One-Pot Synthesis of Fluorescent 2,5-Dihydro-1,2,3-triazine Derivatives from a Cascade Rearrangement Sequence in the Reactions of 1,2,3-Triazolium-1-aminide 1,3-Dipoles with Propiolate Esters
Abstract:The reactions of 1,2,3-triazolium-1-aminides 1 (readily available from benzil bishydrazones) with propiolate esters leads to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 2, 3 in one pot. These synthetic reactions can be carried out in acetone, in water, or under solvent-free conditions. The reactions involve a Huisgen cycloaddition followed by a sequence of rearrangements. The final ring-expansion step was blocked by linking a six-methylene hydrocarbon chain between the prospective 1,2,3-triazine C-4 and… Show more
“…Although the primary objective of the present work was to establish the mechanism of the reactions given in Scheme , the very recent work of Butler et al suggests that product 11 in principle can undergo further rearrangement to yield ring-expanded triazine derivatives. They have shown that the reaction of 1,2,3-triazolium-1-aminides ( 14 ) with propiolate esters, for example, gives rise to a mixture of fused pyrrolo[2,3-d]triazine derivatives ( 15 ) and 1,2,3-triazine derivatives ( 16 ), depending on the reaction conditions (Scheme ) . They have suggested that the pyrrolo[2,3-d]triazines ( 17 ) are the precursors for the triazine derivatives ( 16 ).…”
Section: Resultsmentioning
confidence: 96%
“…However, subsequent X-ray crystallographic analysis had revealed that the adducts were correctly represented by structures 4 and 6a , b , formed through a facile and unusual rearrangement of the corresponding primary adducts 3 and 5a , b , respectively (Scheme ). Subsequent to our initial report on the involvement of bisphenylazoalkenes as potential 1,3-dipolar substrates, Butler et al − have extensively investigated the reactions of 1,2,3-triazolium-1-imide 1,3-dipoles and related systems with alkene and alkyne dipolarophiles. They have shown that the initially formed cycloadducts undergo facile sigmatropic rearrangement to give fused pyrrolo[2,3-d]triazoline derivatives. , Butler and Huisgen have correctly designated these rearrangements as allowed suprafacial thermal 1,4-sigmatropic rearrangements of conjugated organic nitrogen systems, which are analogues of the 1,5-sigmatropic rearrangement of carbon systems .…”
Section: Introductionmentioning
confidence: 99%
“…This implies a process which does not allow for bond rotations during the rearrangement. In a very recent work, Butler et al have demonstrated that further rearrangement of pyrrolo[2,3-d]triazoline can yield ring-expanded triazine derivatives, and their photonic properties were suggested for potential applications in labeling experiments in biological systems. In the present work, we undertake a theoretical study using the density functional theory (DFT) method to unravel the details of the mechanism of these transformations.…”
The 1,3-dipolar cycloaddition of bis(phenylazo)stilbene with activated ethene and ethyne derivatives and the subsequent rearrangement of the cycloadducts have been studied using model compounds at the B3LYP/6-31G(d) level of density functional theory (DFT). From the structural and electronic features, a five-membered zwitterionic ring system 9 (1,2,3-triazolium-1-imide system) formed from bis(phenylazo)ethylene is confirmed as the active 1,3-dipole species in the reaction. Formation of the 1,3-dipolar cycloadduct from the alkyne derivative is found to be 26.0 kcal/mol exergonic, and it requires an activation free energy of 19.4 kcal/mol. The 1,3-cycloadduct formed in the reaction undergoes a very facile migration of a nitrogen-bearing fragment, passing through a zwitterionic transition state. A small activation free energy of 8.2 kcal/mol is observed for this step of the reaction, and it is 19.6 kcal/mol exergonic. Further activation of the newly formed rearranged product is possible under elevated temperatures, again passing through a zwitterionic transition state and resulting in the formation of 2,5-dihydro-1,2,3-triazine derivatives. Such derivatives have been recently reported by Butler et al. (J. Org. Chem. 2006, 71, 5679). The charge separation in 9 and the zwitterionic transition states are stabilized through the pi-system of the phenyl rings and the carbonyl groups. Similar structural, electronic, and mechanistic features are obtained for the reaction of 9 with the ethylenic dipolarophile acrylonitrile. Molecular electrostatic potential analyses of the 1,3-dipole and the zwitterionic transitions states are found to be very useful for characterizing their electron delocalization features. The solvation effects can enhance the feasibility of these reactions as they stabilize the zwitterionic transition states to a great extent.
“…Although the primary objective of the present work was to establish the mechanism of the reactions given in Scheme , the very recent work of Butler et al suggests that product 11 in principle can undergo further rearrangement to yield ring-expanded triazine derivatives. They have shown that the reaction of 1,2,3-triazolium-1-aminides ( 14 ) with propiolate esters, for example, gives rise to a mixture of fused pyrrolo[2,3-d]triazine derivatives ( 15 ) and 1,2,3-triazine derivatives ( 16 ), depending on the reaction conditions (Scheme ) . They have suggested that the pyrrolo[2,3-d]triazines ( 17 ) are the precursors for the triazine derivatives ( 16 ).…”
Section: Resultsmentioning
confidence: 96%
“…However, subsequent X-ray crystallographic analysis had revealed that the adducts were correctly represented by structures 4 and 6a , b , formed through a facile and unusual rearrangement of the corresponding primary adducts 3 and 5a , b , respectively (Scheme ). Subsequent to our initial report on the involvement of bisphenylazoalkenes as potential 1,3-dipolar substrates, Butler et al − have extensively investigated the reactions of 1,2,3-triazolium-1-imide 1,3-dipoles and related systems with alkene and alkyne dipolarophiles. They have shown that the initially formed cycloadducts undergo facile sigmatropic rearrangement to give fused pyrrolo[2,3-d]triazoline derivatives. , Butler and Huisgen have correctly designated these rearrangements as allowed suprafacial thermal 1,4-sigmatropic rearrangements of conjugated organic nitrogen systems, which are analogues of the 1,5-sigmatropic rearrangement of carbon systems .…”
Section: Introductionmentioning
confidence: 99%
“…This implies a process which does not allow for bond rotations during the rearrangement. In a very recent work, Butler et al have demonstrated that further rearrangement of pyrrolo[2,3-d]triazoline can yield ring-expanded triazine derivatives, and their photonic properties were suggested for potential applications in labeling experiments in biological systems. In the present work, we undertake a theoretical study using the density functional theory (DFT) method to unravel the details of the mechanism of these transformations.…”
The 1,3-dipolar cycloaddition of bis(phenylazo)stilbene with activated ethene and ethyne derivatives and the subsequent rearrangement of the cycloadducts have been studied using model compounds at the B3LYP/6-31G(d) level of density functional theory (DFT). From the structural and electronic features, a five-membered zwitterionic ring system 9 (1,2,3-triazolium-1-imide system) formed from bis(phenylazo)ethylene is confirmed as the active 1,3-dipole species in the reaction. Formation of the 1,3-dipolar cycloadduct from the alkyne derivative is found to be 26.0 kcal/mol exergonic, and it requires an activation free energy of 19.4 kcal/mol. The 1,3-cycloadduct formed in the reaction undergoes a very facile migration of a nitrogen-bearing fragment, passing through a zwitterionic transition state. A small activation free energy of 8.2 kcal/mol is observed for this step of the reaction, and it is 19.6 kcal/mol exergonic. Further activation of the newly formed rearranged product is possible under elevated temperatures, again passing through a zwitterionic transition state and resulting in the formation of 2,5-dihydro-1,2,3-triazine derivatives. Such derivatives have been recently reported by Butler et al. (J. Org. Chem. 2006, 71, 5679). The charge separation in 9 and the zwitterionic transition states are stabilized through the pi-system of the phenyl rings and the carbonyl groups. Similar structural, electronic, and mechanistic features are obtained for the reaction of 9 with the ethylenic dipolarophile acrylonitrile. Molecular electrostatic potential analyses of the 1,3-dipole and the zwitterionic transitions states are found to be very useful for characterizing their electron delocalization features. The solvation effects can enhance the feasibility of these reactions as they stabilize the zwitterionic transition states to a great extent.
“…Prolonged heating causes cleavage of the C–N bond (between C–3a and N-4) in 168 and rearrangement of the obtained betaines 169 to more stable 2,5-dihydro-1,2,3-triazines 170 . This relatively complex process produces triazines 170 in moderate yields (35–52%) 2006TL1721 , 2006JOC5679 . Scheme 18 …”
Section: Reactivity Of Fully Conjugated Ringsmentioning
“…As specific needs arise, “click chemistry” , reactions will inevitably depart from the goal of simple reactions to more complicated adaptations. , Other reactant azides or 1,3-dipoles will be sought, opening up possibilities for rearrangement. Encountering unexpected rearrangements subsequent to cycloadditions, often involving multistep cascades, − is a significant feature of the synthetic versatility of the original Huisgen 1,3-dipolar cycloaddition reaction. An early example is the synthesis of diazapentalene isomers that was used to confirm calculations of aromaticity in 10π electron systems.…”
The reaction surfaces leading to rearrangements and ring expansions of azapentalene cycloadducts of imidazolo- and triazolodicyanomethanide 1,3-dipoles with alkynes are studied with the B3LYP DFT method using the 6-31G(d) and 6-311+G(2d,p) basis sets. The surprisingly complex surface involves (1) consecutive but not combined pericyclic steps, a coarctate TS, and pseudopericyclic mechanisms, (2) anchimerically assisted H-atom transfer competing effectively with concerted symmetry-allowed sigmatropic steps, and (3) azolium methanide zwitterions and ketenimines as key intermediates. The azolium methanide is identified as the intermediate detected previously in a variable-temperature NMR experiment that converted the unstable cycloadduct to product imine.
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