Methylene Selectivity

We believe that the selectivity of methine (CH) insertion over methylene (CH2) insertion (Tab. 16.6) is a reflection of the polarizabihty of the rhodium carbenoid. As the carbenoid approaches the target C-H, the methine C-H is more electron-rich than the methylene C-H. A more easily polarized carbenoid would respond more fully to this and give proportionally more of the methine insertion product. Our design of the a-diazo ester 32 included the p-methoxy group on the benzene ring, so that the reactivity of the methylene benzylic C-H would approach that of the methine. Statistically, due to geometric constraints, only one of the two benzyhc methylene C-H groups is available for the insertion necessary for the cyclization to 36/37. 

In the carboxylate series, the TPA catalyst (entry 4) was the most selective for methine over methylene insertion. Should this remarkable chemoselectivity prove to be general, this complex may add a possibility for high chemoselectivity not previously observed with rhodium(ll) catalysts. The other carboxylate catalysts show less preference for CH over CH2 insertion. We expect that the CH/CH2 ratios would be more pronounced with a less carefully balanced substrate. In the carboxamidate class, MPPIM catalyst (entry 9) was more selective than the corresponding MeOX catalyst (entry 10), with the MEPY catalyst (entry 8) being the least discriminating for CH over CH2 insertion. 

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Gilpin, R. K., Jaroniec, M., and Lin, S., Dependence of the methylene selectivity on the composition of hydro-organic eluents for reversed-phase liquid chromatographic systems with alkyl bonded phases, Chromatographia, 30,393, 1990. 

The polarity values of binary acetonitrile/water and methanol/water mobile phases used in RPLC were measured and compared with methylene selectivity (acH2) for both traditional siliceous bonded phases and for a polystyrene-divinylbenzene resin reversed-phase material [82], The variation in methylene selectivity for both was found to correlate best with percent organic solvent in methanol/water mixtures, whereas the polarity value provided the best correlation in acetonitrile/water mixtures. The polymeric resin column was found to provide higher methylene selectivity than the siliceous-bonded phase at all concentrations of organic solvent. 

Sander and Wise [88] reported a new standard reference material SRM 870, which contains the neutral compounds ethylbenzene and toluene, to monitor hydrophobicity and methylene selectivity uracil (void volume marker) quinizarin to measure activity toward metal chelators and amitriptyline to measure activity toward bases. The... 

FIGURE 9.16 Variation of methylene selectivity ( cH2) function of carbon atom nnmber... 

Temperature variation was more influential on methylene selectivity for the mixtures with high percentages of acetonitrile, while the reverse was true for methanol/C02 mixtures. Like in nonaqueous reversed-phase HPLC, a temperature increase lowered the methylene selectivity. The main conclusion from this work is that acetonitrile/C02 mixtures would be preferred over methanol/C02 mixtures as a flrst attempt to separate homologs. 

The only valuable comparison of different columns found so far is so-called methylene selectivity. Methylene selectivity is the slope of the dependence of the logarithm of retention factor of the members of homologous series on the number of carbon atoms in their alkyl chain (Figure 3-13). This parameter reflects the surface interaction energy of one CH2 group and is found to be very similar on all Cl 8-type columns (and even C8). 

Phenyl-Type Phases. Phenyl-type phases have been studied for a long time [58,59]. The presence of a phenyl ring on the surface of a bonded phase introduces so-called n-n interactions with some analytes that are capable of these types of interactions. This introduces an additional specificity for HPLC separations on these stationary phases. Compared to common alkyl-type phases, phenyl columns show lower methylene selectivity in other words, the separation of members of homologous series will be less selective on phenyl columns than on alkyl-modified phases. 

A dependency on the type of ligand, its density, the eluent used and temperature is found when evaluating hydrophobicities of stationary phases. This property can be assessed by the retention factor of a hydrophobic solute or by the ratio of the retention factors of two non-polar solutes. The latter is called selectivity for example, when the components differ only in one methyl group, the term methylene selectivity coefficient is applied. Hence, hydrophobic properties describe the polarity of a column and its selectivity towards solutes with only small differences in polarity. This becomes rather important when endcapped stationary phases are compared (Section 3.2.3.1) as some new types of adsorbents allow separation with 100% water as eluent. 

An original study was done with a perfluoiinated stationary phase whose properties were compared to a classical CIS bonded phase [27, 28]. An important decrease of the methylene selectivity for a homologue series of alkylphenones was obtained with the fluorinated phase with both an SDS... 

Table 9.1 Methylene Selectivity between Successive Members of Homologous Series, Eluted with Micellar Mobile Phases in a C8 Column [7]...

The results commented above show tiiat, in MLC, usually methylene selectivity decreases as the carbon number increases (Table 9.1). The methylene selectivity between n-pentyl- and n-butylbenzenes is, for instance, smaller than between ethylbenzene and toluene. The observe variations are quite small and in certain cases their statistical significance might be questionable. However, the decrease in a(CH2) values with an increase in the molecular size is observed in almost all cases. For aqueous-organic... 

Since a(CH2) is the ratio of the retention factors of two compounds differing only in a methylene group, it should be independent of the series type for a given mobile and stationary phase system, such is the case for the aqueous-organic mobile phases. In contrast, as shown in Table 9.1, for micelles the a(CH2 ) values are dependent on the type of series, as the methylene selectivity for alkylphenones are consistently greater than for alkylbenzenes [7]. 

The curvature in the log k vs. n plots, observal with micellar and hybrid mobile phases, was first attributed to the different locations (with different microenvironment polarities) in the micelle, for different members of a homologous series [6, 7], Methylene selectivity decreases as the difference between mobile and stationary phase polarities is reduced. For a given mobile phase composition, the larger and more hydrophobic homologous compounds are located in a less polar environment of micelles, it is then conceivable to assume that these compounds experience a smaller change in their microenvironment polarity upon being transferred from the micellar pseudo-phase to the bonded alkyl stationary phase. The a(CH2) value between n-pentylbenzene and n-butylbenzene is smaller than it is between ethylbenzene and toluene (Table 9.1), because the former pair is located in a more nonpolar environment than the latter. 

When our analytes and our analytical goal are known, then we can select the column directed toward this aim. If, for example, we want to separate organic acids differing primarily in the chain length of the aliphatic rest, that is, in then-hydrophobic selectivity, then it is best to try a classical endcapped, hydrophobic reversed phase, because this provides the methylene selectivity necessary for this problem. 

In reversed-pha.se chromatography the retention volume depends very much on the molecular mass of the analyte. Methylene selectivity (i.e., the relative retention of two successive homologues) varies over a much wider range in reversed-phase LC than in GC, and can be quite large [45],... 

Kahle KA, Foley JP. Chiral microemulsion electrokinetic chromatography effect of cosurfactant identity on enantio-selectivity, methylene selectivity, resolution, and other chromatographic figures of merit. Electrophoresis 2006 27 4321 333. 

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