Selective in photoreactions in cyclodextrin media

Abstract

The cyclodextrins (?, ? and ?) are known to form inclusion complexes with organic substrates and thus provide a microheterogeneous reaction medium for the substrates in aqueous solutions. Alternately, cyclodextrin complexes are known to exist in the solid state also. Cyclodextrin complexation, both in the solid state and in aqueous solutions, is known to influence the excited?state reactivity of the included substrate. Modification may be brought about by the cyclodextrin, either in the partitioning of the excited state into various decay modes or in the partitioning of the intermediate radicals into various modes of recombination. A few systems have been investigated to examine these two aspects by which cyclodextrin may modify photoreactions. The results of such an investigation are embodied in the thesis titled “Selectivity in Photoreactions in Cyclodextrin Media.” The thesis is comprised of five chapters which illustrate the potential of cyclodextrins in bringing about alterations in the photoreactivity of the included substrates in comparison to their behaviour in an isotropic medium. Chapter I gives a brief history of the cyclodextrins and their established ability in catalysing thermal reactions. A few examples of selective thermal transformations have also been outlined. These are followed by a brief survey of photoreactions in cyclodextrins which illustrate the tremendous potential offered by the cyclodextrin media for modification of photoreactivity. The ability of cyclodextrins to sterically block certain potential reactive sites in a molecule, thus regulating the attack of the reactive species to the exposed sites, is termed ‘molecular traffic control’. Chapters II–IV deal with the unimolecular rearrangements in which such a molecular traffic control is brought about by the cyclodextrin medium, essentially by modifying the recombination modes of the initially formed radicals. Chapter II deals with the photo?Fries rearrangement of anilides 1–7 (Chart) in ??cyclodextrin medium. A brief review of the literature on the photorearrangement of anilides in organic solvents is presented which indicates that the reaction proceeds by a mechanism similar to the photo?Fries rearrangement of phenyl esters (Scheme). Anilides, when unsubstituted, yield a mixture of the ortho? and para?rearranged anilines upon photolysis in organic solvents. When provided with a meta?substituent, the anilide may rearrange, upon photolysis, to produce a mixture of two ortho? and a para?rearranged products. Interestingly, the ??cyclodextrin medium, both in aqueous solutions and in the solid state, is found to bring about an impressive ortho?selectivity in the case of the unsubstituted anilides, while a remarkable regioselectivity for the formation of 2?amino?4?methylphenyl ketones is observed in the meta?substituted anilides. The above alterations in the photorearrangement behaviour have been attributed to inclusion?complex formation between the anilides and ??cyclodextrin. Evidence for complexation in the solid state is provided by an examination of the X?ray powder patterns of the solid complexes, while that in aqueous solutions is provided by a ¹H?NMR analysis of the D?O solutions of the complexes. The ¹H?NMR analyses also provide an indication of the probable orientations of the substrates into the ??cyclodextrin cavity, on the basis of which the observed selective behaviour is rationalised as due to the geometric constraints imposed on the molecule by the encircling cyclodextrin sleeve. Investigation on yet another unimolecular photo?rearrangement, namely, the photo?Claisen rearrangement of meta?alkoxyphenyl allyl ethers 8–12 (Chart) in the cyclodextrin media, is presented in Chapter III. A brief outline of the literature reports of this photo?rearrangement is presented which reveals its mechanism to be similar to that of the photo?Fries rearrangement of phenyl esters and anilides (Scheme). The meta?alkoxyphenyl allyl ethers 8–12, when photolysed in ethanol, are found to yield a mixture of two ortho? and a para?rearranged phenols, in addition to the cleavage product, namely, the meta?alkoxy phenol. The substrates, when investigated in the ?? and ??cyclodextrin media, in aqueous solutions and in the solid state, show interesting variations in their photobehaviour. A remarkable regioselectivity brought about in the solid ??cyclodextrin complex, in favour of 2?allyl?5?alkoxyphenol, decreases as the length of the alkoxy chain of the substrate increases (i.e., from 8 to 12). On the contrary, the regioselectivity in the solid ??cyclodextrin complexes increases as the alkoxy chain length increases. Complexation between the substrates and cyclodextrin has been established by X?ray powder patterns for the solid complexes and by ¹H?NMR analyses and dissociation?constant measurements for the aqueous solutions. The apparent dependence of regioselectivity on the alkoxy chain length and the host cavity dimensions is attributed to the requirement of a tight host–guest fit for selective rearrangement. The role of the alkoxy chain as an intramolecular spacer in the ??cyclodextrin complexes, in inducing a tight fit and hence improving the regioselectivity, is discussed. Prompted by the results on the photo?Claisen rearrangement of meta?alkoxyphenyl allyl ethers in ?? and ??cyclodextrin media, the role of the alkyl chain as an intramolecular appendix in the photo?Fries rearrangement behaviour of esters 13–19 (Chart) and anilides 20 and 21 was explored and the results are presented in Chapter IV. Three groups of substrates, namely, meta?alkoxyphenyl acetates (13–16) with a lengthening alkoxy chain, and the esters 17–19, and anilides 20 and 21 of long?chain carboxylic acids were chosen for investigation. All these substrates are found to behave in a similar nonselective manner in organic solvents. While a mixture of two ortho? and a para?rearranged anilines is formed in the cases of anilides 20 and 21, a mixture of two ortho?rearranged products (phenols) and the cleavage product are formed in the cases of the esters 17–19 and 13–16. The three groups of substrates, however, were found to behave in different ways in the cyclodextrin medium. The meta?alkoxyphenyl acetates 13–16, in their solid ?? and ??cyclodextrin complexes, showed a selectivity trend similar to that observed for the meta?alkoxyphenyl allyl ethers 8–12. The anilides of long?chain carboxylic acids 20 and 21 showed moderate regioselectivity in the solid ??cyclodextrin complexes, in favour of the 2?amino?4?methylphenyl ketone formation, while a total nonselectivity was seen in the cases of esters 17–19. The results are rationalised in terms of different modes of binding for the three groups of substrates, where the alkyl chain attached to the molecule at different sites guides the molecule into adopting different orientations in the ??cyclodextrin cavity, leading to their different photobehaviour in the cyclodextrin medium. Moreover, a change of the meta?substituent from the hydrophobic methyl group to the relatively more hydrophilic methoxyl is found to bring about a striking alteration in the photobehaviour of the substrates. This has been rationalised on the basis of the H?bonding ability of the –OCH? group which may enable the substrate to adopt a totally different orientation in the ??cyclodextrin cavity compared to that of its meta?methyl counterpart. Chapter V deals with a photoreaction that is most sensitive to environmental constraints, namely, photoisomerisation. A brief review of the earlier work on the photoisomerisation in various media is presented to expose the different possible ways in which the isomerisation pathway may be altered by the environment. This is followed by a description of the results of the photoisomerisation of stilbenes (Chart) in aqueous ??cyclodextrin medium. Stilbenes, either cis or trans, undergo facile photoisomerisation in isotropic media to afford a photostationary state rich in the cis?isomer (>80%). Interestingly, the ??cyclodextrin medium is found to restrict the trans ? cis isomerisation, while the cis ? trans process proceeds unabated. The altered photoisomerisation behaviour is attributed to the formation of fairly stable inclusion complexes with ??cyclodextrin in aqueous solutions by the stilbenes, as indicated by the dissociation?constant values. A restricted trans ? cis isomerisation of stilbenes is not accompanied by an increased fluorescence yield in contrast to earlier reports. Based on an investigation of the fluorescence behaviour of stilbenes in ??cyclodextrin, the restricted isomerisation of trans?stilbene is attributed to the geometric constraints imposed by the cyclodextrin cavity over the 90° twisted intermediate state, preventing its decay to the cis?isomer. An appendix to Chapter V gives a description of the photodimerisation of stilbenes in aqueous solutions. The hydrophobic aggregation of organic solutes in aqueous solution can lead to tremendous catalysis of bimolecular reactions. The photodimerisation of stilbenes investigated in aqueous solution is an illustration of this phenomenon. Stilbenes, either cis or trans, undergo efficient dimerisation in ~10??–10?? M aqueous solutions, in contrast to the total lack of dimerisation in organic solvents of similar concentrations. The efficient dimerisation in aqueous solutions of the cis? and trans?stilbenes has been attributed to the ground?state aggregation of the solutes in water. Support for the aggregation proposal has been provided by a deviation from Beer's law and by the results of experiments conducted in the presence of additives that alter the aggregation in known ways. A mechanism has been suggested to explain the various modes of decay of the stilbene singlet excited state in aqueous solutions.