Synthesis and Properties of 6-Aryl-4-azidocinnolines and 6-Aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines

Abstract

An efficient approach towards the synthesis of 6-aryl-4-azidocinnolines was developed with the aim of exploring the photophysical properties of 6-aryl-4-azidocinnolines and their click reaction products with alkynes, 6-aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines. The synthetic route is based on the Richter-type cyclization of 2-ethynyl-4-aryltriazenes with the formation of 4-bromo-6-arylcinnolines and nucleophilic substitution of a bromine atom with an azide functional group. The developed synthetic approach is tolerant to variations of functional groups on the aryl moiety. The resulting azidocinnolines were found to be reactive in both CuAAC with terminal alkynes and SPAAC with diazacyclononyne, yielding 4-triazolylcinnolines. It was found that 4-azido-6-arylcinnolines possess weak fluorescent properties, while conversion of the azido function into a triazole ring led to complete fluorescence quenching. The lack of fluorescence in triazoles could be explained by the non-planar structure of triazolylcinnolines and a possible photoinduced electron transfer (PET) mechanism. Among the series of 4-triazolylcinnoline derivatives a compound bearing hydroxyalkyl substituent at triazole ring was found to be cytotoxic to HeLa cells.

4-Azidocinnoline—Cinnoline-4-amine Pair as a New Fluorogenic and Fluorochromic Environment-Sensitive Probe

“…We chose a CN-substituted azide 5/amine 6 pair as the object of the studies because of the direct conjugation of a CN group with N 3 /NH 2 groups in azide 5 and amine 6, respectively, which is crucial for the fluorescence through the intramolecular charge transfer (ICT) mechanism [17]. The synthesis of azide 5 was achieved by the synthetic protocol reported earlier [35] with a slight modification: the replacement of the chromatographic purification of 4-bromocinnoline 4 with recrystallization improved the yield of compound 4 from 62% up to 91% (Scheme 1). Two types of reducing conditions were tested: the Staudinger reduction and the use of sodium borohydride.…”

“…Recently, we have developed an efficient synthetic route towards 6-aryl-4-azidocinnolines based on the nucleophilic substitution of a bromine atom at the C4 position of 6-arylcinnolines with sodium azide [35]. The azidocinnolines possessed weak fluorescence (quantum yield (QY) < 1%); therefore, we believed that switching to the corresponding 4-(triazolyl)cinnolines would improve the fluorescent properties, providing a fluorogenic azide/triazole probe.…”

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

“…There are fewer ways to access indolone derivatives, mainly based on the use of di- [ 12 , 38 – 39 ] or triketones [ 10 , 13 ] and enaminones [ 40 – 43 ] as starting materials. For the synthesis of cinnoline derivatives, aryldiazenes and aryltriazenes are substrates of choice for transition-metal-catalyzed (Rh, Pd, Cu) cross-coupling reactions, followed by intramolecular cyclizations [ 44 – 47 ]. Moreover, arylhydrazones and arylhydrazines/hydrazines can be used as well, respectively, as partners in [4 + 2] cyclization reactions [ 48 – 51 ] or by reacting mostly with carbonyl derivatives [ 52 – 55 ].…”

Tuneable access to indole, indolone and cinnoline derivatives from a common 1,4-diketone Michael acceptor

“…There are fewer ways to access indolone derivatives mainly based on the use of di- [12,38,39] or tri-ketones [10,13] and enaminones [40][41][42][43] as starting materials. For the synthesis of cinnoline derivatives, aryldiazenes and aryltriazenes are substrates of choice for transition-metal catalyzed (Rh, Pd, Cu) cross-coupling reactions followed by intramolecular cyclizations [44][45][46][47]. Moreover arylhydrazones and arylhydrazines/hydrazines car be used as well respectively as partners in 4+2 cyclization reaction [48][49][50][51] or by reacting mostly with carbonyl derivatives [52][53][54][55].…”