Optical Purity Determination and 1H NMR Spectral Simplification with Lanthanide Shift Reagents: Glutethimide, 3-Ethyl-3-phenyl-2,6-piperidinedione, 1

1983 ◽  
Vol 37 (3) ◽  
pp. 292-296 ◽  
Author(s):  
Suzanne Eberhart ◽  
Robert Rothchild
Keyword(s):  
Aromatic Ring ◽  
Optical Purity ◽  
Shift Reagent ◽  
Coupling Constants ◽  
Line Broadening ◽  
Molar Ratios ◽  
H Nmr ◽  
A Value ◽  
Chiral Shift Reagent ◽  
Lanthanide Shift Reagents

The 60 MHz 1H NMR spectra of racemic glutethimide, 1, have been studied with the chiral shift reagent, tris[3-(trifluoromethylhydroxymethylene)- d-camphorato] europium(III), 2, and the achiral tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(III), 3. Appreciable values of the enantiomeric shift difference, ΔΔδ, were observed at relatively low molar ratios of 2:1 for the CH3 group in CDCl3 solution at 28°C. Optical purity determinations should easily be carried out by using this absorption with a 2:1 ratio of approximately 0.25; 3 to 5% of one enantiomer should be detectable in a sample. Lanthanide-induced line broadening was relatively low, thereby facilitating these measurements. A substantial ΔΔδ was also observed for the ortho hydrogens of the aromatic ring and the NH. For example, at a 2:1 ratio of 0.254, the CH3 resonance displayed a value of ΔΔδ of 7.3 Hz (0.12 δ) and was free of overlap with the absorptions of the shift reagent, 2. The relative slopes of the plots of induced shift, Δδ, vs molar ratios of 2:1 or 3:1, as well as values of coupling constants, support assignments for the proton absorptions of the aromatic ring.

Optical Purity Determination and 1H NMR Spectral Simplification with Lanthanide Shift Reagents. II. Thiamylal, 5-Allyl-5-(1-methylbutyl)-2-thiobarbituric Acid

1984 ◽  
Vol 38 (1) ◽  
pp. 74-78 ◽  
Author(s):  
S. Eberhart ◽  
R. Rothchild
Keyword(s):  
Optical Purity ◽  
Thiobarbituric Acid ◽  
Carbonyl Oxygen ◽  
Shift Reagent ◽  
Coupling Constants ◽  
Molar Ratio ◽  
Line Broadening ◽  
A Value ◽  
Purity Evaluation

A racemic sample of thiamylal, 5-allyl-5-(1-methylbutyl)-2-thiobarbituric acid, 1, has been shown to exhibit significant enantiomeric shift differences, ΔΔδ, for the CH3- CH proton absorptions when treated with the chiral lanthanide shift reagent, tris[3-(trifluoromethylhydroxy-methylene)- d-camphorato| europium (III), 2, in CDC13 at 28°. For example, at the relatively low molar ratio of 2:1 of 0.181, a value of ΔΔδ of 22 Hz (0.36δ) was observed, which increased to 26 Hz (0.43δ) at a molar ratio of 0.226. These large values, with relatively little lanthanide-induced line-broadening, should make possible the facile determination of optical purity of 1 even with a 60 MHz nmr spectrometer. Parallel studies were run using the achiral shift reagent, tris-(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium (III), 3, to confirm peak assignments. The considerable values of ΔΔδ may reflect the “soft base” character of the sulfur atom in 1. Less effective binding by sulfur to the lanthanide atom could lead to coordination by europium on the carbonyl oxygen, relatively close to the chiral center, providing enhanced AA5 values compared to some related compounds. While several other proton absorptions of 1 appear to show some observable ΔΔδ, they are less valuable for optical purity evaluation because of lower intensity, greater multiplicity, or small ΔΔδ value. The relative slopes of the plots of chemical shift, δ, for runs with 2 or 3, are consistent with the full assignment of the proton absorptions of 1 based on expected proximity of the protons to the complexed europium atom. The observed coupling constants of the vinyl hydrogens of 1 further support the assignments.

1H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Part II: Ethosuximide, 3-Ethyl-3-Methyl-2,5-Pyrrolidinedione, and Comparisons with Analogs

1986 ◽  
Vol 40 (4) ◽  
pp. 531-537 ◽  
Author(s):  
John Avolio ◽  
Suzanne Thomson Eberhart ◽  
Robert Rothchild ◽  
Paul Simons
Keyword(s):  
1H Nmr ◽  
Nmr Spectra ◽  
Shift Reagent ◽  
Ethyl Group ◽  
Molar Ratios ◽  
H Nmr ◽  
Lanthanide Shift Reagents ◽  
Shift Reagents

The 60 MHz 1H NMR spectra of racemic ethosuximide, 1, have been studied in detail with the achiral shift reagent, tris(6,6,7,7,8,8,8-hepta-fiuoro-2,2-dimethyl-3,5-octanedionato)europium(III), 2, and the chiral tris(3-trifluoromethylhydroxymethylene)- d-camphorato]europium(III), 3. Enantiomeric shift differences, ΔΔδ, were clearly observed for the CH3 of the ethyl group of 1 at molar ratios of 3:1 as low as 0.0385, with ΔΔδ valaues of about 12 Hz seen at a 3:1 ratio of 0.340 for CDCl3 solutions at 28°, 0.634 molal in 1. Smaller ΔΔδ values were also seen for the quaternary methyl and for one of the hydrogens at C-4. Parallel studies with 2 were performed to support assignments. Results are compared with a group of important drugs that are structurally related, including ethotoin, mephenytoin, glutethimide, methsuximide, phensuximide, and paramethadione, in terms of steric and basicity effects. Correlations of both lanthanide-induced shift (Δδ) and ΔΔδ could generally be made from simple electronic considerations related to infrared carbonyl stretching frequencies. Of the 28 sets of Δδ values assigned for the substrates, 3 gave significantly larger values than 2 in only two cases.

1H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Part III:* Vinclozolin

1986 ◽  
Vol 40 (6) ◽  
pp. 743-745 ◽  
Author(s):  
Alexander Hatzis ◽  
Robert Rothchild
Keyword(s):  
1H Nmr ◽  
Nmr Spectra ◽  
Optical Purity ◽  
Molar Ratio ◽  
Molar Ratios ◽  
Chiral Reagent ◽  
H Nmr ◽  
Lanthanide Induced Shifts ◽  
Lanthanide Shift Reagents ◽  
Shift Reagents

The 60 MHz 1H NMR spectra of racemic vinclozolin, 1, have been studied at 28° in CDCI3 solution with the achiral reagent tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III), 2, and the chiral reagents tris[3-(trifluoromethylhydroxymethylene)- d-camphorato] europium(III), 3, and tris[3-(heptafluoropropylhydroxymethylene)- d-camphorato]europium(III), 4. Reagent 3 produced only small lanthanide-induced shifts and no observable enantiomeric shift differences, ΔΔδ, with 3:1 molar ratios as high as 1.40. In contrast, chiral reagent 4 produced substantial ΔΔδ for the proton, Hβ, at C-2 of the ethenyl group syn to the oxazolidinedione ring and smaller ΔΔδ for the anti proton, Hβ, at the above carbon and for the CH3. With a 4:1 molar ratio of 0.581, ΔΔδ of 7.0 Hz was seen for Hβ. A 4:1 ratio of about 0.41 should be optimum for optical purity determinations; as little as 5% of the minor enantiomer should be detectable.

Optical Purity Determination and 1H NMR Spectral Simplification with Lanthanide Shift Reagents III: Ethotoin, 3-Ethyl-5-Phenyl-2, 4-Imidazolidinedione

1984 ◽  
Vol 38 (5) ◽  
pp. 734-737 ◽  
Author(s):  
John Avolio ◽  
Robert Rothchild
Keyword(s):  
1H Nmr ◽  
Nmr Spectra ◽  
Optical Purity ◽  
Shift Reagent ◽  
Methine Proton ◽  
Molar Ratio ◽  
Purity Determination ◽  
H Nmr ◽  
Lanthanide Shift Reagents ◽  
Shift Reagents

The 60 MHz 1H NMR spectra of racemic ethotoin, a, have been studied with the achiral shift reagent tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimeth-yl-3,5-octanedionato) europium (III), b, and the chiral tris[3-(rrifluoromethylhydroxymethylene)- d-camphorato] europium (III), c Appreciable values of the enantiomeric shift difference, ΔΔδ, were observed for the NH, CH3, CH, and ortho aryl protons in CDCl3 solutions at 28°C with the use of samples about 045 molal in a Optical purity assays should be feasible with the use of the NH or CH3 absorptions that display ΔΔδ of 224 and 70 Hz, respectively, at a c:a molar ratio of about 03, with the former resonance being optimal With a c:a ratio between 04–05, the methine proton can be used, with ΔΔδ 11 – 13 Hz Results are interpreted in terms of major coordination of the europium at the C-2 oxygen

The 1H NMR spectra and the conformation of 1,6-anhydro-β-D-hexopyranoses and their triacetates

1979 ◽  
Vol 44 (6) ◽  
pp. 1949-1964 ◽  
Author(s):  
Miloš Buděšínský ◽  
Tomáš Trnka ◽  
Miloslav Černý
Keyword(s):  
Nmr Spectra ◽  
Chemical Shifts ◽  
Shift Reagent ◽  
Point Of View ◽  
Coupling Constants ◽  
Lanthanide Shift Reagent ◽  
Pyranose Ring ◽  
H Nmr ◽  
Vicinal Coupling Constants

The 1H NMR spectra of 1,6-anhydro-β-D-hexopyranoses and their triacetates, measured in hexadeuteriodimethyl sulfoxide or deuteriochloroform, confirmed the existence of these compounds in 1C4(D) conformations, with the pyranose ring partly planarized in dependence on the configuration of the substituents in positions C(2), C(3) and C(4). The effects of the substituents on the chemical shifts and the adjusted relationship for the dependence of vicinal coupling constants on the torsion angle are discussed in detail from the point of view of the determination of the configuration and the conformation of 1,6-anhydro-β-D-hexopyranoses and their derivatives. The 1H NMR spectra of triacetates were also measured in the presence of the lanthanide shift reagent, tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione) europium (III) [Eu.(FOD)3].

scholarly journals Microsolvation and sp2-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

2014 ◽  
Vol 10 ◽  
pp. 2521-2530 ◽  
Author(s):  
Rudolf Knorr ◽  
Monika Knittl ◽  
Eva C Rossmann
Keyword(s):  
Title Compound ◽  
Low Temperatures ◽  
Ion Pair ◽  
Coupling Constants ◽  
Ionic Mechanism ◽  
Line Broadening ◽  
Aryl Group ◽  
H Nmr ◽  
Nmr Signals ◽  
Butyl Methyl Ether

The β-unsubstituted title compound dissolves in THF as a uniformly trisolvated monomer, whereas it forms exclusively disolvated monomers in tert-butyl methyl ether, Et2O, TMEDA, or toluene with TMEDA (1.4 equiv). This was established at low temperatures through the observation of separated NMR signals for free and lithium-coordinated ligands and/or through the patterns and magnitudes of 13C,6Li NMR coupling constants. An aggregated form was observed only with Et2O (2 equiv) in toluene as the solvent. The olefinic geminal interproton coupling constants of the H2C= part can be used as a secondary criterion to differentiate between these differently solvated ground-states (3, 2, or <2 coordinated ligands per Li). Due to a kinetic trisolvation privilege of THF, the cis/trans sp2-stereoinversion rates could be measured through analyses of 1H NMR line broadening and coalescence only in THF as the solvent: The pseudomonomolecular (because THF-catalyzed), ionic mechanism is initialized by a C–Li bond heterolysis with the transient immobilization of one additional THF ligand, followed by stereoinversion of the quasi-sp2-hybridized carbanionic center in cooperation with a “conducted tour” migration of Li+(THF)4 along the α-aryl group within the solvent-separated ion pair.

scholarly journals The Bull–James assembly as a chiral auxiliary and shift reagent in kinetic resolution of alkyne amines by the CuAAC reaction

2016 ◽  
Vol 14 (46) ◽  
pp. 10778-10782 ◽  
Author(s):  
William D. G. Brittain ◽  
Brette M. Chapin ◽  
Wenlei Zhai ◽  
Vincent M. Lynch ◽  
Benjamin R. Buckley ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Boronic Acid ◽  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Shift Reagent ◽  
Chiral Auxiliary ◽  
H Nmr ◽  
Chiral Shift Reagent ◽  
Cuaac Reaction

The Bull–James boronic acid assembly is used simultaneously as a chiral auxiliary for kinetic resolution and as a chiral shift reagent for in situ enantiomeric excess (ee) determination by 1H NMR spectroscopy.

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