Carbonic acid, diprotonated

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. 

Protonated carbonic acid (fFCCF-1-, 175) is recognized as a stable species in superacids and even a salt was isolated with its X-ray crystal structure obtained. In strong superacids, diprotonated carbonic acid (30) was found to undergo ionic hydrogenation to methane (eq 45).77... 

Protonation of formic acid similarly leads, after the formation at low temperature of the parent carboxonium ion, to the formyl cation. The persistent formyl cation was observed by high-pressure NMR only recently (Horvath and Gladysz). An equilibrium with diprotonated carbon monoxide causing rapid exchange can be involved, which also explains the observed high reactivity of carbon monoxide in supera-cidic media. Not only aromatic but also saturated hydrocarbons (such as isoalkanes and adamantanes) can be readily formylated. 

Carbon monoxide, hydrogen cyanide, and nitriles also react with aromatic compounds in the presence of strong acids or Friedel-Crafts catalysts to introduce formyl or acyl substituents. The active electrophiles are believed to be dications resulting from diprotonation of CO, HCN, or the nitrile.64 The general outlines of the mechanisms of these reactions are given below. 

Hydroxyazobenzene and 4-hydroxyazobenzene-4 -sulphonic acid become diprotonated in 100% sulphuric acid, the second proton going on the phenolic 0-site, rather than on carbon (Strachan et al., 1969). 

Protonation and diprotonation of formic acid and acetic acid have also been studied theoretically (HF and MP2/6-312G levels).553,558 Both cations can be visualized as the donor-acceptor complex of H20 and diprotonated carbon monoxide (HCOH2+) and protonated acetyl cation (CHaCOH23"), respectively. Both dications 277 and 278 are characterized by a long C-OH2 bond and a shorter C-OH bond, suggesting that the latter retains substantial double-bond character. 

Evidence for the involvement of the diprotonated species 40 and 42 includes 13C NMR data, which shows deshielding of the involved carbons as the acidity of the media increases from H0 —8 to —26 (mesityl oxide is estimated to be fully monoprotonated in acids of about H0 —8). Dication 42 has been shown to be capable of reacting even with very weak nucleophiles, for example, abstracting hydride from cyclohexane.19b An analogous species (43) has been proposed in interaction with excess AICI3. Protonated cyclohex-2-enone is converted to 3-methylcyclo-pent-2-enone in HF-SbFs solution at 50°C.20 The reaction mechanism is thought to involve the dicationic intermediate 44 (eq 13). Likewise, aryl-substituted indenones are converted to the dications by reaction in superacid (eq 14).21... 

The dicationic species arising from phthahc acid and its esters have also been studied. Diprotonated phthahc acid (157) is observed by low temperature 1H and 13C NMR, with its carboxonium carbons found at cleavage product, the acyl-carboxonium dication 158 (eq 55). 

Azoloazines having NH functions are weakly acidic and are also basic. TV-Alkylated derivatives act only as bases. Carbon-13 NMR studies on l-isopropyl-4-amino-pyrazolo[3,4-r/]pyrimidine and isomeric 2-isopropyl derivative indicate that N-5 and N-7 are the respective protonation sites <77JA7257>. Allopurinol as well as its derivatives have been shown by UV and NMR to form mono-and diprotonated species in sulfuric acid solutions <75KGS838>. 

Upon treatment with HF-SbFj, para-substituted phenols (or their methyl ethers) can be diprotonated [66], first on the oxygen atom and then on the meta carbon [67]. The resulting dipositively charged species are exceedingly reactive towards a variety of arenes [67], 4-Arylcyclohexanones, the primary products of the reactions, can be further transformed to 3-arylcyclohexanones. The ratio of the two isomers depends on conditions such as the reaction time, amount of acid, and the nature of the substrates. For example, when p-cresol is reacted with benzene in the presence of HF-SbFs, 4-methyl-4-phenylcyclohexenone and 3-phenyl-4-methylcyclohexenone are obtained in yields of 29 and 33 %, respectively, after 90 s. By increasing the reaction time to 15 min, the yield of 3-phenyl-4-methylcyclohexenone is increased to 90 % whereas that of 4-methyl-4-phenylcyclohexenone decreased to 2-3 % (Eq. 27). 

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. 

Both 3-amino- and 3,4-diaminothiophene exhibit enaminic character. On acid-catalyzed deu-teration, deuterium enters the thiophene a-positions. On this basis, it was concluded that 3,4-diaminothiophene is C-protonated in acid. However, a detailed potentiometric as well as H NMR study of the protonation of 3,4-diaminothiophene has revealed that both monoprotonation as well as diprotonation occurs on the nitrogen atoms (Scheme 104) there was no evidence for protonation at the a-carbon atoms <93JOC4696>. The pK, values in 50 /o DMSO-water mixture are 3.96 and 0.98. 

Carbocations can be generated by protonation of unsaturated hydrocarbons such as alkenes and cycloalkenes, cyclopenta-dlenes, benzenes and naphthalenes (eq 4), pyrenes and cyclophanes, unsaturated heterocycles,and their derivatives with carbon-heteroatom multiple bonds, Including carbonyl and nitrile compounds and diazoalkanes (eq 5). Compounds with two sites for protonation may undergo diprotonation to give dicatlons In Magic Acid (eq 6). ... 

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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