Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: IV. Cyclosulfenylation of 5-hexenoic acid amides and nucleophilic cleavage of reaction products

Article abstract of DOI:10.1134/S1070428013080125

Anilides of 5-hexenoic acid react with arylsulfenyl chlorides in nitromethane in the presence of lithium perchlorate affording products of electrophilic cyclization, N-{6-[(arylsulfanyl)methyl]tetrahydro-2H-pyran-2- ylidene}anilinium perchlorates. The tre

Full text of DOI:10.1134/S1070428013080125

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 8, pp. 1168−1174. © Pleiades Publishing, Ltd., 2013.
Original English Text © A.I. Vas’kevich, N.M. Tsizorik, V.I. Staninets, M.V. Vovk, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 8,
pp. 1185−1191.
Electrophilic Intramolecular Cyclization
of Functional Derivatives of Unsaturated Compounds: IV.*
Cyclosulfenylation of 5-Hexenoic Acid Amides and
Nucleophilic Cleavage of Reaction Products
A. I. Vas’kevich, N. M. Tsizorik, V. I. Staninets, and M. V. Vovk
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, 02094 Ukraine
e-mail: vaskevich@ioch.kiev.ua
Received March 11, 2013
Abstract—Anilides of 5-hexenoic acid react with arylsulfenyl chlorides in nitromethane in the presence of lithium
perchlorate affording products of electrophilic cyclization, N-{6-[(arylsulfanyl)methyl]tetrahydro-2Н-pyran-2-
ylidene}anilinium perchlorates. The treatment of the latter with sodium acetate or secondary cycloalkylamines in
the presence of water results in the opening of the tetrahydropyran ring and provides anilides or cycloalkylamides
of 6-arylsulfanyl-5-hydroxyhexanoic acid.
DOI: 10.1134/S1070428013080125
Electrophilic intramolecular cyclizations of amides of
unsaturated carboxylic acids is an efficient synthetic tool
for designing lactones and lactams containing in the side
chain halogen atoms and selenyl moieties [2, 3].
arylsulfenyl chlorides with N-substituted amides of cin-
namyl- [6], styryl- [1], allylacetic acids [7]. In the latter
case stable intermediates of iminium type were isolated
and the conditions were developed for their selective
conversion into 5-[(arylsulfanyl)methyl]furan-2-ones.
It looked reasonable to carry out this type reaction with
5-hexenoic acid amides, homologs of allylacetamides.
It was expected that the introducing of an additional
methylene unit between the nucleophilic sites, alkenyl
and carbamoyl groups, would somehow affect both the
Yet the cyclosulfenylation of unsaturated acid is
described in the literature far less often [4, 5], and this
promoted us to carry out a systematic research in order to
establish the effect of the structural parameters of reagents
and of the external conditions on the cyclization process.
In particular, we formerly investigated the reaction of
Scheme 1.
SAr'
O
a
b
NHAr
O
Cl
IIIа_IIIc
+
Ar'SCl
NHAr
_
ClO4
IIа_IIc
Iа, Ib
+
O
NHAr
SAr'
IVа_IVf
I, Ar = Ph (а), 4-MeOC6H4 (b); II, Ar′ = Ph (а), 4-MeC6H4 (b), 4-NO2C6H4 (c); III, Ar = 4-MeOC6H4, Ar′ = 4-MeC6H4 (а),
4-NO2C6H4 (b); Ar = Ph, Ar′ = 4-MeC6H4 (c); IV, Ar = Ph, Ar′ = 4-NO2C6H4 (а), Ph (c), 4-MeC6H4 (d); Ar = 4-MeOC6H4,
Ar′ = 4-NO2C H4 (b), Ph (e), 4-MeC6H4 (f).
____________ 6
* For Communication III, see [1]
1168

ELECTROPHILIC INTRAMOLECULAR CYCLIZATION...: IV.
1169
formation of cyclic compounds IV at the application
as solvent of nitromethane with equimolar addition of
LiClO4. Under these conditions the reaction of amides
Іа, Ib with arylsulfenyl chlorides ІІа, IIb gave rise to
N-aryl-N-{6-[(arylsulfanyl)methyl]tetrahydropyran-
2Н-ylidene}aminium perchlorates ІVc–IVf in 58–91%
yields. Salt-like compounds ІVa–IVf are stable in the
absence of air moisture and gradually decompose at pro-
longed storage. They belong to the rare type of iminium
salts, only two of which have been isolated before in the
individual state [13, 14].
stage of the formation of the primary cyclic structure
and the stages of further transformations. Formerly the
5-hexenoic acid [8] and its nitrile [9, 10] were used as
initial compounds in the synthesis of 6-functionalized
δ-lactones.
Here we report on the study of the reaction between
N-arylhex-5-enamides Іа, Ib with arylsulfenyl chlorides
ІIа–IIc in chloroform, acetic acid, and nitromethane.
It was found by an example of anilide Ib and sulfenyl
chlorides IIb, IIc that in the weakly polar chloroform
the sulfenyl chlorides added to the multiple bond С=С
of the unsaturated acid amide with the formation of
5-arylsulfanyl-6-chlorohexanoic acid amides IIIа, IIIb
in 54–64% yields (Scheme 1, а).
The structure of all compounds synthesized is con-
1
sistent with their spectral parameters. In the Н NMR
spectra of addition products ІІІа–IIIc the informative
signals are the multiplets of the protons Н5 at 3.80–4.02
ppm, and in the 13С NMR spectra, the signals of atoms
The increase in the ionizing ability of the environment
at the use of acetic acid and equimolar addition of lithium
perchlorate was successfully used to obtain the products
of electrophilic intramolecular cyclization [11, 12]. We
found that these conditions were hardly suitable for the
reactions of hexenamides Іа, Ib with sulfenyl chlorides
ІIа, IIb since in most events mixtures of addition products
III and cyclization products IV formed in the ratio 1 :
1. Due to instability of these products in the conditions
of chromatography we failed to separate these mixtures.
Only solid noncyclic compound IIIc was isolated indi-
vidually from the reaction mixture in a 38% yield. In
the case of the more electrophilic 4-nitrophenylsulfenyl
chloride (ІІc) the reaction occurred with a high selectivity
and led to the formation in 74 and 85% yields of spar-
ingly soluble in the acetic acid cyclic perchlorates IVа,
IVb (Scheme 1, b).
1
С5 at 42–47 ppm. In their turn in the Н NMR spectra
of iminium salts IVа–IVf multiplets are observed from
the protons Н6 of the tetrahydropyran ring in the range
4.79–5.05 ppm, and also multiplets of an exocyclic
methylene group in the region 3.22–3.61 ppm. The most
characteristic signals in the 13С NMR spectra are the
signals of atoms С6 at 85–86 ppm.
N-{5-[(Arylsulfanyl)methyl]dihydrofuran-2(3Н)-
ylidene}-N-alkyl(aryl)aminium perchlorates under the
action of sodium acetate converted into the corresponding
5-[(arylsulfanyl)methyl]lactones, and under the treatment
with secondary cycloalkylamines in the presence of
water suffered a transamidation with the opening of the
tetrahydrofuran ring and the formation of 5-arylsulfanyl-
4-hydroxypentanoic acid amides [7]. It seemed reasonable
to estimate the behavior of their closest structural analogs,
The most effectively the reaction was directed to the
Scheme 2.
OH
O
_
NaOAc
OH
IVа, IVe, IVf
+
NHAr
O
NHAr
SAr'
SAr'
Vа_Vc
OH
O
H2O
NHR2
NR2
NHAr _NH2Ar
NHR2
+
O
O
NHAr
NR2
SAr'
SAr'
SAr'
А
VIа_VIe
V, Ar = Ph, Ar′ = 4-NO2C6H4 (а); Ar = 4-MeOC6H4, Ar′ = Ph (b), 4-MeC6H4 (c); VI, R2 = (CH2)5, Ar′ = Ph (a), 4-MeC6H4
(b), 4-NO2C6H4 (c); R2 = (CH2)4, Ar′ = 4-NO2C6H4 (d); R2 = (CH2)2O(CH2)2, Ar′ = 4-NO2C6H4 (e).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

VAS’KEVICH et al.
1170
N-aryl-N-{6-[(arylsulfanyl)methyl]tetrahydropyran-2Н-
ylidene}aminium perchlorates ІV, in the reactions with
the mentioned nucleophilic reagents.
were carried out on an instrumentAgilent110\DAD\HSD\
VLG 119562.
CompoundsꢀІІІа, IIIb. To a solution of 2 mmol of
amide Іb in 10 ml of chloroform at 15°С was added drop-
wise while stirring a solution of 2 mmol of arylsulfenyl
chloride ІІb, IIc in 5 ml of chloroform. The reaction mix-
ture was stirred at room temperature for 12 h, the solvent
was evaporated in a vacuum, to the residue 5 ml of ethyl
ether was added, the formed precipitate was filtered off
and dried in air.
Salts ІVа, IVe, IVf are less stable against sodium
acetate than the furanylideneaminium analogs and in
such reactions under mild conditions undergo the open-
ing of the tetrahydropyran ring with the formation of
6-arylsulfanyl-5-hydroxyhexanoic acid amides Vа–Vc
(Scheme 2). We believe that the most probable scheme
should assume the primary attack of the hydroxyl anion
on the atom С6 of the tetrahydropyran followed by the
opening of the iminolactone ring.
5-[(4-Methylphenyl)sulfanyl]-N-(4-methoxy-
phenyl)-6-chlorohexanamideꢀꢁІІІаꢂ. Yield 54%, mp 80–
81°С. 1Н NMR spectrum (DMSO), δ, ppm: 1.41–1.93 m
(4Н, 2СН2), 2.23–2.41 m (5Н, СН3, СН2), 3.58–3.80 m
(6Н, ОСН3, СН2, СН), 6.87 d (2Нarom, J 8.7 Hz), 7.17 d
(2Нarom, J 8.1 Hz), 7.37 d (2Нarom, J 7.8 Hz), 7.49 d
(2Нarom, J 8.7 Hz), 9.78 s (1Н, NH). 13С NMR spectrum
(DMSO), δ, ppm: 21.09 (СН3), 22.92 (С3), 30.87 (С4),
37.11 (С2), 47.44 (С6), 50.65 (С5), 55.47 (OСH3), 114.13,
121.92, 129.40, 129.94, 131.05, 133.42, 138.18, 156.47
(Сarom), 170.65 (С1). Found, %: С 63.51; H 6.45; N 3.67.
C20H24ClNO2S. Calculated, %: С 63.56; H 6.40; N 3.71.
In the reaction with the secondary cyclic amines in the
presence of water salts ІVа, IVe, IVf behave similarly to
furanylideneaminium analogs; consequently, the pyran
ring undergoes the opening forming the transamidation
products VIа–VIe. This reaction apparently proceeds
through a cyclic intermediate А that easily opens at the
subsequent water attack on the atom С6. The results
obtained to a certain extent are in agreement with the
HSAB principle which requires that the attack of hard
nucleophiles, hydroxyl anion and water, should be di-
rected at the hard electrophilic site С6, and the attack of
softer amines should be directed at a softer electrophilic
site С2 of iminium salts IV.
ꢃ-(4-Methoxyphenyl)-5-[(4-nitrophenyl)sulfanyl]-
6-chlorohexanamide (ІІІb). Yield 64%, mp 81–82°С.
1Н NMR spectrum (DMSO), δ, ppm: 1.58–2.00 m (4Н,
2СН2), 2.26–2.38 m (2Н, СН2), 3.72 s (3Н, ОСН3),
3.82–3.96 m (3Н, СН2, СН), 6.86 d (2Нarom, J 9 Hz),
7.49 d (2Нarom, J 8.5 Hz), 7.62 d (2Нarom, J 8.5 Hz), 8.14 d
(2Нarom, J 8.5 Hz), 9.83 s (1Н, NH). 13С (NMR spectrum
(DMSO), δ, ppm: 22.83 (С3), 31.33 (С4), 36.24 (С2),
47.63 (С5), 47.98 (С6), 55.62 (OСH3), 114.24, 121.09,
124.54, 128.82, 132.93, 145.63, 145.69, 155.53 (Сarom),
170.69 (С1). Mass spectrum: m/z 409.2 [M + 1]+. Found,
%: С 55.90; H 5.14; N 6.90. C19H21ClN2O4S. Calculated,
%: С 55.81; H 5.18; N 6.85. m 408.9.
Compounds Vа–Vc, VІа–VIe are new specimen of
5-hydroxyhexanoic acid amides that lately attract the
attention of researchers [15–17]. Their sulfanyl group is
easy for modification as we have shown by the example of
the oxidation of 6-sulfanyl-substituted amides VІc, VId,
VIe into 6-sulfonyl derivatives VІІа–VIIc (Scheme 3).
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
UR-20 from pellets with KBr or solutions in CH2Cl2. 1Н
and 13С NMR spectra were registered on a spectrometer
BrukerAdvance DRX-500 (500.13, 125.75 MHz respec-
tively), internal reference TMS. GC-MS measurements
Compounds ІІІc, ІVа, IVb. To a solution of
2.2 mmol of amide Іа, Ib and 0.23 g (2.2 mmol) of
lithium perchlorate in 10 ml of acetic acid at 15°С was
added dropwise 2.2 mmol of arylsulfenyl chloride in
5 ml of acetic acid. The reaction mixture was stirred at
room temperature for 4 h. The solvent was evaporated
in a vacuum, the residue was extracted with chloroform
(5 ml), the inorganic precipitate was filtered off, the
filtrate was evaporated, the residue was treated with a
mixture ether–hexane, 1:2 (5 ml), the formed precipitate
(compound ІІІc) was filtered off and washed with hexane.
To isolate compounds ІVа, IVb the precipitate from the
reaction mixture was filtered off and washed with acetic
Scheme 3.
OH
O
O
O
KHSO5
S
VIc, VId, VIe
Ar
NR2
VIIа_VIIc
VII, Ar′ = 4-NO2C6H4, R2 = (CH2)5 (a), (CH2)4 (b),
(CH2)2O(CH2)2 (c).
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ELECTROPHILIC INTRAMOLECULAR CYCLIZATION...: IV.
1171
(10 ml), the inorganic precipitate was filtered off, the
filtrate was evaporated. The residue was diluted with
hexane (10 ml), the formed precipitate was filtered off
and washed with hexane.
acid and hexane.
5-[(4-Methylphenyl)sulfanyl]-ꢃ-phenyl-6-
chlorohexanamide ꢁІІІc). Yield 38%, mp 62°С. 1Н NMR
spectrum (CDCl3), δ, ppm: 1.67–2.03 m (3Н, СН2, СН),
2.07–2.55 m (6Н, СН3, СН2, CH), 2.97–3.17 m (1Н, СН),
3.22–3.42 m (1Н, СН), 3.80–4.02 m (1Н, СН), 6.83–
7.61 m (9Нarom). 13С NMR spectrum (CDCl3), δ, ppm:
21.00 (СН3), 22.20 (С3), 35.78 (С4), 36.89 (С2), 42.82
(С6), 60.78 (С5), 119.94, 124.34, 129.01, 130.02, 131.11,
131.18, 137.25, 137.83 (Сarom), 170.51 (С1). Found, %:
С 65.63; H 6.41; N 4.07. C19H22ClNOS. Calculated, %:
С 65.59; H 6.37; N 4.03.
ꢃ-{6-[(Phenylsulfanyl)methyl]tetrahydro-2Н-
pyran-2-ylidene}anilinium perchlorate (ІVc). Yield
58%, mp 63–64°С. IR spectrum, ν, cm–1: 1660 (С=N),
1125. 1Н NMR spectrum (CD3CN), δ, ppm: 1.81–2.07 m
(3H, CH2, CH), 2.17–2.26 m (1H, CH), 2.90–3.08 m
(2H, CH2), 3.29–3.37 m (1Н, СН), 3.38–3.45 m
(1Н, СН), 4.84–4.94 m (1H, CH), 7.24 d (1Нarom
J 7.2 Hz), 7.30 t (2Нarom, J 7.2 Hz), 7.38 d (2Нarom
,
,
J 7.6 Hz), 7.42–7.46 m (1Нarom), 7.47–7.58 m (4Нarom),
10.76 s (1Н, NH). 13С NMR spectrum (CD3CN), δ, ppm:
15.46 (C4), 25.80 (С3), 26.69 (С5), 37.50 (CH2S), 85.99
(С6), 123.34, 126.93, 128.99, 129.34, 129.60, 129.86,
133.04, 134.73 (Сarom), 176.96 (С2). Found, %: С 54.36;
H 5.09; N 3.48. C18H20ClNO5S. Calculated, %: С 54.33;
H 5.07; N 3.52.
ꢃ-(6-{[(4-Nitrophenyl)sulfanyl]-methyl}tetra-
hydro-2Н-pyran-2-ylidene)anilinium perchlorate
(ІVа). Yield 74%, mp 163–164°С. IR spectrum, ν,
cm–1: 1675 (С=N), 1505, 1350, 1110. 1Н NMR spectrum
(CD3CN), δ, ppm: 1.85–2.09 m (3H, CH2, CH), 2.19–
2.28 m (1H, CH), 2.91–3.07 m (2H, CH2), 3.42–3.49 m
(1Н, СН), 3.53–3.59 m (1Н, СН), 4.93–5.04 m (1H, CH),
7.32–7.44 m (7Нarom), 7.99 d (2Нarom, J 9 Hz), 10.74 s
(1Н, NH). 13С NMR spectrum (CD3CN), δ, ppm: 15.46
(C4), 25.89 (C3), 26.61 (С5), 35.57 (CH2S), 85.91 (С6),
123.28, 123.89, 127.26, 128.93, 129.49, 132.77, 145.32,
145.71 (Сarom), 176.92 (С2). Found, %: С 48.84; H 4.27;
N 6.37. C18H19ClN2O7S. Calculated, %: С 48.81; H 4.32;
N 6.33.
ꢃ-(6-{[(4-Methylphenyl)sulfanyl]-methyl}tetra-
hydro-2Н-pyran-2-ylidene)anilinium perchlorate
(ІVd). Yield 70%, mp 66–67°С. IR spectrum, ν, cm–1:
1
1655 (С=N), 1120. Н (CD3CN), δ, ppm: 1.84–2.06 m
(3H, CH2, CH), 2.15–2.24 m (1H, CH), 2.26 s (3Н,
СН3), 2.88–3.06 m (2H, CH2), 3.24–3.31 m (1Н, СН),
3.33–3.40 m (1Н, СН), 4.82–4.91 m (1H, CH), 7.11 d
(2Нarom, J 8 Hz), 7.29 d (2Нarom, J 8.4 Hz), 7.39–7.59 m
(5Нarom), 10.69 s (1Н, NH). 13С NMR spectrum (CD3CN),
δ, ppm: 15.46 (C4), 20.06 (СH3), 25.74 (C3), 26.70
(С5), 38.18 (CH2S), 86.19 (С6), 123.24, 128.92, 129.58,
129.97, 130.69, 130.93, 133.03, 137.39 (Сarom), 176.90
(С2). Found, %: С 55.37; H 5.41; N 3.36. C19H22ClNO5S.
Calculated, %: С 55.40; H 5.38; N 3.40.
4-Methoxy-ꢃ-(6-{[(4-nitrophenyl)-sulfanyl]
methyl}tetrahydro-2Н-pyran-2-ylidene)anilinium
perchlorate (ІVb). Yield 85%, mp 155–156°С. IR
spectrum, ν, cm–1: 1650 (С=N), 1515, 1335, 1115.
1Н NMR spectrum (CD3CN), δ, ppm: 2.02–2.12 m (3H,
CH2, CH), 2.23–2.30 m (1H, CH), 2.92–3.06 m (2H,
CH2), 3.43–3.50 m (1Н, СН), 3.54–3.61 m (1Н, СН),
3.80 s (3H, CH3), 4.97–5.05 m (1H, CH), 6.89 d (2Нarom
,
4-Methoxy-ꢃ-{6-[(phenylsulfanyl)-methyl]
tetrahydro-2Н-pyran-2-ylidene}anilinium perchlorate
(ІVe). Yield 58%, mp 114–115°С. IR spectrum, ν, cm–1:
J 9 Hz), 7.33 d (2Нarom, J 9 Hz), 7.41 d (2Нarom, J 9 Hz),
7.99 d (2Нarom, J 9 Hz), 10.60 s (1Н, NH). 13С NMR
spectrum (CD3CN), δ, ppm: 15.54 (C4), 25.98 (C3), 26.44
(С5), 35.49 (CH2S), 55.34 (ОСН3), 85.67 (С6), 114.46,
123.80, 124.73, 125.42, 127.06, 145.50, 145.55, 159.68
(Сarom), 175.90 (С2). Found, %: С 48.36; H 4.45; N 5.87.
C19H21ClN2O8S. Calculated, %: С 48.26; H 4.48; N 5.92.
1
1660 (С=N), 1515, 1120. Н NMR spectrum (CD3CN),
δ, ppm: 1.81–2.04 m (3H, CH2, CH), 2.16–2.27 m (1H,
CH), 2.86–3.04 m (2H, CH2), 3.27–3.36 m (1Н, СН),
3.37–3.44 m (1Н, СН), 3.82 s (3H, CH3), 4.82–4.90 m
(1H, CH), 6.99 d (2Нarom, J 8.8 Hz), 7.24 d (1Нarom
J 6.4 Hz), 7.30 t (2Нarom, J 7.2 Hz), 7.38 d (2Нarom
,
,
Compounds ІVc–IVf. To a solution of 2.2 mmol of
amide Іа, Ib and 0.23 g (2.2 mmol) of lithium perchlorate
in 10 ml of nitromethane at 15°С was added dropwise
a solution of 2.2 mmol of arylsulfenyl chloride ІІа, IIb
in 5 ml of nitromethane, and the mixture was stirred at
room temperature for 4 h. The solvent was evaporated
in a vacuum, the residue was extracted with chloroform
J 7.6 Hz), 7.44 d (2Нarom, J 8.8 Hz), 10.60 s (1Н, NH).
13С NMR spectrum (CD3CN), δ, ppm: 15.52 (C4),
25.87 (С3), 26.53 (С5), 37.49 (CH2S), 55.42 (ОСН3),
85.64 (С6), 114.65, 124.71, 125.85, 126.88, 129.29,
129.78, 134.81, 159.69 (Сarom), 175.81 (С2). Found, %:
С 53.46; H 5.06; N 3.34. C19H22ClNO6S. Calculated, %:
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VAS’KEVICH et al.
1172
С 53.33; H 5.18; N 3.27.
42.10 (С6), 55.46 (ОСН3), 69.19 (С5), 114.08, 121.75,
126.65, 129.07, 130.00, 131.04, 135.15, 156.39 (Сarom),
171.18 (С1). Mass spectrum: m/z 346.2 [M + 1]+. Found,
%: С 66.11; H 6.65; N 4.01. C19H23NO3S. Calculated, %:
С 66.06; H 6.71; N 4.05. m 345.5.
4-Methoxy-ꢃ-(6-{[(4-methylphenyl)-sulfanyl]
methyl}tetrahydro-2Н-pyran-2-ylidene)anilinium
perchlorate (ІVf). Yield 91%, mp 125–126°С. IR
1
spectrum, ν, cm–1: 1660 (С=N), 1520, 1115. Н NMR
spectrum (CD3CN), δ, ppm: 1.80–2.03 m (3H, CH2, CH),
2.13–2.21 m (1H, CH), 2.27 s (3Н, СН3), 2.84–3.01 m
(2H, CH2), 3.22–3.29 m (1Н, СН), 3.31–3.38 m (1Н, СН),
5-Hydroxy-ꢃ-(4-methoxyphenyl)-6-[(4-methyl-
phenyl)sulfanyl]hexanamideꢀꢁVcꢂ. Yield 56%, mp
110–111°С. IR spectrum, ν, cm–1: 1655 (С=О), 1530,
1245. 1Н NMR spectrum (CDCl3), δ, ppm: 1.47–1.66 m
(2Н, СН2), 1.76–1.87 m (2Н, СН2), 2.22–2.39 m (5H,
CH3, CH2), 2.73–2.83 m (1Н, СН), 3.01-3.09 m (1Н, СН),
3.81 s (3H, CH3), 4.79–4.87 m (1H, CH), 6.98 d (2Нarom
,
J 8.8 Hz), 7.10 d (2Нarom, J 8 Hz), 7.27 d (2Нarom, J 8 Hz),
7.40 d (2Нarom, J 8.8 Hz), 10.53 s (1Н, NH). 13С NMR
spectrum (CD3CN), δ, ppm: 15.51 (C4), 20.04 (СH3),
25.81 (C3), 26.54 (С5), 38.18 (CH2S), 55.42 (ОСН3),
85.79 (С6), 114.63, 124.65, 125.87, 129.97, 130.61,
131.03, 137.32, 159.69 (Сarom), 175.74 (С2). Found, %:
С 54.41; H 5.43; N 3.24. C20H24ClNO6S. Calculated, %:
С 54.36; H 5.47; N 3.17.
3.59–3.66 m (1Н, СН), 3.76 s (3Н, СН3), 6.82 d (2Нarom
,
J 7.6 Hz), 7.08 d (2Нarom, J 7.2 Hz), 7.20–7.30 m (2Нarom),
7.37 d (2Нarom, J 8.8 Hz). 13С NMR spectrum (CDCl3),
δ, ppm: 21.01 (СН3), 21.94 (С3), 34.94 (С2), 37.00 (С4),
42.91 (С6), 55.47 (ОСН3), 69.07 (С5), 114.10, 121.73,
129.89, 130.91, 131.08, 131.15, 137.03, 156.37 (Сarom),
171.11 (С1). Mass spectrum: m/z 360.2 [M + 1]+. Found,
%: С 66.74; H 7.10; N 3.87. C20H25NO3S. Calculated,
%: С 66.82; H 7.01; N 3.90. m 359.5.
Compounds Vа–Vc. To a solution of 1 mmol of im-
inium salt IVа, IVe, IVf in 3 ml of ethanol was added a
solution of 1.5 mmol of sodium acetate in 2 ml of water,
and the mixture was left standing for 24 h. Ethanol was
evaporated, organic layer insoluble in water was extracted
with chloroform (2 × 5 ml), the extract was dried with
anhydrous magnesium sulfate, filtered, evaporated, the
residue was crystallized from benzene.
Compounds VIа–VIe. To 1 ml of piperidine,
pyrrolidine, or morpholine was added 1 mmol of iminium
salt IVа, IVe, IVf, and the mixture was left standing for
12 h and then it was diluted with 5 ml of water. The oily re-
action product was extracted with chloroform (2 × 5 ml),
the extract was dried with anhydrous magnesium sulfate,
the solvent was evaporated, the residue was chromato-
graphed on silica gel (eluent ethyl acetate–chloroform,
3:1) (compounds VIа, VIb) or crystallized from an ap-
propriate solvent (compounds VIc––VIe).
5-Hydroxy-6-[(4-nitrophenyl)sulfanyl]-ꢃ-phenyl-
hexanamideꢀꢁVаꢂ. Yield 55%, mp 136–137°С. 1Н NMR
spectrum (CD3CN), δ, ppm: 1.49–1.60 m (1Н, СН), 1.62–
1.78 m (2Н, СН2), 1.79–1.87 m (1Н, СН), 2.34 t (2Н,
СН2, J 6.8 Hz), 3.06–3.13 m (1Н, СН), 3.16–3.23 m (1Н,
СН), 3.76–3.85 m (1Н, СН), 7.06 t (1Нarom, J 7.2 Hz),
7.30 t (2Нarom, J 7.6 Hz), 7.44 d (2Нarom, J 8.8 Hz), 7.54 d
(2Нarom, J 7.6 Hz), 8.08 d (2Нarom, J 8.8 Hz), 8.28 s (1Н,
NH). 13С NMR spectrum (CD3CN), δ, ppm: 21.33 (С3),
35.64 (С2), 36.39 (С4), 38.95 (С6), 69.17 (С5), 119.43,
123.51, 123.78, 126.44, 128.76, 139.10, 145.06, 148.07
(Сarom), 171.49 (С1). Mass spectrum: m/z 361.0 [M +
1]+. Found, %: С 60.10; H 5.54; N 7.81. C18H20N2O4S.
Calculated, %: С 59.98; H 5.59; N 7.77. m 360.4.
5-Hydroxy-1-(piperidin-1-yl)-6-(phenylsulfanyl)
hexan-1-oneꢀꢁVIаꢂ. Yield 60%, oily substance. 1Н NMR
spectrum (CDCl3), δ, ppm: 1.43–1.66 m (8Н, 4СН2),
1.69–1.79 m (2Н, СН2), 2.23–2.38 m (2Н, СН2), 2.86–
2.94 m (1Н, СН), 3.02–3.10 m (1Н, СН), 3.29–3.37 m
(2Н, СН2), 3.45–3.53 m (2Н, СН2), 3.61–3.69 m (1Н,
СН), 7.16 t (1Нarom, J 7.4 Hz), 7.25 t (2Нarom, J 7.4 Hz),
7.34 d (2Нarom, J 6.8 Hz). 13С NMR spectrum (CDCl3),
δ, ppm: 21.03 (С3), 24.55, 25.60, 26.53, 42.79, 46.64
(Сpiperidine), 32.79 (С2), 35.75 (С4), 41.71 (С6), 69.04
(С5), 126.31, 128.98, 129.69, 135.68 (Сarom), 171.20 (С1).
Mass spectrum: m/z 308.2 [M + 1]+. Found, %: С 66.50;
H 8.18; N 4.53. C17H25NO2S. Calculated, %: С 66.41;
H 8.20; N 4.56. m 307.4.
5-Hydroxy-ꢃ-(4-methoxyphenyl)-6-(phenylsulfanyl
)
hexanamideꢀꢁVbꢂ. Yield 53%, mp 88–89°С. IR spectrum,
1
ν, cm–1: 1655 (С=О), 1520, 1235. Н NMR spectrum
(CDCl3), δ, ppm: 1.50–1.71 m (2Н, СН2), 1.77–1.89 m
(2Н, СН2), 2.29–2.41 m (2H, CH2), 2.81–2.90 m (1Н,
СН), 3.07–3.17 m (1Н, СН), 3.62–3.74 m (1Н, СН),
3.78 s (3Н, СН3), 6.84 d (2Нarom, J 8.8 Hz), 7.17–7.31 m
(3Нarom), 7.34–7.44 m (4Нarom). 13С NMR spectrum
(CDCl3), δ, ppm: 21.88 (С3), 35.03 (С2), 36.95 (С4),
5-Hydroxy-6-[(4-methylphenyl)sulfanyl]-1-
(piperidin-1-yl)hexan-1-oneꢀꢁVIbꢂ. Yield 42%, oily
1
substance. Н NMR spectrum (CDCl3), δ, ppm: 1.45–
1.67 m (8Н, 4СН2), 1.71–1.80 m (2Н, СН2), 2.23–2.41 m
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ELECTROPHILIC INTRAMOLECULAR CYCLIZATION...: IV.
1173
(CDCl3), δ, ppm: 20.51 (С3), 32.35 (С2), 35.99 (С4),
39.69 (С6), 42.08, 45.92, 66.59, 66.90 (Cmорф.), 69.35
(С5), 123.98, 126.73, 145.26, 147.06 (Сarom), 171.59 (С1).
Mass spectrum: m/z 355.2 [M + 1]+. Found, %: С 54.31;
H 6.29; N 7.85. C16H22N2O5S. Calculated, %: С 54.22;
H 6.26; N 7.90. m 354.4.
(5Н, СН3, СН2), 2.81–2.90 m (1Н, СН), 3.01–3.09 m
(1Н, СН), 3.32–3.40 m (2Н, СН2), 3.48–3.57 m (2Н,
СН2), 3.60–3.67 m (1Н, СН), 7.10 d (2Нarom, J 8 Hz),
7.29 d (2Нarom, J 8 Hz). 13С NMR spectrum (CDCl3),
δ, ppm: 21.03 (CH3), 21.09 (С3), 24.57, 25.60, 26.53,
42.78, 46.65 (Сpiperidine), 32.83 (С2), 35.67 (С4), 42.54
(С6), 68.97 (С5), 129.78, 130.69, 131.65, 136.70 (Сarom),
171.19 (С1). Mass spectrum: m/z 322.2 [M + 1]+. Found,
%: С 67.28; H 8.43; N 4.39. C18H27NO2S. Calculated,
%: С 66.41; H 8.20; N 4.56. m 321.5.
Compounds VIIа–VIIc. To a solution of 1 mmol
of compound VIc, VId, VIe in 5 ml of methanol was
added at stirring 1.2 g (2 mmol) of KHSO5 dissolved in
5 ml of water. The reaction mixture was stirred for 5 h at
70°С, cooled, the inorganic precipitate was filtered off,
the filtrate was evaporated, the residue was crystallized
from water.
5-Hydroxy-6-[(4-nitrophenyl)sulfanyl]-1-
(piperidin-1-yl)hexan-1-oneꢀꢁVIcꢂ. Yield 75%, mp
103–104°С (ether). IR spectrum, ν, cm–1: 1630 (С=О),
1585, 1510, 1340. 1Н NMR spectrum (CDCl3), δ, ppm:
1.48–1.57 m (4Н, 2СН2), 1.58–1.66 m (3Н, СН2, СН),
1.67–1.74 m (1Н, СН), 1.76–1.87 m (2Н, СН2), 2.32–
2.44 m (2Н, СН2), 3.10–3.18 m (2Н, СН2), 3.35–3.41 m
(2Н, СН2), 3.51–3.57 m (2Н, СН2), 3.79–3.85 m (1Н,
СН), 7.39 d (2Нarom, J 8.5 Hz), 8.10 d (2Нarom, J 9 Hz).
13С NMR spectrum (CDCl3), δ, ppm: 20.61 (С3), 24.49,
25.59, 26.50, 42.90, 46.62 (Сpiperidine), 32.49 (С2), 36.10
(С4), 49.60 (С6), 69.26 (С5), 123.86, 126.63, 145.90,
147.39 (Сarom), 171.19 (С1). Mass spectrum: m/z 353.1 [M
+ 1]+. Found, %: С 57.86; H 6.94; N 7.91. C17H24N2O4S.
Calculated, %: С 57.93; H 6.86; N 7.95. m 352.4.
5-Hydroxy-6-[(4-nitrophenyl)sulfonyl]-1-
(piperidin-1-yl)hexan-1-one ꢁVIIаꢂ. Yield 96%, mp
104–105°С. IR spectrum, ν, cm–1: 1620 (С=О), 1540,
1350. 1Н NMR spectrum (CDCl3), δ, ppm: 1.42–1.57 m
(6Н, 3СН2), 1.58–1.72 m (3Н, СН2, СН), 1.75–1.84 m
(1Н, СН), 2.25–2.42 m (2Н, СН2), 3.23 d (1Н, СН,
J 14.8 Hz), 3.31–3.41 m (3Н, СН2, СН), 3.46–3.56 m
(2Н, СН2), 4.11–4.20 m (1Н, СН), 8.14 d (2Нarom
,
J 8.4 Hz), 8.38 d (2Нarom, J 8.8 Hz). 13С NMR spectrum
(CDCl3), δ, ppm: 19.72 (С3), 24.46, 25.56, 26.46, 42.98,
46.59 (Сpiperidine), 32.05 (С2), 36.53 (С4), 62.70 (С6), 65.43
(С5), 124.18, 129.79, 145.77, 150.80 (Сarom), 171.09 (С1).
Mass spectrum: m/z 385.2 [M + 1]+. Found, %: С 53.15;
H 6.25; N 7.32. C17H24N2O6S. Calculated, %: С 53.11;
H 6.29; N 7.29. m 384.4.
5-Hydroxy-6-[(4-nitrophenyl)sulfanyl]-1-(pyr-
rolidin-1-yl)hexan-1-oneꢀꢁVIdꢂ. Yield 74%, mp 90–
91°С (hexane). IR spectrum, ν, cm–1: 1625 (С=О),
1585, 1520, 1340. 1Н NMR spectrum (CDCl3), δ, ppm:
1.59–1.75 m (2Н, СН2), 1.80–2.00 m (6Н, 3СН2),
2.25–2.42 m (2Н, СН2), 3.09–3.20 m (2Н, СН2), 3.34–
3.50 m (4Н, 2СН2), 3.78–3.89 m (1Н, СН), 4.20 s (1Н,
ОН), 7.40 d (2Нarom, J 8.5 Hz), 8.11 d (2Нarom, J 8 Hz).
13С NMR spectrum (CDCl3), δ, ppm: 20.06 (С3), 24.37,
26.07, 45.82, 46.63 (Сpyrrolidine), 33.93 (С2), 36.18 (С4),
39.53 (С6), 69.18 (С5), 123.84, 126.55, 145.13, 147.52
(Сarom), 171.65 (С1). Found, %: С 56.81; H 6.52;
N 8.31. C16H22N2O4S. Calculated, %: С 56.78; H 6.55;
N 8.28.
5-Hydroxy-6-[(4-nitrophenyl)sulfonyl]-1-
(pyrrolidin-1-yl)hexan-1-oneꢀꢁVIIbꢂ. Yield 95%, mp
134–135°С. 1Н NMR spectrum (CDCl3), δ, ppm: 1.47–
1.58 m (2Н, СН2), 1.62–1.72 m (1Н, СН), 1.74–2.00 m
(5Н, 2СН2, СН), 2.17–2.27 m (1Н, СН), 2.28–2.39 m
(1Н, СН), 3.17–3.25 m (1Н, СН), 3.28–3.47 m (5Н,
2СН2, СН), 4.09–4.20 m (1Н, СН), 8.11 d (2Нarom
,
J 7.2 Hz), 8.35 d (2Нarom, J 8.4 Hz). 13С NMR spectrum
(CDCl3), δ, ppm: 19.07 (С3), 24.34, 26.04, 45.89, 46.62
(Сpyrrolidine), 33.47 (С2), 36.64 (С4), 62.73 (С6), 65.28
(С5), 124.16, 129.74, 145.86, 150.78 (Сarom), 171.58 (С1).
Mass spectrum: m/z 371.2 [M + 1]+. Found, %: С 51.92;
H 5.96; N 7.61. C16H22N2O6S. Calculated, %: С 51.88;
H 5.99; N 7.56. m 370.4.
5-Hydroxy-1-(morpholin-4-yl)-6-[(4-nitrophenyl)
sulfanyl]hexan-1-oneꢀ ꢁVIeꢂ. Yield 70%, mp 100–
101°С (benzene). IR spectrum, ν, cm–1: 1640 (С=О),
1
5-Hydroxy-1-(morpholin-4-yl)-6-[(4-nitro-phenyl)
sulfonyl]hexan-1-one ꢁVIIcꢂ. Yield 98%, mp 70–71°С.
IR spectrum, ν, cm–1: 1635 (С=О), 1535–1540, 1350.
1Н NMR spectrum (CDCl3), δ, ppm: 1.53–1.61 m (2Н,
СН2), 1.70–1.83 m (2Н, СН2), 2.27–2.44 m (2Н, СН2),
3.21–3.28 m (1Н, СН), 3.32–3.39 m (1Н, СН), 3.42–
1585, 1520, 1340. Н NMR spectrum (CDCl3), δ,
ppm: 1.56–1.75 m (2Н, СН2), 1.78–1.88 m (2Н, СН2),
2.30–2.46 m (2Н, СН2), 3.05–3.13 m (1Н, СН), 3.15–
3.22 m (1Н, СН), 3.41–3.50 m (2Н, СН2), 3.57–3.70 m
(6Н, 3СН2), 3.78–3.87 m (1Н, СН), 7.39 d (2Нarom
,
J 8.8 Hz), 8.11 d (2Нarom, J 8.8 Hz). 13С NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

VAS’KEVICH et al.
1174
p. 1130.
3.48 m (2Н, СН2), 3.57–3.62 m (2Н, СН2), 3.63–3.71 m
7. Vas’kevich, A.I., Tsizorik, N.M., Rusanov, E.B., Stani-
nets, V.I., and Vovk, M.V., Zh. Org. Khim., 2012, vol. 48,
p. 206.
8. Murai, K., Matsushita, T., Nakomura, A., Fukushima, S.,
Shimura, M., and Fujioka, H., Angew. Chem., 2010, vol. 49,
p. 9174.
9. Abd, El, Samii, Z.K.M., Al, Ashmawy, M.I., and Mel-
lor, J.M., Tetrahedron Lett., 1986, vol. 27, p. 5293.
10. Abd, El, Samii, Z.K.M., Al, Ashmawy, M.I., and Mel-
lor, J.M., J. Chem. Soc., Perkin, Trans. I, 1988, p. 2523.
11. Zefirov, N.S., Smit, V.A., Bodrikov, I.V., and Krimer, M.Z.,
Dokl. Akad. Nauk SSSR., 1978, vol. 240, p. 858.
12. Krimer, M.Z., Smit, V.A., and Shamshurin, A.A., Dokl.
AN, SSSR., 1973, vol. 208, p. 864.
13. Deslongchamps, P., Dube, S., Lebreux., Patterson, D.R.,
and Tailleref, R. Can. J. Chem., 1975, vol. 53, p. 2791.
14. Nader, R.B. and Kaloustian, M.K., Tetrahedron Lett., 1979,
vol. 20, p. 1447.
(4Н, 2СН2), 4.17–4.25 m (1Н, СН), 8.14 d (2Нarom
,
J 8.8 Hz), 8.40 d (2Нarom, J 8.8 Hz). 13С NMR spectrum
(CDCl3), δ, ppm: 19.69 (С3), 31.94 (С2), 36.34 (С4),
42.13, 45.88, 66.52, 66.83 (Cmorph.), 62.57 (С6), 65.54
(С5), 124.37, 129.62, 145.58, 150.88 (Сarom), 171.51 (С1).
Mass spectrum: m/z 387.0 [M + 1]+. Found, %: С 49.81;
H 5.73; N 7.27. C16H22N2O7S. Calculated, %: С 49.73;
H 5.74; N 7.25. m 386.4.
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