Ethanolysis rate

Accordingly, the simplest mechanism that accounts for the enhanced ethanolysis rates in the presence of metal ions is shown in IV, where a metal-bound ethanol molecule, made acidic by metal coordination, serves as a general acid catalyst for C—N bond cleavage. Here again enhanced reactivity is exhibited by the 18C6-complexed metal ethoxide species [13]. 

Mutual interchanges between pKr values, gas-phase hydride affinities, and ethanolysis rate constants can, in principle, be derived from Eqs. (9-12). Because of the use of more extended data sets and of uncorrected ethanolysis rate constants, the correlations presented in Ref. 19 are slightly different. 

On the basis of these considerations it has been concluded that under given reaction conditions (Lewis acid/solvent) the reactivity maximum is found for an alkylating system (RA7R+) that is approximately half-ionized [60,61]. Scheme 11 suggests that the electrophilic reactivity of RA" increases with increasing stabilization of R+ if only small equilibrium concentrations of carbocations are involved. In accord with this analysis, the relative alkylating abilities of alkyl chlorides have been found to be proportional to their ethanolysis rates (Fig. 2) [62]. The only compound that deviates from this correlation is trityl chloride which alkylates considerably more slowly than expected from its solvolysis rate. 

Figure 2 Correlation of the relative reactivities of alkyl chlorides la-x toward allyltrimethylsilane (CH2CI2, —70° C) with their ethanolysis rate constants (25° C). The value for PluCCl has not been used for calculating the correlation equation log fcrd = 1.036 log (EtQH) + 10.1 (r = 0.971). (From Ref. 62, reprinted with permission of VCH Verlagsgesellschaft.)...

The first order rate constant for ethanolysis of the allylic chloride 3 chloro 3 methyl 1 butene is over 100 times greater than that of tert butyl chloride at the same temperature... 

It occasionally happens that a reaction proceeds much faster or much slower than expected on the basis of electrical effects alone. In these cases, it can often be shown that steric effects are influencing the rate. For example, Table 9.2 lists relative rates for the Sn2 ethanolysis of certain alkyl halides (see p. 390). All these compounds are primary bromides the branching is on the second carbon, so that field-effect differences should be small. As Table 9.2 shows, the rate decreases with increasing P branching and reaches a very low value for neopentyl bromide. This reaction is known to involve an attack by the nucleophile from a position opposite to that of the bromine (see p. 390). The great decrease in rate can be attributed to steric hindrance, a sheer physical blockage to the attack of the nucleophile. Another example of steric hindrance is found in 2,6-disubstituted benzoic acids, which are difficult to esterify no matter what the resonance or field effects of the groups in the 2 or the 6 position. Similarly, once 2,6-disubstituted benzoic acids are esterified, the esters are difficult to hydrolyze. 

An implication of the kinetic analysis presented in Sec. IV.A is that the rate of chain scission of polyesters can be retarded by endcapping to reduce the initial carboxylic acid end-group concentration. Alternatively, the rate may be increased by acidic additives that supplement the effect of the carboxy end groups. The first expectation was confirmed by partial ethanolysis of high molecular weight... 

Because of certain misconceptions with regard to the choice of solvent and the occurrence of sulfur-oxygen bond fission in hydroxylic solvents - , it is important to emphasize that one can greatly reduce the rate of this competing process by the use of weak bases. In systems which can undergo facile C—O as well as S—O bond fission, it is possible to control the type of bond cleavage by choosing the appropriate base . A remarkable illustration of this behavior is found in the ethanolysis of sulfinate 6a. In anhydrous ethanol at 90.0° with acetate ion as the added base, 6a yielded ethyl 2, 6-dimethylbenzenesulfinate plus a trace of sulfone 7a. Under the same conditions but with 2,6-lutidine the reaction was slower and sulfone 7a was the only detectable reaction product . ... 

Having established the speciation, we now have a very powerful tool for analyzing the kinetic data for the pH dependence of the La3 + catalysis of the alcoholysis of various substrates. Included in the Figs 1 and 2 plots are the second-order rate constants for La3 + -catalysis of the ethanolysis of paraoxon (1) and the methanolysis of /xnitrophenyl acetate (PNPA, 2) as a function of pH in ethanol and methanol, respectively. The kinetic data mainly follow the rise/fall behavior of the Lal+( OR)2 species with some involvement of the other species, La2 + ( OR)i, La2 1 ( OR)3 and Lal+(-OR)4. 

To determine the activities for the various Lal+( OR) we analyze the k2bs data as a linear combination of individual rate constants (Equation 8), where ki4, kf2... " are the second-order rate constants for each La2+( OR) promoting ethanolysis and methanolysis of 1 and 2 respectively. 

The catalysis afforded by the La3 + system for the transesterifications of paraoxon in ethanol and methanol is quite spectacular relative to the background reactions that are assumed to be promoted by the lyoxide. The reaction rate constant of ethoxide with paraoxon in ethanol at 5.1 x 10-3 dm3 mol-1 s-133 is roughly a factor of two lower than the rate constant of methoxide with paraoxon in methanol (1.1 x 10 2dm3mol 1 s-1).17a However a solution 2mmoldm-3 in total [La3 + ], which contains 1 mmol dm-3 of Lal+, has a maximum rate constant of 7 x 10-4s-1 for decomposition of 1 in ethanol at pH of 7.3, and accelerates the rate of ethanolysis of paraoxon by a factor of 4.4 x 10n-fold relative to the ethoxide reaction at the same pH.34 By way of comparison, the acceleration afforded by a 1 mmol dm-3 solution of the La + dimer catalyzing the methanolysis of 1 at the maximal pH of 8.3 (kobs = 0.0175 s 1) is 109-fold greater than its background methoxide reaction. On this simple basis La2+ in ethanol appears to be catalytically superior to La2+ in methanol, but this stems almost exclusively from the pH values... 

While the acceleration afforded to the cyclization of 32 by La3 + in methanol is certainly spectacular, this is not a biologically relevant metal ion and its charge exceeds that of the natural metal ion Zn2+. Very recent investigations of Zn2+-catalysis of the methanolysis and ethanolysis of 32 indicated that there were indeed interesting catalytic effects, and that the situation in pure ethanol is quite different.85 Shown in Figs 15 and 16 are plots of the pseudo-first-order rate constant (kobs) for ethanolysis and methanolysis of HPNPP (32) as a function of [Zn2+]total when the [ OR]/[Zn2+] ratio is 0.5. This ratio was chosen to buffer the system at the half neutralization jjpH of 7 in ethanol8 and 9.5 in methanol at [Zn2+]to)ai = l-2 mM7... 

Since the active species for the ethanolysis of 2 is 9 Z2 + ( OEt), the true-second-order rate constant for the reaction would be twice the gradient of the plot, or 1.62 dm3 moP1 s 1... 

The normal effect of NO2 on S l solvolysis of substrates such as benzhydryl chloride is to retard reaction. Thus in the ethanolysis of XQdLjCIIPhCI, logfc values (first-order rate coefficients, s 1) are as follows (50 °C) H, —3.05 m-N()2, —5.64 p-NCT. —5.99198. The p value for this reaction is about —3.7, so the logfc values for the m-NCT and p-NCT derivatives correspond fairly closely to the a values of 0.71 (or 0.73) and 0.78, respectively (Section III.B). This reaction is, of course, strongly accelerated by —R para-substituents through cross-conjugation in the carbocationic transition state (Section n.A). 

Menthyl p-iodobenzenesulfinate 62 exists in two diastereomeric forms having [a]u + 46 and -146 (79,103). Herbrandson and Cusano (103) determined their absolute configurations on the basis of kinetic studies of the hydrogen chloride-catalyzed equilibration (+>62 (-)-62 and ethanolysis of both diastereomeric esters. They found that the equilibration reaction carried out in nitrobenzene at room temperature results in the formation of a mixture containing 59 3% of the dextrorotatory diastereomer. On the other hand, the rate of ethanolysis of the thermodynamically more stable (+)-62 isomer was found to be twice as large as that of the (->isomer. 

Bender and Glasson (1959), in studies of alcoholysis and hydrolysis of idkyl esters in aqueous alcohol, found that the rate of disappearance of ester is decreased by increasing alcohol concentration. However, product analysis led to the conclusion that both methanolysis and ethanolysis are faster than hydrolysis in alcohol-water mixtures. It was calculated that in pure water attack by hydroxide, methoxide and ethoxide ions would occur at about the same rates. 

Even more surprising is the finding that the reactivity picture exhibited by the various ethoxide species in the ethanolysis of phenyl acetate is very similar to that found in the ethanolysis of the activated amide N-methyl-2,2,2-trifluoroacetanilide [Eq. (3)], despite the different mechanisms of the two reactions [13]. Schowen ef al. [14] showed that C-N bond breaking in the rate-limiting decomposition of the tetrahedral intermediate is assisted by proton transfer from a general acid to the leaving group. 

The sample kinetic data listed in Table 5.2 shows that the size of rate enhancement critically depends on the substrate-metal ion combination, and is markedly influenced by the solvent. The largest effect is displayed by 2-AcO-21 C6, which reacts with EtOBaBr half a million times faster than with EtONMe4. The conclusion was reached [6] that the huge rate enhancements observed in the ethanolysis reactions are a consequence of the fact that not only cation-anion electrostatic binding but also coordinative binding to the polyether chain in the metal-bound transition states are much more efficient in EtOH than in MeOH. 

In the presence of a large excess of EtO ion, the bimetallic catalyst is fully saturated with EtO as shown by structure I in Scheme 5.3. Incremental additions of a carboxylate substrate would cause the gradual conversion of I into the 1 1 productive complex II, but further additions would yield the unproductive complex III. As expected from this mechanism a bell-shaped profile is observed in a plot of initial rate versus substrate concentration related to the catalyzed ethanolysis of 16 (Figure 5.5). The fairly good quality of the fit supports the validity of Scheme 5.3. Further confirmation comes from the finding that benzoate anions behave as competitive inhibitors of the reaction. Since the reaction product of the ethanolysis of 16 is also a benzoate anion, product inhibition is expected. Indeed, only four to five turnovers are seen in the ethanolysis of 16 before product inhibition shuts down the reaction. The first two turnovers are shown graphically in Figure 5.6. 

In conclusion, the bis-barium complex of 17 catalyzes the ethanolysis of anilide and ester substrates endowed with a distal carboxylate anchoring group (Table 5.7). The catalyst shows recognition ofthe substrate, induces fairly high reaction rates with catalytic turnover, and is subjected to competitive inhibition by carboxylate anions, as... 

Figure 5.6 Turnover bimetallic catalysiswith product inhibition in the ethanolysis of 16 under the conditions outlined in Figure 5.5. One molar equivalent of 16 is added attimezero. A second molar equivalent of 16 is added at the time indicated by the arrow. Further portions of 16 (1 mol equiv) solvolyze with increasingly lower rates (not shown in the plot). number of turnovers.

The dinuclear Sr complex of the ditopic ligand 17 increases the rate of basic ethanolysis ofthe malonate derivative 19 by a surprising 5700-fold, but increases by only 9.5-fold the rate of cleavage of 14 [28]. It is remarkable that such a huge rate-enhancement occurs under extremely dilute conditions, namely 15 pM 19 and 30 pM 17-Sr2. A slightly lower rate enhancement is observed in the presence of 17-Ba2. It seems likely that under the dilute conditions of the catalytic experiments several crown-complexed metal species occur simultaneously (Scheme 5.4). Given the plethora of species involved in such a complicated system of multiple equilibria, quantitative kinetic treatment is out of reach. Nevertheless, a comparison with the reactivity of model compounds, particularly that of the malonate derivative 20, provides insight into the composition of the reactive intermediate (Table 5.8),... 

Figure 5.9 Basic ethanolysis of 0.025 mM 29 in EtOH/MeCN in the presence of 1.00mM Me4NOEt and 0.10mM trans-28-Ba2. Repeated photoconversions into quasi-cis and quasi-trans forms are obtained upon alternate irradiations at 370 and 480 nm for 40 s. Specific rates are reported on the right-hand ordinate axis. 

In contrast to this demonstration of bimolecularity, Hall and Lueck82 showed the possibility of acylium ion formation from benzoyl chloride by its reaction with mercuric perchlorate. In common with dimethylcarbamyl chloride, dimethylsulphamyl and tetramethyldiamidophosphochloridate, benzoyl chloride reacted readily to form the corresponding acylium ion /i-butyl chloroformate however was inert. Kivinen138 studied the effect of mercuric chloride on the ethanolysis of 4-methoxybenzoyl chloride, benzoyl chloride and 4-nitrobenzoyl chloride and obtained the following approximate relative rates for the effect of mercuric chloride (0.30 M) in ethanol, 4-MeO, 2.91 4-H, 1.00 4-NOz, 1.03, confirming the SN2 character of the 4-nitro-... 

RATE COEFFICIENTS FOR ETHANOLYSIS OF BENZOYL CHLORIDE159 AND THE EMPIRICAL SOLVENT PARAMETERS Z, 0a AND Er161... 

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