Proton and acidity

No reports of reactions of simple tetrazines have been collected during the past year. However, studies of the protonation and acid stability of the fused ring tetrazine antitumour agent "Temozolomide" (76) have been carried out and the NMR spectra of a number of Temozolomide derivatives carrying NMR active nuclei (l3C, l5N) at different positions have been recorded (95JCS(P1)249],... 

Ostwald s dilution law — A weak - electrolyte is dissociated incompletely upon dissolution in a solvent. The chemical equilibrium of dissociation of a weak acid HA into protons and acid anions is described by ... 

Protonation and Acid-Catalyzed Oligomerization 2.1 Equilibrium Protonation... 

The macroscopic dissociation constants are those determined directly from titration curves and can be used directly for calculation of the charge of the molecules at various pH values. They do not reveal which protons and acid groups are involved in the different ionization steps. For the simple monoamino monocarboxylic acids it is well known that the first pK value corresponds to that of the COOH group, the second to that of the NHJ group in agreement with the top part of the following scheme ... 

This complex ion behaves as an acid in water, losing protons, and a series of equilibria are established (H is used, rather than for simplicity) ... 

We have seen that a base can be defined as combining with a proton and, therefore, requires at least one lone pair of electrons. A more general definition of acids and bases, due to G. N. Lewis, describes a base as any species (atom, ion or molecule) which can donate an electron pair, and an acid as any species which can accept an electron pair— more simply, a base is an electron-pair donor, an acid an electron-pair acceptor. Some examples of Lewis acids and bases are ... 

Edsall, J. T. George Scatchard, John G. Kirkwood, and the electrical interactions of amino acids and proteins. Trends Biochem. Sci. 7 (1982) 414-416. Eigen, M. Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Angew. Chem. Int. Ed. Engl. 3 (1964) 1-19. 

In superacidic systems, water is completely protonated and no equilibrium containing free water is indicated. However, the nonbonded electron pair of H30 is still a potential electron donor and at very high acidities can be further protonated (however limited the equilibrium with H30 may be). Thus the acidity of such superacidic systems can exceed that of H30 and the leveling ont is by that of H40 . We found that similar situations exist with other electrophiles, raising their electrophilic nature (electrophilicity) substantially. 

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. 

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

Alkenes react with sulfuric acid to form alkyl hydrogen sulfates A proton and a hydrogen sulfate ion add to the double bond in accordance with Markovnikov s rule Alkenes that yield tertiary carboca tions on protonation tend to polymerize in concentrated sulfuric acid (Section 6 21)... 

A diol (CgHig02) does not react with periodic acid Its H NMR spectrum contains three singlets at 8 1 2 (12 protons) 1 6 (4 protons) and 2 0 (2 protons) What is the structure of this dioH... 

FIGURE 22 5 The diazo mum ion generated by treatment of a primary al kylamine with nitrous acid loses nitrogen to give a car bocation The isolated prod ucts are derived from the carbocation and include in this example alkenes (by loss of a proton) and an al cohol (nucleophilic capture by water)... 

Many of the properties of phenols reflect the polarization implied by the resonance description The hydroxyl oxygen is less basic and the hydroxyl proton more acidic in phenols than m alcohols Electrophiles attack the aromatic ring of phenols much faster than they attack benzene indicating that the ring especially at the positions ortho and para to the hydroxyl group is relatively electron rich... 

Monoprotic weak acids, such as acetic acid, have only a single acidic proton and a single acid dissociation constant. Some acids, such as phosphoric acid, can donate more than one proton and are called polyprotic weak acids. Polyprotic acids are described by a series of acid dissociation steps, each characterized by it own acid dissociation constant. Phosphoric acid, for example, has three acid dissociation reactions and acid dissociation constants. 

An acidimetric quantitative determination is based on treatment of the hydantoia with silver nitrate and pyridine ia aqueous solution. Complexation of the silver ion at N-3 Hberates a proton, and the pyridinium ions thus formed are titrated usiag phenolphthaleia as an iadicator. In a different approach, the acidity of N-3—H is direcdy determined by neutralization with tetrabutylammonium hydroxide or sodium methoxide ia dimethylformarnide. 

Maleic and fiimaric acids have physical properties that differ due to the cis and trans configurations about the double bond. Aqueous dissociation constants and solubiUties of the two acids show variations attributable to geometric isomer effects. X-ray diffraction results for maleic acid (16) reveal an intramolecular hydrogen bond that accounts for both the ease of removal of the first carboxyl proton and the smaller dissociation constant for maleic acid compared to fumaric acid. Maleic acid isomerizes to fumaric acid with a derived heat of isomerization of —22.7 kJ/mol (—5.43 kcal/mol) (10). The activation energy for the conversion of maleic to fumaric acid is 66.1 kJ/mol (15.8 kcal/mol) (24). 

The higher aUphatic amine oxides are commercially important because of their surfactant properties and are used extensively in detergents. Amine oxides that have surface-acting properties can be further categorized as nonionic surfactants however, because under acidic conditions they become protonated and show cationic properties, they have also been called cationic surfactants. Typical commercial amine oxides include the types shown in Table 1. 

Wool has a complex chemical stmcture, composed mainly of a large number of different proteins (87). It is amphoteric in character because of the presence of basic amino and acidic carboxyl groups in the side chains of some of the component amino acids. In an aqueous acidic dyebath, protonation of the amino and carboxyl groups results in a net positive charge on the fiber. 

Another successhil strategy for derivatization of erythromycin employed modification of functional groups involved in intramolecular cyclizations. The C-9 ketone, C-6 hydroxyl group, C-8 proton, and/or C-ll,12-diol of erythromycin were converted into functional groups which participate poorly, if at all, in intramolecular cyclizations. Some derivatives which have been extensively evaluated in preclinical and clinical trials exhibit such desirable properties as better stabiUty under acidic conditions, greater oral bioavadabihty, and higher and more prolonged concentrations of antibiotic in semm and tissues. 

According to Figure 3, hydroperoxides are reduced to alcohols, and the sulfide group is oxidized to protonic and Lewis acids by a series of stoichiometric reactions. The sulfinic acid (21), sulfonic acid (23), sulfur trioxide, and sulfuric acid are capable of catalyzing the decomposition of hydroperoxides to nonradical species. 

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