Zoon Ha Ryu

Correlation of the Rates of Solvolysis of Two Arenesulfonyl Chlorides and of trans-β-Styrenesulfonyl Chloride – Precursors in the Development of New Pharmaceuticals

Additional specific rates of solvolysis have been determined, mainly in fluoroalcohol containing solvents, for benzenesulfonyl chloride (1) and p-nitrobenzene-sulfonyl chloride (2). For trans-β-styrenesulfonyl chloride (3), a study has been carried out in 43 pure and binary solvents, covering a wide range of hyroxylic solvent systems. For the specific rates of solvolyses of each of the three substrates, a good correlation was obtained over the full range of solvents when the extended Grunwald-Winstein equation was applied. The sensitivities to changes in solvent nucleophilicity and solvent ionizing power are similar to values determined earlier and an SN2 process is proposed. For 3, kinetic solvent isotope effects of 1.46 for kH2O/kD2O and 1.76 for kMeOH/kMeOD were determined. These are also compared to literature values for other sulfonyl chlorides.

A relationship between selectivity and solvent composition for nucleophilic attack on carbocations in alcohol–water mixtures

Rate constants and products of solvolyses of p-methoxybenzyl chloride 1, chlorodiphenylmethane 2(Y = Z = H), chloro(4-chlorophenyl)phenylmethane 2(Y = H, Z = Cl) and chlorobis(4-chlorophenyl)methane 2(Y = Z = Cl) are reported in ethanol– and methanol–water mixtures at 25 °C. Product selectivities (S), defined by: S=[ether product][water]/[alcohol product][alcohol solvent] are related to four rate constants for reactions involving one molecule of solvent as nucleophile and another molecule of solvent as general base catalyst (e.g. kwa involves water as nucleophile and alcohol as general base, and kww, kaw and kaa are defined similarly). A linear relationship between 1/S and molar ratios of solvent 1/S=(kwa/kaw)([alcohol solvent]/[water])+kww/kaw is derived theoretically and validated experimentally for solvolyses of the above substrates from water up to 70% alcohol–water—in this range of solvents, the contribution from kaa can be neglected. For solvolyses of p-methoxybenzyl chloride, S is independent of pH between pH 2 and 12, S decreases when acetone is added but increases if acetonitrile is added and for 90% ethanol–water S increases with added LiCl and LiClO4 and increases further if acetonitrile is also present.

Rate and product studies in the solvolyses of two arenesulfonic anhydrides

The specific rates of solvolysis of benzenesulfonic anhydride (1) and p-toluenesulfonic anhydride (2) have been measured conductometrically at −10°C in 34 solvents for 1 and 33 solvents for 2. Studies at higher temperatures have allowed extrapolated values in additional solvents to be calculated. All of the values, for 35 solvents for 1 and for 37 solvents for 2, have been used in an extended Grunwald–Winstein equation treatment using NT and YOTs values. Activation parameters in several solvents and kinetic solvent isotope effects (MeOH/MeOD) have been determined for both substrates. Product selectivity values (S) have been determined for binary mixtures of water with ethanol, methanol, or 2, 2, 2-trifluoroethanol. The results from the kinetic and product studies are compared to those previously reported for methanesulfonic anhydride (3). An SN2 mechanism is proposed for the solvolytic displacement reactions of the three substrates in all of the solvents used in the investigation.

Reaction mechanism studies involving the correlation of the rates of solvolysis of benzoyl and p -nitrobenzoyl p -toluenesulfonates

The solvolyses of benzoyl and p-nitrobenzoyl p-toluenesulfonates (tosylates) are considerably slower than those of the previously studied mixed anhydride of acetic and p-toluenesulfonic acids (acetyl tosylate), which, even with application of rapid-response conductivity could only be studied at considerably reduced temperatures. For the presently studied compounds, the specific rates over a wide variety of solvents could be conveniently studied at −10 °C. For solvolyses of benzoyl tosylate, application of the extended (two-term) Grunwald-Winstein equation gives sensitivities to changes in solvent nucleophilicity and solvent ionising power consistent with an ionisation (SNl) pathway Indeed, a good correlation is obtained against only solvent ionising power. For the solvolyses of the p-nitro-derivative, very different sensitivities are obtained, with an appreciable dependence on solvent nucleophilicity, and a dominant biomolecular pathway for the substitution is proposed for all of these solvolyses, except for those in solvents rich in fluoroalcohol. Studies of solvent deuterium isotope effects in methanolysis, of leaving-group effects relative to a halide and of temperature variation effects are consistent with the proposed mechanistic pathways.

Kinetic solvent isotope effects and correlations of rates of solvolyses for α-methylthio and other substituted acetyl chlorides

Kinetic data for solvolyses of α-methylthioacetyl chloride, phenylthioacetyl chloride and thiophene-2-acetyl chloride in at least 33 aqueous solvent systems including 2,2,2-trifluoroethanol–ethanol solvent were determined at 10 °C by a conductimetric method, and their rates of solvolyses were correlated using Grunwald–Winstein type equations with the ionizing power parameter (YCl: based on the solvolyses of 1-adamantyl chloride) and the nucleophilicity parameter (NT). Kinetic solvent isotope effects (KSIEs) in water and methanol were investigated for the above compounds and in methanol also for phenyl, diphenyl, and trimethylacetyl and isobutyryl chlorides. The results show similar absolute rate constants, similar large amounts of nucleophilic solvent assistance, but different KSIE values (explained by general base catalysis).

Methanolyses of para-substituted benzoyl chlorides in isodielectric binary mixtures

The kinetics and mechanism of solvolysis of p-substituted benzoyl chlorides have been investigated in three isodielectric systems: methanol–acetonitrile, methanol–nitrobenzene, and methanol–nitromethane mixtures. Only SN1–SN2 processes are favoured by electron-donating substituents in all binary systems, but carbonyl addition processes become dominant in the low basicity (β) region of binary mixtures, especially in methanol–nitromethane for compounds with electron-withdrawing substituents. The rates for unsubstituted substrates as well as those substitutes with electron-withdrawing groups are higher than those for p-methyl substituted substrates, suggesting the contribution of a combined SN1–SN2 and carbonyl addition pathway, rather than the involvement of a concerted displacement with variable transition state.

Correlation analysis of the rates of solvolysis of 4-bromopiperidine: A reaction following a Grob fragmentation pathway

A Grunwald-Winstein treatment of the specific rates of solvolysis of 4-bromopiperidine gives for aqueous ethanol, methanol, acetone, and dioxane a very good logarithmic correlation against the YBr solvent ionizing power values with a slope (m value) of 0.46±0.02, consistent with the operation of a synchronous Grob fragmentation mechanism. When the organic component of the solvent is 2,2,2-trifluoroethanol (TFE), the data points show a negative deviation, consistent with an appreciable deactivating interaction of the acidic TFE component of the solvent with the lone-pair of electrons present on the nitrogen.