Langmuir 2007, 23, 7545-7554
7545
Preorientation of Olefins toward a Single Photodimer: Cucurbituril-Mediated Photodimerization of Protonated Azastilbenes in Water Murthy V. S. N. Maddipatla, Lakshmi S. Kaanumalle, Arunkumar Natarajan, Mahesh Pattabiraman, and V. Ramamurthy* Department of Chemistry, UniVersity of Miami, Coral Gables, Florida 33124 ReceiVed March 19, 2007. In Final Form: April 25, 2007 With the view to establishing the generality of cucurbit[8]uril as a template, the photodimerization of hydrochloride salts of eight azastilbenes has been investigated in an aqueous medium. Whereas in solution upon excitation all of these olefins yield products of geometric isomerization, cyclization, and hydration, in the presence of cucurbit[8]uril the predominant product is that of dimerization. Such a change in product distribution is attributed to the localization of the olefins by the host cucurbit[8]uril. Most importantly, instead of a mixture of dimers, predominantly a single dimer was obtained in each case. The nature of the dimer that was formed could be rationalized on the basis of the principles of “best fit” and “minimization of electrostatic repulsion”. The superior ability of cucurbit[8]uril compared to micelles to act as a templating agent is attributed to its ability to provide a reaction cavity that is tight and timeindependent.
Introduction The possibility of various stereo- and regioisomeric dimers obtaining product selectivity during the photodimerization of olefins such as cinnamic acids has been a challenging task.1 Attempts to control dimerization in the solid state and in solution have resulted in success only when the reactant molecules were preorganized in the ground state toward a particular regioisomer. Both intermolecular and intramolecular crystal-engineering principles have been used to template reactant olefins toward a single dimer in the solid state.2 In spite of moderate success, the above templating strategies in the solid state are less general, and in aqueous solution, they remain a challenging task. To our knowledge, de Mayo was the first to exploit the hydrophobichydrophilic interface of a micelle to preorient enones toward a single dimer.3-5 Although the approach resulted in dimerization, it failed to give significant selectivity. However, Whitten and co-workers succeeded in obtaining a syn head-head dimer selectively from protonated stilbazoles within a reverse micelle that has a much smaller and more rigid reaction cavity.6,7 These pioneering studies paved the way for recent studies on the use of well-defined and rigid hydrophobic cavities of cyclodextrins,8-13 * Corresponding author. E-mail:
[email protected]. (1) Bassani, D. M. In CRC Handbook of Organic Photochemistry and Photobiology, 2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, FL, 2003; pp 20-1-20-20. (2) Natarajan, A.; Ramamurthy, V. In The Chemistry of Cyclobutanes; Rappoport, Z., Liebman, J. F., Eds.; John Wiley & Sons, Ltd.: Chichester, U.K., 2005; pp 807-872. (3) Lee, K. H.; de Mayo, P. J. Chem. Soc., Chem. Commun. 1979, 493-495. (4) de Mayo, P.; Sydnes, L. K. Chem. Commun. 1980, 994-995. (5) Lee, K. H.; de Mayo, P. Photochem. Photobiol. 1980, 31, 311-314. (6) Takagi, K.; Suddaby, B. R.; Vadas, S. L.; Backer, C. A.; Whitten, D. G. J. Am. Chem. Soc. 1986, 108, 7865-7867. (7) Backer, C. A.; Whitten, D. G. In Photochemistry in Solid Surfaces; Anpo, M., Matsuura, T., Eds.; Elsevier: Amsterdam, 1989; Vol. 47, pp 216-235. (8) Moorthy, J. N.; Venkatesan, K.; Weiss, R. G. J. Org. Chem. 1992, 57, 3292-3297. (9) Herrmann, W.; Wehrle, S.; Wenz, G. Chem. Commun. 1997, 1709-1710. (10) Rao, K. S. S. P.; Hubig, S. M.; Moorthy, J. N.; Kochi, J. K. J. Org. Chem. 1999, 64, 8098-8104. (11) Herrmann, W.; Schneider, M.; Wenz, G. Angew. Chem., Int. Ed. 1997, 36, 2511-2514. (12) Ikeda, H.; Nihei, T.; Ueno, A. J. Org. Chem. 2005, 70, 1237-1242. (13) Nakamura, A.; Inoue, Y. J. Am. Chem. Soc. 2003, 125, 966-972.
calixarenes,14,15 Pd nanocages,16-21 and cucurbiturils22-25 to template olefins toward selective photodimers in aqueous solution. In this presentation, we have utilized cucurbit[8]uril as the reaction medium to achieve selective photodimerization of hydrochloride salts of bispyridyl ethylenes and stilbazoles. Cucurbiturils, depending on the number [n] of glycouril units coupled during the acid-catalyzed condensation reaction, exist as different oligomers (CB[n]).26-29 To date, cucurbiturils comprising of 5, 6, 7, 8, and 10 glycoluril units have been isolated and characterized. These moderately water-soluble hosts having polar carbonyl groups as portals and hydrophobic interiors can encapsulate organic molecules in aqueous solution. For example, CB[6] having a cavity diameter of 5.7 Å can encapsulate a single benzene molecule, whereas CB[7] with a 7.3 Å cavity diameter can accommodate aromatic guests such as ortho- and metaxylenes. CB[8], in particular because of its larger cavity diameter (8.8 Å), can encapsulate two molecules of dimensions similar (14) Kaliappan, R.; Kaanumalle, L. S.; Natarajan, A.; Ramamurthy, V. Photochem. Photobiol. Sci. 2006, 5, 925-930. (15) Ananchenko, G. S.; Udachin, K. A.; Ripmeester, J. A.; Perrier, T.; Coleman, A. W. Chem.sEur. J. 2006, 12, 2441-2447. (16) Takaoka, K.; Kawano, M.; Ozeki, T.; Fujita, M. Chem. Commun. 2006, 15, 1625-1627. (17) Yoshizawa, M.; Takeyama, Y.; Okano, T.; Fujita, M. J. Am. Chem. Soc. 2003, 125, 3243-3247. (18) Yoshizawa, M.; Takeyama, Y.; Kusukawa, T.; Fujita, M. Angew. Chem., Int. Ed. 2002, 41, 1347-1349. (19) Karthikeyan, S.; Ramamurthy, V. Tetrahedron Lett. 2005, 46, 44954498. (20) Karthikeyan, S.; Ramamurthy, V. J. Org. Chem. 2006, 71, 6409-6413. (21) Karthikeyan, S.; Ramamurthy, V. J. Org. Chem. 2007, 72, 452-458. (22) Pattabiraman, M.; Natarajan, A.; Kaanumalle, L. S.; Ramamurthy, V. Org. Lett. 2005, 7, 529-532. (23) Wang, R.; Yuan, L.; Macartney, D. H. J. Org. Chem. 2006, 71, 12371239. (24) Pattabiraman, M.; Kaanumalle, L. S.; Natarajan, A.; Ramamurthy, V. Langmuir 2006, 22, 7605-7609. (25) Pattabiraman, M.; Natarajan, A.; Kaliappan, R.; Mague, J. T.; Ramamurthy, V. Chem. Commun. 2005, 4542-4544. (26) Mock, W. L. Top. Curr. Chem. 1995, 175, 1-24. (27) Lee, J. W.; Samal, S.; Selvapalam, N.; Kim, H.-J.; Kim, K. Acc. Chem. Res. 2003, 36, 621-630. (28) Gerasko, O. A.; Samsonenko, D. G.; Fedin, V. P. Russ. Chem. ReV. 2002, 71, 741-760. (29) Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L. Angew. Chem., Int. Ed. 2005, 44, 4844-4780.
10.1021/la700803k CCC: $37.00 © 2007 American Chemical Society Published on Web 06/01/2007
7546 Langmuir, Vol. 23, No. 14, 2007
Maddipatla et al. Scheme 1
to those of stilbene. The exploitation of CB[8] to mediate the selective photodimerization of cationic olefins in solution began with the work of Kim and co-workers on diaminostilbene hydrochlorides.30 Recently, we reported the dimerization of neutral substituted cinnamic acids within CB[8] and demonstrated that it can facilitate photodimerization selectively to yield syn head-head dimers.24 To explore the templating ability of CB[8] further in an aqueous medium, we have investigated the photodimerization of azastilbenes 1-8 (Scheme 1)31-35 as hydrochloride salts included within the CB[8] cavity. Our main goals are to establish the generality of CB[8] to control the photodimerization of olefins in water and, if possible, to formulate a model that would allow one to predict the nature of the dimers that would be obtained with CB[8] as a template. The olefins investigated as models in this study carry a positive charge; therefore, the model that we propose is restricted to positively charged olefins.
Results In designing this project, we have exploited the efficient binding ability of CB[7] and CB[8] toward cationic species. We have chosen three classes of guest molecules, namely, watersoluble hydrochloride salts of symmetrical bispyridyl ethylenes (1-3), unsymmetrical bispyridyl ethylenes (4-6), and stilbazoles (7, 8) for photodimerization studies (Scheme 1). As discussed below, all of these guest molecules bind to CB[7] and CB[8] Complexation Studies. Procedures adopted for the preparation and irradiation of CB[7] and CB[8] inclusion complexes of olefins 1-8 are provided in the Experimental Section. To avoid a (30) Jon, S. Y.; Ko, Y. H.; Park, S. H.; Kim, H.-J.; Kim, K. Chem. Commun. 2001, 1938- 1939. (31) Williams, J. L. R. J. Org. Chem. 1960, 25, 1839-1840. (32) Takagi, K.; Itoh, M.; Usami, H.; Imae, T.; Sawaki, Y. J. Chem. Soc., Perkin Trans. 2 1994, 1003-1009. (33) Shim, S. C.; Kim, M. S.; Lee, K. T.; Jeong, B. M.; Lee, B. H. J. Photochem. Photobiol. A 1992, 65, 121-131. (34) Whitten, D. G.; Lee, Y. J. J. Am. Chem. Soc. 1972, 94, 9142-9148. (35) Whitten, D. G.; McCall, M. T. J. Am. Chem. Soc. 1969, 91, 5097-5103.
repetitive presentation of the results, three olefins, namely, 1, 4, and 7, have been chosen as representative examples of each class. A turbid solution of CB[8] in water (2.75 × 10-4 M) became transparent upon addition of 4-BPE‚2HCl (1) (5.5 × 10-4 M), suggesting a host-guest complexation. The encapsulation and stoichiometry of the complexes were confirmed by 1H NMR, MALDI-TOF, and UV-vis absorption data. An upfield shift in guest 1H NMR signals relative to that in water suggested the complexation of 1 with CB[7] and CB[8] (Figure 1). During 1H NMR titration experiments, a continuous upfield shift of guest proton signals was observed until the addition of 1 equiv of CB[7] or 0.5 equiv of CB[8] to 5.5 × 10-4 M 1, suggesting the H/G complex ratios to be 1:1 in the case of CB[7] and 1:2 in the case of CB[8]. Further addition did not result in any shift in 1H NMR signals. The extent of the shift was greater in the case of CB[8] as compared to that for CB[7] possibly because of the inclusion of two molecules within the hydrophobic cavity. MALDI-TOF mass spectral data (peaks at 1346 (BPE@CB[7]) and 1693 (2.BPE@CB[8])) were consistent with the above stoichiometry. In Figure 2, 1H NMR spectra of 1‚HCl upon addition of various amounts of CB[8] are shown. As can be seen, there is continuous shift in the NMR signals, and at no stage were there two sets of peaks, one due to uncomplexed and the other due to complexed olefins. The overall binding constant of the complex between 1 and CB[8] as estimated by 1H NMR titration experiment was ∼108 M-2; K11 ) 8.6 × 105 M-1 and K12 ) 1.03 × 103 M-1, where K11 and K12 are the stepwise binding constants for 1:1 and 1:2 H/G complexes. (See the Experimental Section for details.) The inclusion of unsymmetrical bispyridyl ethylene 4 within CB[7] and CB[8] resulted in an upfield shift in the 1H NMR signals of the guest olefin (Figure 3). Relatively large upfield shifts of Ha and Hb protons suggested the inclusion of the 4-pyridyl ring within the hydrophobic cavities of CB[7] and CB[8]. A similar trend was observed upon the inclusion of 2,4-BPE‚2HCl (5) and 2,3-BPE‚2HCl (6) within CB[7] and CB[8]. The formation of stable inclusion complexes of 4 with CB[7] (1:1) and CB[8]
Preorientation of Olefins toward a Photodimer
Langmuir, Vol. 23, No. 14, 2007 7547
Figure 1. 1H NMR spectra of (a) 4-BPE‚2HCl (1) in D2O, (b) in 1 equiv of CB[7], and (c) in 0.5 equiv of CB[8] in D2O.
Figure 2. 1H NMR spectra of (a) 4-BPE‚2HCl (1) in D2O, (b) in 0.15 equiv of CB[8], (c) in 0.25 equiv of CB[8], (d) in 0.35 equiv of CB[8], and (e) in 0.5 equiv of CB[8].
(2:1) was also suggested by the observation of peaks at m/z 1346 and 1693 in the MALDI-TOF mass spectra. 1H NMR titration and MALDI-TOF mass spectral data suggested the complexes of stilbazole hydrochlorides 7 and 8 with CB[7] and CB[8] to be 1:1 and 2:1. Because the shift of the phenyl ring protons alone was observed in the case of the CB[7] complex, we believe the phenyl ring of 7 to be encapsulated within the CB[7] cavity (Figure 4). This is consistent with the relatively more hydrophobic nature of the phenyl ring compared to that of the pyridinium ring. In case of CB[8], the upfield shifts for both phenyl and pyridyl protons of the guests were observed, indicating the inclusion of both rings within the cavity (Figure 4). 1H NMR and mass spectral data presented above are consistent with the conclusion that 1, 4, and 7 form a 1:1 complex with CB[7] and a 2:1 complex with CB[8] with more hydrophobic group residing within the cavity of the host. In all three examples, because there were no signals due to free olefins even at low
concentrations of the host (Figure 2), we believe that the exchange between bound and free guest is fast on the 1H NMR (400 MHz) time scale. The lack of shift in 1H NMR signals upon the addition of more than 1 equiv of CB[7] or 0.5 equiv of CB[8] suggested that under our irradiation conditions (to be described in the next section) no free olefins existed. Although we did not measure the binding constant for any olefin except 1‚HCl, we anticipate the K measured for 1‚HCl@CB[8] to be representative of all substrates investigated here. Photochemistry of CBs Encapsulated Guests. Because photochemical results for all symmetrical olefins 1-3 were similar (Table 1), to avoid repetition we present the results on 4-BPE‚ 2HCl (1) in detail. The irradiation of trans-1,2-bis(4-pyridyl)ethylene dihydrochloride (5.5 × 10-4 M) in water under aerated conditions for 2 h produced 11 as the major product (78%) and corresponding cis isomer 9 and 2,9-phenanthroline 10 as minor products (17 and 5%, respectively; Scheme 2, Table 1). However, the irradiation of an aqueous solution containing 0.5 equiv of
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Figure 3. 1H NMR spectra of (a) 3,4-BPE‚2HCl (4) in D2O, (b) in 1 equiv of CB[7], and (c) in 0.5 equiv of CB[8] in D2O.
Figure 4. 1H NMR spectra of (a) 4-Stb‚HCl(7) in D2O, (b) in 1 equiv CB[7], and (c) 0.5 equiv of CB[8]. Table 1. Product Distributiona (Percent) upon Irradiation of Symmetric Bispyridyl Ethylene Dihydrochlorides 1-3 in Various Mediab,c 4-BPE‚2HCl (1) water CB[7] CB[8] 3-BPE‚2HCl (2) water CB[7] CB[8] 2-BPE‚2HCl (3) water CB[7] CB[8]
9
10
11
17 67 02
05 12 04
78 21
12
13
90
04
14
15
16
17
82 91 08
18 09 03
87
02
18
19
20
21
86 89 04
14 11 02
88
06
a
The percentage was calculated on the basis of the integration of 1H NMR signals at 90% conversion. b See Schemes 2 and 3 for the structures of 9-21. c Concentration of the guest: 5.5 × 10-4 M.
CB[8] and 1 equiv of 4-BPE‚2HCl resulted in syn dimer 12 as the main product. Similarly, the irradiation of trans-1,2-(3pyridyl)ethylene dihydrochloride 2 (3-BPE‚2HCl) and trans1,2-(2-pyridyl)ethylene dihydrochloride 3 (2-BPE‚2HCl) in the
presence of 0.5 equiv of CB[8] gave predominantly syn dimers 16 and 20 (Scheme 3, Table 1). The irradiation of olefins 1, 2, and 3 in the presence of CB[7] gave only the corresponding cis isomers 9, 14, and 18 and cyclized products 10, 15, and 19; no dimers were obtained. To explore the use of CB[8] further as a template in bimolecular reactions, we investigated the photodimerization of unsymmetrical bispyridylethylene dihydrochlorides 4-6 (Scheme 1), where four dimers are possible. The irradiation of trans-3,4-BPE‚2HCl (4) in water (7.8 × 10-4 M, for 2 h) under aerated conditions gave hydration product 24 (66%), corresponding cis isomer 22 (28%), and 2,8-phenanthroline 23 (6%) (Scheme 4, Table 2). In contrast, the irradiation of an aqueous solution of 4 in the presence of 0.5 equiv of CB[8] (7.8 × 10-4 M of 4 and 3.9 × 10-4 M of CB[8]) led to anti-HT dimer 27 in 80% yield along with syn-HH dimer 25 (15%) and cis isomer 22 (5%). The irradiation of a 1:1 CB[7] complex of 4 gave cis isomer 22 as the major product along with minor amounts of cyclization and hydration products 23 and 24, respectively. The irradiation of an aqueous solution of 5 and 6 resulted in cis, cyclized, and hydrated products (Scheme 5, Table 2). However, the irradiation of 5 and 6 as complexes of CB[8] gave anti-HT dimers 31 and 35, but in the presence of 1 equiv of CB[7], they gave isomerization products 29 and 33 (Table 2).
Preorientation of Olefins toward a Photodimer
Langmuir, Vol. 23, No. 14, 2007 7549 Scheme 2
Scheme 3
To complete the study, we investigated the photobehavior of trans-n-stilbazole hydrochlorides 7 and 8 (Scheme 1). The irradiation of 7 and 8 in aqueous solution (5.6 × 10-4 M) resulted mainly in the cis isomer along with a mixture of anti-HH and anti-HT dimers in ∼4% yield. The irradiation of 7 and 8 as complexes of CB[8] in water gave anti-HT dimers 42 and 46 (Scheme 6, Table 3). On the basis of the results with eight olefins, we believe that macrocyclic synthetic host CB[8] can selectively direct olefins to either a syn or anti dimer.
Discussion The main excited-state reactions of the eight olefins (1‚HCl to 8‚HCl) investigated here are geometric isomerization, cyclization, and addition to water (Schemes 2 and 4). Under normal conditions, these three unimolecular processes are apparently too fast for bimolecular dimerization to compete. Our aim is to reverse the above trend and make the latent photoreaction, namely, dimerization dominate the excited-state chemistry of these olefins. Furthermore, we were interested in templating the reactant olefins to a single dimer. We have established in this study that hydrochloride salts of azastilbenes 1-8 could be dimerized in water provided that their local concentration is increased and the
excited CdC bond of the olefin is protected from water. Furthermore, we have demonstrated that a stereochemically selective dimer could be obtained if the olefins were preoriented in the ground state. The results presented above raise the following questions: (a) Why were there no products of water addition in the presence of hosts CB[7] and CB[8]? (b) Why were the dimers formed only in the presence of CB[8] but not in the presence of CB[7]? (c) When there was more than one dimer possible, why was a single isomer preferentially formed within CB[8]? (d) Could an intuitive model be developed to predict the stereochemistry of the dimer that would be formed in the presence of CB[8]? Olefins 1‚HCl and 4‚HCl upon irradiation in water yielded hydrated products 11 and 24 in greater than 60% yield. However, when these olefins as complexes of CB[8] and CB[7] were irradiated, negligible amounts of hydrated products were formed. Given the fact that the cavities of CB[7] and CB[8] are hydrophobic, no water molecules are expected to be present within their cavities, especially when the olefins occupy them. Therefore, the absence of hydration products is not surprising. Clearly, the two hosts serving as molecular sleeves protected the excited CdC bond of 1‚HCl to 8‚HCl from water. The fact that
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Maddipatla et al. Scheme 4
CB[8] completely suppressed the hydration suggested that all olefin molecules were fully complexed under our conditions and at no stage did the excited olefin leave the hydrophobic cavity to face water molecules. This observation is consistent with the 1H NMR results. Suppression of the hydration process allowed us to pursue our main goal of obtaining selective dimers from olefins 1‚HCl to 8‚HCl. Within CB[7], the only observed photoreaction was the isomerization to the corresponding cis isomers (and subsequent cyclization). The absence of dimers within the CB[7] cavity is consistent with the dimensions of the host cavity and with 1H NMR and mass spectral data that suggested that olefins 1-8‚HCl formed a 1:1 complex. Our goal of obtaining controlled photodimerization was achieved with CB[8] as the host. Before going into the details, it is important to note the nomenclature used in this presentation. The names of the four dimers shown in Scheme 7 are dictated by the relative stereochemistry and location of the groups A and B. Also included in the Scheme are the conventional names used in the literature that do not make the stereochemistry obvious. In olefins 1, 2, and 3, A and B are the same whereas in 4-8 they Table 2. Product Distributiona (Percent) upon Irradiation of Bispyridyl Ethylene Dihydrochlorides 4-6 in Various Mediab,c 3,4-BPE‚2HCl (4) water CB[7] CB[8] 2,4-BPE‚2HCl (5) water CB[7] CB[8] 2,3-BPE‚2HCl (6) water CB[7] CB[8]
22
23
24
28 78 05
06 19
66 03
29
32
37
35 91 05
40 09
25
33
36
38
39 81 05
47 19 30
14
25
27
15
80
30
31
30
65
34
35
10
55
a The percentage was calculated on the basis of the integration of 1H NMR signals at 80% conversion. b See Schemes 4 and 5 for the structures of 22-38. c Concentration of the guest: 7.8 × 10-4 M.
are different. Because of this, in the cases of 1, 2, and 3 only two dimers are possible (syn-HH ) anti-HT and syn-HT ) antiHH) whereas in 4-8 four dimers can be formed. As would be expected, the four dimers shown in Scheme 7 have different dimensions. The energy-optimized (Spartan program at the MM1 level) structures of the four dimers are shown in Figure 5. In the same Figure, the required prearrangements of the olefins to form the dimers are also shown. In syn head-tail and anti head-head dimers, the two hydrophobic aryl rings present on the same side at the 1 and 3 positions are far apart (>11 Å) whereas in syn head-head and anti head-tail dimers the aryl rings present on the same side at the 1 and 2 positions are within ∼8 Å. Within CB[8], whose internal cavity diameter is ∼8 Å, only the syn head-head and anti head-tail dimers could fit. More importantly, the two olefin molecules that are prearranged to form syn head-head and anti head-tail dimers would fit better within the CB[8] cavity than the ones that are set to form syn head-tail and anti head-head dimers. In the latter two arrangements, a substantial part of the hydrophobic groups of the olefin would be exposed to water. On the basis of the above argument and conventional knowledge that hydrophobic aryl groups would prefer to stay within a hydrophobic cavity, we believe that irradiation of the hydrochloride salts of olefins 1-8 should give only syn head-head and anti head-tail dimers. With this model in mind, we explored the use of CB[8] to template the dimerization of the hydrochloride salts of 1-8. Table 3. Product Distributiona (Percent) upon Irradiation of Stilbazole Hydrochlorides 7 and 8 in Water and within CB[8]b,c 4-SA‚HCl (7)
39
40
41
42
water CB[8]
93 04
02 01
03 05
02 90
2-SA‚HCl (8)
43
44
45
46
water CB[8]
95 17
01 02
02
02 81
a The percentage was calculated on the basis of the integration of 1H NMR at 90% conversion. b See Scheme 6 for the structures of 39-46. c Concentration of the guest: 5.6 × 10-4 M.
Preorientation of Olefins toward a Photodimer
Langmuir, Vol. 23, No. 14, 2007 7551 Scheme 5
Scheme 6
Scheme 7
We believe that three factors play a major role in determining the stereochemistry of the dimer being formed within CB[8]. These are the “best fit” of the two olefins within the reaction cavity, minimization of electrostatic repulsion, and maximization of weak attractions between the reactive olefins present within CB[8]. Results of olefins 1‚HCl, 2‚HCl, and 3‚HCl emphasize the importance of best fit in controlling the dimerization process.
One would expect the electrostatic repulsion to be lower in the anti dimer where the pyridinium groups are at the 1 and 3 positions than in the syn dimer where these groups are attached to adjacent carbons (1 and 2 positions). On the basis of the principle of minimization of electrostatic repulsion between pyridinium groups, one would expect the anti dimer to be formed within CB[8]. However, the principle of best fit suggests that we should get only the syn dimer. (See above.) As seen in Table 1, in all three cases the main dimer (>85%) is syn. Clearly the first condition for selective dimerization is “fit within the reaction cavity”. Now the question is when the two possible dimers and the precursor olefin arrangements are similar in size which one would be preferred. We have experimented with 4‚HCl, 5‚HCl, and 6‚HCl to address this question. In these examples, the two ends, although positively charged, are not the same. These olefins in principle can give four dimers (Scheme 4). Of these four dimers, syn head-tail and anti head-head dimers are too large to fit within the CB[8] cavity. Indeed they were not formed. However,
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Figure 5. Energy-optimized structures of the dimers of 3,4BPE‚2HCl (4).
the remaining two dimers, syn head-head and anti head-tail, are similar in size, and they both, as well as their precursor olefins, could fit within the CB[8] cavity. A closer examination of the structures reveals that in the anti head-tail dimer the location of positive charge is slightly offset and therefore the electrostatic repulsion is expected to be lower than in the syn head-head dimer (Scheme 4). The fact that the anti head-tail is the major product in each of these examples (Table 2) suggests that the minimization of electrostatic repulsion plays an important role in determining which of the two dimers of equal size is formed. The above qualitative model is further supported by the photobehavior of 7‚HCl and 8‚HCl (Scheme 7). The irradiation of these olefins as complexes of CB[8] gave a single dimer, namely, anti head-tail 42 and 46 (Table 3). The preference for this dimer is easily understood on the basis of the minimization of electrostatic repulsion between like charges and fit within the cavity. In the syn head-head arrangement, the positively charged pyridinium groups would be closer (adjacent) than in the anti head-tail arrangement. Achieving photodimerization of olefins that normally do not dimerize in solution requires an increase in the local concentration of the olefin in a given medium. This could be achieved by using water as the solvent where olefins often tend to aggregate as a result of hydrophobic forces.42-46 Increasing the local concentration alone is insufficient to obtain a selective dimer. Molecules (36) Quina, F. H.; Whitten, D. G. J. Am. Chem. Soc. 1977, 99, 877-883. (37) Quina, F. H.; Whitten, D. G. J. Am. Chem. Soc. 1975, 97, 1602-1603. (38) Usami, H.; Takagi, K.; Sawaki, Y. J. Chem. Soc., Faraday Trans. 1992, 88, 77-81. (39) Takagi, K.; Usami, H.; Fukaya, H.; Sawaki, Y. Chem. Commun. 1989, 1174-1175. (40) Banu, H. S.; Lalitha, A.; Pitchumani, K.; Srinivasan, C. Chem. Commun. 1999, 607-608. (41) MacGillivray, L. R.; Papaefstathiou, G. S.; Friscic, T.; Varshney, D. B.; Hamilton, T. D. Top. Curr. Chem. 2005, 248, 201-221. (42) Breslow, R. Acc. Chem. Res. 2004, 37, 471-478. (43) Lindstrom, U. M.; Andersson, F. Angew. Chem., Int. Ed. 2006, 45, 548551. (44) Muthuramu, K.; Ramamurthy, V. J. Org. Chem. 1982, 47, 3976-3979. (45) Syamala, M. S.; Ramamurthy, V. J. Org. Chem. 1986, 51, 3712-3715. (46) Devanathan, S.; Ramamurthy, V. J. Photochem. Photobiol. 1987, 40, 67-77.
need to be preorganized, and this is often achieved at an interface between hydrophobic and hydrophilic phases. Although conventional micelles provide an interface, they most often do not yield a single dimer.3-5,32,47-51 A study by Whitten and coworkers on the photodimerization of 4-stilbazolium and 2-stilbazolium cations in micelles, reverse micelles, monolayers, and clays highlights the importance of one more factor that must be controlled during the photodimerization process.6,7 Although only isomerization occurred within conventional micelles, surprisingly within an AOT reverse micelle a syn head-head dimer was obtained as the major product from 4-stilbazolium and 2-stilbazolium cations. The more rigid reaction cavity of a reverse micelle not only helped to increase the local concentration and align molecules at an interface but also favored a single dimer by restricting the freedom of the preorganized reactive olefins. Thus, it is important to use a reaction cavity that is tight and time-independent (micelles unfortunately are dynamic and loose) to obtain a selective dimer. To predict the dimer that would be formed in a given medium, one needs to have an intuitive model on hand. We have generated one in this study. In this presentation, we have demonstrated that CB[8] has the ability to template the hydrochloride salts of various bispyridyl ethylenes and stilbazoles toward a single dimer. Unlike micelles, modestly water-soluble CB[8] did not provide freedom to reactive olefins that helped to maintain the preorientation of olefins until the completion of the dimerization process. Before closing, we wish to point out that cucurbiturils are not unique in orienting olefins toward a single photodimer. Hosts such as cyclodextrins, calixarenes, and a Pd nanohost with features similar to that of cucurbiturils have been used to template photodimerizations in water, and the model developed here correctly predicts the dimer being formed in each case.8-25 (47) Nakamura, Y.; Kato, T.; Morita, Y. Tetrahedron Lett. 1981, 22, 10251028. (48) Nakamura, Y. J. Chem. Soc., Chem. Commun. 1988, 477-478. (49) Berenjian, N.; de Mayo, P.; Sturgeon, M.-E.; Sydnes, L. K.; Weedon, A. C. Can. J. Chem. 1982, 60, 425-436. (50) Muthuramu, K.; Ramanath, N.; Ramamurthy, V. J. Org. Chem. 1983, 48, 1872-1876. (51) Mayer, H.; Schuster, F.; Sauer, J. Tetrahedron Lett. 1986, 27, 12891292.
Preorientation of Olefins toward a Photodimer
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Scheme 8. Stepwise Binding Model for the Formation of a 1:2 Host/Guest Complex
Experimental Section Materials. Cucurbiturils were synthesized according to the procedure reported by Day et al.52 Symmetrical bispyridyl ethylenes 1 and 3 and unsymmetrical bispyridyl ethylenes 4-6 obtained from Sigma-Aldrich were used without further purification. trans-1,2Bis-(3-pyridyl) ethylene (2) and stilbazoles 7 and 8 were synthesized according to the procedure reported in the literature.53,54 The hydrochloride form of olefins 1-8 was obtained by dissolving them in a minimal amount of a methanol/10% HCl solution and evaporating the methanol under reduced pressure. Preparation and Irradiation of trans-Bispyridyl Ethylene Complexes with Cucurbiturils (CBs) in Water. Two milligrams of bispyridyl ethylene dihydrochloride taken in 50 mL of deionized water was sonicated at 70 °C for 5-10 min. Half an equivalent of CB[8] (or 1 equiv of CB[7]) was added to this solution and sonicated for an additional 1 h to obtain a clear solution. The solution was cooled to room temperature and filtered through a Whatmann filter paper of fine porosity to remove any insoluble particles. The complexes were irradiated for 1 h using a 450 W medium-pressure mercury lamp immersed in a water-cooled Pyrex jacket. Following irradiation, the solution was transferred to a separatory funnel, and 10% NaOH(aq) was added dropwise until basic pH (>9) was obtained; then extraction was carried out with chloroform. The organic layer was separated, dried over anhydrous Na2SO4, filtered, vacuum dried, and analyzed by 1H NMR. Titration Studies of Bispyridylethylene Dihydrochlorides with CB[8]. One milligram of the guest (1-8) was dissolved in 0.6 mL of D2O, and the solution was transferred to an NMR tube. To the (52) Day, A.; Arnold, A. P.; Blance, R. J.; Snushall, B. J. Org. Chem. 2001, 66, 8094-8100. (53) Gromov, S. P.; Vedrinikov, A. I.; Ushakov, E. N.; Lobova, N. A.; Botsmanova, A. A.; Kuz’mina, L. G.; Churakov, A. V.; Strelenko, Y. A.; Alfimov, M. V.; Howard, J. A. K.; Johnels, D.; Edlund, U. G. New J. Chem. 2005, 29, 881-894. (54) Williams, J. L. R.; Adel, R. E.; Carlson, J. M.; Reynolds, G. A.; Borden, D. G.; Ford, J. A., Jr. J. Org. Chem. 1963, 28, 387-390.
guest solution, finely powdered CB[8] was added in 0.1 equiv increments, and 1H NMR was recorded after each addition. Determination of Binding Constants by 1H NMR Titration. 1H NMR titration experiment of 1‚HCl@CB[8] was conducted on the basis of the model depicted in Scheme 8. The upfield shift of the olefinic proton (Hc) of guest 1‚HCl (compared to the free guest in D2O) was measured as a function of the concentration of guest added to a fixed concentration of host CB[8]. This complexation can be explained by the stepwise mechanism (Scheme 8) involving the initial formation of the 1:1 host/guest complex as represented by eq 1, followed by the addition of a second host to give the 2:1 host/ guest complex described in eq 3.1H NMR titration results (change in chemical shift (δ) vs [guest]) of the H/G complex were fit to eq 5 using nonlinear least-square fitting program Graphpad prism software. The nonlinear nature of the curve, which was plotted between changes in the chemical shift of the olefinic proton signal against the concentration of the guest added at fixed concentration of the host, indicates the presence of higher-order inclusion
Figure 6. Nonlinear fitting curve obtained for the observed trend in the chemical shift of guest olefinic (Hc) protons.
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complexes. Fitting yielded an R2 value of 0.9908, indicating that the assumed stepwise equilibrium model fits the observed experimental trend and is adequately represented by the equilibrium constant expression (eq 5)
∆)
∆11 K1 [L] +∆12 Κ1 Κ2 [L]2 1+ K1 [L] + K1 K2 [L]2
(5)
where ∆ is the observed chemical shift of the complex, [L] ) [BPE], ∆11 ) δHG - δG, ∆12 ) δHG2 - δG, and δG is the 1H NMR chemical shift of guest in D2O. The best fit presented in Figure 6 was obtained with the parameters ∆11) -1.356 and ∆12 ) 0.089. The binding constants, K1 and K2, were calculated to be 1.03 × 103 M-1 and 8.6 × 105 M-1, respectively. The overall binding constant was calculated to be 8.85 × 108 M-2. The calculated binding constants K1 and K2 are reasonable, and K2 > K1 means that the formation of the 1:2 H/G complex is more favorable. 1H
NMR Data for Dimers. Syn dimer of 4BPE‚2HCl (12): 1H NMR (400 MHz, CDCl3, TMS) δ 4.52 (d, 4H), 6.95 (d, 8H, J ) 8.4 Hz), 8.42 (d, 8H, J ) 8.4 Hz). Anti Dimer of 4BPE‚2HCl (13). 1H NMR (400 MHz, CDCl3, TMS) δ 3.72 (s, 4H), 7.12 (d, 8H, J ) 8.4 Hz), 8.52 (d, 8H, J ) 8.4 Hz).
Syn Dimer of 3BPE‚2HCl (16). 1H NMR (400 MHz, CDCl3, TMS) δ 4.53 (s, 4H), 7.07 (m, 4H), 7.38 (d, 4H), 8.35 (d, 4H), 8.42 (s, 4H) 6.95. Anti Dimer of 3BPE‚2HCl (17). 1H NMR (400 MHz, CDCl3, TMS) δ 3.71 (s, 4H), 7.15 (m, 4H), 7.45 (d, 4H), 8.4 (m,8H). Syn Dimer of 2BPE‚2HCl (20). 1H NMR (400 MHz, CDCl3, TMS) δ 5.18 (s, 4H), 6.90 (q, 4H), 7.07 (d, 4H), 7.39 (t, 4H), 8.6 (d, 4H). Anti Dimer of 2BPE‚2HCl (21). 1H NMR (400 MHz, CDCl3, TMS) δ 4.39 (s, 4H), 7.1 (q, 4H), 7.25 (d, 4H), 7.55 (d, 4H), 8.65 (d, 4H). Anti HT Dimer of 2,4BPE‚2HCl (31). 1H NMR (400 MHz, CDCl3, TMS) δ 4.75 (dd, 2H), 4.95 (dd, 2H), 7.1-7.8 (m, 12 H), 8.40 (d, 4H). Anti HT Dimer of 2,3BPE‚2HCl (35). 1H NMR (400 MHz, CDCl3, TMS) δ 4.71 (dd, 2H), 4.98 (dd, 2H), 7.1-7.8 (m, 12 H), 9.00 (d, 2H), 9.15 (s, 2H). Syn HH Dimer of 2,3BPE‚2HCl (34). 1H NMR (400 MHz, CDCl3, TMS) δ 4.65 (d, 2H), 5.00 (dd, 2H), 7.1-7.8 (m, 12 H), 8.86 (d, 2H), 9.38 (s, 2H). Anti HT Dimer of 4SA‚HCl (42). 1H NMR (400 MHz, CDCl3, TMS) δ 4.48 (m, 4H), 7.08-7.4 (m, 14 H), 8.35 (d, 4H). Anti HT Dimer of 2SA‚HCl (46). 1H NMR (400 MHz, CDCl3, TMS) δ 4.9-5.0 (bs, 4H), 7.1-7.6 (m, 16 H), 8.42 (d, 2H).
Acknowledgment. V.R. thanks the NSF for financial support (CHE-0213042 and CHE-0531802). LA700803K
