Hydrolytic reactions thermodynamics

Proofreading involves kinetic as well as thermodynamic considerations.264 266 The relative rates of a hydrolytic reaction and the competing activating reaction must always be considered. These ratios can be strongly affected by conformational changes, which may occur in several steps (see also Section C,2). 

Lipases have been extensively used for the kinetic resolution of racemic alcohols or carboxylic acids in organic solvents. Chiral alcohols are usually reacted with achiral activated esters (such as vinyl, isopropenyh and trichloroethyl esters) for shifting the equilibrium to the desired products and avoiding problems of reversibility. For the same reasons, chiral acids are often resolved by using acidolysis of esters. In both cases, the overall stereoselectivity is affected by the thermodynamic activity of water of water favors hydrolytic reactions leading to a decrease in the optical purity of the desired ester. Direct esterifications are therefore difficult to apply since water formed during the reaction may increase the o of the system, favors reversibiUty, and diminishes the overall stereoselectivity. 

CoFg(cr) being thermally unstable around 900 K, while Stewart (8) recently showed that CoP2(cr) was formed by hydrolytic reactions and not by thermal decomposition. The derived A G values for CoP (cr) indicate that it is thermodynamically more stable than... 

The differing flavor effects of hydrolytic reactions in aged wines and heated juices can be understood in terms of the conditions under which different volatile monoterpenes are formed. In aged wines, slow transformations of both free monoterpenes and glycosides give the more thermodynamically stable products which are mainly cyclic compounds of high flavor threshold. Additionally, monoterpene ether formation would be expected (53,54) and this too... 

We need to know the equilif>rium constant (or AF ), therefore, to ascertain the conditions necessary for a high yield and to avoid wasted efforts on reactions that are thermodynamically impossible. There are several methods for obtaining data from which the equilibrium constant may be calculated. Some of these are illustrated in discussing the thermodynamics of the following hydrolytic reactions. 

In commercial processes, whether a reaction goes fast or slow is extremely important, and thus the rate at which a chemical reaction approaches equilibrium is significant. If the reaction is thermodynamically possible but proceeds with a velocity that is not economically practical, some means must be found by which the rate is increased. In addition to the variation of temperature, pressure, and concentration ratios, a catalyst may be employed to bring about the desired results. Although reaction conditions and catalysts are usually determined experimentally, a discussion, of typical hydrolytic reactions from the theoretical point of view may throw some light on the mechanism of these reactions and make the approach to future problems less arbitraiy. 

Ishiguro, S. and Ohtaki, H. (1981) A thermodynamic study on hydrolytic reactions of lead(n) ions in an aqueous solution and dioxane-water mixtures. II. A calorimetric study. BuU. Chem. Soc. Jpn., 54, 335-342. 

The regioselectivity of Michael additions of thiolates to 2,4-dienones can be altered drastically by variation of the reaction conditions and addition of Lewis acids to the reaction mixture. Lawton and coworkers examined the reaction of 2-mercaptoethanol with l-(3-nitrophenyl)-2,4-pentadien-l-one and observed a high regioselectivity in favor of the 1,6-addition product at 45 °C (equation 42)123,124. Lowering of the reaction temperature caused an increase in the amount of 1,4-adduct, and at —40°C, a product ratio of 40 60 was found. These events suggest that kinetic control favors the 1,4-addition product whereas the 1,6-adduct is thermodynamically more stable. If, however, the reaction was carried out with a complex of the dienone and titanium tetrachloride, only the 1,4-adduct was isolated after hydrolytic workup123. Obviously, this product is trapped as a metal chelate which prevents formation of the 1,6-adduct by retro-Michael/Michael addition. In the absence of the chelating Lewis acid, the 1,4-addition product can indeed be converted... 

Eichhom and his co-workers have thoroughly studied the kinetics of the formation and hydrolysis of polydentate Schiff bases in the presence of various cations (9, 10, 25). The reactions are complicated by a factor not found in the absence of metal ions, i.e, the formation of metal chelate complexes stabilizes the Schiff bases thermodynamically but this factor is determined by, and varies with, the central metal ion involved. In the case of bis(2-thiophenyl)-ethylenediamine, both copper (II) and nickel(II) catalyze the hydrolytic decomposition via complex formation. The nickel (I I) is the more effective catalyst from the viewpoint of the actual rate constants. However, it requires an activation energy cf 12.5 kcal., while the corresponding reaction in the copper(II) case requires only 11.3 kcal. The values for the entropies of activation were found to be —30.0 e.u. for the nickel(II) system and — 34.7 e.u. for the copper(II) system. Studies of the rate of formation of the Schiff bases and their metal complexes (25) showed that prior coordination of one of the reactants slowed down the rate of formation of the Schiff base when the other reactant was added. Although copper (more than nickel) favored the production of the Schiff bases from the viewpoint of the thermodynamics of the overall reaction, the formation reactions were slower with copper than with nickel. The rate of hydrolysis of Schiff bases with or/Zw-aminophenols is so fast that the corresponding metal complexes cannot be isolated from solutions containing water (4). 

When one is using proteases in a direct reversal of their normal hydrolytic function, the equilibrium position is very important in limiting the attainable yield in equilibrium-controlled enzymatic peptide synthesis. If both reactants and products are largely undissolved in the reaction medium as suspended solids, thermodynamic analysis of such a system shows the reaction will proceed until at least one reactant has dissolved completely, towards either products or reactants ( switchlike behavior). In case of a favorable equilibrium for synthesis, the yield is maximized in the solvent of least solubility for the starting materials (Hailing, 1995). Thermolysin-catalyzed reactions ofX-Phe-OH (X = formyl, Ac, Z) with Leu-NH2 yielded X-Phe-Leu-NH2 with equilibrium yields > 90% over a range of solvents. Some predictions, such as a linear decrease in yield with the reciprocal of the initial reactant concentrations, could be verified (Hailing, 1995). 

Reactions of cisplatin and its hydrolytes with longer-chain amino acids +NH3(CH2)nC02 are less relevant to the biological properties of platinum because these compounds are less abundant in vivo. The six- and seven-membered chelate rings formed with /3-alanine (n = 2) and y-aminobutyric acid (n = 3) are progressively less stable kinetically and thermodynamically than the five-membered A/, 0-chelate ring formed with glycine [3]. 

The kinetics of hydrolysis of energetic material precursors - mono- and dinitro derivatives of pyrazole, imidazole, 1,2,4-triazole, and isoxazole has been studied by the polarographic and photometric methods [647], The alkaline hydrolysis rate constants experimentally determined depend on the nature of the heterocycle. A possible mechanism for hydrolytic transformations of nitroazoles is proposed on the basis of the calculated thermodynamic parameters of the reaction. 

This procedure has also been used to prepare a series of hydrolytically stable dipyranoid disaccharide mimetics from homologous dihydroxy-a,oo-dialdehydes37 (Scheme 5.16). While the FruA and FucA reactions are selective for the (W)-aldchydc, the RhuA reactions are selective for the (S)-aldehydes, all giving thermodynamically more stable product with retention of the natural stereochemistry for the two newly formed carbon centers. 

From the above it can be seen that the hydrolytic behavior of N2F2 is quite different from those of the other binary nitrogen fluorides discussed earlier. Difluorodiazine is strongly endothermic (12) and thermodynamically unstable (11) this makes it necessary to consider not only direct chemical attack by water but also the thermal decomposition to the elements. The reactivity of d -N2F2 toward glass (2) presents an additional question of possible competing reactions with the container walls. 

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