Sterically hindered and completely arrested nitrogen inversion in pyrazolidines

Usachev, S. V.; Никифоров, Г. А.; Nelubina, Yulia V.; Levkin, Pavel A.; Kostyanovsky, Remir G.

doi:10.1016/j.tetasy.2007.06.022

Cited by 6 publications

(3 citation statements)

References 20 publications

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“…Nevertheless, for cations in 5c – e and 6 with similar conformations, the mean atomic deviation doesn′t exceed 0.5Å ( Figure 2 b). The positive charge on quaternary ammonium atom causes elongation of N(1)-N(2) and N(1)-C(1) bonds as it was previously demonstrated for 5-aryl-3-[2-(piperidin-1-yl)ethyl]-1,2,4-oxadiazoles [ 9 ], 2-amino-8-thia-1-aza-5-azoniaspiro[4.5]dec-1-ene [ 7 ], 1-( tert -butyl)-4,5-dihydro-1 H -pyrazol-1-ium [ 19 ] and 1,1,3-trimethyl-Δ 2 -pyrazolinium [ 20 ] analogs.…”

Section: Resultsmentioning

confidence: 69%

Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties

Kаyukova¹,

Вологжанина

Praliyev³

et al. 2021

Molecules

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The analysis of stability of biologically active compounds requires an accurate determination of their structure. We have found that 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles are generally unstable in the presence of acids and bases and are rearranged into the salts of spiropyrazolinium compounds. Hence, there is a significant probability that it is the rearranged products that should be attributed to biological activity and not the primarily screened 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles. A series of the 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium (spiropyrazoline) benzoates and chloride was synthesized by Boulton–Katritzky rearrangement of 5-substituted phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles and characterized using FT-IR and NMR spectroscopy and X-ray diffraction. Spiropyrazolylammonium chloride demonstrates in vitro antitubercular activity on DS (drug-sensitive) and MDR (multidrug-resistant) of MTB (M. tuberculosis) strains (1 and 2 µg/mL, accordingly) equal to the activity of the basic antitubercular drug rifampicin; spiropyrazoline benzoates exhibit an average antitubercular activity of 10–100 μg/mL on MTB strains. Molecular docking studies revealed a series of M. tuberculosis receptors with the energies of ligand–receptor complexes (−35.8–−42.8 kcal/mol) close to the value of intermolecular pairwise interactions of the same cation in the crystal of spiropyrazolylammonium chloride (−35.3 kcal/mol). However, only in complex with transcriptional repressor EthR2, both stereoisomers of the cation realize similar intermolecular interactions.

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Section: Resultsmentioning

confidence: 69%

Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties

Kаyukova¹,

Вологжанина

Praliyev³

et al. 2021

Molecules

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“…Structures of pyrazolines 4 were determined on the basis of analysis of their 1D and 2D NMR spectra and unambiguously proved by single‐crystal X‐ray data for compound 4h This is the first example of X‐ray data for 1‐alkylpyrazolines bearing no other substituents …”

Section: Resultsmentioning

confidence: 93%

Synthesis of 1‐Substituted Pyrazolines by Reaction of Donor‐Acceptor Cyclopropanes with 1,5‐Diazabicyclo[3.1.0]hexanes

et al. 2019

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Substituted pyrazolines were obtained by Ni(ClO4)2·6H2O‐catalyzed reaction of 1,5‐diazabicyclo[3.1.0]hexanes with donor‐acceptor cyclopropanes. The mechanism of this reaction includes alkylation of diaziridine nitrogen with Lewis acid‐activated donor‐acceptor cyclopropane followed by hydration of the formed 1,6‐zwitterionic intermediate and oxidation of pyrazolidine with air oxygen. This pathway is realized when starting bicyclic diaziridines have bulky alkyl substituent(s) at the C(6) atom preventing (3+3)‐annulation of two three‐membered rings.

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“…In what concerns nitrogen inversion, it has been reported and reviewed for pyrrolidines [12–14], of the two pyrrolines, only the 3‐pyrroline has been reported [15], and the barrier in pyrazolidines has been studied by several authors including ourselves [8,9,11,16]. Finally, the 3‐pyrazolines are the object of the present paper.…”

Section: Introductionmentioning

confidence: 99%

A theoretical study of inversion barriers and NMR chemical shifts of 3‐pyrazolines (2,3‐dihydro‐1H‐pyrazoles)

Alkorta

Elguero

2021

Journal of Heterocyclic Chem

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A rather neglected family of heterocyclic compounds, the 3‐pyrazolines or 2,3‐dihydro‐1H‐pyrazoles, has been studied theoretically at the B3LYP/6–311++G(d,p) level to obtain geometries and energies and at the GIAO/B3LYP/6–311++G(d,p) level for NMR chemical shifts. The calculated barriers of inversion of the N‐substituents reproduce adequately the scarce experimental data. The calculated 1H and 13C chemical shifts are consistent with those reported in the literature. A combination of both results, geometries, and 13C chemical shifts, shed light on the conformation of N‐phenyl groups.

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Sterically hindered and completely arrested nitrogen inversion in pyrazolidines

Cited by 6 publications

References 20 publications

Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties

Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties

Synthesis of 1‐Substituted Pyrazolines by Reaction of Donor‐Acceptor Cyclopropanes with 1,5‐Diazabicyclo[3.1.0]hexanes

A theoretical study of inversion barriers and NMR chemical shifts of 3‐pyrazolines (2,3‐dihydro‐1H‐pyrazoles)

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