Acid- and base-catalyzed modifications of 3-[aryl(hetaryl)hydrazinylidene]-3H-furan-2-ones

Article abstract of DOI:10.1134/S107042801509016X

3-[Aryl(hetaryl)hydrazinylidene]furan-2(3H)-ones tend to undergo rearrangements involving different reaction centers and accompanied by opening of the furan ring. The reaction direction is determined by the conditions and nature of substituent in the hydr

Full text of DOI:10.1134/S107042801509016X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 9, pp. 1305–1307. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © E.A. Maksimov, O.A. Mayorova, A.Yu. Yegorova, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 9,
pp. 1330–1332.
Acid- and Base-Catalyzed Modifications
of 3-[Aryl(hetaryl)hydrazinylidene]-3H-furan-2-ones
E. A. Maksimov, O. A. Mayorova, and A. Yu. Yegorova
Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia
e-mail: Beloousova011@yandex.ru
Received March 30, 2015
Abstract—3-[Aryl(hetaryl)hydrazinylidene]furan-2(3H)-ones tend to undergo rearrangements involving dif-
ferent reaction centers and accompanied by opening of the furan ring. The reaction direction is determined by
the conditions and nature of substituent in the hydrazinylidene fragment. The products were characterized by
physicochemical methods.
DOI: 10.1134/S107042801509016X
Heterocyclic compounds containing a hydrazinyli-
dene fragment are capable of undergoing various
chemical transformations, and the resulting compounds
exhibit pronounced biological activity [1]. Various
heterocyclic structures can be obtained from hydra-
zinylidene-substituted furanones [2]. Many known and
widely used medicinal agents (e.g., α-methyltrypt-
amine, Carbidin, 5-methoxytryptamine, Pyrazidol,
etc.) were synthesized by the Fischer rearrangement of
hydrazinylidene-substituted compounds under acidic
conditions. Hydrazinylidene derivatives contain sever-
al reaction centers and mobile double bond system
with lone electron pairs, which favor their various
transformations.
figuration [3, 4]. The direction of heterocyclization of
3-hydrazinylidene-substituted furan-2(3H)-ones in the
reaction with o-phenylenediamine is determined
mainly by the solvent polarity [5].
In continuation of our studies on the reactivity of
3-hydrazinylidenefuran-2(3H)-ones, in the present
work we examined their behavior under conditions of
acid and base catalysis and in the presence of a Lewis
acid (aluminum chloride). By heating 5-aryl-3-(phe-
nylhydrazinylidene)furan-2(3H)-ones 1a and 1b in
formic acid we obtained 5-aryl-1-phenyl-1H-pyrazole-
3-carboxylic acids 2a and 2b (Scheme 1). The
1H NMR spectra of compounds 2 contained singlets
from the COOH proton (δ 11.46 ppm) and 4-H in the
pyrazole ring (δ 7.41 ppm) and multiplets in the region
δ 7.08–8.27 ppm due to aromatic protons.
The formation of indole structure according to
Fischer could be expected; however, compounds 1a
and 1b undergo acid-catalyzed intramolecular recy-
clization following the ANRORC mechanism (addition
of nucleophile–ring opening–ring closure). Protonation
of the endocyclic oxygen atom in 1 leads to opening of
By azo coupling of arene(hetarene)diazonium salts
with 5-arylfuran-2(3H)-ones we obtained new 3-[aryl-
(hetaryl)hydrazinylidene]furan-2-ones [3, 4]. Their
1
structure was determined by IR and H NMR spec-
1
troscopy, including two-dimensional H, 13C, and 15N
heteronuclear correlation techniques (HMQC, HMBC),
as well as by X-ray analysis; it was found that these
compounds in crystal and in solution have E con-
Scheme 1.
O
Ph
NH
Ph
NH
Ph
NH
OH
R
N
N
N
H+, ∆
N
R
O
N
R
O
R
O
O
O
HO
H
Ph
1a, 1b
2a, 2b
R = Ph (a), 4-MeC6H4 (b).
1305

MAKSIMOV et al.
1306
Scheme 2.
Ph
NH
Ph
O
N
N
N
NH
R
AlCl3, CHCl3
N
O
R
O
R
O
AlCl3
O
O
1a, 1b
3a, 3b
R = Ph (a), 4-MeC6H4 (b).
Scheme 3.
O
N
N
R
N
Et3N, EtOH
R
N
N
N
H
N
N
O
H
O
N
N
O
4a, 4b
6a, 6b
O
N
R
N
N
Et3N, EtOH
R
N
N
H
O
H
O
N
N
O
N
5a, 5b
7a, 7b
R = Ph (a), 4-MeC6H4 (b).
the furan ring, followed by intramolecular C,N-hetero-
cyclization with formation of pyrazole ring.
two doublets of doublets at δ 3.97–4.05 and 4.50–
4.55 ppm due to methylene protons and a triplet at
δ 6.14–6.33 ppm (6-H in 6 or 3-H in 7), which con-
firmed the proposed structures.
Heating of compounds 1a and 1b in chloroform in
the presence of 2 equiv of aluminum chloride led to the
formation of 3-(2-aryl-2-oxoethyl)cinnolin-4(3H)-ones
3a and 3b (Scheme 2). Presumably, coordination of
aluminum chloride to the carbonyl oxygen atom in 1
enhances polarization of the C=O bond, which favors
opening of the furan ring. The subsequent intramolec-
ular acylation of the ortho-carbon atom of the aryl
substituent in the hydrazinylidene fragment closes the
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
MSL-400 spectrometer at 400 MHz using CDCl3 as
solvent and tetramethylsilane as internal standard.
Initial 5-aryl-3-[aryl(hetaryl)hydrazinylidene]furan-
2(3H)-ones were synthesized according to the proce-
dure described in [6].
1
pyridazine ring. The H NMR spectra of compounds
3a and 3b in CDCl3 confirmed the assumed structure.
The 3-H proton resonated as a triplet at δ 5.80–
5.93 ppm), protons in the methylene group linked to C3
gave two doublets at δ 2.65–2.71 and 2.85–2.92 ppm,
and signals from the aromatic protons appeared as
a multiplet in the region δ 7.27–8.13 ppm.
1,5-Diphenyl-1H-pyrazole-3-carboxylic acid
(2a). A mixture of 1 g (3.79 mmol) of 5-phenyl-3-
(phenylhydrazinylidene)furan-2(3H)-one (1a) and
20 mL of formic acid was heated for 10 h at 40°C. The
mixture was cooled and neutralized with sodium car-
bonate, and the precipitate was filtered off and recrys-
tallized from propan-2-ol. Yield 0.79 g (79%), red–
A different heterocyclization pathway was observed
for compounds 4a, 4b, 5a, and 5b with a heterocyclic
substituent in the hydrazinylidene fragment. The reac-
tions were carried out by heating furanones 4 and 5 in
boiling ethanol in the presence of triethylamine, and
the products were [1,2,4]triazolo[3,4-c][1,2,4]triazin-
5(6H)-ones 6a and 6b or [1,2,4]triazino[4,3-a]benzim-
idazol-4(3H)-ones 7a and 7b, respectively (Scheme 3).
1
brown crystals, mp 221–223°C. H NMR spectrum, δ,
ppm: 7.40 s (1H, CH), 7.12–8.27 m (10H, Harom), 11.46 s
(1H, OH). Found, %: C 77.81; H 4.30; N 10.83.
C16H12N2O2. Calculated, %: C 72.72; H 4.58; N 10.60.
5-(4-Methylphenyl)-1-phenyl-1H-pyrazole-3-car-
boxylic acid (2b) was synthesized in a similar way
from 5-(4-methylphenyl)-3-(phenylhydrazinylidene)-
1
Compounds 6 and 7 displayed in the H NMR spectra
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015

ACID- AND BASE-CATALYZED MODIFICATIONS OF 3-[ARYL(HETARYL)...
1307
furan-2(3H)-one (1b). Yield 0.65 g (65%), red–brown
crystals, mp 235–237°C. H NMR spectrum, δ, ppm:
2.29 s (3H, CH3), 7.08–8.18 m (9H, Harom), 7.51 s
(1H, 4-H), 11.26 s (1H, OH). Found, %: C 73.08;
H 4.80; N 10.34. C17H14N2O2. Calculated, %: C 73.37;
H 5.07; N 10.07.
spectrum, δ, ppm: 2.34 s (3H, CH3), 3.97–4.00 d.d and
4.51–4.53 d.d (1H each, CH2), 6.14–6.16 t (1H, 6-H),
7.29–8.12 m (4H, Harom), 9.78 s (1H, 3-H). Found, %:
C 58.21; H 4.40; N 25.84. C13H11N5O2. Calculated, %:
C 57.99; H 4.12; N 26.01.
1
3-(2-Oxo-2-phenylethyl)[1,2,4]triazino[4,3-a]-
benzimidazol-4(3H)-one (7a). Yield 0.83 g (83%),
3-(2-Oxo-2-phenylethyl)cinnolin-4(3H)-one (3a).
Anhydrous aluminum chloride, 10 g (7.58 mmol), was
added under stirring to a mixture of 1 g (3.79 mmol) of
compound 1a and 20 mL of chloroform. The mixture
was cooled, and 30 mL of cold water and 10 mL of
concentrated aqueous HCl were added dropwise under
stirring. The precipitate was filtered off and recrystal-
lized from ethanol.
1
light brown crystals, mp 117–118°C. H NMR spec-
trum, δ, ppm: 4.01–4.03 d.d and 4.50–4.54 d.d
(1H each, CH2), 6.30–6.32 t (1H, 3-H), 7.31–8.27 m
(9H, Harom). Found, %: C 66.97; H 4.01; N 18.00.
C17H12Ν4O2. Calculated, %: C 67.10; H 3.98; N 18.41.
3-[2-(4-Methylphenyl)-2-oxoethyl][1,2,4]triazino-
[4,3-a]benzimidazol-4(3H)-one (7b). Yield 0.82 g
1
3-[2-(4-Methylphenyl)-2-oxoethyl]cinnolin-
4(3H)-one (3b) was synthesized in a similar way from
5-(4-methylphenyl)-3-(phenylhydrazinylidene)furan-
2(3H)-one. Yield 0.63 g (63%), brown crystals,
(82%), light brown crystals, mp 120–121°C. H NMR
spectrum, δ, ppm: 2.30 s (3H, CH3), 4.02–4.05 d.d and
4.52–4.55 d.d (1H each, CH2), 6.30–6.33 t (1H, 3-H),
7.29–8.26 m (8H, Harom). Found, %: C 68.03; H 4.26;
N 17.38. C18H14Ν4O2. Calculated, %: C 67.91; H 4.43;
N 17.60.
1
mp 120–122°C. H NMR spectrum, δ, ppm: 2.29 s
(3H, CH3), 2.68–2.71 d.d and 2.85–2.87 d.d (1H each,
CH2), 5.90–5.93 t (1H, 3-H), 7.40–8.13 m (8H, Harom).
Found, %: C 73.45; H 5.00; N 10.29. C17H14N2O2. Cal-
culated, %: C 73.37; H 5.07; N 10.07.
This study was performed under financial support
by the Russian Science Foundation (project no. 15-13-
10 007) and by the Russian Foundation for Basic
Research (synthesis of the initial compounds, project
no. 13-03-00318a).
6-(2-Oxo-2-phenylethyl)[1,2,4]triazolo[3,4-c]-
[1,2,4]triazin-5(6H)-one (6a). A mixture of 1 g
(3.92 mmol) of 5-phenyl-3-[(1H-1,2,4-triazol-5-yl)hy-
drazinylidene]furan-2(3H)-one (4a), 20 mL of ethanol,
and 5 μL of triethylamine was heated for 5 h at 50°C.
The mixture was cooled to room temperature and
acidified with aqueous HCl to pH 7, and the precipitate
was filtered off and recrystallized from ethanol. Yield
0.87 g (87%), light brown crystals, mp 102–103°C.
1H NMR spectrum, δ, ppm: 4.00–4.03 d and 4.50–
4.52 d (1H each, CH2), 6.14–6.17 t (1H, 6-H), 7.49–
8.14 m (5H, Harom), 9.77 s (1H, 3-H). Found, %:
C 56.83; H 3.39; N 27.12. C12H9N5O2. Calculated, %:
C 56.47; H 3.55; N 27.44.
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a similar way.
5. Maiorova, O.A. and Egorova, A.Yu., Russ. J. Org. Chem.,
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[3,4-c][1,2,4]triazin-5(6H)-one (6b). Yield 0.86 g
1
(86%), light brown crystals, mp 115–116°C. H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015