Theoretical study of reaction mechanism and regioselectivity of spiro-isoxazoline derivatives synthesized by intermolecular 1,3-dipolar cycloaddition

Zhao, Haitao; Li, Xiaofang; Ran, Xiaorong; Zhang, Wenqin

doi:10.1016/j.theochem.2004.06.019

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…The reaction products have exothermic by 55.95 and 28.15 kcal/mol for 6a and 6a′ , respectively. These results can be explained by the presence of only a stabilizing π/π interaction in 6a compared to the 6a′ product . Selected geometrical parameters of the TSs and products for the two reaction possible pathways are shown in Figure .…”

Section: Resultsmentioning

confidence: 98%

“…The structural analysis of these TSs indicates the presence of unfavorable steric interactions between the chlorine atom in the 5a framework and π electron of the phenyl group in the 4a framework in TSB, see Figure 5, whereas in TSA the steric interactions are not observed. The reaction products have exothermic by 55.95 and 28.15 kcal/mol for 6a and 6a′, respectively. These results can be explained by the presence of only a stabilizing π/π interaction in 6a compared to the 6a′ product.…”

Section: Mechanistic Studymentioning

confidence: 99%

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Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

et al. 2022

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A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N-alkylation and 1,3-dipolar cycloaddition reactions, as well as their structures were established through spectroscopic methods and confirmed by mass spectrometry. To get more light on the regioselective synthesis of new hybrid compounds, mechanistic studies were performed using DFT calculations with B3LYP/6-31G(d,p) basis set. Additionally, the results of the preliminary screening indicate that some of the examined hybrids showed potent antimicrobial activity, compared to standard drugs. The results confirm that the antimicrobial activity is strongly dependent on the nature of the substituents linked pyrazole and isoxazoline rings. Furthermore, molecular docking studies were conducted to highlight the interaction modes between the investigated hybrid compounds and the Escherichia coli and Candida albicans receptors. Notably, the results demonstrate that the investigated compounds have strong protein binding affinities. The stability of the formed complexes by the binding between the hybrid compound 6c, and the target proteins was also confirmed using a 100 ns molecular dynamics simulation. Finally, the prediction of ADMET properties suggests that almost all hybrid compounds possess good pharmacokinetic profiles and no signs of observed toxicity, except for compounds 6e, 6f, and 6g.

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Section: Resultsmentioning

confidence: 98%

Section: Mechanistic Studymentioning

confidence: 99%

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

et al. 2022

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“…Donor substituents on BNOs, especially methoxyls, increased the reaction rate and yields of products of the both 4 and 5 . Because of a bulkiness of the BNO substituents, the regioselectivity of those reactions seems to be predetermined also by a volume and mutual interactions of three aromatic substituents close each to other in the position 3, 4, and 5 of the isoxazoline products …”

Section: Resultsmentioning

confidence: 99%

Prediction by ¹³C NMR of regioselectivity in 1,3‐dipolar cycloadditions of acridin‐9‐yl dipolarophiles

Vilková

Maľučká

Imrich

2015

Magnetic Reson in Chemistry

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Strong correlation was found between (13)C NMR chemical shifts of dipolarophilic CH=CH carbons and regioselectivity in 1,3-dipolar cycloadditions of new acridin-9-yl dipolarophiles with stable benzonitrile oxides (BNO). Accordingly, two starting dipolarophiles, (acridin-9-yl)-CH=CH-R (R = COOCH3 or Ph), reacted with three BNOs (2,4,6-trimethoxy, 2,4,6-trimethyl, and 2,6-dichloro) to give a mixture of two target isoxazoline regioisomers in which the acridine was bound either to isoxazoline C-4 carbon (4-Acr) or C-5 one (5-Acr). Methyl 3-(acridin-9-yl)propenoate afforded major 4-(acridin-9-yl)-isoxazoline-5-carboxylates (4-Acr) and minor 5-(acridin-9-yl)-4-carboxylates (5-Acr). 9-(2-Styryl)acridine regiospecifically afforded only 4-Acr cycloadducts. The ratios of regioisomers were compared with analogous reactions of acridin-4-yl dipolarophiles. Regioselectivity was dependent on a polarity of the CH=CH bond, donor effects in BNO, and stabilization by stacking of aromatic substituents in the products.

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“…48 A careful analysis of reactivity indices showed that the regioselectivity could be explained simply by pairing the strongest nucleophilic and electrophilic sites of the reactant. 1,3-Dipolar cycloaddition reactions were also studied by Zhang and co-workers, 49 once again at the B3LYP/6-31G(d) level of theory. In the case of competing pathways they found good agreement between the predicted and experimental products and rationalised the selectivity in terms of both steric and orbital overlap effects.…”

Section: Pericyclic Reactionsmentioning

confidence: 99%

10 Computational organic chemistry

Yates

2005

Annu. Rep. Prog. Chem., Sect. B

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Theoretical study of reaction mechanism and regioselectivity of spiro-isoxazoline derivatives synthesized by intermolecular 1,3-dipolar cycloaddition

Cited by 11 publications

References 48 publications

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

Prediction by ¹³C NMR of regioselectivity in 1,3‐dipolar cycloadditions of acridin‐9‐yl dipolarophiles

10 Computational organic chemistry

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Theoretical study of reaction mechanism and regioselectivity of spiro-isoxazoline derivatives synthesized by intermolecular 1,3-dipolar cycloaddition

Cited by 11 publications

References 48 publications

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

Prediction by 13C NMR of regioselectivity in 1,3‐dipolar cycloadditions of acridin‐9‐yl dipolarophiles

10 Computational organic chemistry

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Prediction by ¹³C NMR of regioselectivity in 1,3‐dipolar cycloadditions of acridin‐9‐yl dipolarophiles