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LETTER
(4) Coates, W. J. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds;
Pergamon Press: Oxford, 1996; Vol. 6, p 1.
(5) (a) Morgan, J. F. J. Am. Chem. Soc. 1948, 70, 2253. (b) Wiley,
R. H.; Ellert, H. G. J. Am. Chem. Soc. 1955, 77, 5187.
(6) (a) Nölken, E.; Ziegler, E. Monatsh. Chem. 1960, 91, 1162.
(b) Deodhar, K. D.; Deval, S. D. Synthesis 1983, 421.
(c) Monge, A.; Palop, J. A.; Goñi, T.; Fernández-Alvarez, E.
J. Heterocycl. Chem. 1986, 23, 141.
(7) (a) KoËevar, M.; Polanc, S.; Tiöler, M.; VerËek, B.
Heterocycles 1990, 30, 227. (b) Treböe, P.; Polanc, S.;
KoËevar, M.; äolmajer T.; GoliË Grdadolnik, S. Tetrahedron
1997, 53, 1383. (c) VraniËar, L.; Polanc S.; KoËevar, M.
Tetrahedron 1999, 55, 271.
2a: mp (uncorrected) 202−205 °C (BuOH/MeCN); 1H NMR δ
0.89 (6H, s, two Me), 2.03 (2H, s, 9-CH2), 2.68 (2H, d, J =
5.45 Hz, 7-CH2), 2.96 (2H, s, 4-CH2), 4.29 (2H, br s, NH2),
7.49 (1H, t, J = 5.45 Hz, 6-H), 9.07 (1H, br s, NH), 9.91 (1H,
br s, NH).
2b: mp 243−245 °C, decomp (DMF/MeOH); 1H NMR δ 0.86
(3H, d, J = 6.65 Hz, Me), 1.99 (1H, m, 9-Ha), 2.15 (1H, m, 8-
H), 2.42 (1H, m, 9Hb), 2.64 (1H, m, 7-Ha), 2.96 (2H, s, 4-
CH2), 3.06 (1H, m, 7-Hb), 4.29 (2H, br s, NH2), 7.40 (1H, deg
t, 6-H), 9.07 (1H, br s, NH), 9.87 (1H, br s, NH).
2c: mp 227−229 °C (DMF); 1H NMR δ 1.80 (2H, m, 8-CH2),
2.36 (2H, m, 9-CH2), 2.96 (2H, s, 4-CH2), 3.01 (2H, m, 7-
CH2), 4.31 (2H, br s, NH2), 7.39 (1H, t, J = 5.5 Hz, 6-H), 9.08
(1H, br s, NH), 9.84 (1H, br s, NH).
(8) KoËevar, M. Acta Chim. Slov. 1996, 43, 143.
5a: mp 140−143 °C (Et2O/hexane); 1H NMR δ 1.01 (6H, s,
two Me), 2.64 (2H, d, J = 6.0 Hz, 7-CH2), 2.95 (2H, s, 9-CH2),
3.98 (3H, s, OMe), 8.13 (1H, s, 4-H), 8.82 (1H, deg t, 6-H).
5b: mp 143−145 °C (Et2O); 1H NMR δ 0.98 (3H, d, J = 6.7 Hz,
8-Me), 2.46 (1H, m, 8-H), 2.62 (1H, m, 7-Ha), 2.86 (1H, m, 9-
Ha), 3.07 (1H, m, 7-Hb), 3.33 (1H, m, 9-Hb), 3.98 (3H, s,
OMe), 8.13 (1H, s, 4-H), 8.70 (1H, t, J = 5.5 Hz, 6-H).
5c: mp 221−224 °C (MeOH); 1H NMR δ 2.09 (2H, m, 8-CH2),
3.01 (2H, m, 7-CH2), 3.23 (2H, m, 9-CH2), 3.98 (3H, m,
OMe), 8.13 (1H, s, 4-H), 8.64 (1H, deg t, 6-H).
(9) Compounds 1b and 1c were prepared from 3-amino-7,8-
dihydro-2H-1-benzopyran-2,5(6H)-dione and its 7-methyl
analog8 with hydrazoic acid by the known7a method.
(10) General procedure for the synthesis of
pyridazino[4,3-c]azepine-3-carboxylic acid hydrazides 2a−c:
A mixture of compound 1 (1 mmol), 98% hydrazine hydrate
(2.2 mmol) and p-toluenesulfonic acid hydrate (0.1 mmol) in
absolute ethanol (4−8 mL) was refluxed for 7−9.5 h. After
cooling, the yellow crystalline substance was filtered off to
give TLC-pure 2b−c. Additional amounts of products can be
obtained by evaporation of the filtrate to dryness and addition
of a small amount of absolute ethanol and cooling. For
isolation of 2a the reaction mixture was evaporated and the
remaining residue was crystallised from BuOH/MeCN. Total
yields 52−65%.
Typical procedure for the synthesis of 5 with TTN: To the
stirred solution of 2a (222 mg, 1 mmol) in methanol (12 mL),
a solution of TTN (1.555 g, 3.5 mmol) in methanol (7 mL)
was added, then it was diluted with an additional amount of
methanol (5 mL) and stirred for 1 h. The solid was filtered off
and washed with methanol (7 mL), the filtrate was evaporated
in vacuo, the residue was diluted with water (30 mL) and
extracted several times with chloroform to give 179 mg (72%)
of TLC-pure product 5a (without optimisation).
6a:1H NMR δ 0.90 (6H, s, two Me), 2.09 (2H, s, 9-CH2), 2.76
(2H, d, J = 6 Hz, 7-CH2), 3.07 (2H, s, 4-CH2), 3.77 (3H, s,
OMe), 7.65 (1H, t, J = 6 Hz, 6-H), 10.35 (1H, br s, NH); MS
m/z 251 (M+, 31%), 191 (100).
(12) (a) Hudlický, M. Oxidations in Organic Chemistry; ACS
Monograph 186: Washington, DC, 1990. (b) McKillop, A.;
Taylor, E. C. In Organic Syntheses by Oxidation with Metal
Compounds; Mijs, W. J, de Jonge, C. R. H. J., Eds.; Plenum:
New York, 1986; p 695. (c) KoËevar, M.; Mihorko, P.; Polanc,
S. J. Org. Chem. 1995, 60, 1466.
(13) Tsuji, J.; Nagashima, T.; Thi Qui, N.; Takayanagi, H.
Tetrahedron 1980, 36, 1311.
(14) ätefane, B.; KoËevar, M.; Polanc, S. Tetrahedron Lett. 1999,
40, 4429.
(11) New compounds gave satisfactory elemental analyses and
were also identified on the basis of their NMR (DMSO-d6, 300
MHz, for 6a 60 MHz), IR and mass spectra. Selected data:
Article Identifier:
1437-2096,E;2000,0,02,0254,0256,ftx,en;G24399ST.pdf
Synlett 2000, No. 2, 254–256 ISSN 0936-5214 © Thieme Stuttgart · New York