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Anion recognition by calix[4]arene-based p-nitrophenyl amides
Tetrahedron Letters 53 (2012) 678–680
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Anion recognition by calix[4]arene-based p-nitrophenyl amides Karolína Flídrová a, Marcela Tkadlecová b, Kamil Lang c, Pavel Lhoták a,⇑ a b c
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic Department of Physical Chemistry, Prague Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic Institute of Inorganic Chemistry of the Academy of Sciences of the Czech Republic, v.v.i., 250 68 Rˇezˇ, Czech Republic
a r t i c l e
i n f o
Article history: Received 11 October 2011 Revised 16 November 2011 Accepted 25 November 2011 Available online 2 December 2011 Keywords: Calixarenes Anion recognition Receptor Complexation UV/Vis titration
a b s t r a c t Calix[4]arene derivatives immobilised in the cone conformation and bearing p-nitrophenyl moieties appended to the upper rim via the amide functions have been synthesised and applied as anion receptors. The 1H NMR and UV/Vis complexation studies towards selected anions proved that the complexation ability depends considerably on the substitution pattern of the calixarene core. Thus, the proximal diamide derivative has a complexation constant for H2 PO4 by one order of magnitude higher than the distal analogue. Ó 2011 Elsevier Ltd. All rights reserved.
Calix[n]arenes,1 macrocyclic molecules with pronounced complexation abilities, are well-known for their significant derivatisation potential. In particular, in the case of calix[4]arene derivatives, the three-dimensional shape can be deliberately tuned using simple alkylation on the lower rim (phenolic oxygens). As a result, four different conformations (atropisomers) can be obtained, that is, cone, partial cone, 1,2-alternate and 1,3-alternate. This unique property of calix[4]arenes makes them perfect candidates for applications in host–guest chemistry where, depending on the substitution pattern, ions or neutral molecules can be trapped/ complexed inside their cavities. Moreover, calix[4]arenes are frequently used as molecular scaffolds in the design of novel receptors as various functional groups can be introduced regioselectively into the macrocyclic skeleton and thereby control the overall geometry (i.e., mutual arrangement and distances in space) of the system. Anion recognition represents one of the most important topics2 in supramolecular chemistry due to the irreplaceable role of anions in various biological systems. Recently, neutral organic molecules capable of highly directional hydrogen bonding interactions were successfully used in the design of novel anion receptors. The incorporation of amidic groups, urea or thiourea moieties3 into the calixarene or thiacalixarene skeleton4 can result in well preorganised systems with good selectivity towards selected anions. During our ongoing research on anion recognition we have prepared many calixarene-based receptors5 bearing urea moieties on ⇑ Corresponding author. Tel.: +420 220 445 055; fax: +420 220 444 288. E-mail addresses: [email protected], [email protected] (P. Lhoták). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.11.127
the upper rim of calixarenes together with chromophoric units enabling visualisation of the complexation. In this Letter, we report the synthesis and complexation behaviour of novel anion receptors based on upper-rim substituted calix[4]arenes bearing amidic functions which are responsible for the recognition and p-nitrophenyl moieties as UV/Vis sensitive subunits. The preparation of the novel anion receptors is depicted in Scheme 1. The starting material, 25,26,27,28-tetrapropoxycalix[4]arene (1), obtained by alkylation of the parent calix[4]arene with PrI/NaH/DMF, was nitrated using NaNO3 in a TFA/acetic acid mixture6 at room temperature. The resulting mixture of monoand dinitro substituted products was separated by column chromatography on silica gel to give the proximal 2a and distal 2b regioisomers in 19% and 21% yields, respectively. Subsequent reduction with SnCl22H2O in hot ethanol led to the amino substituted derivatives7 3a and 3b in 75% and 97% yields, respectively. The corresponding amides were obtained by reaction with p-nitrobenzoyl chloride in THF in the presence of Et3N as base. Stirring the reaction mixture overnight at room temperature followed by work-up gave the amides 4a (86%) and 4b (89%) in high yields.8 The structures of the receptors 4a,b were confirmed by 1H NMR and MS analysis. Both 4a and 4b showed completely identical patterns in ESI MS: a signal at m/z 943.39 (100%), corresponding to the amide complex with a sodium cation [M+Na]+, and another peak at m/z 959.36 (30%) matching with an [M+K]+ complex. The 1H NMR spectrum (CDCl3) of the distal regioisomer 4b showed two doublets (J = 13.5 Hz) due to methylene bridges (4.49 and 3.19 ppm), typical for the cone conformation, while the aromatic singlet at 6.65 ppm confirmed the symmetrical disubstitution of the system.
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R
R
i) O Pr
R
R
+ OO O Pr Pr Pr
O Pr
OO O Pr Pr Pr 1
2a, R = NO2 3a, R = NH2
O Pr
OO O Pr Pr Pr
2b, R = NO2
ii)
3b, R = NH2
ii)
iii) iii) NO2
NO2
NO2
NO2
O NH
HN
O
O
HN
NH
4b
4a O Pr
O
OO O Pr Pr Pr
O Pr
OO O Pr Pr Pr
Scheme 1. Reagents and conditions: (i) NaNO3/TFA-AcOH, rt, 4.5 h, 2a (19%), 2b (21%); (ii) SnCl22H2O/EtOH, reflux, 12 h, 3a (75%), 3b (97%); (iii) p-O2N-C6H4-COCl/Et3N/THF, rt, overnight, 4a (86%), 4b (89%).
The expected splitting pattern of axial hydrogens (three doublets) in 4a collapsed into one unresolved doublet at 4.38 ppm. Fortunately, the multiplet due to the equatorial protons centred at 3.15 ppm confirmed the lower symmetry of the proximal derivative 4a (Cs symmetry) compared with that of 4b (C2v symmetry). The UV/Vis titration experiments9 with selected anions were performed in MeCN and CHCl3. The titrations resulted in welldefined isosbestic points suggesting 1:1 binding stoichiometry (Fig. 1). The stoichiometry could not be confirmed by Job analysis because of the small absorbance changes induced by the complexation. The obtained sets of recorded absorption spectra were analysed by the non-linear least-squares method assuming 1:1 stoichiometry. It is well known that the complexation of neutral receptors bearing amide or ureido functions is based on the hydrogen bonding interactions of –NH– groups with anions. The resulting complexation constants are expected to be solvent-dependent with the highest values for the least competitive solvents (e.g., CHCl3). By contrast, the titrations in acetonitrile always showed higher complexation constants than in chloroform (Table 1). Thus, the receptor 4a binds H2 PO4 anions much more strongly in MeCN 0.6
0.55
0.50 Absorbance
Absorbance
0.5 0.4 0.3
a
0.15
0.2
b
0.20
0
-4
5x10 -1 c / mol L
-3
1x10
0.1 0.0
350
400 450 Wavelength / nm
500
550
Figure 1. UV/Vis titration of 4b (5.4 10 5 M) with AcO in MeCN; arrows show changes due to the increasing concentration of AcO up to 1.22 10 3 M. Inset: Binding isotherms recorded at 340 (a) and 400 (b) nm. The solid line is a global least-squares fit to the experimental data.
Table 1 Complexation constants K [M 1] in MeCN, CHCl3 and DMSO at room temperature (298 K) calculated for the 1:1 stoichiometry
a b
Aniona
Solvent
K (4a)
K (4b)
H2 PO4 H2 PO4 H2 PO4 BzO BzO AcO AcO
DMSO MeCN CHCl3 MeCN CHCl3 MeCN CHCl3
400 ± 60 5300 ± 400 350 ± 120 2500 ± 700 740 ± 30 4200 ± 200 1300 ± 100
—b 390 ± 30 410 ± 60 3200 ± 100 970 ± 40 7200 ± 300 1100 ± 100
Anions were used as tetrabutylammonium salts. No spectral changes observed.
(K = 5300 M 1) than in CHCl3 (K = 350 M 1). A similar trend was also found for benzoate (K = 2500 M 1 vs K = 740 M 1) and acetate anions (K = 4200 M 1 vs K = 1300 M 1). The distal diamide 4b behaved analogously, except with H2 PO4 which had essentially the same affinity toward 4b in both solvents. Dilution experiments carried out with 4a and 4b in CDCl3 revealed a significant shift of the NH signals to a weaker field with increasing concentration of the receptor (Fig. 2a). This indicates the aggregation/dimerisation behaviour of both receptors at higher concentrations. While proximal isomer 4a showed a remarkable 0.5 ppm concentration-induced shift in CDCl3, a similar experiment in CD3CN did not show any changes. In addition, titration of 4a in CDCl3 with MeCN (Fig. 2b) indicated the complexation of acetonitrile itself, most likely within the calixarene cavity (albeit the resulting complexation constant was small, K 1 M 1). Therefore, the observed solvent-dependency of the complexation ability is the result of the interplay of two competitive effects, (i) aggregation of the receptor molecules in CHCl3, and (ii) complexation of solvent molecules by the receptors.10 As follows from Table 1, the complexation abilities of 4a and 4b towards some anions are considerably different. Thus, the distal receptor 4b shows higher complexation constants (KBzO = 3200 M 1 , KAcO = 7200 M 1) for carboxylates than the proximal diamide 4a (KBzO = 2500 M 1, KAcO = 4200 M 1) both in MeCN. On the other hand, the selectivity was completely reversed in the case of H2 PO4 , as the receptor 4a exhibited an almost 14 times higher
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8.1
(a)
8
2.
δ [ppm]
7.9 7.8 7.7 3.
7.6 7.5 0
0.01
0.02 0.03 c [mol·l-1]
4a 4b 0.04 0.05
4.
(b) 5.
6. 7.
8.
Figure 2. (a) Dilution experiments with 4a and 4b in CDCl3 (NH signals); (b) Titration curve of 4a with MeCN in CDCl3 (1H NMR, 298 K, 300 MHz, NH signals).
complexation constant (K = 5300 M 1) than 4b (K = 390 M 1). These differences in behaviour of the distal and proximal receptors 4a and 4b indicate the crucial role of the substitution pattern in the complexation process recently observed for TTF-substituted calix[4] arene analogues.11 In conclusion, the introduction of p-nitrophenyl amidic functions onto the upper rim of calix[4]arene immobilised in the cone conformation led to novel anion receptors. While the proximally disubstituted derivative 4a exhibited stronger complexation of H2 PO4 than the distally substituted analogue 4b, carboxylates (AcO , BzO ) were complexed with reversed preferences. This different complexation behaviour indicates the crucial role of the substitution pattern in the design of novel calix[4]arene-based receptors. Acknowledgements This research was supported by the Czech Science Foundation (Nr. 203/09/0691) and by the Grant Agency of the Academy of Sciences of the Czech Republic (Nr. IAAX08240901). K.F. would like to acknowledge the financial support from specific university research (MSMT No 21/2011).
9.
References and notes 1. For books on calixarenes, see: (a) Gutsche, C. D. In Calixarenes An Introduction 2nd Edition; The Royal Society of Chemistry, Thomas Graham House: Cambridge, 2008; (b)Calixarenes in the Nanoworld; Vicens, J., Harrowfield, J., Backlouti, L., Eds.; Springer: Dordrecht, 2007; (c)Calixarenes 2001; Asfari, Z., Böhmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic Publishers: Dordrecht, 2001; (d)Calixarenes in Action; Mandolini, L., Ungaro, R., Eds.;
10.
11.
Imperial College Press: London, 2000; (e) Gutsche, C. D. Monographs in Supramolecular Chemistry In Calixarenes Revisited; Stoddart, J. F., Ed.; The Royal Society of Chemistry: Cambridge, 1998; Vol. 6,. For recent books and reviews on anion recognition, see: (a) Gale, P. Acc. Chem. Res. 2011, 44, 216–226; (b)Anion Receptor Chemistry; Sessler, J. L., Gale, P. A., Cho, W. S., Eds.; The Royal Society of Chemistry: Cambridge, 2006; (c) Gale, P. A. Coord. Chem. Rev. 2006, 250, 3219–3244; (d) In Structure and Bonding In Recognition of Anions; Vilar, R., Ed.; Springer: Berlin, 2008; Vol. 129, (e) Gale, P. A.; Garcia-Garrido, S. E.; Garric, J. Chem. Soc. Rev. 2008, 37, 151–190; (f) Schottel, B. L.; Chifotides, H. T.; Dunbar, K. R. Chem. Soc. Rev. 2008, 37, 68–83; (g) Schmidtchen, F. P. Chem. Soc. Rev. 2010, 39, 3916–3935. (a) For reviews on calixarene-based anion receptors, see: Calixarenes; Matthews, S. E., Beer, P. D., Eds.; Kluwer Academic Publishers: Dordrecht, 2001; pp 421–439; (b) Lhoták, P. Top. Curr. Chem. 2005, 255, 65–96; (c) Matthews, S. E.; Beer, P. D. Supramol. Chem. 2005, 17, 411–435. For some recent examples of urea-substituted calixarene-based receptors, see: (a) Jeon, N. J.; Ryu, B. J.; Park, K. D.; Lee, Y. J.; Nam, K. C. Bull. Kor. Chem. Soc. 2010, 31, 3809–3811; (b) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am. Chem. Soc. 2006, 128, 8607–8614; (c) Babu, J. N.; Bhalla, V.; Kumar, M.; Mahajan, R. K.; Puri, R. K. Tetrahedron Lett. 2008, 49, 2772–2775; (d) Quinlan, E.; Matthews, S. E.; Gunnlaugsson, T. J. Org. Chem. 2007, 72, 7497–7503; (e) Schazmann, B.; Diamond, D. New J. Chem. 2007, 31, 587–592. (a) Curinová, P.; Pojarova, M.; Budka, J.; Lang, K.; Stibor, I.; Lhoták, P. Tetrahedron 2010, 66, 8047–8050; (b) Curinová, P.; Stibor, I.; Budka, J.; Sykora, J.; Lang, K.; Lhoták, P. New J. Chem. 2009, 33, 612–619; (c) Lhoták, P.; Svoboda, J.; Stibor, I. Tetrahedron 2006, 62, 1253–1257; (d) Stibor, I.; Budka, J.; Michlová, V.; Tkadlecová, M.; Pojarová, M.; Curinová, P.; Lhoták, P. New J. Chem. 2008, 32, 1597–1607; (e) Kroupa, J.; Stibor, I.; Pojarová, M.; Tkadlecová, M.; Lhoták, P. Tetrahedron 2008, 64, 10075–10079. Casnati, A.; Fochi, M.; Minari, P.; Pochini, A.; Reggiani, M.; Ungaro, R. Gazz. Chim. Ital. 1996, 126, 99–106. Kelderman, E.; Derhaeg, L.; Heesink, G. J. T.; Veroom, W.; Engbersen, J. F. J.; Van Hulst, N. F.; Persoons, A.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1992, 31, 1075–1077. 5,11-Bis(4-nitrophenylcarbonylamino)-25,26,27,28-tetrapropoxycalix[4]arene (cone) (4a): A solution of p-nitrobenzoyl chloride (0.30 g, 1.64 mmol) in dry THF (10 ml) was added dropwise to a solution of Et3N (0.23 ml, 1.64 mmol) and 5,11-diamino-derivative 3a (0.27 g, 0.41 mmol) in THF (50 ml). The reaction mixture was stirred at room temperature overnight. Subsequently, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel using CH2Cl2 as eluent to yield the title diamide 4a as a bright orange powder (0.36 g, 89%); mp 179–181 °C. 1H NMR (DMSO-d6, 300 MHz, 298 K): 10.19 (s, 2H, NH), 8.31 (d, 4H, J = 8.5 Hz, ArH), 8.07 (d, 4H, J = 8.5 Hz, ArH), 7.13 (d, 4H, J = 2.1 Hz, ArH), 6.56–6.64 (m, 4H, ArH), 6.43–6.55 (m, 2H, ArH), 4.38 (d, 4H, J = 13.2 Hz, ArCH2Ar, ax.), 3.66–3.82 (m, 8H, OCH2), 3.08–3.22 (m, 4H, ArCH2Ar, eq), 1.80–1.95 (m, 8H, OCH2CH2), 0.95 (t, 12H, J = 7.3 Hz, CH3); 13C NMR (CDCl3, 75.4 MHz, 298 K): d 164.0; 156.0, 154.5, 149.7, 140.8, 136.3, 135.7, 135.1, 131.5, 128.8, 128.7, 128.3, 124.0, 121.8, 121.6, 121.2, 50.9, 31.4, 23.5, 10.3; HRMS (ESI+) m/z for C54H56N4O10 calculated: 920.3996, found: 943.3895 [M+Na]+ (100%), 959.3618 [M+K]+ (30%). IR (KBr) mmax (cm 1): 3295 (NH), 1650 (CO). 5,17-Bis(4-nitrophenylcarbonylamino)-25,26,27,28-tetrapropoxycalix[4]arene (cone) (4b): A solution of p-nitrobenzoyl chloride (0.25 g, 1.36 mmol) in dry THF (10 ml) was added dropwise to a solution of Et3N (0.2 ml, 1.36 mmol) and 5,17-diamino-derivative 3b (0.22 g, 0.34 mmol) in THF (50 ml). The reaction mixture was stirred at room temperature overnight, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel using CH2Cl2 as eluent. The title compound 4b was obtained as a light yellow powder (0.27 g, 86%); mp 293–295 °C. 1H NMR (CDCl3, 300 MHz, 298 K): d 7.99 (d, 4H, J = 8.8 Hz, ArH), 7.72 (d, 4H, J = 8.2, ArH), 7.60 (s, 2H, NH), 6.93 (d, 4H, J = 7.0 Hz, ArH), 6.81 (t, 2H, J = 7.6 Hz, ArH), 6.65 (s, 4H, ArH), 4.49 (d, 4H, J = 13.5 Hz, ArCH2Ar, ax.), 3.97 (t, 4H, J = 7.9 Hz, OCH2), 3.74 (t, 4H, J = 7.0 Hz, OCH2), 3.19 (d, 4H, J = 13.5 Hz, ArCH2Ar, eq), 1.85–2.02 (m, 8H, OCH2CH2), 1.05 (t, 6H, J = 7.6 Hz, CH3), 0.94 (t, 6H, J = 7.3 Hz, CH3); 13C NMR (DMSO-d6, 75.4 MHz, 298 K): d 157.3, 154.2, 140.6, 135.8, 135.4, 130.9, 128.9, 128.3, 123.7, 122.5, 121.6, 31.3, 23.6, 23.3, 10.8, 10.3; HRMS (ESI+) m/z for C54H56N4O10 calculated: 920.3996, found: 943.3858 [M+Na]+ (100%), 959.3597 [M+K]+ (55%). IR (KBr) mmax (cm 1): 3306 (NH), 1639 (CO). Titration experiments: All UV/Vis spectra were measured on a PerkinElmer Lambda 35 spectrometer. Binding experiments were performed at room temperature (298 K) in quartz 10 mm cells. The recorded sets of absorption spectra were globally analysed using the Specfit program (v. 3.0, Spectrum Software Associates) to give the corresponding binding constants. As suggested by a referee, another factor possibly influencing the anion recognition is ion pairing. Obviously, ion-pair interactions are enhanced in less polar chloroform if compared with acetonitrile. Flidrova, K.; Tkadlecova, M.; Lang, K.; Lhotak, P. Dyes Pigments 2011, 92, 668– 673.
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Anion recognition by calix[4]arene-based p-nitrophenyl amides Karolína Flídrová a, Marcela Tkadlecová b, Kamil Lang c, Pavel Lhoták a,⇑ a b c
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic Department of Physical Chemistry, Prague Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic Institute of Inorganic Chemistry of the Academy of Sciences of the Czech Republic, v.v.i., 250 68 Rˇezˇ, Czech Republic
a r t i c l e
i n f o
Article history: Received 11 October 2011 Revised 16 November 2011 Accepted 25 November 2011 Available online 2 December 2011 Keywords: Calixarenes Anion recognition Receptor Complexation UV/Vis titration
a b s t r a c t Calix[4]arene derivatives immobilised in the cone conformation and bearing p-nitrophenyl moieties appended to the upper rim via the amide functions have been synthesised and applied as anion receptors. The 1H NMR and UV/Vis complexation studies towards selected anions proved that the complexation ability depends considerably on the substitution pattern of the calixarene core. Thus, the proximal diamide derivative has a complexation constant for H2 PO4 by one order of magnitude higher than the distal analogue. Ó 2011 Elsevier Ltd. All rights reserved.
Calix[n]arenes,1 macrocyclic molecules with pronounced complexation abilities, are well-known for their significant derivatisation potential. In particular, in the case of calix[4]arene derivatives, the three-dimensional shape can be deliberately tuned using simple alkylation on the lower rim (phenolic oxygens). As a result, four different conformations (atropisomers) can be obtained, that is, cone, partial cone, 1,2-alternate and 1,3-alternate. This unique property of calix[4]arenes makes them perfect candidates for applications in host–guest chemistry where, depending on the substitution pattern, ions or neutral molecules can be trapped/ complexed inside their cavities. Moreover, calix[4]arenes are frequently used as molecular scaffolds in the design of novel receptors as various functional groups can be introduced regioselectively into the macrocyclic skeleton and thereby control the overall geometry (i.e., mutual arrangement and distances in space) of the system. Anion recognition represents one of the most important topics2 in supramolecular chemistry due to the irreplaceable role of anions in various biological systems. Recently, neutral organic molecules capable of highly directional hydrogen bonding interactions were successfully used in the design of novel anion receptors. The incorporation of amidic groups, urea or thiourea moieties3 into the calixarene or thiacalixarene skeleton4 can result in well preorganised systems with good selectivity towards selected anions. During our ongoing research on anion recognition we have prepared many calixarene-based receptors5 bearing urea moieties on ⇑ Corresponding author. Tel.: +420 220 445 055; fax: +420 220 444 288. E-mail addresses: [email protected], [email protected] (P. Lhoták). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.11.127
the upper rim of calixarenes together with chromophoric units enabling visualisation of the complexation. In this Letter, we report the synthesis and complexation behaviour of novel anion receptors based on upper-rim substituted calix[4]arenes bearing amidic functions which are responsible for the recognition and p-nitrophenyl moieties as UV/Vis sensitive subunits. The preparation of the novel anion receptors is depicted in Scheme 1. The starting material, 25,26,27,28-tetrapropoxycalix[4]arene (1), obtained by alkylation of the parent calix[4]arene with PrI/NaH/DMF, was nitrated using NaNO3 in a TFA/acetic acid mixture6 at room temperature. The resulting mixture of monoand dinitro substituted products was separated by column chromatography on silica gel to give the proximal 2a and distal 2b regioisomers in 19% and 21% yields, respectively. Subsequent reduction with SnCl22H2O in hot ethanol led to the amino substituted derivatives7 3a and 3b in 75% and 97% yields, respectively. The corresponding amides were obtained by reaction with p-nitrobenzoyl chloride in THF in the presence of Et3N as base. Stirring the reaction mixture overnight at room temperature followed by work-up gave the amides 4a (86%) and 4b (89%) in high yields.8 The structures of the receptors 4a,b were confirmed by 1H NMR and MS analysis. Both 4a and 4b showed completely identical patterns in ESI MS: a signal at m/z 943.39 (100%), corresponding to the amide complex with a sodium cation [M+Na]+, and another peak at m/z 959.36 (30%) matching with an [M+K]+ complex. The 1H NMR spectrum (CDCl3) of the distal regioisomer 4b showed two doublets (J = 13.5 Hz) due to methylene bridges (4.49 and 3.19 ppm), typical for the cone conformation, while the aromatic singlet at 6.65 ppm confirmed the symmetrical disubstitution of the system.
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R
R
i) O Pr
R
R
+ OO O Pr Pr Pr
O Pr
OO O Pr Pr Pr 1
2a, R = NO2 3a, R = NH2
O Pr
OO O Pr Pr Pr
2b, R = NO2
ii)
3b, R = NH2
ii)
iii) iii) NO2
NO2
NO2
NO2
O NH
HN
O
O
HN
NH
4b
4a O Pr
O
OO O Pr Pr Pr
O Pr
OO O Pr Pr Pr
Scheme 1. Reagents and conditions: (i) NaNO3/TFA-AcOH, rt, 4.5 h, 2a (19%), 2b (21%); (ii) SnCl22H2O/EtOH, reflux, 12 h, 3a (75%), 3b (97%); (iii) p-O2N-C6H4-COCl/Et3N/THF, rt, overnight, 4a (86%), 4b (89%).
The expected splitting pattern of axial hydrogens (three doublets) in 4a collapsed into one unresolved doublet at 4.38 ppm. Fortunately, the multiplet due to the equatorial protons centred at 3.15 ppm confirmed the lower symmetry of the proximal derivative 4a (Cs symmetry) compared with that of 4b (C2v symmetry). The UV/Vis titration experiments9 with selected anions were performed in MeCN and CHCl3. The titrations resulted in welldefined isosbestic points suggesting 1:1 binding stoichiometry (Fig. 1). The stoichiometry could not be confirmed by Job analysis because of the small absorbance changes induced by the complexation. The obtained sets of recorded absorption spectra were analysed by the non-linear least-squares method assuming 1:1 stoichiometry. It is well known that the complexation of neutral receptors bearing amide or ureido functions is based on the hydrogen bonding interactions of –NH– groups with anions. The resulting complexation constants are expected to be solvent-dependent with the highest values for the least competitive solvents (e.g., CHCl3). By contrast, the titrations in acetonitrile always showed higher complexation constants than in chloroform (Table 1). Thus, the receptor 4a binds H2 PO4 anions much more strongly in MeCN 0.6
0.55
0.50 Absorbance
Absorbance
0.5 0.4 0.3
a
0.15
0.2
b
0.20
0
-4
5x10 -1 c / mol L
-3
1x10
0.1 0.0
350
400 450 Wavelength / nm
500
550
Figure 1. UV/Vis titration of 4b (5.4 10 5 M) with AcO in MeCN; arrows show changes due to the increasing concentration of AcO up to 1.22 10 3 M. Inset: Binding isotherms recorded at 340 (a) and 400 (b) nm. The solid line is a global least-squares fit to the experimental data.
Table 1 Complexation constants K [M 1] in MeCN, CHCl3 and DMSO at room temperature (298 K) calculated for the 1:1 stoichiometry
a b
Aniona
Solvent
K (4a)
K (4b)
H2 PO4 H2 PO4 H2 PO4 BzO BzO AcO AcO
DMSO MeCN CHCl3 MeCN CHCl3 MeCN CHCl3
400 ± 60 5300 ± 400 350 ± 120 2500 ± 700 740 ± 30 4200 ± 200 1300 ± 100
—b 390 ± 30 410 ± 60 3200 ± 100 970 ± 40 7200 ± 300 1100 ± 100
Anions were used as tetrabutylammonium salts. No spectral changes observed.
(K = 5300 M 1) than in CHCl3 (K = 350 M 1). A similar trend was also found for benzoate (K = 2500 M 1 vs K = 740 M 1) and acetate anions (K = 4200 M 1 vs K = 1300 M 1). The distal diamide 4b behaved analogously, except with H2 PO4 which had essentially the same affinity toward 4b in both solvents. Dilution experiments carried out with 4a and 4b in CDCl3 revealed a significant shift of the NH signals to a weaker field with increasing concentration of the receptor (Fig. 2a). This indicates the aggregation/dimerisation behaviour of both receptors at higher concentrations. While proximal isomer 4a showed a remarkable 0.5 ppm concentration-induced shift in CDCl3, a similar experiment in CD3CN did not show any changes. In addition, titration of 4a in CDCl3 with MeCN (Fig. 2b) indicated the complexation of acetonitrile itself, most likely within the calixarene cavity (albeit the resulting complexation constant was small, K 1 M 1). Therefore, the observed solvent-dependency of the complexation ability is the result of the interplay of two competitive effects, (i) aggregation of the receptor molecules in CHCl3, and (ii) complexation of solvent molecules by the receptors.10 As follows from Table 1, the complexation abilities of 4a and 4b towards some anions are considerably different. Thus, the distal receptor 4b shows higher complexation constants (KBzO = 3200 M 1 , KAcO = 7200 M 1) for carboxylates than the proximal diamide 4a (KBzO = 2500 M 1, KAcO = 4200 M 1) both in MeCN. On the other hand, the selectivity was completely reversed in the case of H2 PO4 , as the receptor 4a exhibited an almost 14 times higher
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8.1
(a)
8
2.
δ [ppm]
7.9 7.8 7.7 3.
7.6 7.5 0
0.01
0.02 0.03 c [mol·l-1]
4a 4b 0.04 0.05
4.
(b) 5.
6. 7.
8.
Figure 2. (a) Dilution experiments with 4a and 4b in CDCl3 (NH signals); (b) Titration curve of 4a with MeCN in CDCl3 (1H NMR, 298 K, 300 MHz, NH signals).
complexation constant (K = 5300 M 1) than 4b (K = 390 M 1). These differences in behaviour of the distal and proximal receptors 4a and 4b indicate the crucial role of the substitution pattern in the complexation process recently observed for TTF-substituted calix[4] arene analogues.11 In conclusion, the introduction of p-nitrophenyl amidic functions onto the upper rim of calix[4]arene immobilised in the cone conformation led to novel anion receptors. While the proximally disubstituted derivative 4a exhibited stronger complexation of H2 PO4 than the distally substituted analogue 4b, carboxylates (AcO , BzO ) were complexed with reversed preferences. This different complexation behaviour indicates the crucial role of the substitution pattern in the design of novel calix[4]arene-based receptors. Acknowledgements This research was supported by the Czech Science Foundation (Nr. 203/09/0691) and by the Grant Agency of the Academy of Sciences of the Czech Republic (Nr. IAAX08240901). K.F. would like to acknowledge the financial support from specific university research (MSMT No 21/2011).
9.
References and notes 1. For books on calixarenes, see: (a) Gutsche, C. D. In Calixarenes An Introduction 2nd Edition; The Royal Society of Chemistry, Thomas Graham House: Cambridge, 2008; (b)Calixarenes in the Nanoworld; Vicens, J., Harrowfield, J., Backlouti, L., Eds.; Springer: Dordrecht, 2007; (c)Calixarenes 2001; Asfari, Z., Böhmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic Publishers: Dordrecht, 2001; (d)Calixarenes in Action; Mandolini, L., Ungaro, R., Eds.;
10.
11.
Imperial College Press: London, 2000; (e) Gutsche, C. D. Monographs in Supramolecular Chemistry In Calixarenes Revisited; Stoddart, J. F., Ed.; The Royal Society of Chemistry: Cambridge, 1998; Vol. 6,. For recent books and reviews on anion recognition, see: (a) Gale, P. Acc. Chem. Res. 2011, 44, 216–226; (b)Anion Receptor Chemistry; Sessler, J. L., Gale, P. A., Cho, W. S., Eds.; The Royal Society of Chemistry: Cambridge, 2006; (c) Gale, P. A. Coord. Chem. Rev. 2006, 250, 3219–3244; (d) In Structure and Bonding In Recognition of Anions; Vilar, R., Ed.; Springer: Berlin, 2008; Vol. 129, (e) Gale, P. A.; Garcia-Garrido, S. E.; Garric, J. Chem. Soc. Rev. 2008, 37, 151–190; (f) Schottel, B. L.; Chifotides, H. T.; Dunbar, K. R. Chem. Soc. Rev. 2008, 37, 68–83; (g) Schmidtchen, F. P. Chem. Soc. Rev. 2010, 39, 3916–3935. (a) For reviews on calixarene-based anion receptors, see: Calixarenes; Matthews, S. E., Beer, P. D., Eds.; Kluwer Academic Publishers: Dordrecht, 2001; pp 421–439; (b) Lhoták, P. Top. Curr. Chem. 2005, 255, 65–96; (c) Matthews, S. E.; Beer, P. D. Supramol. Chem. 2005, 17, 411–435. For some recent examples of urea-substituted calixarene-based receptors, see: (a) Jeon, N. J.; Ryu, B. J.; Park, K. D.; Lee, Y. J.; Nam, K. C. Bull. Kor. Chem. Soc. 2010, 31, 3809–3811; (b) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am. Chem. Soc. 2006, 128, 8607–8614; (c) Babu, J. N.; Bhalla, V.; Kumar, M.; Mahajan, R. K.; Puri, R. K. Tetrahedron Lett. 2008, 49, 2772–2775; (d) Quinlan, E.; Matthews, S. E.; Gunnlaugsson, T. J. Org. Chem. 2007, 72, 7497–7503; (e) Schazmann, B.; Diamond, D. New J. Chem. 2007, 31, 587–592. (a) Curinová, P.; Pojarova, M.; Budka, J.; Lang, K.; Stibor, I.; Lhoták, P. Tetrahedron 2010, 66, 8047–8050; (b) Curinová, P.; Stibor, I.; Budka, J.; Sykora, J.; Lang, K.; Lhoták, P. New J. Chem. 2009, 33, 612–619; (c) Lhoták, P.; Svoboda, J.; Stibor, I. Tetrahedron 2006, 62, 1253–1257; (d) Stibor, I.; Budka, J.; Michlová, V.; Tkadlecová, M.; Pojarová, M.; Curinová, P.; Lhoták, P. New J. Chem. 2008, 32, 1597–1607; (e) Kroupa, J.; Stibor, I.; Pojarová, M.; Tkadlecová, M.; Lhoták, P. Tetrahedron 2008, 64, 10075–10079. Casnati, A.; Fochi, M.; Minari, P.; Pochini, A.; Reggiani, M.; Ungaro, R. Gazz. Chim. Ital. 1996, 126, 99–106. Kelderman, E.; Derhaeg, L.; Heesink, G. J. T.; Veroom, W.; Engbersen, J. F. J.; Van Hulst, N. F.; Persoons, A.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1992, 31, 1075–1077. 5,11-Bis(4-nitrophenylcarbonylamino)-25,26,27,28-tetrapropoxycalix[4]arene (cone) (4a): A solution of p-nitrobenzoyl chloride (0.30 g, 1.64 mmol) in dry THF (10 ml) was added dropwise to a solution of Et3N (0.23 ml, 1.64 mmol) and 5,11-diamino-derivative 3a (0.27 g, 0.41 mmol) in THF (50 ml). The reaction mixture was stirred at room temperature overnight. Subsequently, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel using CH2Cl2 as eluent to yield the title diamide 4a as a bright orange powder (0.36 g, 89%); mp 179–181 °C. 1H NMR (DMSO-d6, 300 MHz, 298 K): 10.19 (s, 2H, NH), 8.31 (d, 4H, J = 8.5 Hz, ArH), 8.07 (d, 4H, J = 8.5 Hz, ArH), 7.13 (d, 4H, J = 2.1 Hz, ArH), 6.56–6.64 (m, 4H, ArH), 6.43–6.55 (m, 2H, ArH), 4.38 (d, 4H, J = 13.2 Hz, ArCH2Ar, ax.), 3.66–3.82 (m, 8H, OCH2), 3.08–3.22 (m, 4H, ArCH2Ar, eq), 1.80–1.95 (m, 8H, OCH2CH2), 0.95 (t, 12H, J = 7.3 Hz, CH3); 13C NMR (CDCl3, 75.4 MHz, 298 K): d 164.0; 156.0, 154.5, 149.7, 140.8, 136.3, 135.7, 135.1, 131.5, 128.8, 128.7, 128.3, 124.0, 121.8, 121.6, 121.2, 50.9, 31.4, 23.5, 10.3; HRMS (ESI+) m/z for C54H56N4O10 calculated: 920.3996, found: 943.3895 [M+Na]+ (100%), 959.3618 [M+K]+ (30%). IR (KBr) mmax (cm 1): 3295 (NH), 1650 (CO). 5,17-Bis(4-nitrophenylcarbonylamino)-25,26,27,28-tetrapropoxycalix[4]arene (cone) (4b): A solution of p-nitrobenzoyl chloride (0.25 g, 1.36 mmol) in dry THF (10 ml) was added dropwise to a solution of Et3N (0.2 ml, 1.36 mmol) and 5,17-diamino-derivative 3b (0.22 g, 0.34 mmol) in THF (50 ml). The reaction mixture was stirred at room temperature overnight, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel using CH2Cl2 as eluent. The title compound 4b was obtained as a light yellow powder (0.27 g, 86%); mp 293–295 °C. 1H NMR (CDCl3, 300 MHz, 298 K): d 7.99 (d, 4H, J = 8.8 Hz, ArH), 7.72 (d, 4H, J = 8.2, ArH), 7.60 (s, 2H, NH), 6.93 (d, 4H, J = 7.0 Hz, ArH), 6.81 (t, 2H, J = 7.6 Hz, ArH), 6.65 (s, 4H, ArH), 4.49 (d, 4H, J = 13.5 Hz, ArCH2Ar, ax.), 3.97 (t, 4H, J = 7.9 Hz, OCH2), 3.74 (t, 4H, J = 7.0 Hz, OCH2), 3.19 (d, 4H, J = 13.5 Hz, ArCH2Ar, eq), 1.85–2.02 (m, 8H, OCH2CH2), 1.05 (t, 6H, J = 7.6 Hz, CH3), 0.94 (t, 6H, J = 7.3 Hz, CH3); 13C NMR (DMSO-d6, 75.4 MHz, 298 K): d 157.3, 154.2, 140.6, 135.8, 135.4, 130.9, 128.9, 128.3, 123.7, 122.5, 121.6, 31.3, 23.6, 23.3, 10.8, 10.3; HRMS (ESI+) m/z for C54H56N4O10 calculated: 920.3996, found: 943.3858 [M+Na]+ (100%), 959.3597 [M+K]+ (55%). IR (KBr) mmax (cm 1): 3306 (NH), 1639 (CO). Titration experiments: All UV/Vis spectra were measured on a PerkinElmer Lambda 35 spectrometer. Binding experiments were performed at room temperature (298 K) in quartz 10 mm cells. The recorded sets of absorption spectra were globally analysed using the Specfit program (v. 3.0, Spectrum Software Associates) to give the corresponding binding constants. As suggested by a referee, another factor possibly influencing the anion recognition is ion pairing. Obviously, ion-pair interactions are enhanced in less polar chloroform if compared with acetonitrile. Flidrova, K.; Tkadlecova, M.; Lang, K.; Lhotak, P. Dyes Pigments 2011, 92, 668– 673.