Concurrent pathways to explain solvent and substituent effects for solvolyses of benzoyl chlorides in ethanol-trifluoroethanol mixtures

Rate constants are reported at 25 ºC for solvolyses of p -Z-substituted benzoyl chlorides (Z = O 2 N, Cl, H, Me, and MeO) in 2,2,2-trifluoroethanol (TFE) in binary mixtures with water or ethanol. Product selectivities ( k TFE / k water ) are also reported. Previous work in which rate constants for solvolyses of benzoyl chlorides are correlated with σ constants is re-evaluated. V-shaped plots (assuming concurrent reactions) are constructed from logarithms of rate constants vs . σ (not σ • ) for substituent effects or a suitable parameter for solvent effects. Conditions are established for which it is predicted that concurrent mechanisms (one dissociative, one associative) each contribute 50% towards the observed rate constants.


Introduction
Differences in reaction mechanisms are usually discussed as if they occur abruptly from one to another due to changes in rate-limiting step, 1 or due to changes enforced by the lifetimes of intermediates. 2 Solvolyses of electron-rich benzoyl halides (e.g. 1, Z = MeO or 2 3a ) occur via a dissociative/ionization processes, whereas electron-deficient substrates (e.g. 1, Z = O2N) occur via addition/associative processes.1b,3b,3c We now investigate conditions under which both of these two processes could occur concurrently.
A change in mechanism from one to another is often inferred from a change in slope for a plot of log k (rate constant) vs. a suitable parameter when substituents or solvents are varied. 4Recent DFT calculations indicate that the rate enhancing effects of both electron-donating and electronwithdrawing substituents on solvolyses of acid chlorides (1) in water can be explained by a concerted SN2 mechanism along with large changes in transition state structure. 5The purpose of our study is to provide further experimental evidence for the alternative mechanistic explanation 6,7 of simultaneous (concurrent) reaction pathways.
Solvent effects in binary trifluoroethanol (TFE) mixtures will be correlated with those for 1, Z = MeO to allow for the effects of solvent ionising power and of aromatic ring solvation. 7It has recently been found that substituent effects for dissociative solvolyses of benzoyl chlorides correlate unexpectedly well with the original Hammett σ function. 8The two types of correlation (for substituents and solvents) will provide the first independent estimates of the locations where each of the two pathways contributes 50% to the observed rate constant.

Results and Discussion
Kinetic data are summarized in Table 1 for TFE-water and in Table 2 for ethanol-TFE.The reliability of some previously published data 9 has been questioned 3b (see also Solvent effects can be explained quantitatively using the extended Grunwald-Winstein equation (1), in which logarithms of rate constants (log k) relative to rate constants in 80% v/v ethanol-water (log k0) are correlated with solvent ionizing power (YCl, based on solvolyses of 1-adamantyl chloride) and solvent nucleophilicity (NT); values of substrate responses l and m are then obtained by fitting data for each substrate to equation ( 1) and c is a residual term.3b log(k/k0) = lNT + mYCl + c (1) Solvolyses of 1, Z = MeO in 37 solvents respond mainly to changes in solvent ionizing power and fit equation ( 1) with l = 0.31 and m = 0.81, 3b consistent with a dissociative reaction mechanism.In contrast, solvolyses of 1, Z = O2N in 34 solvents respond mainly to changes in solvent nucleophilicity and fit equation ( 1) with l = 1.78 and m = 0.54, 3b consistent with an associative mechanism.Solvolyses of 1, Z = Me gave l = 0.41 and m = 0.73, also consistent with a dissociative mechanism, but two equations were required for each substrate to fit the responses of other substrates (1, H and Cl), indicating concurrent reaction pathways.3b How reliable are conclusions based on equation (1)?Multi-parameter correlations should be applied cautiously, 14 and it is known that aromatic ring solvation effects are not accounted for explicitly; this can achieved using Kevill's solvent parameter, (I), 15,16 but an alternative is to chose a different similarity model for Y. Liu et al. 17,18 based a YBnCl scale on solvolyses of 2-aryl-2adamantyl chloride, data for which is limited by inadequate solubility in less aqueous media.As an alternative, we chose solvolyses of 1, Z = MeO as a similarity model for solvolyses of acid chlorides. 6,7Comparisons of solvolyses of 1, Z = MeO with YBnCl indicate that rates of solvolyses of 1, Z = MeO are enhanced by weak nucleophilic solvent assistance, 9 consistent with l = 0.31 (equation 1).3b In addition to refining the correlations of solvent effects, additional and independent support for concurrent pathways will be obtained from substituent effects.Recent research has provided new insights into the selection of appropriate substituent constants (e.g. the original Hammett σ or an alternative for cations σ + ).There is a measurable resonance effect in some σ constants, 19,20 and there is also a large effect of electron-donating substituents on the C-Cl bond length and on the negative charge at the chlorine atom in benzoyl chlorides (1). 21The stabilisation energies, calculated from equation (2), 21 were recently shown to correlate with σ, 8 so the resonance demand incorporated into Hammett's σ constants may be sufficient to account for substituent effects on cationic reactions of benzoyl chlorides.In contrast, 2,6-dimethylbenzoyl chlorides (2) require the enhanced resonance demand of σ constants, 3a probably because the unconjugated perpendicular conformation of the chloride (2) leads to a greater change in conjugation energy in the acylium transition state. 8 1.
Addition of 3% water to TFE causes small rate increases (Table 1) for solvolyses of 1, Z = MeO, Me, H and Cl).Our kinetic data confirm that there is a large rate decrease on changing from 97% to 100% TFE for 1, Z = O2N, 3b consistent with a mechanistic change.The σ plot for 100% TFE is linear (Figure 4), and this may be due to a switch to the dissociative pathway, even for 1, Z = O2N for which ΔS ≠ = -10.7 cal mol -1 K -1 (Table 1, footnote c,); in contrast, solvolyses of 1, Z = O2N in 97% TFE-water have a more highly negative ΔS ≠ of -30.4 cal mol -1 K -1 .10a As the associative pathway is highly sensitive to changes in solvent nucleophilicity, 3b and the nucleophilicity of 97% TFE is greater than 100% TFE, 23 a relatively abrupt change from associative in 97% TFE to dissociative pathways in 100% TFE is plausible.From a linear σ + plot, we proposed previously 10a that solvolyses of 1, Z = O2N in 97% TFE-water were dissociative, but a highly negative ΔS ≠ was unexplained, and σ-plots are now preferred. 8he products of reaction with TFE-water are a carboxylic acid (3), and a TFE ester (4).Product selectivities (S, equation 3, Table 3) vary significantly with solvent composition for solvolyses of 1, Z = O2N, but not for the other substrates.Absolute values of S for solvolyses of 1, Z = MeO, Me, H and Cl vary from substrate to substrate, as observed for 4-substituted benzyl chlorides, 22 and consistent with solvolyses within the SN2-SN1 mechanistic spectrum.

S = [TFE ester product]/ [acid product] × [water]/ [TFE]
(3) Most of the σ plots for TFE-water mixtures (Figure 2) are strongly curved, consistent with mechanistic changes by transition state variation 5 (but not excluding competing pathways).There is much stronger evidence for mechanistic changes in the plots for ethanol-TFE (Figures 3 and 4), because the log k plots for both solvents and substituents show clear minima.The slope of the solvent effect plot (Figure 3, left) is +1.0 for 1, Z = MeO (by definition) and solvolyses of 1, Z = Me give a good linear correlation from 100% TFE to 60% ethanol/TFE (slope: 0.80 ± 0.03, r = 0.996, n = 7); the data for 80% ethanol/TFE and 100% ethanol are above an extrapolated correlation line (not shown), consistent with a mechanistic change between 60 and 80% ethanol/TFE for solvolyses of 1, Z = Me; the -plots for 60 and 80% ethanol/TFE (Figure 4, right) have minima around  = -0.1 (approximately corresponding to Z = Me), so provides independent support.The solvent effect plot for 1, Z = O2N (Figure 3, right) can be approximated by an initial linear region having a negative slope from ethanol to 40% ethanol/TFE (as with Figure 1, the linearity of plots is partly due to the limited range of solvents).Solvolyses of 1, Z = Cl show similarly negative slopes to solvolyses of 1, Z = O2N over this solvent range (Figure 3, right), in to the positive slopes for solvolyses of 1, Z = MeO and Me (Figure 3, left); the plot for solvolyses of 1, Z = Cl then crosses from below to above the plot for 1, Z = O2N and solvolyses in 5 and 10% ethanol/TFE show a positive slope similar to that for 1, Z = MeO and Me.Therefore, based on Figure 3, a mechanistic change for solvolyses of 1, Z = Cl occurs around 20% ethanol/TFE, consistent with the minimum at  = 0.2 for 20% ethanol/TFE (Figure 4, left).
The solvent effect plot for 1, Z = H (Figure 3, left) shows two clear linear regions, with a shallow minimum around log k = -1.5 on the x-axis, corresponding to 40% ethanol/TFE; substituent effects in 40% ethanol/TFE (Figure 4, left) show a minimum around  = 0, also consistent with a mechanistic change for 1, Z = H in 40% ethanol/TFE.These results (Figures 3 and 4) provide much clearer evidence for competing reaction channels (based on changes in slopes) than previous investigations using binary aqueous mixtures; 7,24 these also include Hammett plots for ten substrates in 60% acetone/water, which show a clear minimum at  = 0, 24b in agreement with the independent prediction that the mechanistic change for benzoyl chloride occurs in 60% acetone (point C in Figure 5 of ref. 7).Also, selectivity data in aqueous alcohols show changes in product (as well as rate) determining steps. 6lthough solvolyses of benzoyl chloride (1, Z = H) in water show cationic character, there is no evidence for a cationic intermediate (SN1 reaction), 10b but there is evidence from solvent effects for SN2 character.3b, 25 We consider that there is only one reaction channel within a mechanistic SN2 -SN1 spectrum, and the competing reaction channel is a carbonyl addition process.10b, 25 Concurrent stepwise and concerted substitution reactions have been proposed in other cases (e.g.reaction of 4methoxybenzyl chloride with azide ion in aqueous acetone 26 ).

Conclusions
Relative rates k (1, Z = MeO)/k (1, Z = O2N) vary from <0.1 in EtOH to >10 5 in TFE.Solvolyses of 1, Z = MeO provide a similarity model for cationic (dissociative) reaction pathways within the SN2-SN1 mechanistic spectrum; this pathway includes relatively nucleophilic weak solvation of the developing positive charge and is favoured by electron-donating substituents and more polar solvents.Solvolyses of 1, Z = O2N proceed via addition (associative) pathway, except possibly in 100% TFE; the associative pathway is favoured by electron-withdrawing substituents and by solvents of low polarity, and may involve varying extents of general base catalysis by a second solvent molecule (the SN3-SN2 mechanistic spectrum 27 ).

Figure 3 .
Figure 3. Logarithms of rate constants for solvolyses of acid chlorides, left (1, Z = MeO, Me, H) and right (1, Z = Cl and O2N), in ethanol-trifluoroethanol vs. data for (1, Z = MeO); the data are directly from Table 2, so are uncorrected for competing reaction pathways; two plots are shown to minimise crowding around log k = -3.

Figure 4 .
Figure 4. Logarithms of rate constants for solvolyses of acid chlorides (1) in ethanoltrifluoroethanol vs. Hammett ; data from Table 2, but halving the rate constants for 1, Z = MeO in EtOH, 1, Z = H in 40 and 60% EtOH/TFE, and 1, Z = Cl in 20% EtOH/TFE to correct approximately for competing reaction pathways; the correlation lines shown for 80% EtOH/TFE are extrapolated to calculate the position of the minimum at  = -0.13.

Table 1 .
1, footnotes c and d, and Table 2, footnote d), and data from this source 9 have been excluded.Rate constants (10 4 k/s -1 ) for solvolyses of p-Z-substituted benzoyl chlorides (1) in trifluoroethanol-water mixtures at 25 ºC a a Determined conductimetrically in duplicate except where stated otherwise; typical errors are ±3%.b This work.c Reference 3b; also 54.2, possibly due to arithmetic error in reference 9; our d Reference 9 reports a significantly higher value of 5010.e Data from reference 10a.f Data from reference 10b.g Calculated from the following data: (10 2 k, ºC): ≠ = 17.8 kcal mol -1 , ΔS ≠