Radical cyclisations onto imidazoles

This thesis describes the development of new pathways towards the synthesis of novel antimicrobial (and anticancer) agents. Two synthetic protocols based on free radical chemistry are studied, which are used to access polycyclic heterocyclic compounds of potential biological importance. Both these procedures involve the generation of radicals using Bu3SnH and AIBN initiators, and the subsequent intramolecular radical cyclisation onto the imidazole ring. Radical cyclisations onto benzimidazoles and pyrroles are also described. [Continues.

1-Fluoro-2,5-dimethoxy-4-nitrobenzene

1-Fluoro-2,5-dimethoxy-4-nitrobenzene was synthesized in 90% yield by the reaction of commercial 2-fluoro-1,4-dimethoxybenzene with nitric acid. The structure was confirmed by X-ray crystallography. The new title compound was characterized by 1H and 13C-NMR, elemental analysis, EI-MS and FT-IR

2-(Fluoromethyl)-4,7-dimethoxy-1-methyl-1H -benzimidazole

Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) substitutes the TEMPO free radical with fluorine on 4,7-dimethoxy-1-methyl-2-{[(2,2,6,6-tetramethylpiperidin-1-yl)oxy]methyl}-1H-benzimidazole to give the title compound in a 77% yield. A mechanism is proposed for the formation of this novel methylene fluoride

Synthesis of N-[(dialkylamino)methyl)]acrylamides and N-[(dialkylamino)methyl]methacrylamides from Schiff base salts : useful building blocks for smart polymers

The traditional thermal Mannich reaction is unsuitable for preparing polymerizable N-methylene amino substituted acrylamides and methacrylamides. Herein we provide a facile multi-gram high yield synthesis of these monomeric precursors to stimuli-responsive polymers by addition of acrylamide and methacrylamide onto in situ generated or freshly isolated methylene Schiff base (iminium) salts. X-ray crystal structure of the hydrated iminium salt, 1-(hydroxymethyl)azocan-1-ium chloride and monomer.HCl salt, (N-[(azocan-1-yl)methyl]prop-2-enamide hydrochloride) is described

Regioselective fluorination of 7-oxo-1,2,4-benzotriazines using selectfluor

7-Oxo-1,2,4-benzotriazines (benzo[1,2,4]triazin-7-ones) are reversible thioredoxin reductase inhibitors that exhibit very strong correlations to pleurotin. In this article, we provide the first synthesis of fluorinated derivatives. Fluorination using Selectfluor of benzo[1,2,4]triazin-7-ones occurs regioselectively and in high yield at the enamine-activated position. This electron N-lone pair activation overrides the activation/deactivation effects of some other substituents. The reaction time was significantly reduced with the use of microwave irradiation at 120 °C and 7 bar. The cytotoxicity and cyclic voltammetry measurements for 8-fluoro-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (2) are presented and compared with its synthetic precursor, 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1a)

Photochemical aryl radical cyclizations to give (E)-3-Ylideneoxindoles

(E)-3-Ylideneoxindoles are prepared in methanol in reasonable to good yields, as adducts of photochemical 5-exo-trig of aryl radicals, in contrast to previously reported analogous radical cyclizations initiated by tris(trimethylsilyl)silane and azo-initiators that gave reduced oxindole adduct

Advances in the synthesis of ring-fused benzimidazoles and imidazobenzimidazoles

This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-f]benzimidazoles, and imidazo[5,4-f]benzimidazoles. These heterocycles have a plethora of biological activities with the iminoquinone and quinone derivatives displaying potent bioreductive antitumor activity. Synthesis is categorized according to the cyclization reaction and mechanisms are detailed. Nitrobenzene reduction, cyclization of aryl amidines, lactams and isothiocyanates are described. Protocols include condensation, cross-dehydrogenative coupling with transition metal catalysis, annulation onto benzimidazole, often using CuI-catalysis, and radical cyclization with homolytic aromatic substitution. Many oxidative transformations are under metal-free conditions, including using thermal, photochemical, and electrochemical methods. Syntheses of diazole analogues of mitomycin C derivatives are described. Traditional oxidations of o-(cycloamino)anilines using peroxides in acid via the t-amino effect remain popular

CF₃-Bis-TEMPO-Vis : new visible light active bis-benzimidazolequinone alkoxyamine

Alkoxyamines of TEMPO usually dissociate thermally at >100 °C; however, room temperature homolysis, activated by visible light, occurs with benzimidazolequinone derivatives. 1,1’-Dimethyl-2,2’-bis{[(2,2,6,6-tetramethylpiperidin-1-yl)oxy]methyl}-6-(trifluoromethyl)-1H,1’H-[5,5’-bibenzimidazole]-4,4’,7,7’-tetrone (CF₃-Bis-TEMPO-Vis) is prepared in a 59% yield through NBS/H₂SO₄ oxidative demethylations of the dimethoxybenzimidazole-benzimidazolequinone precursor with aqueous work up. The alternative basic work up in air gave the epoxide derivative of CF₃-Bis-TEMPO-Vis. Unlike the latter CF₃-epoxide, both alkoxyamine residues are labile under green light (470−600 nm), and the rate of TEMPO release is three times slower than Bis-TEMPO-Vis