Reaction of N-arenesulfonyl-1,4-benzoquinone imines with acetylacetone

Article abstract of DOI:10.1134/S1070428016040060

N-Arenesulfonyl-1,4-benzoquinone imines reacted with acetylacetone to afford different products, depending on the isolation procedure. Crystallization from polar protic solvents gave N-[4-hydroxy- 3-(2-hydroxy-4-oxopent-2-en-3-yl)phenyl]arenesulfonamides

Full text of DOI:10.1134/S1070428016040060

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 4, pp. 516–522. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © S.A. Konovalova, A.P. Avdeenko, E.N. Lysenko, V.V. D’yakonenko, S.V. Shishkina, 2016, published in Zhurnal Organicheskoi
Khimii, 2016, Vol. 52, No. 4, pp. 529–536.
Reaction of N-Arenesulfonyl-1,4-benzoquinone Imines
with Acetylacetone
S. A. Konovalovaa, A. P. Avdeenkoa, E. N. Lysenkoa, V. V. D’yakonenkob, and S. V. Shishkinab
a Donbass State Engineering Academy, ul. Shkadinova 72, Kramatorsk, 84313 Ukraine
e-mail: chimist@dgma.donetsk.ua
b Institute for Single Crystals, National Academy of Ukraine, pr. Lenina 60, Kharkiv, 61001 Ukraine
Received January 25, 2015
Abstract—N-Arenesulfonyl-1,4-benzoquinone imines reacted with acetylacetone to afford different products,
depending on the isolation procedure. Crystallization from polar protic solvents gave N-[4-hydroxy-
3-(2-hydroxy-4-oxopent-2-en-3-yl)phenyl]arenesulfonamides and 6-(2-oxopropyl)-4-(arenesulfonamido)phenyl
acetates, whereas N-(3-acetyl-2,6-dimethyl-1-benzofuran-5-yl)arenesulfonamides were isolated by crystalliza-
tion from nonpolar aprotic solvents.
DOI: 10.1134/S1070428016040060
Benzofuran derivatives exhibit a broad spectrum of
biological activity, in particular hypotensive, antian-
ginal [1], antiarrhythmic [1, 2], analgesic, antispas-
modic [3], local anesthetic [3, 4], anti-allergic [5],
antimicrobial [6], and CNS activity [7]. Benzofuran
derivatives were synthesized previously by reactions of
CH acids with 1,4-benzoquinones [8–12] and N-(ben-
zenesulfonyl)-1,4-benzoquinone imines [13, 14]. In
most cases, the syntheses included several steps, one of
which was treatment of intermediate products with
inorganic acids [8–11, 13, 14] since the first step was
1,4-addition of CH acid to 1,4-benzoquinone or
1,4-benzoquinone imine. Martyak and Obushak [12]
found conditions for one-step preparation of benzo-
furans from 2-aryl-1,4-benzoquinones, whereas we
have revealed no published data on one-step synthesis
of benzofuran derivatives from 1,4-benzoquinone
imines. Furthermore, spectral characteristics of benzo-
furan derivatives obtained from N-benzenesulfonyl-
1,4-benzoquinone imines were not reported.
After treatment of the residue with water, we isolat-
ed 1,4-addition products for which keto–enol tautom-
erism is possible (3
5, 4
6; Scheme 1). Accord-
ing to the 1H NMR data, enol tautomers 5a–5g, 6a, 6c,
and 6e–6g were present in solution. Prolonged treat-
ment with water (24 h) led to the formation of com-
pounds 11b, 11e, 11g, and 12a–12g via the transforma-
tion sequence 1 → 3
5 → 7 → 11 or 2 → 4
6 →
8 → 12. These products result from irreversible open-
ing of the furan ring in 7 and 8 through cleavage of
the C2=C3 bond. Analogous products of C=C bond
cleavage in benzofuran derivatives were isolated in the
reactions of 2,3,5-trimethyl-1,4-benzoquinone with
various CH acids [11].
Compounds 7a–7d, 7f, 7g, 8a, 8c, 8d, 8f, and 8g
were synthesized in two ways. The first of these, as in
the reactions with 1,4-benzoquinone [8–11], included
two steps. 1,4-Addition products 5a–5g, 6a, 6c, and
6e–6g were treated with concentrated aqueous HCl on
heating for 3 h under reflux. In some cases, prolonged
treatment (6 h) gave compounds 9b, 9e, and 10e in
51–56% yield.
The goal of the present study was to find optimal
conditions for the synthesis of benzofuran derivatives
from N-arenesulfonyl-1,4-benzoquinone imines and
acetylacetone. For this purpose, 1,4-benzoquinone
imines 1a–1g and 2a–2g were reacted with acetyl-
acetone in anhydrous dioxane in the presence of
a catalytic amount of sodium methoxide. The solvent
was removed, and the oily residue was treated with
polar protic reagents or nonpolar aprotic solvent.
In the second way, the oily residue obtained after
removal of the solvent was treated with hexane, and
benzofuran derivatives 7a–7d, 7f, 7g, 8a, 8c, 8d, 8f,
and 8g crystallized from the hexane solution (yield 40–
63%). Compounds 7 and 8 in acetone were converted
into 11 and 12 in several days.
516

REACTION OF N-ARENESULFONYL-1,4-BENZOQUINONE IMINES
517
Scheme 1.
HO
OH
O
Me
O
Me
O
O
N
OH
R1
R2
R1
R2
Me
R1
R2
Me
O
O
+
R3
R3
SO2Ar
R3
SO2Ar
Me
Me
HN
HN
SO2Ar
1a–1g, 2a–2g
3a–3g, 4a, 4c, 4e–4g
5a–5g, 6a, 6c, 6e–6g
R1
O
Me
H+
R2
–AcOH
R1
ArSO2NH
O
R3
Me
H2O
R2
9b, 9e, 10e
–H2O
R1
Me
Me
ArSO2NH
O
R3
O
R2
O
7a–7d, 7f, 7g, 8a, 8c, 8d, 8f, 8g
ArSO2NH
11b, 11e, 11g, 12a–12g
Me
R3
O
1, 3, 5, 7, 9, 11, Ar = Ph; 2, 4, 6, 8, 10, 12, Ar = 4-MeC6H4; R1 = R2 = R3 = H (a); R1 = Me, R2 = R3 = H (b); R1 = R3 = H,
R2 = Me (c); R1 = R2 = Me, R3 = H (d); R1 = R3 = Me, R2 = H (e); R1 = H, R2 = R3 = Me (f); R1 = Cl, R2 = R3 = H (g).
The structure of the synthesized compounds was
204.73 ppm (MeCOCH2). In the IR spectra of 11b,
11e, 11g, and 12a–12g, absorption bands at 1750–1710
(ester carbonyl) and 3280 cm–1 (N–H) were observed.
1
confirmed by IR and H and 13C NMR spectra and
elemental analyses. The 1H NMR spectra of 5a–5g, 6a,
6c, and 6e–6g contained a singlet at δ 1.66–1.78 ppm
from two methyl groups and a singlet at δ 16.73–
16.79 ppm typical of enolic hydroxy proton. Com-
pounds 7a–7d, 7f, 7g, 8a, 8c, 8d, 8f, and 8g showed in
The structure of 12c and 12d was determined by
X-ray analysis (Figs. 1, 2). The independent part of
a unit cell of 12d contained two molecules A and B
differing by some structural parameters. The C12–C17
aromatic ring appears in –sc conformation with respect
to the C1–N1 bond: the torsion angles C1N1S1C12 are
–55.6(3)° (12c), –59.9(3)° (12d, A), and –63.6(3)°
(12d, B); the torsion angles N1S1C12C13 (rotation about
the S1–N1 bond) are 79.7(4)° (12c) and 91.4(2)° (12d,
A and B). The tosyl substituent adopts –sc conforma-
tion about the C1–C6 bond in molecule 12c and is
orthogonal to that bond in 12d [torsion angle S1N1C1C6
–59.2(3)° (12c), 92.7(3) (12d, A), 92.9(3)° (12d, B)].
Molecules 12c and 12d in crystal are linked through
intramolecular hydrogen bonds N–H···O [12c: (–1 +
x, y, z), H···O 2.02 Å, ∠NHO 156.4°; 12d: (–1 + x, y,
z), H···O 2.10 Å (A) 2.07 Å (B), ∠NHO 162.0° (A),
163.8° (B)] to form stacks along the [100] and [010]
crystallographic directions, respectively.
1
the H NMR spectra a singlet at δ 2.38–2.55 ppm due
to methyl group on C2 and a singlet at δ 2.58–2.82 ppm
1
due to acetyl group. In the H NMR spectra of 9b, 9e,
and 10e we observed singlets at δ 2.40–2.42 (2-Me)
and 6.40–6.50 ppm (3-H). Protons of the methylene
group in 11b, 11e, 11g, and 12a–12g resonated in the
1H NMR spectra in the region δ 3.45–3.66 ppm, and
methyl proton signals of the MeCOCH2 and MeCOO
fragments were observed at δ 2.00–2.07 and 2.21–
2.30 ppm, respectively.
The 13C NMR spectra of 5b and 5c showed methyl
carbon signals at δC 23.55–23.68 [C=C(OH)Me] and
23.60–23.75 ppm (MeCO) and signals at δC 109.66–
110.10, 191.42–191.61, and 192.19–192.38 ppm from
the C=C(OH)Me, C=C(OH)Me, and MeCO carbon
atoms, respectively. Compound 12f showed in the
13C NMR spectrum signals at δC 21.42 (MeCOCH2),
29.17 (MeCOO), 43.03 (CH2), 186.04 (MeCOO), and
Thus, we have proposed a fast one-step procedure
for the synthesis of benzofuran derivatives from
N-arenesulfonyl-1,4-benzoquinone imines and acetyl-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 4 2016

KONOVALOVA et al.
ceptor substituents in the initial 1,4-quinone imines
518
O4
N1
C13
O5
S1
C7
reduces the probability of biological activity of prod-
ucts of their reaction with acetylacetone as compared
to unsubstituted compounds 7a and 8a.
C6
O3
C8
C5
C1
C12
C9
C17
EXPERIMENTAL
O1
C10
C4
The H and 13C NMR spectra were recorded on
1
C2
C14
C3
C11
a Varian VXR-300 spectrometer at 300 and 75.4 MHz,
respectively, using acetone-d6 as solvent and tetra-
methylsilane as internal standard. The purity of the
initial quinone imines and isolated products was
checked by TLC on Silufol UV-254 plates; quinone
imines 1a–1g and 2a–2g were applied from solutions
in chloroform, and benzene–hexane (10:1) was used
as eluent; compounds 5–12 were applied from solu-
tions in acetone, and ethanol–chloroform (1:10) was
used as eluent; spots were detected under UV light.
C16
C19
C15
C18
O2
Fig. 1. Structure of the molecule of 5-methyl-4-(4-methyl-
benzenesulfonamido)-2-(2-oxopropyl)phenyl acetate (12c)
according to the X-ray diffraction data.
acetone. Treatment of the addition products with polar
solvents leads to opening of the furan ring with forma-
tion of compounds which, as well as benzofuran deriv-
atives, are potentially biologically active.
The X-ray diffraction data for compounds 12c and
12d were obtained at 21°C on an Xcalibur-3 diffrac-
tometer (MoKα radiation, CCD detector, graphite
monochromator, ω-scanning, 2θmax = 50°). The struc-
tures were solved by the direct method using
SHELXTL software package [16] and refined against
F2 by the full-matrix least-squares method in aniso-
tropic approximation for non-hydrogen atoms. Hydro-
gen atoms were localized by difference synthesis of
electron density, and their positions were refined
according to the riding model (Uiso = nUeq; n = 1.5 for
methyl groups and n = 1.2 for other hydrogen atoms).
The coordinates of atoms and complete tables of bond
lengths and bond angles for structures 12c and 12d
were deposited to the Cambridge Crystallographic
Data Centre (entry nos. CCDC 1439271 and 1439272,
respectively).
PASS Online (Prediction of Activity Spectra for
Substances) [15] analysis of possible biological ac-
tivities of compounds 7a–7d, 7f, 7g, 8a, 8c, 8d, 8f, 8g,
9b, 9e, and 10e revealed high probability for inhibition
of glutamyl endopeptidase II (0.640–0.801), insulin-
degrading enzyme (insulysin, 0.635–0.756), and ompT
protease (omptin, 0.511–0.687). Compounds 11b, 11e,
11g, and 12a–12g were found to be potential inhibitors
of gluconate 2-dehydrogenase (probability 0.802–
0.823), glutamyl endopeptidase II (0.679–0.782), and
ompT protease (0.596–0.714), as well as fibrinolytics
(0.597–0.715) and antipyretics (0.453–0.657). It was
also found that the presence of both donor and ac-
C19
O4
O5
Compound 12c. Triclinic crystal system, space
–
N1
C2
group P1; unit cell parameters: a = 9.7759(8), b =
10.3223(10), c = 11.0012(9) Å; α = 65.828(9), β =
72.329(7), γ = 75.656(8)°; V = 955.23(16) Å3;
M 375.43; Z = 2; dcalc = 1.305 g/cm3; μ(MoKα) =
0.198 mm–1; F(000) = 396. Number of reflections
C20
S1
C1
C3
C4
C12
O2
C17
C6
C13
8226, including 4346 independent reflections (Rint
=
C5
C7
C16
0.0349). Final divergence factors R1 = 0.066 [for
4346 reflections with F > 4σ(F)], wR2 = 0.117 (for all
8226 reflections); goodness of fit S = 1.005.
O1 C10
C14
C11
C15
C8
O3
Compound 12d. Orthorhombic crystal system,
space group Pca21; unit cell parameters: a =
20.4599(14), b = 5.2412(3), c = 36.669(3) Å; V =
3932.2(5) Å3; M 389.45; Z = 8; dcalc = 1.316 g/cm3,
μ(MoKα) = 0.195 mm–1; F(000) = 1648. Number of
C9
C18
Fig. 2. Structure of the molecule of 2,3-dimethyl-4-(4-
methylbenzenesulfonamido)-6-(2-oxopropyl)phenyl acetate
(12d) according to the X-ray diffraction data.
reflections 34132; 8960 independent reflections (Rint
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 4 2016

REACTION OF N-ARENESULFONYL-1,4-BENZOQUINONE IMINES
519
0.1217). Final divergence factors R1 = 0.084 [for
8960 reflections with F > 4σ(F)], wR2 = 0.1742 (for all
34132 reflections); goodness of fit S = 0.989.
N-[4-Hydroxy-3-(2-hydroxy-4-oxopent-2-en-3-
yl)-5-methylphenyl]benzenesulfonamide (5b). Yield
89%, mp 188–189°C. H NMR spectrum, δ, ppm:
1
1.70 s (6H, Me), 2.19 s (3H, 5-Me), 6.63 d (1H, 6-H,
J = 2.7 Hz), 7.02 d (1H, 2-H, J = 2.7 Hz), 7.51–7.73 m
(5H, Ph), 8.58 br.s (1H, NH), 16.77 s (1H, OH).
13C NMR spectrum, δC, ppm: 16.56 (5-Me), 23.55
[ C = C ( O H ) C H 3 ] , 2 3 . 6 0 ( C O C H 3 ) , 1 0 9 . 6 6
[C=C(OH)Me], 123.61 (C3), 125.38 (C2), 126.55 (C5),
127.00 (C6), 127.97 (Co), 129.55 (Cm), 129.86 (C1),
133.21 (Cp), 140.49 (Ci), 152.06 (C4), 191.61
[C=C(OH)Me], 192.38 (MeCO). Found, %: N 4.31;
S 9.02. C18H19NO5S. Calculated, %: N 3.88; S 8.86.
Initial quinone imines 1a–1g and 2a–2g were syn-
thesized according to the procedure described in [17].
Compounds 1a [18, 19], 1b, 1c, 1g, 2a [19, 20], 2b,
2c, 2g [19], 1d, 2d [21], 1e, 1f, 2e, and 2f [22] were
reported previously.
Reaction of quinone imines 1a–1g and 2a–2g
with acetylacetone (general procedure). Sodium
methoxide, 20 mg, was added under stirring to a solu-
tion of 2 mmol of quinone imine 1a–1g or 2a–2g and
2.2 mmol of acetylacetone in 25 mL of anhydrous
dioxane. The solution turned colorless, the solvent was
distilled off under reduced pressure, and the oily
residue was treated as described below.
N-[4-Hydroxy-5-(2-hydroxy-4-oxopent-2-en-3-
yl)-2-methylphenyl]benzenesulfonamide (5c). Yield
1
87%, mp 196°C. H NMR spectrum, δ, ppm: 1.78 s
(6H, Me), 2.09 s (3H, 2-Me), 6.67 s (1H, 3-H), 6.77 s
(1H, 6-H), 7.52–7.72 m (5H, Ph), 8.31 s (1H, NH),
16.75 s (1H, OH). 13C NMR spectrum, δC, ppm: 18.07
(2-Me), 23.68 [C=C(OH)CH3], 23.75 (COCH3),
110.10 [C=C(OH)Me], 118.60 (C6), 127.66 (C5),
128.09 (Co), 129.83 (Cm), 129.92 (C1), 132.77 (C3),
133.42 (Cp), 138.14 (C2), 141.52 (Ci), 155.06 (C4),
191.42 [C=C(OH)Me], 192.19 (MeCO). Found, %:
N 3.84; S 8.90. C18H19NO5S. Calculated, %: N 3.88;
S 8.86.
a. The oily residue was treated with water, the mix-
ture was kept for 1 h, and the light brown crystalline
solid was filtered off and recrystallized from ethanol or
aqueous ethanol. We thus isolated pure compounds
5a–5f, 6a, 6c, and 6f, while compounds 5g, 6e, and 6g
were not isolated in the pure state.
b. The oily residue was treated with water, the mix-
ture was kept for 24 h, and the light brown crystalline
solid was filtered off and recrystallized from ethanol or
aqueous ethanol. We thus isolated compounds 11b,
11e, 11g, and 12a–12g.
N-[4-Hydroxy-5-(2-hydroxy-4-oxopent-2-en-
3-yl)-2,3-dimethylphenyl]benzenesulfonamide (5d).
1
Yield 91%, mp 174°C. H NMR spectrum, δ, ppm:
c. The oily residue was treated with hexane, and the
mixture was kept for 24 h. The light brown crystalline
residue was filtered off and recrystallized from
ethanol. We thus isolated compounds 7b, 7d, 7g, 8a,
8d, and 8g.
1.73 s (6H, Me), 2.12 s (3H, 3-Me), 2.17 s (3H, 2-Me),
6.45 s (1H, 6-H), 7.50–7.71 m (5H, Ph), 8.25 br.s (1H,
NH), 16.77 s (1H, OH). Found, %: N 3.56; S 8.49.
C19H21NO5S. Calculated, %: N 3.73; S 8.53.
N-[4-Hydroxy-3-(2-hydroxy-4-oxopent-2-en-
Compounds 7a–7d, 7f, 7g, 8a, 8c, 8f, 8g, 9b, 9e,
and 10e (general procedure). A 10-mL round-bottom
flask was charged with 1 mmol of 5a–5g, 6a, 6c, or
6e–6g and 5 mL of concentrated aqueous HCl, and the
mixture was refluxed for 3 or 6 h. The dark brown
crystalline solid was filtered off from the hot mixture
and recrystallized from benzene. The product was
compound 7a–7d, 7f, 7g, 8a, 8c, 8f, or 8g (3 h) or 9b,
9e, or 10e (6 h).
3-yl)-2,5-dimethylphenyl]benzenesulfonamide (5e).
1
Yield 83%, mp 177–179°C. H NMR spectrum, δ,
ppm: 1.72 s (6H, Me), 2.11 s (3H, 5-Me), 2.17 s (3H,
2-Me), 6.78 s (1H, 6-H), 7.50–7.71 m (5H, Ph),
8.10 br.s (1H, NH), 16.77 s (1H, OH). Found, %:
N 3.56; S 8.49. C19H21NO5S. Calculated, %: N 3.73;
S 8.53.
N-[4-Hydroxy-5-(2-hydroxy-4-oxopent-2-en-
3-yl)-2,6-dimethylphenyl]benzenesulfonamide (5f).
Yield 84%, mp 199°C. H NMR spectrum, δ, ppm:
1.69 s (3H, 6-Me), 1.74 s (6H, Me), 2.10 s (3H, 2-Me),
6.71 s (1H, 3-H), 7.54–7.72 m (5H, Ph), 8.14 br.s (1H,
NH), 16.74 s (1H, OH). Found, %: N 3.80; S 8.59.
C19H21NO5S. Calculated, %: N 3.73; S 8.53.
N-[4-Hydroxy-3-(2-hydroxy-4-oxopent-2-en-
3-yl)phenyl]benzenesulfonamide (5a). Yield 83%,
mp 169–170°C. H NMR spectrum, δ, ppm: 1.72 s
(6H, Me), 6.82 d (1H, 2-H, J = 3.0 Hz), 6.87 d (1H,
5-H, J = 6.0 Hz), 7.09 d.d (1H, 6-H, J = 3.0, 6.0 Hz),
7.51–7.73 m (5H, Ph), 8.35 br.s (1H, NH), 8.66 s (1H,
OH), 16.75 s (1H, OH). Found, %: N 3.93; S 8.96.
C17H17NO5S. Calculated, %: N 4.00; S 9.21.
1
1
N-[3-Chloro-4-hydroxy-5-(2-hydroxy-4-oxopent-
2-en-3-yl)phenyl]benzenesulfonamide (5g). 1H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 4 2016

KONOVALOVA et al.
520
spectrum, δ, ppm: 1.72 s (6H, Me), 6.83 d (1H, 6-H,
J = 2.4 Hz), 7.26 d (1H, 2-H, J = 2.7 Hz), 7.53–7.79 m
(5H, Ph), 8.85 br.s (1H, NH), 16.77 s (1H, OH).
Found, %: N 3.73; S 8.47. C17H16NO5S. Calculated, %:
N 3.67; S 8.38.
N-(3-Acetyl-2-methyl-1-benzofuran-5-yl)ben-
zenesulfonamide (7a). Yield 54%, mp 191°C.
1H NMR spectrum, δ, ppm: 2.51 s (3H, 2-Me), 2.74 s
(3H, MeCO), 7.19 d.d (1H, 6-H, J = 3.0, 9.0 Hz),
7.39 d (1H, 7-H, J = 9.0 Hz), 7.48–7.78 m (5H, Ph),
7.86 d (1H, 4-H, J = 3.0 Hz), 8.98 s (1H, NH). Found,
%: N 4.36; S 9.81. C17H15NO4S. Calculated, %:
N 4.25; S 9.72.
N-[4-Hydroxy-3-(2-hydroxy-4-oxopent-2-en-3-
yl)phenyl]-4-methylbenzenesulfonamide (6a). Yield
1
84%, mp 169–171°C. H NMR spectrum, δ, ppm:
N-(3-Acetyl-2,7-dimethyl-1-benzofuran-5-yl)-
benzenesulfonamide (7b). Yield 61%, mp 223°C.
1H NMR spectrum, δ, ppm: 2.38 s (3H, 7-Me), 2.49 s
(3H, 2-Me), 2.74 s (3H, MeCO), 7.02 d (1H, 6-H, J =
0.9 Hz), 7.48–7.78 m (5H, Ph), 7.66 d (1H, 4-H, J =
0.9 Hz), 8.89 br.s (1H, NH). Found, %: N 3.89; S 9.17.
C18H17NO4S. Calculated, %: N 4.08; S 9.32.
1.70 s (6H, Me), 2.34 s (3H, 4′-CH3), 6.79 d (1H, 2-H,
J = 3.0 Hz), 6.85 d (1H, 5-H, J = 6.0 Hz), 7.07 d.d
(1H, 6-H, J = 3.0, 6.0 Hz), 7.29 d (2H, 3′-H, 5′-H, J =
9.0 Hz), 7.57 d (2H, 2′-H, 6′-H, J = 9.0 Hz), 8.54 s
(1H, NH), 16.73 s (1H, OH). Found, %: N 4.27;
S 8.92. C18H19NO5S. Calculated, %: N 3.88; S 8.86.
N-[4-Hydroxy-5-(2-hydroxy-4-oxopent-2-en-3-
yl)-2-methylphenyl]-4-methylbenzenesulfonamide
(6c). Yield 87%, mp 169–170°C. 1H NMR spectrum, δ,
ppm: 1.77 s (6H, Me), 2.09 s (3H, 2-Me), 2.40 s (3H,
4′-CH3), 6.68 s (1H, 3-H), 6.77 s (1H, 6-H), 7.35 d
(2H, 3′-H, 5′-H, J = 8.1 Hz), 7.59 d (2H, 2′-H, 6′-H,
J = 8.1 Hz), 8.31 s (1H, NH), 16.76 s (1H, OH).
Found, %: N 3.79; S 8.56. C19H21NO5S. Calculated, %:
N 3.73; S 8.53.
N-(3-Acetyl-2,6-dimethyl-1-benzofuran-5-yl)-
benzenesulfonamide (7c). Yield 58%, mp 200–202°C.
1H NMR spectrum, δ, ppm: 2.22 s (3H, 6-Me), 2.44 s
(3H, 2-Me), 2.74 s (3H, MeCO), 7.34 s (1H, 7-H),
7.52–7.73 m (5H, Ph), 7.57 s (1H, 4-H), 8.40 br.s (1H,
NH). Found, %: N 4.26; S 9.47. C18H17NO4S. Calcu-
lated, %: N 4.08; S 9.32.
N-(3-Acetyl-2,6,7-trimethyl-1-benzofuran-5-yl)-
benzenesulfonamide (7d). Yield 61%, mp 208–
210°C. 1H NMR spectrum, δ, ppm: 2.18 s (3H, 6-Me),
2.37 s (3H, 7-Me), 2.38 s (3H, 2-Me), 2.75 s (3H,
MeCO), 7.39 s (1H, 4-H), 7.51–7.72 m (5H, Ph),
8.42 br.s (1H, NH). Found, %: N 3.87; S 8.88.
C19H19NO4S. Calculated, %: N 3.92; S 8.96.
N-[4-Hydroxy-3-(2-hydroxy-4-oxopent-2-en-
3-yl)-2,5-dimethylphenyl]-4-methylbenzenesulfon-
1
amide (6e). H NMR spectrum, δ, ppm: 1.64 s (3H,
5-Me), 1.66 s (6H, Me), 2.18 s (3H, 2-Me), 2.39 s (3H,
4′-CH3), 6.77 s (1H, 6-H), 7.33 d (2H, 3′-H, 5′-H, J =
6.0 Hz), 7.53 d (2H, 2′-H, 6′-H, J = 6.0 Hz), 8.11 br.s
(1H, NH), 16.79 s (1H, OH). Found, %: N 3.62;
S 8.25. C20H23NO5S. Calculated, %: N 3.59; S 8.22.
N-(3-Acetyl-2,4,6-trimethyl-1-benzofuran-5-yl)-
benzenesulfonamide (7f). Yield 56%, mp 199°C.
1H NMR spectrum, δ, ppm: 2.10 s (3H, 4-Me), 2.14 s
(3H, 6-Me), 2.50 s (3H, 2-Me), 2.58 s (3H, MeCO),
7.16 s (1H, 7-H), 7.52–7.72 m (5H, Ph), 8.24 br.s (1H,
NH). Found, %: N 4.01; S 9.03. C19H19NO4S. Calcu-
lated, %: N 3.92; S 8.96.
N-[4-Hydroxy-5-(2-hydroxy-4-oxopent-2-en-
3-yl)-2,6-dimethylphenyl]-4-methylbenzenesulfon-
amide (6f). Yield 85%, mp 184°C. 1H NMR spectrum,
δ, ppm: 1.70 s (3H, 6-Me), 1.73 s (6H, Me), 2.10 s
(3H, 2-Me), 2.41 s (3H, 4′-CH3), 6.69 s (1H, 3-H),
7.35 d (2H, 3′-H, 5′-H, J = 7.8 Hz), 7.58 d (2H, 2′-H,
6′-H, J = 8.1 Hz), 8.00 br.s (1H, NH), 16.75 s (1H,
OH). Found, %: N 3.65; S 8.29. C20H23NO5S. Cal-
culated, %: N 3.59; S 8.22.
N-(3-Acetyl-7-chloro-2-methyl-1-benzofuran-
5-yl)benzenesulfonamide (7g). Yield 59%, mp 213°C.
1H NMR spectrum, δ, ppm: 2.55 s (3H, 2-Me), 2.82 s
(3H, MeCO), 7.29 d (1H, 6-H, J = 1.8 Hz), 7.50–
7.82 m (5H, Ph), 7.85 d (1H, 4-H, J = 1.8 Hz),
9.16 br.s (1H, NH). Found, %: N 3.77; S 8.63.
C17H14ClNO4S. Calculated, %: N 3.85; S 8.80.
N-[3-Chloro-4-hydroxy-5-(2-hydroxy-4-oxopent-
2-en-3-yl)phenyl]-4-methylbenzenesulfonamide
1
(6g). H NMR spectrum, δ, ppm: 1.71 s (6H, Me),
N-(3-Acetyl-2-methyl-1-benzofuran-5-yl)-
4-methylbenzenesulfonamide (8a). Yield 57%,
2.35 s (3H, 4′-CH3), 6.82 s (1H, 2-H, J = 2.1 Hz),
7.26 m.d (1H, 6-H, J = 2.7 Hz), 7.33 d (2H, 3′-H, 5′-H,
J = 7.8 Hz), 7.61 d (2H, 2′-H, 6′-H, J = 8.1 Hz),
8.36 br.s (1H, NH), 16.77 s (1H, OH). Found, %:
N 3.66; S 8.42. C18H18NO5S. Calculated, %: N 3.54;
S 8.09.
1
mp 229°C. H NMR spectrum, δ, ppm: 2.33 s (3H,
4′-CH3), 2.52 s (3H, 2-Me), 2.75 s (3H, MeCO), 7.19 q
(1H, 5-H, J = 3.0, 9.0 Hz), 7.28 d (2H, 3′-H, 5′-H, J =
9.0 Hz), 7.39 d (1H, 7-H, J = 9.0 Hz), 7.65 d (2H,
2′-H, 6′-H, J = 9.0 Hz), 7.86 d (1H, 4-H, J = 3.0 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 4 2016

REACTION OF N-ARENESULFONYL-1,4-BENZOQUINONE IMINES
521
8.91 s (1H, NH). Found, %: N 3.92; S 8.99.
C18H17NO4S. Calculated, %: N 4.08; S 9.32.
Found, %: N 4.12; S 9.97. C17H17NO3S. Calculated, %:
N 4.44; S 10.15.
4-Methyl-N-(2,4,7-trimethylbenzofuran-5-yl)-
benzenesulfonamide (10e). Yield 54%, mp 125°C.
1H NMR spectrum, δ, ppm: 2.10 s (3H, 4-Me), 2.30 s
(3H, 7-Me), 2.38 s (3H, 4′-CH3), 2.42 s (3H, 2-Me),
6.44 s (1H, 3-H), 6.75 s (1H, 6-H), 7.29 d (2H, 3′-H,
5′-H, J = 7.8 Hz), 7.53 d (2H, 2′-H, 6′-H, J = 7.8 Hz),
8.21 br.s (1H, NH). Found, %: N 4.37; S 9.92.
C18H19NO3S. Calculated, %: N 4.25; S 9.72.
N-(3-Acetyl-2,6-dimethyl-1-benzofuran-5-yl)-
4-methylbenzenesulfonamide (8c). Yield 59%,
mp 189°C. H NMR spectrum, δ, ppm: 2.23 s (3H,
6-Me), 2.40 s (3H, 4′-CH3), 2.44 s (3H, 2-Me), 2.74 s
(3H, MeCO), 7.35 d (2H, 3′-H, 5′-H, J = 8.1 Hz),
7.36 s (1H, 7-H), 7.60 d (2H, 2′-H, 6′-H, J = 8.1 Hz),
7.64 s (1H, 4-H), 8.34 br.s (1H, NH). Found, %: N 4.00;
S 9.12. C19H19NO4S. Calculated, %: N 3.92; S 8.96.
1
4-(Benzenesulfonamido)-2-methyl-6-(2-oxo-
propyl)phenyl acetate (11b). Yield 86%, mp 175–
176°C. 1H NMR spectrum, δ, ppm: 1.96 s (3H, 2-Me),
2.02 s (3H, MeCOCH2), 2.23 s (3H, MeCOO), 3.57 s
(2H, CH2), 7.00 d (1H, 3-H, J = 0.6 Hz), 7.17 br.s (1H,
5-H), 7.49–7.76 m (5H, Ph), 8.51 br.s (1H, NH).
Found, %: N 3.96; S 9.01. C18H19NO5S. Calculated, %:
N 3.88; S 8.86.
4-(Benzenesulfonamido)-3,6-dimethyl-2-(2-oxo-
propyl)phenyl acetate (11e). Yield 84%, mp 165–
166°C. 1H NMR spectrum, δ, ppm: 1.90 s (3H, 3-Me),
2.01 s (3H, 6-Me), 2.02 s (3H, MeCOCH2), 2.30 s
(3H, MeCOO), 3.63 s (2H, CH2), 6.94 s (1H, 5-H),
7.51–7.70 m (5H, Ph), 8.37 br.s (1H, NH). Found, %:
N 3.59; S 8.37. C19H21NO5S. Calculated, %: N 3.73;
S 8.53.
N-(3-Acetyl-2,6,7-trimethyl-1-benzofuran-5-yl)-
4-methylbenzenesulfonamide (8d). Yield 63%,
mp 181–182°C. H NMR spectrum, δ, ppm: 2.18 s
(3H, 6-Me), 2.35 s (3H, 4′-CH3), 2.36 s (3H, 7-Me),
2.39 s (3H, 2-Me), 2.72 s (3H, MeCO), 7.33 d (2H,
3′-H, 5′-H, J = 8.1 Hz), 7.34 s (1H, 4-H), 7.57 d (2H,
2′-H, 6′-H, J = 8.1 Hz), 8.31 br.s (1H, NH). Found, %:
N 3.85; S 8.73. C20H21NO4S. Calculated, %: N 3.77;
S 8.62.
1
N-(3-Acetyl-2,4,6-trimethyl-1-benzofuran-5-yl)-
4-methylbenzenesulfonamide (8f). Yield 40%,
1
mp 134–135°C. H NMR spectrum, δ, ppm: 2.12 s
(3H, 4-Me), 2.16 s (3H, 6-Me), 2.42 s (3H, 4′-CH3),
2.51 s (3H, 2-Me), 2.59 s (3H, MeCO), 7.16 s (1H,
7-H), 7.36 d (2H, 3′-H, 5′-H, J = 8.1 Hz), 7.59 d
(2H, 2′-H, 6′-H, J = 8.1 Hz), 8.16 s (1H, NH). Found,
%: N 3.84; S 8.70. C20H21NO4S. Calculated, %:
N 3.77; S 8.62.
4-(Benzenesulfonamido)-2-chloro-6-(2-oxo-
propyl)phenyl acetate (11g). Yield 87%, mp 155–
1
156°C. H NMR spectrum, δ, ppm: 2.07 s (3H,
MeCOCH2), 2.30 s (3H, MeCOO), 3.66 s (2H, CH2),
6.95 d (1H, 3-H, J = 2.7 Hz), 7.16 d (1H, 5-H, J =
2.7 Hz), 7.53–7.79 m (5H, Ph), 8.80 br.s (1H, NH).
Found, %: N 3.42; S 7.95. C17H16ClNO5S. Calculated,
%: N 3.67; S 8.38.
4-(4-Methylbenzenesulfonamido)-2-(2-oxo-
propyl)phenyl acetate (12a). Yield 83%, mp 123°C.
1H NMR spectrum, δ, ppm: 2.03 s (3H, MeCOCH2),
2.25 s (3H, MeCOO), 2.37 s (3H, 4′-CH3), 3.51 s (2H,
CH2), 6.96 br.s (2H, 3-H, 5-H), 7.02 br.s (1H, 6-H),
7.22 d (2H, 3′-H, 5′-H, J = 8.1 Hz), 7.65 d (2H, 2′-H,
6′-H, J = 8.1 Hz). Found, %: N 3.65; S 8.71.
C18H19NO5S. Calculated, %: N 3.88; S 8.86.
N-(3-Acetyl-7-chloro-2-methyl-1-benzofuran-
5-yl)-4-methylbenzenesulfonamide (8g). Yield 59%,
mp 248°C. H NMR spectrum, δ, ppm: 2.33 s (3H,
4′-CH3), 2.54 s (3H, 2-Me), 2.81 s (3H, MeCO), 7.28 d
(1H, 6-H, J = 2.1 Hz), 7.31 d (2H, 3′-H, 5′-H, J =
8.1 Hz), 7.68 d (2H, 2′-H, 6′-H, J = 8.1 Hz), 7.84 d
(1H, 4-H, J = 2.1 Hz), 9.09 br.s (1H, NH). Found, %:
N 3.63; S 8.21. C18H16ClNO4S. Calculated, %: N 3.70;
S 8.47.
1
N-(2,7-Dimethyl-1-benzofuran-5-yl)benzenesul-
1
fonamide (9b). Yield 56%, mp 112–113°C. H NMR
spectrum, δ, ppm: 2.34 s (3H, 7-Me), 2.40 s (3H,
2-Me), 6.40 s (1H, 3-H), 6.85 br.s (1H, 6-H), 7.13 d
(1H, 4-H, J = 2.1 Hz), 7.45–7.75 m (5H, Ph), 8.79 br.s
(1H, NH). Found, %: N 4.89; S 10.97. C16H15NO3S.
Calculated, %: N 4.65; S 10.62.
2-Methyl-(4-methylbenzenesulfonamido)-
6-(2-oxopropyl)phenyl acetate (12b). Yield 87%,
1
mp 131–132°C. H NMR spectrum, δ, ppm: 1.96 s
(3H, 2-Me), 2.02 s (3H, MeCOCH2), 2.23 s (3H,
MeCOO), 2.34 s (3H, 4′-CH3), 3.51 s (2H, CH2),
7.01 d (2H, 3-H, 5-H, J = 6.0 Hz), 7.31 d (2H, 3′-H,
5′-H, J = 8.1 Hz), 7.69 d (2H, 2′-H, 6′-H, J = 8.1 Hz).
Found, %: N 3.85; S 8.61. C19H21NO5S. Calculated, %:
N 3.73; S 8.53.
N-(2,4,7-Trimethyl-1-benzofuran-5-yl)benzene-
1
sulfonamide (9e). Yield 51%, mp 114°C. H NMR
spectrum, δ, ppm: 2.17 s (3H, 4-Me), 2.30 s (3H,
7-Me), 2.42 s (3H, 2-Me), 6.50 s (1H, 3-H), 6.72 s
(1H, 6-H), 7.50–7.69 m (5H, Ph), 8.34 br.s (1H, NH).
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KONOVALOVA et al.
522
5-Methyl-4-(4-methylbenzenesulfonamido)-
REFERENCES
2-(2-oxopropyl)phenyl acetate (12c). Yield 86%,
mp 127–128°C. H NMR spectrum, δ, ppm: 2.02 s
1
1. Kadieva, M.G., Oganesyan, E.T., Abaev, V.T.,
Butin, A.V., Gutnov, A.V., and Ivashev, M.N., RU Patent
no. 2138492, 1997.
2. Druzgala, P., RU Patent 2373199, 2005; Byull. Izobret.,
2009, no. 32; Druzgala, P., US Patent no. 5364880,
2005.
(3H, MeCOCH2), 2.05 s (3H, 5-Me), 2.21 s (3H,
MeCOO), 2.39 s (3H, 4′-CH3), 3.56 s (2H, CH2),
6.92 s (1H, 6-H), 7.10 s (1H, 3-H), 7.33 d (2H, 3′-H,
5′-H, J = 8.1 Hz), 7.60 d (2H, 2′-H, 6′-H, J = 8.1 Hz),
8.36 br.s (1H, NH). Found, %: N 3.59; S 8.39.
C19H21NO5S. Calculated, %: N 3.73; S 8.53.
3. Mashkovskii, M.D., Lekarstva XX veka (XXth Century
Drugs), Moscow: Novaya Volna, 1998, p. 239.
2,3-Dimethyl-4-(4-methylbenzenesulfonamido)-
4. Grinev, A.N., Zotova, S.A., Stolyarchyk, A.A.,
Gaevoi, B.P., and Matsak, B.B., Pharm. Chem. J., 1979,
vol. 13, no. 1, p. 44.
6-(2-oxopropyl)phenyl acetate (12d). Yield 92%,
1
mp 158°C. H NMR spectrum, δ, ppm: 1.95 s (3H,
2-Me), 1.99 s (3H, 3-Me), 2.06 s (3H, MeCOCH2),
2.28 s (3H, MeCOO), 2.40 s (3H, 4′-CH3), 3.45 s (2H,
CH2), 6.86 s (1H, 5-H), 7.34 d (2H, 3′-H, 5′-H, J =
7.8 Hz), 7.59 d (2H, 2′-H, 6′-H, J = 7.8 Hz), 8.33 br.s
(1H, NH). Found, %: N 3.48; S 8.01. C20H23NO5S.
Calculated, %: N 3.60; S 8.22.
5. Atkinson, J.G., Guindon, Y., and Lau, S.K., US Patent
no. 4663347, 1985; Ref. Zh., Khim., 1988, no. 3O90P.
6. Grinev, A.N., Zotova, S.A., Mikhailova, I.H., Stolyar-
chyk, A.A., Stepanyuk, G.I., Matsak, B.B., Sizova, T.N.,
and Pershin, G.N., Pharm. Chem. J., 1979, vol. 13,
no. 8, p. 814.
7. Bathe, A., Helfert, B., and Böttcher, H., RU Patent
no. 2278862, 2000; Byull. Izobret., 2006, no. 18.
8. Ionescu, M.V., Bull. Soc. Chim. Fr., 1927, vol. 41,
3,6-Dimethyl-4-(4-methylbenzenesulfonamido)-
2-(2-oxopropyl)phenyl acetate (12e). Yield 84%,
1
mp 138–139°C. H NMR spectrum, δ, ppm: 1.90 s
p. 1094.
(3H, 3-Me), 2.00 s (3H, 6-Me), 2.00 s (3H,
MeCOCH2), 2.28 s (3H, MeCOO), 2.37 s (3H,
4′-CH3), 3.61 s (2H, CH2), 6.94 s (1H, 5-H), 7.32 d
(2H, 3′-H, 5′-H, J = 7.8 Hz), 7.55 d (2H, 2′-H, 6′-H,
J = 7.8 Hz), 8.27 br.s (1H, NH). Found, %: N 3.83;
S 8.51. C20H23NO5S. Calculated, %: N 3.60; S 8.22.
9. Smith, L.I. and MacMullen, C.W., J. Am. Chem. Soc.,
1936, vol. 58, p. 629.
10. Smith, L.I. and Dale, W.J., J. Org. Chem., 1950, vol. 15,
p. 832.
11. Smith, L.I. and Kaiser, E.W., J. Am. Chem. Soc., 1940,
vol. 62, p. 133.
3,5-Dimethyl-4-(4-methylbenzenesulfonamido)-
12. Martyak, R. and Obushak, M., Vіsnik L’vіv. Univ., Ser.
Khіm., 2008, no. 49, part 2, p. 81.
13. Adams, R. and Whitaker, L., J. Am. Chem. Soc., 1956,
2-(2-oxopropyl)phenyl acetate (12f). Yield 85%,
1
mp 163°C. H NMR spectrum, δ, ppm: 1.93 s (3H,
5-Me), 2.04 s (3H, 3-Me), 2.06 s (3H, MeCOCH2),
2.25 s (3H, MeCOO), 2.42 s (3H, 4′-CH3), 3.65 s (2H,
CH2), 6.84 s (1H, 6-H), 7.36 d (2H, 3′-H, 5′-H, J =
8.1 Hz), 7.59 d (2H, 2′-H, 6′-H, J = 8.1 Hz), 8.15 s
(1H, NH). 13C NMR spectrum, δC, ppm: 16.19
(4′-CH3), 19.09 (5-Me), 20.84 (3-Me), 21.42
(MeCOCH2), 29.17 (MeCOO), 43.03 (CH2), 122.80
(C6), 126.33 (C5), 127.89 (C2′, C6′), 130.45 (C3′, C5′),
132.20 (C4), 138.75 (C2), 139.99 (C1′), 144.18 (C3),
149.39 (C4′), 169.43 (C1), 186.04 (MeCOO), 204.73
(MeCOCH2). Found, %: N 3.52; S 7.98. C20H23NO5S.
Calculated, %: N 3.60; S 8.22.
vol. 78, p. 658.
14. Adams, R. and Reifschneider, W., Bull. Soc. Chim. Fr.,
1958, no. 1, p. 23.
15. Filimonov, D.A., Lagunin, A.A., Gloriozova, T.A.,
Rudik, A.V., Druzhilovskii, D.S., Pogodin, P.V., and
Poroikov, V.V., Chem. Heterocycl. Compd., 2014,
vol. 50, no. 3, p. 444.
16. Sheldrick, G.M., Acta Crystallogr., Sect. A, 2015,
vol. 71, p. 3.
17. Adams, R. and Nagarkatti, A., J. Am. Chem. Soc., 1950,
vol. 72, p. 4601.
18. Burmistrov, S.I. and Titov, E.A., Zh. Obshch. Khim.,
4-(4-Methylbenzenesulfonamido)-2-chloro-
1952, vol. 22, p. 999.
6-(2-oxopropyl)phenyl acetate (12g). Yield 89%,
mp 143–144°C. H NMR spectrum, δ, ppm: 2.02 s
19. Avdeenko, A.P. and Konovalova, S.A., Russ. J. Org.
Chem., 2006, vol. 42, p. 349.
1
(3H, MeCOCH2), 2.27 s (3H, MeCOO), 2.30 s (3H,
4′-CH3), 3.66 s (2H, CH2), 6.95 d (1H, 3-H, J =
2.4 Hz), 7.16 d (1H, 5-H, J = 1.8 Hz), 7.33 d (2H,
3′-H, 5′-H, J = 8.1 Hz), 7.61 d (2H, 2′-H, 6′-H, J =
8.1 Hz), 9.32 s (1H, NH). Found, %: N 3.36; S 8.18.
C18H18ClNO5S. Calculated, %: N 3.54; S 8.09.
20. Adams, R. and Looker, J.H., J. Am. Chem. Soc., 1951,
vol. 73, p. 1145.
21. Avdeenko, A.P., Konovalova, S.A., and Ludchen-
ko, O.N., Russ. J. Org. Chem., 2006, vol. 42, p. 683.
22. Avdeenko, A.P. and Konovalova, S.A., Russ. J. Org.
Chem., 2006, vol. 42, p. 669.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 4 2016