Carboxylic acids, diprotonated

Acetic acid and other carboxylic acids are protonated in superacids to form stable carboxonium ions at low temperatures. Cleavage to related acyl cations is observed (by NMR) upon raising the temperature of the solutions. In excess superacids a diprotonation equilibrium, indicated by theoretical calculations, can play a role in the ionization process. 

Protonated amides and carboxylic acids have also been shown to activate adjacent electrophilic centers. Although protonated carboxylic acids and amides are not typically considered stable cationic groups, in superacidic media they can be readily generated and many have been observed by spectroscopic studies.16 As an example of electrophilic activation by a protonated carboxylic acid, P-phenylcinnamic acid (35) is diprotonated in super- acid to give the dication (36, observable by NMR) which then reacts with benzene and gives the indanone (37) in good yield (eq 12).17 It is known that the 1,1-diphenylethyl... 

Several gitonic superelectrophiles have been reported having closely oriented oxonium and carboxonium ion centers, some of which may be considered 1,3-dications. A series of hydroxy-substituted carboxylic acids were studied in FSOsH-SbFs in solution and the oxonium-carbonium dications could be directly observed at low temperature.57 In the case of lactic acid, dication 147 is a persistent ion at — 80°C, but at temperatures above — 60°C, formation of the diprotonated lactide (148) is observed (eq 48). 

On the other hand, 13C NMR spectroscopy has extensively been used to study the structure of oxonium, carboxonium and oxycarbenium ions and diprotonated carboxylic acids,144-146 since it allows the direct monitoring of the cationic centre and since the chemical shifts and coupling constants can be correlated with the geometry and hybridization of the cation. This technique has also been used by Olah et al. to provide... 

In Table 18 are displayed the global electrophilicity values for a series of alkyloxonium and carboxonium dications and diprotonated carboxylic acids. The values are presented in the order of increasing electrophilicity for each group, with reference to the neutral parent compounds (see last column in Table 18). 

In Table 19 are depicted the electrophilic Fukui function at site k, fk, and the local electrophilicity cok. The relevant electrophilic sites are the carbon atom in the series of the alkyloxonium ions and the carbonyl carbon atom in the carboxonium and diprotonated carboxylic acids. Also, we have incorporated in Table 19 the theoretical computed 13C NMR and 170 NMR chemical shifts available from the literature154,155 to compare our results. 

Protonated and diprotonated carbonic acid and carbon dioxide may also have implications in biological carboxylation processes. Although behavior in highly acidic solvent systems cannot be extrapolated to in vivo conditions, related multidentate interactions at enzymatic sites are possible. 

In addition to phosphate and halide anion binding, carboxylate chelation by sapphyrin macrocycles has been the subject of recent investigation. To date, two crystal structures have been solved. A 2 1 complex formed between diprotonated sapphyrin 3 and trifluoroacetic acid shows that the oxyanions are chelated above and below the sapphyrin plane (Figure 10). ° Greater complexity of organi-... 

The different chemistry of the dications 99 and 101 seems to reflect the superelectrophilic nature of the gitonic dication. It has also been shown that simple peptides may be multiply protonated in acids like FSOsH-SbFs, generally being protonated at the terminal amino group, the carboxyl group, and at the peptide bonds. In a study of the chemistiy of /V-tosylated phenylalanine derivatives, the diprotonated intermediate (103) was proposed in a reaction with superacid CF3SO3H (eq 33).42... 

In order to support the contention that the protonated forms of sapphyrin have a role to play as anion receptors, particularly for physiologically important species such as phosphates and carboxylates, efforts were made to crystallize complexes containing these anions. In the case of phosphate, a number of such structures have in fact been obtained. Two are considered particularly informative. The first involves the 1 1 complex formed between monobasic phosphoric acid and diprotonated sapphyrin 10.6 (Figure 10.5.15) and the second, the mixed salt of diprotonated sapphyrin 10.29, chloride anion, and cyclic-AMP (Figure 10.5.16). ... 

The direct reaction of indoles with carbon dioxide at atmospheric pressure to give the 3-carboxylated derivatives has been reported. The reaction occurs in dimethyl for-mamide in the presence of a large excess in lithium t-butoxide whose function is to deprotonate the indole. Although the N-H proton is more acidic, the C(3) anion yields the thermodynamically more stable carboxylated product. Acyl transfer from amides, such as A-(4-nitrophenyl)acetamide to benzene may occur in triflic acid. The mechanism is likely to involve diprotonation of the amide, as shown in (39), and dissociation of the C-N bond to give an acyl cation. The methodology allows the formation of aromatic ketones by inter- or intra-molecular reaction. The acylation of arenes may also be... 

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