On the synthesis of the first representatives of bis(benzo)-bispidinoaza- 14-crown-4 ethers

Full text of DOI:10.1007/s10593-008-0084-7

Chemistry of Heterocyclic Compounds, Vol. 44, No. 5, 2008
ON THE SYNTHESIS OF THE FIRST
REPRESENTATIVES OF BIS(BENZO)-
BISPIDINOAZA-14-CROWN-4 ETHERS
A. I. Komarova1, A. N. Levov2, A. T. Soldatenkov2, and S. A. Soldatova2
Keywords: bis(benzo)bispidinoaza-14-crown-4-ethers, condensation with aromatic aldehydes and
ammonia.
In previous work [1-3], we reported the first syntheses of dibenzoazacrown ethers containing a
constituent γ-piperidone fragment in the macrocycle. This success led us to consider the possibility of using
these compounds for the construction of a new, more complicated heterocyclic system containing a bispidine
fragment in the crown ether part of the macrocycle. Hence, we studied the condensation of azacrownophane 1
[3] with aromatic aldehydes 2a,b and ammonium acetate. Maintenance of this mixture in a solution of ethanol
and acetic acid for seven days at 20°C followed by crystallization gave compounds 3a in 15% yield and 3b in
11% yield. These azacrown ethers belong to a new group of lariat ethers [4], in which the constituent
H
24
N
O
R
O
R
23
24
1
22
21
23
22
21
3
19
1
2
N
H
18
17
N
H
4
5
+ RCHO + NH4OAc
20
2a,b
O
O
O
O
7
15
6
16
O
O
13
9
10
12
1
3a,b
2, 3 a R = 4-FC6H4, b R = (MeO)2C6H3
3,7-diazabicyclo[3.3.1]nonane fragment has additional sites for coordination with metal cations. These sites are
auxiliary upon cooperation with the crown ether part of the molecule. Furthermore, the functionality of this
fragment may lead to derivatives of this new heterocyclic system with enhanced potential for biological activity
since, as predicted by the PASS Internet program [5], 3a,b may display cardioprotective (69-76%) and
antineoplastic activity (62-68%).
__________________________________________________________________________________________
1D. Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia; e-mail:
alexkom18@yandex.ru. 2Russian Peoples' Friendship University, Moscow 117198, Russia; e-mail:
asoldatenkov@mail.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 784-786,
May, 2008. Original article submitted March 18, 2008.
624
0009-3122/08/4405-0624©2008 Springer Science+Business Media, Inc.

1
The H NMR spectra were taken on a Bruker WP-400 spectrometer at 400 MHz in DMSO-d6 with the
residual protons of the deuterated solvent serving as the internal standard. The electron impact mass spectra
were taken on a Finnigan MAT Incos 50 mass spectrometer at 70 eV. The IR spectra were taken on an IR-75
spectrometer for KBr pellets.
Azacrownophanes 3a,b. A solution of azacrownophane 1 (2.0 g, 5.7 mmol), aldehyde 2a or 2b
(11.4 mmol), and ammonium acetate (0.87 g, 11.4 mmol) in a mixture of ethanol (30 ml) and acetic acid (2 ml)
was maintained for seven days at 20°C. The crystalline precipitate was filtered off, washed with ethanol, and
recrystallized from ethanol to give 3a or 3b.
23,25-Bis(4-fluorophenyl)-8,11,14-trioxa-24,27-diazapentacyclo[19.5.1.122,26.02,7.015,20]octacosa-
2,4,6,15(20),16,18-hexaen-28-one (3a) was obtained in 15% yield (0.48 g); mp 251-252°C, Rf 0.55 (Silufol,
1
ethanol). IR spectrum, ν, cm-1: 3259 and 3312 (NH), 1719 (C=O), 1060 (C–F). H NMR spectrum, δ, ppm
(J, Hz): 2.63 (2H, H-22, H-26); 2.82 (2H, br. s, NH); 3.41-3.93 (8H, m, OCH2CH2OCH2CH2O); 3.98-4.32 (4H,
3
3
3
m, H-1, H-21, H-23, H-25); 6.22, 6.44, 6.75, and 7.01 (2H each, ABCD system, J = 7.47, J = 7.50, J = 8.12,
3
4J = 0.82, H-6,16, H-5,17, H-3,19, H-4,18, respectively); 7.11 and 7.63 (2H each, AA'BB' system, J = 8.49);
C6H4F-4). Mass spectrum, m/z (Irel, %): 582 [M]+ (20), 566 (7), 459(15), 352 (40), 297 (30), 230 (13), 183 (14),
162 (14), 149 (50), 121 (100), 107 (51), 91 (78), 77 (59). Found, %: C 72.03; H 5.67; N 4.70. C35H32FN2O4.
Calculated, %: C 72.15; H 5.54; N 4.81.
23,25-Bis(3,4-dimethoxyphenyl)-8,11,14-trioxa-24,27-diazapentacyclo[19.5.1.122,26.02,7.015,20]octacosa-
2,4,6,15(20),16,18-hexaen-28-one (3b) was obtained in 11% yield (0.41 g); mp 230-232°C. Rf 0.36 (Silufol,
ethyl acetate). IR spectrum, ν, cm-1: 3314 and 3304 (NH), 1719 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.87
(2H, m, H-22, H-26); 3.10 (2H, br. s, NH); 3.69 and 3.73 (6H each, both s, OCH3); 3.63-3.91 (8H, m,
OCH2CH2OCH2CH2O); 3.98-4.34 (4H, m, H-1, H-21, H-23, H-25); 6.23, 6.43, 6.73, and 6.99 (2H each,
ABCD system, 3J = 7.25, 3J = 7.36, 3J = 8.10, and 4J = 0.73 (H-6,16, H-5,17, H-3,19, H-4,18, respectively); 6.89
and 7.11 (2H each, 2d, 3J = 8.20, C6H3O2); 7.09 (2H, s, C6H3O2). Mass spectrum, m/z (Irel, %): 666 [M]+ (1), 665
(1), 650 (1), 501 (20), 310 (42), 394 (12), 352 (100), 315 (57), 297 (33), 191 (40), 164 (61), 151 (31), 131 (44),
121 (27), 105 (28), 91 (48), 77 (48). Found, %: C 70.31; H 6.49; N 4.03. C39H42N2O8. Calculated, %: C 70.25; H
6.35; N 4.20.
REFERENCES
1.
2.
3.
4.
5.
A. N. Levov, V. M. Strokina, A. I. Komarova, Le Tuan Anh, and A. T. Soldatenkov, Khim. Geterotsikl.
Soedin., 139 (2006). [Chem. Heterocycl. Comp., 42, 125 (2006)].
A. N. Levov, V. M. Strokina, Le Tuan Anh, A. I. Komarova, A. T. Soldatenkov, and V. N. Khrustalev,
Mendeleev Commun., 35 (2006).
A. N. Levov, Le Tuan Anh, A. I. Komarova, V. M. Strokina, A. T. Soldatenkov, and V. N. Khrustalev,
Zh. Org. Khim., 43, 457 (2007).
A. V. Bordunov, P. C. Hellier, J. S. Bradshaw, N. K. Dally, X. Kou, X. X. Zang, and R. M. Izatt, J. Org.
Chem., 60, 6097 (1995).
http://195.178.207.233/PASS.
625