Fully Selective Synthesis of Spirocyclic-1,2-oxazine N-Oxides via Non-Catalysed Hetero Diels-Alder Reactions with the Participation of Cyanofunctionalysed Conjugated Nitroalkenes

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The molecular mechanism of the [3+2] cycloaddition reactions between aryl azides and ethyl propiolate was evaluated in the framework of the Molecular Electron Density Theory. It was found that independently of the nature of the substituent within the azide molecule, the cycloaddition process is realized via a polar but single-step mechanism. All attempts of localization as postulated earlier by Abu-Orabi and coworkers’ zwitterionic intermediates were not successful. At the same time, the formation of zwitterions with an “extended” conformation is possible on parallel reaction paths. The ELF analysis shows that the studied cycloaddition reaction leading to the 1,4-triazole proceeds by a two-stage one-step mechanism. It also revealed that both zwitterions are created by the donation of the nitrogen atom’s nonbonding electron densities to carbon atoms of ethyl propiolate.

Section: Resultsmentioning

confidence: 99%

On the Question of Zwitterionic Intermediates in the [3+2] Cycloaddition Reactions between Aryl Azides and Ethyl Propiolate

Dresler,

Woliński,

Wróblewska

et al. 2023

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“…Analysis of the electronic properties of organic molecules is an important and universal tool for predicting their reactivity [67][68][69]. This approach was recently and successfully applied to interpret the reactivity of different types of molecular segments and the course of many bimolecular organic processes [70][71][72][73][74].…”

Section: Power Of the Global And Local Interactions In The Context Of...mentioning

confidence: 99%

Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study

Dresler,

Wróblewska,

Jasiński

2024

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Regioselectivity and the molecular mechanism of the [3+2] cycloaddition reaction between nitro-substituted formonitrile N-oxide 1 and electron-rich alkenes were explored on the basis of the wb97xd/6-311+G(d) (PCM) quantum chemical calculations. It was established that the thermodynamic factors allow for the formation of stable cycloadducts along all considered models. The analysis of the kinetic parameters of the main processes show that all [3+2] cycloadditions should be realized with full regioselectivity. In all cases, the formation of 5-substituted 3-nitro-2-isoxazolidines is clearly preferred. It is interesting that regiodirection is not determined by the local electrophile/nucleophile interactions but by steric effects. From a mechanistic point of view, all considered reactions should be treated as polar, one-step reactions. All attempts to locate the hypothetical zwitterionic intermediates along the cycloaddition paths were, however, not successful.

“…These compounds exhibit various biological activities such as antibacterial [ 5 , 6 ] or antifungal [ 7 ]. This makes CNAs often used in many reactions such as Michael addition [ 8 , 9 ] as well as cycloaddition (CA) reactions, to synthesize heterocycles, especially for the preparation of five-membered rings [ 10 ] like pyrazolines [ 11 , 12 ], isoxazolines [ 13 , 14 , 15 , 16 ] or pyrrolidine [ 17 , 18 ], and six-membered rings in the Diels-Alder reaction [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

(1E,3E)-1,4-Dinitro-1,3-butadiene—Synthesis, Spectral Characteristics and Computational Study Based on MEDT, ADME and PASS Simulation

Sadowski,

Synkiewicz-Musialska,

Kula

2024

The chemistry of conjugated nitrodienes is becoming increasingly popular. These molecules are successfully applied in cycloaddition to synthesize six-membered rings in Diels-Alder reactions. Nitrodienes can be also applied to obtain bis-compounds in [3+2] cycloaddition. Moreover, the presence of a nitro group in the structure provides a possibility of further modification of the products. The simplest symmetrical representative of conjugated nitrodienes is (1E,3E)-1,4-dinitro-1,3-butadiene. Although the first mentions of the compound date back to the early 1950s, the compound has not yet been examined thoroughly enough. Therefore, in this article, a comprehensive study of (1E,3E)-1,4-dinitro-1,3-butadiene has been described. For this purpose, an experimental study including the synthesis process as well as an evaluation of the spectral characteristics has been conducted. So as to better understand the properties of this compound, a computational study of reactivity indices based on MEDT and also an assessment of pharmacokinetics and biological activity according to ADME and PASS methodologies have been made. On this basis, some future application trends of (1E,3E)-1,4-dinitro-1,3-butadiene have been proposed.