Strategy for the Synthesis of Pyridazine Heterocycles and Their Derivatives

Abed, Hassen Bel; Mammoliti, Oscar; Bande, Omprakash; Lommen, Guy Van; Herdewijn, Piet

doi:10.1021/jo400989q

Cited by 52 publications

(7 citation statements)

References 51 publications

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“…However, there are only limited protocols for assembling 3-carbonyl substituted pyridazine derivatives, important intermediates in organic synthesis . Traditional methods include diaza-Wittig reactions of 1,3-diketones, addition of diazo compounds to Morita–Baylis–Hillman carbonates, [4 + 2] cycloaddition of substituted 1,2,3-triazines, cascade reactions of pyridiniumylides, and cycloaddition of 1,2,4,5-tetrazine with alkynes . Despite the impressive progress made in this area, it is still a great challenge to synthesize functionalized pyridazines from readily available and easily varied starting materials using a simple procedure.…”

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confidence: 99%

A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization

et al. 2015

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A facile synthesis of functionalized 3-carbamide pyridazines starting from readily available chlorovinyl aldehydes and oxamic acid thiohydrazides via cascade imination/electrocyclization is reported. In the presence of p-toluenesulfuric acid, various ketones have been efficiently incorporated into the pyridazine derivatives through a two-step sequence involving a Vilsmeier-Haack reaction and imination. The synthetic value of this method has been demonstrated by efficient synthesis of steroidal pyridazines.

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confidence: 99%

A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization

et al. 2015

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“…The molecular structures of all the objectives with bond length in Å are shown in Schemes –. Some of these molecules or their analogues have already been reported previously, such as A1–1, A2–1, B2–1, C1–2, E1–1, F1–1, G1, G1–1, G1–2, G2–1, H1, H1–1, H1–2, H2, H2–1, H2–5, H3, I1, I1–1, I1–4, and J1, providing sufficient bases for comparing the calculated and experimental results.…”

Section: Resultsmentioning

confidence: 90%

Influence of N-Oxide Introduction on the Stability of Nitrogen-Rich Heteroaromatic Rings: A Quantum Chemical Study

2016

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N-Oxidization is an important strategy for enhancing the density and energy of energetic materials. Nevertheless, the influence of N-O introduction on molecular stability remains relatively unknown. Thus, the present work comprehensively studied 102 basic N-rich ring structures, including azoles, furazans, and azines, as well as their N-oxides by quantum chemical calculations. The introduction of N-O weakens molecular stability in most cases because the process elongates chemical bonds, decreases ring aromaticity, narrows the gaps between the highest occupied and lowest unoccupied molecular orbitals, and increases the photochemical reactivity. Besides, the easy H transfer to the neighboring O atom, which forms a N-OH isomer in azoles, renders the stabilization by N-oxide introduction ineffective. However, N-oxide introduction can enhance the molecular stability of 1,2,3,4-tetrazine-1,3-dioxide and tetrazino-tetrazine 1,3,6,8-tetraoxide by promoting σ-π separation and relieving lone-pair repulsion. Moreover, the alternate arrangement of positive and negative charges is another factor stabilizing the 1,2,3,4-tetrazine ring by 1,3-dioxidation. Finally, we assess the accessibility of N-oxidized azoles and azines by regarding NO and HO as oxidizers. We find that all the oxidations were exothermic, thermodynamically spontaneous, and kinetically feasible. After an overall evaluation, we propose 19 N-oxides as basic structures for high-energy materials with considerable stability.

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“…Indeed, the dual mechanism (deprotonation/nucleophilic addition) induced by LDA in THF at a low temperature has been highlighted on α,β-ethylenic esters and thoroughly investigated . Moreover, the addition of PPh 3 , Ge[N(SiMe 3 ) 2 ] 2 , or a carbon nucleophile on the diazo function of diazodicarbonyl moieties as well as the addition of Et 3 N on the diazo function of diazomalodinitrile have been well-documented. In the light of these examples, an original mechanistic rationale was proposed to explain the outcome of the aldolisation between TIPS-diazoacetone 1 and benzaldehyde 2a in the presence of LDA (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

TIPS-Diazoacetone Aldol Addition: Mechanistic Aspects and Contribution to the Synthesis

et al. 2021

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Aldol addition of α-triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone), promoted by excess lithium diisopropylamide (LDA), was developed and applied to the synthesis of original C-TIPS diazoaldols, C-TIPS diazoketols, and a related Mannich-type product. An unprecedented mechanistic pathway has been proposed, involving a lithiated triazene intermediate resulting from the nucleophilic addition of LDA on the diazo moiety, supported by experimental results and DFT calculations.

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Strategy for the Synthesis of Pyridazine Heterocycles and Their Derivatives

Cited by 52 publications

References 51 publications

A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization

A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization

Influence of N-Oxide Introduction on the Stability of Nitrogen-Rich Heteroaromatic Rings: A Quantum Chemical Study

TIPS-Diazoacetone Aldol Addition: Mechanistic Aspects and Contribution to the Synthesis

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