Isotope with sulphones

The above brief outline indicates that secondary deuterium isotope effect studies provide a powerful supplementary isotopic technique, shedding new light on obscure kinetic problems encountered in nucleophilic solvolytic substitution reactions with sulphonate esters215-217. 

Kinetic isotope effects have not been observed in the reaction of 1-naphthol-4-sulphonic-2-acid with 2-methoxydiazobenzene127, imidazole-2,4,5-d3 with 4-diazobenzene sulphonic acid128, or indole-3- / with 4-nitrodiazobenzene12S, nor has base catalysis been observed in those cases where it has been measured in each of these reactions one or both of the reagents is relatively reactive. 

Photochemical irradiation of dimethyl and diethyl sulphoxides yields the corresponding sulphone in the presence of air and a photosensitizer such as methylene blue in yields up to 99% . Sulphoxides are also oxidized when they act as traps for persulphoxides, the intermediate formed on reaction of a sulphide with photochemically generated singlet oxygen - , equation (9). Isotope studies have shown that such reactions proceed through a linear sulphurane intermediate . Persulphones also react with sulphoxides in a similar manner , equation (10). 

The combined RIA-technique and isotope dilution has been successfully developed to estimate SULINDAC along with its two prominent metabolites, namely its sulphone and its sulphide present in the plasma-level as shown in the following chemical structures X and Y. 

We should note that there is a problem with the sulphonate leaving groups in that the isotope effects in Table 19 are much closer to unity. Furthermore they show very little temperature variation (Heppolette and Robertson, 1961). It seems probable that the sulphonate groups interact more specifically with the... 

In the NMR spectrum integrated signals are exactly proportional to the number of contributing nuclei. The Comite Consultatif pour la Quantite de Matiere (CCQM) has started international comparison of quantitative NMR experiments. In the first round the possible reproducibility should be established. The composition of a mixture of organic compounds has been determined by integration of the NMR signals. Already the first experiments (Fig. 9) have shown the problems arising by isomerization (ethyl-4-toluene sulphonate), decomposition (1,3-dimethoxybenzene), purity of standard compound and superimposition of isotopic satellites. Additional experiments with a new composition are necessary. 

Presumably less nucleophilically assisted solvolyses could show higher a-deuterium isotope effects, and there is a linear relationship between the magnitude of nucleophilic solvent assistance (Table 2) and the a-deuterium isotope effect for solvolyses of 2-propyl sulpho-nates (Fig. 7). Another measure of nucleophilic assistance is the ratio k2 (OH )/, where k2 is the second-order rate constant for nucleophilic attack by OH and kx is the first-order rate constant for reaction with the solvent water, and a linear correlation was obtained by plotting the ratio versus the experimentally observed isotope effects for methyl and trideuteriomethyl sulphonates, chlorides, bromides and iodides (Hartman and Robertson, 1960). Using fractionation factors the latter correlation may also be explained by a leaving group effect on initial state vibrational frequencies (Hartshorn and Shiner, 1972), but there seems to be no sound evidence to support the view that Sn2 reactions must give a-deuterium isotope effects of 1-06 or less. 

B. Isotope Effect Studies with Labelled Sulphonic Acid Derivatives. 658... 

In the cyclopentyl series, 5y/i-elimination occurs from a planar transition state, but a/in -elimination is slightly distorted from a dihedral angle of 180°. Consequently, the preference for n/m -elimination is less marked in the five-than in the six-membered ring systems (Table 12). With the small neutral base trimethylamine, electrostatic forces of attraction between the sulphonate ester and the partially neutralised base balance the normal preference for n/iti-elimination and the reaction is almost non-stereospecific. None of the reactions follows the carbanion mechanism, as general base catalysis is observed for the 2-p-tolylsulphonylcyclopentyl tosylate elimination and the studies on 2-phenylcyclopentyl tosylates revealed large isotope effects (A h/A d) and p values smaller than in the 2-phenylethyl series (see Table 9, p. 209) " . 

The Eco2 reaction of 9-fluorenyl toluene-p-sulphonate with sodium hydroxide in 90% methanolic acetone has a primary kinetic hydrogen isotope effect of only 2.3 at 25°C . It is difficult to compare this result with that for the corresponding nitrate but if a transition state with considerable carbanion character is involved, then the indications are that nitrite is a better leaving group than toluene-p-sulphinate. It would be worth while to investigate the sulphur isotope effect for this latter reaction. 

The base-catalysed isomerization of /3-epoxy-sulphones (126) to y-hydroxy-ajS-unsaturated sulphones (127) was shown by kinetic data, an isotope effect, and stereochemistry to involve an intramolecular suprafacial 1 -> 3 hydrogen migration, with a carbanion-like transition state. " 4-Hydroxy-2-sulpholen, 3-hydroxy-4-chlorosulpholan, and 3,4-epoxysulpholan were found to react with thiolates to give mixtures of cis- and tran5-3-hydroxy-4-(alkylthio)sulpholans in a ratio of 2 3." ... 

No exchange was detected between water and dimethylsulphoxide (48 R = CH3) (Leonard and Johnston, 1962) or diphenylsulphoxide (48 R = CeHs) in either 1-On hydrochloric acid or 1-0n sodium hydroxide at 100°C (Samuel and Weiss-Broday, unpublished results). Oae et al. (1961) found no exchange on pouring diphenyl sulphoxide in concentrated sulphuric acid into 0 -enriched water indicating that ionization to a doubly charged cation R2S++, did not occur. Diphenyl sulphone (49) does not undergo isotopic exchange with water even under fairly drastic acid or... 

The reaction of p-chlorobenzene diazonium ion with 1-naphtholate-4-sulphonic-2-d acid is not catalysed by pjnidine and does not show an isotope efifect (Ernst et al., 1958). It corresponds therefore to Melander s nitrations and brominations (ig[B]/I i 1). 

Counteranion effects on the [Os(bipy)2(PVP)ioCl] redox polymer were stud-ied 052,153) para-toluene sulphonate (pTS ), NOJ, SO4, and Cl electrolytes, significant solvent transfer was observed that was thought to be related to the increased solvent content of the polymer layers in the initial state when converted into these salt forms. The large movement of solvent in pTS electrolytes was confirmed from isotopic substitution of H2O with In perchlorate no... 

ApK = p sH — P BH where SH is the carbon acid and B the base with which it reacts ApK is positive for all the reactions listed of ethyl a-methyl-acetoacetate and sodium propan-2-one-l-sulphonate (except for the reaction of the latter with hydroxide ion), and k /kP increases with decreasing ApK. However, a new factor emerges if we consider the much stronger carbon acid ethyl nitroacetate, for which both positive and negative values of ApK (i.e., both uphill and downhill reactions) are accessible. Here there is clear evidence of a maximum isotope effect in the neighbourhood of ApK = 0, with a decrease for reactions which are either markedly uphill or markedly downhill. 

Many other examples could be cited which show a smooth variation of k /kP with the strength of the base, and in a few cases some indication of a maximum isotope effect when ApK (and hence the standard free energy change of the reaction) is close to zero. Such a maximum may well be concealed in the results for sodium propan-2-one-l-sulphonate in Table 25, since kP/k has almost the same value for reaction with 2,6-lutidine and hydroxide, for which ApK is -h7.4 and —2.0 respectively. One way of changing the value of Api is to modify the nature of the solvent, and in particular the addition of dimethyl sulphoxide to aqueous solutions containing hydroxide ions will displace the equilibrium SH-hOH"... 

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