Acid-catalyzed reaction of phenols with N-(4,4-diethoxybutyl)sulfonamides – a new method for the synthesis of 2-aryl-1-sulfonylpyrrolidines

Article abstract of DOI:10.1007/s10593-017-2034-8

[Figure not available: see fulltext.]We have developed a new method for the synthesis of 2-aryl-1-sulfonylpyrrolidines on the basis of reactions between various phenols and N-(4,4-diethoxybutyl)sulfonamides in the presence of trifluoroacetic acid. The str

Full text of DOI:10.1007/s10593-017-2034-8

DOI 10.1007/s10593-017-2034-8
Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
Acid-catalyzed reaction of phenols
with N-(4,4-diethoxybutyl)sulfonamides – a new
method for the synthesis of 2-aryl-1-sulfonylpyrrolidines
Andrey V. Smolobochkin1, Almir S. Gazizov1*, Ekaterina A. Anikina2,
Alexander R. Burilov1, Michael A. Pudovik1
1
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences,
8 Akademika Arbuzova St., Kazan 420088, Russia; е-mail: agazizov@iopc.ru
2
Kazan National Research Technological University,
68 Karla Marksa St., Kazan 420015, Russia; е-mail: Smolobochkin@iopc.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(2), 161–166
Submitted October 7, 2016
Accepted January 23, 2017
We have developed a new method for the synthesis of 2-aryl-1-sulfonylpyrrolidines on the basis of reactions between various phenols
and N-(4,4-diethoxybutyl)sulfonamides in the presence of trifluoroacetic acid. The structures of the obtained products were confirmed by
1Н and 13С NMR spectroscopy, IR spectroscopy, and X-ray structural analysis.
Keywords: 2-aryl-1-sulfonylpyrrolidines, N-(4,4-diethoxybutyl)sulfonamides, 2-ethoxypyrrolidines, phenols, sulfonyl chlorides.
Pyrrolidine derivatives containing sulfonamide and aryl
groups represent an important class of organic compounds,
which includes many compounds with high pharmaco-
logical activity. 2-Aryl-1-sulfonylpyrrolidine derivatives
can be used as drugs for the treatment and prevention of
thromboembolism1,2 and neurodegenerative conditions,
such as Huntington's, Parkinson's,3,4 and Alzheimer's5
diseases. According to published data, such compounds are
also able to inhibit matrix metalloproteinase 2.6
synthesis of the starting compounds. Thus, the development
of a new and effective method for the synthesis of 2-aryl-
1-sulfonylpyrrolidines would be of significant interest.
We have previously developed a method for the
synthesis of 2-aryl-1-carboxamidopyrrolidines, based on a
trifluoroacetic acid-catalyzed reaction between 4,4-di-
ethoxybutylureas and phenols, allowing to obtain the target
compounds in high yields under mild conditions
(Scheme 1).26–30
Since the amide and sulfonamide groups are isosteric
and have similar electronic properties, we proposed that the
use of N-(4,4-diethoxybutyl)sulfonamides in this reaction
instead of 4,4-diethoxybutylureas should enable us to
perform the synthesis of 2-aryl-1-sulfonylpyrrolidines. Our
expectations were additionally confirmed by published
reports31,32 on the formation of heterocyclic products upon
The most common approach to the synthesis of 2-aryl-
1-sulfonylpyrrolidines is intramolecular cyclization of aryl-
substituted unsaturated compounds containing
a
sulfonamide group. Such examples include the cyclization
of 3-buten-1-amine,7–14 3-butyn-1-amine,15 and 4-penten-
1-amine16–18 derivatives. These compounds have been
synthesized by oxidative cyclization of sulfonamides,19–22
carbonylation of N-tosylpentenamine derivatives,23,24 or the
reaction of 2-arylpyrrolidines with sulfonyl chlorides.25
The most frequently used catalysts of such reactions are
palladium(II)7,8,21 or rhodium salts,24 as well as hypervalent
iodine compounds.14,19–21 Common drawbacks of the
existing methods for the synthesis of 2-aryl-1-sulfonyl-
pyrrolidines include the use of costly catalysts and
reagents, harsh reaction conditions, and the often laborious
Scheme 1
0009-3122/17/53(02)-0161©2017 Springer Science+Business Media New York
161

Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
the interaction of 4,4-diethoxybutan-1-amine with aryl-
ethoxybutyl)sulfonamides and phenols did not exert a
clearly pronounced effect on the course of this reaction.
The marked differences in the yields of individual
compounds were linked to their different solubility
affecting the losses during purification.
According to spectral data, compounds 2b, 3b, and 4b
were present in the reaction mixture in trace amounts, and
thus could not be isolated as individual samples.
According to the literature data, 2-alkoxypyrrolidines in
the presence of Lewis acids are able to undergo substitution
reactions with organosilicon compounds,34–38 alkenes
activated by the presence of electron-withdrawing groups,39,40
carbonyl compounds,41,42 and sterically hindered phenols,43
leading to formation of the corresponding 2-substituted
pyrrolidine derivatives.
We anticipated that the use of 2-ethoxy-1-sulfonyl-
pyrrolidines 5 instead of the respective acetals 1 in this
reaction should also lead to the formation of 2-aryl-
1-sulfonylpyrrolidines 2–4 (Scheme 2).
sulfonyl chlorides.
Synthesis of the starting N-(4,4-diethoxybutyl)aryl-
sulfonamides 1а,b was accomplished according to a pre-
viously described method33 based on the reaction of 4,4-di-
ethoxybutan-1-amine with p-toluene- and benzenesulfonyl
chlorides in the presence of triethylamine (Scheme 2).
Besides that, we additionally obtained N-(4,4-diethoxy-
butyl)alkylsulfonamides 1c,d in order to identify the effects
associated with the nature of substituents at the sulfur atom
on the feasibility of intramolecular cyclization of these
compounds.
The obtained acetal 1a was involved in reactions with
4-chlororesorcinol, 2-naphthol, and 2,7-dihydroxynaphtha-
lene in CHCl3, which was accomplished in the presence of
an equimolar amount of trifluoroacetic acid (Scheme 2).
The products of this reaction were identified as the
respective 2-aryl-1-p-toluenesulfonylpyrrolidines 2а, 3a,
and 4а (Table 1).
At the next stage of our study we performed reactions of
4-chlororesorcinol, 2-naphthol, and 2,7-dihydroxynaphtha-
lene with acetals 1b–d. The respective pyrrolidine
derivatives 2c,d, 3c,d, and 4c,d were obtained in yields that
varied from 21 to 93% (Table 1). It should be noted that,
according to NMR spectral data, the content of 2-aryl-
pyrrolidines 2a,c,d, 3a,c,d, and 4a,c,d in the reaction
mixtures was in the range from 80 to 95%, while the
structural and electronic features of the starting N-(4,4-di-
A method for the preparation of 2-ethoxy-1-tosyl-
pyrrolidine by the cyclization of N-(4,4-diethoxybutyl)-
4-methylbenzenesulfonamide under acidic conditions has
been described in the literature.33 As a result of our studies,
conditions were selected that allowed to obtain 2-ethoxy-
pyrrolidine 5a in a single step, without isolation of the
intermediate acetal 1а. Analogous synthesis provided
access to N-benzenesulfonyl-2-ethoxypyrrolidine 5b
(Scheme 2).
Scheme 2
Table 1. Yields of products from the reactions of
phenols with acetals 1а–d
Phenol
Sulfonamide
Product
Yield, %
43
–*
82
45
93
–*
93
21
71
–*
62
40
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
Table 2. Yields of products from the reactions of
phenols with 2-ethoxy-1-tosylpyrrolidines 5a,b
Phenol
Pyrrolidine
Product
Yield, %
53
79
71
64
34
26
5a
5b
5a
5b
5a
5b
2a
2b
3a
3b
4a
4b
*The product could not be isolated as individual compound.
162

Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
It was established that the reactions of 2-ethoxy-
pyrrolidine 5а with 4-chlororesorcinol, 2-naphthol, and
2,7-dihydroxynaphthalene in CHCl3 solution in the
presence of trifluoroacetic acid led to the formation of the
respective 2-aryl-1-sulfonylpyrrolidines 2a, 3a, and 4a
(Scheme 2, Table 2). It should be noted that the reaction of
2-ethoxypyrrolidine 5b with the corresponding phenols
allowed to obtain compounds 2b, 3b, and 4b in 26–79%
yields. Similarly to the case of acetals 1a–d, the difference
in yields of the individual compounds 2a,b, 3a,b, and 4a,b
could be explained largely by the losses during the
isolation and purification of the products, rather than by the
nature of the starting materials.
Figure 1. The molecular structure of compound 3а with atoms
represented by thermal vibration ellipsoids of 50% probability.
The structures of the obtained compounds were
confirmed by 1Н and 13С NMR, as well as IR spectroscopy.
The spatial structure of compound 3a was established by
X-ray structural analysis of crystals obtained after
recrystallization from DMSO. As shown by the data of
X-ray structural analysis, the bond lengths, bond angles,
and torsion angles were within the typical limits for each
type of bond (Fig. 1). An interesting feature in the
molecular structure of this compound was the formation of
a C1C2O23H23N1C11 "pseudoring" in the plane of the
naphthalene system due to the OH···N type intramolecular
hydrogen bond O(23)–H(23)···N(1) (the H(23)···N(1)
distance 1.80(6) Å, O(23)···N(1) distance 2.647(6) Å,
O(23)–H(23)···N(1) angle 155(5)°). The molecular packing
in the crystal structure (Fig. 2) consisted of layers formed
by CH···O interactions involving the oxygen atoms of SO2
groups (the C···O distances were equal to 3.249(6) and
3.448(7) Å) and π–π-interactions between the benzene and
naphthol rings (the distances between the planes of
interacting aromatic rings were 3.0–3.7 Å).
Thus, the reactions of N-(4,4-diethoxybutyl)sulfon-
amides with phenols of benzene series, as well as with
naphthols under mild conditions allowed to obtain 2-aryl-
1-sulfonylpyrrolidines containing both aromatic and
aliphatic substituents at the sulfonamide group.
Figure 2. Molecular packing in crystals of compound 3а.
in CH2Cl2 (100 ml). The reaction mixture was stirred at
room temperature for 12 h, then washed with saturated
NaHCO3 solution (100 ml), the organic layer was separated
and the residual solvents were removed under reduced
pressure.
Experimental
IR spectra were recorded on a UR-20 spectrometer (400–
3600 cm−1) in KBr pellets. 1Н NMR spectra were acquired on
a Bruker MSL 400 spectrometer (400 MHz) in DMSO-d6,
CDCl3, and CD3OD. Internal standard – residual proton
signals of the deuterated solvents (δ 2.50 ppm in DMSO-d6,
δ 7.26 ppm in CDCl3, δ 3.31 ppm in CD3OD). 13С NMR
spectra were acquired on a Bruker Avance 600 spectro-
meter (150 MHz) in DMSO-d6, CDCl3, and CD3OD.
Internal standard – 13C NMR signals of the solvent mole-
cules (δ 39.5 for DMSO-d6, δ 77.0 for CDCl3, δ 49.0 ppm
for CD3OD). Elemental analysis was performed on a Carlo
Erba EA 1108 instrument. Schöniger method was applied
for chlorine and sulfur determination.44 Melting points
were determined in glass capillaries, by using a Stuart SMP
10 digital melting point apparatus.
N-(4,4-Diethoxybutyl)-4-methylbenzenesulfonamide
1
(1а). Yield 6.20 g (93%), yellow oil. Н NMR spectrum
(CDCl3), δ, ppm (J, Hz): 1.19 (6H, t, J = 7.1, 2CH3); 1.54–
1.64 (4Н, m, 2СН2); 2.44 (3Н, s, СН3); 2.94–3.01 (2Н, m,
СН2); 3.42–3.51 (2Н, m, СН2); 3.58–3.66 (2Н, m, СН2);
4.42 (1Н, t, J = 5.1, СН); 4.88 (1Н, br. s, NH); 7.31 (2Н, d,
J = 8.0, Н Ar); 7.76 (2Н, d, J = 8.2, Н Ar).
N-(4,4-Diethoxybutyl)benzenesulfonamide (1b). Yield
4.82 g (80%), yellow oil. 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.11 (6H, t, J = 7.1, 2CH3); 1.44–1.59 (4Н, m,
2СН2); 2.92 (2Н, q, J = 6.5, СН2); 3.35–3.42 (2Н, m, СН2);
3.50–3.59 (2Н, m, СН2); 4.36 (1Н, t, J = 5.1, СН); 5.41
(1H, s, NH); 7.44 (2H, t, J = 7.7, Н Ph); 7.50 (1H, t,
J = 7.4, Н Ph); 7.81 (2H, d, J = 7.7, Н Ph). 13C NMR
spectrum (CDCl3), δ, ppm: 15.2; 15.3; 24.6; 30.8; 43.1;
61.4; 102.5; 126.9; 129.0; 132.4; 140.2.
Synthesis of N-(4,4-diethoxybutyl)sulfonamides 1a–d
(General method). 4,4-Diethoxybutan-1-amine (3.4 g,
20 mmol) was added to a cooled (5–8°С) solution of the
appropriate sulfonyl chloride (20 mmol) and Et3N (3.5 ml)
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Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
N-(4,4-Diethoxybutyl)methanesulfonamide
(1c).
Yield 3.76 g (97%), yellow oil. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 0.97 (6H, t, J = 7.1, 2CH3); 1.35–
1.51 (4Н, m, 2СН2); 2.72 (3Н, s, СН3); 2.84–2.93 (2Н, m),
3.21–3.33 (2Н, m) and 3.36–3.50 (2Н, m, 3СН2); 4.23–
4.31 (1Н, m, СН). 13C NMR spectrum (CDCl3), δ, ppm:
15.1; 24.9; 30.6; 39.6; 42.8; 61.2; 102.4.
Method II. The appropriate phenol (0.93 mmol) and
trifluoroacetic acid (0.14 ml, 1.86 mmol) were added to a
solution of 2-ethoxy-1-pyrrolidine 5 (1.86 mmol) in CHCl3
(10 ml). The reaction mixture was stirred at room
temperature for 12 h. The solvent was then removed at
reduced pressure, the residue was washed with Et2O and
the solids were filtered off. The product was isolated as a
white powder that was dried under vacuum.
N-(4,4-Diethoxybutyl)ethanesulfonamide (1d). Yield
1
4.60 g (90%), yellow oil. H NMR spectrum (CDCl3), δ,
4-Chloro-6-(1-tosylpyrrolidin-2-yl)benzene-1,3-diol (2а).
Yield 0.25 g (43%, method I), 0.36 g (53%, method II),
white powder, mp 144–145°С. IR spectrum, ν, cm−1: 1152
ppm (J, Hz): 1.17 (6H, t, J = 7.1, 2CH3); 1.20 (3H, t, J = 7.5,
CH3); 1.45–1.59 (4Н, m), 2.89 (2Н, q, J = 7.4), 2.96 (2Н, q,
J = 5.9), 3.29–3.41 (2Н, m), and 3.45–3.58 (2Н, m, 6СН2);
4.34 (1Н, t, J = 5.1, CH); 5.12 (1H, t, J = 5.4, NН).
13C NMR spectrum (CDCl3), δ, ppm: 8.1; 15.2; 25.2; 30.7;
42.8; 46.5; 61.3; 102.4.
1
(SO2), 1598 (СН Ar), 3422 (О–Н). H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.54–1.63 (1Н, m) and 1.67–
1.88 (3Н, m, 2СН2); 2.41 (3Н, s, СН3); 3.31–3.39 (1Н, m)
and 3.55–3.63 (1Н, m, СН2); 4.92–4.97 (1Н, m, СН); 6.42
(1Н, s, Н Ar); 7.11 (1Н, s, Н Ar); 7.36 (2Н, d, J = 8.0,
Н Ar); 7.70 (2Н, d, J = 8.3, Н Ar). 13C NMR spectrum
(DMSO-d6), δ, ppm: 20.2; 23.4; 33.7; 49.2; 58.4; 103.2;
110.3; 122.6; 127.3; 127.7; 129.4; 134.5; 143.8; 152.1; 153.1.
Found, %: С 55.70; H 5.15; Cl 9.47; N 3.93; S 8.56.
C17H18ClNO4S. Calculated, %: С 55.51; H 4.93; Cl 9.64;
N 3.81; S 8.72.
Synthesis of 2-ethoxypyrrolidines 5a,b (General
method). The appropriate sulfonyl chloride (20 mmol) was
added with cooling (5–8°С) to a solution of 4,4-di-
ethoxybutan-1-amine (3.4 g, 20 mmol) and Et3N (3.5 ml) in
CH2Cl2 (100 ml). The reaction mixture was stirred at room
temperature for 12 h. The reaction mixture was then
washed with saturated aqueous NaHCO3 solution (100 ml),
the organic layer was separated, and the solvent was
removed under reduced pressure.
1-(1-Tosylpyrrolidin-2-yl)naphthalen-2-ol (3а). Yield
0.54 g (93%, method I), 0.48 g (71%, method II), white
powder, mp 162–163°С. IR spectrum, ν, cm−1: 1162 (SO2),
1598 (СН Ar), 3200, 3438 (О–Н). 1H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.23–1.37 (1Н, m), 1.87–1.97
(1Н, m) and 2.00–2.21 (2Н, m, 2СН2); 2.41 (3Н, s, СН3);
3.59–3.67 (1Н, m) and 3.70–3.81 (1Н, m, СН2); 5.37–5.44
(1Н, m, СН); 7.16 (1Н, d, J = 8.8, Н Ar); 7.29 (1Н, t,
J = 7.4, Н Ar); 7.40 (2Н, d, J = 7.0, Н Ar); 7.46 (1Н, t, J = 7.3,
Н Ar); 7.69 (1Н, d, J = 8.8, Н Ar); 7.73 (2Н, d, J = 8.1,
Н Ar); 7.79 (1Н, d, J = 7.9, Н Ar); 8.15 (1Н, d, J = 8.7,
Н Ar); 9.81 (1Н, s, OH). 13C NMR spectrum (DMSO-d6),
δ, ppm: 21.5; 25.5; 32.8; 50.1; 56.9; 118.7; 118.8; 122.6;
123.7; 126.3; 128.0; 129.1 (2С); 129.2; 130.0; 132.4;
134.4; 143.6; 153.2. Found, %: С 68.71; H 5.65; N 3.93;
S 8.66. C21H21NO3S. Calculated, %: С 68.64; H 5.76;
N 3.81; S 8.72.
2-Ethoxy-1-tosylpyrrolidine (5a). Yield 2.21 g (58%),
beige powder, mp 85–86°С. IR spectrum, ν, cm−1: 1161
1
(SO2), 1596 (СН Ar). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.20 (3H, t, J = 7.0, CH3); 1.35–1.52 (1Н, m), 1.69–
1.80 (1Н, m), 1.82–1.92 (1Н, m), and 1.95–2.09 (1Н, m,
2CH2); 2.44 (3Н, s, СН3); 3.09–3.20 (1Н, m), 3.37–3.44
(1Н, m), 3.54–3.60 (1Н, m), and 3.78–3.84 (1Н, m, 2CH2);
5.20–5.25 (1Н, m, СН); 7.32 (2Н, d, J = 8.1, Н Ar); 7.74
(2Н, d, J = 8.2, Н Ar). 13C NMR spectrum (CDCl3), δ, ppm:
15.0; 21.5; 23.2; 32.9; 47.2; 63.1; 90.2; 127.4; 129.6;
136.1; 143.3. Found, %: С 58.09; H 7.23; N 5.07; S 11.81.
C13H19NO3S. Calculated, %: С 57.97; H 7.11; N 5.20;
S 11.90.
2-Ethoxy-1-(phenylsulfonyl)pyrrolidine (5b). Yield 4.59 g
(95%), beige powder, mp 81–82°С. IR spectrum, ν, cm−1:
1
1156 (SO2), 1585 (СН Ar). H NMR spectrum (CDCl3),
1-(1-Tosylpyrrolidin-2-yl)naphthalene-2,7-diol (4а).
Yield 0.43 g (71%, method I), 0.24 g (34%, method II),
white powder, mp 168–169°С. IR spectrum, ν, cm−1: 1156
δ, ppm (J, Hz): 1.11 (3H, t, J = 7.1, CH3); 1.30–1.42 (1Н,
m), 1.64–1.73 (1Н, m), 1.76–1.85 (1Н, m), 1.90–2.07 (1Н,
m), 3.06–3.15 (1Н, m), 3.30–3.40 (1Н, m), 3.42–3.53 (1Н,
m), and 3.68–3.78 (1Н, m, 4СН2); 5.12–5.20 (1Н, m, СН);
7.39–7.47 (2Н, m, Н Ph); 7.48–7.56 (1Н, m, Н Ph); 7.75–
7.82 (2Н, m, Н Ph). 13C NMR spectrum (CDCl3), δ, ppm:
15.0; 23.2; 32.9; 47.3; 63.1; 90.2; 127.3; 129.0; 132.6;
139.0. Found, %: С 58.18; H 7.28; N 5.31; S 12.71.
C13H19NO3S. Calculated, %: С 57.97; H, 7.11; N 5.20; S 12.56.
Synthesis of 2-aryl-1-sulfonylpyrrolidines 2–4
(General methods). Method I. The appropriate phenol
(0.80 mmol) and trifluoroacetic acid (0.12 ml, 1.59 mmol)
were added to a solution of N-(4,4-diethoxybutyl)sulfon-
amide 1 (1.59 mmol) in CHCl3 (10 ml). The reaction
mixture was stirred for 12 h at room temperature. The
solvent was then removed at reduced pressure, the residue
was washed with Et2O and the solids were filtered off. The
product was isolated as white powder, which was dried
under vacuum.
1
(SO2), 1597 (СН Ar), 3423 (О–Н). H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.17–1.28 (1Н, m), 1.86–2.02
(2Н, m), and 2.05–2.17 (1Н, m, 2СН2); 2.42 (3Н, s, СН3); 3.59–
3.68 (1Н, m) and 3.79–3.89 (1Н, m, СН2); 5.28–5.37 (1Н,
3
4
m, СН); 6.85 (1Н, dd, J = 8.7, J = 2.2, Н Ar); 6.90 (1Н,
d, J = 8.7, Н Ar); 7.38 (1Н, d, J = 2.0, Н Ar); 7.40 (2Н, d,
J = 6.6, Н Ar); 7.52 (1Н, d, J = 8.7, Н Ar); 7.61 (1Н, d,
J = 8.8, Н Ar); 7.78 (2Н, d, J = 7.9, Н Ar); 9.63 (1Н, br. s,
OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 21.5; 25.4;
32.3; 50.1; 56.9; 106.0; 115.0; 115.3; 117.0; 123.8; 128.1;
128.9; 130.0; 130.6; 133.9; 134.3; 143.5; 153.5; 155.6.
Found, %: С 65.61; H 5.65; N 3.53; S 8.40. C21H21NO4S.
Calculated, %: С 65.78; H 5.52; N 3.65; S 8.36.
4-Chloro-6-[1-(methylsulfonyl)pyrrolidin-2-yl]benzene-
1,3-diol (2c) was obtained according to the method I. Yield
0.38 g (82%), white powder, mp 227–230°С. IR spectrum,
ν, cm−1: 1152 (SO2), 1600 (СН Ar), 3390, 3439 (О–Н).
164

Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.59–1.95
J = 7.3, СН3); 1.85–2.00 (1Н, m), 2.04–2.13 (1Н, m), 2.19–
2.33 (2Н, m), 2.71–2.86 (2Н, m), 3.64–3.71 (1Н, m), and
3.76–3.83 (1Н, m, 4СН2); 5.62–5.75 (1Н, m, СН); 7.16
(1Н, d, J = 8.8, Н Ar); 7.28 (1Н, t, J = 7.4, Н Ar); 7.44
(1Н, t, J = 7.3, Н Ar); 7.69 (1Н, d, J = 8.8, Н Ar); 7.78
(1Н, d, J = 7.9, Н Ar); 8.14 (1Н, d, J = 8.7, Н Ar); 9.80
(1Н, s, OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 8.0;
26.5; 33.1; 44.1; 49.6; 56.5; 118.7; 118.9; 122.6; 123.4;
126.4; 128.9; 129.0; 129.3; 132.7; 153.4. Found, %:
С 63.18; H 6.15; N 4.77; S 10.49. C16H19NO3S. Calculated,
%: С 62.93; H 6.27; N 4.59; S 10.57.
(3Н, m) and 2.07–2.26 (1Н, m, 2СН2); 2.89 (3Н, s, СН3); 3.30–
3.44 (2Н, m, СН2); 4.77–4.89 (1Н, m, СН); 6.49 (1Н, s,
Н Ar); 7.06 (1Н, s, Н Ar); 9.61 (1Н, s, OH); 9.78 (1Н, s,
OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 24.1; 34.1;
34.5; 49.3; 58.2; 104.0; 109.5; 122.9; 127.8; 152.5; 153.5.
Found, %: С 45.05; H 4.69; Cl 12.34; N 5.01; S 11.17.
C11H14ClNO4S. Calculated, %: С 45.28; H 4.84; Cl 12.15;
N 4.80; S 10.99.
1-[1-(Methylsulfonyl)pyrrolidin-2-yl]naphthalen-2-ol (3c)
was obtained according to the method I. Yield 0.43 g
(93%), white powder, mp 183–184°С. IR spectrum, ν,
cm−1: 1129 (SO2), 1583 (СН Ar), 2972, 3063, 3383 (О–Н).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.91–2.02
(1Н, m), 2.04–2.12 (1Н, m), 2.16–2.24 (1Н, m), and 2.25–
2.32 (1Н, m, 2СН2); 2.83 (3Н, s, СН3); 3.66–3.74 (2Н, m,
СН2); 5.55–5.64 (1Н, m, СН); 7.15 (1Н, d, J = 8.8, Н Ar);
7.28 (1Н, t, J = 7.4, Н Ar); 7.44 (1Н, t, J = 7.1, Н Ar); 7.68
(1Н, d, J = 8.8, Н Ar); 7.78 (1Н, d, J = 7.8, Н Ar); 8.18
(1Н, d, J = 8.7, Н Ar); 9.78 (1Н, s, OH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 25.9; 33.1; 34.9; 49.7; 56.9;
118.9; 119.1; 122.6; 123.6; 126.3; 128.9; 129.0; 129.2; 132.6;
153.2. Found, %: С 61.71; H 6.03; N 4.95; S 10.82.
C15H17NO3S. Calculated, %: С 61.83; H 5.88; N 4.81;
S 11.01.
1-[1-(Ethylsulfonyl)pyrrolidin-2-yl]naphthalene-2,7-
diol (4d) was obtained according to the method I. Yield
0.20 g (40%), white powder, mp 118–120°С. IR spectrum,
1
ν, cm−1: 1141 (SO2), 1592 (СН Ar), 3411 (О–Н). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 1.06 (3Н, t, J = 7.3,
СН3); 1.84–2.01 (1Н, m), 2.04–2.13 (1Н, m), 2.16–2.32
(2Н, m), 2.67–2.85 (2Н, m), and 3.67–3.86 (2Н, m, 4СН2);
5.55–5.67 (1Н, m, СН); 6.84 (1Н, d, J = 6.9, Н Ar); 6.90 (1Н,
d, J = 8.5, Н Ar); 7.36 (1Н, s, Н Ar); 7.52 (1Н, d, J = 8.8,
Н Ar); 7.60 (1Н, d, J = 8.8, Н Ar); 9.56 (1Н, s, OH); 9.62
(1Н, s, OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 8.0;
26.3; 32.8; 44.3; 49.4; 56.5; 105.6; 115.1; 115.4; 116.7;
123.6; 129.1; 130.6; 131.6; 134.1; 153.7; 155.7. Found, %:
С 59.95; H 6.11; N 4.51; S 10.18. C16H19NO4S. Calculated,
%: С 59.79; H 5.96; N 4.36; S 9.98.
1-[1-(Methylsulfonyl)pyrrolidin-2-yl]naphthalene-2,7-
diol (4c) was obtained according to the method I. Yield
0.30 g (62%), white powder, mp 175–176°С. IR spectrum,
ν, cm−1: 1129 (SO2), 1590 (СН Ar), 2926, 2977, 3258,
3421 (О–Н). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
1.89–2.01 (1Н, m) and 2.03–2.12 (1Н, m, СН2); 2.15–2.30
(2Н, m, СН); 2.79 (3Н, s, СН3); 3.65–3.81 (2Н, m, СН2);
4-Chloro-6-[1-(phenylsulfonyl)pyrrolidin-2-yl]benzene-
1,3-diol (2b) was obtained according to the method II.
Yield 0.52 g (79%), white powder, mp 148–150°С.
IR spectrum, ν, cm−1: 1150 (SO2), 1602 (СН Ar), 3438,
3611 (О–Н). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
1.41–1.52 (1Н, m), 1.56–1.75 (3Н, m), 3.20–3.29 (1Н, m),
and 3.51–3.63 (1Н, m, 3СН2); 4.75–4.84 (1Н, m, СН); 6.51
(1Н, s, Н Ar); 7.06 (1Н, s, Н Ar); 7.65 (2Н, t, J = 7.2,
Н Ar); 7.72 (1Н, t, J = 7.3, Н Ar); 7.81 (2Н, d, J = 7.0,
Н Ar); 9.64 (1Н, s, OH); 9.82 (1Н, s, OH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 23.8; 34.0; 49.6; 58.4; 104.0;
109.6; 122.5; 127.6; 127.9; 129.9; 133.5; 137.5; 152.7;
153.5. Found, %: С 54.47; H 4.39; Cl 9.86; N 3.80; S 9.22.
C16H16ClNO4S. Calculated, %: С 54.31; H 4.56; Cl 10.02;
N 3.96; S 9.06.
3
4
5.44–5.53 (1Н, m, СН); 6.85 (1Н, dd, J = 8.7, J = 2.2,
Н Ar); 7.00 (1Н, d, J = 8.8, Н Ar); 7.39 (1Н, d, J = 1.9,
Н Ar); 7.52 (1Н, d, J = 8.8, Н Ar); 7.60 (1Н, d, J = 8.8,
Н Ar); 9.55 (1H, s, OH); 9.61 (1H, s, OH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 25.8; 32.7; 35.1; 49.6; 56.9;
105.9; 115.0; 115.4; 116.9; 123.7; 128.9; 130.6; 134.1; 153.5;
155.7. Found, %: С 58.81; H 5.33; N 4.75; S 10.29.
C15H17NO4S. Calculated, %: С 58.62; H 5.58; N 4.56;
S 10.43.
4-Chloro-6-[1-(ethylsulfonyl)pyrrolidin-2-yl]benzene-
1,3-diol (2d) was obtained according to the method I. Yield
0.22 g (45%), white powder, mp 171–172°С. IR spectrum,
ν, cm−1: 1140 (SO2), 1600 (СН Ar), 3406, 3456 (О–Н).
1H NMR spectrum (CD3OD), δ, ppm (J, Hz): 1.31 (3Н, t,
J = 7.4, СН3); 1.85–2.02 (3Н, m), 2.21–2.34 (1Н, m), 3.01
(2Н, q, J = 7.4), and 3.54–3.60 (2Н, m, 4СН2); 5.01–5.08
(1Н, m, СН); 6.44 (1Н, s, Н Ar); 7.16 (1Н, s, Н Ar).
13C NMR spectrum (CD3OD), δ, ppm: 6.7; 24.0; 33.9;
43.8; 48.8; 58.3; 103.4; 110.2; 122.5; 127.8; 152.3; 153.3.
Found, %: С 47.33; H 5.12; Cl 11.70; N 4.38; S 10.64.
C12H16ClNO4S. Calculated, %: С 47.14; H 5.27; Cl 11.59;
N 4.58; S 10.49.
1-[1-(Phenylsulfonyl)pyrrolidin-2-yl]naphthalen-2-ol
(3b) was obtained according to the method II. Yield 0.42 g
(64%), white powder, mp 84–86°С. IR spectrum, ν, cm−1:
1
1159 (SO2), 1585 (СНAr), 3411 (О–Н). H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.55–1.73 (1Н, m), 2.00–2.12
(1Н, m), 2.16–2.37 (2Н, m) and 3.79–3.87 (2Н, m, 3СН2);
5.58–5.67 (1Н, m, СН); 7.00 (1Н, d, J = 8.8, Н Ar); 7.29–
7.23 (1Н, m, Н Ar); 7.39–7.46 (3Н, m, Н Ar); 7.52–7.58
(1Н, m, Н Ar); 7.61 (1Н, d, J = 8.8, Н Ar); 7.68–7.76 (3Н,
m, Н Ar); 8.14 (1Н, d, J = 8.7, Н Ar). 13C NMR spectrum
(DMSO-d6), δ, ppm: 25.1; 32.4; 49.5; 57.1; 117.5; 117.6;
122.0; 122.7; 125.6; 127.4; 128.3; 128.4; 128.9; 129.2;
132.3 (2C); 137.5; 152.8. Found, %: С 68.18; H 5.19;
N 3.83; S 8.87. C16H19NO4S. Calculated, %: С 67.97;
H 5.42; N 3.96; S 9.07.
1-[1-(Ethylsulfonyl)pyrrolidin-2-yl]naphthalen-2-ol (3d)
was obtained according to the method I. Yield 0.10 g
(21%), white powder, mp 176–177°С. IR spectrum, ν,
cm−1: 1139 (SO2), 1582 (СН Ar), 2882, 2969, 3409 (О–Н).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.07 (3Н, t,
1-[1-(Phenylsulfonyl)pyrrolidin-2-yl]naphthalene-2,7-
diol (4b) was obtained according to the method II. Yield
1.18 g (26%), white powder, mp 118–119°С. IR spectrum,
165

Chemistry of Heterocyclic Compounds 2017, 53(2), 161–166
ν, cm−1: 1155 (SO2), 1598 (СН Ar), 3278, 3424 (О–Н).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.19–1.30
(1Н, m), 1.86 (2Н, m), 2.07–2.18 (1Н, m), 3.63–3.73 (1Н,
m), and 3.78–3.89 (1Н, m, 3СН2); 5.30–5.42 (1Н, m, СН);
6.84 (1Н, dd, J = 8.7, J = 2.2, Н Ar); 6.89 (1Н, d, J = 8.6,
Н Ar); 7.38 (1Н, s, Н Ar); 7.51 (1Н, d, J = 8.7, Н Ar); 7.58–
7.65 (4Н, m, Н Ar); 7.69 (1Н, t, J = 7.4, Н Ar); 7.87 (1Н,
d, J = 7.6, Н Ar). 13C NMR spectrum (DMSO-d6), δ, ppm:
25.4; 32.3; 50.1; 57.0; 115.0; 115.3; 117.0; 117.0; 123.9;
126.6; 128.0; 129.0; 129.4; 129.5; 130.7; 133.3; 153.6;
155.6. Found, %: С 65.16; H 4.97; N 3.98; S 8.55.
C20H19NO4S. Calculated, %: С 65.02; H 5.18; N 3.79; S 8.68.
Monocrystal X-ray structural study of compound 3a
was performed on a Bruker SMART Apex II diffractometer
(graphite monochromator, λ(МоKα) 0.71073 Å). Crystals
of compound 3а (C21H21NO3S) were triclinic. At 20°С:
a 8.315(12), b 9.836(14), c 11.323(16) Å, α 92.846(15),
β 103.917(15), γ 99.573(16)°; V 882(2) Å3; Z 2; dcalc
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-
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The work was performed with financial support from the
Russian Science Foundation (grant 16-13-10023).
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