88
HETEROCYCLES, Vol. 90, No. 1, 2015
sequence was required, 2,6-diaminoazulene derivatives 2−4 were also obtained from 1 under much milder
reaction conditions. Since compound 1 is readily available as a starting material by the selective
bromination of diethyl 2-aminoazulene-1,3-dicarboxylate at the 6-position, our synthetic methodologies
have potentials to be an efficient procedure for the synthesis of azulene derivatives with multiple-amino
functional groups.
ACKNOWLEDGEMENTS
This work was partially supported by a Grant-in-Aid for Research from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan (Grant No. 25810019 to T. S.).
REFERENCE AND NOTE
1. (a) J. Kido and Y. Okamoto, Chem. Rev., 2002, 102, 2357; (b) A. C. Grimsdale, K. L. Chan, R. E.
Martin, P. G. Jokisz, and A. B. Holmes, Chem. Rev., 2009, 109, 897.
2. J.-P. Corbet and G. Mignani, Chem. Rev., 2006, 106, 2651.
3. T. Nozoe, K. Takase, and M. Tada, Bull. Chem. Soc. Jpn., 1963, 36, 1006.
4. T. Nozoe, K. Takase, and M. Tada, Bull. Chem. Soc. Jpn., 1965, 38, 247.
5. (a) R. Yokoyama, S. Ito, T. Okujima, T. Kubo, M. Yasunami, A. Tajiri, and N. Morita, Tetrahedron,
2003, 59, 8191; (b) S. Ito, T. Kubo, N. Morita, T. Ikoma, S. Tero-Kubota, J. Kawakami, and A.
Tajiri, J. Org. Chem., 2005, 70, 2285.
6. T. Nozoe, T. Asao, H. Susumago, and M. Ando, Bull. Chem. Soc. Jpn., 1974, 47, 1471.
7. J. J. Li, Z. Wang, and L. H. Mitchell, J. Org. Chem., 2007, 72, 3606.
8. General procedure: The solution of 1 (366 mg, 1.00 mmol) in the corresponding amines (5 mL)
was stirred at 130 °C in a sealed-tube for 6 h under an Ar atmosphere. The reaction mixture was
poured into a 1M HCl solution and extracted with CH2Cl2. The organic layer was washed with brine,
dried with Na2SO4, and concentrated under reduced pressure. The residue was purified by column
chromatography on silica gel with CH2Cl2 to give 2,6-diaminoazulenes 2−4 (yield of the products is
summarized in Table 1).
1
9. Selected data of compound 2: mp 208.0 – 210.0 °C (MeOH); H NMR (500 MHz, CDCl3): δH =
9.01 (d, 2H, J = 11.7 Hz, 4,8-H), 7.05 (br s, 2H, NH2), 6.87 (d, 2H, J = 11.7 Hz, 5,7-H), 4.42 (q, 4H,
J = 7.2 Hz, CO2Et), 3.53 (t, 4H, J = 6.3 Hz, 2,5-H of pyrrolidine), 2.13 (t, 4H, J = 6.3 Hz, 3,4-H of
pyrrolidine), 1.45 (t, 6H, J = 7.2 Hz, CO2Et).
10. Selected data of compound 3: Orange oil; 1H NMR (500 MHz, CDCl3): δH = 8.97 (d, 2H, J = 11.8
Hz, 4,8-H), 7.32 (br s, 2H, NH2), 7.12 (d, 2H, J = 11.8 Hz, 5,7-H), 4.42 (q, 4H, J = 7.2 Hz, CO2Et),
3.49 (t, 4H, J = 5.5 Hz, 2,6-H of piperidine), 1.72 (br s, 6H, 3,4,5-H of piperidine), 1.45 (t, 6H, J =
7.2 Hz, CO2Et).
1
11. Selected data of compound 4: mp 139.0 – 140.0 °C (MeOH); H NMR (500 MHz, CDCl3): δH =
9.02 (d, 2H, J = 11.8 Hz, 4,8-H), 7.40 (br s, 2H, NH2), 7.15 (d, 2H, J = 11.8 Hz, 5,7-H), 4.43 (q, 4H,
J = 7.2 Hz, CO2Et), 3.88 (t, 4H, J = 4.9 Hz, 3,5-H of morpholine), 3.43 (t, 4H, J = 4.9 Hz, 2,6-H of
morpholine), 1.45 (t, 6H, J = 7.2 Hz, CO2Et).
12. T. Kanzian, T. A. Nigst, A. Maier, S. Pichl, and H. Mayr, Eur. J. Org. Chem., 2009, 6379.