Determination of the Enantiomerization Barrier of the Residual Enantiomers of C₃‐Symmetric Tris[3‐(1‐Methyl‐2‐Alkyl)Indolyl]Phosphane Oxides: Case Study of a Multitasking HPLC Investigation Based on an Immobilized Polysaccharide Stationary Phase

Abstract

The residual enantiomers of three tris-(3-indolyl)-phosphane oxides bearing different alkyl groups (methyl, ethyl or i-propyl) in position 2 of the indole rings constituting the blades were separated on the immobilized type Chiralpak IC column in polar organic and reversed-phase modes. The good enantioselectivity and versatility of the IC CSP allowed easy isolation of the enantiomerically highly enriched samples suitable for configurational stability studies. The enantiomerization barriers of residual phosphane oxides were evaluated both by off-column techniques (CD signal and enantiomeric purity decay kinetics) and by dynamic enantioselective high-performance liquid chromatography (HPLC).

BITHIENOLs: Promising C2‐Symmetric Biheteroaromatic Diols for Organic Transformation

“…Nevertheless, a careful consideration of the highly negative value found for Δ S ≠ also suggests that such a consistent reduction of entropy cannot be associated with the progress of a true elemental monomolecular first‐order process of the type that should occur if the monitored enantiomerization were due to a direct interconversion between the aS and aR enantiomers of 16 by simple rotation around the interannular bond. Instead, the entropy value of –46.5 cal mol –1 K –1 is perfectly compatible with a change in entropy associated with the progress of a pseudo‐first‐order event, which is the expression of a bimolecular process in which one of the species involved in the considered reaction is present in constant concentration , …”

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…For example, the effect of acidic and basic additives to 2propanol and acetonitrile based mobile phases on the enantiomer elution order of chiral β-blockers and other basic drugs on commercial polysaccharide chiral columns has been reported [135,136]. The influence of the 2,2'-alkyl chains of atropisomeric 1,1'-bibenzimidazole derivatives on an amylose tris- (3,5-dimethylphenylcarbamate) stationary phase was studied and it was noted that the chain length affected binding strength (accounted for analysis time) as well as enantiomer elution order [122]. The effect of halogen substitution in a large variety of structurally diverse analytes has also been summarized recently [124].…”

“…The additives are usually used at very low proportion (0.05-0.5%, v/v) and include mainly diethylamine (DEA), triethylamine (TEA), isopropylamine (iPA), 2-aminoethanol (AE), ethylenediamine (EDA) or trifluoroacetic acid (TFA), acetic acid (AA) and formic acid (FA). Among the basic additives, DEA is the most commonly used and has proved to be effective for screening and method development of many basic compounds [40,50,51,67,68,60,74,73,55,84,95,111,58,78,62,75,122,87,93,80] (see Tables 2-4). As a general rule, basic additives are employed for enantiomer separation of basic compounds, while acidic additives are essential for acidic ones.…”

“…37, α=1.24 [66] β-receptor blockers (Standard stock solution) [110] (A)=analytical, (S)=semipreparative, MeOH=methanol, EtOH=ethanol, IPA=2-propanol, BuOH=1-butanol, ACN=acetonitrile, w=water, HFor=Formic acid, TFA=Trifluoroacetic acid, n-Hex=n-hexane, PE=petroleum ether. (II) (d)Rs~1.5 [122] Farnesyl phenolic compounds (Extract of Genoderma sinense) n-Hex/IPA (65:35) IE (A) Rs~1.5 [123] (A)=analytical, (S)=semipreparative, (P)=preparative, MeOH=methanol, EtOH=ethanol, IPA=2-propanol, BuOH=1-butanol, t-BuOH=tert-butanol, ACN=acetonitrile, THF=tetrahydrofuran, w=water, DEA=diethylamine, BA=butyl amine, TFA=Trifluoroacetic acid, n-Hex=n-hexane, n-Hep=n-heptane, DCM=dichloromethane.…”

Theory and Practice of UHPLC and UHPLC–MS

“…Conformational changes are normally based on monomolecular mechanisms and, as such, do not require the assistance of a secondary molecular partner. Atropoisomerism is an intramolecular event that falls into this class of reactions, featuring pure first-order kinetics (Gasparrini et al, 1997a(Gasparrini et al, , 2000(Gasparrini et al, , 2001(Gasparrini et al, , 2002aDell'Erba et al, 2002;Andreani et al, 2004;Borsato et al, 2004;Dalla Cort et al, 2005;Lunazzi et al, 2010;Levi Mortera et al, 2012;Rizzo et al, 2013Rizzo et al, , 2014Rizzo et al, , 2015Chiarucci et al, 2014;Sabia et al, 2014Sabia et al, , 2016Menta et al, 2015). On the other hand, configurational isomerizations (i.e., processes involving rupture and reformation of chemical bonds) are commonly promoted by species that act as catalysts and that therefore do not modify their concentration during the interconversion (a bimolecular mechanism).…”