Malcolm J. D’Souza

CORRELATION OF THE RATES OF SOLVOLYSIS OF PHENYL CHLOROFORMATE

The specific rates of solvolysis of phenyl chloroformate in 21 solvents can be very well correlated using the extended Grunwald–Winstein equation, with incorporation of the NT solvent nucleophilicity scale and the YCl solvent ionizing scale, with sensitivities towards changes in the scale having values of 1.68 ± 0.10 and 0.57 ± 0.06, respectively. This is a solvolysis which, on the basis of several other types of evidence, is believed to follow an addition–elimination pathway with addition being rate-determining (or possibly an enforced concerted variant), and these sensitivities can be considered to be representative values for chloroformate esters following such a pathway.

Grunwald-Winstein Analysis - Isopropyl Chloroformate Solvolysis Revisited

Specific rates of solvolysis at 25 °C for isopropyl chloroformate (1) in 24 solvents of widely varying nucleophilicity and ionizing power, plus literature values for studies in water and formic acid, are reported. Previously published solvolytic rate constants at 40.0 °C are supplemented with two additional values in the highly ionizing fluoroalcohols. These rates are now are analyzed using the one and two-term Grunwald-Winstein Equations. In the more ionizing solvents including ten fluoroalcohols negligible sensitivities towards changes in solvent nucleophilicity (l) and very low sensitivities towards changes in solvent ionizing power (m) values are obtained, evocative to those previously observed for 1-adamantyl and 2-adamantyl chloroformates 2 and 3. These observations are rationalized in terms of a dominant solvolysis-decomposition with loss of the CO2 molecule. In nine of the more nucleophilic pure alchohols and aqueous solutions an association-dissociation mechanism is believed to be operative. Deficiencies in the acid production indicate 2-33% isopropyl chloride formation, with the higher values in less nucleophilic solvents.

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.

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.

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.

Application of the aromatic ring parameter (I ) tosolvolyses of β-arylalkyl toluene-p-sulfonates

The specific rates of solvolysis of a variety of β-arylalkyl toluene-p-sulfonates, where the solvolyses proceed with anchimeric assistance (a kΔ pathway), are shown to be very well correlated by a Grunwald–Winstein treatment involving YOTs and I (the aromatic ring parameter), previously successfully applied to kc solvolyses of substrates with aryl groups at the α-carbon. A recently proposed alternative treatment, using YOTs in conjunction with YΔ [a scale derived from 2-methyl-2-(p-methyoxyphenyl)propyl toluene-p-sulfonate solvolyses], is shown to be equivalent to use of YOTs plus I; the sensitivity coefficients from the two treatments can be readily interconverted. Three methods (similarity models of type YBnX, use of YX plus I and use of YX plus YΔX have now been proposed for treatment of dispersion in Grunwald–Winstein plots due to the presence in the substrate of conjugated π electrons. The relative efficiencies of these three methods are discussed.

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.

Evaluation of Electronic Effects in the Solvolyses of p-Methylphenyl and p-Chlorophenyl Chlorothionoformate Esters.

The solvolyses of p-tolyl chlorothionoformate and p-chlorophenyl chlorothionoformate are studied in a variety of organic mixtures of widely varying nucleophilicity and ionizing power values. This solvolytic data is accumulated at 25.0 °C using the titration method. An analysis of the rate data using the extended (two-term) Grunwald-Winstein equation, and the concept of similarity of substrates based on their l/m ratios, shows the occurrence of simultaneous side-by-side addition-elimination and unimolecular SN1 mechanisms.

Data Talks: Obesity-Related Influences on US Mortality Rates

Background In the US, obesity is an epidemiologic challenge and the population fails to comprehend this complex public health issue. To evaluate underlying obesity-impact patterns on mortality rates, we data-mined the 1999-2016 Center for Disease Control WONDER databases vital records. Methods Adopting SAS programming, we scrutinized the mortality and population counts. Using ICD-10 diagnosis codes connected to overweight and obesity, we obtained the obesity-related crude and age-adjusted causes of death. To understand divergent and prevalence trends we compared and contrasted the tabulated obesity-influenced mortality rates with demographic information, gender, and age-related data. Key Results From 1999 to 2016, the obesity-related age-adjusted mortality rates increased by 142%. The ICD-10 overweight and obesity-related death-certificate coding showed clear evidence that obesity factored in the male age-adjusted mortality rate increment to 173% and the corresponding female rate to 117%. It also disproportionately affected the nation-wide minority population death rates. Furthermore, excess weight distributions are coded as contributing features in the crude death rates for all decennial age-groups. Conclusions The 1999-2016 data from ICD-10 death certificate coding for obesity-related conditions indicate that it is affecting all segments of the US population.

Correlation of the rates of solvolysis of α-bromoisobutyrophenone using both simple and extended forms of the Grunwald-Winstein equation and the application of correlation analysis to related studies

A Grunwald-Winstein treatment of the specific rates of solvolysis of α-bromoisobutyrophenone in 100% methanol and in several aqueous ethanol, methanol, acetone, 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) mixtures gives a good logarithmic correlation against a linear combination of NT (solvent nucleophilicity) and YBr (solvent ionizing power) values. The l and m sensitivity values are compared to those previously reported for α-bromoacetophenone and to those obtained from parallel treatments of literature specific rate values for the solvolyses of several tertiary mesylates containing a C(=O)R group attached at the α-carbon. Kinetic data obtained earlier by Pasto and Sevenair for the solvolyses of the same substrate in 75% aqueous ethanol (by weight) in the presence of silver perchlorate and perchloric acid are analyzed using multiple regression analysis.