Unusual Result of the Reaction of 5,7-Dinitroquinolin-8-ol with Hydrazine Hydrate

Article abstract of DOI:10.1134/S1070428020040259

Abstract: The reaction of 5,7-dinitroquinolin-8-ol with hydrazine hydrate afforded5-aminopyrido[2,3-d]pyridazin-8(7H)-one in 50%yield instead of expected product of reduction of the 7-nitro group,7-amino-5-nitroquinolin-8-ol.

Full text of DOI:10.1134/S1070428020040259

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 4, pp. 723–725. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 4, pp. 649–652.
SHORT
COMMUNICATIONS
Unusual Result of the Reaction of 5,7-Dinitroquinolin-8-ol
with Hydrazine Hydrate
I. I. Ustinova,*, N. V. Khlytina, Yu. M. Atroshchenkoa, and I. V. Shakhkeldyana
a Tolstoy Tula State Pedagogical University, Tula, 300026 Russia
*e-mail: bai2688@yandex.ru
Received September 18, 2019; revised February 14, 2020; accepted February 15, 2020
Abstract—The reaction of 5,7-dinitroquinolin-8-ol with hydrazine hydrate afforded 5-aminopyrido[2,3-d]-
pyridazin-8(7H)-one in 50% yield instead of expected product of reduction of the 7-nitro group, 7-amino-5-
nitroquinolin-8-ol.
Keywords: nitroquinolines, pyridopyridazines, hydrazine hydrate, reduction, 5,7-dinitroquinolin-8-ol, 5-amino-
pyrido[2,3-d]pyridazin-8(7H)-one, molecular spectroscopy
DOI: 10.1134/S1070428020040259
It is known that hydrazine reduces aromatic nitro
compounds to the corresponding amines. These reac-
tions are carried out in the presence of various catalysts
[1–8]. There are published data on selective reduction
of substituted dinitro arenes with hydrazine over Raney
nickel in ethanol–dichloroethane [9] and in the pres-
ence of FeCl3 in methanol [10, 11]. Ayyangar et al. [9]
reported selective reduction of 2,4-dinitrophenol in the
absence of a catalyst.
5-nitroquinolin-8-ol by selective reduction of 5,7-di-
nitroquinolin-8-ol with hydrazine hydrate.
We have found that catalytic reduction of 5,7-dini-
troquinolin-8-ol (1) with hydrazine hydrate is not
selective (Scheme 1). We succeeded in isolating only
the product of reduction of both nitro groups, diamine
3, as dihydrochloride. Compound 3 was identified by
comparing its characteristics with those reported
previously [15, 16]. We failed to obtain 7-amino-5-
nitroquinolin-8-ol (2) despite variation of the reaction
conditions.
Nitroquinoline derivatives exhibit a broad spectrum
of pharmacological activity [12–14]; therefore, synthe-
sis of new compounds of the nitroquinoline series is
practically important. The goal of the present work was
aimed at studying the possibility of obtaining 7-amino-
Unexpected result was obtained when compound 1
was heated in a 60% solution of hydrazine hydrate.
During the process, the reaction mixture changed in
Scheme 1.
NO2
NH2
N2H4·H2O, Raney Ni
or Pd/C, 50°C
+
NO2
N
NH2
N
NH2
OH
OH
2
3
N
NO2
NH2
OH
N2H4·H2O, 75°C, 2 h
N
1
50%
NH
N
O
4
723

USTINOV et al.
724
a way typical of reduction of dinitroarenes; in partic-
ular, the mixture turned red, and the initial compound
gradually dissolved. However, the NMR spectra of
the isolated product were not consistent with structure
2 or 3. The 1H NMR spectrum lacked signal assignable
to 6-H, whereas a downfield signal was observed at
δ 11.73 ppm, which could be assigned to NH proton. In
addition, a broadened singlet typical of aromatic amino
group was present at δ 6.07 ppm. Protons of the pyri-
dine ring resonated in the expected regions, at δ 7.87
(3-H), 8.48 (4-H), and 9.03 ppm (2-H). Furthermore,
the 13C NMR spectrum of the product displayed only
seven signals instead of nine signals necessary for the
quinoline structure. These findings led us to presume
that compound 1 reacts with hydrazine hydrate to give
a rearrangement product, 5-aminopyrido[2,3-d]pyrida-
zin-8(7H)-one 4 (Scheme 1).
328 mg (50%), off-white powder, mp 320–322°C
(from water); published data [17]: mp 320–330°C. IR
spectrum, ν, cm–1: 3205, 3359 br (NH2), 1685 s (C=O),
1637 v.s (NH), 1494, 1550 m (C–N), 1367 w (C–NH2).
1H NMR spectrum (500 MHz), δ, ppm: 6.07 br.s (2H,
NH2), 7.87 d.d (1H, 3-H, J = 4.6, 8.2 Hz), 8.48 d.d
(1H, 4-H, J = 1.53, 8.24 Hz), 9.03 d.d (1H, 2-H,
J = 1.5, 4.6 Hz), 11.73 br.s (1H, CONH). 13C NMR
spectrum (126 MHz), δC, ppm: 121.61 (C4a), 127.32
(C3), 132.65 (C4), 143.88 (C8a), 145.93 (C5), 153.34
(C2), 157.41 (C8). Mass spectrum, m/z (Irel, %):
162 (100) [M]+, 147 (1), 131 (4), 104 (21), 79 (29),
52 (17), 29 (14).
The IR spectrum was recorded in KBr on a Nicolet
iS10 spectrometer. The NMR spectra were recorded on
a Bruker Avance III spectrometer from solutions in
DMSO-d6 using hexamethyldisiloxane as internal
standard. The mass spectrum (electrospray ionization)
was obtained on a Bruker maXis instrument. The
melting point was measured on a Boetius hot stage.
The progress of the reaction was monitored by TLC
on Sorbfil UV-254 plates using DMF–toluene (2:5 by
volume) as eluent; detection under UV light.
Compound 4 was studied in more detail by IR spec-
troscopy. As expected, no strong bands typical of sym-
metric and antisymmetric stretching vibrations of nitro
group were observed. Amide I (νC=O) and amide II
bands (δN–H) were located at 1685 and 1637 cm–1,
respectively, and two bands at 3205 and 3359 cm–1
were assigned to symmetric and antisymmetric vibra-
tions of the primary amino group. Stretching vibrations
of the exocyclic C5–N bond appeared at 1367 cm–1,
and vibrations of the skeletal C–N bonds gave rise to
absorption bands at 1494 and 1550 cm–1. The proposed
structure of 4 was also confirmed by the presence of
the molecular ion peak at m/z 162 in the mass spectrum.
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
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