Acid-catalyzed ring opening in 2-(2-hydroxynaphthalene-1-yl)-pyrrolidine-1-carboxamides: Formation of dibenzoxanthenes, diarylmethanes, and calixarenes

Article abstract of DOI:10.1016/j.tet.2014.12.011

2-(2-Hydroxynaphthalene-1-yl)pyrrolidine-1-carboxamides undergo ring opening in the presence of trifluoroacetic acid and 2-naphthol leading to the formation of new substituted dibenzoxanthenes. Reaction of 2-(2-hydroxynaphthalene-1-yl)pyrrolidine-1-carboxamides with polyatomic phenols at the same conditions was found leading to diarylmethane derivatives and calix[4]resorcinols with naphthyl fragment acting as a leaving group.

Full text of DOI:10.1016/j.tet.2014.12.011

Tetrahedron 71 (2015) 445e450
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Acid-catalyzed ring opening in 2-(2-hydroxynaphthalene-1-yl)-
pyrrolidine-1-carboxamides: formation of dibenzoxanthenes,
diarylmethanes, and calixarenes
*
A.S. Gazizov , A.V. Smolobochkin, J.K. Voronina, A.R. Burilov, N.A. Pudovik
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzova Str., Kazan,
Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2014
Received in revised form 18 November 2014
Accepted 1 December 2014
Available online 6 December 2014
2-(2-Hydroxynaphthalene-1-yl)pyrrolidine-1-carboxamides undergo ring opening in the presence of
trifluoroacetic acid and 2-naphthol leading to the formation of new substituted dibenzoxanthenes. Re-
action of 2-(2-hydroxynaphthalene-1-yl)pyrrolidine-1-carboxamides with polyatomic phenols at the
same conditions was found leading to diarylmethane derivatives and calix[4]resorcinols with naphthyl
fragment acting as a leaving group.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Pyrrolidine
Ring opening
Xanthene
Diarylmethane
Calixarene
1. Introduction
and involves aromatic,13e16 heteroaromatic,17e20 and aliphatic
aldehydes.15,16
Xanthene and, in particular, benzoxanthene derivatives are of
considerable interest for synthetic chemists due to their anti-
bacterial,1e3 antiviral,4 and anti-inflammatory5 properties. In ad-
dition, these compounds can be used as dyes,6,7 active laser
media,8e10 as well as rO-sensitive fluorescent probes for the study
of biological objects.11,12 A broad series of benzoxanthene de-
rivatives containing various aryl,13e16 hetaryl,17e20 and alkyl sub-
stituents15,16 in pyran ring have been synthesized. However, despite
intensive studies in this field, only small number of publications are
devoted to the synthesis of alkyl-substituted benzoxanthenes with
functional groups in the alkyl chain. In particular, the synthesis of
sulfur21 and selenium-containing benzoxanthenes21,22 and ben-
zoxanthenes having hydroxyl,23 carboxylic groups,24,25 as well as
multiple bonds26,27 in alkyl substituent, have been described. In
addition, there are a series of works of French authors,28e30 which
describe the synthesis of benzoxanthenes having methyl and eth-
ylaminoalkyl substituents.
2. Results
Recently, we have studied the reaction of 2-naphthol with (4,4-
diethoxyethylbutyl)urea derivatives and it was shown that the
products of this reaction are heterocyclic compounds, namely, 2-
arylpyrrolidine derivatives 2. We did not notice the formation of
corresponding benzoxanthenes, even upon the use of an excess of
2-naphthol31 (Scheme 1).
The principal method for the synthesis of benzoxanthenes is
acid-catalyzed reaction of naphthols with aldehydes and
acetals.13e20 The range of reacting carbonyl compounds is broad
* Corresponding author. Tel./fax: þ7 843 272 7324; e-mail address: agazizov@
iopc.ru (A.S. Gazizov).
Scheme 1. Reaction of 2-naphthol with (4,4-diethoxyethylbutyl)urea derivatives.
http://dx.doi.org/10.1016/j.tet.2014.12.011
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

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A.S. Gazizov et al. / Tetrahedron 71 (2015) 445e450
A literature survey revealed only one work,32 where the pyrroli-
dine ring opening is described in N-phenacyl-2-phenylpyrrolidine
under the action of trifluoromethanesulfonicacid. Based on these
data, we suggested that the pyrrolidine ring in compounds 2 can also
open under the action of strong acids.
We
chose
2-(2-hydroxynaphthalene-1-yl)-pyrrolidine-1-
carboxamide 2a as a model compound.31 The study of the re-
action of compound 2a with 2-naphthol in chloroform with tri-
fluoroacetic acid showed that pyrrolidine ring opening proceeds
under these conditions with the formation of dibenzoxanthene 3a,
which contains a urea fragment. Optimization of the reaction
conditions showed that the highest yield of the target dibenzox-
anthene is achieved upon use of 3 equiv of naphthol and 3 equiv of
trifluoroacetic acid (Scheme 2).
Scheme 3. Synthesis of starting 2-(2-hydroxynaphthalene-1-yl)-pyrrolidine-1-
carboxamides 2c,d.
carboxamide 2, followed by NeC bond cleavage. Carbocation A
thus formed then reacts with naphthol molecule to give (4,4-bis(2-
hydroxynaphthalen-1-yl)butyl)urea derivative B. Finally, elimina-
tion of water molecule from this intermediate compound leads to
the formation of dibenzoxanthene3. It should be noted that in
previously published work, a 10-fold excess of triflic acid was
needed to open the pyrrolidine ring in N-phenacyl-2-
Scheme 2. Synthesis of dibenzoxanthenes 3 and bis(dibenzoxanthenes) 5.
Subsequent studies revealed that the reactions of 2-naphthol
with pyrrolidine-1-carboxamides 2bed having aryl, alkyl, and
cycloalkyl substituents in urea fragment proceed similarly (Scheme
2). Starting compounds 2c,d were synthesized in accordance with
Scheme 3; the synthesis of compound 2b was described else-
where.31 It should be noted that the highest yields were achieved in
the case of pyrrolidine-1-carboxamides 2b,d having phenyl and
cyclohexyl substituents, respectively. The reactions of compounds
4a,b31 containing two pyrrolidine fragments with 6 equiv of 2-
naphthol under identical conditions also gave bis(dibenzox-
anthenes) 5a,b (Scheme 2).
Scheme 4 illustrates proposed mechanism of this reaction,
which includes protonation of urea fragment in pyrrolidine-1-
Scheme 4. Proposed mechanism for the formation of dibenzoxanthenes.

A.S. Gazizov et al. / Tetrahedron 71 (2015) 445e450
447
phenylpyrrolidines.32 However, in our case, trifluoroacetic acid
taken at only three-fold excess was enough. This may be attributed
to higher basicity of ureas compared to acid amides,33 which fa-
cilitates the initial protonation of urea. Also 2-hydroxynaphtyl
group stabilizes intermediate carbocation A more effectively than
less electron-rich phenyl group and thus, favors ring-opening.
The possibility of using other phenols in this reaction and thus,
preparation of unsymmetrical benzoxanthenes was also of interest
for us. For this purpose, we studied the reaction of pyrrolidine-1-
carboxamide 2b with 4-bromoresorcinol. The reaction of com-
pound 2b with 1 equiv of 4-bromoresorcinol gave a complex
mixture of products and we did not succeed in isolating any in-
dividual compound. Performing the reaction with a three-fold ex-
cess of 4-bromoresorcinol gave unexpectedly the polyphenol 6a,
which contains two resorcinol fragments, in 28% yield (Scheme 5).
Further studies showed that the interaction of 2,6-dimethylphenol
with pyrrolidine-1-carboxamide 2b also leads to the formation of
polyphenolic compound 6b.
Scheme 6. Synthesis of calixarenes 7.
The structure of compound 7b was also confirmed by X-ray
analysis data (Fig. 1). Analyzed crystals of compound 7b are the
crystalline solvates with DMSO and water in a ratio of 1.5:1. X-ray
structure analysis revealed that the calixarene is in the cone con-
formation, bond lengths, and angles in the molecule of compound
7b in crystals are within the standard limits for each type of
chemical bond. The molecular packing in this crystal is formed by
the classic OeH/O and NeH/O hydrogen bonds both between
calixarene molecules and with the participation of solvent
molecules.
Scheme 5. Reaction of pyrrolidine-1-carboxamide 2b with phenols.
Analysis of the literature revealed that the carbonecarbon bond
cleavage in (2-hydroxynaphtyl)methane derivatives in acidic media
is known.34e36 Thus, this reaction turned out to be unsuitable for
the synthesis of unsymmetrical benzoxanthenes.
Fig. 1. X-ray structure of calixarene 7.
3. Conclusion
It should be noted that the most common way of synthesis of
dimeric polyphenols,37,38 as well as calix[4]resorcinols,39,40 is the
reaction of appropriately substituted acetals or aldehydes with
phenols in acidic media. However, this method cannot be used in
the case of acetals containing urea fragment, since they undergo
intramolecular cyclization in these conditions, giving rise to het-
erocyclic compounds.41e43 Thus, we decided to further investigate
this reaction and check its applicability to the synthesis of calix[4]
resorcinols containing urea substituent.
We have developed a new method for the synthesis of diben-
zoxanthenes modified with urea fragments, which is based on the
acid-catalyzed opening of the pyrrolidine ring in pyrrolidine-1-
carboxamides in the presence of naphthol. In addition, a new re-
action of 2-(2-hydroxynaphthalene-1-yl)pyrrolidine-1-carbox-
amides with polyatomic phenols, which leads to the formation of
linear and macrocyclic polyphenols, where naphthyl fragment acts
as a leaving group, was discovered.
The reaction of pyrrolidine-1-carboxamide 2b with a three-fold
excess of resorcinol and 2-methylresorcinol in chloroform gave
a mixture of products. The analysis of the reaction mass via mass-
spectrometry showed that there are both dimer compounds and
macrocyclic polyphenols, calix[4]resorcinols. Carrying out the re-
action of compound 2b with these phenols taken at an equimolar
amount allowed us obtaining macrocycles 7a,b as the main product
in 87 and 74% yield correspondingly (Scheme 6). Reaction of pyr-
rolidine-1-carboxamide 2a with resorcinol and 2-methylresorcinol
proceeds similarly and leads to the formation of macrocycles 7c,d,
although the yields are lower in this case. Interestingly, there is
signals of acetone in the NMR spectra of compound 7c (approx.
0.5 mol per 1 mol of calixarene) even after prolonged heating in
vacuum; probably, this is due to hosteguest complex formation.
4. Experimental
4.1. General
1H NMR spectra were recorded on Bruker MSL 400 spectrometer
(working frequency 400.13 MHz) in (CD3)2SO relative to the re-
sidual solvent protons. 13C NMR spectra were recorded on Bruker
Avance 600 spectrometer (working frequency 150.90 MHz). The
MALDI-TOF mass spectra were recorded on a Bruker ULTRAFLEX III
TOF/TOF instrument (with 2,5-dihydroxybenzoic acid matrix). IR
spectra were obtained with a Bruker Vector 22 spectrometer. Ele-
mental analysis was performed on Carlo Erba EA 1108 instrument.

448
A.S. Gazizov et al. / Tetrahedron 71 (2015) 445e450
Melting points were determined in glass capillaries with a Stuart
SMP 10 apparatus. Single-crystal X-ray diffraction analysis was
performed at 295(2) K on Smart Apex II automatic diffractometer
using graphite monochromated radiation. All solvents were puri-
fied and dried according to standard procedures.
((CD3)2SO, 150 MHz), d (ppm): 24.9, 25.7, 26.5, 30.3, 33.7, 33.9, 39.8,
48.0, 117.0, 117.6, 123.6, 124.9, 127.3, 128.9, 129.1, 131.1, 131.5, 149.8,
157.5. IR (KBr): 1593, 1635, 2853, 2935, 3069 cmꢁ1. Anal. Calcd (%)
for S31H32N2O2: C, 80.14; H, 6.94; N, 6.03. Found: C, 79.92; H, 6.84;
N, 6.30. MALDI TOF, m/z: 487 [MþNa]þ.
4.2. Synthesis of xanthenes 3
4.3. Synthesis of bis-xanthenes 5
To a solution of 2-napthol (0.17 g, 1.17 mmol) in 10 ml of dry
chloroform pyrrolidine-1-carboxamide 2 (0.39 mmol) and tri-
fluoroacetic acid (0.13 g, 1.17 mmol) was added. The mixture was
stirred at room temperature for 72 h. Solvent was evaporated in
vacuo, residue was washed with diethyl ether, filtered, and dried in
vacuo (1 h, 0.01 Torr) to give the title compound 3.
To a solution of 2-napthol (0.15 g, 1.04 mmol) in 10 ml of dry
chloroform bis-pyrrolidine-1-carboxamide 4 (0.17 mmol) and tri-
fluoroacetic acid (0.12 g, 1.05 mmol) was added. The mixture was
stirred at room temperature for 72 h. Solvent was evaporated in
vacuo. Residue was washed with diethyl ether, filtered, and dried in
vacuo (1 h, 0.01 Torr) to give the title compound 5.
4.2.1. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl)urea (3a). White
solid. Yield 0.079 g (53%). Mp: 177e178 ꢀC. 1O NMR ((CD3)2SO,
4.3.1. 1,10-(Hexane-1,6-diyl)bis(3-(3-(14H-dibenzo[a,j]xanthen-14-yl)
propyl)urea) (5a). White solid. Yield 0.10 g (76%). Mp: 245e246 ꢀC.
400 MHz),
d
(ppm): 0.94e1.04 (2O, m, SO2), 1.85e1.94 (2O, m,
1O NMR ((CD3)2SO, 400 MHz),
d (ppm): 0.91e1.00 (4O, m, SO2),
SO2), 2.59e2.68 (2O, m, SO2), 5.69e5.75 (1O, m, CH), 7.44 (2O, d, J
8.9 Hz, COAr), 7.48e7.54 (2O, m, COAr), 7.65e7.71 (2O, m, COAr),
7.90 (2O, d, J 8.9 Hz, COAr), 7.94e7.99 (2O, m, COAr), 8.52e8.57 (2O,
1.02e1.09 (4O, m, SO2), 1.10e1.22 (4O, m, SO2), 1.83e1.93 (4O, m,
SO2), 2.58e2.67 (4O, m, SO2), 2.73e2.82 (4O, m, SO2), 5.45 (4O,
br s, NH), 5.67e5.73 (2O, m, CH), 7.42 (4O, d, J 8.8 Hz, COAr),
7.46e7.52 (4O, m, COAr), 7.62e7.70 (4O, m, COAr), 7.89 (4O, d, J
m, COAr). 13C NMR ((CD3)2SO, 150 MHz),
d (ppm): 26.3, 30.3, 33.9,
39.8, 117.0, 117.6, 123.5, 124.9, 127.4, 128.9, 129.1, 131.1, 131.5, 149.9,
158.8. IR (KBr): 1592, 1651, 2937, 3066, 3329 cmꢁ1. Anal. Calcd (%)
for S25H22N2O2: C, 78.51; H, 5.80; N, 7.32. Found: C, 78.82; H, 5.97;
N, 7.04. MALDI TOF, m/z: 405 [MþNa]þ.
8.8 Hz, COAr), 7.93e7.98 (4O, m, COAr), 8.49e8.56 (4O, m, COAr). 13
C
NMR ((CD3)2SO, 150 MHz),
d (ppm): 26.5, 26.5, 30.32, 33.9, 39.8,
117.0, 117.6, 123.5, 124.8, 127.3, 128.9, 129.1, 131.1, 131.5, 149.8, 158.2.
IR (KBr): 1593, 1624, 2845, 2928 cmꢁ1. Anal. Calcd (%) for
S56H54N4O4: C, 79.40; H, 6.43; N, 6.61. Found: C, 79.22; H, 6.67; N,
6.79. MALDI TOF, m/z: 870 [MþNa]þ.
4.2.2. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl)-3-phenylurea
(3b). White solid. Yield 0.14 g (78%). Mp: 240e241 ꢀC. 1O NMR
((CD3)2SO, 400 MHz),
d
(ppm): 1.00e1.11 (2O, m, SO2), 1.89e1.99
4.3.2. 1,10-(1,4-Phenylene)bis(3-(3-(14H-dibenzo[a,j]xanthen-14-yl)
(2O, m, SO2), 2.71e2.79 (2O, m, SO2), 5.72e5.77 (1O, m, CH),
5.81e8.84 (1O, m, NH), 6.82 (1O, t, J 7.1 Hz, COAr), 7.13 (2O, t, J
8.2 Hz, COAr), 7.23 (2O, d, J 7.8 Hz, COAr), 7.44 (2O, d, J 8.9 Hz, COAr),
7.49e7.54 (2O, m, COAr), 7.65e7.71 (2O, m, COAr), 7.91 (2O, d, J
8.9 Hz, COAr), 7.96e8.00 (2O, m, COAr), 8.15 (1O, br s, NH),
propyl)urea) (5b). White solid. Yield 0.11 g (77%). Mp: >250 ꢀC. 1O
NMR ((CD3)2SO, 400 MHz),
d (ppm): 0.99e1.09 (4O, m, SO2),
1.87e1.97 (4O, m, SO2), 2.66e2.76 (4O, m, SO2), 5.66e5.71 (2O, m,
CH), 5.71e5.76 (2O, m, NH), 6.99 (4O, s, COAr), 7.44 (4O, d, J 8.9 Hz,
COAr), 7.47e7.53 (4O, m, COAr), 7.64e7.70 (4O, m, COAr), 7.90 (4O,
d, J 8.9 Hz, COAr), 7.94e7.99 (4O, d, J 8.02 Hz, COAr), 8.53e8.58 (4O,
8.54e8.59 (2O, m, COAr). 13C NMR ((CD3)2SO, 150 MHz),
d (ppm):
26.3, 30.3, 33.9, 39.5, 117.0, 117.6, 118.0, 121.3, 123.6, 124.9, 127.4,
129.0, 129.1, 131.1, 131.5, 140.9, 149.9, 155.3. IR (KBr): 1592, 1650,
2937, 3065, 3328 cmꢁ1. Anal. Calcd (%) for S31H26N2O2: C, 81.20; H,
5.72; N, 6.11. Found: C, 81.46; H, 5.58; N, 5.93. MALDI TOF, m/z: 481
[MþNa]þ.
d, J 8.96 Hz, COAr). 13C NMR ((CD3)2SO, 150 MHz),
d (ppm): 26.3,
30.3, 33.9, 39.8, 117.0, 117.6, 118.8, 123.5, 124.9, 127.4, 128.9, 129.1,
131.1, 131.5, 149.9, 155.5. IR (KBr): 1592, 1652, 2857, 2937,
3065 cmꢁ1. Anal. Calcd (%) for S56H46N4O4: C, 80.17; H, 5.53; N,
6.68. Found: C 79.93; H 5.73; N 6.57. MALDI TOF, m/z: 861 [MþNa]þ.
4.2.3. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl)-3-hexylurea
4.4. Synthesis of dimers 6
(3c). White solid. Yield 0.09 g (53%). Mp: 183e184 ꢀC. 1O NMR
((CD3)2SO, 400 MHz),
d
(ppm): 0.83 (3O, t, J 7.04 Hz, SO3),
To a mixture of 2-(2-hydroxynaphthalen-1-yl)-N-phenyl-
0.91e1.02 (2O, m, SO2), 1.08e1.27 (8O, m, SO2), 1.84e1.93 (2O, m,
SO2), 2.59e2.67 (2O, m, SO2), 2.76e2.83 (2O, m, SO2), 5.42e5.51
(2O, m, NH), 5.69e5.74 (1O, m, SO),7.43 (2O, d, J 8.9 Hz, SOAr),
7.47e7.54 (2O, m, SOAr), 7.64e7.70 (2O, m, SOAr), 7.91 (2O, d, J
8.9 Hz, SOAr), 7.94e7.99 (2O, m, SOAr), 8.51e8.56 (2O, m, SOAr).
pyrrolidine-1-carboxamide 2b (0.1 g, 0.30 mmol) in dry chloroform
(10 ml) appropriate phenol (0.90 mmol) and trifluoroacetic acid
(0.1 g, 0.30 mmol) was added. The mixture was stirred at room
temperature for 72 h. Solvent was evaporated in vacuo. Residue was
washed with diethyl ether, filtered, and dried in vacuo (1 h,
0.01 Torr) to give the title compound 6.
13C NMR ((CD3)2SO, 150 MHz),
d (ppm): 14.3, 15.6, 22.5, 26.4, 26.5,
26.5, 30.3, 31.4, 33.9, 39.4, 117.0, 117.6, 123.5, 124.8, 127.3, 128.9,
129.1, 131.1, 131.5, 149.8, 158.2. IR (KBr): 1592, 1625, 2857, 2927,
3069, 3417 cmꢁ1. Anal. Calcd (%) for S31H34N2O2: S, 79.79; O, 7.34;
N, 6.00. Found: S, 79.88; O, 7.12; N, 6.26. MALDI TOF, m/z: 489
[MþNa]þ.
4.4.1. 1-(4,4-Bis(5-bromo-2,4-dihydroxyphenyl)butyl)-3-phenylurea
(6a). White solid. Yield0.05 g (28%). Mp: 132e133 ꢀC. 1O NMR
((CD3)2SO, 400 MHz),
d (ppm): 1.27e1.37 (2O, m, SO2), 1.77e1.86
(2O, m, SO2), 3.02e3.10 (2O, m, SO2), 4.25 (1O, t, J 7.9 Hz, COAr),
6.08 (1O, t, J 5.8 Hz, NH), 6.45 (2O, s, COAr), 6.84e6.89 (1O, m,
COAr), 7.03 (2O, s, COAr), 7.16e7.22 (2O, m, COAr), 7.33e7.38 (2O, m,
4.2.4. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl)-3-
cyclohexylurea (3d). White solid. Yield 0.15
g
(83%). Mp:
COAr). IR (KBr): 1597, 1652, 2868, 2937, 3402 cmꢁ1 13C NMR
.
246e247 ꢀC. 1O NMR ((CD3)2SO, 400 MHz),
d
(ppm): 0.84e1.00 (4O,
((CD3)2SO, 150 MHz), d (ppm): 29.0, 31.5, 36.1, 65.4, 98.2, 104.0,
m, SO2), 1.02e1.22 (3O, m, SO2), 1.41e1.49 (1O, m, SO2), 1.50e1.61
(4O, m, SO2), 1.85e1.93 (2O, m, SO2), 2.59e2.67 (2O, m, SO2),
3.10e3.21 (1O, m, SO2), 5.35e5.39 (1O, m, SO), 5.39 (1O, br s, NH),
5.69e5.74 (1O, m, SO), 7.43 (2O, d, J 8.8 Hz, COAr), 7.49e7.54 (2O,
m, COAr), 7.65e7.70 (2O, m, COAr), 7.91 (2O, d, J 8.8 Hz, COAr),
7.95e8.00 (2O, m, COAr), 8.52e8.56 (2O, m, COAr). 13C NMR
118.1, 121.3, 124.4, 129.0, 131.7, 141.0, 152.7, 155.5, 155.6. Anal. Calcd
(%) for S23H22Br2N2O5: C, 48.79; H, 3.92; Br, 28.22; N, 4.95. Found:
C, 48.54; H, 3.71; Br, 28.39; N, 5.12. MALDI TOF, m/z: 589 [MþNa]þ.
4.4.2. 1-(3,3-Bis(4-hydroxy-3,5-dimethylphenyl)propyl)-3-
phenylurea (6b). White solid. Yield 0.08 g (62%). Mp: 181e182 ꢀC.

A.S. Gazizov et al. / Tetrahedron 71 (2015) 445e450
449
1O NMR ((CD3)2CO, 400 MHz),
d
(ppm): 1.42e1.50 (2O, m, SO2),
112.1, 121.6, 125.1, 149.5, 159.3. IR (KBr): 1596, 1654, 2862, 2931,
3064, 3381 cmꢁ1. Anal. Calcd (%) for S48H64N8O12: C 61.00; H 6.83;
N 11.86. Found: C 61.19; H 7.02; N 11.97. MALDI TOF, m/z: 968
[MþNa]þ.
1.96e2.04 (2O, m, SO2), 2.19 (12O, s, SO3), 2.21e2.27 (2O, m,
SO2), 3.66 (1H, t, J 7.9 Hz, CH), 5.80e5.87 (1H, br s, NH), 6.07 (4O, s,
COAr), 6.88e6.93 (1O, m, COAr), 6.96e6.99 (1H, br s, NH), 7.17e7.23
(2O, m, COAr), 7.45e7.49 (2O, m, COAr). 13C NMR ((CD3)2CO,
150 MHz),
d (ppm): 15.9, 39.6, 49.5, 65.2, 118.3, 121.4, 123.5, 127.6,
4.6. X-ray diffraction study of calixarene 7b
128.5, 137.0, 140.7, 151.2, 155.5. IR (KBr): 1596, 1644, 1686, 2862,
2936, 3011, 3319, 3565. Anal. Calcd (%) for C27H32N2O3: C, 74.97; H,
7.46; N, 6.48. Found: C, 74.80; H, 7.52; N, 6.33. MALDI TOF, m/z: 432
[M]þ; 455 [MþNa]þ; 471 [MþL]þ.
The X-ray diffraction data for the crystals of 7 were collected on
a Smart Apex II automatic diffractometer using graphite mono-
chromated radiation. The structures were solved by direct methods
and refined by full-matrix least-squares using the SHELXL9744
program. All figures were made using programs PLATON45 and
MERCURY.46 Crystallographic data (excluding structure factors) for
the structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary publi-
cation number CCDC 1013421. For compound C82H82N8O18S5:
4.5. Synthesis of calixarenes 7
To
a mixture of 2-(2-hydroxynaphthalen-1-yl)-N-phenyl-
pyrrolidine-1-carboxamide 2b (0.1 g, 0.30 mmol) and appropriate
phenol (0.30 mmol) in dry chloroform (5 ml) trifluoroacetic acid
(0.45 g, 3.92 mmol) was added. The mixture was stirred at room
temperature for 72 h. Solvent was evaporated in vacuo. Residue was
washed with diethyl ether and acetone, filtered, and dried in vacuo
(1 h, 0.01 Torr) to give the title compound 7.
M¼1627.86, triclinic, space group P-1, a¼13.846(11), b¼18.260(14),
ꢀ
c¼20.513(15) A,
a
¼70.141(10),
b
¼71.080(10),
g
¼68.412(10)ꢀ;
V¼4416(6) A ; Z¼2; rcalc¼1.224 g cmꢁ3
,
m
(Mo-Ka)¼0.71073 mmꢁ1
,
3
ꢀ
F(000)¼1708, 2qmax¼52ꢀ, 17,173 reflections collected, 7640 ob-
served (I>2s(I)) reflections, 1165 refined parameters, R1 value
4.5.1. 1,10,100,1000-((14,16,34,36,54,56,74,76-Octahydroxy-1,3,5,7(1,3)-tet-
rabenzenacyclooctaphane-2,4,6,8-tetrayl)tetrakis(propane-3,1-diyl))
tetrakis(3-phenylurea) (7a). White solid. Yield 0.08 g (87%). Mp:
0.0851, wR2¼0.1722 (all data R¼0.1722, wR2¼0.3221), S¼1.045,
minimum and maximum transmissions 0.013 and 0.013, re-
spectively, maximum and minimum residual electron densities
>250 ꢀC. 1O NMR (CD3OH, 400 MHz),
d (ppm): 1.42e1.52 (8O, m,
3
ꢀ
þ0.864 and ꢁ0.366 e A .
SO2), 2.24e2.33 (8O, m, SO2), 3.18e3.26 (8O, m, SO2), 4.32 (4O, t,
J 7.3 Hz, CO), 6.23 (4O, s, COAr), 6.88e6.96 (4O, m, COAr), 7.16e7.24
(8O, m, COAr), 7.28e7.36 (12O, m, COAr). 13C NMR (CD3OH,
Acknowledgements
150 MHz),
d (ppm): 28.8, 31.0, 33.3, 39.4, 102.8, 119.1, 122.2, 123.5,
This work was supported by the Russian Scientific Foundation
124.0, 128.5, 139.5, 151.8, 157.1. IR (KBr): 1598, 1653, 2866, 2935,
3340 cmꢁ1. Anal. Calcd (%) for C68H72N8O12: C, 68.44; H, 6.08; N,
9.39. Found: C, 68.32; H, 6.15; N, 9.28. MALDI TOF, m/z: 1193 [M]þ;
1194 [MþO]þ; 1216 [MþNa]þ; 1232 [MþL]þ.
(grant no. 14-50-00014).
Supplementary data
Procedures for the synthesis of pyrrolidine-1-carboxamides 2c,d
and copies of 1H and 13C NMR spectra of all products. Supple-
mentary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.12.011. These data include MOL files
and InChiKeys of the most important compounds described in this
article.
4.5.2. 1,10,100,1000-((14,16,34,36,54,56,74,76-Octahydroxy-15,35,55,75-tet-
ramethyl-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-2,4,6,8-tetrayl)
tetrakis(propane-3,1-diyl))tetrakis(3-phenylurea) (7b). White solid.
Yield 0.07 g (74%). Mp: >250 ꢀC. 1O NMR ((CD3)2SO, 400 MHz),
d
(ppm): 1.43e1.59 (8O, m, SO2), 2.00e2.18 (8O, m, SO2), 2.04
(12O, s, SO3), 2.23e2.32 (8O, m, SO2), 3.18e3.28 (8O, m, SO2),
4.40 (4O, t, J 7.80 Hz, CO), 6.90e6.96 (4O, m, COAr), 7.15 (4O, s, O
Ar), 7.17e7.22 (8O, m, COAr), 7.27e7.34 (8O, m, COAr). 13C NMR
References and notes
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d (ppm): 1.19e1.36 (8O, m, SO2),
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