Amines, acid-base equilibria acidities

Griess (1864a) had already observed that the diazo compounds obtained from primary aromatic amines in acid solution are converted by alkalis into salts of alkalis. The reaction is reversible. The compounds which Hantzsch (1894) termed sjw-diazotates exhibit apparently the same reactions as the diazonium ions into which they are instantaneously transformed by excess of acid. Clearly the reaction depends on an acid-base equilibrium. 

Uncatalyzed amidations of acids have been realized under solvent-free conditions and with a very important microwave effect [67 a]. The best results were obtained by use of a slight excess of either amine or acid (1.5 equiv.). The reaction involves thermolysis of the previously formed ammonium salt (acid-base equilibrium) and is promoted by nucleophilic attack of the amine on the carbonyl moiety of the acid and removal of water at high temperature. The large difference in yields (MW > A) might be a consequence of interaction of the polar TS with the electric field (Eq. (15 a) and Tab. 3.6). 

Amine acid-base equilibrium mixing entropy... 

For the acid-base equilibrium of the allyl-amines and thiol groups, the equilibrium constants are given by ... 

To probe the thermodynamics of amine encapsulation, the binding affinities for different protonated amines for 1 were investigated. By studying the stabilization of the protonated form of encapsulated amines, the feasibility of stabilizing protonated intermediates in chemical reactions could be assessed. The thermodynamic cycle for encapsulation of a hypothetical substrate (S) is shown in Scheme 7.5. The acid-base equilibrium of the substrate is defined by Ki and the binding constant of the protonated substrate in 1 is defined by K2. Previous work has shown that neutral substrates can enter 1 [94] however, the magnitude of this affinity (K4) remains unexplored. Although neutral encapsulated amines were not observable in the study of protonated substrates, the thermodynamic cycle can be completed with K3, which is essentially the acid-base equilibrium inside 1. 

The definition of pH is pH = —log[H+] (which will be modified to include activity later). Ka is the equilibrium constant for the dissociation of an acid HA + H20 H30+ + A-. Kb is the base hydrolysis constant for the reaction B + H20 BH+ + OH. When either Ka or Kb is large, the acid or base is said to be strong otherwise, the acid or base is weak. Common strong acids and bases are listed in Table 6-2, which you should memorize. The most common weak acids are carboxylic acids (RC02H), and the most common weak bases are amines (R3N ). Carboxylate anions (RC02) are weak bases, and ammonium ions (R3NH+) are weak acids. Metal cations also are weak acids. For a conjugate acid-base pair in water, Ka- Kb = Kw. For polyprotic acids, we denote the successive acid dissociation constants as Kal, K, K, , or just Aj, K2, A"3, . For polybasic species, we denote successive hydrolysis constants Kbi, Kb2, A"h3, . For a diprotic system, the relations between successive acid and base equilibrium constants are Afa Kb2 — Kw and K.a Kbl = A w. For a triprotic system the relations are A al KM = ATW, K.d2 Kb2 = ATW, and Ka2 Kb, = Kw. 

In reactions with amine nucleophiles the reaction leads to a zwitterionic adduct that is in rapid acid-base equilibrium with its anionic form, Equation (45). In some cases, the zwitterion is strongly... 

The acid equilibrium constant KL involves the COOH termination the base equilibrium constant K2 involves the amine termination. At the isoelectric point (pH = (l/2)(pRi pR2) the amino acid is a zwitterion or betaine The proton is detached from the carboxylate end and is attached at the amine end. Dipeptides are formed by the addition of any two amino acids and a loss of a water molecule, for example ... 

Crystal structures have been reported for the octahedral phenolate [Tc(dppo)3] (307), thiolate [Tc(dppbt)3] (307, 308), and propionate [Tc(dppp)3]-2dmso (306). In each case the three P atoms occupy mer positions. For the amine ligand (25) (R = NH2) an acid-base equilibrium is established and either the triply deprotonated [Tc(dppba)3] or salts of the doubly deprotonated [Tc(dppba)2(dppbaH)]+ may be isolated depending on the pH. The crystal structure of [Tc(dppba)2(dppbaH)]-... 

Sections 3.3.1 and 4.2.1 dealt with Bronsted acid/base equilibria in which the solvent itself is involved in the chemical reaction as either an acid or a base. This Section describes some examples of solvent effects on proton-transfer (PT) reactions in which the solvent does not intervene directly as a reaction partner. New interest in the investigation of such acid/base equilibria in non-aqueous solvents has been generated by the pioneering work of Barrow et al. [164]. He studied the acid/base reactions between carboxylic acids and amines in tetra- and trichloromethane. A more recent compilation of Bronsted acid/base equilibrium constants, determined in up to twelve dipolar aprotic solvents, demonstrates the appreciable solvent influence on acid ionization constants [264]. For example, the p.Ka value of benzoic acid varies from 4.2 in water, 11.0 in dimethyl sulfoxide, 12.3 in A,A-dimethylformamide, up to 20.7 in acetonitrile, that is by about 16 powers of ten [264]. 

The amine radical cation of triethylamine formed in these reactions can exist in an acid-base equilibrium, as shown in Scheme 6. 

Thus, for every [H ], seven equations have to be solved simultaneously in order to compute the relative concentrations of each species present. Five mass laws (four stability expressions for the four different amine complexes and the acid-base equilibrium of NH4 -NH3) and two concentration conditions make up the seven equations. As concentration conditions one can formulate equations defining Cut- and NH3/. 

The effect of a solvent on the rate of the two-step aromatic nucleophilic substitution reactions of primary or secondary amines are sometimes complicated by the acid-base equilibrium (30) and by the fact that the transition state,... 

Titanium tetrachloride and amine yield an equilibrium mixture of Lewis acid-base complexes. At least one of these complexes has an increased reactivity towards the carbonyl oxygen and forms a ternary ketone—amine—TiCl,j complex [1] which in the presence of excess amine yields a titanium enolate. The reaction then proceeds as... 

M. This result can be understood by taking into account the fact that EAN can act as a Bronsted acid and establishes an acid-base equilibrium with the amine, making it possible to predict nucleophile competition. For the reaction with BU, the above differences in the absorbance values with the increase of the EAN concentration cannot be observed because the wavelengths of absorption for both products are similar. In the light of these results, the corresponding reactions with both amines at preparative scale were carried out. The only substitution product A-(2,4-dinitrophenyl) ethyl amine was observed in both cases, and it was confirmed by H NMR, NMR and mass spectroscopy. 

For the discussed reactions, it was possible to confirm that EAN can take part in an acid-base equilibrium with amines even at very low concentration, generating a nucleophile species which can participate in the reaction. The substitution product A-(2,4-dintrophenyl)ethylamine was obtained, and therefore, the second-order rate constant for ethylamine could be determined. 

In the nucleophilic addition reactions of amines to substituted aromatic aldehydes where acid catalysis is required, the use of EAN seems to be convenient. The EAN can take part in an acid-base equilibrium with the aromatic aldehydes substituted by electron-withdrawing groups. The imine products from the selected aldehydes could be obtained, confirming the dual behaviour of EAN as Brbnsted acid and potential nucleophile in these type of processes (Fig. 13.7). 

These studies were extended with triazole free base 4 as nucleophiles. Introduction of an undercharge of a basic nucleophile such as an amine introduces a new fast acid-base equilibrium (Equation 21.8). 

Complete understanding of the shape of the curves in Figure 7.5 requires a kinetic expression somewhat more complicated than we wish to deal with here. However, the nature of the extremities of the curve can be understood on the basis of qualitative arguments. The rate decreases with pH in the acidic region because formation of the zwitterionic tetrahedral intermediate TI+ - is required for expulsion of the amine (Step 5). The concentration of the zwitterionic species decreases with increasing acidity, since its concentration is governed by an acid-base equilibrium. 

---