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Synthesis, crystal structure and dynamic behavior of naphthalene-based calix[3]amide: Cyclic trimers of 2-alkylamino-6-naphthoic acid
Journal of Molecular Structure 891 (2008) 346–350
Contents lists available at ScienceDirect
Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc
Synthesis, crystal structure and dynamic behavior of naphthalene-based calix[3]amide: Cyclic trimers of 2-alkylamino-6-naphthoic acid Kosuke Katagiri, Kanako Sawano, Miho Okada, Shiho Yoshiyasu, Reiko Shiroyama, Norio Ikejima, Hyuma Masu, Takako Kato, Masahide Tominaga, Isao Azumaya * Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
a r t i c l e
i n f o
Article history: Received 6 February 2008 Received in revised form 2 April 2008 Accepted 7 April 2008 Available online 22 April 2008 Keywords: Naphthalene-based calix[3]amide Cyclic trimer Aromatic amide Channel structure Syn/anti conformation
a b s t r a c t Treatment of 6-amino-2-naphthoic acid with dichlorotriphenylphosphorane afforded a new naphthalene ring-based calix[3]amide in moderate yield. The macrocyclic calix[3]amide exists in an anti-form in the crystalline state and forms a channel structure along its b axis. In CDCl3 solution it exists in equilibrium between the syn- and anti-forms in solution (100:57). The energy barrier between the anti- to syn-forms was calculated to be 17.8 ± 0.2 kcal/mol. Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
2. Experimental
Cyclic oligomers containing a cavity are frequently used to design compounds having molecular recognition abilities. Calixarenes [1,2] and cyclodextrins [3,4] which are constructed from a repeating monomer unit are extensively studied examples of such cyclic oligomers. These particular macrocyclic oligomers can easily be synthesized by single step reactions from an appropriate monomer. In the course of our study on the stereochemistry of aromatic amides, [5–14] we found that a novel class of macrocyclic compounds, ‘‘calixamides,” were easily obtained by treatment of alkylaminobenzoic acids with dichlorotriphenylphosphorane, as a result of the observation that tertiary aromatic amides preferably exist in their cis conformations. Cyclic trimers (‘‘calix[3]amides”) were the major compounds in the condensation reactions of p(alkylamino)- and m-(alkylamino)benzoic acids, respectively [15]. Based on this finding, larger macrocyclic calixamides having larger cavities are expected to be obtained by condensation of monomers having larger dimensions. Here we report the synthesis and the crystal structure of a naphthalene ring-based analogue of calix[3]amide. The dynamic behavior of these new cyclic amides was also studied by variable temperature NMR measurement.
2.1. General procedure Melting points were determined by using an ATM-01 (AS ONE). H NMR and 13C NMR spectra were performed on a Bruker Avance 400 spectrometer (400 MHz) at 298 K. Low resolution mass spectra was obtained on a JEOL MStation JMS-700 spectrometer, and high resolution mass spectra was obtained on a JEOL AccuTOF JMST100LC mass spectrometer. IR spectra were determined by using a JASCO FT-IR-6300 series spectrometer with ATR PR0410-S. X-ray data were collected on a Bruker SMART ApexII diffractometer. Crystal structures were solved by direct methods SHELXS-97 (Sheldrick, 1996) and were refined by full-matrix least-squares SHELXL-97 (Sheldrick, 1997). All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were included at their calculated positions. Column chromatography was performed by using a Wakogel C200, and thin-layer chromatography was carried out on 0.25 mm Merck precoated silica gel glass plates. Gel Permeation Chromatography (GPC) was performed using recycling preparative HPLC (LC-9204, Japan Analytical Industry Co., Ltd.) and a JAIGEL H series column (Japan Analytical Industry Co., Ltd.). Elemental analyses were within ±0.3% of their theoretical values.
1
2.2. Methyl 6-allylamino-2-naphthoate (3) * Corresponding author. Tel.: +81 87 894 5111; fax: +81 87 894 0181. E-mail address: [email protected] (I. Azumaya). 0022-2860/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2008.04.020
To a solution of methyl 6-amino-2-naphthoate (4.29 g, 23.2 mmol) in HMPA (116 mL) was added allyl bromide (0.98 mL,
K. Katagiri et al. / Journal of Molecular Structure 891 (2008) 346–350
11.6 mmol) with stirring at 80 °C. After 2 h, the reaction mixture was poured into ice and was extracted with AcOEt. The organic layer was washed with 2 N HCl, sat. NaHCO3, brine and dried over Na2SO4. The solvent was evaporated and the remaining HMPA in the residue was removed azeotropically with toluene under reduced pressure. The crude product was purified by silica gel column chromatography (eluent = CHCl3: toluene: NEt3 = 1:6:0.025) to give pure methyl 6-allylamino-2-naphthoate (3) (1.71 g, 61%): pale yellow powder; mp 113–114 °C; 1H NMR (400 MHz, CDCl3) d8.42 (s, 1H), 7.93 (dd, 1H, J = 8.8, 1.6 Hz), 7.71 (d, 1H, J = 8.8 Hz), 7.59 (d, 1H, J = 8.4 Hz), 6.91 (dd, 1H, J = 8.8, 2.4 Hz), 6.79 (s, 1H), 6.00 (m, 1H), 5.33 (dd, 1H, J = 15.6, 1.6 Hz), 5.22 (dd, 1H, J = 10.4, 1.6 Hz), 4.20 (bs, 1H), 3.93 (s, 3H), 3.90 (d, 2H, J = 2.4 Hz); 13C NMR (400 MHz, CDCl3) d167.7, 147.7, 137.8, 134.6, 131.0, 130.6, 126.2, 126.0, 125.8, 123.3, 118.4, 116.8, 104.1, 51.9, 46.2; IR (ATR system in CDCl3) 3377, 2948, 1527, 1621, 1620, 1545 cm 1; MS (FAB) m/z 241 (M+); HRMS (FAB) m/z found 241.1120, Calcd. for C15H16NO2 (M+) m/z 241.1103; Anal. Calcd. for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.48; H, 6.25; N, 5.98. 2.3. 6-Allylamino-2-naphthoic acid (4) To a solution of methyl 6-allylamino-2-naphthoate (1.51 g, 6.27 mmol) in ethanol (47 mL) was added aqueous 4.0 M NaOH (15.7 mL) with stirring, and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled with ice-water bath and was neutralized by aqueous 4.0 M HCl with cooling. The precipitate collected by filtration, was 6-allylamino-2-naphthoic acid (4) (1.22 g, 86%): pale yellow powder; mp 189– 190 °C; 1H NMR (400 MHz, CDCl3 (1% CD3OD)) d8.45 (s, 1H), 7.94 (dd, 1H, J = 8.8, 2.0 Hz), 7.72 (d, 1H, J = 9.2 Hz), 7.60 (d, 1H, J = 8.8 Hz), 6.93 (dd, 1H, J = 8.8, 2.4 Hz), 6.81 (s, 1H), 6.00 (m, 1H), 5.33 (dd, 1H, J = 1.6, 17.2 Hz), 5.22 (dd, 1H, J = 8.8, 1.6 Hz), 3.91 (d, 1H, J = 8.8 Hz); 13C NMR (400 MHz, CDCl3 (1% CD3OD)) d169.7, 147.8, 144.9, 137.9, 134.6, 131.5, 130.6, 126.2, 125.8, 123.0, 118.4, 116.7, 104.0, 46.1; IR (ATR system in CDCl3) 3409, 1675, 1618, 1496 cm 1; MS (FAB) m/z 227 (M+); HRMS (FAB) m/ z found 227.1006, Calcd. for C14H13NO2 (M+) m/z 227.0946; Anal. Calcd. for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.77; H, 5.65; N, 6.18. 2.4. 2,5,8-Triallyl-2,5,8-triaza-1(2,6),4(2,6),7(2,6)trisnaphthalenacyclononaphane-3,6,9-trione (5) To a solution of 6-allylamino-2-natphthoic acid (4) (1.22 g, 5.4 mmol) in 1,1,2,2,-tetrachloroethane (54 mL) under Ar was added dichlorotriphenylphosphorane (4.32 g, 13.0 mmol) with stirring for 6 h at 120 °C. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: CHCl3) to give a mixture of the trimer and a hexamer. The mixture was purified by GPC (JAIGEL, CHCl3) to give trimer 5 as white solid (342 mg, 30%): mp 263–264 °C; 1H NMR (400 MHz, CDCl3): d7.596 (s, 1 H), 7.538 (s, 1H), 7.336–7.408 (m, 4H), 7.303 (s, 1H), 7.277 (d, J = 4 Hz, 1H), 7.233 (d, J = 4 Hz, 1H), 7.188 (dd, J = 2.1, 8.6 Hz, 2H), 7.172 (s, 1H), 7.152 (t, J = 2.3 Hz, 1H), 7.132 (d, J = 1.8 Hz, 1H), 7.100 (m, 1H), 7.068 (dd, J = 2.0, 8.7 Hz, 1H), 6.998 (s, 1H), 6.998 (dd, J = 2.2, 8.7 Hz, 1H), 6.056– 6.003 (m, 3H), 5.231–5.177 (m, 6H), 4.64–4.588 (m, 3H), 4.526– 4.475 (m, 3H); 13C NMR (400 MHz, CDCl3): d213.65, 199.37, 188.65, 171.40, 140.75, 133.01, 129.14, 127.36, 123.19, 119.03, 83.80, 64.57, 52.37, 29.76; IR (CDCl3): 3058, 2919, 1645, 1602 cm 1; FAB-MS m/z 625.23; ESI-HRMS m/z found 648.2260, Calcd. for C42H31N3O3Na m/z 648.2263. Elemental Anal. Calcd. for C42H33N3O3: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.14; H, 5.20; N, 6.63.
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2.5. Hexamer of 6-allylamino-2-naphthoic acid (6) To a solution of 6-allylamino-2-natphthoic acid (4) (1.22 g, 5.4 mmol) in 1,1,2,2,-tetrachloroethane (54 mL) under Ar was added dichlorotriphenylphosphorane (4.32 g, 13.0 mmol) with stirring for 6 h at 120 °C. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: CHCl3) to give a mixture of the trimer and a hexamer. The mixture was purified by GPC (JAIGEL, CHCl3) to give hexamer 6 as white solid (35 mg, 3%): mp >300 °C; 1H NMR (400 MHz, CDCl3): d8.53 (s, 6 H), 8.22–7.25 (m, 24 H), 7.01 (s, 6 H), 5.83–5.71 (m, 6 H), 5.02–4.98 (m, 12 H), 4.33–4.28 (m, 6 H), 4.25–4.16 (m, 6 H); 13C NMR (400 MHz, CDCl3): d210.55, 198.23, 188.54, 170.21, 140.13, 130.20, 124.04, 127.36, 123.01, 117.76, 81.00, 64.55, 52.00, 30.06; IR (CDCl3): 3002, 2900, 1660, 1600 cm 1; FAB-MS m/z 1254.50. 2.6. 2,5,8-Tripropyl-2,5,8-triaza-1(2,6),4(2,6),7(2,6)trisnaphthalenacyclononaphane-3,6,9-trione (7) The Pd/C (34 mg) was added to a suspension of cyclic trimer 5 (342 mg, 0.3 mmol) in ethanol, and the mixture stirred for 10 h under H2 atmosphere. The Pd/C was filtrated and the solvent was removed under reduced pressure. The residue was purified by recrystallization from CHCl3 to give 7 as white solid (131 mg, 70%): mp >300 °C; 1H NMR (400 MHz, CDCl3): d7.302 (s, 1H), 7.288 (s, 1H), 7.230 (m, 4H), 7.198 (m, 4H), 7.121 (m, 6H), 6.997 (s, 2H), 4.033 (m, 3H), 3.834 (m, 3H), 1.701 (br, 6H), 0.989 (t, J = 7.2 Hz, 9H); 13C NMR (400 MHz, CDCl3): d196.09, 179.73, 174.37, 160.09, 138.90, 137.18, 130.33, 127.95, 123.19, 106.83, 99.98, 48.80, 34.22, 24.10; IR (CDCl3): 3058, 2919, 1645, 1602 cm 1; FAB-MS m/z 633.30; ESI-HRMS m/z found 656.2878, Calcd. for C42H39N3O3Na m/z 656.2889. 3. Results and discussion 3.1. Synthesis of calix[3]amides 5 and 7 The synthesis of the naphthalene ring-based cyclic trimer 5 is shown in Scheme 1 [16–20]. After esterification of 6-amino-2naphthoic acid, the resulting methyl 6-amino-2-naphthoate was N-allylated using 0.5 eq. of allyl bromide in HMPA at 80 °C for 2 h to give methyl 6-allylamino-2-naphthoate 3 in 61% yield (based on allyl bromide). 6-Allylamino-2-naphthoic acid 4, which was obtained by hydrolysis of 3, was successfully cyclized using dichlorotriphenylphosphorane in 1,1,2,2-tetrachloroethane at 120 °C to give the cyclic trimer 5 as a major product (30% yield). A cyclic hexamer (6) was also obtained as a by-product but was not fully characterized. The corresponding N-propyl cyclic trimer 7 was synthesized by catalytic hydrogenation of 5 (Scheme 2) because sufficient refinement for the X-ray diffraction data of 5 could not be obtained for crystals of 5 due to the disorder of the N-allyl group. 3.2. Crystal structure of 7 X-ray single crystal analysis was carried out for crystals of 7 (Table 1), which were grown in CHCl3 solution. An ORTEP drawing is shown in Fig. 1. The possible conformations of 7 are syn in which three naphthalene rings are directed to the same sides and anti in which one of the three naphthalene rings is directed to the opposite side. Both conformations have molecular chirality based on the directions of the amide bond and the naphthalene ring (Fig. 2). The molecule in the crystal of 7 exists in the anti conformation and as would be expected, has a larger cavity than that of the corresponding benzene ring-containing calix[3]amide.
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Scheme 1. The synthesis of naphthalene-based cyclic trimer 5.
Scheme 2. Catalytic hydrogenation of 5.
Table 1 Basic crystallographic data, data collection and refinement parameters for 7 Identification code
7
Empirical formula Formula weight Crystal size (mm) Crystal colour Temperature (K) a (Å) b (Å) c (Å) Volume (Å3) Z Calculated density (Mg/m3) Crystal system Space group Absorption coefficient (mm 1) F(0 0 0) Diffractometer and radiation Completeness to theta = 25.00 ° Index range Theta range for data collection (°) Independent reflections Reflections collected Absorption correction Max. and min. transmission Refinement method Goodness-of-fit on F2 Final R indices [I>2sigma(I)] R indices (all data) Largest diff. peak and hole (e Å 3)
C42H39N3O3 633.76 0.45 0.10 0.05 Colourless 90 16.52(1) 13.970(9) 14.84(1) 3424(4) 4 1.230 Orthorhombic Pca2(1) 0.078 1344 Bruker Smart APEX II, MoKa k = 0.71073 Å 99.9% 20 6 h 6 20, 10 6 k 6 17, 18 6 l 6 18 1.46–26.49 7000 [Rint = 0.1011] 17,296 Empirical (SADABS Sheldrick 1997) 0.9961 and 0.9659 Full-matrix least-squares on F2 0.895 R = 0.097, wR = 0.203 R = 0.255, wR = 0.266 0.354 and 0.184
Fig. 1. ORTEP drawing of 7. The hydrogen atoms are omitted for clarity.
K. Katagiri et al. / Journal of Molecular Structure 891 (2008) 346–350
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Fig. 2. Syn and anti conformations of 7.
The packing diagram of 7 is shown in Fig. 3. The crystals belong to space group Pca21. The unit cell has the same number of enantiomeric conformers, resulting in the crystals having no chiral property (the enantiomeric conformers are shown in red and blue, respectively). In this crystal, there are some intermolecular C–HO interactions (C42–H42O1: 2.553 Å, C25–H25O2: 2.533 Å, C28–H28O3: 2.377 Å). Arrangement of the conformers with C–HO interactions of O2 and O3 constructs the same enantiomeric rows along the a axis of the unit cell. The aggregate of single enantiomer align along the b axis to be shown the columnar structure, and both enantiomeric rows align alternately along the c axis. 3.3. Dynamic behavior of 5
Fig. 3. Packing diagram of cyclic amide 7. (a) View along the b axis of a unit cell. (b) View along the a axis.
Two sets of peaks were observed in the 1H NMR spectrum of a single crystal of 5 in CDCl3 at room temperature, showing that the cyclic trimer exists in equilibrium between two conformations in solution. Each of the set of peaks were assigned to the syn or anti conformations due to the symmetrical nature of each conformation and its dynamic properties. The solvent does not have any significant effect on the syn/anti conformation ratio, which was decided by the integration of the aryl peaks (the ratio of syn/anti was 100:57 in CDCl3, 100:53 in CD3OD, 100:55 in C6D6, 100:51 in (CDCl2)2 or 100:46 in CD3CN at room temperature). The two sets of peaks at room temperature were broad but coalesced as the temperature was raised (the coalescence point of N–CH2 was 363 K, Fig. 4). The energy barrier (17.8 ± 0.2 kcal mol 1) was calculated from the coalescence point and the chemical shift difference of the N–CH2 peaks, [21] corre-
Fig. 4. Dynamic 1H NMR of 5 in (CDCl2)2.
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sponding to the rotational barrier of naphthalene ring; i.e., the barrier of the conversion from syn to anti. 4. Conclusions A new calix[3]amide having a naphthalene ring backbone was effectively synthesized by a reaction with just a few-steps from the commercially available 2-amino-6-naphthoic acid. The macrocycle existed in the anti conformation in the solid state with as would be expected, a larger cavity than that of the benzene ring-based calix[3]amide. In solution this trimer was shown to exist in equilibrium between its syn and anti conformations. Furthermore, the conformers with same enantiomer were aggregated along the ab plane, and both enantiomeric rows are alternately aligned along the c axis. We postulate that the macrocycle can be used as a host molecule with potential molecular recognition abilities and as a new building block molecule to construct a useful network structures. We are now exploring diversification and the potential metal coordination by this new class of macrocycle. Supplementary data Additional material comprising full details of the X-ray data collection and final refinement parameters including anisotropic thermal parameters and full list of the bond lengths and angles have been deposited with the Cambridge Crystallographic Data Center in the CIF format as supplementary Publication Nos. CCDC 675496. Copies of the data can be obtained free of charge on the application to CCDC, 12 Union Road, Cambridge, CB21EZ, UK, (fax: +44 1223 336 033; email: [email protected]).
Acknowledgement This work was supported by a Grant-in-Aid for Young Scientists (Start-up), Japan (No. 18890226) (K.K.). References [1] C.D. Gutsche, Acc. Chem. Res. 16 (1983) 161. [2] C.D. Gutsche, Pure Appl. Chem. 62 (1990) 385. [3] M.L. Bender, M. Komiyama, Cyclodextrin Chemistry, Springer-Verlag, Berlin, 1978. [4] M. Komiyama, M.L. Bender, New Comprehens. Biochem. 6 (1984) 505–527. [5] V.T. D’Souza, M.L. Bender, Acc. Chem. Res. 20 (1987) 146. [6] H. Kagechika, T. Himi, E. Kawachi, Y. Hashimoto, K. Shudo, J. Med. Chem. 32 (1989) 2292. [7] K. Yamaguchi, K. Shudo, J. Agric. Food Chem. 39 (1991) 793. [8] A. Itai, Y. Toriumi, N. Tomioka, H. Kagechika, I. Azumaya, K. Shudo, Tetrahedron Lett. 30 (1989) 6177. [9] I. Azumaya, H. Kagechika, Y. Fujiwara, M. Itoh, K. Yamaguchi, K. Shudo, J. Am. Chem. Soc. 113 (1991) 2833. [10] K. Yamaguchi, G. Matsumura, H. Kagechika, I. Azumaya, Y. Ito, A. Itai, et al., J. Am. Chem. Soc. 113 (1991) 5474. [11] A. Itai, Y. Toriumi, S. Saito, H. Kagechika, K. Shudo, J. Am. Chem. Soc. 114 (1992) 10649. [12] S. Saito, Y. Toriumi, N. Tomioka, A. Itai, J. Org. Chem. 60 (1995) 4715. [13] I. Azumaya, H. Kagechika, K. Yamaguchi, K. Shudo, Tetrahedron 51 (1995) 5277. [14] A. Tanatani, K. Yamaguchi, I. Azumaya, R. Fukutomi, K. Shudo, H. Kagechika, J. Am. Chem. Soc. 120 (1998) 6433. [15] I. Azumaya, T. Okamoto, F. Imabeppu, H. Takayanagi, Tetrahedron 59 (2003) 2325. [16] P.E. Georghiou, Z. Li, Tetrahedron Lett. 34 (1993) 2887. [17] B.J. Shorthill, T.E. Glass, Org. Lett. 3 (2001) 577. [18] S. Mizyed, M. Ashram, D.O. Miller, P.E. Georghiou, J. Chem. Soc. Perkin Trans. 2 (2001) 1916. [19] P.E. Georghiou, Z. Li, M. Ashram, S. Chowdhury, S. Mizyed, A.H. Tran, et al., Synlett 6 (2005) 879. [20] A.H. Tran, D.O. Miller, P.E. Georghiou, J. Org. Chem. 70 (2005) 1115. [21] M. Oki, Applications of Dynamic NMR Spectroscopy to Organic Chemistry, VCH Publishers Inc., Florida, 1985.
Contents lists available at ScienceDirect
Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc
Synthesis, crystal structure and dynamic behavior of naphthalene-based calix[3]amide: Cyclic trimers of 2-alkylamino-6-naphthoic acid Kosuke Katagiri, Kanako Sawano, Miho Okada, Shiho Yoshiyasu, Reiko Shiroyama, Norio Ikejima, Hyuma Masu, Takako Kato, Masahide Tominaga, Isao Azumaya * Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
a r t i c l e
i n f o
Article history: Received 6 February 2008 Received in revised form 2 April 2008 Accepted 7 April 2008 Available online 22 April 2008 Keywords: Naphthalene-based calix[3]amide Cyclic trimer Aromatic amide Channel structure Syn/anti conformation
a b s t r a c t Treatment of 6-amino-2-naphthoic acid with dichlorotriphenylphosphorane afforded a new naphthalene ring-based calix[3]amide in moderate yield. The macrocyclic calix[3]amide exists in an anti-form in the crystalline state and forms a channel structure along its b axis. In CDCl3 solution it exists in equilibrium between the syn- and anti-forms in solution (100:57). The energy barrier between the anti- to syn-forms was calculated to be 17.8 ± 0.2 kcal/mol. Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
2. Experimental
Cyclic oligomers containing a cavity are frequently used to design compounds having molecular recognition abilities. Calixarenes [1,2] and cyclodextrins [3,4] which are constructed from a repeating monomer unit are extensively studied examples of such cyclic oligomers. These particular macrocyclic oligomers can easily be synthesized by single step reactions from an appropriate monomer. In the course of our study on the stereochemistry of aromatic amides, [5–14] we found that a novel class of macrocyclic compounds, ‘‘calixamides,” were easily obtained by treatment of alkylaminobenzoic acids with dichlorotriphenylphosphorane, as a result of the observation that tertiary aromatic amides preferably exist in their cis conformations. Cyclic trimers (‘‘calix[3]amides”) were the major compounds in the condensation reactions of p(alkylamino)- and m-(alkylamino)benzoic acids, respectively [15]. Based on this finding, larger macrocyclic calixamides having larger cavities are expected to be obtained by condensation of monomers having larger dimensions. Here we report the synthesis and the crystal structure of a naphthalene ring-based analogue of calix[3]amide. The dynamic behavior of these new cyclic amides was also studied by variable temperature NMR measurement.
2.1. General procedure Melting points were determined by using an ATM-01 (AS ONE). H NMR and 13C NMR spectra were performed on a Bruker Avance 400 spectrometer (400 MHz) at 298 K. Low resolution mass spectra was obtained on a JEOL MStation JMS-700 spectrometer, and high resolution mass spectra was obtained on a JEOL AccuTOF JMST100LC mass spectrometer. IR spectra were determined by using a JASCO FT-IR-6300 series spectrometer with ATR PR0410-S. X-ray data were collected on a Bruker SMART ApexII diffractometer. Crystal structures were solved by direct methods SHELXS-97 (Sheldrick, 1996) and were refined by full-matrix least-squares SHELXL-97 (Sheldrick, 1997). All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were included at their calculated positions. Column chromatography was performed by using a Wakogel C200, and thin-layer chromatography was carried out on 0.25 mm Merck precoated silica gel glass plates. Gel Permeation Chromatography (GPC) was performed using recycling preparative HPLC (LC-9204, Japan Analytical Industry Co., Ltd.) and a JAIGEL H series column (Japan Analytical Industry Co., Ltd.). Elemental analyses were within ±0.3% of their theoretical values.
1
2.2. Methyl 6-allylamino-2-naphthoate (3) * Corresponding author. Tel.: +81 87 894 5111; fax: +81 87 894 0181. E-mail address: [email protected] (I. Azumaya). 0022-2860/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2008.04.020
To a solution of methyl 6-amino-2-naphthoate (4.29 g, 23.2 mmol) in HMPA (116 mL) was added allyl bromide (0.98 mL,
K. Katagiri et al. / Journal of Molecular Structure 891 (2008) 346–350
11.6 mmol) with stirring at 80 °C. After 2 h, the reaction mixture was poured into ice and was extracted with AcOEt. The organic layer was washed with 2 N HCl, sat. NaHCO3, brine and dried over Na2SO4. The solvent was evaporated and the remaining HMPA in the residue was removed azeotropically with toluene under reduced pressure. The crude product was purified by silica gel column chromatography (eluent = CHCl3: toluene: NEt3 = 1:6:0.025) to give pure methyl 6-allylamino-2-naphthoate (3) (1.71 g, 61%): pale yellow powder; mp 113–114 °C; 1H NMR (400 MHz, CDCl3) d8.42 (s, 1H), 7.93 (dd, 1H, J = 8.8, 1.6 Hz), 7.71 (d, 1H, J = 8.8 Hz), 7.59 (d, 1H, J = 8.4 Hz), 6.91 (dd, 1H, J = 8.8, 2.4 Hz), 6.79 (s, 1H), 6.00 (m, 1H), 5.33 (dd, 1H, J = 15.6, 1.6 Hz), 5.22 (dd, 1H, J = 10.4, 1.6 Hz), 4.20 (bs, 1H), 3.93 (s, 3H), 3.90 (d, 2H, J = 2.4 Hz); 13C NMR (400 MHz, CDCl3) d167.7, 147.7, 137.8, 134.6, 131.0, 130.6, 126.2, 126.0, 125.8, 123.3, 118.4, 116.8, 104.1, 51.9, 46.2; IR (ATR system in CDCl3) 3377, 2948, 1527, 1621, 1620, 1545 cm 1; MS (FAB) m/z 241 (M+); HRMS (FAB) m/z found 241.1120, Calcd. for C15H16NO2 (M+) m/z 241.1103; Anal. Calcd. for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.48; H, 6.25; N, 5.98. 2.3. 6-Allylamino-2-naphthoic acid (4) To a solution of methyl 6-allylamino-2-naphthoate (1.51 g, 6.27 mmol) in ethanol (47 mL) was added aqueous 4.0 M NaOH (15.7 mL) with stirring, and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled with ice-water bath and was neutralized by aqueous 4.0 M HCl with cooling. The precipitate collected by filtration, was 6-allylamino-2-naphthoic acid (4) (1.22 g, 86%): pale yellow powder; mp 189– 190 °C; 1H NMR (400 MHz, CDCl3 (1% CD3OD)) d8.45 (s, 1H), 7.94 (dd, 1H, J = 8.8, 2.0 Hz), 7.72 (d, 1H, J = 9.2 Hz), 7.60 (d, 1H, J = 8.8 Hz), 6.93 (dd, 1H, J = 8.8, 2.4 Hz), 6.81 (s, 1H), 6.00 (m, 1H), 5.33 (dd, 1H, J = 1.6, 17.2 Hz), 5.22 (dd, 1H, J = 8.8, 1.6 Hz), 3.91 (d, 1H, J = 8.8 Hz); 13C NMR (400 MHz, CDCl3 (1% CD3OD)) d169.7, 147.8, 144.9, 137.9, 134.6, 131.5, 130.6, 126.2, 125.8, 123.0, 118.4, 116.7, 104.0, 46.1; IR (ATR system in CDCl3) 3409, 1675, 1618, 1496 cm 1; MS (FAB) m/z 227 (M+); HRMS (FAB) m/ z found 227.1006, Calcd. for C14H13NO2 (M+) m/z 227.0946; Anal. Calcd. for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.77; H, 5.65; N, 6.18. 2.4. 2,5,8-Triallyl-2,5,8-triaza-1(2,6),4(2,6),7(2,6)trisnaphthalenacyclononaphane-3,6,9-trione (5) To a solution of 6-allylamino-2-natphthoic acid (4) (1.22 g, 5.4 mmol) in 1,1,2,2,-tetrachloroethane (54 mL) under Ar was added dichlorotriphenylphosphorane (4.32 g, 13.0 mmol) with stirring for 6 h at 120 °C. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: CHCl3) to give a mixture of the trimer and a hexamer. The mixture was purified by GPC (JAIGEL, CHCl3) to give trimer 5 as white solid (342 mg, 30%): mp 263–264 °C; 1H NMR (400 MHz, CDCl3): d7.596 (s, 1 H), 7.538 (s, 1H), 7.336–7.408 (m, 4H), 7.303 (s, 1H), 7.277 (d, J = 4 Hz, 1H), 7.233 (d, J = 4 Hz, 1H), 7.188 (dd, J = 2.1, 8.6 Hz, 2H), 7.172 (s, 1H), 7.152 (t, J = 2.3 Hz, 1H), 7.132 (d, J = 1.8 Hz, 1H), 7.100 (m, 1H), 7.068 (dd, J = 2.0, 8.7 Hz, 1H), 6.998 (s, 1H), 6.998 (dd, J = 2.2, 8.7 Hz, 1H), 6.056– 6.003 (m, 3H), 5.231–5.177 (m, 6H), 4.64–4.588 (m, 3H), 4.526– 4.475 (m, 3H); 13C NMR (400 MHz, CDCl3): d213.65, 199.37, 188.65, 171.40, 140.75, 133.01, 129.14, 127.36, 123.19, 119.03, 83.80, 64.57, 52.37, 29.76; IR (CDCl3): 3058, 2919, 1645, 1602 cm 1; FAB-MS m/z 625.23; ESI-HRMS m/z found 648.2260, Calcd. for C42H31N3O3Na m/z 648.2263. Elemental Anal. Calcd. for C42H33N3O3: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.14; H, 5.20; N, 6.63.
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2.5. Hexamer of 6-allylamino-2-naphthoic acid (6) To a solution of 6-allylamino-2-natphthoic acid (4) (1.22 g, 5.4 mmol) in 1,1,2,2,-tetrachloroethane (54 mL) under Ar was added dichlorotriphenylphosphorane (4.32 g, 13.0 mmol) with stirring for 6 h at 120 °C. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: CHCl3) to give a mixture of the trimer and a hexamer. The mixture was purified by GPC (JAIGEL, CHCl3) to give hexamer 6 as white solid (35 mg, 3%): mp >300 °C; 1H NMR (400 MHz, CDCl3): d8.53 (s, 6 H), 8.22–7.25 (m, 24 H), 7.01 (s, 6 H), 5.83–5.71 (m, 6 H), 5.02–4.98 (m, 12 H), 4.33–4.28 (m, 6 H), 4.25–4.16 (m, 6 H); 13C NMR (400 MHz, CDCl3): d210.55, 198.23, 188.54, 170.21, 140.13, 130.20, 124.04, 127.36, 123.01, 117.76, 81.00, 64.55, 52.00, 30.06; IR (CDCl3): 3002, 2900, 1660, 1600 cm 1; FAB-MS m/z 1254.50. 2.6. 2,5,8-Tripropyl-2,5,8-triaza-1(2,6),4(2,6),7(2,6)trisnaphthalenacyclononaphane-3,6,9-trione (7) The Pd/C (34 mg) was added to a suspension of cyclic trimer 5 (342 mg, 0.3 mmol) in ethanol, and the mixture stirred for 10 h under H2 atmosphere. The Pd/C was filtrated and the solvent was removed under reduced pressure. The residue was purified by recrystallization from CHCl3 to give 7 as white solid (131 mg, 70%): mp >300 °C; 1H NMR (400 MHz, CDCl3): d7.302 (s, 1H), 7.288 (s, 1H), 7.230 (m, 4H), 7.198 (m, 4H), 7.121 (m, 6H), 6.997 (s, 2H), 4.033 (m, 3H), 3.834 (m, 3H), 1.701 (br, 6H), 0.989 (t, J = 7.2 Hz, 9H); 13C NMR (400 MHz, CDCl3): d196.09, 179.73, 174.37, 160.09, 138.90, 137.18, 130.33, 127.95, 123.19, 106.83, 99.98, 48.80, 34.22, 24.10; IR (CDCl3): 3058, 2919, 1645, 1602 cm 1; FAB-MS m/z 633.30; ESI-HRMS m/z found 656.2878, Calcd. for C42H39N3O3Na m/z 656.2889. 3. Results and discussion 3.1. Synthesis of calix[3]amides 5 and 7 The synthesis of the naphthalene ring-based cyclic trimer 5 is shown in Scheme 1 [16–20]. After esterification of 6-amino-2naphthoic acid, the resulting methyl 6-amino-2-naphthoate was N-allylated using 0.5 eq. of allyl bromide in HMPA at 80 °C for 2 h to give methyl 6-allylamino-2-naphthoate 3 in 61% yield (based on allyl bromide). 6-Allylamino-2-naphthoic acid 4, which was obtained by hydrolysis of 3, was successfully cyclized using dichlorotriphenylphosphorane in 1,1,2,2-tetrachloroethane at 120 °C to give the cyclic trimer 5 as a major product (30% yield). A cyclic hexamer (6) was also obtained as a by-product but was not fully characterized. The corresponding N-propyl cyclic trimer 7 was synthesized by catalytic hydrogenation of 5 (Scheme 2) because sufficient refinement for the X-ray diffraction data of 5 could not be obtained for crystals of 5 due to the disorder of the N-allyl group. 3.2. Crystal structure of 7 X-ray single crystal analysis was carried out for crystals of 7 (Table 1), which were grown in CHCl3 solution. An ORTEP drawing is shown in Fig. 1. The possible conformations of 7 are syn in which three naphthalene rings are directed to the same sides and anti in which one of the three naphthalene rings is directed to the opposite side. Both conformations have molecular chirality based on the directions of the amide bond and the naphthalene ring (Fig. 2). The molecule in the crystal of 7 exists in the anti conformation and as would be expected, has a larger cavity than that of the corresponding benzene ring-containing calix[3]amide.
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Scheme 1. The synthesis of naphthalene-based cyclic trimer 5.
Scheme 2. Catalytic hydrogenation of 5.
Table 1 Basic crystallographic data, data collection and refinement parameters for 7 Identification code
7
Empirical formula Formula weight Crystal size (mm) Crystal colour Temperature (K) a (Å) b (Å) c (Å) Volume (Å3) Z Calculated density (Mg/m3) Crystal system Space group Absorption coefficient (mm 1) F(0 0 0) Diffractometer and radiation Completeness to theta = 25.00 ° Index range Theta range for data collection (°) Independent reflections Reflections collected Absorption correction Max. and min. transmission Refinement method Goodness-of-fit on F2 Final R indices [I>2sigma(I)] R indices (all data) Largest diff. peak and hole (e Å 3)
C42H39N3O3 633.76 0.45 0.10 0.05 Colourless 90 16.52(1) 13.970(9) 14.84(1) 3424(4) 4 1.230 Orthorhombic Pca2(1) 0.078 1344 Bruker Smart APEX II, MoKa k = 0.71073 Å 99.9% 20 6 h 6 20, 10 6 k 6 17, 18 6 l 6 18 1.46–26.49 7000 [Rint = 0.1011] 17,296 Empirical (SADABS Sheldrick 1997) 0.9961 and 0.9659 Full-matrix least-squares on F2 0.895 R = 0.097, wR = 0.203 R = 0.255, wR = 0.266 0.354 and 0.184
Fig. 1. ORTEP drawing of 7. The hydrogen atoms are omitted for clarity.
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Fig. 2. Syn and anti conformations of 7.
The packing diagram of 7 is shown in Fig. 3. The crystals belong to space group Pca21. The unit cell has the same number of enantiomeric conformers, resulting in the crystals having no chiral property (the enantiomeric conformers are shown in red and blue, respectively). In this crystal, there are some intermolecular C–HO interactions (C42–H42O1: 2.553 Å, C25–H25O2: 2.533 Å, C28–H28O3: 2.377 Å). Arrangement of the conformers with C–HO interactions of O2 and O3 constructs the same enantiomeric rows along the a axis of the unit cell. The aggregate of single enantiomer align along the b axis to be shown the columnar structure, and both enantiomeric rows align alternately along the c axis. 3.3. Dynamic behavior of 5
Fig. 3. Packing diagram of cyclic amide 7. (a) View along the b axis of a unit cell. (b) View along the a axis.
Two sets of peaks were observed in the 1H NMR spectrum of a single crystal of 5 in CDCl3 at room temperature, showing that the cyclic trimer exists in equilibrium between two conformations in solution. Each of the set of peaks were assigned to the syn or anti conformations due to the symmetrical nature of each conformation and its dynamic properties. The solvent does not have any significant effect on the syn/anti conformation ratio, which was decided by the integration of the aryl peaks (the ratio of syn/anti was 100:57 in CDCl3, 100:53 in CD3OD, 100:55 in C6D6, 100:51 in (CDCl2)2 or 100:46 in CD3CN at room temperature). The two sets of peaks at room temperature were broad but coalesced as the temperature was raised (the coalescence point of N–CH2 was 363 K, Fig. 4). The energy barrier (17.8 ± 0.2 kcal mol 1) was calculated from the coalescence point and the chemical shift difference of the N–CH2 peaks, [21] corre-
Fig. 4. Dynamic 1H NMR of 5 in (CDCl2)2.
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sponding to the rotational barrier of naphthalene ring; i.e., the barrier of the conversion from syn to anti. 4. Conclusions A new calix[3]amide having a naphthalene ring backbone was effectively synthesized by a reaction with just a few-steps from the commercially available 2-amino-6-naphthoic acid. The macrocycle existed in the anti conformation in the solid state with as would be expected, a larger cavity than that of the benzene ring-based calix[3]amide. In solution this trimer was shown to exist in equilibrium between its syn and anti conformations. Furthermore, the conformers with same enantiomer were aggregated along the ab plane, and both enantiomeric rows are alternately aligned along the c axis. We postulate that the macrocycle can be used as a host molecule with potential molecular recognition abilities and as a new building block molecule to construct a useful network structures. We are now exploring diversification and the potential metal coordination by this new class of macrocycle. Supplementary data Additional material comprising full details of the X-ray data collection and final refinement parameters including anisotropic thermal parameters and full list of the bond lengths and angles have been deposited with the Cambridge Crystallographic Data Center in the CIF format as supplementary Publication Nos. CCDC 675496. Copies of the data can be obtained free of charge on the application to CCDC, 12 Union Road, Cambridge, CB21EZ, UK, (fax: +44 1223 336 033; email: [email protected]).
Acknowledgement This work was supported by a Grant-in-Aid for Young Scientists (Start-up), Japan (No. 18890226) (K.K.). References [1] C.D. Gutsche, Acc. Chem. Res. 16 (1983) 161. [2] C.D. Gutsche, Pure Appl. Chem. 62 (1990) 385. [3] M.L. Bender, M. Komiyama, Cyclodextrin Chemistry, Springer-Verlag, Berlin, 1978. [4] M. Komiyama, M.L. Bender, New Comprehens. Biochem. 6 (1984) 505–527. [5] V.T. D’Souza, M.L. Bender, Acc. Chem. Res. 20 (1987) 146. [6] H. Kagechika, T. Himi, E. Kawachi, Y. Hashimoto, K. Shudo, J. Med. Chem. 32 (1989) 2292. [7] K. Yamaguchi, K. Shudo, J. Agric. Food Chem. 39 (1991) 793. [8] A. Itai, Y. Toriumi, N. Tomioka, H. Kagechika, I. Azumaya, K. Shudo, Tetrahedron Lett. 30 (1989) 6177. [9] I. Azumaya, H. Kagechika, Y. Fujiwara, M. Itoh, K. Yamaguchi, K. Shudo, J. Am. Chem. Soc. 113 (1991) 2833. [10] K. Yamaguchi, G. Matsumura, H. Kagechika, I. Azumaya, Y. Ito, A. Itai, et al., J. Am. Chem. Soc. 113 (1991) 5474. [11] A. Itai, Y. Toriumi, S. Saito, H. Kagechika, K. Shudo, J. Am. Chem. Soc. 114 (1992) 10649. [12] S. Saito, Y. Toriumi, N. Tomioka, A. Itai, J. Org. Chem. 60 (1995) 4715. [13] I. Azumaya, H. Kagechika, K. Yamaguchi, K. Shudo, Tetrahedron 51 (1995) 5277. [14] A. Tanatani, K. Yamaguchi, I. Azumaya, R. Fukutomi, K. Shudo, H. Kagechika, J. Am. Chem. Soc. 120 (1998) 6433. [15] I. Azumaya, T. Okamoto, F. Imabeppu, H. Takayanagi, Tetrahedron 59 (2003) 2325. [16] P.E. Georghiou, Z. Li, Tetrahedron Lett. 34 (1993) 2887. [17] B.J. Shorthill, T.E. Glass, Org. Lett. 3 (2001) 577. [18] S. Mizyed, M. Ashram, D.O. Miller, P.E. Georghiou, J. Chem. Soc. Perkin Trans. 2 (2001) 1916. [19] P.E. Georghiou, Z. Li, M. Ashram, S. Chowdhury, S. Mizyed, A.H. Tran, et al., Synlett 6 (2005) 879. [20] A.H. Tran, D.O. Miller, P.E. Georghiou, J. Org. Chem. 70 (2005) 1115. [21] M. Oki, Applications of Dynamic NMR Spectroscopy to Organic Chemistry, VCH Publishers Inc., Florida, 1985.