Thermodynamics intramolecular proton

On the basis of distribution of products obtained in these reactions with the change of solvents, temperature and molar ratio of reactants, a mechanism has been suggested for the anomalous annulation which does not involve an initial attack of the tetrasub-stituted isomer of the enamine (equation 16)51. Alkylation of the more stable cis isomer of the enamine (80) with methyl vinyl ketone (MVK) would afford zwitterion 81 (attack by the other side of the enamine leads to strong steric interactions in the transition state). Reaction of the thermodynamically less favorable trans isomer 83 gives rise to zwitterions 84 and 89 (both without axial-axial interactions), and ion 84 is sterically able to undergo intramolecular proton shift to afford enamine 85. Zwitterionic intermediates 81 and 89 can be stabilized by conversion to dihydropyrans 82 and 90, or protonated to immonium ions. The pair 81-82 will lead to enamine 85, while the pair 89-90 will afford enamine 91. Then, cyclization of 85 or 91 will afford the enone expected from the normal enamine version of the Robinson annulation. 

The intramolecular proton transfer (IPT) reaction is unfavorable in the ground state from both the thermodynamic as well as kinetic reasons for both compounds. However, both factors favor the ESIPT process in the lowest excited singlet and triplet states. 

Howard, S.T. (2000) Relationship between basicity, strain and intramolecular hydrogen-bond energy in proton sponges. Journal of the American Chemical Society, 122, 8238-8244. Smith, P.B., Dye, J.L., Cheney, J. and Lehn, J.-M. (1981) Proton cryptates. Kinetics and thermodynamics of protonation of the [ 1.1.1 ] macrobicyclic cryptand. Journal of the American Chemical Society, 103, 6044-6048. 

Before analysis of the interactions of the nucleic acid bases with the clay minerals in the presence of water and cation one needs to understand the individual interactions of NAs with isolated water and with a cation. Such theoretical study was performed for 1 -methylcytosine (MeC) [139]. The study revealed influence of water and cation in the proton transfer for this compound. This leads to the formation of imino-oxo (MeC ) tautomer. Topology of the proton transfer potential surface and thermodynamics of stepwise hydration of MeCNa+ and MeC Na+ complexes is further discussed. The one dimensional potential energy profile for this process followed by the proton transfer with the formation of hydrated MeC Na+ is presented in Fig. 21.2. One-dimensional potential energy profile for amino-imino proton transfer in monohydrated N1-methylcytosine (this represents the situation when tautomerization is promoted by a single water molecule without the influence of Na+ cation) and for the case of pure intramolecular proton transfer (tautomerization is not assisted by any internal interactions) is also included. The most important features of this profile do not depend on the presence or absence of Na+ cation. All the potential energy curves have local minima corresponding to MeC and MeC. However, the significant difference is observed in the relative position of local minima and transition state, which results in a different thermodynamic and kinetic behavior for all presented cases (see Fig. 21.2). 

THERMODYNAMICS AND KINETICS OF INTRAMOLECULAR PROTON-TRANSFERS. TEMPERATURE-JUMP STUDIES. 

Gorb L, Kaczmarek A, Gorb A et al (2005) Thermodynamics and kinetics of intramolecular proton transfer in guanine. Post Hartree-Fock study. J Phys Chem B 109 13770-13776. doi 10.1021/jp050394m... 

As mentioned above, the appearance of the so-called rare tautomers of the nucleobases may cause severe health problems. A number of theoretical papers [70-73] investigate the thermodynamic conditions for their formations. Intramolecular proton migrations are unlikely in the gas phase. However, hydrogen-bonded pairs can be formed in DNA and RNA. The rare form can come into existence through a double proton-relay. Whether the process is concerted or sequential, it is a matter of debate and could depend also on the system (A-T/U... 

Another elegant example of the thermal generation and subsequent intramolecular cycloaddition of an o-QM can be found in Snider s biomimetic synthesis of the tetracyclic core of bisabosquals.2 Treatment of the starting material with acid causes the MOM ethers to cleave from the phenol core (Fig. 4.3). Under thermal conditions, a proton transfer ensues from one of the phenols to its neighboring benzylic alcohol residue. Upon expulsion of water, an o-QM forms. The E or Z geometry of the o-QM intermediate and its propensity toward interception by formaldehyde, water, or itself, again prove inconsequential as the outcome is decided by the relative thermodynamic stabilities among accessible products. 

All these reactions are thermodynamically favourable in the direction of proton transfer to hydroxide ion but the rate coefficients are somewhat below the diffusion-limited values. In broad terms, the typical effect of an intramolecular hydrogen bond on the rate coefficient for proton removal is to reduce the rate coefficient by a factor of up to ca 105 below the diffusion limit. Correspondingly the value of the dissociation constant of the acid is usually decreased by a somewhat smaller factor from that of a non-hydrogen-bonded acid. There are exceptions, however. 

In this region, the equilibrium constant for the proton-transfer step in Scheme 7 has a value K2> 1 and the proton transfer step is strongly favourable thermodynamically in the forward direction. This reaction step is a normal proton transfer between an oxygen acid which does not possess an intramolecular hydrogen bond and a base (B) and will therefore be diffusion-limited with a rate coefficient k2 in the range 1 x 109 to 1 x 1010dm3mol-1 s 1. It follows from (65) that kB will have a value which is... 

The reasons for the reluctance of the diamines to undergo protonation is due to the inaccessibility of the basic sites. The high thermodynamic basicity is probably due to a combination of the formation of a strong intramolecular hydrogen bond and to unfavourable lone pair interactions in the diamines that cannot be relieved by solvation. 

Formation of a highly electrophilic iodonium species, transiently formed by treatment of an alkene with iodine, followed by intramolecular quenching with a nucleophile leads to iodocyclization. The use of iodine to form lactones has been elegantly developed. Bartlett and co-workers216 reported on what they described as thermodynamic versus kinetic control in the formation of lactones. Treatment of the alkenoic acid 158 (Scheme 46) with iodine in the presence of base afforded a preponderance of the kinetic product 159, whereas the same reaction in the absence of base afforded the thermodynamic product 160. This approach was used in the synthesis of serricorin. The idea of kinetic versus thermodynamic control of the reaction was first discussed in a paper by Bartlett and Myerson217 from 1978. It was reasoned that in the absence of base, thermodynamic control could be achieved in that a proton was available to allow equilibration to the most stable ester. In the absence of such a proton, for example by addition of base, this equilibration is not possible, and the kinetic product is favored. 

Immobilization of the aminosilane molecule changes its interaction characteristics. Because the surface silanols are more acidic than silane silanols, the interaction with the surface silanols is thermodynamically favoured over intramolecular interaction. Kelly and Leyden10 measured the enthalpy of adsorption of the aminosilane molecules. Their results indicate that interaction with the surface involves more proton transfer than in the closed form dissolved molecules. 

The thermodynamic and kinetic characteristics of an intramolecular transimination reaction observed in solutions containing pyridoxal-5-phosphate and ethylenediamine have been investigated (75JA6530). The open-chain structure Schiff bases and the cyclic tautomers such as 54 are in equilibrium in aqueous solution over the pH range 7.5-14, but these equilibria are rather complex owing to the different states of the ionization (protonation) in both tautomers. The ring-chain equilibrium constant (the sum of all cyclic tautomers versus all open-chain tautomers) varies by less than a factor of 4 over the pH range 7-14. At pH 14, KT = 1.2 at pH 10,... 

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