah et al. studied triflic acid catalyzed phenylamination of aromatics with phenyl azide and they propose two alternative intermediates, a phenylaminodiazonium ion or phenylnitrenium ion11. In this paper, we report the reaction of various ortho-substituted aryl azides with strong acids like trifluoroacetic acid, trifluoromethanesulfonic acid and aluminum chloride to form nitrenium ion intermediates that collapse to a nitrogen five and seven-membered ring. Also we compare these results with thermal decomposition of the same azides in which a nitrene is the reactive intermediate.   Results and Discussion trans-2-Azidostilbene 1, prepared by the procedure of Sundberg12, was treated in dichloromethane at 0 °C with trifluoromethanesulfonic acid (triflic acid) or trifluoroacetic acid. The temperature was allowed to reach the ambient and after neutralization, the crude material was purified by thick layer chromatography on silica gel to give 2-phenyl-1H-indole 3, mp 187-188 °C13, in 85% yield. This cyclization suggests that protonated azide, a nitrenium like ion or a nitrenium ion, resulting from the protonated azide by loss of nitrogen7a,9a, is responsible for the formation of the five membered ring (Scheme 1). Since Takeuchi reported formation of arylnitrenium ion (or a nitrenium-AlCl3 complex) from decomposition of azides in presence of AlCl3, we treated 1 under the same conditions9c. After the evolution of nitrogen stopped, the excess AlCl3 was destroyed by 10% NaOH and after purification on silica gel plates, we isolated trans-2-aminostilbene, mp 101-103 Â°C13, (formed by triplet nitrenium ion hydrogen atom abstraction) in 45% yield and only traces of 3. Thermolysis of 1 in ethylene glycol (reflux for 4 h) also furnished the 2-phenyl-1H-indole in 87% yield but in this

【 授权许可】

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