Aromatic acids ionized-form

All these kinetic results can be accommodated by a general mechanism that incorporates the following fundamental components (1) complexation of the alkylating agent and the Lewis acid (2) electrophilic attack on the aromatic substrate to form the a-complex and (3) deprotonation. In many systems, there m be an ionization of the complex to yield a discrete carbocation. This step accounts for the fact that rearrangement of the alkyl group is frequently observed during Friedel-Crafts alkylation. 

The action of these two pancreatic exopeptidases on synthetic substrates, proteins, and peptides has been reviewed in detail by Neurath (1960). The specificity requirements which were deduced from studies with synthetic peptides have been confirmed by studies with polypeptides. The structural requirements of specific substrates for both types of carboxy-peptidase are analogous except for the nature of the amino acids which contain the free, ionized a-carboxyl group at the terminus of the substrate. Carboxypeptidase B hydrolyzes most rapidly those bonds formed by terminal lysyl and arginyl residues, whereas carboxypeptidase A hydrolyzes terminal bonds formed by a variety of aromatic, neutral, or acidic amino acids. Of the natural amino acids only carboxyl-terminal prolyl residues are resistant to the action of the enzyme. The rate of hydrolysis depends upon the nature of the side chains of the amino acids which form the susceptible bonds. Thus, differences in the rate of hydrolysis of different substrates may vary several thousandfold. The methods for application of these peptidases to hydrolysis of proteins have been discussed in detail by Canfield and Anfinsen (1963). 

Aromatic diazonium ions normally couple only with active substrates, such as amines and phenols.Many of the products of this reaction are used as dyes (azo dyes) Presumably because of the size of the attacking species, substitution is mostly para to the activating group, unless that position is aheady occupied, in which case ortho substitution takes place. The pH of the solution is important both for phenols and amines. For amines, the solutions may be mildly acidic or neutral. The fact that amines give ortho and para products shows that even in mildly acidic solution they react in their un-ionized form. If the acidity is too high, the reaction does not occur, because the concentration of free amine becomes too small. Phenols must be coupled in slightly alkaline solution where they are converted to the more reactive phenoxide ions, because phenols themselves are not active enough for the... 

The initial step of the mechanism is the coordination of the first equivalent of the Lewis acid to the carbonyl group of the acylating agent. Next, the second equivalent of Lewis acid ionizes the initial complex to form a second donor-acceptor complex which can dissociate to an acylium ion in ionizing solvents. The typical SsAr reaction gives rise to an aromatic ketone-Lewis acid complex that has to be hydrolyzed to the desired aromatic ketone. 

In contrast, reversed-phase sorbents have non-polar functional groups, e.g. octadecyl, octyl and methyl, and conversely are more likely to retain non-polar compounds, e.g. polycyclic aromatic hydrocarbons. Ion-exchange sorbents have either cationic or anionic functional groups and when in the ionized form attract compounds of the opposite charge. A cation-exchange phase, such as benzene-sulfonic acid, will extract analytes with positive charges (e.g. phenoxyacid herbicides) and vice versa. A summary of the commercially available silica-bonded sorbents is given in Table 8.1. 

We have also discussed the use of the electrostatic potential for the analysis of substituent effects in aromatic systems. Substituent effects on gas phase and solution acidities of benzoic acids and phenols are dominantly determined by the relative stabilization of the negative charge in the ionized forms of these systems. The oxygen Vmin is an excellent tool for the analysis of this stabilization effect. On the other hand, we have found that the homol5dic O-H bond dissociation energy in phenols depends both on the substituent s ability to stabilize the parent molecule (the phenol) and the radical. The relative stabilization energies of the parent molecule and the radical can be estimated from their computed Vmin and surface maxima in the spin density, respectively. 

Table 6.8 Molecular properties of aromatic acids, p ai values were predicted from the atomic partial charge, pK 2 values were calculated using Hammett s equation, fcn, values are for the molecular form and k values are for the ionized form. Reproduced by permission of Springer, ref. 9.

Table 6.9 Molecular properties of molecular-form and ionized-form aromatic acids. Reproduced by permission of Springer, ref. 9.

Figure 6.25 The relationship between molecular interaction energy and the measured (Aimes) capacity ratios for molecular- and ionized-form aromatic acids.

Table 6.9. The correlation coefficient between the log k values of ionized aromatic acid derivatives and MIFSi was 0.916. The relationships between the molecular interaction energy values and the log k values of the molecular- and ionized-form aromatic acid derivatives are shown in Figure 6.25.

There are a couple of reasons why these arenes do not undergo electrophilic aromatic substitution when AICI3 is used. First, AICI3 decomposes in the presence of protic acids (ionizable hydrogens) to form HCI. Second, AICI3 (a Lewis acid) reacts with —OH, —SH, and —NH2 groups, which are Lewis bases.These two reactions destroy the catalyst. 

Step 2 A proton is lost from the sp hybridized carbon of the intermediate to restore the aromaticity of the ring The species shown that abstracts the proton is a hydrogen sulfate ion formed by ionization of sulfunc acid... 

The ionization of (E)-diazo methyl ethers is catalyzed by the general acid mechanism, as shown by Broxton and Stray (1980, 1982) using acetic acid and six other aliphatic and aromatic carboxylic acids. The observation of general acid catalysis is evidence that proton transfer occurs in the rate-determining part of the reaction (Scheme 6-5). The Bronsted a value is 0.32, which indicates that in the transition state the proton is still closer to the carboxylic acid than to the oxygen atom of the methanol to be formed. If the benzene ring of the diazo ether (Ar in Scheme 6-5) contains a carboxy group in the 2-position, intramolecular acid catalysis is observed (Broxton and McLeish, 1983). 

The FAB plasma provides conditions that allow to ionize molecules by either loss or addition of an electron to form positive molecular ions, M" , [52,89] or negative molecular ions, M, respectively. Alternatively, protonation or deprotonation may result in [Mh-H]" or [M-H] quasimolecular ions. Their occurrence is determined by the respective basicity or acidity of analyte and matrix. Cationization, preferably with alkali metal ions, is also frequently observed. Often, [Mh-H]" ions are accompanied by [MH-Na]" and [Mh-K]" ions as already noted with FD-MS (Chap. 8.5.7). Furthermore, it is not unusual to observe and [Mh-H]" ions in the same FAB spectmm. [52] In case of simple aromatic amines, for example, the peak intensity ratio M 7[Mh-H] increases as the ionization energy of the substrate decreases, whereas 4-substituted benzophenones show preferential formation of [Mh-H]" ions, regardless of the nature of the substituents. [90] It can be assumed that protonation is initiated when the benzophenone carbonyl groups form hydrogen bonds with the matrix. 

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