The solution phase acidity

In both of these solvents, there are several examples of a trend in which the elaboration of a alkyl group on an acidic site, in the usual series of methyl, ethyl, isopropyl, and f-butyl, results in a decrease in the solution phase acidity and an increase in the gas phase acidity. First noted for the alcohol acidities, this trend has been observed for a wide variety of acids since then. ... 

As an experimental proof of the prediction of the calculations, the cyclic disilazane 1,1,3,3-hexamethyl-l, 3-disila-2-aza-cyclopentane was synthesized and its gas phase acidity determined. With the disilazide moiety constrained to a bent geometry within the five-membered ring, the acidity is weakened by 11.5 kcal/mol relative to the acyclic hexamethydisilazane. This places the cyclic disilazane s acidity as essentially within the general trend of gas versus solution phase acidities in Figure 9, and validates the concept that the counterion s locking of the geometry of the anion is the controlling fector in the solution phase acidity of the acyclic form. 

The ultraviolet absorption spectrum of thiazole was first determined in 1955 in ethanolic solution by Leandri et al. (172), then in 1957 by Sheinker et al. (173), and in 1967 by Coltbourne et al. (174). Albert in 1957 gave the spectrum in aqueous solution at pH 5 and in acidic solution (NHCl) (175). Nonhydroxylic solvents were employed (176, 177), and the vapor-phase spectrum was also determined (123). The results summarized in Table 1-15 are homogeneous except for the first data of Leandri (172). Both bands A and B have a red shift of about 3 nm when thiazole is dissolved in hydrocarbon solvents. This red shift of band A increases when the solvent is hydroxylic and, in the case of water, especially when the solution becomes acidic and the extinction coefficient increases simultaneously. 

Comparison of the gas-phase acidity of benzoic acids with pAT values of the same compounds in aqueous solution provides some interesting relationships. 

Normal-phase LC tends to separate according to solute polarity since the stationary phase is polar and retention is often dominated by hydrogen bonding. Thus, normal-phase LC is useful in sorting out classes of materials according to the polarity of the solutes. Fatty acids are easily separated from monoglycerides, but the separation of individual saturated fatty acids from each other on the basis of their carbon... 

SOMe the enhancement in the meta-position is almost as large as in the para-position. The authors go on to show the applicability of op (g) values to certain solution processes, particularly those in non-aqueous solvents, but including the dissociation of thiophenols in 48% ethanol, the results of Bordwell and Andersen80 to which reference has been made earlier (Section III.A.1). A separation of field/inductive and resonance effects is also essayed for the gas-phase acidities of the phenols, and SOMe and S02Me feature in the discussion. There is reference to a oR° value of + 0.07 for SOMe as an unpublished result of Adcock, Bromilow and Taft (cf. 0.00 from Ehrenson and coworkers65 and — 0.07 from Katritzky, Topsom and colleagues128.)... 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

THF and methanol employed as organic modifiers of mobile phase provided a considerable difference in selectivity based on the polar interactions between solutes and the organic solvent molecules in the stationary phase. Acidic compounds, phenols and nitroaromatics, were preferentially retained in the THF-based mobile phase, whereas esters and ketones were preferentially retained in the methanol (a hydrogen-bond donor) containing mobile phase. The system presented here seems to be very practical because any laboratory possessing two sets of HPLC equipment and two C j g columns can attempt similar 2D HPLC by simply changing the mobile phase for the two dimensions. 

To use this method, the sample is dissolved in a system containing two phases (e.g., water and octanol) such that the solution is at least about 5 x 10-4 M. The solution is acidified (or basified) and titrated with base (or acid) under controlled conditions. The shape of the ensuing titration curve is compared with the shape of a simulated curve, which is created in silico. The estimated p0Ka values (together with other variables used to construct the simulated curve such as substance concentration factor, CO2 content of the solution and acidity error) are allowed to vary systematically until the simulated curve fits as closely as possible to the experimental curve. The p0Ka values required to achieve the best fit are assumed to be the correct measured p0Ka values. This computerized calculation technique is called refinement , and is described elsewhere [14, 15]. 

Each microreactor consists of a polymer-bound substrate and a radiofrequency encoded microchip enclosed within a small porous vessel. The radiofrequency tag allows the identity of the substrate contained within each microreactor to be established readily. Using this technology, the polymer-bound substrates 86 were individually elaborated, within separate microreactors, by sequential reactions with acids 87 and alcohols 88 in a similar way to the solution-phase processes [25c]. Each of the microreactors was then subjected to the tandem RCM resin-cleavage conditions employing initiator 3. The products from each microreactor were obtained as a mixture of four compounds (89-92). The library of analogs prepared by this technique was then screened for biological activity [25c]. 

Except for phthalic acid, all other carboxylic acids studied induce considerable increases in the light compared to the dark values (the relatively high rate of iron oxide dissolution induced by oxalic acid has been extensively studied (5,8). Phthalic acid actually appears to stabilize the iron oxide against photodissolution despite the solution phase complex exhibiting some photoactivity. 

The major activity in gas-phase studies now depends on the use of modem techniques such as ion cyclotron resonance (ICR). Thus, as already mentioned (Section ELD). Fujio, Mclver and Taft131 measured the gas-phase acidities, relative to phenol, of 38 meta- or para-substituted phenols by the ICR equilibrium constant method, and their results for +R substituents led them to suggest that such substituents in aqueous solution exerted solvation-assisted resonance effects. It was later163 shown by comparison of gas-phase acidities of phenols with acidities of phenols in solution in DMSO that solvation-assisted resonance effects could also occur even when the solvent did not have hydrogen-bond donor properties. Indeed for p-NC>2 and certain other substituents these effects appeared to be larger than in aqueous solution. 

Figure 2-36 shows the inft ared spectra in 0.5 M sulfuric acid at various potentials for oxidation of COad adsorbed at 300 mV. The peaks around 2070 cm l- were assigned to the stretching mode of linearly-adsorbed CO. This frequency is smaller than that of gas phase CO (2150 cm l) . which means the C-0 bond is weakened by Pt-C bond. The peaks with wave number of 2340 cm l is assigned to the asymmetric stretching vibration mode of CO2 in the solution phase. 

A library of piperazine containing fused azepine-tetrazoles 183 was built by Nixey et al. via Ugi reaction in the solution phase [55]. This library comprises an example of a building block introduced piperazine (Scheme 32). The reaction of A-Boc-a-amino aldehyde 184, methyl isocyanoacetate 185, substituted piperazines 186, and trimethylsilylazide 181 in methanol, followed by acid treatment, proton scavenging, and reflux affords bicyciic azepine-tetrazoles 183. This efficient protocol with three diversity points can be used to generate arrays of biologically... 

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