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Synlett 2006(20): 3431-3434  
DOI: 10.1055/s-2006-958419
LETTER
© Georg Thieme Verlag Stuttgart · New York

Recyclization of Hydrazides of 2-Carboxyphenyldifurylmethanes: Synthesis of Novel 4,10-Dihydro-3H-pyridazino[1,6-b]isoquinolin-10-one System

Alexander V. Butin*a, Artem S. Dmitrieva, Vladimir T. Abaevb, Valery E. Zavodnikc
a Research Institute of Heterocyclic Compounds Chemistry, Kuban State University of Technology, Moskovskaya st. 2, Krasnodar 350072, Russian Federation
Fax: +7(861)2596592; e-Mail: alexander_butin@mail.ru;
b North-Ossetian State University, Vatutina st. 46, Vladikavkaz 362025, Russian Federation
c Karpov Institute of Physical Chemistry, Vorontsovo pole st. 10, Moscow 103064, Russian Federation
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Publikationsverlauf

Received 27 July 2006
Publikationsdatum:
08. Dezember 2006 (online)

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Abstract

A novel heterocyclic system of 4,10-dihydro-3H-pyr­idazino[1,6-b]isoquinolin-10-one has been synthesized via acid-catalyzed recyclization of hydrazides of 2-carboxyphenyldifurylmethanes as well as by alternative synthesis by interaction of the corresponding isocoumarine ketones with hydrazine hydrate.

Key words

furans - ring opening - ring closure - fused-ring systems - pyridazino[1,6-b]isoquinolin-10-one

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Preparation of Compounds 10a-f; General Procedure A mixture of compound 9 (5.81 mmol), NH2NH2·H2O (9 mL) and n-BuOH (9 mL) was refluxed for 20 min. Then it was poured into H2O (300 mL). The resulting precipitate was filtered off, air-dried and used in the next step as such.

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Preparation of Compounds 13a-f (Method A); General Procedure To a 15% solution of p-TsOH in benzene (20 mL), prepared by refluxing p-TsOH·H2O in benzene with azeotropic removal of H2O, compound 10 (4.19 mmol) was added and the mixture was refluxed for 10 min. The resulting solution was poured into H2O (300 mL). The slurry was extracted with CH2Cl2 (3 × 50 mL). The combined extract was washed with H2O, dried over anhyd Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel (hexane-EtOAc, 4:1). Solvent was stripped off of the eluate and the residue was recrystallized from hexane-EtOAc (10:1) at temperature below 0 °C.
Selected analytical data of 13b: mp 173-174 °C. IR: 1667 (CO) cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.33 (s, 3 H, CH3), 2.33 (t, J = 7.5 Hz, 2 H, CH2), 2.38 (s, 3 H, CH3), 2.84 (t, J = 7.5 Hz, 2 H, CH2), 6.15 (d, J = 3.1 Hz, 1 H, 4-HFur), 6.31 (d, J = 3.1 Hz, 1 H, 3-Hfur), 7.33 (d, J = 8.7 Hz, 1 H, HAr), 7.51 (dd, J = 2.2, 8.7 Hz, 1 H, HAr), 8.52 (d, J = 2.2 Hz, 1 H, HAr). 13C NMR (50 MHz, CDCl3): δ = 13.82, 22.54, 24.43, 24.65, 105.25, 106.95, 113.16, 126.36, 126.80, 128.09, 132.69, 133.04, 134.63, 135.08, 145.49, 152.92, 158.27, 163.19. MS: m/z (%) = 329, 327 (5, 15) [M+ + 1], 328, 326 (28, 83) [M+], 293 (28), 292 (100), 249 (18), 208 (15), 43 (20). Anal. Calcd for C18H15ClN2O2: C, 66.16; H, 4.63. Found: C, 66.08; H, 4.69.

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Preparation of Compounds 13a-f (Method B); General Procedure A suspension of compound 14 (3.37 mmol) in ethylene glycol (50 mL) with NH2NH2·H2O (1 mL) was stirred at r.t. until complete dissolution of the starting material was observed (30 min, TLC monitoring). The resulting solution was refluxed for 15 min, poured into H2O (300 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined extract was washed with H2O, dried over anhyd Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel (hexane-EtOAc, 4:1). The solvent was stripped off of the eluate and the residue was recrystallized from hexane-EtOAc (10:1) at temperature below 0 °C.

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Crystal data of compound 13f: C18H15BrN2O2, monoclinic, space group C2/c; a = 32.028(6) Å, b = 11.022(2) Å, c = 9.016(2) Å, α = 90°, β = 90.48(3)°, γ = 90°, V = 3182.6(11) Å3, Z = 8, D calcd = 1.550 Mg/m3, F(000) = 1504; 3330 reflections collected, 3116 unique (R int = 0.0269); final R indices (3116 observed collections I >2σI): R 1 = 0.0331, wR 2 = 0.0818; final R indices (all data): R 1 = 0.1677, wR 2 = 0.0945. Crystallographic data (excluding structure factors) for the structure in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 614755. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or E-mail: deposit@ccdc.cam.ac.uk]. Each request should be accompanied by the complete citation of this paper.