HETEROCYCLES

Note | Special issue | Vol. 77, No. 1, 2009, pp. 565-574
Received, 9th April, 2008, Accepted, 12th May, 2008, Published online, 15th May, 2008.
DOI: 10.3987/COM-08-S(F)8

■ Synthesis of [Poly(2-pyridyl)-Substituted]-1-azaazulenes

Tomoyuki Ariyoshi, Tomonori Noda, Satomi Watarai, Shoji Tagashira, Yoshiko Murakami, Hiroyuki Fujii, and Noritaka Abe*

Graduate School of Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan

Abstract

2-(2-Pyridyl)-1-azaazulenes were derived from 2-bromo- or 2-iodo-1-azaazulenes and 3-(2-pyridyl)-1-azaazulenes were derived from 3-iodo-1-azaazulenes by Suzuki coupling. Reaction of 3-iodo-1-azaazulenes with B(NPDEA) gave corresponding 3-(2-pyridyl)-1-azaazulenes together with 3-borylated-2-chloor-1-azaazulene (9a) or 3,3’-bi(2-methoxy-1-azaazulene) (10b). Reactions of 8-(2-pyridyl)-1-azaazulene with 2-pyridyllithium gave 4,8-di(2-pyridyl)- and 6,8-di(2-pyridyl)-1-azaazulenes. Reactions of 4,8-di(2-pyridyl)-1-azaazulene with 2-pyridyllithium gave 4,6,8-tri(2-pyridyl)-1-azaazulene. The reactivity of the seven-menbered ring is C8 > C6 > C4. Reaction of 3-(2-pyridyl)-1-azaazulenes with 2-pyridyllithium gave 3,4-di(2-pyridyl)- and 3,8-di(2-pyridyl)-1-azaazulenes.

INTRODUCTION
In the chemistry of 1-azaazulenes,1 pyridyl-1-azaazulenes are especially of interest for their physical and chemical properties for comparison with pyridyl-azulenes,2 but synthetic reports were few. Recently, we reported the synthesis and some properties of 2-(2-pyridyl)-1-azaazulene (1a)3 and 8-(2-pyridyl)-1-azaazulene (2a,b),4,5 which behaved as bidentate ligands. We previously reported that Suzuki coupling of halo-1-azaazulene is suitable for introducing aryl group on five-membered ring of 1-azaazulene,4 and the addition-dehydrogenation reaction of aryllithium is good method for introducing aryl groups to 8-position of 1-azaazulenes.4 Therefore, for synthesis of poly(2-pyridyl)-1-azaazulenes, we exploited the combination of Suzuki coupling and the addition-dehydration reaction of 2-pyridyllithium with (2-pyridyl)-1-azaazulenes.

RESULTS AND DISCUSSION
Reaction of 2-chloro-1-azaazulene (3a) did not undergo Suzuki coupling. Reaction of 2-bromo-1-azaazulene (3b) with pyridineboronic acid N-phenyl-diethylamine ester (B(NPDEA)) in the presence of PdCl2(PPh3)2, CuI, and K2CO3 in dry THF under heating for 24 h at 80 ℃ in a sealed tube gave a 2-(2-pyridyl)-1-azaazulene-Cu complex. Using Cs2CO3 as base in the reaction gave similar result. Treatment of the complex with aq. Solution of EDTA gave free 2-(2-pyridyl)-1-azaazulene (1a) (23%) together with recovered 3b (14%). When the reaction was carried out using 2-iodo-1-azaazulene (3c), which was produced in 66% yield by the treatment of 3b with Mg-metal and I2, the yield was slightly raised to 25%. Similar reaction of 2-bromo-3-methyl-1-azaazulene (3d) with B(NPDEA) gave 3-methyl-2-(2-pyridyl)-1-azaazulene (1b) (12%).

Treatment of 2-chloro-8-(2-pyridyl)-1-azaazulene (2a) with an equivalent molar of 2-pyridyllithium (PyLi) followed by MeOH gave only recovered (2a) in over 80% yield. Treatment of 2a with excess molar of PyLi (2.4 eq. mole) at -80 ℃ for 0.5 h followed by MeOH gave addition products, and a successive dehydrogenation of the intermediates with tetrachloro-o-benzoquinone (o-chloranil) at 50 ℃ for 17 h afforded 2-chloro-6,8-di(2-pyridyl)-1-azaazulene (4) and 2-chloro-4,8-di(2-pyridyl)-1-azaazulene (5) in 58% and 4% yields, respectively. Reaction of 5 with PyLi under similar conditions to that descrived above gave 2-chloro-4,6,8-tri(2-pyridyl)-1-azaazulene (6) in 68% yield. Further treatment of 6 with an excess equivalent of PyLi proceeded but only unstable yellow tar was obtained in spite of the treatment with o-chloranil at 50 ℃ for 6 d, along with recovered (6) (4%). In the reaction, the addition reaction would undergo but successive dehydrogenation would be prevented, being ascribable to the steric hindrance. The results showed that the reactivity of the seven-menbered ring is C8 > C6 > C4.
In the similar manner, we examined of 1a with PyLi, but the reaction did not undergo and 1a (97%) was recovered. Chelation of Li+ with 1a would keep apart the pyridyl moiety from seven-membered ring and this would cause to prevent the reaction.
The structures of obtained products were deduced by spectroscopic data as well as elemental analysis. Electronic spectra of 3a, 2a, 4, and 6 were shown in Fig. 1. It is shown that introduction of pyridine on 1-azaazulene nuclei caused bathochromic shift.

Reaction of 2-chloro-3-iodo-1-azaazulene (7a) with B(NPDEA) in the presence of PPh3, Pd(OAc)2, K2CO3, and CuI in dry THF under heating for 24 h at 80 ℃ in a sealed tube gave 2-chloro-3-(2-pyridyl)-1-azaazulene (8a) (50%) together with (2-chloro-1-azaazulen-3-yl)-(2-pyridyl)-[N-(2-hydroxylethyl)]-(N-phenyl)aminoethylborate (9a) (3%). Similar treatment of 3-iodo-2-methoxy-1-azaazulene (7b) with B(NPDEA) in the presence of PdCl2(PPh3)2, K2CO3 , and CuI in dry THF under heating for 3 h at 80 ℃ in a sealed tube gave 2-methoxy-3-(2-pyridyl)-1-azaazulene (8b) (84%) together with 3,3’-bi(2-methoxy-1-azaazulene) (10b) (6%).
We previously reported that reaction of 7a with bis(pinacolato)diborane gave 11 and 10a. Therefore, it is thought that 9 would be produced by the reaction of 7 and B(NPDEA). Successive reaction of 9b and 7b would produce 10b under the conditions. Lower reactivity of 9a than 9b and 11 would cause to give none of 10a.

We examined the following reaction of 8 with PyLi similarly. Treatment of 8a with PyLi followed by quenching with MeOH and successive dehydrogenation gave a mixture of 12a (30%), 13a (30%), 12b (7%), and 13b (9%). Compounds 12b and 13b would form via a substitution of 12a and 13a by methoxide. Existence of aryl group at C-3 would enhance the reactivity of C-2.4 Similar reaction of 8b with PyLi gave 12b (26%) and 13b (30%). In these reactions, attacks of PyLi at C-4 and C-8 of 1-azaazulene nuclei were practically equal, and 3,6-di(2-pyridyl)-1-azaazulenes were not obtained. Coordination of electropositive lithium atom of the reagent on nitrogen atoms of 1-azaazulene and pyridine is thought to controll the reaction position.

To expect the formation of 13a, we performed Suzuki coupling of 14. In the reaction, only insoluble dark material, which was considered to be 14-Cu complex, was precipitated. Previously, we reported about the formation of Cu-complex with 2a.4

ACKNOWLEDGEMENTS
This work was partially supported by a Grant-in-Aid for Scientific Research (No.18510075) to S. T. from the Japan Society for Promotion of Science (JSPS).

EXPERIMENTAL
Mps were measured using a Yanagimoto micro-melting apparatus and uncorrected. 1H NMR spectra (including HH-COSY and CH-COSY NMR) were recorded on a Bruker AVANCE 400S (400 MHz) and 13C NMR spectra were recorded on a Bruker AVANCE 400S (100.6 MHz) using CDCl3 as a solvent with tetramethylsilane as an internal standard unless otherwise stated; J values are recorded in Hz. IR spectra were recorded for KBr pellets on a Nicolet FT-IR Avatar 370DTGS. Electronic spectra were recorded with JASCO V-670 spectrophotometer using CHCl3 as a solvent. MS spectra were taken with an LC-MS Waters Integrity System. Elemental analyses were taken with a Perkin Elmer 2400II. Kieselgel 60 was used for column chromatography and Kieselgel 60G was used for thin-layer chromatography.

Synthesis of 2-iodo-1-azaazulene (3c)
Under argon atmosphere, Mg (0.032 g, 1.3 mmol) was activated by stirring overnight with small amounts of iodine. A mixture of the Mg, iodine (0.300 g, 1.2 mmol), and 2-bromo-1-azaazulene (3b) (0.207 g, 1.0 mmol) in dry THF (20 mL) was heated at 80 ℃ for 5 h. To the mixture was added water (30 mL), then the mixture was extracted with CHCl3. The extract was dried over sodium sulfate and evaporated. Chromatography of the residue with hexane-CHCl3 (1 : 1) gave 2-iodo-1-azaazulene (3c) (0.177 g, 66%).
3c: Red needles (from hexane-CH2Cl2), mp 71-74 ℃: δH 7.56 (1H, s, H-3), 7.68 (1H, dd, J 9.9 and 9.7, H-7), 7.77 (1H, t, J 9.9, H-5), 7.93 (1H, t, J 9.9, H-6), 8.51 (1H, d, J 9.9, H-4), and 8.66 (1H, d, J 9.7, H-8); m/z (rel intensity) 255 (M+, 100), 207 (8), 128 (39), 127 (21), 101 (44), and 77 (25). Anal. Calcd for C9H6NI: C, 42.38; H, 2.37; N, 5.49. Found: C, 42.53; H, 2.29; N, 5.33.

Synthesis of 2-(2-pyridyl)-1-azaazulene
A) Under argon atmosphere, a mixture of 3b (0.104 g, 0.50 mmol), pyridineboronic acid N-phenyldiethylamine ester (B(NPDEA)) (0.402 g, 1.5 mmol), PdCl2(PPh3)2 (0.0175 g, 0.025 mmol, 5 mol%), CuI (0.280 g, 1.5 mmol), K2CO3 (0.138 g, 1,0 mmol) in THF (20 mL) was stirred for 4 h at 80℃. The precipitate was collected by filtration and washed with water and CHCl3. The precipitate was suspended in EDTA (1.0 g, 2.5 mmol) and water (10 mL), then the suspension was stirred for 24 h at 80℃. The suspension was combined with the filtrate and washed solution, and the mixture was extracted with CHCl3. The extract was dried over Na2SO4 and evaporated. The residue was chromatographed on silica gel column with hexane-CHCl3 (1 : 1) to give 2-(2-pyridyl)-1-azaazulene3 (1a) (0.024 g, 23%) and recovered 3b (0.015 g, 14%).
B) Under argon atmosphere, a mixture of 3c (0.1335 g, 0.50 mmol), B(NPDEA) (0.400 g, 1.5 mmol), PdCl2(PPh3)2 (0.0175 g, 0.025 mmol, 5 mol%)、CuI (0.285 g, 1.5 mmol), Cs2CO3 (0.243 g, 0.75 mmol) in THF (10 mL) was stirred for 4 h at 80 ℃. The precipitate was collected by filtration and washed with water and CHCl3. The precipitate was suspended in EDTA (1.0 g, 2.5 mmol) and water (10 mL), then the suspension was stirred for 24 h at 80 ℃. The suspension was combined with the filtrate and washed solution, and the mixture was extracted with CHCl3. The extract was dried over Na2SO4 and evaporated. The residue was chromatographed on silica gel column with hexane-CHCl3 (1 : 1) to give 1a (0.025 g, 25%).

In the similar manner, 3-methyl-2-(2-pyridyl)-1-azaazulene (1b) was obtained in 12%.
1b: Red violet powders (from hexane-CH2Cl2), mp 86-89 ℃: 1H NMR δ 2.96 (3H, s, Me), 7.31 (1H, ddd, J 7.7, 4.7, and 1.0, H-5’), 7.60 (1H, dd, J 9.9 and 9.8 H-5), 7.69 (1H, dd, J 9.8 and 9.6, H-7), 7.81 (1H, t, J 9.8, H-6), 7.85 (1H, ddd, J 7.9, 7.5, and 0.9, H-4’), 8.47 (1H, dd, J 7.9 and 1.0, H-3’), 8.48 (1H, d, J 9.9, H-4), 8.67 (1H, d, J 9.6, H-8), and 8.81 (1H, dd, J 4.7 and 0.7, H-6’): 13C NMR δ 11.12, 122.13, 123.00, 124.76, 127.26, 128.76, 134.15, 136.17, 136.41, 137.58, 145.83, 149.46, 155.78, 157.22, and 162.81. Anal. Calcd for C15H12N2: C, 81.79; H, 5.49; N, 12.72. Found: C, 81.55; H, 5.45; N, 12.59.

Reaction of 2-chloro-3-iodo-1-azaazulene (7a) with B(NPDEA)
Under argon atmosphere, a mixture of 7a (0.288 g, 1.00 mmol), B(NPDEA) (0.800 g, 3.00 mmol), PPh3 (0.053 g, 0.20 mmol), Pd(OAc)2 (0.011 g, 0.02 mmol, 5mol%), CuI (0.570 g, 3.00 mmol), and K2CO3 (0.276 g, 2.00 mmol) in dry THF (20 mL) was heated for 24 h at 80 ℃ in a sealed tube. The mixture was poured into water and extracted with CHCl3. The extract was dried over Na2SO4 and evaporated. The residue was chromatographed on silica gel column with hexane-EtOAc (5 : 3) to give 2-chloro-3-(2-pyridyl)-1-azaazulene (8a) (0.122 g, 50%) and (2-chloro-1-azaazulen-3-yl)-(2-pyridyl)-[N-
(2-hydroxylethyl)]-(N-phenyl)aminoethylborate (9a) (0.012 g, 3%).
8a: Orange needles (from hexane-CH2Cl2), mp 127-129 ℃: 1H NMR δH 7.30 (1H, ddd, J 7.9, 4.9, and 1.5, H-5’), 7.77 (1H, dd, J 10.1 and 9.8, H-5), 7.83 (1H, dd, J 10.8 and 9.7, H-7), 7.86 (1H, ddd, J 7.3, 1.5, and 0.9, H-3’), 7.92 (1H, ddd, J 7.9, 7.3, and 1.7, H-4’), 7.97 (1H, ddd, J 10.8, 9.8, and 0.9, H-6), 8.66 (1H, dd, J 9.7 and 0.9, H-8), 8.81 (1H, ddd, J 4.9, 1.7 and 0.9, H-6’), and 9.21 (1H, d, J 10.1, H-4): 13C NMR δ 121.76, 121.81, 125.03, 130.92, 131.16, 136.31, 136.50, 136.60, 139.11, 144.15, 149.69, 152.27, 155.49, and 155.92; λmax nm (log ε) 280 (4.56), 299 (4.60), 330 (3.91), 363 (3.81), and 483 (3.09). Anal. Calcd for C14H9N2Cl: C, 69.86; H, 3.77; N, 11.64. Found: C, 69.63; H, 4.05; N, 11.59.9a: Orange powders (from hexane-CH2Cl2), mp 137-138 ℃: 1H NMR δ 3.62 (2H, d, J 5.1, NCH2), 3.83 (2H, t, J 5.1, NCH2), 3.92, (2H, t, J 5.7, OCH2), 4.60 (1H, br s, OH), 5.03 (2H, t, J 5.7, OCH2), 6.64 (1H, t, J 7.2, H-p-phenyl), 6.82 (2H, d, J 8.8, H-o-phenyl), 7.11 (2H, dd, J 8.8 and 7.2, H-m-phenyl), 7.18 (1H, ddd, J 7.5, 4.9, and 1.1, H-Py-4), 7.55-7.65 (3H, m, H-5, 6, and 7), 7.76 (1H, ddd, J 8.0, 7.5, and 1.8, H-Py-5), 7.93 (1H, ddd, J 8.0, 1.1, and 0.9, H-Py-3), 8.25-8.30 (1H, m, H-8), 8.74 (1H, ddd, J 4.9, 1.8, and 0.9, H-Py-6), and 9.35 (1H, dm, J 10.9, H-4): 13C NMR δ 52.07, 55.17, 60.09, 109.57, 112.81, 116.99, 119.66, 123.83, 129.13, 130.74, 131.02, 131.21, 133.07, 134.81, 136.21, 144.37, 148.24, 149.22, 153.23, 155.00, and 172.10; λmax nm (log ε) 284 (4.57), 306 (4.58), 314 (4.58), 375 (3.85, sh), 387 (3.86), and 461 (3.37). Anal. Calcd for C24H23N3O2BCl: C, 66.77; H, 5.37; N, 9.73. Found: C, 66.29; H, 5.28; N, 9.55.

Reaction of 3-iodo-2-methoxy-1-azaazulene (7b) with B(NPDEA)
Under argon atmosphere, a mixture of 7b (0.143 g, 0.50 mmol), B(NPDEA) (0.400 g, 1.00 mmol), CuI (0.286 g, 1.00 mmol), PdCl2(PPh3)2 (0.018 g, 0.026 mmol, 5mol%), and K2CO3 (0.140 g, 1.0 mmol) in dry THF (15 mL) was heated for 3 h at 80 ℃ in a sealed tube. Then the solvent was evaporated. The residue was chromatographed on silica gel column with hexane-CHCl3 (1 : 1) to give 8b (0.099 g, 84%) and 3,3’-bis(2-methoxy-1-azaazulene) (10b) (0.0045 g, 6%).
8b: Red prisms (from hexane-CH2Cl2), mp 88-89 ℃: 1H NMR δ 4.36 (3H, s, OCH3), 7.13 (1H, dd, J 7.2, and 4.6, H-5’), 7.50-7.61 (3H, m, H-5,6,7), 7.73 (1H, td, J 8.1 and 7.2 , H-4’), 7.99 (1H, d, J 8.1, H-3’), 8.27-8.33 (1H, m, H-8), 8.74 (1H, d, J 4.6, H-6’), and 9.43-9.52 (1H, m, H-4): 13C NMR δ 56.58, 109.54, 120.46, 123.67, 130.42, 130.80, 131.21, 133.08, 134.52, 136.10, 144.47, 149.15, 153.53, 155.61, and 173.18; λmax nm (log ε) 285 (4.53), 308 (4.57, sh), 315 (4.60), and 461 (3.41). Anal. Calcd for C15H12N2O: C, 76.25; H, 5.12; N, 11.86. Found: C, 76.15; H, 5.28; N, 11.80.
10b: Red prisms (from hexane-CH2Cl2), mp 223-225 ℃: 1H NMR δ 4.30 (6H, s, OCH3), 7.39 (2H, dddd, J 10.4, 9.8,1.2 and 0.9, H-5,5’), 7.54 (2H, ddd, J 9.8, 9.2 and 0.6, H-7,7’), 7.60 (2H, dd, J 9.9 and 9.8, H-6,6’), 7.86 (2H, dd, J 9.2 and 0.6, H-4,4’), and 8.29 (1H, dd, J 10.4 and 1.2, H-8,8’). Anal. Calcd for C20H16N2O2: C, 75.93; H, 5.10; N, 8.86. Found: C, 75.88; H, 5.22; N, 8.60.

Reaction of 2-chloro-8-(2-pyridyl)-1-azaazulene (2a) with 2-pyridyllithium
Under argon atmosphere, 1.5 M butyllithium (1.7 mL, 2.60 mmol) was added to the solution of 2-bromopyridine (0.23 mL, 2.40 mmol) in dry THF (15 mL) at –90 ℃. To the mixture 2a (0.240 g, 1.00 mmol) in dry THF (15 mL) was added, and the mixture was stirred for 15 min at –80 ℃, then MeOH (10 mL) was added. After the mixture was warm to rt, o-chloranil (0.260 g, 2.4 mmol) was added to the mixture and the mixture was stirred for 17 h at 50 ℃. The mixture was poured into water and extracted with CHCl3. The extract was dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel column with ACOEt-hexane (2 : 5) to give 2-chloro-6,8-bis(2-pyridyl)-1-
azaazulene (4) (0.185 g, 58%) and 2-chloro-4,8-bis(2-pyridyl)-1-azaazulene (5) (0.013 g, 4%).
4: Orange needles (from hexane-CH2Cl2), mp 168-170 ℃: 1H NMR δ 7.31 (1H, s, H-3), 7.36 (1H, ddd, J 7.5, 4.7, and 1.1, H-5’’), 7.39 (1H, ddd, J 7.3, 4.8, and 1.3, H-5’), 7.82 (1H, dd, J 8.0 and 7.5, H-4’’), 7.87 (1H, dd, J 7.9 and 7.3, H-4’), 7.93 (1H, dd, J 8.0 and 1.1, H-3’’), 8.30 (1H, dd, J 7.9 and 1.3, H-3’), 8.36 (1H, dd, J 10.4 and 1.9, H-5), 8.57 (1H, d, J 10.4, H-4), 8.78 (1H, d, J 4.7, H-6’’), 8.81 (1H, d, J 4.8 , H-6’), and 8.91 (1H, s, H-7): 13C NMR δ 113.49, 123.54, 123.86, 129.05, 129.72, 134.08, 134.30, 136.19, 137.58, 145.09, 148.15, 148.22, 150.08, 150.32, 152.71, 158.86, 158.52, and 159.94; λmax nm (log ε) 294 (4.38), 358 (3.84), 372 (3.89), and 492 (3.00). Anal. Calcd for C19H12N3Cl: C, 71.81; H, 3.81; N, 12.98. Found: C, 71.80; H, 4.12; N, 12.93.
5: Orange brown needles (from hexane-CH2Cl2), mp 168-170 ℃: 1H NMR δ 7.18 (1H, s, H-3), 7.40 (1H, ddd, J 7.5, 4.8, and 0.8, H-5’), 7.46 (1H, ddd, J 7.6, 4.8, and 0.8, H-5’’), 7.75 (1H, dd, J 7.8 and 0.8, H-3’’), 7.87 (1H, d, J 9.7 H-5), 7.88 (1H, ddd J 7.9, 7.5 and 1.9, H-4’), 7.91 (1H, ddd, J 7.8, 7.6 and 1.7, H-4’’), 8.04 (1H, dd, J 10.8 and 9.7, H-6), 8.27 (1H, dd, J 7.9 and 0.8, H-3’), 8.33 (1H, d, J 10.8, H-7), 8.82 (1H, dd, J 4.8 and 1.9, H-6’), and 8.85 (1H, dd, J 4.8 and 1.7, H-6’’): 13C NMR δ 112.71, 123.47, 123.54, 124.72, 129.05, 128.76, 131.68, 133.20, 135.75, 136.12, 136.72, 146.06, 146.26, 146.43, 149.63, 150.07, 153.58, 157.35, 157.89, and 159.47; λmax nm (log ε) 286 (4.63), 348 (3.80, sh), and 494 (3.30). Anal. Calcd for C19H12N3Cl: C, 71.81; H, 3.81; N, 12.98. Found: C, 71.88; H, 4.02; N, 12.89.

Reaction of 2-chloro-4,8-di(2-pyridyl)-1-azaazulene (5) with 2-pyridyllithium
Under argon atmosphere, 1.5 M butyllithium (1.25 mL, 1.95 mmol) was added to the solution of 2-bromopyridine (0.172 mL, 1.80 mmol) in dry THF (15 mL) at –90 ℃, and the mixture was stirred for 30 min. To the mixture 5 (0.160 g, 0.50 mmol) in dry THF (15 mL) was added, and the mixture was stirred for 30 min at –80 ℃, then MeOH (10 mL) was added. After the mixture was warm to rt, o-chloranil (0.260 g, 2.4 mmol) was added to the mixture and the mixture was stirred for 17 h at 50 ℃. The mixture was poured into water and extracted with CHCl3. The extract was dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel column with EtOAc-hexane (1 : 1) to give 2-chloro-4,6,8-tris(2-pyridyl)-1-azaazulene (6) (0.134 g, 68%).
6: Orange needles (from hexane-CH2Cl2), mp 211-214 ℃: 1H NMR δ 7.18 (1H, s, H-3), 7.33 (1H, ddd, J 7.8, 4.8, and 1.0, H-5’’’), 7.40 (1H, ddd, J 7.9, 5.0, and 1.1, H-5’’), 7.45 (1H, ddd, J 7.8, 4.9, and 1.1, H-5’), 7.80 (1H, dt, J 7.8 and 1.0, H-3’’’), 7.82 (1H, td, J 7.8, and 1.0, H-4’’’), 7.88 (1H, td, J 7.9 and 1.8, H-4’’), 7.91 (1H, td, J 7.8 and 1.8, H-4’), 7.96 (1H, dt, J 7.9, and 0.9, H-3’’), 8.27 (1H, dt, J 7.8 and 1.0, H-3’), 8.60 (1H, d, J 1.6, H-5), 8.75 (1H, ddd, J 4.8, 1.7 and 0.9, H-6’’’), 8.83 (1H, ddd, J 5.0, 1.8, and 0.9, H-6’’), 8.84 (1H, ddd, J 5.0, 0.8, and 0.9, H-6’), and 8.91 (1H, d, J 1.6, H-7): 13C NMR δ 113.01, 123.14, 123.31, 123.45, 123.52, 124.84, 128.78, 131.98, 133.34, 135.73, 136.73, 137.16, 145.23, 145.65, 235.73, 146.87, 149.64, 149.84, 150.00, 153.21, 157.71, 158.26, 159.66, and 159.82; λmax nm (log ε) 298 (5.02), 314 (4.95, sh), 365 (4.40), 378 (4.40), and 506 (3.74). Anal. Calcd for C24H15N4Cl: C, 73.00; H, 3.83; N, 14.19. Found: C, 73.03; H, 4.09; N, 13.92.

Reaction of 2-chloro-3-(2-pyridyl)-1-azaazulene (8a) with 2-pyridyllithium
Under argon atmosphere, 1.5 M butyllithium (0.89 mL, 1,40 mmol) was added to the solution of 2-bromopyridine (0.12 mL, 1.20 mmol) in dry THF (15 mL) at –90 ℃. To the mixture 8a (0.150 g, 0.62 mmol) in dry THF (20 mL) was added, and the mixture was stirred for 15 min at –80 ℃, then MeOH (10 mL) was added. After the mixture was warm to rt, o-chloranil (0.260 g, 2.4 mmol) was added to the mixture and the mixture was stirred for 17 h at 50 ℃. The mixture was poured into water and extracted with CHCl3. The extract was dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel column with EtOAc-hexane (1 : 1) to give 2-chloro-3,8-bis(2-pyridyl)-1-azaazulene (13a) (0.058 g, 30%), 2-chloro-3,4-bis(2-pyridyl)-1-azaazulene (12a) (0.038 g, 30%), 2-methoxy-3,8-bis(2-pyridyl)-1-azaazulene (13b) (0.017 g, 9%) and 2-methoxy-3,4-bis(2-pyridyl)-1-azaazulene (12b) (0.014 g, 7%).
12a: Red brown prisms (from hexane-CH2Cl2), mp 179-182 ℃: 1H NMR δ 6.92 (1H, ddd, J 7.4, 4.9, and 0.9, H-5’’), 6.98 (1H, ddd, J 7.6, 4.1, and 0.9, H-5’), 7.13 (1H, dt, J 7.7 and 0.9, H-3’), 7.15 (1H, dt, J 7.7 and 0.9, H-3’’), 7.26 (1H, ddd, J 7.7, 7.4, and 1.7, H-4’), 7.41 (1H, ddd, J 7.7, 7.4 and 1.9, H-4’’), 7.88 (1H, dd, J 9.8 and 9.5, H-7), 7.95 (1H, dd, J 10.1 and 1.3, H-5), 8.01 (1H, ddd, J 10.1, 9.5, and 1.0, H-6), 8.24 (1H, dd, J 4.9 and 1.9, H-6’), 8.34 (1H, dd, J 4.9 and 1.7, H-6’’), and 8.78 (1H, dd, J 9.8 and 1.0, H-8): 13C NMR δ 119.64, 121.33, 122.55, 124.42, 125.02, 129.48, 133.72, 134.04, 136.11, 136.34, 139.28, 146.45, 147.80, 147.83, 151.94, 156.21, 157.05, and 157.49; λmax nm (log ε) 290 (4.60), 338 (3.83, sh), and 490 (3.20). Anal. Calcd for C19H12N3Cl: C, 71.81; H, 3.81; N, 13.22. Found: C, 71.70; H, 3.87; N, 13.31.
13a: Orange powders (from hexane-CH2Cl2), mp 197-198 ℃: 1H NMR δ 7.33 (1H, ddd, J 6.8, 4.1, and 0.9, H-5’’), 7.42 (1H, ddd, J 7.6, 4.1, and 0.9, H-5’), 7.77 (1H, dd, J 10.1 and 9.4, H-5), 7.89 (3H, m, H-3’’, 4’, and H-4’’), 8.04 (1H, dd, J 10.8, 9.7, and 0.8, H-6), 8.31 (1H, td, J 8.9 and 0.9, H-3’), 8.37 (1H, d, J 10.8, H-7), 8.83 (1H, dd, J 4.1 and 0.9, H-6’), 8.85 (1H, dd, J 4.3 and 1.0, H-6’’), and 9.19 (1H, dd, J 10.1 and 0.8, H-4): 13C NMR δ 120.80, 121.38, 122.52, 124.44, 127.63, 129.48, 133.01, 134.80, 135.09, 135.48, 137.14, 144.46, 145.35, 148.66, 148.71, 151.37, 154.50, and 156.15; λmax nm (log ε) 276 (4.42), 314 (4.56), 348 (4.14, sh), and 496 (3.21). Anal. Calcd for C19H12N3Cl: C, 71.81; H, 3.81; N, 13.22. Found: C, 71.67; H, 3.98; N, 13.11.
12b: Orange powders (from hexane-CH2Cl2), mp 137-139 ℃: 1H NMR δ 4.31 (3H, s, OCH3), 6.84 (1H, ddd, J 7.5, 4.9, and 1.3, H-5’’), 6.93 (1H, ddd, J 7.4, 4.9, and 1.3, H-5’), 7.10 (1H, dt, J 7.7 and 0.9, H-3’), 7.13 (1H, dt, J 7.9 and 1.0, H-3’’), 7.21 (1H, td, J 7.8, and 1.7, H-4’), 7.33 (1H, ddd, J 7.7, 7.5 and 1.8, H-4’’), 7.66 (2H, m , H-5 and 7), 7.76 (1H, m, H-6), 8.19 (1H, ddd, J 4.9, 1.7, and 0.9, H-6’), 8.33 (1H, ddd, J 4.9, 1.7, and 0.9, H-6’’), and 8.41 (1H, m, H-8): 13C NMR δ 56.64, 112.87, 119.89, 121.74, 125.05, 125.46, 130.21, 131.34, 132.54, 134.29, 134.77, 134.88, 140.77, 143.31, 148.56, 148.61, 153.09, 157.16, 159.72, and 173.93; λmax nm (log ε) 290 (4.56), 295 (4.56), 374 (3.75), 391 (3.77), and 466 (3.33). Anal. Calcd for C20H15N3O: C, 76.66; H, 4.82; N, 13.41. Found: C, 69.63; H, 4.05; N, 11.59.
13b: Orange powders (from hexane-CH2Cl2), mp 142-143 ℃: 1H NMR δ 4.26 (3H, s, OCH3), 7.17 (1H, ddd, J 7.8, 4.9, and 1.0, H-5’’), 7.35 (1H, ddd, J 7.4, 4.2, and 1.0, H-5’), 7.61 (1H, dd, J 10.4, 9.2 and 0.6, H-5), 7.71 1H, ddd, J 10.8, 9.2 and 1.0, H-6), 7.76 (1H, ddd, J 8.0, 7.8, and 1.9, H-4’’), 7.82 (1H, td, J 7.4 and 1.8, H-4’), 7.98 (1H, ddd, J 8.0, 1.0, and 0.9, H-3’’), 8.15 (1H, d, J 10.8, H-7), 8.31 (1H, ddd, J 7.4, 1.0, and 0.9 and 1.0, H-3’), 8.77 (1H, ddd, J 4.8, 1.8, and 0.9, H-6’’), 8.82 (1H, ddd, J 4.2, 1.8, and 0.9, H-6’), and 9.49 (1H, dd, J 10.4 and 1.0, H-4): 13C NMR δ 56.95, 110.11, 120.94, 123.00, 124.42, 128.78, 130.57, 133.26, 133.73, 134.01, 135.38, 136.56, 141.66, 146.32, 149.64, 152.40, 153.99, 158.98, and 173.40; λmax nm (log ε) 279 (4.32), 325 (4.49), 354 (4.08, sh), 394 (3.79), and 476 (3.39). Anal. Calcd for C20H15N3O: C, 76.66; H, 4.82; N, 13.41. Found: C, 69.63; H, 4.05; N, 11.59.

Reaction of 2-methoxy-3-(2-pyridyl)-1-azaazulene (8b) with 2-pyridyllithium
Under argon atmosphere, 1.5 M butyllithium (0.48 mL, 0.75 mmol) was added to the solution of 2-bromopyridine (0.064 mL, 0.68 mmol) in dry THF (10 mL) at –90 ℃. To the mixture 8b (0.080 g, 0.34 mmol) in dry THF (15 mL) was added, and the mixture was stirred for 15 min at –80 ℃, then MeOH (10 mL) was added. After the mixture was warm to rt, o-chloranil (0.070 g, 0.68 mmol) was added to the mixture and the mixture was stirred for 17 h at 50 ℃. The mixture was poured into water and extracted with CHCl3. The extract was dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel column with EtOAc-hexane (1 : 1) to give 13b (0.032 g, 30%) and 12b (0.028 g, 26%).

† Dedicated to Professor Emeritus Keiichiro Fukumoto on occasion of his 75th birthday.

References

1. For reviews see, N. Abe, ‘Recent Research Developments in Organic and Bioorganic Chemistry,’ 2001, 4, 14; Transworld Research Network; T. Nishiwaki and N. Abe, Heterocycles, 1981, 15, 547; CrossRef M. Kimura, Yuki Gosei Kagaku Kyokai Shi, 1981, 39, 690.
2. S. Wakabayashi, R. Uriu, T. Asakura, C. Akamatsu, and Y. Sugihara, Heterocycles, 2008, 75, 383. CrossRef
3. M. Oda, K. Ogura, N. C. Thanh, S. Kishi, S. Kuroda, K. Fujimori, T. Noda, and N. Abe, Tetrahedron Lett., 2007, 48, 4471. CrossRef
4. N. Abe, E. Hashimoto, H. Fujii, Y. Murakami, S. Tagashira, and A. Kakehi, Heterocycles, 2004, 63, 2341. CrossRef
5. N. Abe, M. Tanaka, T. Maeda, H. Fujii, and A. Kakehi, Heterocycles, 2005, 66, 229. CrossRef