Intramolecular electrophilic cyclization of functional derivatives of unsaturated compounds: III. Reaction of N,4-Diarylbut-3-enamides with arenesulfenyl chlorides. Synthesis of 5-aryl-4-arylsulfanyl-2,3,4,5-tetrahydro- 1H-1-benzazepin-2-ones

Article abstract of DOI:10.1134/S107042801212007X

N-Aryl-4-phenylbut-3-enamides reacted with arenesulfenyl chlorides in chloroform to give N,4-diaryl-3-arylsulfanyl-4-chlorobutanamides, whereas in acetic acid in the presence of lithium perchlorate N-[4-arylsulfanyl-5- phenyltetrahydrofuran-2-ylidene]arenaminium perchlorates were obtained. Reactions of arenesulfenyl chlorides with N,4-diarylbut-3-enamides having strong electron-donating groups in positions 3 and 4 of the N-aryl substituent afforded 5-aryl-4-arylsulfanyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones.

Full text of DOI:10.1134/S107042801212007X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1536–1543. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.I. Vas’kevich, N.M. Tsyzoryk, V.I. Staninets, E.B. Rusanov, M.V. Vovk, 2012, published in Zhurnal Organicheskoi Khimii, 2012,
Vol. 48, No. 12, pp. 1565–1572.
Intramolecular Electrophilic Cyclization
of Functional Derivatives of Unsaturated Compounds:
III.* Reaction of N,4-Diarylbut-3-enamides with Arenesulfenyl
Chlorides. Synthesis of 5-Aryl-4-arylsulfanyl-2,3,4,5-tetrahydro-
1H-1-benzazepin-2-ones
A. I. Vas’kevich, N. M. Tsyzoryk, V. I. Staninets, E. B. Rusanov, and M. V. Vovk
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
e-mail: vaskevich@ioch.kiev.ua
Received April 20, 2012
Abstract—N-Aryl-4-phenylbut-3-enamides reacted with arenesulfenyl chlorides in chloroform to give N,4-di-
aryl-3-arylsulfanyl-4-chlorobutanamides, whereas in acetic acid in the presence of lithium perchlorate
N-[4-arylsulfanyl-5-phenyltetrahydrofuran-2-ylidene]arenaminium perchlorates were obtained. Reactions of
arenesulfenyl chlorides with N,4-diarylbut-3-enamides having strong electron-donating groups in positions 3
and 4 of the N-aryl substituent afforded 5-aryl-4-arylsulfanyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones.
DOI: 10.1134/S107042801212007X
Unsaturated carboxylic acid amides possess two
competitive nucleophilic centers and are therefore
convenient models for studying the effect of structural
factors on chemo- and regioselectivity of electrophilic
intramolecular cyclizations [2]. We previously studied
cyclization of allyl- and cinnamylacetamides with
arenesulfenyl chlorides [1, 3] and found that the size of
the resulting heteroring and the formation of iminolac-
tones or lactams are determined by the position and
degree of substitution of the double bond in the initial
amide, as well as by the nature of the substituent on the
nitrogen atom. In particular, allylacetamides gave rise
to 2-iminotetrahydrofuran derivatives, whereas six-
membered lactams or lactones were formed from cin-
namylacetamides, depending on the steric parameters
of the amide fragment.
be expected that such structural specificity of amides
Іa–Ig should affect the cyclization path and product
structure.
As we showed in [1, 3], the cyclization requires the
use of a strong electrolyte in a highly polar medium
owing to reduced electrophilicity of arenesulfenyl
chlorides. The same turned out to be also valid for the
reactions of N-aryl amides Іa–Id with arenesulfenyl
chlorides ІІa–IIc. The reaction in weakly polar chloro-
form gave 66–78% of N,4-diaryl-3-arylsulfanyl-4-
chlorobutanamides IІІa–IIIf as electrophilic addition
products at the C=C bond (Scheme 1). When the reac-
tion was carried out in acetic acid in the presence of
lithium perchlorate [4, 5], amides Іc and Id having
electron-donating 4-methoxy or 3,4-dimethyl substit-
uents in the N-aryl group gave rise to air-stable
N-[4-arylsulfanyl-5-phenyltetrahydrofuran-2-ylidene]-
arenaminium perchlorates ІVa–IVf in 44–78% yield.
The cyclization of amides Іa and Ib containing no
activating substituents was less selective, and the
reaction mixtures contained the corresponding per-
chlorates IV and open-chain adducts III (according to
In the present work we selected as substrates
N-aryl-substituted styrylacetamides Іa–Ig in which the
N-aryl groups were characterized by different electron-
donor powers. The double C=C bond in Іa–Ig is sep-
arated from the carboxamide fragment by one methy-
lene group, and (as in cinnamylacetamides) the carbon
chain terminates with an aromatic substituent. It might
1
the H NMR data); we failed to separate these product
mixtures.
* For communication II, see [1].
1536

INTRAMOLECULAR ELECTROPHILIC CYCLIZATION OF FUNCTIONAL ... III.
1537
Scheme 1.
Cl
H
CHCl3
N
Ph
Ar
SAr'
O
H
N
IIIa–IIIf
+
Ar'SCl
IIa–IIc
Ph
Ar
O
Ar'S
LiClO4, AcOH
Ia–Id
ClO4
NH
Ar
O
Ph
IVa–IVf
I, Ar = Ph (a), 4-ClC6H4 (b), 4-MeOC6H4 (c), 3,4-Me2C6H3 (d); II, Ar′ = Ph (a), 4-MeC6H4 (b), 4-O2NC6H4 (c); III, Ar = Ph, Ar′ =
Ph (a), 4-MeC6H4 (b), 4-O2NC6H4 (c); Ar = 4-ClC6H4, Ar′ = 4-MeC6H4 (d), 4-O2NC6H4 (e); Ar = 4-MeOC6H4, Ar′ = 4-O2NC6H4 (f);
IV, Ar = 4-MeOC6H4, Ar′ = Ph (a), 4-MeC6H4 (b), 4-O2NC6H4 (c); Ar = 3,4-Me2C6H3, Ar′ = Ph (d), 4-MeC6H4 (e), 4-O2NC6H4 (f).
The site of the addition of arenesulfenyl chlorides
donating substituents in positions 3 and 4 of the
N-phenyl ring were quite surprising. Compounds Іe–Ig
reacted with sulfenyl chlorides ІІa and IIb in acetic
acid in the presence of lithium perchlorate to give
5-aryl-4-arylsulfanyl-2,3,4,5-tetrahydro-1H-1-benzaz-
epin-2-ones Va–Vf (Scheme 2) which were isolated in
31–82% yield. Analysis of the reaction mixtures by
1H NMR also revealed the presence of perchlorates IV
and adducts ІІІ. The major products of the reactions of
4-nitrobenzenesulfenyl chloride (ІІc) with amides Ie
and If were perchlorate IVg and 3-arylsulfanyl-4-
chlorobutanamide ІІІg, respectively; the amounts of
the corresponding benzazepinones V were so small
that they cannot be isolated and characterized.
to amides Іa–Id follows from the structure of com-
1
pounds ІІІa–IIIf which displayed in the H NMR
spectra a multiplet signal at δ 4.06– 4.35 ppm due to
3-H and a doublet at δ 5.11–5.13 ppm (J = 7–8.8 Hz)
due to 4-H. Thus the reaction is highly regioselective.
1
The H NMR spectra of iminium salts IVa–IVf con-
tained a multiplet at δ 4.14–4.61 ppm due to 4-H and
a doublet at δ 5.87–6.03 ppm (J = 6.4–9.6 Hz) due to
5-H, indicating trans orientation of the phenyl and
arylsulfanyl substituents in the tetrahydrofuran ring.
Unlike analogous salts obtained from allylacetamides
[1], the hydrolysis of IVa–IVf in the presence of
sodium acetate or ethoxide was not selective, and we
failed to isolate the corresponding γ-lactones.
Presumably, compounds Va–Vf are formed as
a result of electrophilic intramolecular cyclization
where the nucleophilic center is the ortho position in
The results of reactions of arenesulfenyl chlorides
with N-aryl amides Іe–Ig having strong electron-
Scheme 2.
Ar
S
Ar
Ar'
SAr'
H
R1
R2
R1
R2
N
R2
R1
LiClO4, AcOH
Ar
+
IIa–IIc
O
N
O
N
H
H
O
Ie–Ig
A
Va–Vf
Cl
O
H
ClO4
Ph
S
N
OMe
S
HN
O
Ph
O2N
OMe
O2N
O
O
IIIg
IVg
I, Ar = Ph, R1 = R2 = MeO (e), R1R2 = OCH2O (f); Ar = 4-FC6H4, R1 = R2 = MeO (g); V, Ar = Ph, R1 = R2 = OMe, Ar′ = Ph (a),
4-MeC6H4 (b); Ar = Ph, R1R2 = OCH2O, Ar′ = Ph (c), 4-MeC6H4 (d); Ar = 4-FC6H4, R1 = R2 = OMe, Ar′ = Ph (e), 4-MeC6H4 (f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

VAS’KEVICH et al.
1538
C11
N1
C7
C6
C1
C2
C3
C8
O2
S1
C4
C5
C24
C14
C19
O3
C9
C10
C13
C15
C23
C12
C20
C22
C18
C17
C16
C25
C21
Structure of the molecule of 7,8-dimethoxy-4-(4-methylphenylsulfanyl)-5-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Vb)
according to the X-ray diffraction data. Selected bond lengths and bond angles: C6–N1 1.417(2), C1–N1 1.350(2), C1–C2 1.499(3),
C2–C3 1.531(3), C3–C4 1.542(3), C4–C5 1.525(3), C5–C6 1.397(3), C1–O1 1.234(2), C3–S1 1.832(2), C19–S1 1.768(2) Å; N1C1C2
116.61(17), C1C2C3 113.77(16), C2C3C4 114.11(15), C5C4C3 113.88(15), C6C5C4 119.99(17), C5C6N1 121.54(18), C19S1C3 101.73(9)°.
the N-phenyl group activated by strong electron-donat-
ing substituents (OCH3 or OCH2O) rather than the
amide oxygen or nitrogen atom. Azepine ring closure
is likely to involve initial generation of cation A
stabilized by perchlorate ion and subsequent 7-endo-
trig cyclization.
in flattened configuration of the N1 atom [the sum of
bond angles at N1 is 358.9(2)°]. The C1–C3 and C1–C19
bonds are nonequivalent [1.832(2) and 1.768(2) Å,
respectively] due to different orbital structure of the
carbon atoms attached to sulfur. Molecules Vb in crys-
tal are linked to centrosymmetric dimers by hydrogen
bonds N1H···O1a [N–H 0.83(2), N1···O1a 2.871(2) Å,
∠NHO 172(2)°]; the O1a atom is related to the base
molecule by the symmetry operation –x, 2–y, –z.
The assumed structure of benzazepinones Va–Vf is
consistent with their NMR and mass spectra. In the
1H NMR spectra, the most informative were singlets
from 6-H and 9-H in the benzene ring at δ 6.20–6.38
and 6.54–6.68 ppm, a doublet from 5-H (δ 4.03–
4.28 ppm, J = 9.5–10.5 Hz), and multiplets from 3-H
(δ 2.21–2.62 and 2.51–2.74 ppm) and 4-H (δ 4.18–
4.53 ppm). The 13C NMR spectra contained signals
from C2 at δC 170–172 ppm and C3–C5 at δC 38–39,
50–51, and 53–54 ppm, respectively.
It is known that polysubstituted partly hydrogenat-
ed benzazepin-2-ones exhibit diverse and often very
important pharmacological properties [6–11]. Methods
for their synthesis generally include a number of steps
and are based on transformations of difficultly acces-
sible anthranilic acid derivatives. In this article we
described an efficient procedure for the synthesis of
benzazepines containing a readily modifiable arylsul-
fanyl substituent in position 4 of the azepine ring. For
example, compounds Vb and Ve were readily oxidized
to derivatives VІa and VIb possessing a biophoric
sulfonyl group (Scheme 3).
The structure of benzazepinones V was unambigu-
ously proved by the X-ray diffraction data obtained for
compound Vb (see figure). The central seven-mem-
bered ring in molecule Vb is not planar. The C4C5C6N1
fragment is almost planar (deviations of atoms from
the mean-square plane do not exceed 0.0204 Å). The
N1C1C3C4 plane (deviation of atoms from the mean-
square plane is 0.0886 Å) with the C4C5C6N1 fragment
forms a dihedral angle of 48.9(1)°, while the C1C2C3
and N1C1C3C4 planes form a dihedral angle of
51.0(2)°. The N1–C1 bond is considerably shortened
[1.350(2)] relative to standard single C–N bond due to
conjugation between the lone electron pair on the ni-
trogen atom and carbonyl π-bond; this is also reflected
Scheme 3.
Ar
SO2Ar'
MeO
KHSO5
Vb, Ve
MeO
N
H
O
VIa, VIb
Ar = Ph, Ar′ = 4-MeC6H4 (a); Ar= 4-FC6H4, Ar′ = Ph (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

INTRAMOLECULAR ELECTROPHILIC CYCLIZATION OF FUNCTIONAL ... III.
1539
EXPERIMENTAL
at 15°C to a solution of 2 mmol of amide Іa–Ic in
10 ml of chloroform. The mixture was stirred for 4 h at
room temperature and evaporated under reduced pres-
sure, the residue was treated with 5 ml of diethyl ether,
and the precipitate was filtered off and dried in air.
The IR spectra were recorded from KBr pellets or
CH2Cl2 solutions on a UR-20 spectrometer. The 1H and
13C NMR spectra were measured on a Bruker Avance
DRX-500 spectrometer at 500.13 and 125.75 MHz,
respectively, using tetramethylsilane as internal refer-
ence. The mass spectra were obtained on an Agilent
110\DAD\HSD\VLG 119562 instrument.
4-Chloro-N,4-diphenyl-3-phenylsulfanylbutan-
1
amide (ІІІa). Yield 75%, mp 101–102°C. H NMR
spectrum (CDCl3), δ, ppm: 2.61–2.70 m (1H, CH),
3.11–3.18 m (1H, CH), 4.08–4.15 (1H, CH), 5.10 d
(1H, CH, J = 7.6 Hz), 7.14–7.34 m (13H, Harom),
7.49 d (2H, Harom, J = 8 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 40.24 (C2), 53.92 (C3), 66.32 (C4);
120.02, 124.48, 127.77, 127.84, 128.33, 128.48,
128.94, 129.01, 133.06, 133.90, 137.67, 138.70
(Carom); 168.08 (C1). Found, %: C 69.07; H 5.22;
Cl 9.16; N 3.58. C22H20ClNOS. Calculated, %:
C 69.19; H 5.28; Cl 9.28; N 3.67.
X-Ray analysis of compound Vb. The X-ray dif-
fraction data were acquired from a 0.16×0.23×0.33-
mm single crystal of Vb at room temperature on
a Bruker Smart Apex II diffractometer (λMoKα irra-
diation, graphite monochromator, θmax = 26.39°, spher-
ical segment –46 ≤ h ≤ 48, –6 ≤ k ≤ 6, –32 ≤ l ≤ 31).
Monoclinic crystal system, space group C2/c; unit
cell parameters: a = 38.8665(9), b = 5.2029(1), c =
25.7886(6) Å; β = 122.457(1)°; V = 4400.33(17) Å3;
Z = 8; dcalc = 1.267 g/cm3; μ = 0.173 mm–1; F(000) =
1776. Total of 20352 reflections were measured, 4506
of which were independent (averaging R-factor
0.0398). A correction for absorption was introduced
by the multiscan method using SADABS program
(Tmin/Tmax = 0.745412). The structure was solved by
the direct method and was refined by the least-squares
procedure using SHELXTL software package [12].
The positions of all non-hydrogen atoms were refined
in anisotropic approximation. Hydrogen atoms (except
for the NH hydrogen atom whose position was refined
in isotropic approximation) were placed into positions
calculated on the basis of geometry considerations and
were refined according to the riding model (along with
the positions and thermal parameters of the corre-
sponding carbon atoms). The refinement procedure
involved 3320 reflections with I > 2σ(I); number of
refined parameters 277, 12 reflections per parameters;
the weight scheme ω = 1/[σ2(Fo2) + (0.07R)2 +2.9P],
where P = (Fo2 + 2Fc2)/3, was used; the ratio of the
maximal (average) deviation to the error in the last
iteration was 0.014 (0.001). The final divergence
factors were R1(F) = 0.0431, wR2(F2) = 0.1146 for re-
flections with I > 2σ(I) and R1(F) = 0.0655, wR2(F2) =
0.1370 for all reflections; goodness of fit 1.052. The
residual electron density from the Fourier difference
series after the last iteration was 0.30 and –0.26 e/Å3.
The set of crystallographic data for compound Vb was
deposited to the Cambridge Crystallographic Data
Centre (entry no. CCDC 873693).
4-Chloro-3-(4-methylphenylsulfanyl)-N,4-diphe-
nylbutanamide (ІІІb). Yield 68%, mp 106–107°C. IR
1
spectrum, ν, cm–1: 1650, 1595, 1540, 1495. H NMR
spectrum (CDCl3), δ, ppm: 2.30 s (3H, CH3), 2.66–
2.73 m (1H, CH), 3.10–3.17 m (1H, CH), 4.06–4.12 m
(1H, CH), 5.13 d (1H, CH, J = 7 Hz), 7.01 d (2H,
Harom, J = 7.5 Hz), 7.11–7.36 m (10H, Harom), 7.54 d
(2H, Harom, J = 7 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 21.12 (Me), 40.04 (C2), 54.05 (C3), 66.31 (C4);
120.05, 124.41, 127.83, 128.37, 128.43, 128.97,
129.76, 129.98, 133.57, 137.78, 138.13, 138.81
(Carom); 168.26 (C1). Found, %: C 69.71; H 5.52;
Cl 8.79; N 3.59. C23H22ClNOS. Calculated, %:
C 69.77; H 5.60; Cl 8.95; N 3.54.
4-Chloro-3-(4-nitrophenylsulfanyl)-N,4-diphe-
nylbutanamide (ІІІc). Yield 78%, mp 134–135°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.68–2.77 m (1H,
CH), 3.29–3.36 m (1H, CH), 4.28–4.35 m (1H, CH),
5.11 d (1H, CH, J = 8.4 Hz), 7.11–7.52 m (12H, Harom),
7.94 d (2H, Harom, J = 8.8 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 40.57 (C2), 53.63 (C3), 65.98 (C4);
120.10, 123.63, 124.83, 127.94, 128.34, 128.78,
129.08, 130.99, 137.39, 138.22, 144.19, 146.34
(Carom); 167.74 (C1). Found, %: C 61.78; H 4.42;
Cl 8.21; N 6.54. C22H19ClN2O3S. Calculated, %:
C 61.89; H 4.49; Cl 8.30; N 6.56.
4-Chloro-N-(4-chlorophenyl)-3-(4-methylphenyl-
sulfanyl)-4-phenylbutanamide (ІІІd). Yield 66%,
1
mp 114–115°C. H NMR spectrum (CDCl3), δ, ppm:
2.29 s (3H, CH3), 2.61–2.69 m (1H, CH), 3.08–3.15 m
(1H, CH), 4.01–4.08 m (1H, CH), 5.10 d (1H, CH, J =
7.2 Hz), 6.99 d (2H, Harom, J = 7.6 Hz), 7.15 d (2H,
Compounds ІІІa–IIIf (general procedure). A solu-
tion of 2 mmol of arenesulfenyl chloride ІІa–IIc in
5 ml of chloroform was added dropwise under stirring
H
arom, J = 7.2 Hz), 7.22–7.32 m (6H, Harom), 7.43–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

VAS’KEVICH et al.
1540
7.49 m (3H, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 21.09 (Me), 39.98 (C2), 53.95 (C3), 66.24 (C4);
121.20, 127.79, 128.41, 128.51, 128.98, 129.45,
129.78, 133.53, 133.73, 136.26, 138.24, 138.69
(Carom); 168.11 (C1). Found, %: C 64.09; H 4.87;
Cl 16.38; N 3.31. C23H21Cl2NOS. Calculated, %:
C 64.19; H 4.92; Cl 16.47; N 3.25.
124.28, 126.02, 127.12, 129.24, 129.32, 129.69,
129.75, 130.58, 133.00, 134.24, 159.85 (Carom); 175.64
(C2). Found, %: C 58. 11; H 4. 62; N 3. 01.
C23H22ClNO6S. Calculated, %: C 58.04; H 4.66; N 2.94.
4-Methoxy-N-[4-(4-methylphenylsulfanyl)-
5-phenyltetrahydrofuran-2-ylidene]anilinium per-
chlorate (ІVb). Yield 70%, mp 127–128°C. IR spec-
trum, ν, cm–1: 1690 (C=N), 1515, 1260, 1115. 1H NMR
spectrum (CDCl3), δ, ppm: 2.30 s (3H, CH3), 3.60–
3.69 m (1H, CH), 3.76 s (3H, CH3) 4.07–4.20 m (2H,
4-Chloro-N-(4-chlorophenyl)-3-(4-nitrophenyl-
sulfanyl)-4-phenylbutanamide (ІІІe). Yield 78%,
1
mp 107–108°C. H NMR spectrum (CDCl3), δ, ppm:
CH), 5.84 d (1H, CH, J = 7.2 Hz), 6.82 d (2H, Harom
,
2.65–2.76 m (1H, CH), 3.27–3.35 m (1H, CH), 4.24–
4.33 m (1H, CH), 5.08 d (1H, CH, J = 7.6 Hz), 7.12–
7.36 m (11H, Harom), 7.92 d (2H, Harom, J = 8 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 40.50 (C2),
53.59 (C3), 66.04 (C4); 121.36, 123.66, 127.95, 128.38,
128.86, 129.12, 129.87, 130.97, 135.93, 138.14,
144.07, 146.41 (Carom); 167.80 (C1). Found, %:
C 67.15; H 3.85; Cl 15.24; N 6.14. C22H18Cl2N2O3S.
Calculated, %: C 67.27; H 3.93; Cl 15.37; N 6.07.
J = 8.8 Hz), 7.12 d (2H, Harom, J = 7.6 Hz), 7.30–
13
7.46 m (9H, Harom), 11.99 s (1H, NH). C NMR spec-
trum (CDCl3), δC, ppm: 35.56 (CH3), 38.74 (C3), 49.03
(C4), 55.51 (OCH3), 97.88 (C5); 114.75, 124.21,
125.53, 126.04, 127.00, 129.37, 130.51, 130.57,
133.07, 135.11, 140.06, 159.85 (Carom); 175.61 (C2).
Found, %: C 58.91; H 4.99; N 2.80. C24H24ClNO6S.
Calculated, %: C 58.83; H 4.94; N 2.86.
4-Methoxy-N-[4-(4-nitrophenylsulfanyl)-5-phe-
nyltetrahydrofuran-2-ylidene]anilinium perchlorate
(ІVc). Yield 44%, mp 144–145°C. IR spectrum, ν,
4-Chloro-N-(4-methoxyphenyl)-3-(4-nitrophe-
nylsulfanyl)-4-phenylbutanamide (ІІІf). Yield 73%,
mp 136–137°C. IR spectrum, ν, cm–1: 1645, 1345,
1
cm–1: 1685 (C=N), 1515, 1340, 1115. H NMR spec-
1
1245. H NMR spectrum (CDCl3), δ, ppm: 2.65–
trum (CDCl3), δ, ppm: 3.66–3.75 m (4H, CH3, CH),
4.39–4.48 m (1H, CH), 4.52–4.61 m (1H, CH), 5.87 d
(1H, CH, J = 9.6 Hz), 6.76 d (2H, Harom, J = 8.8 Hz),
7.18–7.49 m (9H, Harom), 7.92 d (2H, Harom, J =
8.4 Hz), 11.87 s (1H, NH). 13C NMR spectrum
(CDCl3), δC, ppm: 39.52 (C3), 47.71 (C4), 55.33
(OCH3), 97.61 (C5); 114.83, 124.08, 124.30, 125.78,
127.49, 129.41, 129.75, 131.02, 132.45, 141.08,
146.63, 159.95 (Carom); 175.64 (C2). Found, %: 53.09;
H 4.11; N 5.31. C23H21ClN2O8S. Calculated, %:
C 53.03; H 4.06; N 5.38.
2.73 m (1H, CH), 3.27–3.33 m (1H, CH), 3.79 s (3H,
CH3), 4.27–4.35 m (1H, CH), 5.11 d (1H, CH, J =
8.8 Hz), 6.86 d (2H, Harom, J = 9.2 Hz), 7.13–7.40 m
13
(9H, Harom), 7.94 d (2H, Harom, J = 8.8 Hz). C NMR
spectrum (CDCl3), δC, ppm: 40.40 (C2), 53.64 (C3),
55.62 (OMe), 65.90 (C4); 107.36, 114.26, 122.10,
123.63, 127.97, 128.36, 128.80, 130.40, 130.98,
138.25, 144.26, 156.84 (Carom); 167.58 (C1). Found, %:
C 60.32; H 4.56; Cl 7.64; N 6.09. C23H21ClN2O4S.
Calculated, %: C 60.46; H 4.63; Cl 7.76; N 6.13.
Compounds ІVa–IVf (general procedure). A solu-
tion of 2.2 mmol of arenesulfenyl chloride IIa–IIc in
5 ml of acetic acid was added dropwise at 15°C to
a solution of 2.2 mmol of amide Іc or Id and 0.23 g
(2.2 mmol) of lithium perchlorate in 10 ml of acetic
acid. The mixture was stirred for 4 h at room tempera-
ture, and the precipitate was filtered off, washed with
acetic acid and hexane, and dried in air.
3,4-Dimethyl-N-[5-phenyl-4-(phenylsulfanyl)-
tetrahydrofuran-2-ylidene]anilinium perchlorate
(ІVd). Yield 78%, mp 129–130°C. IR spectrum, ν,
1
cm–1: 1690 (C=N), 1535, 1120–1125. H NMR spec-
trum (CDCl3), δ, ppm: 2.20 s (3H, CH3), 2.21 s (3H,
CH3), 3.67–3.74 m (1H, CH), 4.13–4.18 m (1H, CH),
4.20–4.27 m (1H, CH), 5.90 d (1H, CH, J = 7 Hz),
7.07–7.11 m (1H, Harom), 7.23–7.46 m (12H, Harom),
12.12 s (1H, NH). 13C NMR spectrum (CDCl3), δC,
ppm: 19.48 (CH3), 19.73 (CH3), 39.00 (C3), 48.99 (C4),
98.11 (C5); 120.03, 123.62, 126.81, 129.38, 129.42,
129.69, 129.74, 130.59, 130.75, 133.11, 134.38,
138.44, 138.46 (Carom); 176.20 (C2). Found, %:
C 61.01; H 5.13; N 2.91. C24H24ClNO5S. Calculated,
%: C 60.82; H 5.10; N 2.95.
4-Methoxy-N-[5-phenyl-4-(phenylsulfanyl)tetra-
hydrofuran-2-ylidene]anilinium perchlorate (ІVa).
Yield 55%, mp 124–125°C. IR spectrum, ν, cm–1: 1690
(C=N), 1515, 1265, 1120. 1H NMR spectrum (CDCl3),
δ, ppm: 3.61–3.79 m (4H, CH3, CH), 4.14–4.25 m (2H,
CH), 5.88 d (1H, CH, J = 6.4 Hz), 6.81 d (2H, Harom
,
J = 8.8 Hz), 7.21–7.48 m (12H, Harom), 12.02 s (1H,
NH). 13C NMR spectrum (CDCl3), δC, ppm: 38.92
(C3), 48.84 (C4), 55.44 (OCH3), 98.02 (C5); 114.79,
3,4-Dimethyl-N-[4-(4-methylphenylsulfanyl)-
5-phenyltetrahydrofuran-2-ylidene]anilinium per-
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INTRAMOLECULAR ELECTROPHILIC CYCLIZATION OF FUNCTIONAL ... III.
1541
chlorate (ІVe). Yield 47%, mp 120–121°C. IR spec-
trum, ν, cm–1: 1690 (C=N), 1535, 1125. 1H NMR spec-
trum (CDCl3), δ, ppm: 2.20 d (6H, CH3, J = 4.8 Hz),
2.30 s (3H, CH3), 3.64–3.73 m (1H, CH), 4.03–4.11 m
(1H, CH), 4.14–4.24 m (1H, CH), 5.88 d (1H, CH, J =
7.2 Hz), 7.07–7.47 m (12H, Harom), 12.05 s (1H, NH).
13C NMR spectrum (CDCl3), δC, ppm: 19.41 (CH3),
19.79 (CH3), 21.11 (CH3), 38.94 (C3), 48.98 (C4),
97.98 (C5); 120.01, 123.60, 125.61, 126.85, 129.29,
130.47, 130.58, 130.77, 133.16, 134.00, 135.09,
138.36, 140.03 (Carom); 176.35 (C2). Found, %:
C 61.60; H 5.31; N 2.90. C25H26ClNO5S. Calculated,
%: C 61.53; H 5.37; N 2.87.
CH), 6.38 s (1H, Harom), 6.54 s (1H, Harom), 7.23–
7.45 m (10H, Harom), 7.63 s (1H, NH). C NMR spec-
13
trum (CDCl3), δC, ppm: 38.36 (C3), 51.03 (C5), 53.54
(C4), 56.04 (OCH3), 56.15 (OCH3), 106.12 (C6),
113.18 (C9); 126.71, 127.34, 127.78, 128.45, 128.74,
129.11, 130.05, 133.34, 134.04, 139.98, 146.64,
148.51 (Carom); 171.58 (C2). Found, %: C 71.02;
H 5.70; N 3.42. C24H23NO3S. Calculated, %: C 71.08;
H 5.72; N 3.45.
7,8-Dimethoxy-4-(4-methylphenylsulfanyl)-
5-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
(Vb). Yield 78%, mp 216–217°C. IR spectrum, ν,
1
cm–1: 1675–1680 (C=O), 1510, 1220. H NMR spec-
3,4-Dimethyl-N-[4-(4-nitrophenylsulfanyl)-
5-phenyltetrahydrofuran-2-ylidene]anilinium per-
chlorate (ІVf). Yield 64%, mp 149–150°C. IR spec-
trum (DMSO-d6), δ, ppm: 2.26–2.32 m (4H, CH3, CH),
2.52–2.57 m (1H, CH), 3.50 s (3H, CH3), 3.71 s (3H,
CH3), 4.08 d (1H, CH, J = 10 Hz), 4.37–4.43 m (1H,
CH), 6.34 s (1H, Harom), 6.65 s (1H, Harom), 7.16 d (2H,
Harom, J = 8 Hz), 7.31 d (2H, Harom, J = 8 Hz), 7.34–
1
trum, ν, cm–1: 1690 (C=N), 1115. H NMR spectrum
(CD3CN), δ, ppm: 2.26 s (6H, CH3), 3.57–3.66 m (1H,
CH), 4.01–4.10 m (1H, CH), 4.46–4.54 m (1H, CH),
6.03 d (1H, CH, J = 9.2 Hz), 7.20–7.27 m (3H, Harom),
7.38–7.52 m (7H, Harom), 8.02 d (2H, Harom, J =
8.8 Hz), 11.22 s (1H, NH). 13C NMR spectrum
(CD3CN), δC, ppm: 18.58 (CH3), 18.91 (CH3), 39.04
(C3), 47.48 (C4), 97.66 (C5); 120.05, 123.35, 130.70,
130.71, 130.73, 130.78, 133.01, 138.83, 138.93,
141.08 (Carom); 177.15 (C2). Found, %: C 55.61;
H 4.52; N 5.36. C24H23ClN2O7S. Calculated, %:
C 55.54; H 4.47; N 5.40.
13
7.40 m (5H, Harom), 9.54 s (1H, NH). C NMR spec-
trum (DMSO-d6), δC, ppm: 20.46 (CH3), 38.17 (C3),
50.45 (C5), 52.31 (C4), 55.55 (OCH3), 55.68 (OCH3),
106.46 (C6), 113.52 (C9); 125.61, 126.88, 128.43,
128.45, 129.64, 130.31, 131.34, 132.32, 136.89,
140.34, 145.28, 147.93 (Carom); 169.95 (C2). Found, %:
C 71.64; H 6.09; N 3.39. C25H25NO3S. Calculated, %:
C 71.57; H 6.01; N 3.34.
9-Phenyl-8-phenylsulfanyl-6,7,8,9-tetrahydro-
5H-[1,3]dioxolo[4,5-h][1]benzazepin-6-one (Vc).
Yield 31%, mp 224–225°C. IR spectrum, ν, cm–1: 1670
Compounds Va–Vf, ІІІg, and ІVg (general
procedure). A solution of 2 mmol of arenesulfenyl
chloride IIa–IIc in 5 ml of acetic acid was added
dropwise at 15°C to a solution of 2 mmol of amide Іe–
Ig and 0.21 g (2 mmol) of lithium perchlorate in 10 ml
of acetic acid, and the mixture was stirred for 4 h at
room temperature. In the reaction of Іe with ІIc, the
precipitate of ІVg was filtered off and washed with
a small amount of acetic acid and then with hexane.
In the other cases, the solvent was removed under
reduced pressure, the residue was treated with chloro-
form (10 ml), the undissolved material (inorganic) was
filtered off, and the filtrate was evaporated. The
residue was treated with a mixture of diethyl ether with
ethanol (10:1), and the precipitate was filtered off and
washed with diethyl ether.
1
(C=O), 1500, 1475–1480, 1215. H NMR spectrum
(CDCl3), δ, ppm: 2.55–2.61 m (1H, CH), 2.68–2.75 m
(1H, CH), 4.18–4.28 m (2H, CH), 5.91 d (2H, CH2, J =
7.2 Hz), 6.36 s (1H, Harom), 6.55 s (1H, Harom), 7.24–
13
7.45 m (10H, Harom), 7.91 s (1H, NH). C NMR spec-
trum (CDCl3), δC, ppm: 38.23 (C7), 51.12 (C9), 53.98
(C8), 101.58 (C2), 103.70 (C4), 109.58 (C10); 127.41,
127.82, 128.46, 128.60, 128.79, 129.06, 131.02,
133.44, 133.99, 139.55, 145.49, 146.97 (Carom); 170.72
(C6). Found, %: C 71.02; H 4.99; N 3.51. C23H19NO3S.
Calculated, %: C 70.93; H 4.92; N 3.60.
8-(4-Methylphenylsulfanyl)-9-phenyl-6,7,8,9-
tetrahydro-5H-[1,3]dioxolo[4,5-h][1]benzazepin-
6-one (Vd). Yield 36%, mp 222–223°C. IR spectrum,
ν, cm–1: 1675 (C=O), 1500, 1480, 1210. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 2.21–2.30 m (4H, CH3, CH),
2.53–2.61 m (1H, CH), 4.03 d (1H, CH, J = 10.4 Hz),
4.38–4.46 m (1H, CH), 5.95 d (2H, CH2, J = 5.6 Hz),
6.20 s (1H, Harom), 6.61 s (1H, Harom), 7.15 d (2H,
7,8-Dimethoxy-5-phenyl-4-phenylsulfanyl-
2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Va).
Yield 67%, mp 145°C. IR spectrum, ν, cm–1: 1670
(C=O), 1515, 1265, 1220. 1H NMR spectrum (CDCl3),
δ, ppm: 2.56–2.62 m (1H, CH), 2.67–2.74 m (1H, CH),
3.64 s (3H, CH3), 3.84 s (3H, CH3), 4.22–4.27 m (2H,
H
arom, J = 7.6 Hz), 7.28–7.38 m (7H, Harom), 9.51 s
13
(1H, NH). C NMR spectrum (DMSO-d6), δC, ppm:
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VAS’KEVICH et al.
1542
21.08 (CH3), 38.41 (C7), 51.00 (C9), 53.19 (C8), 101.87
(C2), 103.70 (C4), 109.12 (C10); 127.59, 127.85,
129.07, 129.18, 130.27, 130.86, 132.75, 132.84,
137.45, 140.42, 144.52, 146.65 (Carom); 170.52 (C6).
Found, %: C 71.51; H 5.20; N 3.35. C24H21NO3S.
Calculated, %: C 71.44; H 5.25; N 3.47.
3,4-Dimethoxy-N-[4-(4-nitrophenylsulfanyl)-
5-phenyltetrahydrofuran-2-ylidene]anilinium per-
chlorate (ІVg). Yield 54%, mp 148–149°C. IR spec-
trum, ν, cm–1: 1685 (C=N), 1515, 1340, 1115. 1H NMR
spectrum (CDCl3), δ, ppm: 3.63–3.87 m (7H, CH3,
CH), 4.32–4.47 m (1H, CH), 4.52–4.64 m (1H, CH),
5.84–5.94 m (1H, CH), 6.64–6.73 m (1H, Harom), 7.01–
7.52 m (9H, Harom), 7.87–7.96 m (2H, Harom), 11.82 s
(1H, NH). Found, %: C 52.21; H 4.16; N 5.14.
C24H23ClN2O9S. Calculated, %: C 52.32; H 4.21;
N 5.08.
5-(4-Fluorophenyl)-7,8-dimethoxy-4-phenylsul-
fanyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
(Ve). Yield 82%, mp 195°C. IR spectrum, ν, cm–1:
1
1680 (C=O), 1515, 1220–1225. H NMR spectrum
(DMSO-d6), δ, ppm: 2.29–2.35 m (1H, CH), 2.58–
2.63 m (1H, CH), 3.53 s (3H, CH3), 3.73 s (3H, CH3),
4.13 d (1H, CH, J = 10.5 Hz), 4.49–4.53 m (1H, CH),
5-Aryl-4-arylsulfonyl-7,8-dimethoxy-2,3,4,5-
tetrahydro-1H-1-benzazepin-2-ones VIa and VIb
(general procedure). A solution of 4 mmol of KHSO5
in 5 ml of water was added under stirring to a solution
of 1 mmol of benzazepinone Vb or Ve in 5 ml of
methanol. The mixture was stirred for 5 h at 70°C and
cooled, the undissolved inorganic material was filtered
off, the filtrate was evaporated, and the residue was
recrystallized from water.
6.34 s (1H, Harom), 6.68 s (1H, Harom), 7.20 t (2H, Harom
,
J = 8.5 Hz), 7.24–7.29 m (1H, Harom), 7.33 t (2H, Harom
,
J = 7 Hz), 7.39 d (2H, Harom, J = 7 Hz), 7.42–7.46 m
(2H, Harom), 9.57 s (1H, NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 38.85 (C3), 50.38 (C5), 52.70
(C4), 56.14 (OCH3), 56.31 (OCH3), 107.35 (C6),
114.10 (C9); 115.51, 115.80, 126.02, 127.54, 129.61,
130.92, 130.97, 131.95, 134.69, 136.96, 136.98,
145.97, 148.63 (Carom); 161.61 d (CF, J = 243.9 Hz),
170.45 (C2). Found, %: C 68.11; H 5.27; N 3.37.
C24H22FNO3S. Calculated, %: C 68.07; H 5.24; N 3.31.
5-(4-Fluorophenyl)-7,8-dimethoxy-4-phenylsul-
fonyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
(VIa). Yield 95%, mp 190–191°C. IR spectrum, ν,
1
cm–1: 1675 (C=O), 1520, 1240. H NMR spectrum
5-(4-Fluorophenyl)-7,8-dimethoxy-4-(4-methyl-
phenylsulfanyl)-2,3,4,5-tetrahydro-1H-1-benzaz-
epin-2-one (Vf). Yield 71%, mp 197°C. IR spectrum,
(DMSO-d6), δ, ppm: 2.36–2.41 m (1H, CH), 2.64–
2.71 m (1H, CH), 3.69 s (3H, CH3), 3.70 s (3H, CH3),
4.51–4.55 m (1H, CH), 4.76–4.78 m (1H, CH), 6.54 s
(1H, Harom), 6.84 s (1H, Harom), 7.05 t (2H, Harom, J =
1
ν, cm–1: 1680 (C=O), 1515, 1225. H NMR spectrum
(DMSO-d6), δ, ppm: 2.25–2.31 m (4H, CH3, CH),
2.51–2.57 m (1H, CH), 3.52 s (3H, CH3), 3.72 s (3H,
CH3), 4.09 d (1H, CH, J = 9.5 Hz), 4.36–4.41 m (1H,
CH), 6.33 s (1H, Harom), 6.66 s (1H, Harom), 7.15 d (2H,
8.8 Hz), 7.14 t (2H, Harom, J = 8 Hz), 7.64 t (2H, Harom
,
J = 8 Hz), 7.76 t (1H, Harom, J = 7.5 Hz), 7.98 d (2H,
Harom, J = 7.5 Hz), 9.54 s (1H, NH). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 33.79 (C3), 45.13 (C5),
55.99 (OCH3), 56.43 (OCH3), 67.95 (C4), 107.66 (C9),
115.93 (C6); 115.35, 115.52, 124.39, 129.64, 129.82,
129.88, 129.94, 130.96, 134.77, 137.02, 137.63,
137.65, 146.24, 148.83 (Carom); 169.01 (C2). Mass
spectrum: m/z 456.2 [M + 1]+. Found, %: C 63.37;
H 4.81; N 3.05. C24H22FNO5S. Calculated, %: C 63.28;
H 4.87; N 3.08. M 455.5.
H
arom, J = 8 Hz), 7.19 t (2H, Harom, J = 9 Hz), 7.30 d
(2H, Harom, J = 8 Hz), 7.39–7.44 m (2H, Harom), 9.54 s
13
(1H, NH). C NMR spectrum (DMSO-d6), δC, ppm:
21.05 s (CH3), 38.77 (C3), 50.44 (C5), 53.35 (C4),
56.21 (OCH3), 56.31 (OCH3), 107.30 (C6), 114.18
(C9); 115.55, 115.72, 126.07, 130.30, 130.81, 130.93,
131.91, 132.97, 137.06, 137.52, 145.94, 148.60
(Carom); 161.59 d (CF, J = 242.7 Hz), 170.48 (C2).
Found, %: C 68.71; H 5.48; N 3.21. C25H24FNO3S.
Calculated, %: C 68.63; H 5.53; N 3.20.
7,8-Dimethoxy-4-(4-methylphenylsulfonyl)-
5-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
(VIb). Yield 96%, mp 122°C. IR spectrum, ν, cm–1:
N-(1,3-Benzodioxol-5-yl)-4-chloro-3-(4-nitro-
phenylsulfanyl)-4-phenylbutanamide (ІІІg). Yield
1
1680 (C=O), 1525. H NMR spectrum (DMSO-d6), δ,
1
ppm: 2.41 s (3H, CH3), 2.63–2.71 m (1H, CH), 3.70 s
(3H, CH3), 3.71 s (3H, CH3), 4.38–4.45 m (1H, CH),
4.74–4.76 m (1H, CH), 6.53 s (1H, Harom), 6.84 s (1H,
Harom), 7.09–7.26 m (5H, Harom), 7.45 d (2H, Harom, J =
7.6 Hz), 7.88 d (2H, Harom, J = 8 Hz), 9.51 s (1H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 21.57 (CH3),
33.95 (C3), 45.93 (C5), 56.04 (OCH3), 56.46 (OCH3),
76%, mp 128°C. H NMR spectrum (CDCl3), δ, ppm:
2.59–2.74 m (1H, CH), 3.22–3.34 m (1H, CH), 4.23–
4.34 m (1H, CH), 5.02–5.11 m (1H, CH), 5.87–5.98 m
(2H, CH2), 6.66–6.79 m (2H, Harom), 7.07–7.38 m (8H,
Harom), 7.85–7.94 m (2H, Harom). Found, %: C 58.54;
H 4.01; Cl 7.62; N 5.89. C23H19ClN2O5S. Calculated,
%: C 58.66; H 4.07; Cl 7.53; N 5.95.
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INTRAMOLECULAR ELECTROPHILIC CYCLIZATION OF FUNCTIONAL ... III.
1543
68.16 (C4), 107.69 (C9), 116.16 (C6); 124.42, 126.96,
127.77, 128.77, 129.72, 130.46, 130.98, 133.94,
141.74, 145.44, 146.28, 148.79 (Carom); 169.00 (C2).
Mass spectrum: m/z 452.2 [M + 1]+. Found, %:
C 66.58; H 5.46; N 3.12. C25H25NO5S. Calculated, %:
C 66.50; H 5.58; N 3.10. M 451.5.
6. Kando, K., Ogawa, H., Shinihara, T., Kurimuta, H.,
Tonada, Y., Kon, K., Yomoshita, M., Nakonuta, S.,
Hirano, T., Yamanura, Y., Mori, I., Tamigata, M., and
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felg, R.R., Borbagelata, N.A., Lerman, J., Braner, S.L.,
Tronge, J., and Orlandi, G.J., Cardiovasc. Pharmacol.
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