DFT calculations of CH acidity of substituted triazoles and experimental study of their ability to undergo mercuration

Halauko, Yury S.; Матулис, Вадим Э.; Ивашкевич, Олег А.; Grigoriev, Yury V.; Гапоник, П. Н.

doi:10.1016/j.tet.2010.03.053

Cited by 19 publications

(7 citation statements)

References 23 publications

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“…1 ). We showed earlier, for related substrates, the impact of the different hydrogen acidities on the regioselectivity of the reaction [ 37 – 38 40 , 42 – 43 ]. Based on these results, we here use CH acidities of the aromatic substrates in THF (calculated using the homodesmic reaction approach within the density functional theory (DFT) framework) to attempt a rationalization of the practical results.…”

Section: Introductionmentioning

confidence: 99%

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

Messaoud¹,

Bentabed‐Ababsa²,

Hedidi³

et al. 2015

Beilstein J. Org. Chem.

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SummaryThe synthesis of N-arylated pyrroles and indoles is documented, as well as their functionalization by deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and 4-bromophenyl, the reactions all took place on the substituent, at the position either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing substituent (OMe, Br). The CH acidities of the substrates were determined in THF solution using the DFT B3LYP method in order to rationalize the experimental results.

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Section: Introductionmentioning

confidence: 99%

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

Messaoud¹,

Bentabed‐Ababsa²,

Hedidi³

et al. 2015

Beilstein J. Org. Chem.

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“…The hybrid B3LYP DFT method is a popular electronic modelling method for molecular thermochemistry; it gives reliable predictions for the acidities of organic compounds 17,20,21 . A study by Karty and co‐workers showed that the experimental deprotonation enthalpies of lactone enolates were in good agreement with the B3LYP/6‐31+G(d) calculations 20 .…”

Section: Calculationsmentioning

confidence: 99%

Tracking the deprotonation site of dehydroandrographolide with electrospray ionization mass spectrometry by deuteration

Huo

Wang

Feng

et al. 2021

Rapid Comm Mass Spectrometry

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Rationale Dehydroandrographolide (DA) is a diterpene compound of biological interest that contains one α,β‐unsaturated lactone group and two hydroxy groups. In the ESI (electrospray ionization) negative ion mode mass spectral analysis of 15‐dideuterodehydroandrographolide (15‐D2‐DA), the deuterium nucleus at the γ position of the α,β‐unsaturated lactone was more easily dedeuterated than deprotonation of the protons from the hydroxy groups. Exploring the rationality of deuteration as a tool for deprotonation position tracking is significant for gas‐phase acidity. Methods The mass spectra of DA and 15‐D2‐DA in positive and negative ion mode were acquired by liquid chromatography/ion trap time‐of‐flight mass spectrometry (LC/IT‐TOF) systems. The deprotonation and dedeuteration energies at specific sites were calculated by the B3LYP and M06‐2X density functional theory (DFT) methods with the program Gaussian 16. Results The [M + H]+ ion of 15‐D2‐DA was 2 amu larger than that of DA due to the substitution of two hydrogens with two deuteriums; however, the anion base peak of 15‐D2‐DA was only 1 amu larger than that of the [M – H]− ion of DA. Dedeuteration at the C15 site was proposed according to the mass spectral data. The deprotonation (dedeuteration) energies calculated by the B3LYP/6‐311++G(3df,3pd)//B3LYP/6‐31 + G(d) and M06‐2X‐D3/ma‐TZVP methods showed that the C–H and C–D bonds at the C15 site have lower deprotonation (dedeuteration) energies than the energies of the hydroxy groups of DA, making their deprotonation (dedeuteration) more thermodynamically favourable. Conclusions Deuteration of DA provided direct evidence of the deprotonation site of DA in the ESI source of the mass spectrometer, and the DFT method well predicted the gas‐phase deprotonation site of DA.

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“…17 Gas-phase deprotonation energies for several triazoles were estimated by means of semi-empirical calculations. 18 We also recently contributed to this field by DFT computed values for substituted triazoles, 19 All the calculations were performed by using the DFT B3LYP method. The geometries were optimized using the 6-31G(d) basis set.…”

Section: Computational Aspectsmentioning

confidence: 99%

“…(C), 149.4 (C); 19 F NMR (CDCl 3 , 282 MHz) -57.9. Iodo-2-(2-iodo-4-trifluoromethoxyphenyl)-2H-1,2,3-triazole (10).…”

Section: -(2-iodo-4-trifluoromethoxyphenyl)-mentioning

confidence: 99%

Deprotometalation–iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

Nagaradja

Bentabed‐Ababsa

Scalabrini

et al. 2015

Bioorganic & Medicinal Chemistry

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1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2'-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line.

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DFT calculations of CH acidity of substituted triazoles and experimental study of their ability to undergo mercuration

Cited by 19 publications

References 23 publications

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

Tracking the deprotonation site of dehydroandrographolide with electrospray ionization mass spectrometry by deuteration

Deprotometalation–iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

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