Intramolecular electrophilic cyclization of functional derivatives of unsaturated compounds: I. synthesis of 5-arylsulfanyl-6-phenylpiperidin-2-ones from cinnamylacetamides and arylsulfenyl chlorides

Article abstract of DOI:10.1134/S1070428011080057

Sterically nonhindered N-alkyl(aryl)amides of cinnamylacetic acid in the reaction with phenyl(4- tolyl)sulfenyl chlorides in acetic acid in the presence of lithium perchlorate undergo a selective cyclization into 5-arylsulfanyl-6- phenylpiperidin-2-ones. Under similar conditions the reaction with arylsulfenyl chlorides of amides containing bulky substituents at the nitrogen atom resulted in 5-arylsulfanyl-6-phenyltetrahydropyran-2- iminium perchlorates, which by treatment with aqueous ethanol were converted into the corresponding derivatives of pyran-2-ones.

Full text of DOI:10.1134/S1070428011080057

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1146−1152. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.I. Vas’kevich, N.M. Tsizorik, E.B. Rusanov, V.I. Stanitets, M.V. Vovk, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 8, pp. 1130−1135.
Intramolecular Electrophilic Cyclization
of Functional Derivatives of Unsaturated Compounds: I.
Synthesis of 5-Arylsulfanyl-6-phenylpiperidin-2-ones
from Cinnamylacetamides and Arylsulfenyl Chlorides
A. I. Vas’kevich, N. M. Tsizorik, E. B. Rusanov, V. I. Stanitets, and M. V. Vovk
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, 02094 Ukraine
e-mail: vaskevich@ioch.kiev.ua
Received January 10, 2010
Abstract—Sterically nonhindered N-alkyl(aryl)amides of cinnamylacetic acid in the reaction with phenyl(4-
tolyl)sulfenyl chlorides in acetic acid in the presence of lithium perchlorate undergo a selective cyclization into
5-arylsulfanyl-6-phenylpiperidin-2-ones. Under similar conditions the reaction with arylsulfenyl chlorides of
amides containing bulky substituents at the nitrogen atom resulted in 5-arylsulfanyl-6-phenyltetrahydropyran-2-
iminium perchlorates, which by treatment with aqueous ethanol were converted into the corresponding derivatives
of pyran-2-ones.
DOI: 10.1134/S1070428011080057
Piperidin-2-ones are compounds with unique biologi-
cal characteristics [1–3]. They underlie the preparation
of piperidine systems included into the composition of
many alkaloids and physiologically active substances
[4–6]. Therefore nowadays new substituted piperidones
are synthesized [7–11].
and aiming at the development of the synthesis of
5-arylsulfanylpiperidin-2-ones we examined in detail the
arylsulfenylation of cinnamylacetamides Iа–Ig. These
compounds react with arylsulfenyl chlorides IIа–IIc at
room temperature in acetic acid in the presence of an
equimolar amount of LiClO4 as “dopping-additive” [16,
17] forming cyclization products whose structure is con-
trolled mainly by the steric parameters of the substituent
at the nitrogen atom of the nucleophilic substrate and
the electronic characteristics of the electrophilic reagent.
The introduction of sulfanyl groups in the piperidone
ring can essentially modify the chemical and biological
characteristics. In particular, among the sulfanyl deriva-
tives of piperidin-2-oneов (δ-lactams) compounds were
found capable to inhibit the activation of p38MAP-kinase
[12], a very important quality both for prophylactic and
treatment of inflammation and autoimmune diseases,
rheumatoid arthritis, infectious diseases, atherosclerosis,
and pancreatitis.
Amide with sterically nonhindered aliphatic (Ib, Ic)
or aromatic (If, Ig) substituents react with phenyl- or
4-tolylsulfenyl chlorides (IIа, IIb) giving 5-arylsulfanyl-
6-phenylpiperidones IIIb–IIIg, IIIi, IIIj (path а) in 81–
95% yield (Scheme 1). In event of 4-nitrophenylsulfenyl
chloride a decreased selectivity of reaction is observed
due to the nucleophilic involvement of the oxygen atom of
the iniial amides (path b), and as a result forms a mixture
of compounds III and IV in the ratio 5 : 1 from amide If
and 4 : 1 from amide Ig.
Although there are well developed approaches to
nonfunctional piperidones, the methods of the synthesis
of 5-alkyl(aryl)sulfanyl-substituted piperidones [12–14]
are multistage and apply difficultly accessible and toxic
reagents.
Considering the synthetic potential of the reaction
of electrophilic cyclization of unsaturated amides [15]
In the reaction of unsubstituted amide Ia with
4-tolylsulfenyl chloride (IIb) lactam IIIa was isolated.
1146

INTRAMOLECULAR ELECTROPHILIC CYCLIZATION..: I.
1147
Scheme 1.
ArS
а
Ph
N
R
O
O
LiClO4
IIIа_IIk
ArSCl
IIа_IIc
+
NHR
Ph
Iа_Ig
ArS
Ph
ArS
Ph
H2O
b
+
O
NHR
ClO4
_
O
Vа_Vc
O
IVа_IVi
I, R = H(а), Bu(b), PhCH2(c), i-Pr(d), t-Bu(e), Ph(f), 4-MeOC6H4(g); II, V, Ar = Ph(а), 4-MeC6H4(b), 4-NO2C6H4(c);
III, R = H, Ar = 4-MeC6H4(а); R=Bu, Ar = Ph(b), 4-MeC6H4(c); R=PhCH2, Ar = Ph(d), 4-MeC6H4(e); R = A r= Ph(f);
R = Ph, Ar = 4-MeC6H4(g), 4-NO2C6H4(h); R = 4-MeOC6H4, Ar = Ph(i), 4-MeC6H4(j), 4-NO2C6H4(k); IV, R = H,
Ar = Ph(a); R = i-Pr, Ar = Ph(b), 4-MeC6H4(c), 4-NO2C6H4(d); R = t-Bu, Ar = Ph(e), 4-MeC6H4(f), 4-NO2C6H4(g); R = Ph,
Ar = 4-NO2C6H4(h); R = 4-MeOC6H4, Ar = 4-NO2C6H4(i).
The application of phenyl- and 4-nitrophenylsulfenyl
chloride resulted in the prevailing formation of pyran-2-
iminium perchlorate (IVа).
tion is not caused by the primary amine elimination from
the addition product А, but by its intramolecular structural
rearrangement involving the cleavage of the С6–О bond
and leading to episulfonium intermediate B, followed by
the cyclization of the latter into lactone VI [14].
Path b prevails also in the reactions of sterically hin-
dered amides Id, Ie with arylsulfenylchlorides IIа–IIc.
As a result tetrahydropyranо-2-iminium perchlorates
IVb–IVg formed in 66–86% yields. Their structure was
reliably proved by spectral methods by an example of
compounds IVb, IVc isolated from the reaction mixture
in the analytically pure state. The salts IVb–IVg without
additional purification were treated with aqueous ethanol
to obtain 5-arylsulfanylpyran-2-ones Vа–Vc in 48–64%
yields.
Proceeding from the concept of the increasing effec-
tive electrophilicity of sulfenyl chlorides in reactions АdЕ
[16, 17] and basing on the previous experimental results
of their application to the reactions of intramolecular
cyclization [18–20], it is presumable that in the reaction
of amides I with arylsulfenyl chlorides II in the medium
of acetic acid in the presence of LiClO4 episulfonium
intermediates C are formed being a solvent-separated
ion pair where the perchlorate prevents the formation of
products of acyclic addition. In the course of the intramo-
lecular electrophilic cyclization depending on substituent
R the episulfonium ring of intermediate C is attacked
either by the nitrogen atom (path а) or the oxygen atom
(path b) leading to the formation of compounds III or
At the treating of iminium salts IVb–IVd with a wa-
ter solution of sodium acetate in acetone alongside with
δ-lactones Va–Vc we detected in the reaction mixture
1
by means of Н spectroscopy and GC-MS method also
γ-lactones VІа–VIc. We succeeded to isolate compound
VIc in 68% yield (Scheme 2). Most probably their forma-
Scheme 2.
Ar
ArS
Ph
_
H
O
Ph
S
S +
Ph
OH
IVb_IVd
O
OH
O
_O
NH
O
Ar
HN Pr-i
VIa_VIc
Pr-i
A
B
VI, Ar = Ph(a), 4-MeC6H4(b), 4-NO2C6H4(c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

VAS’KEVICH et al.
1148
IV respectively (Scheme 3). The low selectivity of the
reaction at the use of 4-NO2C6H4SCl (IIc) compared to
sulfenyl chlorides IIa, IIb originates from the decreased
stability and increased reactivity of intermediate C due
to the electron-withdrawing character of the nitro group.
13С NMR spectra the signals of the atoms С5 and С6 of
the piperidine ring appear in the regions 46–49 and 63–69
ppm respectively. The unambiguous confirmation of the
structure of the lactams synthesized was obtained by XRD
analysis of a single crystal of compound IIIg the general
arrangement of whose molecule is shown on the figure.
a
The distribution of bond lengths and bond angles in
the central six-membered hetrocycle N1С8С12 is usual
for such systems. The bond lengths C8–C9, C9–C10, and
C10–C11 fall in the range typical of the sp3-hybridized
carbon atoms whereas the bond C11–C12 1.501(3) Å is
slightly shortened. Endocyclic С–N bonds are nonequiva-
lent due to the conjugation of the lone electron pairs of
atom N1 with the π-system of the С=О bond as shows
the flattening of the atom N1 [sum of bond angles at this
atom is 359.73(16)°]. The central heterocycle proper is
not planar and exists in the semichair conformation. The
group of atoms N1C8C10C11C12 forms a plane, and the
maximum deviation of atoms from this plane does not
exceed 0.070(1) Å, and the plane С8С9С10 forms with it
an angle of 49.14(13)°. The lengths of the С–S bonds are
not equal apparently due to different hybridization of С1
and С9 atoms, namely, because of the conjugation of the
lone electron pairs of sulfur atom with the π-system of
the tolyl substituent.
a
Ph
III
IV
NR
+
S
_
ClO4
O
sol
b
Ar
b
C
The structure of compounds synthesized was con-
1
firmed by physicochemical investigations. Н NMR
spectra of piperidinones IIIа–IIIk contain a single set
of doublets of atom Н5 in the region 4.40–5.08 ppm
with the coupling constant 3.0–3.6 Hz and a multiplet
of atom Н4 in the region 3.55–4.33 ppm indicating their
axial-equatorial location and proving the diastereoselec-
tive character of the arylsulfanyllactamization. In the
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer UR-
20 from pellets with KBr or from solutions in CH2Cl2.
1Н and 13С NMR spectra were registered on a spectrom-
eter Bruker Advance DRX-500 (500.13, 125.75 MHz
respectively), internal reference TMS. GC-MS measure-
ments were performed on an instrument Agilent 110\
DAD\HSD\VLG 119562.
N1
XRD investigation of the single crystal of compound
IIIg of the size 0.20 × 0.40 × 0.50 mm was carried out
at room temperature on a diffractometer Bruker Smart
Apex II (λMoKα-radiation, graphite monochromator,
θmax 26.5°, spherical segment –14 ≤ h ≤ 14, –22 ≤ k ≤
18, –23≤ l ≤ 22). Total collected reflections 19504,
among them 4079 independent (R-factor of averaging
0.0368). The correction for extinction was performed
by multiscanning using SADABS program (the ratio of
minimal to maximal correction Tmin/Tmax 0.681997). The
structure was solved by the direct method and refined by
the least-squares method in the anisotropic approxima-
tion for all nonhydrogen atoms applying SHELXS97
General view of the molecule of 1,6-diphenyl-5-[(4-methyl-
phenyl)sulfanyl]piperidin-2-one (ІІІg). Main bond lengths and
bond angles: C8–N1 1.474(2), C8–C9 1.526(3), C9–C10 1.512(3),
C10–C11 1.521(3), C11–C12 1.501(3), С12–N1 1.361(2), C12–O1
1.222(2), C9–S1 1.826(2) C1–S1 1.773(2) Е; N1C8C9 111.59(15),
C8C9C10 110.67(16), C9C10C11 110.48(18), C10C11C12
116.56(17), N1C12C11 118.68(18), C12N1C8 125.41(16), C10C9S1
108.23(14), C8C9S1 113.27(14), C1S1C9 101.15(9)°.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

INTRAMOLECULAR ELECTROPHILIC CYCLIZATION..: I.
1149
and SHELXL97 software [21, 22]. The positions and
thermal parameters of all hydrogen atoms were refined
together with the positions and thermal parameters of
the corresponding carbon atoms. In the refinement 2694
reflections were utilized with I > 2σ(I), 240 refined pa-
rameters, number of reflections per parameter 6.7, weight
scheme was used ω = 1/[σ2(Fo2) + (0.0442Р)2 +1.8675P],
where Р = (Fo2 + 2Fc2)/3, the ratio of the maximal (av-
erage) shift to the error in the last cycle 0.081 (0.002).
The final values of divergence factors are R1(F) 0.0463,
wR2(F2) 0.1030, for reflections with I > 2σ(I) and R1(F)
0.0813, wR2(F2) 0.1218, GOF 1.004 for all reflections.
The residual electron density from the difference Fourier
series after the last refinement cycle 0.25 and –0.32 е/Å3.
3.85–3.90 m (1Н, СН), 4.61 d (1Н, СН, J 3.3 Hz), 7.18 d
(2Нarom, J 6.9 Hz), 7.31–7.45 m (6Нarom.), 7.54 d (2Нarom.
,
J 7.5 Hz). 13С NMR spectrum, δ, ppm: 13.39 (СН3),
19.42 (СН2), 20.59 (СН2), 27.77 (С4), 28.80 (С3), 44.72
(СН2N), 47.92 (С5), 63.41 (С6), 126.41, 127.21, 127.61,
128.57, 129.18, 131.37, 133.49, 140.04 (Сarom.), 167.84
(C2). Found, %: С 74.45; H 7.38; N 4.10; S 9.30. [M +
1]+ 340. C21H25NOS. Calculated, %: С 74.28; Н 7.41;
N 4.12; S 9.42. M 339.5.
1-Butyl-5-(4-methylphenylsulfanyl)-6-phenyl-
piperidin-2-one (ІІІc). Yield 87%, mp 63–64°С. IR
1
spectrum, ν, cm–1: 1650 (С=О). Н NMR spectrum,
δ, ppm: 0.81 t (3Н, СН3, J 7.8 Hz), 1.10–1.47 m (4Н,
2СН2), 1.54–1.66 m (1Н, СН), 1.82–1.96 m (1Н, СН),
2.17–2.25 m (1Н, СН), 2.32 s (3Н, СН3), 2.40–2.55 m
(2Н, СН2), 3.73–3.75 m (1Н, СН), 3.80–3.90 m (1Н,
СН), 4.57 d (1Н, СН, J 3.1 Hz), 7.15 d (2Нarom., J 7.5 Hz),
7.23 d (2Нarom., J 7.8 Hz), 7.32–7.46 m (5Нarom.).
13С NMR spectrum, δ, ppm: 13.60 (СН3), 19.45 (СН2),
20.54 (СН3), 20.55 (СН2), 27.77 (С4), 28.82 (С3), 44.74
(СН2N), 48.39 (С5), 63.44 (С6), 126.50, 127.60, 128.69,
129.73, 129.85, 131.97, 137.14, 140.14 (Сarom.), 167.91
(C2). Found, %: С 74.63; Н 7.63; N 3.84. [M + 1]+ 354.
C22H27NOS. Calculated, %: C 74.73; H 7.69; N 3.94.
M 353.5.
5-Arylsulfanyl-1-R-6-phenylpiperidin-2-ones IIIа–
IIIk and N-[5-(arylsulfanyl)-6-phenyltetrahydro-2Н-
pyran-2-ylidene]propan-2-iminium perchlorates IVb,
IVc. To a solution of 2.2 mmol of amide Іа–Ig in 10 ml of
acetic acid was added in succession while stirring a solu-
tion of 0.23 g (2.2 mmol) of lithium perchlorate in 5 ml
of acetic acid and a solution of 2.2 mmol of arylsulfenyl
chloride ІІа–IIc in 3 ml of acetic acid. The reaction mix-
ture was stirred at room temperature for 4 h, the solvent
was distilled off in a vacuum, the residue was treated
with 10 ml of water. The organic products were extracted
into chloroform (2×10 ml), the extract was dried with
anhydrous magnesium sulfate, filtered, and evaporated.
Compounds IIIa–IIIk were purified by recrystallization
from ethanol. Compounds IV were used without further
purification.
1-Benzyl-6-phenyl-5-(phenylsulfanyl)piperidin-
2-one (IIId). Yield 80%, mp 68–69°С. IR spectrum, ν,
1
cm–1: 1645 (C=O). Н NMR spectrum, δ, ppm: 1.65–
1.78 m (1Н, СН), 1.96–2.13 m (1Н, СН), 2.44–2.61 m
(2Н, СН2), 3.24 d (1Н, СН, J 10.0 Hz), 3.66–3.75 m
(1Н, СН), 4.40 d (1Н, СН, J 3.0 Hz), 5.35 d (1Н, СН,
5-[(4-Methylphenyl)sulfanyl]-6-phenylpiperidin-
2-one (IIIа). Yield 88%, mp 154–155°С. IR spectrum,
ν, cm–1: 3340 (N–H), 1655 (С=О). 1Н NMR spectrum,
δ, ppm: 1.65–1.72 m (1H, CH), 1.85–1.94 m (1Н, СН),
2.32 s (3Н, СН3), 3.34–3.37 m (2Н, СН2), 3.58–3.60 m
(1Н, СН), 4.42 d (1Н, СН, J 6 Hz), 7.18–7.36 m
(9Нarom.), 7.87 s (1H, NH). 13С NMR spectrum, δ, ppm:
20.30 (СН3), 22.85 (С4), 28.42 (С3), 47.96 (С5), 59.10
(С6), 126.60, 127.35, 128.19, 129.63, 132.16, 129.72,
137.03, 141.92 (Сarom.), 169.42 (С2). Found, %: С 72.62;
Н 6.34; N 4.62. [M + 1]+ 298. C18H19NOS. Calculated,
%: С 72.70; Н 6.44; N 4.71. M 297.4.
J 9.0 Hz), 7.07 d (2Нarom, J 8.2 Hz), 7.16 d (2Нarom
,
J 9 Hz), 7.25–7.44 m (11Нarom.). 13С NMR spectrum, δ,
ppm: 20.67 (С4), 27.89 (С3), 47.40 (СН2N), 48.46 (С5),
63.30 (С6), 126.52, 127.05, 127.52, 127.84, 127.91,
128.32, 128.82, 129.16, 132.02, 132.94, 136.85, 139.55
(Carom.), 168.41 (С2). Found, %: С 77.10; Н 5.91; N
3.83. [M + 1]+ 374. C24H23NOS. Calculated, %: C 77.17;
H 5.96; N 3.91. M 373.5.
1-Benzyl-5-[(4-methylphenyl)sulfanyl]-6-
phenylpiperidin-2-one (ІІІe). Yield 73%, mp 104–
1
105°С. IR spectrum, ν, cm–1: 1660 (C=O). Н NMR
1-Butyl-6-phenyl-5-(phenylsulfanyl)piperidin-2-
spectrum, δ, ppm: 1.60–1.73 m (1Н, СН), 2.01–2.09 m
(1Н, СН), 2.27 s (3С, СН3), 2.55–2.61 m (2Н, СН2),
3.25 d (1Н, СН, J 9.0 Hz), 3.55–3.63 m (1Н, СН),
4.40 d (1Н, СН, J 3.1 Hz), 5.38 d (1Н, СН, J 9.0 Hz),
7.06–7.19 m (8Нarom.), 7.29–7.42 m (6Нarom.). 13С NMR
spectrum, δ, ppm: 20.54 (СН3), 20.63 (С4), 27.86 (С3),
one (ІІІb). Yield 81%, mp 54–55°С. IR spectrum, ν,
1
cm–1: 1650 (С=О). Н NMR spectrum, δ, ppm: 0.81 t
(3Н, СН3), 1.12–1.41 m (4Н, 2СН2), 1.59–1.72 m (1Н,
СН), 1.86–2.01 m (1Н, СН), 2.18–2.30 m (1Н, СН),
2.37–2.56 m (2Н, СН2), 3.79–3.93 m (2Н, СН + СН),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

VAS’KEVICH et al.
1150
47.38 (СН2N), 49.08 (С5), 62.88 (С6), 126.42, 127.05,
127.76, 127.89, 128.25, 128.80, 129.21, 129.76, 132.62,
136.88, 137.30, 139.63 (Carom.), 168.39 (С2). Found, %:
С 77.75; Н 6.24; N 3.34. [M + 1]+ 388. C25H25NOS.
Calculated, %: C 77.69; H 6.34; N 3.27. M 387.5.
(1Н, СН), 4.85 d (1Н, СН, J 2.1 Hz), 6.80 d (2Нarom
,
J 8.8 Hz), 6.96 d (2Нarom., J 8.7 Hz), 7.24–7.45 m
(8Нarom.), 7.59 d (2Нarom., J 8.8 Hz). Found, %: С 73.87;
Н 5.86; N 3.46. [M + 1]+ 390. C24H23NO2S. Calculated,
%: C 73.99; H 5.94; N 3.59. M 389.5.
1-(4-Methoxyphenyl)-5-[(4-methylphenyl)
sulfanyl]-6-phenylpiperidin-2-one (ІІІj). Yield 79%,
mp 122–123°С. IR spectrum, ν, cm–1: 1655 (С=О).
1Н NMR spectrum, δ, ppm: 1.71–1.85 m (1Н, СН), 2.01–
2.16 m (1Н, СН), 2.31 s (3Н, СН3), 2.54–2.63 m (2Н,
СН2), 3.66 s (3Н, СН3О), 3.79–3.83 m (1Н, СН), 4.82 d
(1Н, СН, J 3.0 Hz), 6.80 d (2Нarom., J 8.7 Hz), 6.96 d
(2Нarom., J 8.7 Hz), 7.22–7.38 m (7Нarom.), 7.49 d (2Нarom.
J 8.7 Hz). 13С NMR spectrum, δ, ppm: 20.52 (СН3), 21.04
(С4), 28.36 (С3), 48.74 (С5), 54.84 (СН3О), 67.94 (С6),
113.66, 126.87, 127.62, 128.41, 128.51, 129.64, 130.00,
132.08, 135.29, 137.27, 139.86, 157.41 (Сarom.), 168.44
(С2). Found, %: С 74.27; Н 6.11; N 3.28. [M + 1]+ 404.
C25H25NO2S. Calculated, %: C 74.39; H 6.23; N 3.45.
M 403.5.
1,6-Diphenyl-5-(phenylsulfanyl)piperidin-2-one
(ІІІf). Yield 61%, mp 99–100°С. IR spectrum, ν, cm–1:
1
1660 (С=О). Н NMR spectrum, δ, ppm: 1.76–1.93 m
(1Н, СН), 2.04–2.20 m (1Н, СН), 2.56–2.75 m (2Н, СН2),
3.90–3.98 m (1Н, СН), 4.92 d (1Н, СН, J 3.0 Hz), 7.06 d
(2Нarom, J 7.2 Hz), 7.14–7.41 m (11Нarom), 7.60 d (2Нarom
,
J 6.8 Hz). 13С NMR spectrum, δ, ppm: 21.16 (С4), 28.43
(С3), 48.38 (С5), 67.78 (С6), 126.42, 126.85, 127.27,
127.42, 127.66, 128.53, 128.57, 129.35, 131.45, 133.36,
139.66, 142.52 (Сarom), 168.37 (С2). Found, %: С 76.73;
Н 5.76; N 3.76. [M + 1]+ 360. C23H21NOS. Calculated,
%: C 76.83; H 5.88; N 3.89. M 359.5.
1,6-Diphenyl-5-[(4-methylphenyl)sulfanyl]
piperidin-2-one (ІІІg). Yield 71%, mp 135–136°С. IR
1
spectrum, ν, cm–1: 1655 (C=O). Н NMR spectrum, δ,
1-(4-Methoxyphenyl)-5-[(4-nitrophenyl)sulfanyl]-
6-phenylpiperidin-2-one (ІІІk). Yield 58%, mp 159°С.
IR spectrum, ν, cm–1: 1665 (С=О). 1Н NMR spectrum,
δ, ppm: 1.89–1.99 m (1Н, СН), 2.17– 2.31 m (1Н, СН),
2.54–2.79 m (2Н, СН2), 3.67 s (3Н, СН3О), 4.28 m (1Н,
СН), 5.01 d (1Н, СН, J 3.0 Hz), 6.81 d (2Нarom., J 8.4 Hz),
6.98 d (2Нarom., J 8.4 Hz), 7.25–7.40 m (5Нarom.), 7.74 d
(2Нarom. J 8.4 Hz), 8.19 d (2Нarom. J 8.1 Hz). 13С NMR
spectrum, δ, ppm: 22.03 (С4), 29.01 (С3), 47.46 (С5),
55.66 (СН3О), 68.89 (С6), 114.22, 124.65, 127.75,
128.38, 128.95, 129.09, 129.33, 135.49, 139.80, 144.77,
145.73, 157.91 (Сarom.), 168.64 (С2). Found, %: C 66.31;
H 5.02; N 6.37. [M + 1]+ 435. C24H22N2O4S. Calculated,
%: C 66.34; H 5.10; N 6.45. M 434.5.
ppm: 1.74–1.87 m (1Н, СН), 2.04–2.14 m (1Н, СН),
2.31 с (3Н, СН3), 2.57–2.67 m (2Н, СН2), 3.80–3.87
m (1Н, СН), 4.89 d (1Н, СН, J 3.3 Hz), 7.06 d (2Нarom
J 7.5 Hz), 7.14–7.38 m (10Нarom), 7.49 d (2Нarom
,
,
J 7.8 Hz). 13С NMR spectrum, δ, ppm: 20.49 (СН3), 21.07
(С4), 28.39 (С3), 48.84 (С5), 67.62 (С6), 126.44, 126.85,
127.32, 127.65, 128.53, 128.60, 129.59, 130.02, 132.12,
137.29, 139.75, 142.57 (Сarom.), 168.39 (С2). Found, %:
С 77.19; Н 6.03; N 3.63. [M + 1]+ 374. C24H23NOS.
Calculated, %: C 77.16; H 6.21; N 3.73. M 373.5.
1,6-Diphenyl-5-[(4-nitrophenyl)sulfanyl]piperidin-
2-one (ІІІh). Yield 74%, mp 203–205°С. IR spectrum,
1
ν, cm–1: 1655 (С=О). Н NMR spectrum, δ, ppm:
1.93–2.05 m (1Н, СН), 2.14–2.30 m (1Н, СН), 2.58–
2.60 m (2Н, СН2), 4.26–4.33 m (1Н, СН), 5.08 d (1Н,
СН, J 3.6 Hz), 7.07–7.43 m (10Нarom), 7.75 d (2Нarom.
J 8.8 Hz), 8.20 d (2Нarom, J 8.7 Hz). 13С NMR spectrum,
δ, ppm: 21.59 (С4), 28.60 (С3), 46.67 (С5), 67.78 (С6),
123.96, 126.37, 127.09, 127.26, 127.78, 128.49, 128.57,
128.74, 139.19, 142.24, 144.31, 145.24 (Сarom), 168.16
(С2). Found, %: С 68.12; Н 4.88; N 6.80. [M + 1]+ 405.
C23H20N2O3S. Calculated, %: C 68.28; H 4.97; N 6.91.
M 404.5.
N-[6-Phenyl-5-(phenylsulfanyl)-tetrahydro-2Н-
pyran-2-ylidene]propan-2-iminium perchlorate (IVb).
Yield 50%, mp 81–82°С. IR spectrum, ν, cm–1: 1705
(C=N). 1Н NMR spectrum, δ, ppm: 1.10–1.16 m (2CH3,
6H), 2.18–2.55 m (1H, CH), 2.57–2.63 m (1H, CH), 2.84–
2.91 m (1H, CH), 3.05–3.12 m (1H, CH), 3.64–3.72 m
(1H, CH), 4.98 d (1H, CH, J 3.9 Hz), 5.52–5.60 m (1H,
CH), 7.31–7.48 m (9Harom.), 11.77 s (1H, NH). 13С NMR
spectrum, δ, ppm: 20.55 (CH3), 20.85 (CH3), 25.65 (C4),
30.23 (C3), 53.64 (C5), 74.23 (CH), 92.36 (C6), 127.56,
128.02, 128.46, 128.59, 129.17, 130.46, 136.24, 137.51
(Carom.), 178.22 (C=N). Found, %: Сl 8.24; S 7.42.
C20H24ClNO5S. Calculated, %: Сl 8.32; S 7.53.
1-(4-Methoxyphenyl)-6-phenyl-5-(phenylsulfanyl)
piperidin-2-one (ІІІi). Yield 83%, mp 114–115°С. IR
1
spectrum, ν, cm–1: 1665 (С=О). Н NMR spectrum, δ,
ppm: 1.76–1.92 m (1Н, СН), 2.04–2.21 m (1Н, СН),
2.56–2.73 m (2Н, СН2), 3.67 s (3Н, СН3О), 3.89–3.95 m
N-{[5-(4-Methylphenyl)sulfanyl]-6-phenyltetra-
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INTRAMOLECULAR ELECTROPHILIC CYCLIZATION..: I.
1151
5.11–5.14 m (1H, CH), 7.26–7.39 m (3Harom.), 7.50–
7.61 m (4Harom.), 8.09 d (2Нarom., J 8.6 Hz). 13С NMR
spectrum, δ, ppm: 27.73 (C4), 28.65 (C3), 52.77 (C5),
80.54 (C6), 124.06, 126.50, 127.95, 128.84, 139.21,
142.27, 144.37, 144.50 (Carom.), 176.31 (С2). Found,
%: С 61.84; Н 4.48; N 4.12; S 9.53. [M + 1]+ 330.
C17H15NO4S. Calculated, %: C 61.99; H 4.59; N 4.25;
S 9.73. M 329.4.
hydro-2Н-pyran-2-ylidene}propan-2-iminium per-
chlorate (IVc). Yield 48%, mp 110–112°С. IR spectrum,
ν, cm–1: 1710 (C=N). 1Н NMR spectrum, δ, ppm: 1.07–
1.20 m (6H, 2CH3), 2.11–2.35 m (1H, CH), 2.28 s (3H,
CH3), 2.47–2.63 m (1H, CH), 2.79–2.98 m (1H, CH),
3.03–3.20 m (1H, CH), 3.60–3.77 m (1H, CH), 4.88 d
(1H, CH, J 3.9Hz), 5.45–5.61 m (1H, CH), 7.22–7.47 m
(9Harom.), 11.68 s (1H, NH). 13С NMR spectrum, δ, ppm:
20.51 (CH3), 20.70 (CH3), 20.77 (CH3), 25.64 (C4),
30.22 (C3), 54.20 (C5), 73.80 (CH), 92.36 (C6), 127.89,
128.34, 128.42, 129.01, 129.74, 132.06, 137.15, 137.46
(Carom.), 178.25 (C=N). Found, %: Сl 10.26; S 9.29.
C21H26ClNO5S. Calculated, %: Сl 10.42; S 9.41.
5-{[4-(Nitrophenyl)sulfanyl](phenyl)methyl}-
dihydro-3Н-furan-2-one (VIc). To a solution of 0.2 g of
unpurified salt IVc in 3 ml of acetone was added 0.05 g
of anhydrous sodium acetate, and the mixture was left
standing for 24 h. The solvent was evaporated, the organic
substance insoluble in water was extracted with chloro-
form (2 × 20 ml), the extract was dried with anhydrous
magnesium sulfate, filtered, and evaporated. The residue
was crystallized from hexane. Yield 68%, mp 125°С.
IR spectrum, ν, cm–1: 1730 (С=О). 1Н NMR spectrum,
δ, ppm: 2.01–2.15 m (1H, CH), 2.27–2.39 m (1H, CH),
2.73–2.85 m (2H, CH2), 4.21–4.33 m (1H, CH), 5.45 d
5-(Arylsulfanyl)-6-phenyltetrahydro-2Н-pyran-2-
ones Vа–Vc. A solution of 1.5 mmol of salt ІVb–IVd
in 5 ml of a mixture ethanol–water, 4:1, was stirred at
room temperature over 8 h, the solvent was evaporated,
the residue was purified by chromatography on silica gel
(eluent ethyl acetate–hexane, 2:3).
6-Phenyl-5-(phenylsulfanyl)tetrahydropyran-2-
one (Vа). Yield 51% from salt IVb, 48% from salt IVe,
mp 72–73°С. IR spectrum, ν, cm–1: 1775 (С=О). 1Н NMR
spectrum, δ, ppm: 1.90–2.06 m (1H, CH), 2.08–2.21 m
(1H, CH), 2.29–2.50 m (2H, CH2), 4.73 d (1H, CH,
J 4.2 Hz), 4.89–5.03 m (1H, CH), 7.21–7.44 m (10Harom.).
13С NMR spectrum, δ, ppm: 25.70 (C3), 27.90 (C4), 54.87
(C5), 80.51 (C6), 127.06, 127.48, 128.17, 128.63, 128.91,
131.07, 133.45, 137.95 (Carom.), 176.42 (C2). Found, %:
С 71.68; Н 5.54; S 11.13. [M + 1]+ 285. C17H16O2S.
Calculated, %: C 71.80; H 5.67; S 11.25. M 284.4.
(1H, CH, J 9 Hz), 7.28–7.45 m (7Harom.), 7.99 d (2Harom.
,
J 8.7 Hz). 13С NMR spectrum, δ, ppm: 25.68 (C4), 28.63
(C3), 44.13 (CPh–CH), 82.63 (C5), 123.53, 127.53, 128.22,
128.64, 128.71, 137.37, 143.91, 145.03 (Carom.), 169.95
(С2). Found, %: С 61.83; Н 4.47; N 4.46; S 9.61. [M +
1]+ 330. C17H15NO4S. Calculated, %: C 61.99; H 4.59;
N 4.25; S 9.73. M 329.4.
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5-[(4-Methylphenyl)sulfanyl]-6-phenyltetra-
hydropyran-2-one (Vb). Yield 64% from salt IVc, 53
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1
1765 (С=О). Н NMR spectrum, δ, ppm 1.89–2.07 m
(1H, CH), 2.11–2.21 m (1H, CH), 2.26 s (3H, CH3),
2.33–2.49 m (2H, CH2), 4.60 d (1H, CH, J 3.9 Hz), 4.86–
5.01 m (1H, CH), 7.11 d (2Harom., J 7.8 Hz), 7.20–7.41 m
(7Harom.). 13С NMR spectrum, δ, ppm: 20.30 (CH3), 25.82
(C3), 27.95 (C4), 55.44 (C5), 80.62 (C6), 127.41, 127.84,
128.12, 128.59, 129.60, 131.86, 136.98, 138.11 (Carom.),
176.48 (С2). Found, %: С 72.55; Н 6.02; S 10.64. [M +
1]+ 299. C18H18O2S. Calculated, %: C 72.45; H 6.08;
S 10.75. M 298.4.
5-[(4-Nitrophenyl)sulfanyl]-6-phenyltetrahydro-
pyran-2-one (Vc). Yield 52% from salt IVd, 49% from
salt IVg, mp 130–131°С. IR spectrum, ν, cm–1: 1770
1
(С=О). Н NMR spectrum, δ, ppm 1.96–2.12 m (2H,
CH2), 2.30–2.55 m (2H, CH2), 4.99–5.07 m (1H, CH),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

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