Solvolysis Rate Constants Research Articles

Effects of Ionic Liquids on the Nucleofugality of Bromide.

The nucleofugality of bromide was measured in solvent mixtures containing ionic liquids. The solvolysis rate constants of the bromides of well-defined electrofuges were determined in mixtures containing different proportions of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide in ethanol. Temperature-dependent kinetic studies allowed an explanation of the observed solvent effects in different mixtures in terms of interactions in solution. Using the solvolysis data, the nucleofugality of bromide in these systems was determined. Likewise, nucleofugality data for bromide were determined in mixtures containing high proportions of seven further ionic liquids. These data allowed quantification of the effects of both varying the amount of ionic liquid and the nature of ionic liquid components on the nucleofugality of bromide. Importantly, ionic liquid mixtures were shown to affect the nucleofugality in a manner similar to chloride, providing a method for predicting the effects of ionic liquids on other electrofuges. Further, the ionic liquids were shown to move the transition state earlier along the reaction coordinate, meaning that there is less charge development in the transition state.

Stereoselective Solvolysis in the Synthesis of Dorzolamide Intermediates.

The key intermediate in the synthesis of dorzolamide, (4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide, can be obtained in the diastereoisomerically pure form in two straightforward steps starting from diastereoisomeric mixtures of cis/trans-(6S)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-yl acetate, regardless of their ratio. The reaction of crucial importance in this scheme is a remarkably stereoselective solvolysis of the acetate ester in an acetone/phosphate buffer mixture as the solvent system. Investigation of this so far unrecognized stereoselective reaction reveals that it proceeds via an SN1-like pathway as indicated by the correlation of the solvolysis rate constants with the YOTs values of different solvent mixtures and by trapping of the reaction intermediate with sodium azide. The structure of (4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide was confirmed by single-crystal X-ray analysis.

Solvolytic behavior of some ferrocenylphenylmethyl‐4‐methoxypyridinium cations in various solvents

AbstractThe nucleofugalities of 4‐methoxypyridine (4‐OMePy) in pure and aqueous solvents were derived from the rate constants for SN1 solvolysis with respect to the corresponding ferrocenylphenylmethyl‐4‐methoxypyridinium salts by applying the linear free energy relationship (LFER) equation, log k (25°C) = sf (Nf + Ef). In more polar solvents, pyridinium ions become more stabilized by solvation in the reactant ground state than in the corresponding transition state and the reactivity (nucleofugality, Nf) of 4‐OMePy decreases increasing solvent polarity. Due to the strong electron‐donor effect of the ferrocenyl group, it seems that 4‐methoxypyridine is a somewhat better leaving group (stronger nucleofuge) if the substrate is benzhydryl‐4‐methoxypyridinium salts rather than ferrocenylphenylmethyl‐4‐methoxypyridinium salts. Given that the electron‐withdrawing substituents on the 4‐position of the pyridine ring increase the rate of the heterolysis step of solvolysis for benzhydryl and ferrocenylphenylmethyl pyridinium salts, the Nf value of substituted pyridine decreases in order Nf (4‐ClPy) > Nf (Py) > Nf (4‐MePy) > Nf (4‐OMePy) across in all examined solvents.

Mechanism of solvolysis of substituted benzyl chlorides in aqueous ethanol

The mechanism of solvolyses of activated ortho-, meta- and para-substituted benzyl chlorides in aqueous ethanol has been studied by using the Hammett-Brown and Yukawa-Tsuno treatments as well as by correlating logarithms of solvolysis rate constants with relative stabilities of corresponding benzyl carbocations in water calculated at the IEFPCM-M06–2X/6-311+G(3df,3pd) level of theory. Benzyl chlorides containing strong conjugative electron-donors in the para-position solvolyze by the SN1 mechanism, whereas other activated benzyl chlorides solvolyze by the SN2 mechanism via loose transition states.

Effects of Ionic Liquids on the Nucleofugality of Chloride.

The nucleofugality of chloride has been measured in solvent mixtures containing ionic liquids for the first time, allowing reactivity in these solvents to be put in context with molecular solvents. Using well-described electrofuges, solvolysis rate constants were determined in mixtures containing different proportions of ethanol and the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide; the different solvent effects observed as the mixture changed could be explained using interactions of the ionic liquid with species along the reaction coordinate, determined using temperature dependent kinetic studies. The solvolysis data allowed determination of the nucleofugality of chloride in these mixtures, which varied with the proportion of salt in the reaction mixture, demonstrating quantitatively the importance of the amount of ionic liquid in the reaction mixture in determining reaction outcome. Nucleofugality data for chloride were determined in seven further ionic liquids, with the reactivity shown to vary over more than an order of magnitude. This outcome illustrates that the components of the ionic liquid are critical in determining reaction outcome. Overall, this work quantitatively extends the understanding of solvent effects in ionic liquids and demonstrates the potential for such information to be used to rationally select an ionic liquid to control reaction outcome.

Kinetic Study on Solvolysis of 2‐Methylfuran‐3‐carbonyl Chloride in Binary Solvent Mixtures

Rate constants for solvolysis of 2‐methylfuran‐3‐carbonyl chloride (1) in ethanol, methanol, and aqueous binary mixtures incorporating ethanol, methanol, acetone, 2,2,2‐trifluoroethanol, and 1,1,1,3,3,3‐hexafluoro‐2‐propanol are reported. The 34 solvents give an extended Grunwald–Winstein correlation with l = 0.26 ± 0.05, m = 0.71 ± 0.04, and correlation coefficient R2 = 0.963. Activation parameters calculated from the rate constants measured at three different temperatures in five different solvents are presented. In the deuterated methanol, a solvent kinetic isotope effect of 1.15 was observed at 0°C. The kinetic features observed indicate that the reaction proceeds through an SN1 mechanism with a little SN2 character. The reactivity–selectivity principle is also followed in alcohol‐water mixtures.

확장된 Gruwald-Winstein 식에 의한 Biphenyl-4-carbonyl chloride의 가용매분해 반응대한 연구

The solvolysis rate constants of biphenyl-4-carbonyl chloride (C6H5C6H5COCl, 1) in 19 different solvents are well correlated with the extended Grunwald-Winstein equation, using the NT solvent nucleophilicity scale, YCl solvent ioniz- ing scale, and I aromatic ring parameter with sensitivity values of 0.31±0.10, 0.46±0.05, and 0.96±0.20 for l, m, and h, respec- tively. These l, m, and h values can be considered to support a dissciative SN2 reaction pathway. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH ‡ (15.3~16.1 kcal/mol) values and large negative ΔS ‡ (�17.2~�20.0 cal/mol·K) values.

Nucleofugality of Pentafluorophenolate in Various Solvents: Solvolytic Behavior of Phenolates

The leaving group ability (nucleofugality) of the pentafluorophenolate anion has been determined from first order solvolytic rate constants (k) of X,Y-substituted benzhydryl pentafluorophenolates measured in a series of solvents, by using the three parameter LFER equation: log k = sf (Ef + Nf). Comparison with other leaving groups reveals that pentafluorophenolate is a moderate leaving group, whose nucleofugality (Nf value) is between the nucleofugalities of phenyl carbonate and 3,5-dinitrobenzoate leaving groups. However, due to its high reaction constant (sf = 1.29 in 80 % aq. ethanol), relative reactivities of benzhydryl pentafluorophenolates and corresponding benzhydryl carboxylates vary with the electrofugality of a carbocation formed in the heterolytic step, i.e., inversion of the reactivity of benzhydryl series with different leaving groups occurs. The plots of Δ‡G° vs. ΔrG° for solvolysis of benzhydryl phenolates and carboxylates reveal that phenolates solvolyze over the lower Marcus intrinsic barrier than corresponding carboxylates. This work is licensed under a Creative Commons Attribution 4.0 International License .

Nucleofugalities of Neutral Leaving Groups in 80 % Aqueous Acetonitrile

Nucleofugalites of tetrahydrothiophene, dimethyl sulfide and differently substituted pyridines in 80 % aqueous acetonitrile have been derived from the SN1 solvolysis rate constants of the corresponding X,Y-substituted benzhydryl derivatives (1–10). In sol-volysis of sulfonium ions in 80 % aqueous acetonitrile, where acetonitrile is a good cation solvator, the solvation of the reactant ground state is an important rate determining variable since the positive charge is almost entirely located on the leaving group. As a consequence, reaction rates of sulfonium ions are more sensitive to the substrate structure in 80 % aqueous acetonitrile than in pure and aqueous alcohols, which are less efficient as cation solvators. In solvolysis of pyridinium ions the solvation of the reactant ground state is less important, since the positive charge is considerably distributed between the carbon at the reaction center and the leaving group. In such cases the important rate determining variable is solvation of the transition state. Slower reactions of pyridinium sub-strates progress over later, carbocation-like transition states in which the solvation is more important, so those substrates solvolyze slightly faster in aqueous acetonitrile than in methanol (k80AN > kM). Faster reactions proceed over earlier TS in which the solvation is diminished, so those substrates solvolyze somewhat faster in methanol than in aqueous acetonitrile (k80AN < kM). This work is licensed under a Creative Commons Attribution 4.0 International License.

Studies of Solvolyses of 1,4‐Benzodioxan‐6‐Sulfonyl Chloride by Extended Grunwald–Winstein Equation

The rate constants of solvolysis of 1,4‐benzodioxan‐6‐sulfonyl chloride (C8H7ClO4Cl, 1) were determined by a conductivity technique. These rate constants of 1 in 28 different solvents correlated well with the extended Grunwald–Winstein equation. The l (1.00) and m (0.59) values support an SN2 reaction pathway having a similar transition state structure to that of the benzenesulfonyl chloride (2, l = 1.10, m = 0.61) reaction. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH ≠ (8.9 to 15.5 kcal/mol) and large negative ΔS ≠ (−27.3 to −49.2 cal/mol/K) values, and the solvent kinetic isotope effect (1.62). The Kivinen's n values (n = 0.03 in methanol, 0.04 in ethanol) obtained in binary solvents were consistent with the proposed bimolecular reaction mechanism.

확장된 Grunwald-Winstein 식에 의한 Di-n-butyl Phosphorochloridate의 가용매 분해반응 연구

The solvolysis rate constants of di-n-butyl phosphorochloridate ((CH3CH2CH2CH2O)2POCl, 1) in 28 different solvents are well correlated with the extended Grunwald-Winstein equation, using the NT solvent nucleophilicity scale and YCl solvent ionizing scale, with the sensitivities values of 1.40 and 0.42 for l and m, respectively. These l and m values can be con- sidered to support an SN2 reaction pathway. This interpretation is further supported by the activation parameters, i.e., rela- tively small positive ΔH ≠ (8.0 to 15.9 kcal·mol �1 ) values and large negative ΔS ≠ (�25.8 to �53.1 cal·mol �1 ·K �1 ) values, the Kivinen's n values (0.9~1.7), and the solvent kinetic isotope effect (1.62).

Solvolysis of 2-adamantyl p-toluenesulfonate in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate

The solvolytic rate constants of 2-adamantyl p-toluenesulfonate were determined in [BMIM][BF4] in the presence/absence of 2,6-lutidine by NMR measurements. The activation parameters suggest that the reaction proceeded by kc mechanism. The solvolysis quantitatively gave 2-adamantanol as a product by the reaction with the water present in the ionic liquid. The solvent ionizing power of [BMIM][BF4] was found to be similar to that of ethanol.

Correlation of Rates of Solvolysis of Diphenylacetyl Chloride Using Extended Grunwald–Winstein Equation

Rate constants for solvolysis involving the displacement of chloride from the carbonyl carbon of diphenylacetyl chloride ((C6H5)2CHCOCl, 1) in ethanol, methanol, aqueous binary mixtures incorporating ethanol, methanol, acetone, 2,2,2‐trifluoroethanol (TFE), and 1,1,1,3,3,3‐hexafluoro‐2‐propanol, and binary mixtures of TFE with ethanol are reported. The kinetic data obtained from the reactions in 34 different solvents and solvent mixtures gave an extended Grunwald–Winstein correlation with the l value of 0.76 ± 0.06, the m value of 0.34 ± 0.04, and the correlation coefficient (R2) of 0.932. The appreciable values for both l and m suggest that the bond formation is ahead of the bond breaking with an SN2 mechanism, and the l/m ratio of 2.2 is also in the range of values found for SN2 reaction. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH≠ (7.7–16.3 kcal/mol) values and large negative ΔS≠ (−24.6 to −53.4 cal/mol/K) values, and the solvent kinetic isotope effect (1.62).

From minutes to years: predicting organotrifluoroborate solvolysis rates.

Organotrifluoroborates solvolyze in water at rates that vary over five orders of magnitude. The negative logarithm of the solvolytic rate constant, pk(B-F), correlates exceptionally well with the pKa of the analogous carboxylic acid (R(2) = 0.984). This unforeseen correlation may be of predictive value for several applications including Suzuki-Miyaura cross-coupling reactions and the design of (18)F-organotrifluoroborate radioprosthetic groups.

Solvolysis Reaction Kinetics, Rates and Mechanism for Phenyl N-Phenyl Phosphoramidochloridate

The rate constants of solvolysis of phenyl N-phenyl phosphoramidochloridate (PhNHPO(Cl)OPh, Target Compound-TC1) have been determined by a conductivity method. The solvolysis rate constants of TC1 are well correlated with the extended Grunwald-Winstein equation, using the <TEX>$N_T$</TEX> solvent nucleophilicity scale and YCl solvent ionizing scale, and sensitivity values of <TEX>$0.85{\pm}0.14$</TEX> and <TEX>$0.53{\pm}0.04$</TEX> for l and m, respectively. These l and m values were similar to those obtained previously for the complex chemical substances dimethyl thiophosphorochloridate; N,N,N',N'-tetramethyldiamidophosphorochloridate; 2-phenyl-2-ketoethyl tosylate; diphenyl thiophosphinyl chloride; and 9-fluorenyl chloroformate. As with the five previously studied solvolyses, an <TEX>$S_N2$</TEX> pathway is proposed for the solvolyses of TC1. For four representative solvents, the rate constants were measured at several temperatures, and activation parameters (<TEX>${\Delta}H^{\neq}$</TEX> and <TEX>${\Delta}S^{\neq}$</TEX>) were estimated. These activation parameters are also in line with the values expected for an <TEX>$S_N2$</TEX> reaction.

Rate and Product Studies of 5-Dimethylamino-Naphthalene-1-Sulfonyl Chloride under Solvolytic Conditions

The solvolysis rate constants of 5-dimethylamino-naphthalene-1-sulfonyl chloride ((CH3)2NC10H6SO2Cl, 1) in 31 different solvents are well correlated with the extended Grunwald-Winstein equation, using the NT solvent nucleophilicity scale and YCl solvent ionizing scale with sensitivity values of 0.96 ± 0.09 and 0.53 ± 0.03 for l and m, respectively; the correlation coefficient value was 0.955. These l and m values can be considered to support an SN2 reaction pathway having a transition state (TS) structure similar to that of the benzenesulfonyl chloride reaction. This interpretation is further supported by the activation parameters, i.e., relatively small positive ΔH ≠ (12.0 to 15.9 kcal·mol �1 ) and large negative ΔS ≠ (�23.1 to �36.3 cal·mol �1 ·K �1 ) values, and the solvent kinetic isotope effects (SKIEs, 1.34 to 1.88). Also, the selectivity values (S = 1.2 to 2.9) obtained in binary solvents are consistent with the proposed mechanism.

A DFT-based model for calculating solvolytic reactivity. The nucleofugality of aliphatic carboxylates in terms of Nf parameters.

The most comprehensive nucleofugality scale, based on the correlation and solvolytic rate constants of benzhydrylium derivatives, has recently been proposed by Mayr and co-workers (Acc. Chem. Res., 2010, 43, 1537-1549). In this work, the possibility of employing quantum chemical calculations in further determination of nucleofugality (Nf) parameters of leaving groups is explored. Whereas the heterolytic transition state of benzhydryl carboxylate cannot be optimized by quantum chemical calculations, the possibility of an alternative model reaction is examined in order to obtain nucleofugality parameters of various aliphatic carboxylates, which can properly be included in the current nucleofugality scale. For that purpose, ground and transition state structures have been optimized for the proposed model reaction, which includes anchimerically assisted heterolytic dissociation of cis-2,3-dihydroxycyclopropyl trans-carboxylates. The validity of the model reaction as well as of applied DFT methods in the presence of the IEFPCM solvation model is verified by correlating calculated free energies of activation of the model reaction with literature experimental data for solvolysis of reference dianisylmethyl carboxylates. For this purpose the ability of several functionals (including popular B3LYP) is examined, among which the M06-2X gives the best results. The very good correlation indicates acceptable accurate relative reactivities of aliphatic carboxylates, and enables the estimation of rate constants for solvolysis of other dianisylmethyl carboxylates in aqueous ethanol mixtures, from which the corresponding Nf parameters are determined using mentioned Mayr's equation. In addition, DFT calculations confirm the previous experimental observation that the abilities of aliphatic carboxylate leaving groups in solution are governed by the inductive effect of substituents attached to the carboxyl group.

Solvolytic Behavior of Aliphatic Carboxylates

AbstractThe leaving group abilities (nucleofugalities) of a series of aliphatic carboxylates have been obtained by determining the nucleofuge‐specific parameters (Nf and sf) from solvolysis rate constants of X,Y‐substituted benzhydryl carboxylates in a series of aqueous ethanol mixtures by applyication of the linear free energy relationship (LFER) equation: log k = sf (Ef + Nf). These values can be employed to compare reactivities of carboxylates with those of other leaving groups previously included in the nucleofugality scale, and also to estimate the solvolysis rates of various carboxylates. It is confirmed that the inductive effect is the most important variable governing the reactivities of halogenated carboxylates in solution. Moreover, both the Hammett correlation and the solvolytic activation parameters have revealed a strong influence of the inductive effect on the nucleofugality of alkyl‐substituted carboxylates. The reaction constants (sf) indicate that carboxylate substrates with weaker leaving groups solvolyze via later, more carbocation‐like, transition states, which is in accord with the Hammond postulate. In addition, due to the weaker demand for solvation of transition states that produce more strongly stabilized benzhydrylium ions, in which more efficient charge delocalization occurs, the reaction constants (sf) obtained with most of the leaving groups investigated here increase as the polarity of the solvent decreases.

Rate-Product Correlations for the Solvolysis of 5-Nitro-2-Furoyl Chloride

The solvolysis rate constants of 5-nitro-2-furoyl chloride (5-NO2(C4H2O)-2-COCl, 1) in 27 different solvents are well correlated with the extended Grunwald-Winstein equation, using the NT solvent nucleophilicity scale and YCl solvent ionizing scale, with sensitivity values of 1.20 ± 0.05 and 0.37 ± 0.02 for l and m, respectively. The activation enthalpies (ΔH ≠ ) were 5.63 to 13.0 kcal·mol �1 and the activation entropies (ΔS ≠ ) were −25.9 to −43.4 cal·mol �1 ·K �1 , which is consistent with the proposed bimolecular reaction mechanism. The solvent kinetic isotope effect (SKIE, kMeOH/kMeOD) of 2.65 was also in accord with the SN2 mechanism and was possibly assisted using a general-base catalysis. The product selectivity (S) for solvolysis of 1 in alcohol/water mixtures was 1.2 to 11, which is also consistent with the proposed bimolecular reaction mechanism.

Method for Estimating SN1 Rate Constants: Solvolytic Reactivity of Benzoates

Nucleofugalities of pentafluorobenzoate (PFB) and 2,4,6-trifluorobenzoate (TFB) leaving groups have been derived from the solvolysis rate constants of X,Y-substituted benzhydryl PFBs and TFBs measured in a series of aqueous solvents, by applying the LFER equation: log k = s(f)(E(f) + N(f)). The heterolysis rate constants of dianisylmethyl PFB and TFB, and those determined for 10 more dianisylmethyl benzoates in aqueous ethanol, constitute a set of reference benzoates whose experimental ΔG(‡) have been correlated with the ΔH(‡) (calculated by PCM quantum-chemical method) of the model epoxy ring formation. Because of the excellent correlation (r = 0.997), the method for calculating the nucleofugalities of substituted benzoate LGs have been established, ultimately providing a method for determination of the S(N)1 reactivity for any benzoate in a given solvent. Using the ΔG(‡) vs ΔH(‡) correlation, and taking s(f) based on similarity, the nucleofugality parameters for about 70 benzoates have been determined in 90%, 80%, and 70% aqueous ethanol. The calculated intrinsic barriers for substituted benzoate leaving groups show that substrates producing more stabilized LGs proceed over lower intrinsic barriers. Substituents on the phenyl ring affect the solvolysis rate of benzhydryl benzoates by both field and inductive effects.