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Synthesis, structures, and ligating ability of 4-tert-butylcalix[n]arene (iso)nicotinoylate
Tetrahedron Letters 53 (2012) 1240–1244
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthesis, structures, and ligating ability of 4-tert-butylcalix[n]arene (iso)nicotinoylate Eun Ji Kim, Jungmin Ahn, Haeri Lee, Tae Hwan Noh ⇑, Ok-Sang Jung ⇑ Department of Chemistry, Pusan National University, Pusan 609-735, Republic of Korea
a r t i c l e
i n f o
Article history: Received 2 December 2011 Revised 24 December 2011 Accepted 26 December 2011 Available online 2 January 2012 Keywords: Absorption spectra 4-tert-Butylcalix[n]arene (iso)nicotinoylate Crystal structures Cobalt(II) complexes Partial substitution
a b s t r a c t 4-tert-Butylcalix[n]arenes react with an excess of (iso)nicotinoyl chloride, yielding selectively n-2 acylated products, calix[n]-(nico)n 2(OH)2, (calix = 4-tert-butylcalix[n]arene; n = 4, 6, and 8; nico = (iso)nicotinoylate) of alternate conformations. Their structures were determined by X-ray single crystallography and NMR spectra. The UV–vis spectra indicated that a new absorption band of the complexes appears upon the addition of cobalt(II) dichloride, and its crystal structure was resolved. Ó 2011 Elsevier Ltd. All rights reserved.
Functionalized calix[n]arenes have been intriguing molecular building blocks for the construction of defined structural supramolecular systems,1–5 owing to their potential application as sensors, catalysts, separation processes, enzymatic models, and ionophores.6–11 Calix[n]arenes can be functionalized in various ways at the phenolic hydroxyl groups, the so-named lower rim, and/or at the para position of the phenolic rings, known as the upper rim.1,2,12,13 Synthesis of desirable calix[n]arene derivatives is essential in order to modulate their conformation via electronic and steric effects, including weak interactions. (Iso)nicotinoylate groups substituted into the lower rim of 4-tert-butylcalix[n]-arenes can be utilized as new multi-N-donor tectonics in the structural and functional modifications of their core molecular architecture which comprises a hollow cavity formed by a hydrophobic upper rim and a hydrophilic low rim. The (iso)nicotinoyl-containing pendants possess characteristic properties such as a potential multidentate ligand, an sp2 angle around C@O (120°), a malleable length, conformational nonrigidity, and manageable solubility.14–18 In this context, we here describe a facile synthesis of unique partial substituted products, calix[n]-(nico)n 2(OH)2, (calix = 4-tert-butylcalix[n]-arene; n = 4, 6, 8; nico = (iso)nicotinoylate) via steric hindrance along with their ligating ability with COCl2 species. This produces the chemical repertoire of the calixarenes, since it provides easy access to novel ligands, allowing the synthesis of supramolecular materials for recognition. ⇑ Corresponding authors. Tel.: +82 51 510 2591; fax: +82 51 516 7421. E-mail addresses: [email protected] (T.H. Noh), [email protected] (O.-S. Jung). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.12.112
OH
m OH
2
4-tert-butylcalix[n]arene O Cl N
N
O O OH
N
N
m
=N
, m = 1 (1a), 2 (2a), 3 (3a)
=
, m = 1 (1b), 2 (2b), 3 (3b)
N
2
CoCl2
Scheme 1. Overall procedure.
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E. J. Kim et al. / Tetrahedron Letters 53 (2012) 1240–1244
All of the products were prepared by the reaction of 4-tertbutylcalix[n]arenes (n = 4, 6, 8) with (iso)nicotinoyl chloride in chloroform in the presence of an excess amount of triethylamine, as indicated in Scheme 1. The reactions were refluxed in chloroform for 3 days, and the product formations were strongly dependent on the reaction temperature and time. That is, the reactions at low temperatures or for 1 2 days produced mixture including the products. Then, 1a, 2a, 2b, and 3a were recrystallized from a mixture of dichloromethane/ethanol, dimethyl sulfoxide/acetonitrile, dioxane/n-hexane, and nitrobenzene/acetonitrile, respectively, to obtain colorless block single crystals suitable for X-ray crystallographic analysis. The reaction of C4V-symmetrical 4-tert-butylcalix[4]arene with an excess amount of isonicotinoyl chloride resulted in partial isonicotinoylation, except for two alternate hydroxyl groups, 1a. Complete substitution did not occur, even in the prolonged presence of an excess of isonicotinoyl chloride. Surprisingly, all of the reactions, similarly, afforded calix[n]-(nico)n 2(OH)2 under the vigorous condition. The products were soluble in chloroform, benzene, and N,N-dimethylformamide, but insoluble in methanol, ethanol, diethyl ether, and n-hexane. The OH bands at around 3535, 3527, 3531, 3522, 3537, and 3457 cm 1 for 1a, 1b, 2a, 2b, 3a, and 3b, respectively, indicated partial substitution of the phenolic hydroxyl groups (see Supplementary data). The 1H, 13C NMR spectra and the elemental analyses were coincident with the structures. The position of the pyridyl nitrogen donor (the para- and meta-pyridyl groups) did not significantly affect the reactivity or the crystal structures. Furthermore, FAB masses of 1a, 2a, and 3a were consistent with the X-ray crystallographic data (m/z = 859.3 [M+H+]+; 843.4 [M CH3+H+]+ for 1a, 1394.1 [M CH3+H+]+; 1378.1 [M 2CH3+H+]+ for 2a, 1928.7 [M e ]+; 1912.7 [M CH3 e ]+ for 3a). Compound 1a is a 1,3-di-substituted species in the 1,2-alternate conformation,19,20 as shown in Fig. 1, causing the isonicotinoylate substituent units to be oppositely oriented, in contrast to the starting 4-tert-butylcalix[4]arene. The molecule is positioned at a symmetry center of the monoclinic unit cell. There is a close approach between a hydrogen atom attached to a tert-butyl group and the neighboring pyridyl aromatic plane (2.801 Å), and the CH ppy interaction can be attributed to the formation of 1,2-alternate conformers. Additionally, the phenolic hydroxyl group interacts with an adjacent oxygen atom of the ester group via the intramolecular hydrogen-bond (2.870 Å, Fig. 2). X-ray characterization of 2a revealed that the molecule is a 1,2,4,5-tetra-substituted species with a C2 symmetry point group (Fig. 1). The orientation between rings A and B (and rings D and E) is in anti-conformation with a CH ppy interaction (2.803 Å). Thus, two isonicotinoylate moieties are directed toward the up-side, and the other two moieties are directed to the down-side. The substitution of phenolic hydroxyl groups attached to rings C and F did not occur, presumably owing to the steric hindrance of the adjacent isonicotinoylate groups, as will be discussed below. The intramolecular hydrogen-bonds between the phenolic hydroxyl group and the oxygen atom of the neighboring ester group were observed (2.109 Å). The crystal structure of 2b is similar to that of 2a, except for the presence of the p p interaction between the two pyridyl rings lying on the lower rim (dihedral angle = 20.7(3)°). Although a few examples of 1,4-alternate conformers induced by immobilization via intramolecular-linker(s) have been reported,21,22 the present 1,4-alternate conformation without such an immobilization is the first example. For 3a, the backbone of the hexa-substituted 4-tert-butylcalix[8]arene approximates a ‘pseudo-chair-like’ conformation.23 This conformation contributes to the 3/4-cone geometry for the rings B C D and F G H (Figs. 1 and 2). In contrast to the known chair-like conformational structures of calix[8]arene analogues,24,25 the tert-butyl group attached to ring C was directed inward into the upper rim of a 3/4-cone conformer defined by rings B, C, and D, presumably
a O3 N1 O1 O2
b
N1 O5 O4 O2
O3
N2
O1
c
O1 O2
N1 N2
O4
O7 O3 O6 O5 N3 Figure 1. Top views of ORTEP drawings of 1a (a), 2a (b), and 3a (c) along with thermal ellipsoids at 30% probability. The annulus aromatic rings are highlighted. The solvated molecules and hydrogen atoms (except for hydroxyl protons) are omitted for clarity.
owing to the face-to-edge p p interaction between the pyridyl rings on their lower rim (CH ppy = 2.816 Å). Whereas 2a lies on a two-fold axis, 3a lies about an inversion center, similarly to 1a. The two pyridyl donors are up-positioned, and the two pyridyl donors are down-positioned from the mean plane of the molecule. The remaining two pyridyl rings are positioned within the macrocyclic ring with the p p interaction (dihedral angle = 0.0(2)°, distance = 3.68(5) Å). Thus, solvated molecules such as nitrobenzene and acetonitrile seem to be inaccessible to the large molecular cavity of 3a in the solid state. The 1H NMR spectrum of 1a in CDCl3 (see Supplementary data) revealed that the methylene proton resonances appear as one doublet (3.85 ppm, J = 21 Hz) and two singlets (3.93 and 3.79 ppm), which is similar to other 1,2-alternate conformers of calix[4]arene
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E. J. Kim et al. / Tetrahedron Letters 53 (2012) 1240–1244
a B 25 ºC
C D
A
0 ºC
−10 ºC
b
C
F A
B
D
−30 ºC
E
4.5
4.0
Figure 3. Temperature-dependent methylene region.
c D
E F
C B
H
G
A
Figure 2. Schematic side views of 1a (a), 2a (b), and 3a (c) showing highlighted parent calix[n]arene rings and hydrogen bonds between phenolic hydrogen and adjacent oxygen. The solvated molecules and the hydrogen atoms (except for hydroxyl protons) are omitted for clarity.
derivatives.19 This pattern is comparable to a pair of broad doublets at 4.26 and 3.49 ppm (JAB = 14.4 Hz) of the starting cone-conformational 4-tert-butylcalix[4]arene. The two pairs of singlet signals for aryl protons and tert-butyl protons (7.47 and 6.89; 1.50 and 0.83 ppm) with the 1:1 integral ratio are consistent with the number of substitutions of the isonicoti-noylate groups. Two doublets (8.35 and 6.79 ppm, J = 5.4 Hz) corresponding to the a- and b-pyridyl protons, respectively, also were observed. For 2a (see Supplementary data), a pair of singlets (1.42 and 0.70 ppm) with the 1:2 integral ratio arising from the tert-butyl protons indicated that four of the six phenolic hydroxyl groups are substituted with the isonicotinoylate pendants. The bridging methylene groups gave rise to an AB system with two separate doublet signals at 4.30 and 3.58 ppm (J = 15.3 Hz), respectively, along with a singlet at 4.03 ppm, owing to the anti-orientation between rings A and B (also D and E; see Fig. 2). The hydroxyl proton signals were relatively downfield-shifted (6.31 ppm) compared with 1a (5.14 ppm), implying their stronger hydrogen-bonds in solution. The 1H NMR spectrum of 2b was similar to that of 2a (see
3.5
3.0
1
H NMR spectra (500 MHz) of 3a showing
Supplementary data), except for four aromatic resonances corresponding to the m-pyridyl moieties. None of the signals of 2a and 2b were significantly affected by the temperature until 30 °C. The 32-membered macrocyclic 3a shows broad signals at room temperature (see Supplementary data), indicating that its structure is flexible in solution. It is well known that cone-cone interconversion can take place via either ‘a tert-butyl or a phenoxy through the annulus’ pathway.26 Thus, the temperature-dependent 1 H NMR spectra of 3a were resolved at 30 °C. There were a hydroxyl singlet, two pairs of doublet, ten aryl singlets, and many tertbutyl singlets, along with the quite complicated methylene proton signals at low temperature (Fig. 3 and see Supplementary data). According to a 2D COSY experiment at 30 °C (see Supplementary data), the doublets at 8.68 and 8.47 ppm correlated with those at 6.79 and 7.11 ppm, respectively, corresponding to the pyridyl groups outward and inward of the shielding region of the macrocycle, as shown in its crystal structure. In particular, the resonances of three AB systems (4.44 and 3.22, J = 15 Hz; d 4.16 and 3.93, J = 17 Hz; d 3.52 and 3.38, J = 15 Hz) along with a singlet at 3.37 ppm for the ArCH2Ar groups were clearly indicative of the restricted movement of the macrocyclic product. From a relatively rigid backbone, the 4-tert-butylcalix[4]-arenes, to a relatively flexible backbone, the 4-tert-butylcalix[8]-arenes, all of the reactions produced calix[n]-(nico)n 2(OH)2. What is the driving force behind these products? Specifically, the coneconformational starting materials change to alternate conformational products. Both the phenolic hydroxyl groups directing toward the adjacent ester group via the intramolecular hydrogenbond and the steric hindrance of the tert-butyl groups seem to be pivotal factors for the partial substitution of moderately flexible calix[n]arenes. To the best of our knowledge, this is first example of systematic partial functionalization and crystallization of calix[n]arene derivatives (n = 4, 6, 8) without a protection-deprotection strategy. Only one example of bipyridi-ne-functionalized calix[4]arene derivatives thus far has been reported.27 1a and 1b change to the 1,2-alternate conformation without the template effects of the base counterions.28 As shown in Figs. 1 and 2, the remaining OH group is covered with an adjacent (iso)nicotinoylate group. That is, the OH group is locked intramolecularly by the (iso)nicotinoylate group, and thus further reaction toward the fully-substituted does not occur under
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E. J. Kim et al. / Tetrahedron Letters 53 (2012) 1240–1244
1.0 0.8
Absorbance
the reaction condition. If so, further reaction should need a more vigorous condition to overcome the 2 20 kJ/mol of such a OH p interaction.29 Reaction time is another important factor. The similar reaction pattern for nicotinoyl and isonicotinoyl chloride suggests that the locked OH p interaction is more rate-determinable than the N-position of pyridyl groups, which is not a significant factor under this reaction condition. The interaction with metal ions was evaluated by means of electronic spectra. Fig. 4 shows the electronic spectra of 1a in dichloromethane/acetone solution in the presence of COCl26H2O. Upon adding COCl26H2O, the absorbance around 674 nm decreases with slight hypsochromic shifts, and new absorption bands appear at around 618 and 576 nm. Since 1a does not absorb in the 400 800 nm region of the spectrum, these traces record only the changes in the d–d transitions due to changes in ligation. This spectral change for 1a is thought to arise from the close contact between the pyridyl groups and the cobalt(II) ion. The electronic spectrum of a mixture of 4-tert-butylcalix[4]arene and COCl2 is similar to that of COCl2, indicating that the cobalt(II) ion interacts with the pyridyl group rather than the hydroxyl group. On the other hand, when NiCl26H2O instead of COCl26H2O was used, no such spectral change was observed. The electronic spectra of 3a in dichloromethane/acetone solution in the presence of CoBr2 decrease the band at 673 nm, and new bands at 635 and 597 nm (Fig. 5). The crystal structure of [COCl2(1a)]n by means of self-assembly of COCl26H2O with 1a in a mixed acetone/dichloro-methane solution was resolved (Fig. 6 and see Supplementary data). Combining COCl2 and 1a in a 1:1 ratio results in the formation of a 1-D single strand, as indicated in Scheme 1. The calixarene entities have 1,2alternate conformations very similar to that of 1a. Each 1a connects two cobalt(II) atoms in a l2-fashion (Co N = 2.058(5), 2.065(5) Å) with the Co Co separation of 14.950(3) and 15.063(4) Å. The local geometry around the cobalt(II) atoms is a tetrahedral arrangement with two nitrogen atoms from two 1a ligands and two chloride atoms (N Co N = 106.6(2)°, Cl Co Cl = 118.91(7)°). One dichloro-methane and two acetone molecules in the stoichiometric units are found. No other exceptional features, neither those of bond lengths or angles, were observed. Selective n 2 O-acylation of 4-tert-butylcalix[n]arene with (iso)nicotinoyl chloride was conducted. The steric effects of 4-tert-butylcalix[n]arene are mostly likely responsible for this selectivity. This reaction produces only a product of general formula, calix[n]-(nico)n 2(OH)2, irrespective of the starting
0.6 0.4 0.2 0.0 400
500
600
700
800
nm Figure 5. Absorption spectra of CoBr2 (3 mM) in dichloro-methane/acetone solution upon the addition of 3a (3 mM). The black, red, and blue lines indicate 3a, CoBr2, and a mixture of CoBr2 and 3a, respectively.
Figure 6. Crystal structure of [COCl2(1a)]n. The hydrogen atoms and the solvated molecules are omitted for clarity.
materials and the macrocyclic ring size. Crystal structures of unique conformation are adopted, which we believe are very good N-pyridyl donor-ligand tectonics. In conclusion, (iso)nicotinoylate containing spacers were synthesized and characterized. Notably, the reaction was prominently stepwise via an intramolecular anisotropic OH p interaction. Preliminary experiments showed that the spacer ligands are good tectonics for desirable supramolecular structures such as molecular boxes, cubes, and strands. Acknowledgment This treatise was supported by the project of National Junior research fellowship which National Research Foundation of Korea conducts from 2011.
1.0
Absorbance
0.8 Supplementary data
0.6 Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.12.112.
0.4
References and notes
0.2 0.0 400
500
600
700
800
nm Figure 4. Absorption spectra of COCl2 (3 mM) in dichloro-methane/acetone solution upon addition of 1a (3 mM). The black, red, and blue lines indicate 1a, COCl2, and a mixture of COCl2 and 1a, respectively.
1. Gutsche, C. D. Calixarenes Revisited; Royal Society of Chemistry: Cambridge, U.K., 1998. 2. For reviews on calixarenes, see: In: Calixarenes; Asfari, Z., Böhmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2001. 3. Harvey, P. D. Coord. Chem. Rev. 2002, 233–234, 289. 4. Bilyk, A.; Hall, A. K.; Harrowfield, J. M.; Hosseini, M. W.; Skelton, B. W.; White, A. H. Inorg. Chem. 2001, 40, 672. 5. Bilyk, A.; Dunlop, J. W.; Fuller, R. O.; Hall, A. K.; Harrowfield, J. M.; Hosseini, M. W.; Koutsantonis, G. A.; Murray, I. W.; Skelton, B. W.; Sobolev, A. N.; Stamps, R. L.; White, A. H. Eur. J. Inorg. Chem. 2010, 2127.
1244 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
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Diamond, D.; McKervey, M. A. Chem. Soc. Rev. 1996, 15. Homden, D. M.; Redshaw, C. Chem. Rev. 2008, 108, 5086. Jose, P.; Menon, S. Bioinorg. Chem. Appl. 2007, 2007, 1. Diamond, D.; Nolan, K. Anal. Chem. 2001, 73, 22A. Ludwig, R. Microchim. Acta 2005, 152, 1. Creaven, B. S.; Donlon, D. F.; McGinley, J. Coord. Chem. Rev. 2009, 253, 893. Calixarenes A Versatile Class of Macrocyclic Compounds; Vicens, J., Böhmer, V., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1991. Tadokoro, M.; Mizugaki, S.; Kozaki, M.; Okada, K. Chem. Commun. 2005, 1140. Ghosh, S.; Mukherjee, P. S. J. Org. Chem. 2006, 71, 8412. Ronson, T. K.; Fisher, J.; Harding, L. P.; Hardie, M. J. Angew. Chem., Int. Ed. 2007, 46, 9086. Chun, I. S.; Kwon, J. A.; Yoon, H. J.; Bae, M. N.; Hong, J.; Jung, O.-S. Angew. Chem., Int. Ed. 2007, 46, 4960. Noh, T. H.; Heo, E.; Park, K. H.; Jung, O.-S. J. Am. Chem. Soc. 2011, 133, 1236. Liang, H.; Cha, M. S.; Lee, Y.-A.; Lee, S. S.; Jung, O.-S. Inorg. Chem. Commun. 2007, 10, 71. Froidevaux, P.; Harrowfield, J. M.; Sobolev, A. N. Inorg. Chem. 2000, 39, 4678.
20. Groenen, L. C.; van Loon, J. D.; Verboom, W.; Harkema, S.; Casnati, A.; Ungaro, R.; Pochini, A.; Ugozzoli, F.; Reinboudt, D. N. J. Am. Chem. Soc. 1991, 113, 2385. 21. Guan, B.; Gong, S.; Wo, X.; Chen, Y. Tetrahedron Lett. 2005, 46, 6041. 22. Blanda, M. T.; Edwards, L.; Salazar, R.; Boswell, M. Tetrahedron Lett. 2006, 47, 7081. 23. Atwood, J. L.; Clark, D. L.; Juneja, R. K.; Orr, G. W.; Robinson, K. D.; Vincent, R. L. J. Am. Chem. Soc. 1992, 114, 7558. 24. Perret, F.; Bonnard, V.; Danylyuk, O.; Suwinska, K.; Coleman, A. W. New J. Chem. 2006, 30, 987. 25. Ferro, R.; Tedesco, C.; Gaeta, C.; Neri, P. J. Inclusion Phenom. Macrocyclic Chem. 2005, 52, 85. 26. Rondelez, Y.; Rager, M.-N.; Duprat, A.; Reinaud, O. J. Am. Chem. Soc. 2002, 124, 1334. 27. Dorta, R.; Shimon, L. J. W.; Rozenberg, H.; Ben-David, Y.; Milstein, D. Inorg. Chem. 2003, 42, 3160. 28. Iwamoto, K.; Fujimoto, K.; Matsuda, T.; Shinkai, S. Tetrahedron Lett. 1990, 31, 7169. 29. Desiraju, G. R. The Crystal as a Supramolecular Entity, Perspectives in Supramolecular Chemistry; John Wiley & Sons: New York, 1996. Vol. 2.
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthesis, structures, and ligating ability of 4-tert-butylcalix[n]arene (iso)nicotinoylate Eun Ji Kim, Jungmin Ahn, Haeri Lee, Tae Hwan Noh ⇑, Ok-Sang Jung ⇑ Department of Chemistry, Pusan National University, Pusan 609-735, Republic of Korea
a r t i c l e
i n f o
Article history: Received 2 December 2011 Revised 24 December 2011 Accepted 26 December 2011 Available online 2 January 2012 Keywords: Absorption spectra 4-tert-Butylcalix[n]arene (iso)nicotinoylate Crystal structures Cobalt(II) complexes Partial substitution
a b s t r a c t 4-tert-Butylcalix[n]arenes react with an excess of (iso)nicotinoyl chloride, yielding selectively n-2 acylated products, calix[n]-(nico)n 2(OH)2, (calix = 4-tert-butylcalix[n]arene; n = 4, 6, and 8; nico = (iso)nicotinoylate) of alternate conformations. Their structures were determined by X-ray single crystallography and NMR spectra. The UV–vis spectra indicated that a new absorption band of the complexes appears upon the addition of cobalt(II) dichloride, and its crystal structure was resolved. Ó 2011 Elsevier Ltd. All rights reserved.
Functionalized calix[n]arenes have been intriguing molecular building blocks for the construction of defined structural supramolecular systems,1–5 owing to their potential application as sensors, catalysts, separation processes, enzymatic models, and ionophores.6–11 Calix[n]arenes can be functionalized in various ways at the phenolic hydroxyl groups, the so-named lower rim, and/or at the para position of the phenolic rings, known as the upper rim.1,2,12,13 Synthesis of desirable calix[n]arene derivatives is essential in order to modulate their conformation via electronic and steric effects, including weak interactions. (Iso)nicotinoylate groups substituted into the lower rim of 4-tert-butylcalix[n]-arenes can be utilized as new multi-N-donor tectonics in the structural and functional modifications of their core molecular architecture which comprises a hollow cavity formed by a hydrophobic upper rim and a hydrophilic low rim. The (iso)nicotinoyl-containing pendants possess characteristic properties such as a potential multidentate ligand, an sp2 angle around C@O (120°), a malleable length, conformational nonrigidity, and manageable solubility.14–18 In this context, we here describe a facile synthesis of unique partial substituted products, calix[n]-(nico)n 2(OH)2, (calix = 4-tert-butylcalix[n]-arene; n = 4, 6, 8; nico = (iso)nicotinoylate) via steric hindrance along with their ligating ability with COCl2 species. This produces the chemical repertoire of the calixarenes, since it provides easy access to novel ligands, allowing the synthesis of supramolecular materials for recognition. ⇑ Corresponding authors. Tel.: +82 51 510 2591; fax: +82 51 516 7421. E-mail addresses: [email protected] (T.H. Noh), [email protected] (O.-S. Jung). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.12.112
OH
m OH
2
4-tert-butylcalix[n]arene O Cl N
N
O O OH
N
N
m
=N
, m = 1 (1a), 2 (2a), 3 (3a)
=
, m = 1 (1b), 2 (2b), 3 (3b)
N
2
CoCl2
Scheme 1. Overall procedure.
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E. J. Kim et al. / Tetrahedron Letters 53 (2012) 1240–1244
All of the products were prepared by the reaction of 4-tertbutylcalix[n]arenes (n = 4, 6, 8) with (iso)nicotinoyl chloride in chloroform in the presence of an excess amount of triethylamine, as indicated in Scheme 1. The reactions were refluxed in chloroform for 3 days, and the product formations were strongly dependent on the reaction temperature and time. That is, the reactions at low temperatures or for 1 2 days produced mixture including the products. Then, 1a, 2a, 2b, and 3a were recrystallized from a mixture of dichloromethane/ethanol, dimethyl sulfoxide/acetonitrile, dioxane/n-hexane, and nitrobenzene/acetonitrile, respectively, to obtain colorless block single crystals suitable for X-ray crystallographic analysis. The reaction of C4V-symmetrical 4-tert-butylcalix[4]arene with an excess amount of isonicotinoyl chloride resulted in partial isonicotinoylation, except for two alternate hydroxyl groups, 1a. Complete substitution did not occur, even in the prolonged presence of an excess of isonicotinoyl chloride. Surprisingly, all of the reactions, similarly, afforded calix[n]-(nico)n 2(OH)2 under the vigorous condition. The products were soluble in chloroform, benzene, and N,N-dimethylformamide, but insoluble in methanol, ethanol, diethyl ether, and n-hexane. The OH bands at around 3535, 3527, 3531, 3522, 3537, and 3457 cm 1 for 1a, 1b, 2a, 2b, 3a, and 3b, respectively, indicated partial substitution of the phenolic hydroxyl groups (see Supplementary data). The 1H, 13C NMR spectra and the elemental analyses were coincident with the structures. The position of the pyridyl nitrogen donor (the para- and meta-pyridyl groups) did not significantly affect the reactivity or the crystal structures. Furthermore, FAB masses of 1a, 2a, and 3a were consistent with the X-ray crystallographic data (m/z = 859.3 [M+H+]+; 843.4 [M CH3+H+]+ for 1a, 1394.1 [M CH3+H+]+; 1378.1 [M 2CH3+H+]+ for 2a, 1928.7 [M e ]+; 1912.7 [M CH3 e ]+ for 3a). Compound 1a is a 1,3-di-substituted species in the 1,2-alternate conformation,19,20 as shown in Fig. 1, causing the isonicotinoylate substituent units to be oppositely oriented, in contrast to the starting 4-tert-butylcalix[4]arene. The molecule is positioned at a symmetry center of the monoclinic unit cell. There is a close approach between a hydrogen atom attached to a tert-butyl group and the neighboring pyridyl aromatic plane (2.801 Å), and the CH ppy interaction can be attributed to the formation of 1,2-alternate conformers. Additionally, the phenolic hydroxyl group interacts with an adjacent oxygen atom of the ester group via the intramolecular hydrogen-bond (2.870 Å, Fig. 2). X-ray characterization of 2a revealed that the molecule is a 1,2,4,5-tetra-substituted species with a C2 symmetry point group (Fig. 1). The orientation between rings A and B (and rings D and E) is in anti-conformation with a CH ppy interaction (2.803 Å). Thus, two isonicotinoylate moieties are directed toward the up-side, and the other two moieties are directed to the down-side. The substitution of phenolic hydroxyl groups attached to rings C and F did not occur, presumably owing to the steric hindrance of the adjacent isonicotinoylate groups, as will be discussed below. The intramolecular hydrogen-bonds between the phenolic hydroxyl group and the oxygen atom of the neighboring ester group were observed (2.109 Å). The crystal structure of 2b is similar to that of 2a, except for the presence of the p p interaction between the two pyridyl rings lying on the lower rim (dihedral angle = 20.7(3)°). Although a few examples of 1,4-alternate conformers induced by immobilization via intramolecular-linker(s) have been reported,21,22 the present 1,4-alternate conformation without such an immobilization is the first example. For 3a, the backbone of the hexa-substituted 4-tert-butylcalix[8]arene approximates a ‘pseudo-chair-like’ conformation.23 This conformation contributes to the 3/4-cone geometry for the rings B C D and F G H (Figs. 1 and 2). In contrast to the known chair-like conformational structures of calix[8]arene analogues,24,25 the tert-butyl group attached to ring C was directed inward into the upper rim of a 3/4-cone conformer defined by rings B, C, and D, presumably
a O3 N1 O1 O2
b
N1 O5 O4 O2
O3
N2
O1
c
O1 O2
N1 N2
O4
O7 O3 O6 O5 N3 Figure 1. Top views of ORTEP drawings of 1a (a), 2a (b), and 3a (c) along with thermal ellipsoids at 30% probability. The annulus aromatic rings are highlighted. The solvated molecules and hydrogen atoms (except for hydroxyl protons) are omitted for clarity.
owing to the face-to-edge p p interaction between the pyridyl rings on their lower rim (CH ppy = 2.816 Å). Whereas 2a lies on a two-fold axis, 3a lies about an inversion center, similarly to 1a. The two pyridyl donors are up-positioned, and the two pyridyl donors are down-positioned from the mean plane of the molecule. The remaining two pyridyl rings are positioned within the macrocyclic ring with the p p interaction (dihedral angle = 0.0(2)°, distance = 3.68(5) Å). Thus, solvated molecules such as nitrobenzene and acetonitrile seem to be inaccessible to the large molecular cavity of 3a in the solid state. The 1H NMR spectrum of 1a in CDCl3 (see Supplementary data) revealed that the methylene proton resonances appear as one doublet (3.85 ppm, J = 21 Hz) and two singlets (3.93 and 3.79 ppm), which is similar to other 1,2-alternate conformers of calix[4]arene
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a B 25 ºC
C D
A
0 ºC
−10 ºC
b
C
F A
B
D
−30 ºC
E
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4.0
Figure 3. Temperature-dependent methylene region.
c D
E F
C B
H
G
A
Figure 2. Schematic side views of 1a (a), 2a (b), and 3a (c) showing highlighted parent calix[n]arene rings and hydrogen bonds between phenolic hydrogen and adjacent oxygen. The solvated molecules and the hydrogen atoms (except for hydroxyl protons) are omitted for clarity.
derivatives.19 This pattern is comparable to a pair of broad doublets at 4.26 and 3.49 ppm (JAB = 14.4 Hz) of the starting cone-conformational 4-tert-butylcalix[4]arene. The two pairs of singlet signals for aryl protons and tert-butyl protons (7.47 and 6.89; 1.50 and 0.83 ppm) with the 1:1 integral ratio are consistent with the number of substitutions of the isonicoti-noylate groups. Two doublets (8.35 and 6.79 ppm, J = 5.4 Hz) corresponding to the a- and b-pyridyl protons, respectively, also were observed. For 2a (see Supplementary data), a pair of singlets (1.42 and 0.70 ppm) with the 1:2 integral ratio arising from the tert-butyl protons indicated that four of the six phenolic hydroxyl groups are substituted with the isonicotinoylate pendants. The bridging methylene groups gave rise to an AB system with two separate doublet signals at 4.30 and 3.58 ppm (J = 15.3 Hz), respectively, along with a singlet at 4.03 ppm, owing to the anti-orientation between rings A and B (also D and E; see Fig. 2). The hydroxyl proton signals were relatively downfield-shifted (6.31 ppm) compared with 1a (5.14 ppm), implying their stronger hydrogen-bonds in solution. The 1H NMR spectrum of 2b was similar to that of 2a (see
3.5
3.0
1
H NMR spectra (500 MHz) of 3a showing
Supplementary data), except for four aromatic resonances corresponding to the m-pyridyl moieties. None of the signals of 2a and 2b were significantly affected by the temperature until 30 °C. The 32-membered macrocyclic 3a shows broad signals at room temperature (see Supplementary data), indicating that its structure is flexible in solution. It is well known that cone-cone interconversion can take place via either ‘a tert-butyl or a phenoxy through the annulus’ pathway.26 Thus, the temperature-dependent 1 H NMR spectra of 3a were resolved at 30 °C. There were a hydroxyl singlet, two pairs of doublet, ten aryl singlets, and many tertbutyl singlets, along with the quite complicated methylene proton signals at low temperature (Fig. 3 and see Supplementary data). According to a 2D COSY experiment at 30 °C (see Supplementary data), the doublets at 8.68 and 8.47 ppm correlated with those at 6.79 and 7.11 ppm, respectively, corresponding to the pyridyl groups outward and inward of the shielding region of the macrocycle, as shown in its crystal structure. In particular, the resonances of three AB systems (4.44 and 3.22, J = 15 Hz; d 4.16 and 3.93, J = 17 Hz; d 3.52 and 3.38, J = 15 Hz) along with a singlet at 3.37 ppm for the ArCH2Ar groups were clearly indicative of the restricted movement of the macrocyclic product. From a relatively rigid backbone, the 4-tert-butylcalix[4]-arenes, to a relatively flexible backbone, the 4-tert-butylcalix[8]-arenes, all of the reactions produced calix[n]-(nico)n 2(OH)2. What is the driving force behind these products? Specifically, the coneconformational starting materials change to alternate conformational products. Both the phenolic hydroxyl groups directing toward the adjacent ester group via the intramolecular hydrogenbond and the steric hindrance of the tert-butyl groups seem to be pivotal factors for the partial substitution of moderately flexible calix[n]arenes. To the best of our knowledge, this is first example of systematic partial functionalization and crystallization of calix[n]arene derivatives (n = 4, 6, 8) without a protection-deprotection strategy. Only one example of bipyridi-ne-functionalized calix[4]arene derivatives thus far has been reported.27 1a and 1b change to the 1,2-alternate conformation without the template effects of the base counterions.28 As shown in Figs. 1 and 2, the remaining OH group is covered with an adjacent (iso)nicotinoylate group. That is, the OH group is locked intramolecularly by the (iso)nicotinoylate group, and thus further reaction toward the fully-substituted does not occur under
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1.0 0.8
Absorbance
the reaction condition. If so, further reaction should need a more vigorous condition to overcome the 2 20 kJ/mol of such a OH p interaction.29 Reaction time is another important factor. The similar reaction pattern for nicotinoyl and isonicotinoyl chloride suggests that the locked OH p interaction is more rate-determinable than the N-position of pyridyl groups, which is not a significant factor under this reaction condition. The interaction with metal ions was evaluated by means of electronic spectra. Fig. 4 shows the electronic spectra of 1a in dichloromethane/acetone solution in the presence of COCl26H2O. Upon adding COCl26H2O, the absorbance around 674 nm decreases with slight hypsochromic shifts, and new absorption bands appear at around 618 and 576 nm. Since 1a does not absorb in the 400 800 nm region of the spectrum, these traces record only the changes in the d–d transitions due to changes in ligation. This spectral change for 1a is thought to arise from the close contact between the pyridyl groups and the cobalt(II) ion. The electronic spectrum of a mixture of 4-tert-butylcalix[4]arene and COCl2 is similar to that of COCl2, indicating that the cobalt(II) ion interacts with the pyridyl group rather than the hydroxyl group. On the other hand, when NiCl26H2O instead of COCl26H2O was used, no such spectral change was observed. The electronic spectra of 3a in dichloromethane/acetone solution in the presence of CoBr2 decrease the band at 673 nm, and new bands at 635 and 597 nm (Fig. 5). The crystal structure of [COCl2(1a)]n by means of self-assembly of COCl26H2O with 1a in a mixed acetone/dichloro-methane solution was resolved (Fig. 6 and see Supplementary data). Combining COCl2 and 1a in a 1:1 ratio results in the formation of a 1-D single strand, as indicated in Scheme 1. The calixarene entities have 1,2alternate conformations very similar to that of 1a. Each 1a connects two cobalt(II) atoms in a l2-fashion (Co N = 2.058(5), 2.065(5) Å) with the Co Co separation of 14.950(3) and 15.063(4) Å. The local geometry around the cobalt(II) atoms is a tetrahedral arrangement with two nitrogen atoms from two 1a ligands and two chloride atoms (N Co N = 106.6(2)°, Cl Co Cl = 118.91(7)°). One dichloro-methane and two acetone molecules in the stoichiometric units are found. No other exceptional features, neither those of bond lengths or angles, were observed. Selective n 2 O-acylation of 4-tert-butylcalix[n]arene with (iso)nicotinoyl chloride was conducted. The steric effects of 4-tert-butylcalix[n]arene are mostly likely responsible for this selectivity. This reaction produces only a product of general formula, calix[n]-(nico)n 2(OH)2, irrespective of the starting
0.6 0.4 0.2 0.0 400
500
600
700
800
nm Figure 5. Absorption spectra of CoBr2 (3 mM) in dichloro-methane/acetone solution upon the addition of 3a (3 mM). The black, red, and blue lines indicate 3a, CoBr2, and a mixture of CoBr2 and 3a, respectively.
Figure 6. Crystal structure of [COCl2(1a)]n. The hydrogen atoms and the solvated molecules are omitted for clarity.
materials and the macrocyclic ring size. Crystal structures of unique conformation are adopted, which we believe are very good N-pyridyl donor-ligand tectonics. In conclusion, (iso)nicotinoylate containing spacers were synthesized and characterized. Notably, the reaction was prominently stepwise via an intramolecular anisotropic OH p interaction. Preliminary experiments showed that the spacer ligands are good tectonics for desirable supramolecular structures such as molecular boxes, cubes, and strands. Acknowledgment This treatise was supported by the project of National Junior research fellowship which National Research Foundation of Korea conducts from 2011.
1.0
Absorbance
0.8 Supplementary data
0.6 Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.12.112.
0.4
References and notes
0.2 0.0 400
500
600
700
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nm Figure 4. Absorption spectra of COCl2 (3 mM) in dichloro-methane/acetone solution upon addition of 1a (3 mM). The black, red, and blue lines indicate 1a, COCl2, and a mixture of COCl2 and 1a, respectively.
1. Gutsche, C. D. Calixarenes Revisited; Royal Society of Chemistry: Cambridge, U.K., 1998. 2. For reviews on calixarenes, see: In: Calixarenes; Asfari, Z., Böhmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2001. 3. Harvey, P. D. Coord. Chem. Rev. 2002, 233–234, 289. 4. Bilyk, A.; Hall, A. K.; Harrowfield, J. M.; Hosseini, M. W.; Skelton, B. W.; White, A. H. Inorg. Chem. 2001, 40, 672. 5. Bilyk, A.; Dunlop, J. W.; Fuller, R. O.; Hall, A. K.; Harrowfield, J. M.; Hosseini, M. W.; Koutsantonis, G. A.; Murray, I. W.; Skelton, B. W.; Sobolev, A. N.; Stamps, R. L.; White, A. H. Eur. J. Inorg. Chem. 2010, 2127.
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