PA ., values

Dioxo compounds are deprotonated at C-2 and C-4 by two equivalents of strong bases (e.g. LDA or BuLi). Carbon atom C-4 of those dianions is much more nucleophilic than the less basic center C-2 (Hauser s rule C.R. Hauser, 1958 K.G. Hampton, 1965). The formation of some typical d -synthons and their pA values are given below. 

A hydrogen attached to the a carbon atom of a p keto ester is relatively acidic Typical p keto esters have pA values of about 11 Because the a carbon atom is flanked by two electron withdrawing carbonyl groups a carbanion formed at this site is highly stabi hzed The electron delocalization m the anion of a p keto ester is represented by the res onance structures... 

Table 2. pA Values of Protonated Amines and Their A Oxides... 

Another example of the effect of resonance is in the relative acidity of carboxylic acids as compared to alcohols. Carboxylic acids derived from saturated hydrocarbons have ipK values near 5, whereas saturated alcohols have pA values in the range 16-18. This implies that the carboxylate anion can accept negative charge more readily than an oxygen on a saturated carbon chain. This can be explained in terms of stabilization of the negative charge by resonance, ... 

There is clearly a conceptual relationship between the properties called nucleophilicity and basicity. Both describe a process involving formation of a new bond to an electrophile by donation of an electron pair. The pA values in Table 5.7 refer to basicity toward a proton. There are many reactions in which a given chemical species might act either as a nucleophile or as a base. It is therefore of great interest to be able to predict viiether a chemical species Y P will act as a nucleophile or as a base under a given set of circumstances. Scheme 5.4 lists some examples. 

Amides are weak bases with pA values in the range of 0 to —2. When amide resonance is prevented, as in l-azabicyclo[2.2.2]octanone, N-protonation is preferred. ... 

The pyrophosphate moiety possesses three negative charges at pH values above 7.5 or so (note the pA values, Figure 3.10a). The hydrolysis products, two mole-... 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

Imoto and co-workers have also studied the pA values of substituted thiazolecarboxylic acids and the alkaline hydrolysis of their ethyl esters, each in three relative positions (2-B-4-Y, 2-B-5-Y, and 5-II-2-Y). In the case of the pA values, the p-values are far from constant, varying from 0.83 to 2,35, This variation is likely to be due to the intervention of tautomeric equilibria and of hydrogen bonds. The /3-ratios for the three sets of ester hydrolyses are roughly constant (0,61-0.73), and, assuming that the introduction of two heteroatoms leads to cumulative (multiplicative) effects on the transmission, this result is of the same order of magnitude as the product of the and values discussed above, i.e. 1.0 and 0.6, respectively. The lowest value for the pA (0,83) for the 2-R-5-COOH series is also of the same order of magnitude. All the available reaction constants are summarized in Table VI. 

The pA/ value always lies between the pAa and values. Because aromatic or partly aromatic heterocycHc species, e.g. 3 (the concentrations of which are included in the pA expression), are weaker bases than the corresponding carbinolamines, e.g. 4 (the concentrations of which are involved in the expression), it follows that pA a < V a- Because the anhydrous species is aromatic (or partly aromatic, if some of the conjugation may be in a —CO. NH— group) the basic value is always higher than that which would be... 

The basic pA/ values of the hydrated species have been measmed... 

Some of the scatter within the groups is undoubtedly due to differences in bond order and also to whether or not the nitrogens are located in the same ring. Nevertheless, some striking exceptions are apparent in which the pA values are much higher than expected. These include quinazoline, 1,3,5-, 1,3,7-, 1,3,8-, and 1,4,6-triazanaph-thalene, pteridine, and 1,4,5,8-tetraazanaphthalene. In all these cases, covalent hydration of the cation has been shown to occur, so the measured pA values are, in fact, equilibrium values involving both hydrated and anhydrous species. The hydrated species are, without... 

In systems such as the 2- and 6-hydroxypteridine series, rapid potentiometric or spectrophotometric pA determinations on neutral solutions usually give values near to the acidic pA of the hydrated series. (Exceptions include 2-hydroxy-4,6,7-trimethyl-, 6-hydroxy-7-methyl-, and 4,6-dihydroxy-pteridine, where the neutral solution contains comparable amounts of hydrated and anhydrous species. In such cases, rapid potentiometric titrations show two well-defined and separated curves, one for the hydrated, the other for the anhydrous, species.) Similarly, from solutions of the anion, an approximate pA value for the anhydrous species is obtained. For convenience, the anhydrous molecule is referred to as HX, its anion as X , the hydrated neutral molecule as HY, and its anion as Y, and the two equilibrium constants are defined as follows ... 

By carrying out the pA determination very slowly, so that equilibrium is reached at every point, an equilibrium pA value is obtained, for which... 

If these measurements are made at a pH where only the neutral molecules are present, the ratio is equal to the constant K. This restriction about pH is necessary because and are ordinarily composite, their relationship to the equilibrium constants and pA values being given by the relevant equations, ... 

If pe lies below the pes line then only H2S is stable for pa values between the pe3 line and the p 4 line, is stable for pa lying above the pa4 line, HSOT is stable. At a pH of 1.9, the dominant S(VI) species changes to. The slope of the pa4 curve changes slightly at pH = 1.9 reflecting a change in the number of protons in the balanced reaction ... 

Proton transfers between oxygen and nitrogen acids and bases are usually extremely fast. In the thermodynamically favored direction, they are generally diffusion controlled. In fact, a normal acid is defined as one whose proton-transfer reactions are completely diffusion controlled, except when the conjugate acid of the base to which the proton is transferred has a pA value very close (differs by g2 pA units) to that of the acid. The normal acid-base reaction mechanism consists of three steps ... 

The strength of weak acids is expressed by pA, the negative log of the acid dissociation constant. Strong acids have low pA values and weak acids have high pAl, values. 

The isoelectric species is the form of a molecule that has an equal number of positive and negative charges and thus is electrically neutral. The isoelectric pH, also called the pi, is the pH midway between pA values on either side of the isoelectric species. For an amino acid such as alanine that has only two dissociating groups, there is no ambiguity. The first pK (R—COOH) is 2.35 and the second pK (R—NH3+) is 9.69. The isoelectric pH (pi) of alanine thus is... 

APPARENT pA VALUES OF CHROMIC ACID IN AQUEOUS SOLUTIONS OF VARIOUS MINERAL ACIDS, ACCORDING TO LEE AND STEWART ... 

We considered micro-pA), values in Section 3.6. A parallel concept applies to partition coefficients (of multiprotic molecules) namely, if an ionizable substance of a particular stoichiometric composition can exist in different structural forms, then it is possible for each form to have a different micro-log P [224,243,273,275], When logP is determined by the potentiometric method (below), the constant determined is the macro-log P. Other log/1 methods may also determine only the macroscopic constant. 

Kansy et al. [550] reported the permeability-lipophilicity relationship for about 120 molecules based on the 10% wt/vol egg lecithin plus 0.5% wt/vol cholesterol in dodecane membrane lipid (model 15.0 in Table 7.3), shown in Fig. 7.23. The vertical axis is proportional to apparent permeability [see Eq. (7.9)]. For log Kd > 1.5, Pa decreases with increasing log Kd. In terms of characteristic permeability-lipophilicity plots of Fig. 7.19, the Kansy result in Fig. 7.23 resembles the bilinear case in Fig. (7.19d). Some of the Pa values may be underestimated for the most lipophilic molecules because membrane retention was not considered in the analysis. 

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