Use of Empirical Correlations to Determine Solvent Effects in the Solvolysis of S-Methyl Chlorothioformate

The specific rates of solvolysis of S-methyl chlorothioformate (MeSCOCl) are analyzed in 20 solvents of widely varying nucleophilicity and ionizing power at 25.0 °C using the extended Grunwald-Winstein Equation. A stepwise SN1 (DN + AN) mechanism is proposed in the more ionizing solvents including six aqueous fluoroalcohols. In these solvents, a large sensitivity value of 0.79 towards changes in solvent nucleophilicity (l) is indicative of profound rearside nucleophilic solvation of the developing carbocation. In twelve of the more nucleophilic pure alchohols and aqueous solutions, the sensitivities obtained for solvent nucleophilicity (l) and solvent ionizing power (m) are similar to those found in acyl chlorides where an association-dissociation (AN + DN) mechanism is believed to be operative

Analysis of the Nucleophilic Solvation Effects in Isopropyl Chlorothioformate Solvolysis

Correlation of the solvent effects through application of the extended Grunwald-Winstein equation to the solvolysis of isopropyl chlorothioformate results in a sensitivity value of 0.38 towards changes in solvent nucleophilicity (l) and a sensitivity value of 0.72 towards changes in solvent ionizing power (m). This tangible l value coupled with the negative entropies of activation observed indicates a favorable predisposition towards a modest rear-side nucleophilic solvation of a developing carbocation. Only in 100% ethanol was the bimolecular pathway dominant. These observations are very different from those obtained for the solvolysis of isopropyl chloroformate, where dual reaction channels were proposed, with the addition-elimination reaction favored in the more nucleophilic solvents and a unimolecular fragmentation-ionization mechanism favored in the highly ionizing solvents

Use of Linear Free Energy Relationships (LFERs) to Elucidate the Mechanisms of Reaction of a γ-Methyl-β-alkynyl and an ortho-Substituted Aryl Chloroformate Ester

The specific rates of solvolysis of 2-butyn-1-yl-chloroformate (1) and 2-methoxyphenyl chloroformate (2) are studied at 25.0 °C in a series of binary aqueousorganic mixtures. The rates of reaction obtained are then analyzed using the extended Grunwald-Winstein (G-W) equation and the results are compared to previously published G-W analyses for phenyl chloroformate (3), propargyl chloroformate (4), p-methoxyphenyl choroformate (5), and p-nitrophenyl chloroformate (6). For 1, the results indicate that dual side-by-side addition-elimination and ionization pathways are occurring in some highly ionizing solvents due to the presence of the electron-donating γ-methyl group. For 2, the analyses indicate that the dominant mechanism is a bimolecular one where the formation of a tetrahedral intermediate is rate-determining

Correlation of the Rates of Solvolysis of i-Butyl Fluoroformate and a Consideration of Leaving-Group Effects

The specific rates of solvolysis of isobutyl fluoroformate (1) have been measured at 40.0 °C in 22 pure and binary solvents. These results correlated well with the extended Grunwald-Winstein (G-W) equation, which incorporated the NT solvent nucleophilicity scale and the YCl solvent ionizing power scale. The sensitivities (l and m-values) to changes in solvent nucleophilicity and solvent ionizing power, and the kF/kCl values are very similar to those observed previously for solvolyses of n-octyl fluoroformate, consistent with the additional step of an addition-elimination pathway being rate-determining. The solvent deuterium isotope effect value (kMeOH/kMeOD) for methanolysis of 1 was determined, and for solvolyses in ethanol, methanol, 80% ethanol, and 70% TFE, the values of the enthalpy and the entropy of activation for the solvolysis of 1 were also determined. The results are compared with those reported earlier for isobutyl chloroformate (2) and other alkyl haloformate esters and mechanistic conclusions are drawn

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

Additional Solvent Ionizing Power Values for Binary Water- 1,1,1,3,3,3-Hexafluoro-2-propanol Solvents

Determinations of the specific rates of solvolysis of 1-adamantyl bromide and 1-adamantyl iodide in 1,1,1,3,3,3-hexafluoro-2-propanol-water mixtures, in conjunction withearlier reported values in 80% ethanol, have led to additional YBr and YI solvent ionizingpower values. These new values will be especially important in avoiding multicollinearitywhen the extended Grunwald-Winstein equation (extended by addition of a term involvingsolvent nucleophilicity) is used to correlate solvent-induced changes in the specific rates ofsolvolyses involving a bromide or iodide ion leaving group

Correlations of the Specific Rates of Solvolysis of Aromatic Carbamoyl Chlorides, Chloroformates, Chlorothionoformates, and Chlorodithioformates Revisited

Additional specific rates of solvolysis are determined for phenyl chloroformate.These values are combined with literature values to give a total of 49 data points, which areused within simple and extended Grunwald-Winstein treatments. Literature values are alsobrought together to allow treatments in more solvents than previously for three N-aryl-N-methylcarbamoyl chlorides, phenyl chlorothionoformate, phenyl chlorodithioformate, andN,N-diphenylcarbamoyl chloride. For the last two listed, moderately strong evidence for ameaningful inclusion of a term governed by the aromatic ring parameter (I) was indicated.No evidence was found requiring inclusion of this parameter for ionization reactions withonly one aromatic ring on the nitrogen of carbamoyl chlorides or for the solvolyses of thechloroformate or chlorothionoformate proceeding by an addition-elimination (association-dissociation) mechanism

The Nature of Nucleophilic Assistance to Ion-Pair Formation. Solvolyses of Cyclohexyl p-Toluenesulfonate

The solvolysis of cyclohexyl tosylate has been shown previously both to proceed with nucleophilic assistance from the solvent and to give among the substitution and elimination products those which involve a 1,2-hydride shift. In the present report, specific rate data for solvolysis in 18 solvents at 25.0 °C are shown to give an excellent correlation, using the two-term Grun- wald-Winstein equation, against NT solvent nucleophilicity values and YoTs solvent ionizing power values, with an l value of 0.35 and a m value of 0.85. This indicates that sensitivities to changes in solvent nucleophilicity (Z values) of as large as 0.35 can reflect nucleophilic solvation of a developing carbocation, rather than bimolecular (SN2 + E2) attack. The temperature dependencies of the Z and m values are given consideration

Mechanistic Studies of the Solvolyses of Carbamoyl Chlorides and Related Reactions

Carbamoyl chlorides are important intermediates, both in the research laboratory and in industrial scale syntheses. The most studied and used are the disubstituted derivatives, incorporating either aryl or alkyl groups (Ar2NCOCl or R2NCOCl). Sometimes, the groups are tied back to give a ring and piperidino- and morpholino-derivatives are commonly encountered. Some studies have been made with two different groups attached. Solvolyses tend to occur at the carbonyl carbon, with replacement of the chloride ion. Studies of both rate and products are reviewed and the solvolysis reactions are usually SN1, although addition of an amine leads to a superimposable bimolecular component. Many of the studies under solvolytic conditions include the application of the extended Grunwald–Winstein equation. The monosubstituted derivatives (ArNHCOCl or RNHCOCl) are less studied. They are readily prepared by the addition of HCl to an isocyanate. In acetonitrile, they decompose to set up and reach equilibrium with the isocyanate (ArNCO or RNCO) and HCl. Considering that the structurally related formyl chloride (HOCOCl) is highly unstable (with formation of HCl + CO2), the unsubstituted carbamoyl chloride (H2NCOCl) is remarkably stable. Recommended synthetic procedures require it to survive reaction temperatures in the 300–400 °C range. There has been very little study of its reactions