Reaction of N-sulfonyl-1,4-benzoquinone imines with enamines

Article abstract of DOI:10.1134/S1070428017040054

N-Sulfonyl derivatives of 1,4-benzoquinone imine reacted with enamines to give 1,4-addition products and products of their subsequent cyclization, substituted 5-aminobenzofurans and 5-aminoindoles, depending on the solvent nature, electron-withdrawing pow

Full text of DOI:10.1134/S1070428017040054

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 4, pp. 525–538. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © S.A. Konovalova, A.P. Avdeenko, V.V. Pirozhenko, A.L. Yusina, G.V. Palamarchuk, S.V. Shishkina, 2017, published in Zhurnal
Organicheskoi Khimii, 2017, Vol. 53, No. 4, pp. 519–532.
Reaction of N-Sulfonyl-1,4-benzoquinone Imines with Enamines
S. A. Konovalovaa, A. P. Avdeenkoa,* V. V. Pirozhenkob, A. L. Yusinaa,
G. V. Palamarchukc, and S. V. Shishkinac, d
a Donbass State Engineering Academy, ul. Shkadinova 72, Kramatorsk, 84313 Ukraine
*e-mail: chimist@dgma.donetsk.ua
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
c Institute for Single Crystals, National Academy of Sciences of Ukraine,
pr. Lenina 60, Kharkiv, 61001 Ukraine
d Karazin Kharkiv National University, pl. Svobody 4, Kharkiv, 61022 Ukraine
Received May 19, 2016
Abstract—N-Sulfonyl derivatives of 1,4-benzoquinone imine reacted with enamines to give 1,4-addition
products and products of their subsequent cyclization, substituted 5-aminobenzofurans and 5-aminoindoles,
depending on the solvent nature, electron-withdrawing power of the substituent on the quinone imine nitrogen
atom, and enamine structure. The presence of strong electron-withdrawing trifluoromethanesulfonyl group on
the quinone imine nitrogen atom favors formation of 1,4-addition products and benzofuran derivatives.
DOI: 10.1134/S1070428017040054
It was found previously that N-arenesulfonyl deriv-
atives of 1,4-benzo- [1–5] and 1,4-naphthoquinone
imines [5, 6] and 1,4-benzoquinone diimine [5, 7] react
with enamines to give 1,4-addition products [2, 5] and
derivatives of 5-aminobenzo(naphtho)furan [1, 2, 4–7],
5-aminoindole [4, 5, 7], and 6-aminoindole [4].
Analogous compounds obtained from 1,4-benzo-
quinone and its derivatives showed high antiviral
activity [8–10] and are widely used as medicinal
agents [11, 12]; examples are local anesthetic benzo-
furocain, antidepressant brofaromine, one of the most
potent nonsteroidal anti-inflammatory drugs indo-
metacin, radioprotector mexamine, antiviral drug
umifenovir, monoamine neurotransmitter serotonin,
and its derivative melatonin which is involved in sleep
cycle synchronization.
The product structure in the reactions of N-arene-
sulfonyl-1,4-benzoquinone imines with enamines is
largely determined by the reaction conditions and
enamine structure [5]; however, the effect of the X
substituent in the XSO2N= fragment on the reaction
course has not been studied so far.
We previously synthesized 1,4-benzoquinone
imines containing a trifluoromethanesulfonyl group on
the nitrogen atom [13]. The CF3SO2 group is a stronger
acceptor than ArSO2, which was demonstrated by
reactions with potassium thiocyanate [13] and sodium
sulfinates [14].
The goal of the present work was to elucidate how
reaction conditions, substituent on the sulfonyl group,
and enamine structure affect the direction of the reac-
tions of N-methanesulfonyl-, N-trifluoromethanesul-
fonyl-, and N-arenesulfonyl-1,4-benzoquinone imines
with 4-(4-methylanilino)pent-3-en-2-one and ethyl
3-(arylamino)but-2-enoates, as well as to obtain new
benzofuran and indole derivatives expected to exhibit
biological activity.
It is known that the solvent nature is the key factor
determining the direction of the reactions of N-arene-
sulfonyl-1,4-benzoquinone imines with enamines [5].
Therefore, the reactions of N-sulfonyl quinone imines
1a–1g with enamines 2a–2c were carried out in
acetone, chloroform, and acetic acid with a view to
obtaining all possible products. In fact, in keeping with
the data of [5], the reaction in acetone gave 1,4-ad-
dition product 3a, indole derivatives 4a–4i were
formed in chloroform and 1,2-dichloroethane, and
benzofuran derivatives 5a–5i were isolated when
acetic acid was used as solvent (Scheme 1).
525

KONOVALOVA et al.
Scheme 1.
526
OH
Ac
NHC6H4Me-4
Me
Me2CO
MeSO2NH
3a
O
Y
R3
R4
R1
XSO2NH
ClCH2CH2Cl, CHCl3
–H2O
+
Me
R2
R3
R4
R2
N
N
HN
C6H4Y-4
R1
XSO2
4a–4i
Me
2a–2c
R3
1a–1g
R4
XSO2NH
R2
AcOH
Me
–4-YC6H4NH2
O
R1
5a–5i
1, X = 4-MeC6H4 (a, b), Me (c–g); R1 = Cl, R2 = R3 = H (a); R1 = Me, R2 = R3= H (b, d); R1 = R2 = R3 = H (c); R2 = Me, R1 =
R3 = H (e); R1 = R2 = Me, R3 = H (f); R2 = R3 = Me, R1 = H (g); 2, R4 = COMe, Y = Me (a); R4 = COOEt, Y = H (b), R4 = COOEt,
Y = OMe (c); 4, R1 = Cl, R2 = R3 = Y = H, R4 = COOEt, X = 4-MeC6H4 (a); R1 = Me, R2 = R3 = Y = H, R4 = COOEt, X =
4-MeC6H4 (b); R1 = X = Y = Me, R2 = R3 = H, R4 = COMe (c); R1 = X = Me, R2 = R3 = Y = H, R4 = COOEt (d); R2 = X = Y = Me,
R1 = R3 = H, R4 = COMe (e); R2 = X = Me, R1 = R3 = Y = H, R4 = COOEt (f); R1 = R2 = X = Y = Me, R3 = H, R4 = COMe (g); R1 =
R2 = X = Me, R3 = Y = H, R4 = COOEt (h); R1 = R2 = X = Me, R3 = H, R4 = COOEt, Y = OMe (i); 5, R1 = Cl, R2 = R3 = H, R4 =
COOEt, X = 4-MeC6H4 (a); R1 = Me, R2 = R3 = H, R4 = COOEt, X = 4-MeC6H4 (b); R1 = R2 = R3 = H, R4 = COMe, X = Me (c);
R1 = X = Me, R2 = R3 = H, R4 = COMe (d); R2 = X = Me, R1 = R3 = H, R4 = COMe (e); R2 = X = Me, R1 = R3 = H, R4 = COOEt (f);
R1 = R2 = X = Me, R3 = H, R4 = COMe (g); R1 = R2 = X = Me, R3 = H, R4 = COOEt (h); R2 = R3 = X = Me, R1 = H, R4 = COOEt (i).
The reactions of N-trifluoromethanesulfonyl deriv-
atives 1h–1k with enamines 2a and 2b were carried
out on cooling to –10°C in chloroform or chloroform–
acetic acid mixture. Unlike quinone imines 1a–1g,
compounds 1h–1k reacted with 4-(4-methylanilino)-
pent-3-en-2-one (2a) to produce only benzofurans 5j–
5o; the reactions of 1h–1k with enamine 2b in chloro-
form afforded 1,4-addition products 3b–3e, whereas
Scheme 2.
R1
R2
OH
Me
OH
NHPh
Me
O
CHCl3
H2O
–PhNH2
F3CSO2NH
F3CSO2NH
Me
C(O)OEt
O
R3
C(O)OEt
R1
3b–3e
6a
+
2a, 2b
R2
R3
R3
R4
N
CF3SO2NH
R2
CHCl3 or
CHCl3–AcOH
F3CSO2
Me
1h–1k
–4-YC6H4NH2
O
R1
5j–5o
1, R1 = R2 = R3 = H (h); R1 = Me, R 2 = R3 = H (i); R2 = Me, R1 = R3 = H (j); R1 = R 2 = Me, R3 = H (k); 3, R1 = R 2 = R3 = H (b);
R1 = Me, R2 = R3 = H (c); R2 = Me, R1 = R3 = H (d); R1 = R2 = Me, R3 = H (e); 5, R1 = R2 = R3 = H, R4 = COMe (j); R1 = Me, R2 =
R3 = H, R4 = COMe (k); R1 = Me, R2 = R3 = H, R4 = COOEt (l); R2 = Me, R1 = R3 = H, R4 = COMe (m); R1 = R 2 = Me, R3 = H,
R4 = COMe (n); R1 = R2 = Me, R3 = H, R4 = COOEt (o).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
527
benzofuran derivatives 5j–5o were obtained in a mix-
ture of acetic acid with chloroform (Scheme 2). We
failed to obtain indole derivatives from N-trifluoro-
methanesulfonyl derivatives 1h–1k. Compound 3d
underwent hydrolysis during the isolation and puri-
fication procedures, so that the isolated product was
compound 6a. Analogous compound was obtained
previously [2].
1,4-benzoquinone imines is Michael addition involving
the electron-deficient carbon atom of quinone imine 1
and β-carbon atom of enamine 2 with formation of
intermediate A (Scheme 3). Benzofurans 5 can be
formed along two paths. The first path (a) includes
intermediate B which is formed by attack of the lone
electron pair on the carbonyl oxygen atom at the elec-
tron-deficient α-carbon atom of the enamine fragment,
and the subsequent elimination of aromatic amine
molecule yields final furan 5. Following the second
According to published data [5, 15, 16], the first
stage of the Nenitzescu reaction of N-substituted
Scheme 3.
O
Y
H
N
+
R
Ar
H
Me
NX
1
2
Ar
N
Ar
Ar
Ar
NH
:
NH
NH
Me
Y
Me
H
Me
H
Me
Y
OH
O
OH
OH
b
Y
Y
H
R
H
R
R
R
NHX
NX
NX
NHX
E
A
C
3
a
Ar
Ar
NHAr
O
Me
Ar
Me
NH
NH
Me
H
Me
Y
N
:
OH
OH
OH
H
Y
H+
Y
–H+
H
R
R
Y
R
R
NHX
NHX
NHX
NHX
F
B
D
3'
–H2O
Me
–ArNH2
Me
Ar
N
O
Y
Y
R
R
NHX
NHX
4
5
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

KONOVALOVA et al.
528
bon atom of the enamine fragment to the nitrogen atom
linked to the sulfonyl group and from the enamine
nitrogen atom to the carbonyl oxygen atom leads to
intermediate E which undergoes cyclization to struc-
ture F. Elimination of water molecule from the latter
yields indole 4 (Scheme 3).
path (b), intermediate A is converted to 1,4-addition
product 3 through tautomeric structure C. Adduct 3 in
the form of mesomeric structure 3′ undergoes protona-
tion at the β-carbon atom of the enamine fragment,
which bears a partial negative charge. Intermediate D
thus formed is converted to structure B via attack on
the α-carbon atom of the enamine fragment by the lone
electron pair on the hydroxyl oxygen atom.
The fact that no indole derivatives were formed
from N-trifluoromethanesulfonyl derivatives 1h–1k
may be accounted for by strong electron-withdrawing
effect of the CF3SO2 group, which reduces the acidity
of the NH proton in the enamine fragment of inter-
mediate A, so that intramolecular protonation of the
XN group is hindered. Therefore, intermediate E
cannot be formed, and the formation of benzofuran
derivatives 5 becomes predominant.
Our results suggest that benzofuran derivatives 5l
and 5o are formed according to path b: A → C → 3 →
3′ → D → B → 5 (Scheme 3). In fact, compounds 5l
and 5o were obtained from N-trifluoromethanesulfonyl
derivatives 1i and 1k and ester 2b only in the presence
of acetic acid which favored protonation of the corre-
sponding 1,4-addition products 3. The formation of
benzofurans 5j, 5k, 5m, and 5n in the absence of acid
can be rationalized as follows. The acetyl group is
a stronger electron acceptor than COOEt [17], so that
the positive charge on the α-carbon atom of the
enamine fragment in intermediate A derived from
enamine 2a is larger. This makes the attack by the
carbonyl oxygen atom more probable, and compounds
5j, 5k, 5m, and 5n are formed along path a: A →
B → 5 (Scheme 3).
In keeping with published data, 1,4-benzoquinone
imines react with enamines containing a Me, OMe,
NMe2, or NHCOMe group in the para position of the
benzene ring attached to nitrogen to give 5-amino-
indole derivatives [4, 5, 7], whereas acceptor substit-
uents in the enamine favor formation of 6-amino-
indoles [4].
We examined reactions of benzoquinone imines
1a–1c, 1e, 1f, 1l, and 1m with enamine 2d containing
an electron-withdrawing nitro group in the para
position of the benzene ring. The reactions in acetone,
The cyclization to give indole derivatives also in-
volves intermediate A. Proton transfer from the β-car-
Scheme 4.
R1
R2
OH
NHC6H4NO2-4
Me
Me2CO
H2O
6a
–4-O2NC6H4NH2
XSO2NH
R3
COOEt
3f–3h
O
N
NO2
R3
COOEt
R1
XSO2NH
ClCH2CH2Cl, CHCl3
–H2O
+
Me
R2
R3
COOEt
R2
N
HN
C6H4NO2-4
R1
XSO2
4j–4o
Me
2d
1a–1c, 1e, 1f
1j, 1l, 1m
NO2
AcOH
Ac
N
H
7
1, X = 4-MeC6H4, R1 = R2 = R3 = H (l); R1 = R3 = H, R2 = Me (m); 3, R1 = R2 = R3 = H, X = 4-MeC6H4 (f); R1 = R3 = H, R2 = Me,
X = 4-MeC6H4 (g); R2 = Me, R1 = R3 = H, X = CF3 (h); 4, R1 = R2 = R3 = H, X = Me (j); R1 = Cl, R2 = R3 = H, X = 4-MeC6H4 (k);
R1 = Me, R2 = R3 = H, X = 4-MeC6H4 (l); R1 = R3 = H, R2 = Me, X = 4-MeC6H4 (m); R1 = R3 = H, R2 = X = Me (n);
R1 = R2 = X = Me, R3 = H (o).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
529
Scheme 5.
R3
COOEt
XSO2NH
Me
–NH3
R1
R2
O
N
O
R1
R2
OH
R1
COOEt
Me
H2N
5a, 5b, 5h, 5l, 5o–5r
+
R2
R3
XSO2NH
NH2
COOEt
Me
OH
R3
O
XSO2
H2O
1a–1f, 1l, 1n–1q
2e
3i–3r
–NH3
XSO2NH
Me
COOEt
6b–6d
1, X = 4-MeC6H4 (n), Ph (o–q); R1 = R2 = R3 = H (o); R1 = H, R2 = R3 = Me (n, p); R1 = R2 = Me, R3 = H (q); 3, X = Ph (i),
4-MeC6H4 (j, k, r), Me (l–n), CF3 (o–q); R1 = R2 = R3 = H (i, l, o, r); R1 = Me, R2 = R3 = H (m, p); R1 = Cl, R2 = R3 = H (j); R1 =
R2 = Me, R3 = H (n, q); R1 = H, R2 = R3 = Me (k); 5, X = Ph, R1 = R2 = Me, R3 = H (p); R1 = H, R2 = R3 = Me (q); X = Me, R1 = Me,
R2 = R3 = H (r); 6, X = Ph (b), 4-MeC6H4 (c), CF3 (d).
chloroform, and dichloroethane afforded 1,4-addition
products 3f–3h and indoles 4j–4o (Scheme 4).
Enamine 2d in acetic acid underwent hydrolysis
followed by acetylation, and the product was p-nitro-
acetanilide 7. No benzofuran derivatives were obtained
from enamine 2d. In the reaction of quinone imine 1j
with enamine 2d we isolated a mixture of compound
6a and p-nitroaniline which were formed as a result of
hydrolysis of compound 3h. The reactions of 2d with
quinone imines 1i and 1k lead to the formation of non-
crystallizable oily products, from which we succeeded
in isolating only p-nitroaniline. We failed to isolate
pure compounds 3g and 4m.
1f, 1l, and 1n–1q in chloroform and acetic acid and
with N-trifluoromethanesulfonyl analogs 1h, 1i, and
1k in chloroform and chloroform–acetic acid mixture.
As reported in [1, 2], all quinone imines in chloroform
gave rise to 1,4-addition products 3i–3r. The reactions
of substituted quinone imines 1a, 1b, 1d–1f, 1i, 1k, 1p,
and 1q with 2e in acetic acid afforded benzofuran
derivatives 5a, 5b, 5h, 5l, 5o, and 5p–5r, whereas
compounds 1h, 1l, and 1o having no substituents in the
quinoid ring were converted to phenols 6b–6d through
1,4-addition products 3i, 3o, and 3r (Scheme 5). Pre-
sumably, the hydrolysis of 1,4-addition products 3i, 3o,
C8
Thus, in no case were 6-aminoindole derivatives
isolated in the reactions of quinone imines with
enamine 2d: 1,4-addition products and 5-aminoindoles
4 were formed in all solvents, except for acetic acid.
C3
C7
O3
C2
C15
Some N-arenesulfonyl-1,4-benzoquinone imines
were previously reported to react with ethyl 3-amino-
but-2-enoate to give 1,4-addition products [1, 2] whose
subsequent treatment with sulfuric, hydrochloric, or
acetic acid at different concentrations led to the forma-
tion of 2,3-dihydrobenzofuran or benzofuran deriva-
tives, or 2-[1-acetyl-1-(ethoxycarbonyl)methyl]-4-
(arenesulfonylamino)phenols analogous to 6a.
C4
C5
O2
S1
C1
O4
C10
C14
O1
C11
N1
C6
O5
F3
C12
N2
C13
C9
F1
F2
Taking into account that the molecule of ethyl
3-aminobut-2-enoate possesses a free amino group,
this enamine was expected to add through the nitrogen
atom to quinone imines. We studied the reactions of
ethyl 3-aminobut-2-enoate (2e) with N-arenesulfonyl-
and N-methanesulfonyl-1,4-benzoquinone imines 1a–
Fig. 1. Structure of the molecule of ethyl 3-amino-2-{2-
hydroxy-3,4-dimethyl-5-[(trifluoromethanesulfonyl)amino]-
phenyl}but-2-enoate (3q) according to the X-ray diffraction
data. Non-hydrogen atoms are shown as thermal vibration
ellipsoids with a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

KONOVALOVA et al.
19F NMR spectra, the CF3 signal of 3b, 3c, and 3e was
530
C5
C6
C4
C3
located at δF –74.59 to –75.53 ppm, and of 5j–5o, at
δ –74.89 to –75.96 ppm. Methylene protons of the
1
C13
ester group of 3i–3r appeared in the H NMR spectra
as two quartets at δ 3.81–3.88 and 3.92–4.09 ppm, and
the amino group gave two broadened singlets at
δ 6.94–7.20 and 7.85–8.41 ppm. The IR spectra of 4a–
4o, and 5a–5o contained absorption bands at 3160–
3280, 1670–1690, and 1620–1630 cm–1 due to stretch-
ing vibrations of the NH and ester and ketone carbonyl
groups, respectively, whereas no absorption at 3350–
3450 cm–1 typical of hydroxy group was observed.
C1
S1
O4
C2
C14
C15
C11
O1
O2
O6
C12
N1
C16
C7
C18
C17
C10
C9
C8
O5
O3
The structure of compounds 3q (Fig. 1) and 6b
(Fig. 2) was unambiguously determined by X-ray
analysis. The trifluoromethanesulfonyl group in mole-
cule 3q is orthogonal to the aromatic ring plane, and
the trifluoromethyl group is almost orthogonal to the
C1–N1 bond: the torsion angles C6C1N1S1 and
C1N1S1C9 are 95.4(2) and –79.2(2)°, respectively. The
substituent on C5 is oriented in such a way that its
planar conjugated fragment is turned through an appre-
ciable angle with respect to the benzene ring plane
[torsion angle C6C5C10C12 73.8(2)°], and fairly weak
intramolecular hydrogen bond O3–H···C11 (H3A···C11
2.79 Å, ∠O3HC11 128°) is formed. The amino group
appears in s-trans configuration with respect to the
C5–C10 bond [torsion angle C5C10C12N2 –178.9(2)°],
which is favored by intramolecular hydrogen bond
N2–H2b ···O5 (H2b ···O5 1.82 Å, ∠N2H2bO5 132°).
Furthermore, the amino group is involved in inter-
molecular hydrogen bond N2–H2A ···O2′ (1 + x, y, z;
H2A···O2′ 2.27 Å, ∠N2H2AO2′ 150°). This is likely to
be responsible for nonequivalence of the NH2 protons
which appear as two broadened singlets in the
1H NMR spectrum. The ester ethyl group is syn-peri-
planar with respect to the C11–O5 carbonyl group, and
the C14–C15 bond is orthogonal to the planar fragment
of the substituent [torsion angles O5C11O4C14 5.8(3),
C11O4C14C15 81.9(2)°]. The OH and NH groups partici-
pate in intermolecular hydrogen bonds O3–H3A···O1′
(0.5 + x, 0.5 – y, –0.5 + z; H3A · · · O1′ 2.26 Å,
∠O3H3AO1′ 149°) and N1–H1A···O5′ (1.5 – x, –0.5 + y,
1.5 – z; H1A···O5′ 1.88 Å, ∠N1H1AO5′ 166°).
Fig. 2. Structure of the molecule of ethyl 2-[5-(benzene-
sulfonyl)amino]-2-hydroxyphenyl}-3-oxobutanoate (6b)
according to the X-ray diffraction data. Non-hydrogen atoms
are shown as thermal vibration ellipsoids with a probability
of 50%.
and 3r derived from unsubstituted quinone imines 1h,
1l, and 1o is faster than the attack of the aromatic
hydroxy group on the α-carbon atom of the enamine
fragment. Compound 3r was not isolated.
The structure of compounds 3–7 was determined on
1
the basis of their elemental analyses and H and 19F
1
NMR and IR spectra. The H NMR spectra of 4a–4o
displayed signals from protons in the ArSO2 or MeSO2
and ArN groups, protons and alkyl substituents in the
indole ring, NH proton, and R4. Likewise, signals from
the Ar(Me)SO2 group, protons and alkyl substituents in
the benzofuran fragment, NH proton, and R4 group
were observed in the 1H NMR spectra of 5a–5o. In the
O4
C16
C15
C22
C21
C14
C11
C20
C19
C17
C23
O5
O1
C1
N2
C12
C18
C9
C13
C10
C8
C7
N1
S1
C2
C28
C29
C3
C30
C6
C5
C24
C27
C26
The benzenesulfonyl group in molecule 6b is
oriented in such a way that the torsion angle C8C7N1S1
is 77.9(1)°. The phenyl substituent appears in +sc con-
formation with respect to the C7–N1 bond and is turned
with respect to the N1–S1 bond [torsion angles
C7N1S1C1 61.9(1), N1S1C1C6 78.9(1)°]. The ester frag-
ment is almost orthogonal to the C7–C12 aromatic ring
and is turned through some angle with respect to the
C4
C25
O3
O2
Fig. 3. Structure of the molecule of ethyl 2-(1-hydroxy-
4-[(4-methylbenzenesulfonyl)amino]naphthalen-2-yl)-3-
(4-methylanilino)but-2-enoate (8) according to the X-ray
diffraction data. Non-hydrogen atoms are shown as thermal
vibration ellipsoids with a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
531
Crystallographic data and parameters of X-ray diffraction experiments for compounds 3q, 6b, and 8
Parameter
Unit cell parameters
3q
6b
8
a, Å
10.8717(7)
12.4884(9)
13.975(1)0
90.00(0)
104.357(9)
90.00(0)
1838.1(2)
824
07.7533(4)
07.9756(5)
15.4074(8)
79.900(5)
81.035(4)
77.745(5)
909.62(9)
396
10.661(3)
12.306(4)
12.609(3)
68.55(3)
69.56(3)
67.88(3)
1382.7(7)
560
b, Å
c, Å
α, deg
β, deg
γ, deg
V, Å3
F(000)
Crystal system
Space group
Z
Monoclinic
P21/n
Triclinic
Triclinic
–
–
P1
P1
4
2
293
2
293
Temperature, K
μ, mm–1
293
0.233
0.212
1.378
60
0.159
1.274
50
d
calc, g/cm3
1.432
2Θmax, deg
50
Total number of reflections
6517
8370
5217
0.017
4025
0237
0.045
0.145
0.995
1473885
9221
4647
0.130
1807
0348
0.073
0.141
0.843
1473886
Number of independent reflections
3194
Rint
0.032
Number of reflections with F > 4σ(F)
2043
Number of variables
R1
0253
0.050
wR2
0.150
Goodness of fit S
CCDC entry no.
1.000
1473884
C11–C15 bond [torsion angles C10C11C15C16 78.0(1),
C11C15C16O5 28.8(2)°]. The orientation of the acyl
group with respect to the endocyclic C10–C11 bond is
close to antiperiplanar [torsion angle C10C11C15C14
–157.9(1)°], and the torsion angle C11C15C14O4 is
–108.2(1)°. The acetyl methyl group and the π-system
of the phenyl substituent on the sulfur atom are
oriented pseudo-cis with respect to the C7···C12 ring
and are located close to each other. As a result, the
methyl proton singlet of 6b and 6c is observed in
a stronger field (δ 1.96 ppm) relative to the corre-
sponding signal of trifluoromethanesulfonyl deriva-
tives 6a or 6d (δ 2.13–2.14 ppm). Molecules 6b in
crystal are linked to form chains through intermolec-
ular hydrogen bonds O3–H3A · · · O4′ (x – 1, y, z;
H3A···O4′ 1.90 Å, ∠O3H3AO4′ 171°) and N1–H1A···O1′
(2 – x, 1 – y, –z; H1A···O1′ 2.35 Å, ∠N1H1AO1′ 125°).
We also performed X-ray analysis of ethyl
3-(4-methylanilino)-2-[1-hydroxy-4-(4-methylben-
zenesulfonylamino)naphthalen-2-yl]but-2-enoate (8)
synthesized previously [5] (Fig. 3) in order to compare
structural parameters of 1,4-addition products derived
from N-substituted 1,4-benzoquinone imine and
1,4-naphthoquinone imine. The tosyl group in mole-
cule 8 is orthogonal to the naphthalene plane [torsion
angle C6C7N1S1 –88.0(5)°]. The tolyl substituent ap-
pears in –sc conformation with respect to the C7–N1
bond and is turned with respect to the N1–S1 bond
[torsion angles C7N1S1C24 –59.3(4), N1S1C24C29
–63.5(4)°]. The planar fragment of the substituent on
C9 (including the C11=C12 double bond and ester,
methyl, and NH groups) is additionally stabilized by
intramolecular hydrogen bond N2–H2A···O4 (H2A···O4
1.98 Å, ∠N2H2AO4 135°) and is oriented almost ortho-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

KONOVALOVA et al.
532
gonally to the naphthalene fragment [torsion angle
C10C9C11C12 112.2(5)°]. The tolyl substituent on N2 is
antiperiplanar with respect to the C11=C12 bond and is
turned relative to the above planar fragment to form
torsion angles C11C12N2C17 –167.1(4) and C12N2C17C18
43.6(7)°. As in molecule 6b, the C13 methyl group in 8
is spatially close to the C24–C29 aromatic π-system, so
that protons on C13 resonate in a strong field (δ 1.61–
Initial quinone imines 1a, 1o [19], 1b, 1m [20],
1c–1k [13], 1l [21], 1q [22], 1n, and 1p [23] were
described previously.
The X-ray diffraction data for compounds 3q, 6b,
and 8 were obtained on an Xcalibur-3 diffractometer
(Mo Kα radiation, CCD detector, graphite mono-
chromator, ω-scanning). The structures were solved by
the direct method implemented in SHELXTL [24]. The
positions of hydrogen atoms were determined from the
difference electron density maps and were refined
according to the riding model (Uiso = nUeq, where
n = 1.5 for methyl and hydroxy groups, and n = 1.2 for
other hydrogen atoms). The crystallographic data and
experimental parameters are given in table. The coor-
dinates of atoms and complete tables of bond lengths
and bond angles for compounds 3q, 6b, and 8 were
deposited to the Cambridge Crystallographic Data
Centre (e-mail: deposit@ccdc.cam.ac.uk); CCDC entry
numbers are given in table.
1
1.66 ppm) in the H NMR spectrum [5]. The C11=C12,
C12–N2, and C11–C14 bond lengths in molecule 8 are
1.367, 1.360, and 1.445 Å, respectively (cf. the
C10=C12, C12–N2, and C10–C11 bond lengths in 3q:
1.372, 1.338, and 1.441 Å, respectively); these values
are typical of such compounds. Molecules 8 in crystal
are linked to chains through intermolecular hydrogen
bonds O1–H1B···O4′ (1 – x, –y, 1 – z; H1B···O4′
2.11 Å, ∠O1H1BO4′ 146°) and N1–H1A···O2′ (–x, 2 – y,
2 – z; H1A···O 2.26 Å, ∠NH1AO 148°).
PASS online prediction [18] of biological activity
of compounds 3–7 revealed antiarrhythmic, cardio-
tonic, and antineoplastic (brain cancer, colorectal
cancer) activities with probabilities of 0.805–0.901,
0.805–0.876, and 0.707–0.880, respectively.
Reaction of quinone imines 1a–1q with enamines
2a–2e (general procedures). a. A mixture of 1.5 mmol
of quinone imine 1a–1e, 1l, or 1m and 1.7 mmol of
enamine 2a–2d in 40 mL of 1,2-dichloroethane was
refluxed for 1 h. The solvent was distilled off under
reduced pressure, a few drops of ethanol were added to
the brown oily residue, and the light brown precipitate
was filtered off and washed with a small amount of
ethanol.
In summary, reactions of N-methanesulfonyl-,
N-trifluoromethanesulfonyl-, and N-arenesulfonyl-1,4-
benzoquinone imines gave 1,4-addition products and
indole and benzofuran derivatives. The reaction direc-
tion is determined by the solvent nature, electron-
withdrawing power of the substituent on the quinone
imine nitrogen atom, and enamine structure. Introduc-
tion of a strong electron-withdrawing trifluoro-
methanesulfonyl group to the nitrogen atom favors
formation of 1,4-addition products and benzofuran
derivatives.
b. A solution of 1.7 mmol of enamine 2a–2e in
10 mL of acetone or chloroform was added to a solu-
tion of 1.5 mmol of quinone imine 1a–1q in 10 mL of
the same solvent. The solution immediately turned
dark brown. Evaporation of the mixture left a light
solid. If the residue was oily, it was treated with a few
drops of ethanol, the mixture was stirred, and the
precipitate was filtered off and washed with a small
amount of ethanol.
EXPERIMENTAL
1
c. Enamine 2a–2e, 1.7 mmol, was added to a sus-
pension or solution of 1.5 mmol of quinone imine 1a–
1i, 1l, or 1m–1q in 10 mL of glacial acetic acid. The
mixture immediately turned dark brown. After a time
(several minutes to several hours), a light solid precip-
itated. In same cases, water was added dropwise to
initiate precipitation. The product was filtered off and
washed with a small amount of ethanol.
The H NMR spectra were recorded on a Varian
VXR-300 spectrometer (300 MHz) using tetramethyl-
silane as internal standard and DMSO-d6 as solvent.
The 19F NMR spectra of compounds 3b–3e, 5j–5o, 6a,
and 6d were measured on a Varian Gemini-200
instrument at 188.14 MHz relative to trichloro(fluoro)-
methane. The IR spectra were recorded in KBr on
a UR-20 spectrometer. The purity of the initial com-
pounds and reaction products was checked by TLC on
Silufol UV-254 plates; samples were applied from
solutions in acetone or THF, and ethanol–chloroform
(1:10) and hexane–ethyl acetate (1:2) were used as
eluents; spots were visualized under UV light.
d. A solution of 1.7 mmol of enamine 2a–2e in
10 mL of glacial acetic acid was added at room
temperature or on cooling to –10°C to a solution of
1.5 mmol of quinone imine 1h–1k in 10 mL of chloro-
form or chloroform–acetic acid mixture. The solution
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
533
immediately turned dark brown or violet. After 24 h,
the mixture was evaporated, and the light precipitate
was filtered off and washed with a small amount
of ethanol.
(3f). Yield 71%, mp 158–159°C. 1H NMR spectrum, δ,
ppm: 1.02 t (3H, CH2Me, J = 5.4 Hz), 1.72 s (3H,
C=CMe), 2.32 s (3H, MeC6H4), 3.99 q (2H, OCH2),
6.67 d (1H, 6-H, J6,5 = 7.8 Hz), 6.70 d (1H, 3-H, J3,5
=
1.2 Hz), 6.79–6.81 d.d (1H, 5-H), 7.28 d (2H, 3″-H,
5″-H, J = 7.8 Hz), 7.33 d (2H, 2″-H, 6″-H, J = 7.8 Hz),
7.53 d (2H, 3′-H, 5′-H, J = 6.8 Hz), 8.18 d (2H, 2′-H,
6′-H, J = 6.8 Hz), 9.10 s (1H, NH), 9.61 s (1H, NH),
11.34 s (1H, OH). Found, %: N 8.17, 8.25; S 6.20,
6.24. C25H25N3O7S. Calculated, %: N 8.21; S 6.27.
All isolated compounds were recrystallized from
ethanol, hexane, aqueous ethanol (1:1), or benzene–
hexane (1:2).
N-{4-Hydroxy-3-[2-(4-methylanilino)-4-oxopent-
2-en-3-yl]phenyl}methanesulfonamide (3a). Yield
1
65%, mp 151–153°C. H NMR spectrum, δ, ppm:
Ethyl 2-{2-hydroxy-5-[(4-methylbenzenesul-
fonyl)amino]-4-methylphenyl)-3-(4-nitroanilino)-
1.71 s (3H, COMe), 1.78 s (3H, C=CMe), 2.31 s (3H,
MeC6H4), 2.87 s (3H, MeSO2), 6.86 d (1H, 6-H, J6,5
=
1
but-2-enoate (3g). H NMR spectrum, δ, ppm: 1.05 t
8.4 Hz), 6.95 d (1H, 3-H, J3,5 = 1.2 Hz), 7.01–7.03 d.d
(1H, 5-H), 7.10 d (2H, 3′-H, 5′-H, J = 8.0 Hz), 7.23 d
(2H, 2′-H, 6′-H, J = 8.0 Hz), 9.21 br.s (2H, NH),
13.51 s (1H, OH). Found, %: N 7.40, 7.45; S 8.54,
8.60. C19H22N2O4S. Calculated, %: N 7.48; S 8.56.
(3H, CH2Me, J = 6.4 Hz), 1.75 s (3H, C=CMe), 1.93 s
(3H, 3-Me), 2.36 s (3H, MeC6H4), 3.99 q (2H, OCH2),
6.53 s (1H, 2-H), 6.58 s (1H, 5-H), 7.27 d (2H, 3″-H,
5″-H, J = 8.7 Hz), 7.34 d (2H, 2″-H, 6″-H, J = 8.7 Hz),
7.51 d (2H, 3′-H, 5′-H, J = 8.4 Hz), 8.19 d (2H, 2′-H,
6′-H, J = 8.4 Hz), 9.15 s (1H, NH), 9.16 s (1H, NH),
11.30 s (1H, OH).
Ethyl 3-anilino-2-{2-hydroxy-5-[(trifluoro-
methanesulfonyl)amino]phenyl}but-2-enoate (3b).
1
Yield 37%, mp 68–70°C. H NMR spectrum, δ, ppm:
Ethyl 3-amino-2-{5-[(benzenesulfonyl)amino]-
1.07 t (3H, CH2Me, J = 6.8 Hz), 1.70 s (3H, C=CMe),
4.01 q (2H, OCH2), 6.69 d (1H, 6-H, J6,5 = 8.1 Hz),
6.72 d (1H, 3-H, J3,5 = 1.2 Hz), 7.00–7.02 d.d (1H,
5-H), 7.19–7.42 m (5H, Ph), 8.40 s (1H, NH),
10.01 br.s (1H, NH), 11.33 s (1H, OH). 19F NMR spec-
trum: δF –75.48 ppm, s. Found, %: N 6.25, 6.55; S 8.50,
8.62. C19H19F3N2O5S. Calculated, %: N 6.30; S 8.56.
2-hydroxyphenyl}but-2-enoate (3i). Yield 68%,
1
mp 120–122°C. H NMR spectrum, δ, ppm: 0.98 t
(3H, CH2Me, J = 7.2 Hz), 1.37 s (3H, MeC=C),
3.86 m and 3.92 m (1H each, OCH2), 6.53 d (1H, 3-H,
J3,5 = 2.4 Hz), 6.60 d (1H, 6-H, J6,5 = 7.8 Hz), 6.75–
6.77 d.d (1H, 5-H), 7.47–7.64 m (5H, Ph), 8.35 br.s
(2H, NH2), 8.76 s (1H, NH), 9.60 br.s (1H, OH).
Found, %: N 7.32, 7.55; S 8.48, 8.54. C18H20N2O5S.
Calculated, %: N 7.44; S 8.52.
Ethyl 3-anilino-2-{2-hydroxy-3-methyl-5-[(tri-
fluoromethanesulfonyl)amino]phenyl}but-2-enoate
(3c). Yield 54%, mp 137–139°C. 1H NMR spectrum, δ,
ppm: 1.07 t (3H, CH2Me, J = 7.2 Hz), 1.70 s (3H,
C=CMe), 2.17 s (3H, 2-Me), 4.00 q (2H, OCH2),
6.73 d (1H, 5-H, J5,3 = 1.4 Hz), 6.91 d (1H, 3-H), 7.18–
7.41 m (5H, Ph), 8.32 s (1H, NH), 8.44 s (1H, NH),
Ethyl 3-amino-2-{3-chloro-2-hydroxy-5-[(4-
methylbenzenesulfonyl)amino]phenyl}but-2-enoate
(3j). Yield 61%, mp 102–104°C. 1H NMR spectrum, δ,
ppm: 0.98 t (3H, CH2Me, J = 6.2 Hz), 1.37 s (3H,
MeC=C), 2.33 s (3H, MeC6H4), 3.88 m and 4.09 m
(1H each, OCH2), 6.52 s (1H, 4-H), 6.93 s (1H, 6-H),
7.20 br.s (1H, NH2), 7.37 d (2H, 3″-H, 5″-H, J =
8.1 Hz), 7.52 d (2H, 2″-H, 6″-H, J = 8.1 Hz), 8.45 br.s
(1H, NH2), 8.71 s (1H, NH), 9.77 br.s (1H, OH).
Found, %: N 6.51, 6.64; S 7.48, 7.54. C19H21ClN2O5S.
Calculated, %: N 6.59; S 7.55.
19
11.31 s (1H, OH). F NMR spectrum: δF –74.59 ppm,
s . F o u n d , % : N 6 . 0 7 , 6 . 1 2 ; S 6 . 9 0 , 6 . 9 5.
C20H21F3N2O5S. Calculated, %: N 6.11; S 6.99.
Ethyl 3-anilino-2-{2-hydroxy-3,4-dimethyl-5-
[(trifluoromethanesulfonyl)amino]phenyl}but-2-
1
enoate (3e). Yield 62%, mp 81–83°C. H NMR spec-
trum, δ, ppm: 1.07 t (3H, CH2Me, J = 6.8 Hz), 1.70 s
(3H, C=CMe), 2.14 s (3H, 2-Me), 2.20 s (3H, 3-Me),
3.99 q (2H, OCH2), 6.72 s (1H, 5-H), 7.16–7.41 m
(5H, Ph), 8.39 s (1H, NH), 10.32 br.s (1H, NH),
11 . 3 2 s ( 1 H , O H ) . 1 9 F N M R s p e c t r u m:
δF –75.53 ppm, s. Found, %: N 5.89, 5.95; S 6.80,
6.85. C21H23F3N2O5S. Calculated, %: N 5.93; S 6.79.
Ethyl 3-amino-2-{6-hydroxy-2,4-dimethyl-3-[(4-
methylbenzenesulfonyl)amino]phenyl}but-2-enoate
(3k). Yield 85%, mp 210–212°C. H NMR spectrum,
δ, ppm: 0.98 t (3H, CH2Me, J = 7.2 Hz), 1.45 s (3H,
MeC=C), 1.53 s (3H, 3-Me), 1.93 s (3H, 5-Me),
3.94 m (2H, OCH2), 6.44 s (1H, 6-H), 6.94 br.s (1H,
NH2), 7.32 d (2H, 3″-H, 5″-H, J = 8.4 Hz), 7.47 d (2H,
2″-H, 6″-H, J = 8.4 Hz), 8.36 br.s (1H, NH2), 8.60 s
(1H, NH), 8.90 br.s (1H, OH). Found, %: N 6.51,
1
Ethyl 2-{2-hydroxy-5-[(4-methylbenzenesul-
fonyl)amino]phenyl}-3-(4-nitroanilino)but-2-enoate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

KONOVALOVA et al.
534
6.64; S 7.58, 7.64. C21H26N2O5S. Calculated, %:
N 6.69; S 7.66.
each, OCH2), 6.63 d (1H, 4-H, J4,6 = 1.8 Hz), 6.85 d
(1H, 6-H), 7.18 br.s and 8.14 s (1H each, NH2),
8.51 br.s (1H, NH), 11.23 br.s (1H, OH). 19F NMR
spectrum: δF –75.33 ppm, s. Found, %: N 7.21, 7.45;
S 8.30, 8.42. C14H17F3N2O5S. Calculated, %: N 7.33;
S 8.39.
Ethyl 3-amino-2-{2-hydroxy-5-[(methanesul-
fonyl)amino]phenyl}but-2-enoate (3l). Yield 72%,
1
mp 174–175°C. H NMR spectrum, δ, ppm: 1.02 t
(3H, CH2Me, J = 7.2 Hz), 1.62 s (3H, MeC=C), 2.82 s
(3H, MeSO2), 3.86 m and 3.95 m (1H each, OCH2),
Ethyl 3-amino-2-{2-hydroxy-3,4-dimethyl-5-
[(trifluoromethanesulfonyl)amino]phenyl}but-2-
enoate (3q). Yield 83%, mp 203–204°C. H NMR
6.71 d (1H, 3-H, J3,4 = 8.4 Hz), 6.81 d (1H, 6-H, J4,6
=
1
1.8 Hz), 6.88–6.91 d.d (1H, 4-H, J = 1.8, 8.4 Hz),
7.02 br.s and 8.41 br.s (1H each, NH2), 8.81 s
(1H, NH), 9.05 br.s (1H, OH). Found, %: N 8.71,
8.95; S 10.09, 10.16. C13H18N2O5S. Calculated, %:
N 8.91; S 10.20.
spectrum, δ, ppm: 1.01 t (3H, CH2Me, J = 6.2 Hz),
1.56 s (3H, MeC=C), 2.11 s (3H, 3-Me), 2.17 s (3H,
4-Me), 3.86 m and 3.96 m (1H each, OCH2), 6.61 s
(1H, 6-H), 7.16 br.s and 8.07 s (1H each, NH2),
8.52 br.s (1H, NH), 10.91 br.s (1H, OH). 19F NMR
spectrum: δF –75.79 ppm, s. Found, %: N 6.98, 7.10;
S 7.97, 8.11. C15H19F3N2O5S. Calculated, %: N 7.07;
S 8.09.
Ethyl 3-amino-2-{2-hydroxy-5-[(methanesul-
fonyl)amino]-3-methylphenyl}but-2-enoate (3m).
1
Yield 74%, mp 165–167°C. H NMR spectrum, δ,
ppm: 1.02 t (3H, CH2Me, J = 6.2 Hz), 1.59 s (3H,
MeC=C), 2.12 s (3H, 3-Me), 2.82 s (3H, MeSO2),
3.86 m and 3.97 m (1H each, OCH2), 6.64 d (1H, 4-H,
J4,6 = 1.8 Hz), 6.81 d (1H, 6-H), 7.12 br.s and 7.83 s
(1H each, NH2), 8.49 br.s (1H, NH), 9.00 br.s
(1H, OH). Found, %: N 8.31, 8.52; S 9.68, 9.74.
C14H20N2O5S. Calculated, %: N 8.53; S 9.76.
Ethyl 7-chloro-2-methyl-5-[(4-methylbenzenesul-
fonyl)amino]-1-phenyl-1H-indole-3-carboxylate
1
(4a). Yield 68%, mp 229–231°C. H NMR spectrum,
δ, ppm: 1.37 t (3H, CH2Me, J = 6.9 Hz), 2.32 s (3H,
MeC6H4), 2.33 s (3H, 2-Me), 4.30 q (2H, OCH2),
6.93 s (1H, 6-H), 7.35 d (2H, 3″-H, 5″-H, J = 7.8 Hz),
7.39–7.55 m (5H, Ph), 7.67 d (2H, 2″-H, 6″-H, J =
7.8 Hz), 7.92 s (1H, 4-H), 10.02 br.s (1H, NH). Found,
%: N 5.79, 5.81; S 6.60, 6.66. C25H23ClN2O4S. Calcu-
lated, %: N 5.80; S 6.64.
Ethyl 3-amino-2-{2-hydroxy-5-[(methanesul-
fonyl)amino]-3,4-dimethylphenyl}but-2-enoate (3n).
1
Yield 68%, mp 197–199°C. H NMR spectrum, δ,
ppm: 1.02 t (3H, CH2Me, J = 6.2 Hz), 1.59 s (3H,
MeC=C), 2.09 s (3H, 3-Me), 2.17 s (3H, 4-Me), 2.83 s
(3H, MeSO2), 3.97 m (2H, CH2Me), 6.67 s (1H, 6-H),
7.14 br.s and 7.85 s (1H each, NH2), 8.52 br.s (1H,
NH), 8.61 br.s (1H, OH). Found, %: N 8.01, 8.19;
S 9.28, 9.35. C15H22N2O5S. Calculated, %: N 8.18;
S 9.36.
Ethyl 2,7-dimethyl-5-[(4-methylbenzenesul-
fonyl)amino]-1-phenyl-1H-indole-3-carboxylate
1
(4b). Yield 53%, mp 207–209°C. H NMR spectrum,
δ, ppm: 1.35 t (3H, CH2Me, J = 6.9 Hz), 1.64 s (3H,
7-Me), 2.32 s (3H, 2-Me), 4.29 q (2H, OCH2), 6.67 s
(1H, 6-H), 7.33 d (2H, 3″-H, 5″-H, J = 8.1 Hz), 7.41–
7.58 m (5H, Ph), 7.66 d (2H, 2″-H, 6″-H, J = 8.1 Hz),
7.76 s (1H, 4-H), 10.02 br.s (1H, NH). Found, %:
N 6.01, 6.10; S 6.88, 6.95. C26H26N2O4S. Calculated,
%: N 6.06; S 6.93.
Ethyl 3-amino-2-{2-hydroxy-5-[(trifluoro-
methanesulfonyl)amino]phenyl}but-2-enoate (3o).
1
Yield 53%, mp 124–126°C. H NMR spectrum, δ,
ppm: 1.01 t (3H, CH2Me, J = 7.2 Hz), 1.60 s (3H,
MeC=C), 3.87 m and 3.95 m (1H each, OCH2), 6.77 d
N-[3-Acetyl-2,7-dimethyl-1-(4-methylphenyl)-
1H-indol-5-yl]methanesulfonamide (4c). Yield 89%,
mp 186–189°C. H NMR spectrum, δ, ppm: 1.74 s
(3H, 7-Me), 2.37 s (3H, 2-Me), 2.45 s (3H, MeC6H4),
2.56 s (3H, COMe), 2.91 (3H, MeSO2), 6.82 br.s (1H,
6-H), 7.34 d (2H, 3′-H, 5′-H, J = 8.2 Hz), 7.40 d (2H,
2′-H, 6′-H, J = 8.2 Hz), 7.98 br.s (1H, 4-H), 9.42 br.s
(1H, NH). Found, %: N 7.50, 7.58; S 7.08, 7.16.
C20H22N2O3S. Calculated, %: N 7.56; S 7.15.
(1H, 3-H, J3,4 = 8.4 Hz), 6.78 d (1H, 6-H, J4,6
=
1
1.8 Hz), 6.92–6.94 d.d (1H, 4-H, J = 1.8, 8.4 Hz),
7.06 br.s and 8.41 br.s (1H each, NH2), 9.11 s (1H,
NH), 11.32 br.s (1H, OH). 19F NMR spectrum:
δF –75.96 ppm, s. Found, %: N 7.54, 7.77; S 8.59,
8.72. C13H15F3N2O5S. Calculated, %: N 7.61; S 8.71.
Ethyl 3-amino-2-{2-hydroxy-3-methyl-5-[(tri-
fluoromethanesulfonyl)amino]phenyl}but-2-enoate
1
(3p). Yield 71%, mp 178–179°C. H NMR spectrum,
Ethyl 5-[(methanesulfonyl)amino]-2,7-dimethyl-
δ, ppm: 1.01 t (3H, CH2Me, J = 6.2 Hz), 1.56 s (3H,
MeC=C), 2.13 s (3H, 3-Me), 3.86 m and 3.99 m (1H
1-phenyl-1H-indole-3-carboxylate (4d). Yield 41%,
mp 191–193°C. H NMR spectrum, δ, ppm: 1.38 t
1
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REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
535
(3H, CH2Me, J = 6.8 Hz), 1.73 s (3H, 7-Me), 2.38 s
(3H, 2-Me), 2.91 s (3H, MeSO2), 4.31 q (2H, OCH2),
6.81 br.s (1H, 6-H), 7.48–7.62 m (5H, Ph), 7.94 br.s
(1H, 4-H), 9.47 br.s (1H, NH). Found, %: N 7.20,
7.26; S 8.28, 8.36. C20H22N2O4S. Calculated, %:
N 7.25; S 8.30.
Found, %: N 6.45, 6.50; S 7.39, 7.43. C22H26N2O5S.
Calculated, %: N 6.51; S 7.45.
Ethyl 5-[(methanesulfonyl)amino]-2-methyl-1-
(4-nitrophenyl)-1H-indole-3-carboxylate 4(j). Yield
1
74%, mp 217–219°C. H NMR spectrum, δ, ppm:
1.40 t (3H, CH2Me, J = 6.8 Hz), 2.57 s (3H, 2-Me),
N-[3-Acetyl-2,6-dimethyl-1-(4-methylphenyl)-
1H-indol-5-yl]methanesulfonamide (4e). Yield 85%,
mp 211–213°C. H NMR spectrum, δ, ppm: 2.33 s
(3H, 2-Me), 2.44 s (3H, MeC6H4), 2.48 s (3H, 6-Me),
2.58 s (3H, COMe), 2.97 s (3H, MeSO2), 6,81 s (1H,
7-H), 7.31 d (2H, 3′-H, 5′-H, J = 8.1 Hz), 7.45 d (2H,
2′-H, 6′-H, J = 8.1 Hz), 8.04 s (1H, 4-H), 9.01 br.s
(1H, NH). Found, %: N 7.54, 7.58; S 8.61, 8.65.
C20H22N2O3S. Calculated, %: N 7.56; S 8.66.
2.92 s (3H, MeSO2), 4.33 q (2H, OCH2), 7.07 d (1H,
7-H, J7,6 = 8.4 Hz), 7.10–7.13 d.d (1H, 6-H, J6,4
=
1
1.2 Hz), 7.83 d (2H, 3′-H, 5′-H, J = 8.0 Hz), 8.04 d
(1H, 4-H), 8.47 d (2H, 2′-H, 6′-H, J = 8.0 Hz),
9.59 br.s (1H, NH). Found, %: N 10.01, 10.10; S 7.59,
7.65. C19H19N3O6S. Calculated, %: N 10.07; S 7.68.
Ethyl 7-chloro-2-methyl-5-[(4-methylbenzenesul-
fonyl)amino]-1-(4-nitrophenyl)-1H-indole-3-carbox-
ylate (4k). Yield 69%, mp 229–230°C. 1H NMR spec-
trum, δ, ppm: 1.39 t (3H, CH2Me, J = 6.1 Hz), 2.34 s
(3H, MeC6H4), 2.38 s (3H, 2-Me), 4.33 q (2H, OCH2),
6.98 br.s (1H, 6-H), 7.37 d (2H, 3″-H, 5″-H, J =
7.5 Hz), 7.68 d (2H, 2″-H, 6″-H, J = 7.5 Hz), 7.79 d
(2H, 3′-H, 5′-H, J = 7.8 Hz), 7.95 br.s (1H, 4-H),
8.40 d (2H, 2′-H, 6′-H, J = 7.8 Hz), 10.36 br.s (1H,
NH). Found, %: N 7.91, 7.95; S 6.01, 6.08.
C25H22ClN3O6S. Calculated, %: N 7.96; S 6.07.
Ethyl 5-[(methanesulfonyl)amino]-2,6-dimethyl-
1-phenyl-1H-indole-3-carboxylate (4f). Yield 90%,
1
mp 167–168°C. H NMR spectrum, δ, ppm: 1.38 t
(3H, CH2Me, J = 5.4 Hz), 2.33 s (3H, 2-Me), 2.50 s
(3H, 6-Me), 2.97 s (3H, MeSO2), 4.33 q (2H, OCH2),
6.84 s (1H, 7-H), 7.45–7.67 m (5H, Ph), 8.01 s (1H,
4-H), 9.00 br.s (1H, NH). Found, %: N 7.18, 7.25;
S 8.24, 8.28. C20H22N2O4S. Calculated, %: N 7.25;
S 8.30.
Ethyl 2,7-dimethyl-5-[(4-methylbenzenesul-
N-[3-Acetyl-2,6,7-trimethyl-1-(4-methylphenyl)-
1H-indol-5-yl]methanesulfonamide (4g). Yield 83%,
mp 165–167°C. H NMR spectrum, δ, ppm: 1.67 s
(3H, 7-Me), 2.20 s (3H, 6-Me), 2.31 s (3H, 2-Me),
2.40 s (3H, MeC6H4), 2.52 s (3H, COMe), 2.91 s (3H,
MeSO2), 7.24 d (2H, 3′-H, 5′-H, J = 8.4 Hz), 7.36 d
(2H, 2′-H, 6′-H, J = 8.4 Hz), 7.96 s (1H, 4-H), 8.99 br.s
(1H, NH). Found, %: N 7.28, 7.31; S 8.34, 8.38.
C21H24N2O3S. Calculated, %: N 7.29; S 8.34.
fonyl)amino]-1-(4-nitrophenyl)-1H-indole-3-carbox-
ylate (4l). Yield 51%, mp 244–246°C. H NMR spec-
1
1
trum, δ, ppm: 1.34 t (3H, CH2Me, J = 6.1 Hz), 1.67 s
(3H, 7-Me), 2.32 s (3H, MeC6H4), 2.33 s (3H, 2-Me),
4.29 q (2H, OCH2), 6.70 br.s (1H, 6-H), 7.32 d (2H,
3″-H, 5″-H, J = 7.5 Hz), 7.64 d (2H, 2″-H, 6″-H, J =
7.5 Hz), 7.75 d (2H, 3′-H, 5′-H, J = 8.1 Hz), 7.78 br.s
(1H, 4-H), 8.37 d (2H, 2′-H, 6′-H, J = 8.1 Hz),
10.05 br.s (1H, NH). Found, %: N 8.21, 8.27; S 6.27,
6.34. C26H25N3O6S. Calculated, %: N 8.28; S 6.32.
Ethyl 5-[(methanesulfonyl)amino]-2,6,7-tri-
methyl-1-phenyl-1H-indole-3-carboxylate (4h).
Yield 87%, mp 154–155°C. H NMR spectrum, δ,
Ethyl 2,6-dimethyl-5-[(4-methylbenzenesul-
1
fonyl)amino]-1-(4-nitrophenyl)-1H-indole-3-carbox-
1
ppm: 1.38 t (3H, CH2Me, J = 6.4 Hz), 1.70 s (3H,
7-Me), 2.24 s (3H, 6-Me), 2.37 s (3H, 2-Me), 2.95 s
(3H, MeSO2), 4.32 q (2H, OCH2), 7.44–7.61 m (5H,
Ph), 7.96 s (1H, 4-H), 9.03 br.s (1H, NH). Found, %:
N 6.95, 7.02; S 7.97, 8.02. C21H24N2O4S. Calculated,
%: N 6.99; S 8.01.
ylate (4m). H NMR spectrum, δ, ppm: 1.24 t (3H,
CH2Me, J = 6.8 Hz), 2.13 s (3H, 2-Me), 2.38 s (3H,
MeC6H4), 2.52 s (3H, 6-Me), 4.23 q (2H, OCH2),
6.90 s (1H, 7-H), 7.07 s (1H, 4-H), 7.36 d (2H, 3″-H,
5″-H, J = 7.5 Hz), 7.57 d (2H, 2″-H, 6″-H, J = 7.5 Hz),
7.80 d (2H, 3′-H, 5′-H, J = 8.1 Hz), 8.45 d (2H, 2′-H,
6′-H, J = 8.1 Hz), 9.43 br.s (1H, NH).
Ethyl 5-[(methanesulfonyl)amino]-1-(4-methoxy-
phenyl)-2,6,7-trimethyl-1H-indole-3-carboxylate
(4i). Yield 84%, mp 174–176°C. 1H NMR spectrum, δ,
ppm: 1.36 t (3H, CH2Me, J = 6.8 Hz), 1.74 s (3H,
7-Me), 2.23 s (3H, 6-Me), 2.36 s (3H, 2-Me), 2.94 s
(3H, MeSO2), 3.86 s (3H, MeO), 4.30 q (2H, OCH2),
7.14 d (2H, 3′-H, 5′-H, J = 8.7 Hz), 7.36 d (2H, 2′-H,
6′-H, J = 8.7 Hz), 7.94 s (1H, 4-H), 9.03 br.s (1H, NH).
Ethyl 5-[(methanesulfonyl)amino]-2,6-dimethyl-
1-(4-nitrophenyl)-1H-indole-3-carboxylate (4n).
1
Yield 67%, mp 210–212°C. H NMR spectrum, δ,
ppm: 1.38 t (3H, CH2Me, J = 7.6 Hz), 2.34 s (3H,
2-Me), 2.56 s (3H, 6-Me), 2.97 s (3H, MeSO2), 4.33 q
(2H, OCH2), 6.98 s (1H, 7-H), 7.83 d (2H, 3′-H, 5′-H,
J = 8.4 Hz), 8.02 s (1H, 4-H), 8.47 d (2H, 2′-H, 6′-H,
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KONOVALOVA et al.
536
J = 8,4 Hz), 9.03 br.s (1H, NH). Found, %: N 9.68,
9.77; S 7.39, 7.42. C20H21N3O6S. Calculated, %:
N 9.74; S 7.43.
215°C. 1H NMR spectrum, δ, ppm: 2.43 s (3H, 6-Me),
2.59 s (3H, COMe), 2.77 s (3H, 2-Me), 3.00 (3H,
MeSO2), 7.51 s (1H, 7-H), 7.91 s (1H, 4-H), 9.11 br.s
(1H, NH). Found, %: N 4.95, 4.99; S 11.41, 11.44.
C13H15NO4S. Calculated, %: N 4.98; S 11.40.
Ethyl 5-[(methanesulfonyl)amino]-2,6,7-tri-
methyl-1-(4-nitrophenyl)-1H-indole-3-carboxylate
1
(4o). Yield 55%, mp 196–197°C. H NMR spectrum,
Ethyl 5-[(methanesulfonyl)amino]-2,6-dimethyl-
δ, ppm: 1.38 t (3H, CH2Me, J = 6.4 Hz), 1.73 s (3H,
7-Me), 2.26 s (3H, 6-Me), 2.40 s (3H, 2-Me), 2.95
(3H, MeSO2), 4.32 q (2H, OCH2), 7.77 d (2H, 3′-H,
5′-H, J = 7.5 Hz), 7.97 s (1H, 4-H), 8.43 d (2H, 2′-H,
6′-H, J = 7.5 Hz), 9.05 br.s (1H, NH). Found, %:
N 9.38, 9.45; S 7.17, 7.22. C21H23N3O6S. Calculated,
%: N 9.43; S 7.20.
1-benzofuran-3-carboxylate (5f). Yield 61%,
mp 172–173°C. H NMR spectrum, δ, ppm: 1.36 t
1
(3H, CH2Me, J = 5.1 Hz), 2.41 s (3H, 6-Me), 2.72 s
(3H, 2-Me), 2.97 s (3H, MeSO2), 4.32 q (2H, OCH2),
7.50 s (1H, 7-H), 7.81 s (1H, 4-H), 9.10 br.s (1H, NH).
Found, %: N 4.45, 4.51; S 10.28, 10.32. C14H17NO5S.
Calculated, %: N 4.50; S 10.30.
Ethyl 7-chloro-2-methyl-5-[(4-methylbenzenesul-
fonyl)amino]-1-benzofuran-3-carboxylate (5a).
Yield 68%, mp 182–184°C. H NMR spectrum, δ,
ppm: 1.37 t (3H, CH2Me, J = 7.5 Hz), 2.33 s (3H,
MeC6H4), 2.72 s (3H, 2-Me), 4.32 q (2H, OCH2),
7.15 d (1H, 6-H, J6,4 = 1.5 Hz), 7.36 d (2H, 3″-H,
5″-H, J = 8.1 Hz), 7.65 d (1H, 4-H), 7.66 d (2H, 2″-H,
6″-H, J = 8.1 Hz), 10.49 br.s (1H, NH). Found, %:
N 3.38, 3.45; S 7.79, 7.86. C19H18ClNO5S. Calculated,
%: N 3.43; S 7.86.
N-(3-Acetyl-2,6,7-trimethyl-1-benzofuran-5-yl)-
methanesulfonamide (5g). Yield 55%, mp 190–
191°C. 1H NMR spectrum, δ, ppm: 2.34 s (3H, 6-Me),
2.42 s (3H, 7-Me), 2.60 s (3H, COMe), 2.81 s (3H,
2-Me), 2.97 s (3H, MeSO2), 7.77 s (1H, 4-H), 9.13 br.s
(1H, NH). Found, %: N 4.65, 4.70; S 10.86, 10.89.
C14H17NO4S. Calculated, %: N 4.74; S 10.86.
1
Ethyl 5-[(methanesulfonyl)amino]-2,6,7-tri-
methyl-1-benzofuran-3-carboxylate (5h). Yield 70%,
1
mp 184–185°C. H NMR spectrum, δ, ppm: 1.37 t
Ethyl 2,7-dimethyl-5-[(4-methylbenzenesul-
fonyl)amino]-1-benzofuran-3-carboxylate (5b).
(3H, CH2Me, J = 6.8 Hz), 2.32 s (3H, 6-Me), 2.40 s
(3H, 7-Me), 2.74 s (3H, 2-Me), 2.95 s (3H, MeSO2),
4.34 q (2H, CH2Me), 7.67 s (1H, 4-H), 9.12 br.s
(1H, NH). Found, %: N 4.20, 4.28; S 9.78, 9.84.
C15H19NO5S. Calculated, %: N 4.30; S 9.85.
1
Yield 72%, mp 167–169°C. H NMR spectrum, δ,
ppm: 1.34 t (3H, CH2Me, J = 6.9 Hz), 2.31 s (3H,
7-Me), 2.34 s (3H, MeC6H4), 2.68 s (3H, 2-Me), 4.29 q
(2H, OCH2), 6.90 d (1H, 6-H, J6,4 = 1.5 Hz), 7.36 d
(2H, 3″-H, 5″-H, J = 7.8 Hz), 7.47 d (1H, 4-H), 7.66 d
(2H, 2″-H, 6″-H, J = 7.8 Hz), 10.16 br.s (1H, NH).
Found, %: N 3.59, 3.68; S 8.19, 8.26. C20H21NO5S.
Calculated, %: N 3.62; S 8.28.
Ethyl 5-[(methanesulfonyl)amino]-2,4,6-tri-
methyl-1-benzofuran-3-carboxylate (5i). Yield 62%,
1
mp 154–156°C. H NMR spectrum, δ, ppm: 1.34 t
(3H, CH2Me, J = 6.4 Hz), 2.44 s (3H, 6-Me), 2.55 s
(3H, 4-Me), 2.61 s (3H, 2-Me), 3.05 s (3H, MeSO2),
4.34 q (2H, OCH2), 7.35 s (1H, 7-H), 8.89 br.s
(1H, NH). Found, %: N 4.29, 4.35; S 9.82, 9.88.
C15H19NO5S. Calculated, %: N 4.30; S 9.85.
N-(3-Acetyl-2-methyl-1-benzofuran-5-yl)-
methanesulfonamide (5c). Yield 75%, mp 170–
1
171°C. H NMR spectrum, δ, ppm: 2.58 s (3H,
COMe), 2.79 s (3H, 2-Me), 2.94 s (3H, MeSO2), 7.21–
7.23 d.d (1H, 6-H, J6,7 = 8.8, J6,4 = 1.2 Hz), 7.57 d (1H,
7-H), 7.92 d (1H, 4-H), 9.65 br.s (1H, NH). Found, %:
N 5.15, 5.22; S 11.97, 12.03. C12H13NO4S. Calculated,
%: N 5.24; S 12.00.
N-(3-Acetyl-2-methyl-1-benzofuran-5-yl)tri-
fluoromethanesulfonamide (5j). Yield 30%, mp 164–
1
165°C. H NMR spectrum, δ, ppm: 2.59 s (3H,
COMe), 2.81 s (3H, 2-Me), 7.22–7.24 d.d (1H, 6-H,
J
6,7 = 8.7, J6,4 = 1.2 Hz), 7.63 d (1H, 7-H), 7.96 d (1H,
N-(3-Acetyl-2,7-dimethyl-1-benzofuran-5-yl)-
methanesulfonamide (5d). Yield 48%, mp 207–
209°C. 1H NMR spectrum, δ, ppm: 2.46 s (3H, 7-Me),
2.58 s (3H, COMe), 2.80 s (3H, 2-Me), 2.95 s (3H,
MeSO2), 7.07 br.s (1H, 6-H), 7.76 br.s (1H, 4-H),
9.58 br.s (1H, NH). Found, %: N 4.85, 4.90; S 11.34,
11.41. C13H15NO4S. Calculated, %: N 4.98; S 11.40.
4-H), 11.82 br.s (1H, NH). 19F NMR spectrum:
δF –74.89 ppm, s. Found, %: N 4.30, 4.37; S 9.92,
9.97. C12H10F3NO4S. Calculated, %: N 4.36; S 9.98.
N-(3-Acetyl-2,7-dimethyl-1-benzofuran-5-yl)-
trifluoromethanesulfonamide (5k). Yield 35%,
mp 197–198°C. H NMR spectrum, δ, ppm: 2.50 s
1
N-(3-Acetyl-2,6-dimethyl-1-benzofuran-5-yl)-
methanesulfonamide (5e). Yield 82%, mp 213–
(3H, 7-Me), 2.59 s (3H, COMe), 2.84 s (3H, 2-Me),
7.09 br.s (1H, 6-H), 7.81 br.s (1H, 4-H), 11.82 br.s (1H,
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REACTION OF N-SULFONYL-1,4-BENZOQUINONE IMINES WITH ENAMINES
537
NH). 19F NMR spectrum: δF –74.91 ppm, s. Found, %:
N 4.11, 4.19; S 9.49, 9.55. C13H12F3NO4S. Calculated,
%: N 4.18; S 9.56.
7.26 s (1H, 7-H), 7.54–7.69 m (5H, Ph), 9.43 br.s
(1H, NH). Found, %: N 3.45, 3.68; S 8.23, 8.30.
C20H21NO5S. Calculated, %: N 3.62; S 8.28.
Ethyl 2,7-dimethyl-5-[(trifluoromethanesul-
Ethyl 5-[(methanesulfonyl)amino]-2,7-dimethyl-
fonyl)amino]-1-benzofuran-3-carboxylate (5l). Yield
54%, mp 145–147°C. H NMR spectrum, δ, ppm:
1-benzofuran-3-carboxylate (5r). Yield 61%,
mp 172–173°C. H NMR spectrum, δ, ppm: 1.36 t
1
1
1.36 t (3H, CH2Me, J = 6.8 Hz), 2.46 s (3H, 7-Me),
2.75 s (3H, 2-Me), 4.34 q (2H, OCH2), 7.06 d (1H,
6-H, J6,4 = 1.2 Hz), 7.66 d (1H, 4-H), 11.85 br.s (1H,
NH). 19F NMR spectrum: δF –75.16 ppm, s. Found, %:
N 3.78, 3.85; S 8.73, 8.79. C14H14F3NO5S. Calculated,
%: N 3.83; S 8.78.
(3H, CH2Me, J = 5.1 Hz), 2.41 s (3H, 6-Me), 2.72 s
(3H, 2-Me), 2.97 s (3H, MeSO2), 4.32 q (2H, OCH2),
7.50 s (1H, 7-H), 7.81 s (1H, 5-H), 9.10 br.s (1H, NH).
Found, %: N 4.35, 4.51; S 10.23, 10.32. C14H17NO5S.
Calculated, %: N 4.00; S 10.30.
Ethyl 2-{2-hydroxy-4-methyl-5-[(trifluoro-
methanesulfonyl)amino]phenyl}-3-oxobutanoate
N-(3-Acetyl-2,6-dimethyl-1-benzofuran-5-yl)-
trifluoromethanesulfonamide (5m). Yield 71%,
1
(6a). Yield 40%, mp 135–136°C. H NMR spectrum,
1
mp 145–167°C. H NMR spectrum, δ, ppm: 2.41 s
δ, ppm: 1.18 t (3H, CH2Me, J = 6.4 Hz), 2.13 s (3H,
4-Me), 2.23 s (3H, MeCO), 4.15 q (2H, OCH2), 5.10 s
(1H, CH), 6.78 s (1H, 3-H), 6.93 s (1H, 6-H),
10.16 br.s (1H, NH), 11.11 br.s (1H, OH). 19F NMR
spectrum: δF –75.58 ppm, s. Found, %: N 3.58, 3.64;
S 8.31, 8.38. C14H16F3NO6S. Calculated, %: N 3.65;
S 8.36.
(3H, 6-Me), 2.57 s (3H, COMe), 2.79 s (3H, 2-Me),
7.56 s (1H, 7-H), 7.89 s (1H, 4-H), 11.80 br.s (1H,
NH). 19F NMR spectrum: δF –75.96 ppm, s. Found, %:
N 4.13, 4.19; S 9.51, 9.58. C13H12F3NO4S. Calculated,
%: N 4.18; S 9.56.
N-(3-Acetyl-2,6,7-trimethyl-1-benzofuran-5-yl)-
trifluoromethanesulfonamide (5n). Yield 65%,
Ethyl 2-{5-[(benzenesulfonyl)amino]-2-hydroxy-
1
mp 183–185°C. H NMR spectrum, δ, ppm: 2.32 s
phenyl}-3-oxobutanoate (6b). Yield 67%, mp 175–
1
(3H, 6-Me), 2.42 s (3H, 7-Me), 2.56 s (3H, COMe),
2.79 s (3H, 2-Me), 7.76 s (1H, 4-H), 11.53 br.s (1H,
NH). 19F NMR spectrum: δF –75.11 ppm, s. Found, %:
N 3.95, 3.99; S 9.11, 9.18. C14H14F3NO4S. Calculated,
%: N 4.01; S 9.18.
177°C. H NMR spectrum, δ, ppm: 1.15 t (3H,
CH2Me, J = 6.2 Hz), 1.96 s (3H, MeCO), 4.04 m (2H,
OCH2), 4.99 s (1H, CH), 6.72 d (1H, 6-H, J6,5
=
7.8 Hz), 6.75 d (1H, 3-H, J3,5 = 1.2 Hz), 6.86–6.90 d.d
(1H, 5-H), 7.48–7.64 m (5H, Ph), 9.80 s (1H, NH),
9.86 s (1H, OH). Found, %: N 3.65, 3.82; S 8.42, 8.61.
C18H19NO6S. Calculated, %: N 3.71; S 8.50.
Ethyl 2,6,7-trimethyl-5-[(trifluoromethanesul-
fonyl)amino]-1-benzofuran-3-carboxylate (5o).
1
Yield 57%, mp 118–120°C. H NMR spectrum, δ,
Ethyl 2-{2-hydroxy-5-[(4-methylbenzenesul-
ppm: 1.23 t (3H, CH2Me, J = 6.8 Hz), 2.10 s (3H,
6-Me), 2.13 s (3H, 7-Me), 2.19 s (3H, 2-Me), 4.29 q
(2H, OCH2), 7.17 s (1H, 4-H), 11.14 br.s (1H, NH).
19F NMR spectrum: δF –75.76 ppm, s. Found, %:
N 3.61, 3.72; S 8.38, 8.44. C15H16F3NO5S. Calculated,
%: N 3.69; S 8.45.
fonyl)amino]phenyl}-3-oxobutanoate (6c). Yield
71%, mp 139–141°C. H NMR spectrum, δ, ppm:
1
1.15 t (3H, CH2Me, J = 6.4 Hz), 1.96 s (3H, MeCO),
4.07 m (2H, OCH2), 4.98 s (1H, CH), 6.72 d (1H, 6-H,
J6,5 = 7.8 Hz), 6.74 d (1H, 3-H, J3,5 = 1.2 Hz), 6.86–
6.90 d.d (1H, 5-H), 7.30 d (2H, 3″-H, 5″-H, J = 8.1 Hz),
7.50 d (2H, 2″-H, 6″-H, J = 8.1 Hz), 9.67 s (1H, NH),
9.79 s (1H, OH). Found, %: N 3.42, 3.65; S 8.13, 8.23.
C19H21NO6S. Calculated, %: N 3.58; S 8.19.
Ethyl 5-[(benzenesulfonyl)amino]-2,6,7-tri-
methyl-1-benzofuran-3-carboxylate (5p). Yield 88%,
1
mp 174–175°C. H NMR spectrum, δ, ppm: 1.23 t
(3H, CH2Me, J = 6.9 Hz), 2.11 s (3H, 7-Me), 2.33 s
(3H, 6-Me), 2.69 s (3H, 2-Me), 4.21 q (2H, OCH2),
7.11 s (1H, 4-H), 7.53–7.65 m (5H, Ph), 9.58 s (1H,
NH). Found, %: N 3.58, 3.75; S 8.28, 8.36.
C20H21NO5S. Calculated, %: N 3.62; S 8.28.
Ethyl 2-{2-hydroxy-5-[(trifluoromethanesul-
fonyl)amino]phenyl}-3-oxobutanoate (6d). Yield
1
55%, mp 127–129°C. H NMR spectrum, δ, ppm:
1.18 t (3H, CH2Me, J = 6.4 Hz), 2.14 s (3H, MeCO),
4.12 m (2H, OCH2), 5.14 s (1H, CH), 6.90 d (1H, 6-H,
J6,5 = 7.8 Hz), 6.98 d (1H, 3-H, J3,5 = 1.2 Hz), 7.07–
7.09 d.d (1H, 5-H), 10.21 s (1H, NH), 11.51 br.s (1H,
OH). 19F NMR spectrum: δF –75.84 ppm, s. Found, %:
N 3.61, 3.81; S 8.56, 8.66. C14H16F3NO6S. Calculated,
%: N 3.79; S 8.68.
Ethyl 5-[(benzenesulfonyl)amino]-2,4,6-tri-
methyl-1-benzofuran-3-carboxylate (5q). Yield 75%,
1
mp 185–186°C. H NMR spectrum, δ, ppm: 1.28 t
(3H, CH2Me, J = 6.9 Hz), 2.01 s (3H, 6-Me), 2.11 s
(3H, 4-Me), 2.58 s (3H, 2-Me), 4.27 q (2H, OCH2),
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KONOVALOVA et al.
538
12. Granik, V.G., Osnovy meditsinskoi khimii (Fundamentals
N-(4-Nitrophenyl)acetamide (7). Yield 48%,
of Medicinal Chemistry), Moscow: Vuzovskaya Kniga,
2001.
13. Avdeenko, A.P., Konovalova, S.A., Mikhailichen-
ko, O.N., Shelyazhenko, S.V., Pirozhenko, V.V., and
Yagupol’skii, L.M., Russ. J. Org. Chem., 2011, vol. 47,
p. 510.
14. Avdeenko, A.P., Konovalova, S.A., Mikhailichen-
ko, O.N., Shelyazhenko, S.V., Pirozhenko, V.V., and
Yagupol’skii, L.M., Russ. J. Org. Chem., 2012, vol. 48,
p. 221.
mp 210–212°C; published data [25]: mp 214°C.
1H NMR spectrum, δ, ppm: 2.12 s (3H, COMe), 7.83 d
(2H, 3-H, 5-H, J = 8.1 Hz), 8.22 d (2H, 2-H, 6-H, J =
8.1 Hz), 10.58 br.s (1H, NH).
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