B718970B

This paper is published as part of a themed issue of Photochemical & Photobiological Sciences containing papers in honour of Professor Jakob Wirz Guest edited by Dario Bassani and Dick Pagni Published in issue 5, 2008 of Photochemical & Photobiological Sciences. Papers in this issue: Perspective: Challenges and opportunities for photochemists on the verge of solar energy conversion C. Chu and D. M. Bassani Photochem. Photobiol. Sci., 2008, 521 Communication: Vibrational deactivation of singlet oxygen: does it play a role in stereoselectivity during photooxygenation? M. Solomon, J. Sivaguru, S. Jockusch, W. Adam and N. J. Turro Photochem. Photobiol. Sci., 2008, 531 Articles: Getting to guanine: mechanism and dynamics of charge separation and charge recombination in DNA revisited F. D. Lewis, H. Zhu, P. Daublain, K. Sigmund, T. Fiebig, M. Raytchev, Q. Wang and V. Shafirovich Photochem. Photobiol. Sci., 2008, 534 Biradicals by triplet recombination of radical ion pairs H. D. Roth Photochem. Photobiol. Sci., 2008, 540 Inhibitory effect of dissolved organic matter on triplet-induced oxidation of aquatic contaminants S. Canonica and HU Laubscher Photochem. Photobiol. Sci., 2008, 547 Ultrafast studies of some diarylcarbenes J. Wang, Y. Zhang, J. Kubicki and M. S. Platz Photochem. Photobiol. Sci., 2008, 552 Theoretical and experimental study of the Norrish I photodissociation of aromatic ketones C. Dietlin, X. Allonas, A. Defoin and J.-P Fouassier Photochem. Photobiol. Sci., 2008, 558 Triplet and ground state potential energy surfaces of 1,4-diphenyl-1,3-butadiene: theory and experiment J. Saltiel, O. Dmitrenko, Z. S. Pillai, R. Klima, S. Wang, T. Wharton, Z.-N. Huang, L. J. van de Burgt and J. Arranz Photochem. Photobiol. Sci., 2008, 566 The photochemistry of some main chain liquid crystalline 4,4-stilbene dicarboxylate polyesters A. P. Somlai, R. A. Cozad, K. A. Page, H. R. Williams, D. Creed and C. E. Hoyle Photochem. Photobiol. Sci., 2008, 578 Formal intramolecular photoredox chemistry of anthraquinones in aqueous solution: photodeprotection for alcohols, aldehydes and ketones Y. Hou and P. Wan Photochem. Photobiol. Sci., 2008, 588 Photoinduced electron-transfer in perylenediimide triphenylamine-based dendrimers: single photon timing and femtosecond transient absorption spectroscopy E. Fron, R. Pilot, G. Schweitzer, J. Qu, A. Herrmann, K. Müllen, J. Hofkens, M. Van der Auweraer and F. C. De Schryver Photochem. Photobiol. Sci., 2008, 597 One- and two-photon induced QD-based energy transfer and the influence of multiple QD excitations S. Dayal and C. Burda Photochem. Photobiol. Sci., 2008, 605 Fluorinated photoremovable protecting groups: the influence of fluoro substituents on the photo- Favorskii rearrangement K. F. Stensrud, D. Heger, P. Sebej, J. Wirz and R. S. Givens Photochem. Photobiol. Sci., 2008, 614 Photochemical synthesis of substituted indan-1-ones related to donepezil T. Pospí il, A. T. Veetil, L. A. P. Antony and P. Klán Photochem. Photobiol. Sci., 2008, 625 Intramolecular exciplexes based on benzoxazole: photophysics and applications as fluorescent cation sensors M. Mac, T. Uchacz, A. Danel, M. A. Miranda, C. Paris and U. Pischel Photochem. Photobiol. Sci., 2008, 633 D ow nl oa de d by H ua qi ao U ni ve rs ity o n 25 N ov em be r 2 01 2 Pu bl ish ed o n 04 M ar ch 2 00 8 on h ttp :// pu bs .rs c. or g | do i:1 0.1 039 /B7 189 70B View Article Online / Journal Homepage / Table of Contents for this issue PAPER www.rsc.org/pps | Photochemical & Photobiological Sciences Formal intramolecular photoredox chemistry of anthraquinones in aqueous solution: photodeprotection for alcohols, aldehydes and ketones†‡ Yunyan Hou and Peter Wan* Received 11th December 2007, Accepted 11th February 2008 First published as an Advance Article on the web 4th March 2008 DOI: 10.1039/b718970b The formal intramolecular photoredox reaction initially discovered for the parent 2-(hydroxymethyl)anthraquinone (1) in aqueous solution has been extended to a variety of anthraquinones derivatives 6–13, to explore the generality of the reaction, and to investigate its potential utility as a photodeprotecting chromophore. In addition, the related diketone 14 was studied to investigate the need for the anthraquinone chromophore in these formal intramolecular reactions. All the anthraquinones studied (except for 9) undergo formal unimolecular photoredox reaction with a range of quantum yields (U = 0.02–0.7). Anthraquinones 7, 8, 10 and 11 photoreleased the corresponding alcohol, aldehyde, or ketone with good yields (80–90%), making it potentially useful for photocaging in aqueous solution. Diketone 14 undergoes an analogous photoredox reaction but only in acid (U = 0.003, pH < 1), to give the formal redox product diphenylisobenzofuran 32 thereby demonstrating that other aromatic diketones can react in an analogous fashion. The ionic photochemistry exhibited by these aromatic ketones is fully compatible with the recent discovery of the surprising acid-catalyzed photochemical hydration of benzophenone reported by Jacob Wirz and coworkers (M. Ramseier, P. Senn and J. Wirz, J. Phys. Chem. A, 2003, 107, 3305–3315). Introduction The photochemistry of anthraquinones has been extensively investigated due to its widespread use as photosensitizer and its propensity as electron acceptor and efficient hydrogen abstractor (via the carbonyl oxygen) from solvent and other donors.1 More recently, the mechanisms of these two processes in aqueous and non-aqueous media have been investigated in more detail using time-resolved transient spectroscopy.2 In general, due to the very high intersystem crossing yield of anthraquinones (U > 0.9), triplet state reactivity is the norm for these compounds.1–3 In the presence of reducing solvents or added reducing agents, hydrogen abstraction by the carbonyl oxygen of triplet excited anthraquinone gives rise to the corresponding semi-quinone (“ketyl”) radical ultimately leading to reduced anthraquinone (9,10-dihydroxyanthracene).1–3 A different kind of photochemical reactivity for a simple anthraquinonederivativewasdiscoveredwhen2-(hydroxymethyl)- anthraquinone (1) was irradiated in water.4 This highly efficient reaction (U = 0.8) was observed only in the presence of water with clean formation of the formal intramolecular redox product 2 (herein termed intramolecular photoredox reaction). On exposure to air or oxygen, the anthraquinone chromophore is regenerated in product 3. Various experimental evidence support a unimolecular Department of Chemistry, Box 3065, University of Victoria, Victoria, British Columbia, Canada V8W 3V6. E-mail: pwan@uvic.ca; Fax: +1(250) 721 7147; Tel: +1(250) 721 8976 † This paper was published as part of the themed issue in honour of Jakob Wirz. ‡ Electronic supplementary information (ESI) available: Experimental procedures for the preparation of 1-aD and 6–14 and isolation and characterization of photoproducts. See DOI: 10.1039/b718970b photochemical pathway from 1 that proceeds via initial protona- tion of the anthraquinone carbonyl oxygen by water followed by deprotonation of the methylene C–H bond, also assisted by water. (1) This somewhat unusual photochemistry for an aromatic ketone is now joined in the literature by an analogous reaction observed for 3-(hydroxymethyl)benzophenone (4), which gives the formal redoxproduct 5onphotolysis in acidic aqueous solution (eqn (2)).5 Although not well-documented for aromatic ketones except the two examples discussed so far, formal intramolecular photoredox chemistry is better understood for nitroaromatic compounds.6 (2) The formal intramolecular photoredox reactions of aromatic ketones and nitroaromatic compounds require mechanisms via ionic intermediates mediated by water (and/or hydronium or hydroxide ions). Mechanisms of this sort are rare for these types of compounds. However, a study by Wirz and coworkers7 on the 588 | Photochem. Photobiol. Sci., 2008, 7, 588–596 This journal is © The Royal Society of Chemistry and Owner Societies 2008 D ow nl oa de d by H ua qi ao U ni ve rs ity o n 25 N ov em be r 2 01 2 Pu bl ish ed o n 04 M ar ch 2 00 8 on h ttp :// pu bs .rs c. or g | do i:1 0.1 039 /B7 189 70B View Article Online acid-catalyzed (in aqueous acid) photohydration of benzophenone and related compounds (e.g., eqn (3)) via their triplet excited states indicates that aromatic ketones can have substantial charge transfer character (in polar solvents) that can mediate ionic chemistry. The benzophenone hydrates that are formed are short- lived in the ground state. Significantly, the mechanism of reaction suggested by Wirz and coworkers7 for the acid-catalyzed photo- hydration of benzophenone can be conveniently used (with some modifications) to explain the formal intramolecular redox reaction of 3-(hydroxymethyl)benzophenone (4) (eqn. (2))5 and probably also 1 (eqn (1)).4 For example, protonation of the carbonyl oxygen of triplet excited 1 or 4 gives rise to an excited state carbocation in which the positive charge is strongly localized at themeta position. This enhances the acidity of thebenzylicC–Hbond (of theCH2OH moiety) sufficiently that it is deprotonated by solvent water, giving rise to an double enolic species that subsequently results in overall intramolecular redox reaction when the alkene enol carbon of the aromatic ketone is protonated by solvent (formal chargemigration from the CH2OH moiety to the aromatic carbonyl carbon). (3) In our original report of the photoredox chemistry of 14 we noted that when the CH2OH side chain was replaced with CH2OMe, the photoredox chemistry was still observed, with one of the products being MeOH, although with an attenuation in yield (the reaction was not observed with a simple CH3 side chain).4 Since the reaction need to be carried out in aqueous solution, we wanted to investigate whether suitably designed anthraquinone derivatives could photodeprotect a variety of functionalities such as alcohols, aldehydes and ketones in aqueous media. Photolabile protecting groups have received considerable attention in recent times, as attested by reviews of Pelliccioli and Wirz8a and Bochet.8b In this paper, we focus on a study of several anthraquinone derivatives (6–13) that have been designed with the possibility of releasing a protected functionality if the intramolecular photore- dox reaction discussed above takes place, as well as to further investigate the generality of the reaction. Additional insights into the photoredox mechanism of 1will also be addressed by studying the competition between the intramolecular photoredox reaction vs. photoreduction in aqueous alcohol solvents, and the possibility of a primary deuterium isotope effect on reaction with 1-aD. In addition, we also wanted to address whether the anthraquinone chromophore is required at all, by studying the photochemistry of a closely related compound, diketone 14 (which when compared to 1, only lacks one of “benzannelated” rings). The emphasis of this study will be on quantum and chemical yields of photoredox reaction of these compounds and the structural diversity of the photochemical products observed. Experimental General NMR spectra were recorded on Bruker instruments, 300 or 500 MHz for 1H, and 75 or 125 MHz for 13C. IR spectra were recorded on a Perkin-Elmer 283 instrument. UV-Vis spectra were taken on a Cary 1 spectrophotometer. Mass spectra were obtained on a Kratos Concept H spectrometer. All solvents for synthesis (ACS grade) were purchased from Aldrich and used as received. Acetonitrile (HPLC grade) and distilled water were used in photolyses. CDCl3, D2O and acetone-d6 were purchased fromCambridge Isotope laboratory andD2SO4 was obtained from Aldrich. Preparative TLC was carried out on 20 cm × 20 cm silica gel GF Uniplates (Analtech). All readily available organic and inorganic reagents required in the synthesis and photolyses were purchased from Aldrich and used as received. Materials Anthraquinones 6 and 12were readily prepared viaNBS bromina- tion of the corresponding alkyl (methyl or ethyl) anthraquinones (Aldrich), followed by hydrolysis. a-Deuteroanthraquinone 1-aD was prepared via reduction of 3 (synthesized using eqn (1)) with NaBD4. Ethers 7 and 8 were prepared from the corresponding benzylic bromides via solvolysis in EtOH or MeOH, respectively. Acetals 10 and 11 were readily prepared from 12 with either benzaldehyde or acetophenone (acid-catalyzed acetal formation). Diketone 14 was made by hydrolysis of the corresponding bro- momethyl precursor,which itself wasmade from the knownmethyl derivative.9 Additional details are provided in the Electronic Supplementary Information, ESI.‡ UV-Vis studies Unless otherwise noted, UV-Vis studies (∼10−5 M in H2O– CH3CN, pH 7) were carried out in 3.0 mL quartz cuvettes. This journal is © The Royal Society of Chemistry and Owner Societies 2008 Photochem. Photobiol. Sci., 2008, 7, 588–596 | 589 D ow nl oa de d by H ua qi ao U ni ve rs ity o n 25 N ov em be r 2 01 2 Pu bl ish ed o n 04 M ar ch 2 00 8 on h ttp :// pu bs .rs c. or g | do i:1 0.1 039 /B7 189 70B View Article Online Solutions were purged with argon for 5 min and irradiated at 300 nm in a Rayonet photochemical reactor. UV-Vis spectra were recorded before and after each photolysis. Product studies Compounds were photolyzed in 100 mL quartz tubes using a Rayonet RPR 100 photochemical reactor equipped with 300 nm or 350 nm lamps. Typically, a solution of the compound (10−4– 10−5 M, H2O–MeCN (1 : 1 or 1 : 3), pH 7 or 0) was purged with argon for 15 min and then irradiated under argon purge. The irradiated solution was extracted by 3 × 50 mL CH2Cl2 in air and the collected organic extracts was dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the photolysate analyzed by NMR, MS and IR. As mentioned in the Introduction, the initial photoredox product derived from the anthraquinone system is sensitive to oxygen. In order to monitor the initially formed redox product, photolyses were carried out (10−3 M, 10% D2O–CD3CN) in deaerated NMR tubes which allowed characterization of the first formed redox products. Additional details are provided in the ESI.‡ Quantum yield measurements Quantum yields were measured using NMR using the reaction of 2-(hydroxymethyl)anthraquinone (1) as a secondary actinometer (U = 0.8).4 A solution of the compound (6–14, 10−4 M, in H2O– MeCN (1 : 1 or 1 : 3), pH 7 or 0) was purged with argon for 15 min and irradiated for 1 min at 300 nm (2 lamps) under argon purge. After irradiation, the conversion to product was determined by 1H NMR and compared to an identical run using 1. All conversions were kept below 30% and repeated twice. Results and discussion Water and isotope effects of photoredox reaction The proposed mechanism4 of intramolecular photoredox reaction of anthraquinone 1 involves two key proton transfer steps. One is protonation of the ketone and the other is deprotonation of the C– H bond of the benzylic CH2OH moiety. To probe the importance of the C–H bond breaking step, compound 1-aDwas made as this substrate offers the choice between a C–H vs. a C–D bond at the CH2OH moiety. We had also intended to study the a,a-dideutero compound (in direct comparison experiments with 1) but were unable to readily synthesize the required compound. In any event, compound 1-aD proved to be just as useful as the C–H vs. C–D bond breakage occurs from the same reactive excited state. Photolysis of 1-aD (10−5 M, 1 : 1 H2O–MeCN, pH 7, argon purged, 300 nm) was carried out at 1–4 min intervals and gave oxidized products 16 and 3 in overall conversions of 25–85%when solutions were worked-up in air, via the initially formed redox products 15 and 2, respectively (eqn (4)). The proportion of 16 vs. 3 was calculated based on the integration of the aldehyde proton vs. one of the aromatic protons (Ha). The product ratio was further confirmed by MS analysis. The ratio of yield for 16 : 3 was 2.1 ± 0.1 which can be equated to an isotope effect for quantum yield of photoredox reaction, UH/UD. That is, there is a preference for breaking the C–H bond compared to the C–D bond in this reaction. Indeed, since both C–H and C–D bonds come from the same excited state, this ratio is also equable to a kinetic isotope effect for deprotonation, kH/kD. (4) Kinetic isotope effects for deprotonation of C–H vs. C–D are not well reported in organic photochemistry since only a few well-defined excited state carbon acids are known.10 We have11 reported a primary kinetic isotope effect (kH/kD) of 2.8 ± 0.4 for the deprotonation of the benzylic protons of dibenzosuberene, a very strong carbon acid in S1, and a primary isotope effect for reaction (at the benzylic position) of 1.9 ± 0.2 for a related photoredox reaction of a nitrobiphenyl alcohol.12 These values are remarkably similar to the value observed for the anthraquinone system under study. This result is consistent with a mechanism in which the product forming step probably involves C–H bond breaking (at the CH2OH moiety) of a prior protonated substrate (at the carbonyl oxygen). This is illustrated in Scheme 1 where the protonated anthraquinone (shown at the ketone para to the CH2OH for convenience, and electronically excited) structure (1- aD-A) undergoes either loss of the C–H to give 1-aD-B and then 15, or loss of the C–D to give 1-aD-C and then 2. Remarkably, recovered 1-aD did not lose deuterium content (in exhaustive Scheme 1 590 | Photochem. Photobiol. Sci., 2008, 7, 588–596 This journal is © The Royal Society of Chemistry and Owner Societies 2008 D ow nl oa de d by H ua qi ao U ni ve rs ity o n 25 N ov em be r 2 01 2 Pu bl ish ed o n 04 M ar ch 2 00 8 on h ttp :// pu bs .rs c. or g | do i:1 0.1 039 /B7 189 70B View Article Online photolyses carried out in H2O) indicating that the deprotonation step is irreversible. To explore the effect of H2O vs. D2O on photoredox reaction of 1, photolyses were carried out in 3 mL quartz cuvettes (deaerated by argon purge) as a function of H2O/D2O content (in MeCN). The extent of photoredox reaction was monitored at 280 nm (formation of 2 or dideutero 2 inD2O) and the observedDA (which is directly proportional to quantum yield for reaction) plotted vs. water content (Fig. 1). Fig. 1 Effect of H2O (�) andD2O (�) content (inMeCN) on photoredox efficiency of 1 (kex = 300 nm) monitored at 280 nm (formation of 2). The photoredox reaction is very sensitive to water content especially at the lower water region noting that no reaction was observed in neat MeCN. It reaches a plateau region (in efficiency) at about 20% (v/v) water. Note also that use of D2O results in a lower quantum yield in most water contents, by as much as 20% at 15% (v/v) H2O(D2O). In low and high water regions, we were unable to detect a significant difference in relative efficiency using the technique employed although in most cases, reaction in the presence of D2O was always less efficient. It seems reasonable to assume that the details of the photoredox mechanism change with water content since the span of water concentrations covered ranges from mostly MeCN to 40% water. An analysis of solvent isotope effects over this range of water content is beyond the scope of this work but it seems clear that proton transfer to the carbonyl oxygen is intimately involved in the reaction mechanism. The generally low solvent isotope effects observed are consistent with fast rates of proton transfer from the solvent to the carbonyl oxygen and this is entirely consistent with excited state proton transfers. Trapping of initial photoredox product and competition betw