Interaction of 2-naphthol with γ-ureidoacetals. A new method for the synthesis of 2-arylpyrrolidines

Article abstract of DOI:10.1007/s10593-014-1524-1

We report a new, single-stage method for the synthesis of 2-arylpyrrolidines, based on an acid-catalyzed reaction of 2-naphthol with γ-ureidoacetals, enabling the preparation of the target compounds under mild conditions, while avoiding costly reagents an

Full text of DOI:10.1007/s10593-014-1524-1

Chemistry of Heterocyclic Compounds, Vol. 50, No. 5, August, 2014 (Russian Original Vol. 50, No. 5, May, 2014)
INTERACTION OF 2-NAPHTHOL WITH
-UREIDOACETALS. A NEW METHOD FOR
THE SYNTHESIS OF 2-ARYLPYRROLIDINES
1
2
*
A. S. Gazizov , A. V. Smolobochkin ,
A. R. Burilov1, and M. A. Pudovik1
We report a new, single-stage method for the synthesis of 2-arylpyrrolidines, based on an acid-
catalyzed reaction of 2-naphthol with γ-ureidoacetals, enabling the preparation of the target
compounds under mild conditions, while avoiding costly reagents and catalysts.
Keywords: acetals, 2-arylpyrrolidines, 2-naphthol, ureas, γ-ureidoacetals.
The 2-arylpyrrolidine fragment is a common feature of many natural and synthetic biologically active
compounds. In particular, 2-arylpyrrolidines have been proposed as anticancer drugs [1], medications for the
treatment of psychiatric and neurophysiological conditions, such as Parkinson's [2] and Alzheimer's disease [2, 3],
glutamate receptor modulators [4], histamine Н3 receptor antagonists [5], and PI3 kinase inhibitors [6].
2-Arylpyrrolidine derivatives have been obtained in the Negishi reaction catalyzed by palladium
complexes [7], as well as by the interaction of pyrrolidines, containing hydroxy, alkoxy, or acetoxy groups at
the α-position, with aromatic organomagnesium or organolithium compounds [8-11]. The arylation of
pyrrolidine derivatives in the presence of ruthenium complexes is also known [12]. Another method for the
synthesis of 2-arylpyrrolidines involves intra- or intermolecular cyclization of aryl-substituted 1,4-diols or their
mesylates [13], 4-hydroxy-substituted amines [14], 1,4-dihalo derivatives of butane [15], and derivatives of
pentenamine [16]. The syntheses of 2-arylpyrrolidines using benzaldehyde imine [17] and 4-halo-substituted
butanal imine [18] should also be noted. The majority of methods for the synthesis of 2-arylpyrrolidines involve
the use of palladium, copper, ruthenium, or iridium complexes as catalysts [16, 19-21].
Several publications [22-24] describe an acid-catalyzed heterocyclization of N-(4,4-diethoxybutyl)-
amides of substituted phenylacetic acids. However, only a few condensed pyrrolidinotetrahydroisoquinolines
have been obtained by this method. In addition, there is a single report of obtaining a moderate yield of
2-(phenylthio)pyrrolidine by the condensation of (4,4-diethoxybutyl)urea in the presence of thiophenol [25], but
this approach was not developed further.
_______
*To whom correspondence should be addressed, e-mail: agazizov@iopc.ru.
1A. E. Arbuzov Institute of Organic and Physical Chemistry of the Kazan Scientific Center, Russian Academy
of Sciences, 8 Akademika Arbuzova St., Kazan 420088, Russia.
2Kazan National Research Technical University, 68 K. Marksa St., Kazan 420015, Russia; e-mail:
smolobochkinav@mail.ru.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 769-776, May, 2014. Original
article submitted December 13, 2013; revision submitted February 25, 2014.
0009-3122/14/5005-0707©2014 Springer Science+Business Media New York
707

The current methods of α-arylpyrrolidine synthesis have several drawbacks – the use of costly catalysts
and/or reagents, harsh reaction conditions, and the often laborious synthesis of starting materials.
Our research group has previously studied the reaction of resorcine and its derivatives with
α-ureidoacetals in the presence of trifluoroacetic acid, which resulted in the formation of 5-arylimidazolidin-
2-ones [26-29]. Based on these results, and also the aforementioned examples of intramolecular
heterocyclization of (4,4-diethoxybutyl)amides in the presence of acidic catalysts [22-24], we assumed that
the interaction of (4,4-diethoxybutyl)ureas (γ-ureidoacetals) with phenols may also lead to the formation of
aryl-substituted heterocyclic compounds.
The starting γ-ureidoacetals 2а-e were obtained according to the following scheme. The acetal 2a was
synthesized by reacting the γ-aminoacetal 1 with trimethylsilyl isocyanate, followed by treatment of the
intermediate with ethanol. The acetal 2b was obtained analogously by the reaction of γ-aminoacetal 1 with phenyl
isocyanate. The acetals 2с-e were obtained by reacting the respective aromatic amines with 1,1'-carbonyl-
diimidazole (CDI), followed by the treatment of the intermediate N-aryl-1H-imidazole-1-carboxamides with the
γ-aminoacetal 1.
The obtained acetals 2а-e reacted in a 1:1 ratio with 2-naphthol in the presence of equimolar
trifluoroacetic acid in chloroform, leading to the pyrrolidines 3a-e containing a naphthyl fragment at position 2
of the heterocycle. This reaction was achieved both with the unsubstituted γ-ureidoacetal 2а, as well as the
γ-ureidoacetals 2b-e, containing an aryl substituent at one of the nitrogen atoms. The target compounds were
obtained in 28-78% yields, and the structures were confirmed by NMR spectroscopy.
EtO
EtO
Me3SiNCO
C6H6, 7 h
EtO
HN
EtO
HN
EtOH, 48 h
Me3Si
N
O
H2N
2a
O
H2N(CH2)3CH(OEt)2
H
1
EtO
EtO
PhNCO
HN
C6H6, 6 h
PhHN
O
2b
EtO
EtO
RHN
O
CDI
CH2Cl2,
45°C, 12 h
1
RNH2
N
HN
CHCl3, 20 h
N
RHN
2c–e
O
RHN
N
OH
CF3CO2H
CHCl3, 24 h
O
HO
2a–e
+
3a–e
a R = H, b R = Ph, c R = p-MeOC6H4, d R = p-BrC6H4, e R = p-O2NC6H4
Taking into account the literature data [24], we propose the following mechanism for the formation of
2-arylpyrrolidine derivatives. One of the ethoxy groups in the acetal molecule is protonated at first, followed by
the elimination of an ethanol molecule and the formation of carbocation A. The final product may be obtained
by two reaction pathways from this point. The first pathway involves an intramolecular cyclization of the
708

carbocation A with the formation of 2-ethoxypyrrolidine B and its subsequent interaction with naphthol. The
second pathway involves an initial intramolecular reaction of the carbocation А with naphthol, leading to the
intermediate C, and a subsequent intramolecular closure of the heterocycle. The available experimental data do
not provide unequivocal evidence in favor of any of these two pathways.
The proposed mechanism also provides an explanation for the substantial decrease of target product
yield in the case of acetal 2e, that contains a para-nitro group in the phenyl ring. According to the literature data
[30, 31], the phenyl ring, the π-electrons of the С=О bond, and the lone electron pairs of both nitrogen atoms
form a conjugated system in phenyl-substituted ureas. The presence of an electron-withdrawing group in the
phenyl substituent causes a decrease of electron density on the nitrogen atoms, and thus interferes with the
intramolecular cyclization leading to the formation of arylpyrrolidine.
In the course of these investigations, we were interested in the synthesis of compounds with two
pyrrolidine fragments in the molecule. For this purpose, we prepared the diacetals 4a,b by interaction of
hexamethylene and para-phenylene diisocyanate with two equivalents of the γ-aminoacetal 1.
The reaction of the obtained diacetates 4a,b with 2-naphthol in chloroform in the presence of
trifluoroacetic acid led to the formation of the target compounds 5а,b with two pyrrolidine nuclei. Remarkably,
the yields of compounds 5а,b were considerably higher than those of compounds 3a-e, and were 94%
(compound 5a) and 90% (compound 5b).
H
N
H
N
H
N
H
N
0.5 equiv. X(NCO)2
EtO
OEt
X
OEt
OEt
1
+
O
O
4a,b
H
H
N
N
N
N
OH
HO
HO
+
CF3CO2H
X
4a,b
O
O
CHCl3, 24 h
5a,b
4, 5 a X = (CH2)6, b X =
709

Due to the presence of two chiral centers in compounds 5а,b, these molecules can exist as two
diastereomers, the NMR spectra of which must be different. Nevertheless, the NMR spectra of products 5а,b
exhibited only a single set of signals. This may be explained both by the diastereoselectivity of the reaction, as
well as by the very small difference of chemical shifts between the respective nuclei of both diastereomers.
Thus, our investigation of γ-ureidoacetal reaction with 2-naphthol has led to the discovery of a
convenient single-stage synthesis of novel 2-arylpyrrolidines. The advantages of the method include high yields
of the target compounds, mild reaction conditions, and the possibility of avoiding costly reagents.
EXPERIMENTAL
1
IR spectra were recorded on a UR-20 spectrometer in the 400-3600 cm-1 interval in Nujol. Н NMR
spectra were acquired on Bruker Avance 600 and Bruker MSL 400 spectrometers (600 and 400 MHz,
respectively) relative to the residual solvent protons (CDCl3 δ = 7.26, (CD3)2SO δ 2.50 ppm). 13С NMR spectra
were acquired on a Bruker Avance 600 spectrometer (150 MHz) relative to the residual solvent protons (CDCl3
δ = 77.0, (CD3)2SO δ 39.5 ppm). The MALDI-TOF mass spectra were recorded on a Bruker ULTRAFLEX III
TOF/TOF instrument (with 2,5-dihydroxybenzoic acid matrix). Elemental analysis was performed on Carlo
Erba EA 1108 instrument. Melting points were determined in glass capillaries with a Stuart SMP 10 apparatus.
Anhydrous solvents were prepared according to the standard procedures.
N-(4,4-Diethoxybutyl)urea (2а). A solution of 4,4-diethoxybutan-1-amine (1) (4.20 g, 26.1 mmol) in
benzene (10 ml) was cooled (5-8°С) and treated by dropwise addition of trimethylsilyl isocyanate (3.00 g,
26.1 mmol). The reaction mixture was stirred for 7 h at room temperature. The solvent was removed under vacuum.
The residue was dissolved in ethanol (30 ml), maintained at 20°С for 48 h. The solvent was removed, the waxy
residue was dried under vacuum (3 h, 0.01 torr). Yield 3.79 g (71%). IR spectrum, , cm-1: 1655 (C=O), 2724, 3207,
3390 (N–H). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.21 (6Н, br. t, J = 7.1, 2СН3); 1.54–1.73 (4Н,
m, (СН2)2); 3.15-3.22 (2Н, m, СН2N); 3.50-3.54 (2Н, m) and 3.65-3.69 (2Н, m, 2OСН2); 4.50 (1Н, t, J = 5.1,
СН). Found, %: C 53.21; H 9.93; N 13.81. С9H20N2O3. Calculated, %: C 52.92; Н 9.87; N 13.71.
N-(4,4-Diethoxybutyl)-N'-phenylurea (2b). A solution of 4,4-diethoxybutan-1-amine (1) (2.03 g,
12.6 mmol) in benzene (10 ml) was cooled (5-8ºС) and treated by dropwise addition of phenyl isocyanate
(1.50 g, 12.6 mmol). The reaction mixture was stirred for 6 h at room temperature. The solvent was removed
under vacuum (20 torr). The light-colored low-melting solid that formed was dried under vacuum (5 h,
0.01 torr) until constant mass. Yield 3.02 g (85%). Mp 66-67°С. IR spectrum, , cm-1: 1598 (Ar), 1637 (C=O),
2870, 2926, 2972, 3320 (N–H). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.16 (6Н, br. t, J = 7.1,
2СН3); 1.46-1.62 (4Н, m, (СН2)2); 3.10-3.16 (2H, m, СН2N); 3.37-3.50 (2Н, m) and 3.51-3.66 (2Н, m, 2OCH2);
4.39 (1Н, t, J = 5.5, CH); 6.96 (1Н, br. t, J = 7.3, Н Ar); 7.20 (2Н, br. t, J = 8.1, Н Ar); 7.25 (2Н, br. d, J = 7.5,
Н Ar). Found, %: C 64.09; H 8.71; N 9.89. C15H24N2O3. Calculated, %: C 64.26; H 8.63; N 9.99.
N-(4,4-Diethoxybutyl)-N'-(4-methoxyphenyl)urea (2c). A solution of para-anisidine (1.38 g,
11.2 mmol) in CH2Cl2 (11 ml) was treated with 1,1'-carbonyldiimidazole (2.00 g, 12.3 mmol). The reaction
mixture was heated for 12 h at 45ºС, then cooled. The precipitate that formed was collected by vacuum
filtration. The obtained N-(4-methoxyphenyl)-1H-imidazole-1-carboxamide solution in chloroform (10 ml) was
treated with 4,4-diethoxybutan-1-amine (1) (1.81 g, 11.2 mmol). The mixture was stirred for 20 h at room
temperature. The precipitate was collected by vacuum filtration and washed with water. The product was dried
under vacuum (3 h, 0.01 torr) until constant mass. Yield 2.23 g (64%). Mp 92-93°С. IR spectrum, , cm-1: 1584
(Ar), 1631 (C=O), 2727, 2875, 2960, 3345 (N–H). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.17
(6Н, br. t, J = 7.0, 2СН3); 1.51-1.67 (4Н, m, (СН2)2); 3.17-3.25 (2Н, m, СН2N); 3.42-3.51 (2Н, m) and 3.58-3.67
(2Н, m, 2ОСН2); 3.76 (3H, s, OСН3); 4.45 (1Н, t, J = 5.3, СН); 5.35 (1Н, br. s, NH); 6.81 (2Н, br. d, J = 8.8,
Н Ar); 7.03 (1Н, br. s, NН); 7.18 (2Н, br. d, J = 8.8, Н Ar). Found, %: C 62.02; H 8.19; N 8.92. C16H26N2O4.
Calculated, %: C 61.91; H 8.44; N 9.03.
710

N-(4-Bromophenyl)-N'-(4,4-diethoxybutyl)urea (2d) was obtained analogously to compound 2с from
para-bromoaniline (1.93 g, 11.3 mmol), 1,1'-carbonyldiimidazole (2.00 g, 12.3 mmol), and 4,4-diethoxybutan-
1-amine (1) (1.63 g, 10.1 mmol). Yield 2.16 g (54%). Mp 134-135°С. IR spectrum, , cm-1: 1591 (Ar), 1636
1
(C=O), 2726, 2870, 2935, 3360 (N–H). H NMR spectrum (400 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.10 (6Н,
br. t, J = 7.0, 2СН3); 1.41-1.56 (4Н, m, (СН2)2); 3.05-3.12 (2Н, m, СН2N); 3.39-3.47 (2Н, m) and 3.52-3.61 (2Н,
m, 2СН2O); 4.46 (1Н, t, J = 5.5, СН); 7.36-7.38 (4Н, br. s, Н Ar). Found, %: C 49.99; H 6.58; Br 22.19; N 7.70.
C15H23BrN2O3. Calculated, %: C 50.15; H 6.45; Br 22.24; N 7.80.
N-(4,4-Diethoxybutyl)-N'-(4-nitrophenyl)urea (2e) was obtained analogously to compound 2с from
para-nitroaniline (1.55 g, 11.2 mmol), 1,1'-carbonyldiimidazole (2.00 g, 12.3 mmol), and 4,4-diethoxybutan-
1-amine (1) (1.11 g, 6.87 mmol). Yield 0.77 g (21%). Mp 61-62°С. IR spectrum, , cm-1: 1333, 1558 (NO2), 1601
(Ar), 1668 (C=O), 2725, 2890, 2920, 3365 (N–H). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.13 (6Н,
br. t, J = 7.1, СН3); 1.52-1.64 (4Н, m, (СН2)2); 3.20-3.27 (2Н, m, СН2N); 3.40-3.51 (2Н, m) and 3.56-3.65 (2Н, m,
СН2O); 4.41-4.45 (1Н, m, СН); 6.07 (1Н, br. s, NН); 7.48 (2Н, br. d, J = 9.0, Н Ar); 8.03 (2Н, br. d, J = 8.9,
Н Ar); 8.62 (1Н, br. s, NН). Found, %: C 55.48; H 7.20; N 12.77. C15H23N3O5. Calculated, %: C 55.37; H 7.13;
N 12.91.
2-(2-Hydroxynaphth-1-yl)pyrrolidine-1-carboxamide (3a). A solution of compound 2а (0.50 g,
2.45 mmol) in anhydrous chloroform (10 ml) was treated with 2-naphthol (0.35 g, 2.45 mmol) and
trifluoroacetic acid (0.28 g, 2.45 mmol). The reaction mixture was stirred for 24 h at room temperature. The
precipitate that formed was filtered off, washed with chloroform, and dried under vacuum (4 h, 0.01 torr). Yield
0.39 g (62%). Mp 214-215°C. IR spectrum, , cm-1: 3459, 3335 (O–H), 3205, 3064, 2976, 2882 (N–H), 1608
(Ar), 1650 (C=O). 1H NMR spectrum (600 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.80-1.93 (1Н, m), 1.95-2.07 (2Н,
m) and 2.19-2.28 (1Н, m, (СН2)2); 3.52-3.60 (1Н, m) and 3.64-3.71 (1Н, m, NСН2); 5.11-5.28 (2Н, br. s, NH2);
5.51-5.56 (1Н, m, СНN); 7.08 (1Н, d, J = 8.8, Н Ar); 7.21-7.26 (1Н, m, Н Ar); 7.35-7.40 (1Н, m, Н Ar); 7.62
(1Н, d, J = 8.8, Н Ar); 7.72-7.76 (1Н, m, Н Ar); 7.93-7.97 (1Н, m, Н Ar). 13C NMR spectrum ((CD3)2SO), δ,
ppm: 25.8; 33.9; 48.1; 54.9; 119.4; 120.0; 123.1; 123.5; 126.9; 129.4; 129.6; 129.7; 132.8; 153.4; 158.1. Mass
spectrum (MALDI), m/z (Irel, %): 279 [M+Na]+ (100), 295 [M+K]+ (10). Found, %: C 70.27; H 6.28; N 10.93.
С15H16N2O2. Calculated, %: C 70.29; H 6.29; N 10.93.
2-(1-Hydroxynaphth-1-yl)-N-phenylpyrrolidine-1-carboxamide (3b) was obtained analogously to
compound 3а from compound 2b (0.50 g, 1.79 mmol), 2-naphthol (0.26 g, 1.70 mmol), and trifluoroacetic acid
(0.20 g, 1.79 mmol) in anhydrous chloroform (10 ml). Yield 0.46 g (78%). Mp 219-220°C. IR spectrum, , cm-1:
1
3388 (O–H), 3053, 2978, 2874 (N–H), 1618 (C=O), 1594 (Ar). H NMR spectrum (600 MHz, (CD3)2SO), δ,
ppm (J, Hz): 1.96-2.24 (3Н, m) and 2.30-2.39 (1Н, m, (СН2)2); 3.79-3.89 (2Н, m, NСН2); 5.78-5.84 (1Н, m,
CHN); 6.83-6.88 (1Н, m, Н Ar); 7.12-7.17 (2Н, m, Н Ar); 7.20 (1Н, d, J = 8.8, Н Ar); 7.25-7.29 (2Н, m, Н Ar);
7.29-7.34 (1Н, m, Н Ar); 7.45-7.50 (1Н, m, Н Ar); 7.71 (1Н, d, J = 8.8, Н Ar); 7.68-7.78 (1H, br. s, NH);
7.80-7.84 (1Н, m, Н Ar); 8.08-8.13 (1Н, m, Н Ar). 13C NMR spectrum ((CD3)2SO), δ, ppm: 26.0; 33.2; 48.3;
55.1; 119.4; 119.9; 122.2; 123.1; 123.4; 126.9; 129.2 (2С); 129.5 (2С); 129.7; 132.9; 141.3; 153.4; 154.4. Mass
spectrum, m/z (Irel, %): 355 [M+Na]+ (100), 370 [M+K]+ (24). Found, %: C 75.87; H 6.08; N 8.42. С21H20N2O2.
Calculated, %: C 75.88; H 6.06; N 8.43.
2-(2-Hydroxynaphth-1-yl)-N-(4-methoxyphenyl)pyrrolidine-1-carboxamide (3c) was obtained
analogously to compound 3а from compound 2с (0.30 g, 0.97 mmol), 2-naphthol (0.12 g, 0.97 mmol), and
trifluoroacetic acid (0.11 g, 0.97 mmol) in anhydrous chloroform (5 ml). Yield 0.17 g (47%). Mp 201-202°C. IR
1
spectrum, , cm-1: 3396 (O–H), 3051, 2976, 2870 (N–H), 1614 (C=O), 1587 (Ar). H NMR spectrum
(400 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.92-2.06 (1Н, m), 2.08-2.20 (2Н, m) and 2.27-2.37 (1Н, m, (СН2)2);
3.64 (3Н, s, ОСН3); 3.75-3.86 (2Н, m, NСН2); 5.72-5.79 (1Н, m, СНN); 6.68-6.73 (2Н, m, Н Ar); 7.10-7.14
(2Н, m, Н Ar); 7.16 (1Н, d, J = 8.4, Н Ar); 7.25-7.30 (1Н, m, Н Ar); 7.41-7.46 (1Н, m, Н Ar); 7.50-7.55 (1Н,
br. s, NH); 7.67 (1Н, d, J = 8.4, Н Ar); 7.76-7.80 (1Н, m, Н Ar); 8.04-8.09 (1Н, m, Н Ar). Mass spectrum, m/z
(Irel, %): 362 [M]+ (10), 385 [M+Na]+ (100), 401 [M+K]+ (5). Found, %: C 72.90; H 6.10; N 7.72. С22H22N2O3.
Calculated, %: C 72.91; H 6.12; N 7.73.
711

N-(4-Bromophenyl)-2-(2-hydroxynaphth-1-yl)pyrrolidine-1-carboxamide
(3d)
was
obtained
analogously to compound 3а from compound 2d (0.10 g, 0.28 mmol), 2-naphthol (0.04 g, 0.28 mmol), and
trifluoroacetic acid (0.03 g, 0.28 mmol) in anhydrous chloroform (5 ml). Yield 0.07 g (62%). Mp 183-184°C. IR
spectrum, , cm-1: 3378 (O–H), 3052, 2980, 2873 (N–H), 1629 (C=O), 1587 (Ar). H NMR spectrum (600
1
MHz, (CD3)2SO), δ, ppm (J, Hz): 1.95-2.05 (1Н, m), 2.06-2.17 (2Н, m) and 2.26-2.35 (1Н, m, (СН2)2);
3.74-3.85 (2Н, m, NСН2); 5.74-5.80 (1Н, m, СН); 7.14 (1Н, d, J = 8.8, Н Ar); 7.25-7.30 (5Н, m, Н Ar);
7.41-7.46 (1Н, m, Н Ar); 7.65 (1Н, d, J = 8.8, Н Ar); 7.76-7.80 (1Н, m, Н Ar); 7.93-8.00 (1Н, br. s, NН);
8.04-8.09 (1Н, m, Н Ar). 13C NMR spectrum ((CD3)2SO), δ, ppm: 26.1; 33.0; 48.4; 55.3; 113.5; 119.5; 120.1;
121.3; 123.1; 123.4; 126.8; 129.2; 129.4; 129.6; 131.9; 133.0; 140.9; 153.2; 154.2. Mass spectrum, m/z (Irel, %):
434 [M+Na]+ (100), 449 [M+K]+ (21). Found, %: C 61.32; H 4.67; Br 19.41; N 6.80. С21H19BrN2O2.
Calculated, %: C 61.33; H 4.66; Br 19.43; N 6.81.
2-(2-Hydroxynaphth-1-yl)-N-(4-nitrophenyl)pyrrolidine-1-carboxamide (3e) was obtained analogously
to compound 3а from compound 2e (0.10 g, 0.31 mmol), 2-naphthol (0.04 g, 0.31 mmol), and trifluoroacetic
acid (0.04 g, 0.31 mmol) in anhydrous chloroform (5 ml). Yield 0.03 g (28%). Mp 185-186°C. IR spectrum, ,
1
cm-1: 3360 (O–H), 3211, 3050, 2973, 2880 (N–H), 1644 (C=O), 1541, 1340 (NO2). H NMR spectrum
(600 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.96-2.07 (1Н, m), 2.07-2.19 (2Н, m) and 2.28-2.37 (1Н, m, СН2);
3.77-3.91 (2Н, m, NСН2); 5.78-5.83 (1Н, m, СНN); 7.12 (1Н, d, J = 8.8, Н Ar); 7.25-7.30 (1Н, m, Н Ar);
7.41-7.46 (1Н, m, Н Ar); 7.58-7.63 (2Н, m, Н Ar); 7.64 (1Н, d, J = 8.8, Н Ar); 7.75-7.79 (1Н, m, Н Ar);
13
8.02-8.09 (3Н, m, Н Ar); 8.64-8.80 (1Н, br. s, NH). C NMR spectrum ((CD3)2SO), δ, ppm: 25.7; 32.4; 48.1;
55.3; 118.1; 119.1; 119.7; 122.6; 122.9; 125.1; 126.4; 128.7; 128.9; 129.1; 132.6; 140.9; 147.9; 152.8; 153.0.
Mass spectrum (MALDI), m/z (Irel, %): 400 [M+Na]+ (100). Found, %: C 66.80; H 5.10; N 11.09. C21H19N3O4.
Calculated, %: C 66.83; H 5.07; N 11.13.
1,1'-Hexane-1,6-diylbis[3-(4,4-diethoxybutyl)urea] (4a). Compound 1 (3.60 g, 22.4 mmol) was added
dropwise with cooling (5-8С) to a solution of 1,6-diisocyanatohexane (1.88 g, 11.2 mmol) in benzene (20 ml).
The reaction mixture was stirred for 72 h at room temperature. The precipitate was filtered off. The white
precipitate was dried under vacuum (3 h, 0.01 torr). Yield 4.79 g (88%). Mp 138-139°С. IR spectrum, , cm-1:
3325, 2983, 2874 (N–H), 1619 (C=O). 1H NMR spectrum (400 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.12 (12Н, br.
t, J = 6.8, 4СН3); 1.20-1.29 (4Н, m, 2СН2); 1.34-1.42 (4Н, m, 2СН2); 1.44-1.52 (4Н, m, 2СН2); 1.53-1.62 (4Н,
m, 2СН2); 3.01-3.16 (8Н, m, 4СН2N); 3.37-3.48 (4Н, m, 2СН2O); 3.52-3.63 (4Н, m, 2СН2O); 4.37-4.44 (2Н,
m, 2СН). Found, %: C 59.00; H 10.02; N 11.11. C24H50N4O6. Calculated, %: C 58.75; H 10.27; N 11.42.
1,1'-Phenylene-1,4-diylbis[3-(4,4-diethoxybutyl)urea] (4b). 1,4-Diisocyanatophenylеne (0.89 g,
5.59 mmol) was added to a solution of compound 1 (1.80 g, 11.2 mmol) in toluene (30 ml). The mixture was
stirred for 96 h. The precipitate was filtered off. The white precipitate was dried under vacuum (3 h, 0.01 torr).
Yield 2.44 g (91%). Mp 189-190°С. IR spectrum, , cm-1: 3331, 2969, 2870 (N–H), 1629 (C=O), 1565 (Ar).
1H NMR spectrum (400 MHz, (CD3)2SO), δ, ppm (J, Hz): 1.11 (12Н, br. t, J = 7.0, 4СН3); 1.39-1.48 (4Н, m, 2СН2);
1.49-1.56 (4Н, m, 2СН2); 3.02-3.10 (4Н, m, 2СН2N); 3.39-3.48 (4Н, m, 2СН2O); 3.52-3.61 (4Н, m, 2СН2O);
4.47 (2Н, t, J = 5.47, 2СН); 7.21 (4Н, br. s, Н Ar). Found, %: C 60.01; H 8.96; N 11.84. C24H42N4O6.
Calculated, %: C 59.73; H 8.77; N 11.61.
N,N'-Hexane-1,6-diylbis[2-(2-hydroxynaphth-1-yl)pyrrolidine-1-carboxamide] (5a). A solution of
compound 4a (0.50 g, 1.02 mmol) in anhydrous chloroform (10 ml) was treated with 2-naphthol (0.29 g,
2.04 mmol) and trifluoroacetic acid (0.24 g, 1.02 mmol). The reaction mixture was stirred for 24 h at room
temperature. The precipitate that formed was filtered off and dried under vacuum (4 h, 0.01 torr). Yield 0.57 g
(94%). Mp 189-190°C. IR spectrum, , cm-1: 3417 (O–H), 3056, 2934, 2872 (N–H), 1609 (C=O), 1590, 1563
1
(Ar). H NMR spectrum (400 MHz, (CD3)2SO), δ, ppm (J, Hz): 0.60-0.65 (4Н, br. m, 2СН2); 0.88-0.95 (4Н,
br. m, 2СН2); 1.85-1.95 (2Н, m), 2.01-2.12 (4Н, m) and 2.21-2.30 (2Н, m, 4СН2); 2.64-2.72 (2Н, m) and 2.74-
2.82 (2Н, m, 2СН2); 3.56-3.64 (2Н, m) and 3.68-3.75 (2Н, m, 2СН2); 5.08-5.15 (2Н, br. s, 2NH); 5.54-5.60
(2Н, m, 2СНN); 7.09 (2Н, d, J= 8.8, Н Ar); 7.21-7.26 (2Н, m, Н Ar); 7.37-7.41 (2Н, m, Н Ar); 7.61 (2Н, d, J=8.8,
712

Н Ar); 7.71-7.75 (2Н, m, Н Ar); 7.96-8.00 (2Н, m, Н Ar). Mass spectrum, m/z (Irel, %): 617 [M+Na]+ (100).
Found, %: C 72.21; H 7.12; N 9.40. С36H42N4O4. Calculated, %: C 72.20; H 7.12; N 9.42.
N,N'-Phenylene-1,4-diylbis[2-(2-hydroxynaphth-1-yl)pyrrolidine-1-carboxamide] (5b) was obtained
analogously to compound 5a from compound 4b (0.50 g, 1.04 mmol), 2-naphthol (0.30 g, 2.07 mmol), and
trifluoroacetic acid (0.24 g, 2.07 mmol). Yield 0.55 g (90%). Mp 218-219°C. IR spectrum, , cm-1: 3390 (O–H),
1
3058, 2973, 2875 (N–H), 1620 (C=O), 1598 (Ar). H NMR spectrum (400 MHz, (CD3)2SO), δ, ppm (J, Hz):
1.84-1.96 (2Н, m), 2.00-2.11 (4Н, m), and 2.18-2.27 (2Н, m, 4СН2); 3.66-3.73 (4Н, m, 2СН2); 5.63-5.69 (2Н,
m, 2СНN); 6.92-6.96 (4H, br. s, Н Ar); 7.07 (2Н, d, J= 8.8, Н Ar); 7.19-7.24 (2Н, m, Н Ar); 7.34-7.39 (2Н, m,
Н Ar); 7.44-7.54 (2H, br. s, 2NH); 7.60 (2Н, d, J = 8.8, Н Ar); 7.70-7.74 (2Н, m, Н Ar); 7.95-8.00 (2Н, m, Н Ar).
Mass spectrum, m/z (Irel, %): 587 [M+H]+ (11), 609 [M+Na]+ (100), 625 [M+K]+ (6). Found, %: C 73.68;
H 5.83; N 9.53. C36H34N4O4. Calculated, %: C 73.70; H 5.84; N 9.55.
The work was performed with financial support from the Russian Foundation for Basic Research
(projects 14-03-00191-а and 14-03-31740 mol_a)
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