Nucleophilic Solvent Research Articles

Kinetic Evidence for the Solvent Intervention in the Solvolysis of Tertiary Benzylic Benzoates†

AbstractRates of solvolyses of 2‐(4‐methylphenyl)‐2‐propyl benzoate (2b), 2‐(4‐methylthiophenyl)‐2‐propyl benzoate (3b) and 2,2‐dimethyl‐1‐(4‐methoxyphenyl)‐1‐phenyl‐1‐propyl benzoate (4b) were measured, respectively, in ten or more different solvent systems. Additional YBnOPNB and YxBnOPNB values in binary trifluoroethanol‐water systems were determined. Grunwald‐Winstein type correlation analysis showed that YBnOPNB values were applicable to benzylic benzoates. The rate ratio, kOPNB/kOBz, was found to be solvent‐dependent in the range of 29 for 4 in ethanol to 4 for 2 in trifluoroethanol‐water. Non‐limiting mechanism, including both nucleophilic and electrophilic solvent assistance, in the solvolysis of 2b was discussed.

Synthesis of Substituted Furans by Pt-Catalyzed Cyclization of Enynones

A platinum-catalyzed cyclization of functionalized 2-(1-alkynyl)-2-alkene-1-ones incorporating nucleophilic addition of the applied solvent leading to the formation of 2,3,5-trisubstituted furans is reported. The reaction occurs under mild conditions and is compatible with many polar nucleophilic solvents including water, alcohols, amines, and ketones. Both cyclic and acyclic enynones undergo cyclizations generally in good to excellent yields.

Solvothermal synthesis of hexagonal CdS nanostructures from a single-source molecular precursor

The controllable synthesis of hexagonal CdS (H-CdS) nanostructures from an air-stable single-source molecular precursor (cadmium N, N-diethyldithiocarbamate: [Cd-(DDTC) 2] 2) has been achieved by two facile steps: firstly, [Cd-(DDTC) 2] 2 was prepared directly from the precipitation reaction of stoichiometric cadmium sulfate and sodium diethyldithiocarbamate in distilled water under the ambient condition; secondly, pure H-CdS nanorods (which often consist of individual and multi-armed nanorods in the ethylenediamine solvent) and quasi-spherical aggregates of nanoparticles (about 20–60 nm) could be produced just via solvothermal treatment of the [Cd-(DDTC) 2] 2 in four nucleophilic solvents (including pyridine, diethylamine, hydrazine hydrate and ethylenediamine) at 100–150 °C for 3–12 h, and characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, selected area electron diffraction and UV–vis absorption spectra. The possible formation mechanisms of different nanostructures of H-CdS in the four nucleophilic solvents were tentatively proposed.

Correlations and predictions of solvent effects on reactivity: some limitations of multi‐parameter equations and comparisons with similarity models based on one solvent parameter

AbstractThree recent publications on multi‐parameter correlations of solvent effects on solvolytic reactivity are re‐examined, by considering ‘similarity’ and/or ‘analogy’. Systematic errors due to compensation effects and to comparisons between dissimilar processes are found. Models for solvent nucleophilicity involving dissimilar spectroscopic processes (e.g. β or B parameters) give insensitive measures of low nucleophilicity. From qualitative considerations based on structural similarities, it is predicted that the sensitivities to changes to solvent polarity for solvolyses of chloroalkanes should be in the order: 1‐adamantyl (3) > 2‐methyl‐2‐adamantyl (1) > t‐butyl (2). The predictions are confirmed quantitatively by simple linear free‐energy relationships and similarity models, involving correlations with YCl (based on solvolyses of 1‐chloroadamantane) or ET(30) (based on solvatochromism). Multi‐parameter correlations, indicating that solvolyses of 1 show a low sensitivity to both solvent polarity and electrophilicity, and also a negative sensitivity to solvent nucleophilicity, are shown to be unreliable. Large errors are also evident in recent KOMPH2 calculations. Conclusions are supported by comparing several multi‐parameter treatments of solvolyses of 4‐methoxyneophyl tosylate, for which there is a reliable set of kinetic data and a generally accepted mechanism. Copyright © 2006 John Wiley & Sons, Ltd.

Tribromoisocyanuric Acid: A New Reagent for Regioselective Cobromination of Alkenes

A simple one-step method for the preparation of tribromoisocyanuric acid in good yield (87%) has been developed. The reaction of tribromoisocyanuric acid with alkenes in presence of nucleophilic solvents (MeOH, i-PrOH, AcOH and a mixture of H 2 O-acetone, 1:5) led to the corresponding β-bromoethers, p-bromoacetates and bromohydrins, in high regioselectivity and good yields (73-98%).

Thermodynamic parameters ΔΔ H# and ΔΔ S# as probes for the transition state in the reaction of N-phenyltriazolinedione with alkenes in nucleophilic solvents

The thermodynamic parameters, ΔΔ H # and ΔΔ S #, were determined for the interception of an intermediate, with the structural characteristics of an aziridinium imide, by nucleophilic solvents during the reaction of 2-methyl-2-butene with N-phenyltriazolinedione. The experimentally measured parameters were found to be in favor of an S N2-‘like’ transition state and showed strong dependence on the bulkiness of the incoming molecule of the nucleophile-solvent.

Correlation of the Specific Rates of Solvolysis of Trimethylsilylmethyl Trifluoromethanesulfonate Using a Two-Term Grunwald–Winstein Equation

The specific rates of solvolysis of trimethylsilylmethyl trifluoromethanesulfonate have been measured at 25.0 °C in ethanol, methanol, and 2,2,2-trifluoroethanol (TFE) and their mixtures with water. Determinations were also made in aqueous acetone and in TFE–ethanol mixtures. An extended (two-term) Grunwald–Winstein equation correlation gave sensitivities towards changes in solvent nucleophilicity and solvent ionising power as expected for an SN2 pathway, consistent with a previous proposal. For four solvents specific rates were determined at three or four additional temperatures and appreciably negative entropies of activation were observed, consistent with the proposed mechanism. At −20 °C, the specific rate of methanolysis is almost identical to that for methyl trifluoromethanesulfonate, suggesting a fortuitous balance between steric hindrance effects and a favourable electronic effect upon the introduction of the trimethylsilyl group.

Novel Phenanthroline Ligands and Their Kinetically Locked Copper(I) Complexes with Unexpected Photophysical Properties

The new, sterically encumbered phenanthroline ligands 1a,b, both characterized by the presence of bulky aryl substituents (3,5-di-tert-butyl-4-methoxyphenyl, 2,4,6-trimethylphenyl) in the 2,9-position, were prepared along with their homoleptic [Cu(1a,b)2]+ and heteroleptic complexes [Cu(1a,b)(phen)]+ (phen = parent 1,10-phenanthroline). Due to the pronounced steric shielding, particularly effective in ligand 1a, the formation of the homoleptic complex [Cu(1a)2]+ becomes very slow (5 days). Once formed, the homoleptic complexes [Cu(1a,b)2]+ do not exchange ligands even with phen added in excess because they are kinetically locked due to the large tert-butylphenyl substituents at the phenanthroline unit. The electronic absorption spectra of the homoleptic complexes [Cu(1a)2]+ and [Cu(1b)2]+ evidence a strongly different ground state geometry of the two compounds, the former being substantially more distorted. This trend is also observed in the excited-state geometry, as derived by emission spectra and lifetimes in CH2Cl2 solution. The less distorted [Cu(1b)2]+, compared to [Cu(1a)2]+, is characterized by a 15- and over 100-fold stronger emission at 298 and 77 K, respectively. Noticeably, the excited-state lifetime of [Cu(1a)2]+ in solution is unaffected by the presence of molecular oxygen and only slightly shortened in nucleophilic solvents. This unusual behavior supports the idea of a complex characterized by a "locked" coordination environment.

Correlation of the rates of solvolysis of 2‐furancarbonyl chloride and three naphthoyl chlorides

AbstractThe correlations of the specific rates of solvolysis of the title compounds using extended forms of the Grunwald–Winstein equation are consistent with the overall picture which is emerging for acyl chloride solvolyses, with competing addition–elimination (with rate‐determining addition) and ionization (assisted by nucleophilic solvation) pathways. Except in the more ionizing solvents of low nucleophilicity, 2‐furancarbonyl chloride follows the addition–elimination pathway, in contrast to 2‐thiophenecarbonyl chloride. Except in solvents of highest nucleophilicity and low ionizing power, the solvolyses of the naphthoyl chlorides (1‐naphthoyl, 2‐naphthoyl and 6‐methyl‐2‐naphthoyl) all favor the ionization pathway. In the correlation of the 1‐naphthoyl chloride solvolyses, there is a slight improvement when a term governed by the sensitivity to changes in the aromatic ring parameter (hI) is incorporated; this can be associated with a rather minor steric hindrance involving the peri‐hydrogen. Copyright © 2006 John Wiley & Sons, Ltd.

Rate and product studies in the solvolyses of N,N-dimethylsulfamoyl and 2-propanesulfonyl chlorides

Contrary to earlier suggestions of an S(N)1 pathway for solvolyses of N,N-dimethylsulfamoyl chloride (1), an extended Grunwald-Winstein equation treatment of the specific rates of solvolysis in 32 solvents shows an appreciable sensitivity towards changes in both solvent nucleophilicity and solvent ionizing power. The actual values are very similar to those obtained in earlier studies of the solvolyses of sulfonyl and phosphoryl chlorides, solvolyses which are believed to proceed by an S(N)2 pathway. The observation of similar selectivities in aqueous-alcohol solvents further supports this assignment. In a recent report, an addition-elimination (association-dissociation) pathway was proposed for solvolyses of 2-propanesulfonyl chloride (2). A severe multicollinearity problem has been removed by the addition of several specific rates of solvolysis in fluoroalcohol-containing solvents. The new analyses using the extended Grunwald-Winstein equation lead to sensitivities similar to those for and the previously studied related compounds, and these solvolyses are also best described as following an S(N)2 pathway.

Evidence for Different Types of Water Participation in the Solvolysis of 1-Adamantyl, tert-Butyl, and Methyl Chlorides from Density Functional Theory Computations

[structure: see text] The activation energy in the gas phase (deltaE(double dagger)) and the free energy of activation (deltaG(double dagger)) in water solution for the hydrolysis of the monohydrates of methyl chloride (MeCl), tert-butyl chloride (t-BuCl), and 1-adamantyl chloride (AdCl) have been computed with the B3LYP/631-G(d) method and the polarizable continuum (PCM) solvation model. There is a fair agreement between the deltaG(double dagger) values computed by us and the experimental data. The mechanistic implications of our computations are in severe contradiction with conventional representations. Thus, the computed nucleophilic solvent assistance (NSA) for the backside attack of a water molecule in the hydrolysis of MeCl is slightly lower than the corresponding NSA for t-BuCl. Hence, the hydrolysis of both MeCl and t-BuCl takes place mainly according to the classical S(N)2 mechanism. The most relevant difference is that deltaG(double dagger) for the frontside attack of water to t-BuCl is disfavored only by ca. 2 kcal/mol with regard to the backside attack but by ca. 23 kcal/mol in the case of MeCl. The higher solvolysis rate in water of t-BuCl in relation to AdCl is not due to steric factors affecting the specific solvation of the corresponding transition states, but to differential bulk solvent effects, which are accounted for by the PCM model.

Kinetics and Mechanism of Monomolecular Heterolysis of Commercial Organohalogen Compounds: XLII. Effect of Aprotic Solvent on the Rate of 3-Methyl-3-chloro-1-butene Dehydrochlorination. Correlation Analysis of Solvation Effects

The kinetics of 3-methyl-3-chloro-1-butene dehydrochlorination in propylene carbonate, γ-butyrolactone, sulfolane, acetone, MeCN, PhNO2, PhCN, PhCOMe, MeCOEt, cyclohexanone, o-dichlorobenzene, PhCl, PhBr, 1,2-dichloroethane, dioxane, and AcOEt were studied; v = k[C5H9Cl], E1 mechanism. The reaction rate is satisfactorily described by the parameters of the polarity, electrophilicity, and cohesion of the solvent; the solvent nucleophilicity and polarizability exert no effect on the reaction rate.

Kinetics and Mechanism of Monomolecular Heterolysis of Commercial Organohalogen Compounds: XLI. Solvent Effect on the Rate of 3-Methyl-3-chloro-1-butene Solvolysis. Correlation Analysis of Solvation Effects and Role of Solvent Nucleophilicity

The kinetics of 3-methyl-3-chloro-1-butene solvolysis at 25°C in MeOH, EtOH, BuOH, i-BuOH, PentOH, 2-PrOH, 2-BuOH, HexOH, OctOH, t-BuOH, t-PentOH, cyclohexanol, and allyl alcohol was studied by the verdazyl method; v = k[C5H9Cl], SN1 + E1 mechanism. The reaction rate shows a satisfactory correlation with the parameter of the solvent ionizing power E T and is independent of the solvent nucleophilicity.

Cyclic Polypeptides by Solvent-Induced Polymerizations of α-Amino Acid N-Carboxyanhydrides

Solutions of dl-phenylalanine-NCA in eight different solvents were thermostated at 20 °C for 4 days (and in two cases at 60 °C) without addition of initiators. Spontaneous polymerizations were observed in dimethylformamide (DMF), in N-methylpyrrolidone (NMP), and in dimethyl sulfoxide (DMSO). In dimethyl sulfoxide also sarcosine-NCA, l-alanine-NCA, d,l-leucine-NCA, and dl-valine-NCA underwent spontaneous polymerizations. However, in N-methylpyrrolidone, only sarcosine-NCA and l-alanine-NCA polymerized. The products of all these solvent-induced polymerizations were identified by MALDI−TOF mass spectrometry as cyclic oligo- and polypeptides. This fact and the finding that only the most nucleophilic solvents induce spontaneous polymerizations indicate a zwitterionic polymerization mechanism.

Role of Nucleophilic Solvation and the Mechanism of Covalent Bond Heterolysis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Determination of the protonation and deprotonation centres for isomers of methyl 3-azido-2,3-dideoxyhexopyranosides

By employing quantum-mechanical calculations using the semiempirical (AM1) and ab initio methods (RHF, MP2 and PCM), the energetic parameters of protonation and deprotonation for four isomers of methyl 3-azido-2,3-dideoxyhexopyranosides with the α/β-d-arabino (1, 2) and β/α-d-ribo (3, 4) configurations have been determined. The calculations of the energy and Gibbs free energy of protonation and deprotonation were acomplished by using a Gaussian 6-31G* basis set. Results of calculation carried out for above four isomers under consideration of six plausible protonation centres enabled to conclude that in all of isomers the preferred protonation centre is the nitrogen atom of the azide group situated at the immediate vicinity of the pyranoside ring. Deprotonation reaction of compounds 1-3 occur more readily with primary hydroxyl group, whereas a reverse sequence of deprotonation was found for the α-d-ribo compound 4. Both the protonation and deprotonation reactions are highly dependent on configuration of the anomeric carbon atom, solvent nucleophilicity and steric effects due to mutual relations in space of substituents in the pyranoside ring.

Correlation of the rates of solvolysis of benzoyl fluoride and a consideration of leaving-group effects.

The specific rates of solvolysis of benzoyl fluoride have been determined at 25.0 degrees C in 37 pure and binary solvents. Together with seven values from the literature, these give a satisfactory correlation over the full range of solvents when the extended Grunwald-Winstein equation is applied. The sensitivities to changes in solvent nucleophilicity and solvent ionizing power are very similar to those for octyl fluoroformate, suggesting that the addition step of an addition-elimination mechanism is rate determining. In the solvent-composition region where benzoyl chloride also shows bimolecular solvolysis, the appreciable k(Cl)/k(F) values are proposed as being primarily due to a more efficient ground-state stabilization for the fluoride.

An Overview of Forty Years Organotin Chemistry Developed at the Free Universities of Brussels ULB and VUB

AbstractFor Abstract see ChemInform Abstract in Full Text.

Kinetics and mechanism of monomolecular heterolysis of commercial organohalogen compounds: XXXVIII. Correlation analysis of solvent effects on the activation parameters of heterolysis of t-BuBr and t-BuI

Heterolysis of t-BuBr and t-BuI in aprotic solvents involves a ΔH≠-Δ S≠ compensation effect. The ΔG≠ of t-BuBr heterolysis in aprotic solvents decreases with increasing solvent polarity and cohesion, whereas the respective value for t-BuI heterolysis decreases with increasing solvent polarity, nucleophilicity, and polarizability. In protic solvents, a negative effect of nucleophilic solvation is observed.

Analysis of solvent nucleophile isotope effects: evidence for concerted mechanisms and nucleophilic activation by metal coordination in nonenzymatic and ribozyme-catalyzed phosphodiester hydrolysis.

Heavy atom isotope effects are a valuable tool for probing chemical and enzymatic reaction mechanisms; yet, they are not widely applied to examine mechanisms of nucleophilic activation. We developed approaches for analyzing solvent (18)O nucleophile isotope effects ((18)k(nuc)) that allow, for the first time, their application to hydrolysis reactions of nucleotides and nucleic acids. Here, we report (18)k(nuc) for phosphodiester hydrolysis catalyzed by Mg(2+) and by the Mg(2+)-dependent RNase P ribozyme and deamination by the Zn(2+)-dependent protein enzyme adenosine deaminase (ADA). Because ADA incorporates a single solvent molecule into the product inosine, this reaction can be used to monitor solvent (18)O/(16)O ratios in complex reaction mixtures. This approach, combined with new methods for analysis of isotope ratios of nucleotide phosphates by whole molecule mass spectrometry, permitted determination of (18)k(nuc) for hydrolysis of thymidine 5'-p-nitrophenyl phosphate and RNA cleavage by the RNase P ribozyme. For ADA, an inverse (18)k(nuc) of 0.986 +/- 0.001 is observed, reflecting coordination of the nucleophile by an active site Zn(2+) ion and a stepwise mechanism. In contrast, the observed (18)k(nuc) for phosphodiester reactions were normal: 1.027 +/- 0.013 and 1.030 +/- 0.012 for the Mg(2+)- and ribozyme-catalyzed reactions, respectively. Such normal effects indicate that nucleophilic attack occurs in the rate-limiting step for these reactions, consistent with concerted mechanisms. However, these magnitudes are significantly less than the (18)k(nuc) observed for nucleophilic attack by hydroxide (1.068 +/- 0.007), indicating a "stiffer" bonding environment for the nucleophile in the transition state. Kinetic analysis of the Mg(2+)-catalyzed reaction indicates that a Mg(2+)-hydroxide complex is the catalytic species; thus, the lower (18)k(nuc), in large part, reflects direct metal ion coordination of the nucleophilic oxygen. A similar value for the RNase P ribozyme catalyzed reaction provides support for nucleophilic activation by metal ion catalysis.