Adduct of dimedone and 1,1,2-tribenzoylethylene. Keto-enol tautomerism and reactions with N-nucleophiles

Article abstract of DOI:10.1134/S107042801502013X

Condensation of dimedone with 1,1,2-tribenzoylethylene provided pentaketone, where the position of the keto-enol equilibrium in the dibenzoylmethane fragment depended on external factors. In reactions with N-nucleophiles the pentaketone behaves as 1,4-diketone, affording with ammonium acetate, methylamine, and hydroxylamine hydrochloride functional derivatives of 4,5,6,7-tetrahydroindole, and with hydrazine hydrate, a pyridazine derivative.

Full text of DOI:10.1134/S107042801502013X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 2, pp. 214–216. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.V. Andina, A.N. Andin, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 2, pp. 226–228.
Adduct of Dimedone and 1,1,2-Tribenzoylethylene.
Keto-Enol Tautomerism and Reactions with N-Nucleophiles
A. V. Andina and A. N. Andin
Far-Eastern Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690950 Russia
e-mail: andin.an@dvfu.ru
Received October 31, 2014
Abstract―Condensation of dimedone with 1,1,2-tribenzoylethylene provided pentaketone, where the position
of the keto-enol equilibrium in the dibenzoylmethane fragment depended on external factors. In reactions with
N-nucleophiles the pentaketone behaves as 1,4-diketone, affording with ammonium acetate, methylamine, and
hydroxylamine hydrochloride functional derivatives of 4,5,6,7-tetrahydroindole, and with hydrazine hydrate, a
pyridazine derivative.
DOI: 10.1134/S107042801502013X
Polycarbonyl compounds containing various
combinations of dicarbonyl functions (1,3- and 1,5-, or
1,3-, 1,4-, and 1,5-) are sufficiently well studied due to
their availability and wide synthetic opportunities for
the preparation of nitrogen heterocyclic systems:
pyrrole, pyridine, pyridazine, and their fused analogs.
Polyketones of these type can contain in their structure
a dibenzoylmethane fragment. The preparation of such
compounds was described resulting from symmetric
[1–3] and unsymmetrical [4] diketone condensation
and also from Michael reaction [5].
ethanol in the presence of catalytic quantity of NaOH.
The yield of pentaketone 1 reached 80% (Scheme 1).
In compound 1 a keto-enol tautomerism in the
dibenzoylmethane fragment is observed, and the
equilibrium position depends on external factors, in
particular, on the solvent. 1Н NMR spectrum registered
in DMSO-d6 confirms the structure of tautomer B
where the dibenzoylmethane fragment is present in the
diketo form. This is in agreement with the known fact
that in polar solvent the amount of the enol form
decreases. The 1Н NMR spectrum contains two
characteristic doublets belonging to protons Н2 and Н3
(J 10.1 Hz) of the main chain at 6.31 and 5.51 ppm
respectively as well as doublets from protons in the
ortho-positions of two benzene rings of the
dibenzoylmethane fragment having very close
chemical shifts (7.86 and 7.88 ppm) of intensity 2Н
each. IR spectrum recorded from a KBr pellet, on the
other hand, fixes the presence of tautomer А. The wide
absorption bands of enol hydroxy groups of the
We formerly studied reactions of N-hetero-
cyclization of dimedone adducts with 1,1-diacetyl-2-
benzoylethylene [6] and 1,2-dibenzoyl-ethylene [7].
Here we report on the synthesis of a dimedone
adduct to 1,1,2-tribenzoylethylene, on the study of its
keto-enol tautomerism, and also of the regiodirection
of its reaction with some nitrogen mono- and
binucleophiles. The dimedone condensation with
1,1,2-tribenzoylethylene was carried out at boiling in
Scheme 1.
O
Ph
O
Ph
4
Ph
O
O
O
Ph
O
O
O
1
3
2
Ph
Ph
NaOH
EtOH
6'
O
O
Ph
+
1''
2'
OH
OH
O
Ph
Ph
OH
OH
1
A
B
214

ADDUCT OF DIMEDONE AND 1,1,2-TRIBENZOYLETHYLENE. KETO-ENOL TAUTOMERISM
215
Scheme 2.
OH
OH
Ph
Ph
O
O
O
O
AcONH4
or CH3NH2
Ph
Ph
Ph
Ph
.
NH2OH HCl/Py
1
EtOH
AcOH
N
N
OH
2c
R
2a, 2b
dimedone and dibenzoylmethane fragments appear in
the region 2650 and 3550 cm–1 respectively.
calculations. For tautomer A we calculated by the
method of density functional theory using basis 6-311
(p) and hybride functional b3lyp applying Firefly 71G
software the partial atomic charges according to
Mulliken. The calculation demonstrated that the
positive charges on the carbonyl and vinyl β-carbon
atoms of the dimedone fragment were somewhat larger
than the charges on analogous atoms of the
dibenzoylmethane fragment. The charges on carbon
atoms in the positions 1, 4, 2', 6', 1" are +0.275,
+0.306, +0.276, +0.308, +0.212 respectively.
We calculated standard enthalpies of formation of
two tautomer forms of pentaketone 1 in the gas phase
by the method AM1 using Firefly 71G software. The
comparison of ΔН° values of tautomers А and B
(–339.2 and –225 kJ mol–1 respectively) shows the
higher stability of the А form.
We examined the regiodirection of adduct 1
reactions with some nitrogen mono- and
binucleophiles: ammonium acetate, methylamine,
hydroxylamine hydrochloride, and hydrazine hydrate.
The reactions with ammonium acetate and
methylamine were carried out in boiling acetic acid,
with hydroxylamine hydrochloride, in boiling ethanol
in the presence of pyridine. Functional derivatives of
4,5,6,7-tetrahydroindole 2а–2c were obtained in 63–
83% yields.
Another regiodirection of the N-heterocyclization
was observed at reacting the initial adduct with
hydrazine hydrate. The reaction was carried out in
ethanol at 60°С. The yield of pyridazine derivative 3
described formerly in [8] was 93% (Scheme 3).
Scheme 3.
O
Ph
In compounds 2а–2c the enol form is preferable both
in solid state and in solutions in CDCl3 or DMSO-d6,
as confirmed by the data of IR and Н NMR spectra.
NH2NH2 . H2O
1
1
Ph
Ph
EtOH
N
N
IR spectra of compounds 2а–2c contain a wide
absorption band of the enol hydroxy group of the
dibenzoylmethane fragment in the region 3120–
3
1
3300 cm–1, in the Н NMR spectra the broadened
Apparently, in the first stage in the reaction with
hydrazine hydrate acting as a base the initial
compound suffers a retro-Michael decomposition. The
formed 1,1,2-tribenzoylethylene reacts further with
hydrazine hydrate as with N-nucleophile giving
compound 3.
singlet of the enol hydroxyl appears at 7.0–7.9 (in
CDCl3) and 10 ppm (in DMSO-d6).
Therefore in the performed reactions compound 1
behaved as 1,4-diketone; therewith the dimedone
fragment was involved in the reaction, and the
dibenzoylmethane moiety remained intact. Apparently
the inertness of the latter is due, on the one hand, to the
steric hindrance from the two benzene rings; on the
other hand, the conservation of the intramolecular
hydrogen bond in the dibenzoylmethane fragment
provides an additional energy gain.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Perkin Elmer Spectrum BX from pellets with KBr. Н
1
NMR spectra were registered on a spectrometer Bruker
AC-400 (operating frequency 400 MHz), internal
reference TMS. Reaction progress was monitored by
TLC on Sorbfil plates, eluent ethyl acetate, develop-
ment in iodine vapor.
The experimentally observed regiodirection of the
N-heterocyclization of the initial compound is well
consistent with the data of quantum-chemical
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 2 2015

ANDINA, ANDIN
216
2-Benzoyl-3-(4,4-dimethyl-2,6-dioxocyclohexyl)-1,4-
(3Н, CH3N), 7.09 t (2НAr, J 7.6 Hz), 7.13–7.20 m (3НAr),
7.21–7.27 m (3НAr), 7.31–7.40 m (5НAr), 7.60 d (2НAr, J
7.7 Hz), 7.89 br.s (1Н, ОН). Found, %: С 80.52; H 6.33; N
3.16. C32H29NO3. Calculated, %: С 80.82; H 6.15; N 2.95.
diphenylbutane-1,4-dione (1). A mixture of 0.123 g
(0.88 mmol) of dimedone and 0.2 g (0.59 mmol) of 1,1,2-
tribenzoylethylene was dissolved at heating in 10 mL
of ethanol, 3 mg (0.08 mmol) of NaOH was added, and the
mixture was boiled for 3 h, then it was poured in 100 g
of ice mixed with sodium chloride. The separated precipi-
tate was filtered off, washed with water, dried in air,
and then it was triturated with cold ethyl ether. Yield
0.227 g (80%). Colorless crystals, mp 145–147°С. IR
spectrum, ν, cm–1: 3550, 2650 (enol ОН), 1688 (С=О),
1597 (Ph). 1Н NMR spectrum (DMSO-d6), δ, ppm: 0.39
s (6Н, 2СН3), 1.43 br.s (4Н, 2СН2), 5.51 d (1Н, Н3, J
10.1 Hz), 6.31 d (1Н, H2, J 10.1 Hz), 7.32 t (2НAr, J
7.6 Hz), 7.40–7.50 m (5НAr), 7.52–7.62 m (2НAr), 7.66 d
(2НAr, J 7.6 Hz), 7.86 d (2НAr, J 7.4 Hz), 7.88 d (2НAr, J
7.4 Hz). Found, %: С 77.06; H 6.02. C31H28O5. Calcu-
lated, %: С 77.48; H 5.87.
2-(1-Hydroxy-6,6-dimethyl-4-oxo-2-phenyl-
4,5,6,7-tetrahydro-1Н-indol-3-yl)-1,3-diphenyl-
propane-1,3-dione (2c). In 5 mL of ethanol was dis-
solved 0.1 g (0.21 mmol) of compound 1 and 30 mg
(0.43 mmol) of hydroxylamine hydrochloride, 2 drops
of pyridine was added, the mixture was boiled for 1 h,
then it was poured in 100 g of ice mixed with sodium
chloride acidified with 1 mL of conc. HCl. The separa-
ted precipitate was filtered off, washed with water, dried
in air, and then it was triturated with cold ethyl ether.
Yield 63 mg (63%). Light yellow crystals, mp 232–233°С.
IR spectrum, ν, cm–1: 3120 (enol ОН), 2750 (ОН), 1622
(С=О), 1600 (Ph). 1Н NMR spectrum (CDCl3), δ, ppm:
0.86 s (3Н, СН3), 0.91 s (3Н, СН3), 1.88 d (1Н, СН2, J
16.4 Hz), 1.93 d (1Н, СН2, J 16.4 Hz), 2.58 s (2Н, СН2),
6.93 d (2НAr, J 7.2 Hz), 6.98 t (2НAr, J 7.2, 7.8 Hz),
7.02–7.09 m (3НAr), 7.12–7.25 m (6НAr), 7.51 d (2НAr, J
7.5 Hz), 9.97 br.s (1Н, ОН). Found, %: С 77.53; H 5.94; N
3.10. C31H27NO4. Calculated, %: С 77.97; H 5.70; N 2.93.
2-(6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetra-
hydro-1Н-indol-3-yl)-1,3-diphenylpropane-1,3-
dione (2а). A solution of 0.1 g (0.21 mmol) of com-
pound 1 and 0.23 g (3 mmol) of ammonium acetate in
5 mL of acetic acid was boiled for 1.5 h, then it was
poured in 100 g of ice mixed with sodium chloride.
The separated precipitate was filtered off, washed with
water, dried in air, and then it was triturated with cold
ethyl ether. Yield 80 mg (83%). Light yellow crystals,
mp 240–242°С. IR spectrum, ν, cm–1: 3385 (NН), 3300
(enol ОН), 1639 (С=О), 1602 (Ph). 1Н NMR spectrum
(CDCl3), δ, ppm: 0.92 s (3Н, СН3), 1.00 s (3Н, СН3),
2.02 d (1Н, СН2, J 16 Hz), 2.12 d (1Н, СН2, J 16 Hz),
2.31 d (1Н, СН2, J 17.9 Hz), 2.36 d (1Н, СН2, J 17.9 Hz),
6.99 br.s (1Н, ОН), 7.08–7.37 m (11НAr), 7.43 d (2НAr,
J 7.3 Hz), 7.70 d (2НAr, J 7.3 Hz), 8.74 br.s (1Н, NH).
Found, %: С 80.29; H 6.09; N 2.78. C31H27NO3. Cal-
culated, %: С 80.67; H 5.90; N 3.03.
4-Benzoyl-3,6-diphenylpyridazine [phenyl(3,6-
diphenylpyridazin-4-yl)methanone] (3). A solution of
0.1 g (0.21 mmol) of compound 1 and 40 mg (0.8 mmol)
of hydrazine hydrate in 5 mL of ethanol was heated for 1 h
at 60°С, cooled, and diluted with 10 mL of water. The se-
parated precipitate was filtered off, washed with 50%
aqueous ethanol and dried in air. Yield 65 mg (93%). Light
yellow crystals. Spectral characteristics and melting
point are consistent with the data published in [8].
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 2 2015