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Synlett 2005(2): 263-266  
DOI: 10.1055/s-2004-837201
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of N-(p-Tolyl)azacalix[n](2,6)pyridines Constructed of Various Numbers of the Recurring Unit

Yutaka Suzuki, Takanori Yanagi, Takaki Kanbara*, Takakazu Yamamoto*
Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan
Fax: +81(45)9245976; e-Mail: tkanbara@res.titech.ac.jp;
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Publikationsverlauf

Received 31 October 2004
Publikationsdatum:
17. Dezember 2004 (online)

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Abstract

Synthetic routes for N-(p-tolyl)-substituted azacalix[n](2,6)pyridines via Cu- and Pd-catalyzed aryl amination reactions have been elaborated, and the macrocycles constructed of various numbers (n = 3-8, and 10) of a N-(p-tolyl)aminopyridine recurring unit have been isolated. A cyclic trimer 1 was obtained in good yield. Molecular structures of some macrocycles and a Cu(I) complex of 1 were determined by X-ray crystallography.

Key words

macrocycles - aminations - pyridines - copper - palladium - complexes

4

Compound 8: A mixture of 2,6-dibromopyridine (3.53 g, 15 mmol) and p-toluidine (535 mg, 5 mmol) was dissolved in toluene (50 mL). Sodium-t-butoxide (1.44 g, 15 mmol), tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3] (230 mg, 0.25 mmol), and 9,9-dimethyl-4,5-bis(diphenylphos-phino)xanthene (XANTPHOS) (290 mg, 0.50 mmol) were added to the solution. The reaction mixture was stirred at 80 °C for 18 h under nitrogen. After cooling to r.t., the mixture was quenched by the addition of an aq solution of EDTA-2K (ca. 100 mL), and the product was extracted with CHCl3. The crude product was purified by column chromatography on silica gel (1.62 g, 78% yield). FAB-MS: m/z = 420 [M + H]+. 1H NMR (400 MHz, CDCl3): δ = 7.36 (t, J = 7.8 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.08 (d, J = 8.4 Hz, 2 H), 7.07 (d, J = 7.3 Hz, 2 H), 6.91 (d, J = 8.0 Hz, 2 H), 2.38 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 157.4, 141.0, 139.5, 136.9, 130.8, 128.1, 122.9, 122.0, 114.9, 21.5.

5

Preparation of compound 9 was carried out in analogy with ref. [4] using 2,6-diaminopyridine and 4-bromotoluene (58% yield). FAB-MS: m/z = 290 [M + H]+. 1H NMR (400 MHz, CDCl3): δ = 7.30 (t, J = 8.1 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 4 H), 7.12 (d, J = 8.3 Hz, 4 H), 6.25 (s, 2 H), 6.24 (d, J = 7.8 Hz, 2 H), 2.33 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 155.5, 139.2, 138.0, 132.2, 129.7, 121.0, 98.1, 20.8.

6

Macrocycle 1 (n = 3): A mixture of 8 (105 mg, 0.25 mmol) and 9 (72 mg, 0.25 mmol) was dissolved in nitrobenzene (50 mL). CuI (70 mg, 0.37 mmol) and anhyd K2CO3 (138 mg, 1.0 mmol) were added to the solution. The reaction mixture was stirred at 190 °C for 6 d under nitrogen. After the reaction, the solvent was removed by vacuum distillation. The remaining mixture was washed with an aq solution of EDTA-2K (ca. 100 mL) and extracted with CHCl3. The organic fraction was concentrated, and the crude product was purified by column chromatography on aminopro-pylated silica gel (100 mg, 73% yield). FAB-MS: m/z = 547 [M + H]+. 1H NMR (400 MHz, CDCl3): δ = 7.32 (d, J = 8.4 Hz, 6 H), 7.27 (d, J = 8.4 Hz, 6 H), 7.16 (t, J = 8.2 Hz, 3 H), 6.06 (d, J = 8.0 Hz, 6 H), 2.41 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 154.6, 146.8, 137.4, 137.0, 130.7, 129.1, 106.9, 21.2.

7

Preparation of macrocycles 2, 4, 6, and 7 was carried out in analogy with ref. [6] using 2,6-dibromopyridine and 9 (yield: 2, 24%; 4, 12%; 6, 1%; 7, trace).
Macrocycle 2 (n = 4): FAB-MS: m/z = 729 [M + H]+, 365 [M + 2 H]2+. 1H NMR (400 MHz, CDCl3): δ = 7.26 (t, J = 7.8 Hz, 4 H), 7.13 (d, J = 8.3 Hz, 8 H), 7.05 (d, J = 8.1 Hz, 8 H), 6.48 (d, J = 7.8 Hz, 8 H), 2.30 (s, 12 H). 13C NMR (100 MHz, CDCl3): δ = 157.8, 142.2, 138.1, 134.2, 129.6, 126.3, 111.1, 21.0.
Macrocycle 4 (n = 6): FAB-MS: m/z 1093 [M + H]+, 547 [M + 2 H]2+. 1H NMR (400 MHz, CDCl3, 50 °C): δ = 7.26 (t, J = 8.0 Hz, 6 H), 6.96 (d, J = 8.3 Hz, 12 H), 6.91 (d, J = 8.5 Hz, 12 H), 6.40 (d, J = 7.8 Hz, 12 H), 2.32 (s, 18 H). 13C NMR (100 MHz, CDCl3): δ = 155.9, 142.3, 137.8, 134.4, 129.4, 128.2, 109.2, 21.1.
Macrocycle 6 (n = 8): FAB-MS: m/z = 1457 [M + H]+, 729 [M + 2 H]2+. 1H NMR (400 MHz, CDCl3): δ = 7.03 (d, J = 8.1 Hz, 16 H), 6.98 (t, J = 8.2 Hz, 8 H), 6.88 (d, J = 7.8 Hz, 16 H), 6.28 (d, J = 7.8 Hz, 16 H), 2.32 (s, 24 H).
Macrocycle 7 (n = 10): FAB-MS: m/z = 1821 [M + H]+, 911 [M + 2 H]2+. 1H NMR (400 MHz, CDCl3, 50 °C): δ = 7.00-6.90 (m, 30 H), 6.85 (d, J = 8.1 Hz, 20 H), 6.31 (d, J = 8.1 Hz, 20 H), 2.29 (s, 30 H).

8

Preparation of compound 10 was carried out in analogy with ref. [4] using 2,6-dibromopyridine and p-toluidine (58% yield). FAB-MS: m/z = 263 [M + H]+. 1H NMR (400 MHz, acetone-d 6): δ = 8.30 (s, 1 H), 7.48 (d, J = 8.4 Hz, 2 H), 7.40 (dd, J = 8.3, 8.3 Hz, 1 H), 7.11 (d, J = 8.1 Hz, 2 H), 6.86 (dd, J = 7.5, 0.6 Hz, 1 H), 6.77 (dd, J = 8.3, 0.7 Hz, 1 H), 2.27 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 156.7, 140.2, 139.6, 136.6, 133.9, 129.9, 121.8, 117.6, 105.3, 20.8.

10

Compound 10 (658 mg, 2.5 mmol) was dissolved in toluene (500 mL). NaOt-Bu (360 mg, 3.75 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), and XANTPHOS (115 mg, 0.2 mmol) were added to the solution. The reaction mixture was stirred at
80 °C for 5 d under nitrogen. Purification of the product was carried out in analogy with ref. [6] (yield: 1, 38%; 2, 31%; 3, 6%; 4, 7%; 5, 2%; 6, trace).
Macrocycle 3 (n = 5): FAB-MS: m/z = 911 [M + H]+. 1H NMR (400 MHz, CDCl3): δ = 7.16 (t, J = 8.0 Hz, 5 H), 7.01 (d, J = 9.0 Hz, 10 H), 6.98 (d, J = 8.8 Hz, 10 H), 6.38 (d, J = 7.8 Hz, 10 H), 2.31 (s, 15 H). 13C NMR (100 MHz, CDCl3): δ = 156.3, 142.1, 137.7, 134.2, 129.4, 127.3, 110.5, 21.1.
Macrocycle 5 (n = 7): FAB-MS: m/z = 1275 [M + H]+. 1H NMR (400 MHz, CDCl3): δ = 7.07 (t, J = 8.1 Hz, 7 H), 6.96 (d, J = 8.1 Hz, 14 H), 6.89 (d, J = 8.3 Hz, 14 H), 6.41 (d, J = 8.1 Hz, 14 H), 2.30 (s, 21 H). 13C NMR (100 MHz, CDCl3): δ = 155.6, 141.6, 137.5, 134.0, 129.1, 127.5, 108.8, 20.8.

11

Crystallographic data for 1: C36H30N6, M = 546.67, mono-clinic, P21/a, a = 11.225 (7), b = 21.541 (13), c = 12.989 (9) Å, β = 113.747 (8)°, V = 2874.8 (32) Å3, Z = 4, D calcd = 1.263 g cm-3, µ(MoKα) = 0.77 cm-1, T = 113 K, F(000) = 1152, 42080 reflections measured, 6688 unique, 3778 observed [I > 3σ(I)], 379 variables, R 1 = 0.037, R w = 0.048, GOF = 0.929.
Crystallographic data for 2: C48H40N8, M = 728.90, triclinic, P1bar, a = 11.111 (9), b = 12.354 (7), c = 14.633 (9) Å, α = 71.37 (3), β = 89.86 (4)°, γ = 82.48 (4)°, V = 1885.4 (22) Å3, Z = 2, D calcd = 1.284 g cm-3, µ(MoKα) = 0.78 cm-1, T = 113 K, F(000) = 768, 28672 reflections measured, 8100 unique, 5582 observed [I > 1σ(I)], 505 variables, R 1 = 0.090, R w = 0.131, GOF = 0.930.
Crystallographic data for 4·2CHCl3: C74H62N12Cl6, M = 1332.10, triclinic, P1bar, a = 13.283 (8), b = 14.980 (7), c = 19.459 (13) Å, α = 70.21 (3), β = 81.90 (3)°, γ = 67.21 (3)°, V = 3358.8 (34) Å3, Z = 2, D calcd = 1.317 g cm-3, µ(MoKα) = 3.09 cm-1, T = 113 K, F(000) = 1384, 49428 reflections measured, 14202 unique, 8401 observed [I > 2σ(I)], 829 variables, R 1 = 0.132, R w = 0.171, GOF = 1.058. [16]

13

Cu(I) complex 11: An MeCN solution (1 mL) of CuI (19 mg, 0.1 mmol) was added to an MeCN solution (1 mL) of 1 (54 mg, 0.1 mmol). The mixture was allowed to stir at r.t. for 30 min. An addition of Et2O (about 1 mL) afforded a yellow precipitate. The precipitate was filtered and washed with Et2O (21 mg, 56% yield). A single crystal was obtained by slow diffusion of hexane into a CH2Cl2 solution of the product. 1H NMR (400 MHz, CD3CN): δ = 7.60-7.20 (m, 15 H), 6.52 (d, J = 8.3 Hz, 2 H), 6.00 (d, J = 8.4 Hz, 4 H), 2.49 (s, 6 H), 2.39 (s, 3 H).

14

Crystallographic data for 11·CH2Cl2: C37H32CuCl2IN6, M = 822.06, triclinic, P1bar, a = 10.253 (5), b = 11.726 (7), c = 16.545 (9) Å, α = 82.68 (3), β = 74.12 (3)°, γ = 66.16 (2)°, V = 1749.5 (17) Å3, Z = 2, D calcd = 1.560 g cm-3, µ(MoKα) = 16.95 cm-1, T = 113 K, F(000) = 824, 25354 reflections measured, 7399 unique, 4688 observed [I > 2σ(I)], 456 variables, R 1 = 0.072, R w = 0.086, GOF = 0.881. [16]

16

Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre; publication numbers CCDC 253651 (1), 241558 (2), 241559 (4), and 253652 (11).