Equilibration studies

Alternatively, lactols react with benzenesulfinic acid in the presence of CaCl2 to yield the sulfones, again at room temperature [307,309]. In the axial series, the bulk of the sulfone group is such that the 4Cj chair is not always the preferred conformation, and it has been shown that a twist-boat conformer is adopted in at least one instance [305]. Nevertheless, equilibration studies have shown that the sulfonyl group has a small anomeric effect and that the axial anomer is preferred [310],... 

Catalytic reduction of bridgehead enol lactone over Pd/C indicates that, indeed, the syn addition from the exo face of the bridgehead double bound establishes the relative configuration of all substituents [264], Equilibration studies performed in EtONa/EtOH also established that the ratio of the epimers corresponds to an equilibrium mixture. Under mild basic conditions (NajCOj/ EtOH), the product isomerization occurs to a very small extent. The product distribution is best understood by rapid conformational relaxation to one of the two low-eneigy half-chair conformations. The stereochemistry is established at the subsequent protonation step. This takes place with a strong preference for axial protonation from the /I face at carbon 2 to produce the most stable chair conformation (Scheme 14.12). 

The rate at which pollutants sorb to sediments has frequently been assumed to occur rapidly and consequently equilibration studies have often been conducted by mixing sample for 24 hours. Karickhoff (I, 66) has reported that sorption may require up to two months to reach an apparent equilibrium. Similarly, desorption has also been observed to require on the order of months to reach completion (67, 68). McCall and Agin (67) observed that the desorption rate of picloram was inversely related to the contact time. 

Most thermodynamic data for solid solutions derived from relatively low-temperature solubility (equilibration) studies have depended on the assumption that equilibrium was experimentally established. Thorstenson and Plummer (10) pointed out that if the experimental data are at equilibrium they are also at stoichiometric saturation. Therefore, through an application of the Gibbs-Duhem equation to the compositional dependence of the equilibrium constant, it is possible to determine independently if equilibrium has been established. No other compositional property of experimental solid solution-aqueous solution equilibria provides an independent test for equilibrium. If equilibrium is demonstrated, the thermodynamic properties of the solid solution are also... 

M. Lucarini, P. Pedrielli, G. F. Pedulli, S. Cabiddu, C. Fattuoni. Bond Dissociation Energies of O-H Bonds in Substituted Phenols from Equilibration Studies. J. Org. Chem. 1996, 61, 9259-9263. 

In the equilibration studies previously cited, two mechanisms for the interconversion of aldol diastereoisomers are possible, the most obvious being via the retroaldol process (28). In some instances, however, base-catalyzed equilibration via the aldolate enolate 18 is certainly possible (eq. [11a]), and such enolates are well documented as useful intermediates in synthesis (19). For example, Frdter has demonstrated that aldolate enolate 18a may be generated from... 

It would be highly desirable to be able to correlate metal ion structure as well as the individual steric requirements of the specific substituents Ri, R2, and Ra with the equilibration studies cited above. Because of the numerous uncertainties associated with the data, however, only qualitative generalizations can be made. The higher-valent metal aldolate complexes (M = ZnL, MgL, AIL2), upon equilibration, appear to favor the threo diastereomer to a greater extent than the monovalent metal aldolates (M = Li, Na). With regard to... 

The role of sulfur in these vents is complex and often obscured by its multiple redox states and by uncertainties in the degree of equilibration. Studies by Styrt et al. (1981), Arnold and Sheppard (1981), Skirrow and Coleman (1982), Kerridge et al.(1983), Zierenberg et al. (1984), and others have shown that the sulfur in these deposits is enriched in S relative to a mantle source (typical 5 " S ranges are between 1 and 5%c), implying small additions of sulfide derived from sea water. 

In Fig. 2, the results of equilibration studies are indicated. In only one case (216 217), as might be expected, is an equilibrium established, and there is little difference in the relative thermodynamic stability of the two isomers (216 and 217). On current knowledge, it is not possible to provide a well-based understanding of the factors that determine the relative thermodynamic stability of meso-ionic isomers. 

Another example is part of the structural elucidation of 3-hydroxy-5-methyl-2-piperidinecar-boxylic acid, which has been identified as a component of some peptide antibiotics (see p 440). The relative configuration was determined by preparing (unselectively) all four racemic diastereomers 8-11 and subsequent H-NMR and equilibration studies. Thus, 8 and 9 were each converted to an equilibrium mixture of these two isomers in the ratio 2 1 (see p 472). From this experiment it was concluded, that 8 and 9 are epimeric at C-2, and that the more stable isomer has the 2,3-trans configuration 8 (the latter conclusion was based on previous results). In the same way the relative configuration at C-2 and C-3 of 10 and 11 was established274. 

Equilibration studies with the lithium dianions of a,/j-unsaturated acids were first carried out by P. E. Pfeffer, L. S. Silbert, J. Org. Chem. 36, 3290 (1971). 

The stereochemistry of ketene to alkcne cycloadditions is such that retention of the alkene configuration is observed. Furthermore, in cycloadditions with unsymmetrically substituted ketenes the larger of the two ketene substituents ends up as with respect to the adjacent alkene substituent (or eiulo in cycloalkene cycloadditions). This stereochemical outcome was originally attributed to the concerted [ff2a + n2a] nature of kctcnc to alkene cycloadditions,21 although more recent experimental and theoretical evidence indicate that these reactions are asynchronous and in some cases in which polarized double bonds are involved actual zwittcrions may be intermediates.9 1195 Also in certain cases the endo product in ketene to alkene cycloadditions may be the thermodynamic product from equilibration studies.22,23 Nevertheless, stereochemical control can be achieved in most such reactions as shown by the examples of 12,24 13,29 14,25 15,26 16,27 and 17.28... 

On the basis of the above results and discussion, the glycosides can now be considered. Efforts have been made previously to evaluate the magnitude of the anomeric effect by undertaking equilibration studies between equatorial and axial isomers at the anomeric center in carbohydrates (48), in monosubstituted 2-alkoxytetrahydropyrans (49, 50) and in more rigid systems (51). The anomeric effect has been evaluated to be of the order of 1.2 to 1.8 kcal/mol from these studies. In these evaluations, the conformation of the OR group in the axial and in the equatorial isomer was not considered the influence of the exo-anomeric effect was therefore neglected (3). Nevertheless, these studies demonstrated the importance of the anomeric effect. 

King and All butt (60, 62) have described the stereoselective hydrolysis of the dioxolenium ion 98 derived from a trans-decalin. Mild acid hydrolysis of 98 afforded almost entirely the axial ester product 99 with only a trace (<0.5%) of the equatorial ester 100. A similar result was obtained by using mild basic conditions. The authors further established by equilibration studies that the equatorial ester 100 is the most stable isomer, demonstrating that the formation of the axial isomer 99 is subject to kinetic rather than thermodynamic control. Essentially identical results were produced with two other dioxolenium salts derived from steroids. 

The rates of (aS-(a/ ) interconversion measured in CDC13 and C6D6 for analogs of colchicine differently substituted at C-l were found to be of the order of 10-4 to 10-5 sec-1 at 22°C, corresponding to a free energy of activation of 22-24 kcal/mol. Equilibration studies by H NMR revealed that an equatorial orientation of the acetamido group in colchicine and... 

In an equilibration study the conjugated vinylcyclopropane 11b was more stable than the unconjugated isomer 11a by 1.2 kcal mol" ... 

Static, equilibration studies also indicated that a molecular association forms at the oil/water interface in the presence of mixed emulsifiers. Spinning drop experiments with pre-equilibrated oil and aqueous phases suggested that the presence of oil in association with the mixed emulsifier molecules in the aqueous phase affects the formation of an interfacial layer. 

Equilibration Studies, Because the formation of an interfacial layer is a dynamic phenomenon, experiments were conducted to study the effect of oil-water phase equilibria on interfacial properties. Two experiments were carried out where aqueous solutions of 1 1 SLS/LA were equilibrated with both styrene and toluene in sealed containers, without agitation for five weeks. Several important observations were made (a) Despite the presence of mixed emulsifiers,... 

M3. MacGregor, J., and Nordin, B. E. C., Equilibration studies with human bone powder. J. Biol. Chem. 235, 1215-1218 (1960). 

On the basis of equilibration studies, pK values and the sign of the 290 m/x band in CD, formosanine (positive 290 m/x CD band) and isoformosanine (negative 290 mp. CD band) have been assigned the 19j8-methyl normal B and 19 -methy normal A conhgurations, respectively (56, 57). These structures have been conhrmed by total synthesis of the two alkaloids (57a). 

The easiest, and probably safest, way to determine which of two forms is the stable one at a given temperature is to perform equilibration studies. Equal amounts of both forms are suspended in a solvent, which dissolves part of the API, and are equilibrated at the temperature for a few days or a week. The suspension is then hltered, and the wet hlter cake is analyzed using x-ray powder diffractometry. If the powder pattern shows an increase of one form, that form is the stable form. The longer it takes for the full transformation to occur, the smaller the driving force (e.g., because the temperature is close to Tj or the solubility difference of both forms is minute). Be aware that equilibration of just one form is insufficient to prove stability—the stable form has to nucleate, and it may not do so readily. 

Equilibration studies on model compounds 109 showed that in those with H-3 and H-5 cis the latter proton appeared as a low-field NMR signal at ca. 

The synthesis of isosophoramine (26) employs as crucial stages the partial hydrogenation of iV-alkyl salts of ) -acyl (or cyano) pyridines, and acid-catalysed cyclization of the resulting l-alkyl-3-acyl (or cyano)-2-piperideines. Alkylation of nicotinonitrile with 6-bromohexan-2-one ethylene ketal afforded the salt (27), which on palladium-catalysed hydrogenation yielded the piperideine (28). Anhydrous acid-catalysed (TsOH) cyclization of (28) gave the three quinolizidine stereoisomers (29)—(31), which were separated and analysed by n.m.r. spectroscopy and equilibration studies in acid (TsOH-CgH ) and alkaline (KOBu -Bu OH)... 

Tables 6 and 7 summarize results from stereochemical equilibration studies performed over the past decade by MaryanofT et al. (22,23), and Vedejs et al. (20, 21c, 39-42). A few other convincing examples are included to expand the scope of the systems covered. Table 6 lists those examples where control experiments establish at least 90% retention of stereochemistry from intermediates-to alkene products. As already discussed, the percentage of equilibration represents the upper limit for loss of stereochemistry from all possible pathways in the control experiments. No attempt has been made to determine whether the minor levels of stereochemical leakage in Table 6 occur at the stage of oxaphosphetanes, betaines, or other potential intermediates. Table 6 includes entries corresponding to all of the principal families of Wittig reagents nonstabilized ylides (entries 1-12, 24, 25, 29, and 30), benzylic ylides (entries 13-17 and 28), allylic ylides (entries 22, 23, 26, and 27), and ester-stabilized ylides (entries 18-21). The corresponding Wittig reactions must take place under dominant kinetic control.

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