Solvent isotope exchange

The proposed elimination (El cb) mechanisms (mechanisms A and B) were the result of studies of the behavior of substrate analogs and secondary deuterium isotope effects in the PAL reaction,solvent isotope exchange studies with HAL, ° and kinetic isotope effects studies of a ring perdeuterated phenylalanine in PAL. Later, a synthetic model putatively mimicking the PAL elimination reaction (mechanism B) was also described (Figure 15), taking into consideration the electrophilic behavior of a Michael acceptor within a sterically appropriate distance from a Phe (l)-like substrate. Upon treatment with a Lewis acid (AICI3) and... 

An enediol proton transfer mechanism for glyoxalase 1, mediated by a single active site base, is now well supported on the basis of solvent isotope exchange studies (107), intermediate trapping experiments (708), and partitioning studies using fluoromethylglyoxal (109, 110) [Eq. (23)] ... 

Other studies with unsaturated carboxylic acids are consistent with the mechanism of Ashby and Halpen. Ohta et al. hydrogenated several such substrates with D2 in MeOH or H2 in MeOD and found a labeling pattern predicted by the mechanism. They, as well as Chan et al., found that P,y-unsaturated carboxylic acids give labeling consistent with formation of a five-membered ring for the Ru-alkyl intermediate. It should be noted, however, that different patterns have been observed with different catalyst precursors, such as (BINAP)Ru(acac), used by Brown et al. and (BINAP)2Ru(H), used by Saburi et al. It is not clear if these represent chemical complications due to gas/solvent isotope exchange or mechanistic differences. Ashby and Halpem, and Ohta et al. examined qualitatively the MeOH/D2 exchange catalyzed by their mthenium hydride complexes. 

Another example is the absence of oxygen exchange with solvent in the hydrolysis of gluconolactone. Simple acyclic esters usually undergo isotopic exchange at a rate that is conqietitive with hydrolysis. This occurs through the tetrahedral addition intermediate. 

If it is assumed that ionization would result in complete randomization of the 0 label in the caihoxylate ion, is a measure of the rate of ionization with ion-pair return, and is a measure of the extent of racemization associated with ionization. The fact that the rate of isotope exchange exceeds that of racemization indicates that ion-pair collapse occurs with predominant retention of configuration. When a nucleophile is added to the system (0.14 Af NaN3), k y, is found to be imchanged, but no racemization of reactant is observed. Instead, the intermediate that would return with racemization is captured by azide ion and converted to substitution product with inversion of configuration. This must mean that the intimate ion pair returns to reactant more rapidly than it is captured by azide ion, whereas the solvent-separated ion pair is captured by azide ion faster than it returns to racemic reactant. 

Xenon [ F]difluoride was synthesized by isotopic exchange between XeF2 and H F, Si F4, or As F, and F-2DFG was prepared - by the action of this reagent on tri-O-acetyl-D-glucal (61). In this reaction, the combination of ethyl ether (as the solvent) and BFj (as the Lewis acid catalyst) was found to give the best result. ... 

Tetralin. Therefore, either trans-Decalin was formed on the surface of the coal with deuterium from the solvent or gas, or it was formed by isomerization from cis-Decalin with accompanying isotopic exchange with a deuterium source. Because the protium content of the cis-Decalins is much greater than the trans-Decalins, cis-trans isomerization is not very important. 

We chose the microwave-enhanced Raney Nickel catalyzed hydrogen isotope exchange of indole and N-methylindole as our substrates and D20, CD3COCD3, CD3OD and CDC13 as the solvents. The thermal reaction had already been the subject of a recent study [44], The microwave-enhanced method was some 500-fold faster than the corresponding thermal reaction (at 40 °C). Furthermore the pattern of labeling (Scheme 13.3) varied with the choice of solvent. Thus in the case of indole it-... 

This is the same mechanism as that given above for esters, in equation (42). The difference between esters and amides is apparent from a comparison of the two tetrahedral intermediates [5] and [17], The former contains three oxygens, any of which can be protonated, resulting in much lsO exchange being observed when the reaction takes place in 180-enriched water,275,276 but [17] contains a much more basic nitrogen, which will be protonated preferentially and lead to much less 180 exchange, as observed.274 277,278 Also, ammonium ion formation makes the overall reaction irreversible, unlike ester hydrolysis. The calculated solvent isotope effect for the Scheme 15 process is 1.00,280 exactly in accord with experimental observation.278,279... 

The observation of a primary solvent deuterium isotope effect (kH/fa>) = 2-4 on the specific acid-catalyzed hydrolysis of vinyl ethers provides evidence for reaction by rate-determining protonation of the alkene.69 Values of kHikD 1 are expected if alkene hydration proceeds by rate-determining addition of solvent to an oxocarbenium ion intermediate, since there is no motion of a solvent hydron at the transition state for this step. However, in the latter case, determination of the solvent isotope effect on the reaction of the fully protonated substrate is complicated by the competing exchange of deuterium from solvent into substrate (see above). 

Evaluation of kinetic data. Rate constants were determined for 2-H exchange from 3-R-4-methylthiazolium ions, catalyzed by D2O (pseudo first order) and DO- (second order).154 The observed rate constants for the pD-independent exchange reaction were corrected for the solvent isotope effect ( h2o/ d2o = 2.6), and the reverse protonation of the carbene by H30+ was assumed to be diffusion-controlled (k = 2 x 1010 M-1 s-1). A similar analysis was performed for the exchange catalysed by DO-. The results agreed nicely, giving pAfa = 18.9 for 213 and p/sfa = 18.0 for thiamine.154 The thiazolium ion 213 seems to be less acidic in water154 than in DMSO152 (Ap/fa = 2.4). Aside from the... 

As a practical matter of cost, studies on solvent isotope effects are usually limited to D/H substituted solvents, although recently a few lsO solvent effects have been measured. Interpretation of enzymatic solvent isotope effects is even more complicated than it is when the isotopic probe is incorporated in the substrate(s). This is because enzyme proteins have many exchangeable protons and, also, this is frequently true for reactants (substrates). Thus the observed isotope effect is the collective result of many different isotopic substitutions, each of which may influence... 

The equilibrium constant for the isotope-exchange equilibrium can be expressed (6) in terms of the solvent isotope effects on the acid-dissociation constants and of the monocarboxylic acid and dicarboxylic acid monoanion, respectively. It follows that a lower value for the fractionation factor of the hydrogen-bonded proton means that the solvent isotope effect on the acid-dissociation constant will be lower for the dicarboxylic acid monoanion than for the monocarboxylic acid. 

The acid-catalysed hydrolysis of the acylal, 1-phenoxyethyl propionate (13), has been studied using the PM3 method in the gas phase. The kinetics and mechanism of the hydrolysis of tetrahydro-2-furyl and tetrahydropyran-2-yl alkanoates (14) in water and water-20% ethanol have been reported. In acidic and neutral media, kinetics, activation parameters, isotope-exchange studies, substituent effects, solvent effects and the lack of buffer catalysis pointed clearly to an Aai-1 mechanism with formation of the tetrahydro-2-furyl or tetrahydropyran-2-yl carbocation as the rate-limiting step (Scheme 1). There is no evidence of a base-promoted Bac2 mechanism up to pH 12. ... 

In the early nineteen-sixties Halpem, James and co-workers studied the hydrogenation of water-soluble substrates in aqueous solutions catalyzed by rathenium salts [6]. RuCh in 3 M HCl catalyzed the hydrogenation of Fe(III) to Fe(II) at 80 °C and 0.6 bar H2. Similarly, Ru(IV) was autocatalytically reduced to Ru(III) which, however, did not react further. An extensive study of the effect of HCl concentration on the rate of such hydrogenations revealed, that the hydrolysis product, [RuCln(OH)(H20)5. ] " was a catalyst of lower activity. It was also established, that the mechanism involved a heterolytic splitting of H2. In accordance with this suggestion, in the absence of reducible substrates, such as Fe(in) there was an extensive isotope exchange between the solvent H2O and D2 in the gas phase. 

Astatobenzoic acid isomers have also been prepared by heterogeneous isotopic exchange by using the corresponding iodobenzoic acid. Halogen exchange has been effected under molten conditions, or with the substrate dissolved in a molten inert high-dielectric solvent, such as acetamide yields of 60-70% have been obtained (35). 

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