Catalytic hydrogenation of persubstituted p-nitrosophenols

Article abstract of DOI:10.1134/S1070428010040111

Catalytic hydrogenation of dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene- 1,3-dicarboxylates over Pd/C gave the corresponding previously unknown dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-dicarboxylates. The first-order rate constants for the hydrogenation process were found to be linearly related to steric constants of the alkyl groups.

Full text of DOI:10.1134/S1070428010040111

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 517–519. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © D.G. Slashchinin, M.S. Tovbis, E.V. Root, V.E. Zadov, V.A. Sokolenko, 2010, published in Zhurnal Organicheskoi Khimii, 2010,
Vol. 46, No. 4, pp. 527–529.
Catalytic Hydrogenation of Persubstituted p-Nitrosophenols
D. G. Slashchinina, M. S. Tovbisa, E. V. Roota, V. E. Zadova, and V. A. Sokolenkob
a Siberian State Technological University, pr. Mira 82, Krasnoyarsk, 660049 Russia
e-mail: tovbis@bk.ru
b Institute of Chemistry and Chemical Technology, Siberian Division, Russian Academy of Sciences
ul. K. Marksa 42, Krasnoyarsk, 660049 Russia
Received July 13, 2009
Abstract—Catalytic hydrogenation of dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates
over Pd/C gave the corresponding previously unknown dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-
dicarboxylates. The first-order rate constants for the hydrogenation process were found to be linearly related to
steric constants of the alkyl groups.
DOI: 10.1134/S1070428010040111
We previously reported on exhaustively substituted
nitrosophenols having ethoxycarbonyl groups in the
ortho positions with respect to the hydroxy group
[1, 2]. We synthesized analogous nitrosophenols with
methoxy-, propoxy-, and butoxycarbonyl groups and
performed their hydrogenation with a view to obtain
new p-aminophenols. The expected products contain
both salicylic acid ester and p-aminophenol fragments
that are typical of known medicines [3]; therefore, they
attracted interest from the viewpoint of synthesis of
biologically active compounds.
Dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-
1,3-dicarboxylates Ia–Id were subjected to hydro-
genation over carbon-supported palladium in anhy-
drous ethyl acetate. The reactions were carried out in
a reduction cell maintained at a constant temperature.
The cell was charged with the solvent, initial nitroso-
phenol, and catalyst, and hydrogen (from a steel cylin-
der) was bubbled through the mixture. The target prod-
ucts were isolated as follows: the reaction mixture was
filtered from the catalyst and was saturated with dry
hydrogen chloride. Dialkyl 5-amino-2-hydroxy-4,6-di-
methylbenzene-1,3-dicarboxylate hydrochlorides sepa-
rated from the solution and were filtered off.
We also performed kinetic measurements. Kinetic
curves were plotted for the consumption of hydrogen,
and dependences of ln(Vo – Vx) versus time were ob-
tained. The regression equation for the hydrogenation
of compound Ia was as follows: y = –0.05x + 3.38, r =
0.994. The dependences for other substituted nitroso-
phenols Ib–Id of this series were also linear and were
characterized by high correlation coefficients, indicat-
ing that catalytic hydrogenation of compounds Ia–Id
under the given conditions conforms to first-order
kinetics. From the obtained dependences we calculated
the first-order rate constants (k, s–1) for hydrogenation
of all the examined dialkyl 2-hydroxy-4,6-dimethyl-5-
nitrosobenzene-1,3-dicarboxylates Ia–Id: Ia, 5.01; Ib,
3.03; Ic, 0.92; Id, 0.83. It is seen that the hydrogena-
tion rate constant strongly depends on the length of the
alkyl radical in the ester moiety: it decreases in going
from methyl to butyl esters.
We revealed a linear relation between the loga-
rithms of hydrogenation rate constants and steric
constants of alkyl groups Es. The following steric
constants Es were used: 0.00 (Me), –0.09 (Et), –0.30
(Pr), and –0.34 (Bu) [4]. The regression equation was
y = 2.35x + 1.30, r = 0.998. We can conclude that the
difference in the rates of catalytic hydrogenation is
determined exclusively by the size of the alkyl group
in the ester fragments.
Scheme 1.
O
OH
O
O
OH
O
H2, Pd/C
RO
OR
RO
OR
Me
Me
Me
Me
NO
NH2
Ia–Id
IIa–IId
R = Me (a), Et (b), Pr (c), Bu (d).
517

SLASHCHININ et al.
Dipropyl 2-hydroxy-4,6-dimethyl-5-nitrosoben-
518
EXPERIMENTAL
zene-1,3-dicarboxylate (Ic). Yield 0.42 g (89%),
white crystals, mp 80–82°C. H NMR spectrum of
1
1
The H NMR spectra were recorded on a Bruker
Avance DRX-200 spectrometer (200 MHz) at the
Krasnoyarsk Regional Collective Use Center (Siberian
Division, Russian Academy of Sciences). Gas chroma-
tographic–mass spectrometric analysis was performed
on an Agilent Technologies GC–MS system consisting
of a Hewlett–Packard HP 6890N gas chromatograph
and a mass-selective detector; HP-5MS quartz capil-
lary column, 30 m×0.25 mm, film thickness 0.33 μm;
injector temperature 230°C, detector temperature
270°C; oven temperature programming from 70 to
280°C at a rate of 20 deg/min; carrier gas helium;
electron impact ionization, 70 eV; total ion current
measurement.
potassium salt (D2O), δ, ppm: 0.89 t (6H, CH3), 1.63–
1.73 m (4H, CH2), 2.36 s (6H, CH3), 4.25 t (4H, CH2).
Mass spectrum, m/z (Irel, %): 321 (30), 292 (15), 276
(10), 261 (65), 219 (20), 202 (70), 175 (15), 147 (15),
119 (10), 91 (10), 67 (10), 51 (10).
Dibutyl 2-hydroxy-4,6-dimethyl-5-nitrosoben-
zene-1,3-dicarboxylate (Id). Yield 0.8 g (88%), white
crystals, mp 65–67°C. 1H NMR spectrum of potassium
salt (D2O), δ, ppm: 0.83 t (6H, CH3), 1.26–1.38 m (4H,
CH2), 1.56–1.70 m (4H, CH2), 2.36 s (6H, CH3), 4.28 t
(4H, CH2). Mass spectrum, m/z (Irel, %): 349 (55), 292
(100), 276 (45), 265 (55), 249 (10), 221 (40), 202 (10),
175 (15), 147 (10), 121 (10), 97 (15), 75 (30), 56 (15).
Dimethyl, diethyl, dipropyl, and dibutyl acetonedi-
carboxylates were synthesized from anhydrous citric
acid and oleum with subsequent esterification of ace-
tonedicarboxylic acid with the corresponding alcohols
according to the procedure described in [5].
Dialkyl 5-amino-2-hydroxy-4,6-dimethylben-
zene-1,3-dicarboxylates IIa–IId (general procedure).
Compounds Ia–Id were hydrogenated in a static sys-
tem under atmospheric pressure at 298±0.1 K under
stirring. A 20-ml glass cell was charged with a suspen-
sion of 0.1 g of 0.5% Pd/C in 5 ml of ethyl acetate. The
cell was evacuated, and filled with hydrogen, this
procedure was repeated five times, and a solution of
0.5 mmol of nitrosophenol Ia–Id in 5 ml of ethyl
acetate was added in a stream of hydrogen. The mix-
ture was stirred, and the volume of absorbed hydrogen
was measured. The mode of stirring did not affect the
rate of hydrogenation, and the rate of hydrogen absorp-
tion did not exceed 3 ml/min. When the reaction was
complete (hydrogen was no longer absorbed), the mix-
ture was filtered from the catalyst, the filtrate was
saturated with dry hydrogen chloride, and the precip-
itate of dialkyl 5-amino-2-hydroxy-4,6-dimethylben-
zene-1,3-dicarboxylate hydrochloride (white crystals)
was filtered off and washed with toluene. Amino-
phenols IIa–IId as free bases (for GC–MS analysis)
were isolated by adding triethylamine to a solution of
the corresponding hydrochloride in benzene.
Dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosoben-
zene-1,3-dicarboxylates Ia–Id were synthesized in
a way similar to cyclization of isonitrosoacetylacetone
with dialkyl acetonedicarboxylates [2]. Isonitroso-
acetylacetone, 5 mmol, and the corresponding dialkyl
acetonedicarboxylate, 10 mmol, were added to a solu-
tion of 5 mmol of potassium hydroxide in 5 ml of an-
hydrous alcohol. The mixture was kept for 20 min at
18–20°C, and it changed from orange to green. Anhy-
drous diethyl ether was added to the solution until it
became turbid, the bright green crystals were filtered
off, dried over Na2SO4 under reduced pressure, and
dissolved in 4 ml of water. The solution was acidified
with dilute (1:3) hydrochloric acid, and an oily mate-
rial separated and rapidly crystallized to form colorless
crystals.
Dimethyl 2-hydroxy-4,6-dimethyl-5-nitrosoben-
zene-1,3-dicarboxylate (Ia). Yield 0.6 g (45%), white
crystals, mp 125–127°C. H NMR spectrum (CDCl3),
δ, ppm: 2.45 s (6H, CH3), 3.97 s (6H, CH3), 11.87 s
(1H, OH). Mass spectrum, m/z (Irel, %): 265 (40), 233
(100), 218 (20), 202 (50), 175 (30), 147 (50), 119 (30),
91 (15), 67 (35), 52 (10).
1
Dimethyl 5-amino-2-hydroxy-4,6-dimethylben-
zene-1,3-dicarboxylate (IIa). Yield of hydrochloride
1
0.1 g (74%), white crystals, mp 178–180°C. H NMR
spectrum (acetone-d6), δ, ppm: 2.34 s (6H, CH3),
2.97 br.s (2H, NH2), 3.99 s (6H, CH3), 11.40 s (1H,
OH). Mass spectrum, m/z (Irel, %): 253 (50) [M]+, 221
(100), 189 (80), 161 (10), 133 (20), 106 (25), 77 (15),
53 (10).
Diethyl 2-hydroxy-4,6-dimethyl-5-nitrosoben-
zene-1,3-dicarboxylate (Ib). Yield 0.75 g (51%),
white crystals, mp 103–105°C. H NMR spectrum of
potassium salt (D2O), δ, ppm: 1.30 t (6H, CH3), 2.35 s
(6H, CH3), 4.34 q (4H, CH2). Mass spectrum, m/z
(Irel, %): 293 (25), 247 (50), 221 (10), 202 (50), 175
(100), 147 (10), 119 (10), 91 (15), 67 (10), 51 (10).
1
Diethyl 5-amino-2-hydroxy-4,6-dimethylben-
zene-1,3-dicarboxylate (IIb). Yield of hydrochloride
0.25 g (68%), white crystals, mp 168–170°C. 1H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

CATALYTIC HYDROGENATION OF PERSUBSTITUTED p-NITROSOPHENOLS
519
spectrum (acetone-d6), δ, ppm: 1.43 t (6H, CH3), 2.39 s
(6H, CH3), 3.01 br.s (2H, NH2), 4.49 q (4H, CH2),
11.55 s (1H, OH). Mass spectrum, m/z (Irel, %): 281
(50) [M]+, 235 (100), 207 (15), 189 (85), 163 (30), 133
(20), 106 (30), 77 (15), 53 (10).
(1H, OH). Mass spectrum, m/z (Irel, %): 337 (100) [M]+,
307 (10), 281 (45), 263 (55), 235 (10), 207 (55), 189
(45), 163 (20), 133 (15), 106 (20), 75 (20), 56 (80).
REFERENCES
Dipropyl 5-amino-2-hydroxy-4,6-dimethylben-
1. Belyaev, E.Yu., Tovbis, M.S., and El’tsov, A.V., Zh. Org.
Khim., 1978, vol. 14, p. 2375.
zene-1,3-dicarboxylate (IIc). Yield of hydrochloride
1
0.1 g (60%), white crystals, mp 135–137°C. H NMR
2. Semin, I.V., Sokolenko, V.A., and Tovbis, M.S., Russ. J.
Org. Chem., 2007, vol. 43, p. 544.
spectrum (acetone-d6), δ, ppm: 1.05 t (6H, CH3), 1.79–
1.89 m (4H, CH2), 2.39 s (6H, CH3), 3.01 br.s (2H,
NH2), 4.40 t (4H, CH2), 11.69 s (1H, OH). Mass spec-
trum, m/z (Irel, %): 309 (45) [M]+, 249 (100), 189 (80),
163 (30), 133 (15), 106 (25), 77 (10), 59 (10).
3. Mashkovskii, M.D., Lekarstvennye veshchestva. Posobie
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p. 328.
Dibutyl 5-amino-2-hydroxy-4,6-dimethylben-
zene-1,3-dicarboxylate (IId). Yield of hydrochloride
0.08 g (45%), white crystals, mp 110–112°C. 1H NMR
spectrum (aceton-d6), δ, ppm: 0.99 t (6H, CH3), 1.42–
1.61 m (4H, CH2), 1.74–1.87 m (4H, CH2), 2.36 s (6H,
CH3), 2.98 br.s (2H, NH2), 4.44 t (4H, CH2), 11.61 s
5. Adams, R. and Chiles, H.M., Organic Syntheses,
Blatt, A.H. Ed., New York: Wiley, 1943, collect. vol. 1,
p. 237.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010