Synthesis and characterization of benzo-15-crown-5 ethers with appended N2O Schiff bases

Article abstract of DOI:10.3390/81200894

New derivatives of benzo-15-crown-5 with flexible appended N₂O unsymmetrical Schiff bases were prepared by a two step procedure which involves: (i) preparation of N₂O Schiff bases by condensation of hydrazine with salicylaldehyde, 3-methoxysalicylaldehyde or 2-hydroxy-1-naphtaldehyde and (ii) reaction of the resulting NH₂ functionalized compounds with 4′-formyl-benzo-15-crown-5.

Full text of DOI:10.3390/81200894

Molecules 2003, 8, 894–900
molecules
ISSN 1420-3049
http://www.mdpi.org
Synthesis and Characterization of Benzo-15-Crown-5 Ethers
with Appended N2O Schiff Bases
Carla Sousa, Cristina Freire* and Baltazar de Castro*
REQUIMTE/ Departamento de Química, Faculdade de Ciências, Universidade do Porto, 4169-007
Porto, Portugal.
* Authors to whom correspondence should be addressed; e-mail: acfreire@fc.up.pt
Received: 14 July 2003; in revised form: 30 October 2003 / Accepted: 3 November 2003 / Published:
31 December 2003
Abstract: New derivatives of benzo-15-crown-5 with flexible appended N2O
unsymmetrical Schiff bases were prepared by a two step procedure which involves: (i)
preparation of N2O Schiff bases by condensation of hydrazine with salicylaldehyde, 3-
methoxysalicylaldehyde or 2-hydroxy-1-naphtaldehyde and (ii) reaction of the resulting
NH2 functionalized compounds with 4’-formyl-benzo-15-crown-5.
Keywords: Schiff base ligands, crown ethers, hetero-binucleating ligands, hydrazine,
salicylaldehyde.
Introduction
The rapidly emerging field of hetero-binucleating ligands and the coordination chemistry of the
heteronuclear complexes derived from such ligands [1-4], have prompted an extension of our work on
the synthesis and redox chemistry of nickel and copper Schiff base complexes [5-10] towards
complexes functionalized with crown ether derivatives. As these latter groups have a large affinity for
alkaline, alkaline earth and lanthanides ions [11-14], the redox and electronic properties of the
transition metal center can be modulated by the size and charge of the hard metal ions bound to the
crown ether moiety. On the other hand, the extent of the interaction of hard cations with transition
metal centers, mediated by hetero-binucleating ligands, can be studied by monitoring the redox and

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electronic properties of the transition metal ions, and these complexes can ultimately be used as
sensors (electrochemical and electronic) for alkaline, alkaline earth and lanthanide metal ions [2-4].
We have already grafted dibenzo18-crown-6-ether and benzo-15-crown-5-ether onto four-dentate
N2O2 Schiff base ligands [15,16]. These ligands were prepared by Schiff condensation of an aldehyde
with a tetra-amine derivative of dibenzo-18-crown-6-ether or with a diamine derivative of benzo-15-
crown-5-ether, and have the crown ether moiety grafted rigidly to the Schiff base [15,16]. We are now
pursuing the synthesis of Schiff base ligands functionalized with crown ethers, but including a flexible
spacer between the two subunits, and in this work we report the synthesis of benzo-15-crown-5
derivatives with appended N2O unsymmetrical Schiff bases derived from salicylaldehydes and
naphthaldehyde.
Results and Discussion
The Schiff base ligands with appended benzo-15-crown-5 were prepared in two steps as depicted
in Scheme 1.
Scheme 1.
H
H
O
N
NH2
(I) R=H
(II) R=3-OCH3
OH
OH
R
R
H2N-NH2
H
H
O
N
NH2
(III)
OH
OH
O
O
OHC
(IV)
O
O
O
H
H
O
N
N
O
O
(V) R=H
HO
(VI) R=3-OCH3
O
R
O
or
H
H
O
N
N
O
(VII)
O
HO
O
O

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In the first step, we have prepared the new unsymmetrical N2O ligands functionalized with NH2
groups by Schiff condensation of hydrazine with an aldehyde: salicylaldehyde, 3-methoxy-
salicylaldehyde or 2-hydroxy-1-naphtaldehyde and the resulting adducts are designated by (Hsh) (I),
(Hmsh) (II) and (Hnh) (III), respectively.
In the second step, the NH2-functionalized compounds were made to react with 4’-formyl-benzo-
15-crown-5 and the products resulting from the second Schiff condensation are the original ligands
with an appended crown ether: Hsh-b-15-c-5 (V), Hmsh-b-15-c-5 (VI) or Hnh-b-15-c-5 (VII).The key
step in the reactions depicted in Scheme 1 is the preparation of unsymmetrical N2O Schiff bases by
condensation of the aldehydes with hydrazine, due to the need to prevent formation of the symmetrical
ligands (azines). The applied methodology was based on that of the preparation of unsymmetrical
Schiff base derived from propylenediamine [17,18], in which the aldehyde is add to a large excess of
the diamine to prevent formation of symmetrical ligands. However, the yield of
N-(aminoformimidoyl)-6-methoxyphenol (II) using this procedure (40.6%) is much smaller than that
obtained by adding hydrazine to a solution of 3-methoxysalicylaldehyde (66.2 %). The unsymmetrical
compounds precipitate readily from cold solutions, and after being collected by filtration were found to
be stable when kept in a dry atmosphere.
In the mass spectra of the unsymmetrical Schiff bases I, II and III, the peak of the molecular ion
[M+] is the most intense, what confirms the proposed structures. The IR spectra of these compounds
show the C=N bond stretching vibration in the region 1623-1617 cm-1 and a strong and sharp
absorption due to free NH2 at 3420-3380 cm-1. The electronic spectra were recorded in N,N'-dimethyl-
formamide (DMF) and in the region from 330 to 550 nm, and those of I and II show one broad band at
355 nm and 358 nm, respectively, which can be deconvoluted into two bands: for I the bands appear at
350 nm (ε ≈ 445 dm3mol-1cm-1) and 364 nm (ε ≈ 90 dm3mol-1cm-1). On the other hand, in the spectrum
of III four bands can be observed: two very intense ones at 348 and 361 nm (ε ≈ 9400 dm3mol-1cm-1)
and two less intense ones at 410 and 430 nm (ε ≈ 2000 dm3mol-1cm-1).
For compound V, the mass spectrum (EI) reveals also the presence of intense peak corresponding to
the molecular ion [M+], whereas for those of VI and VII (FAB), the [MH+] peak was observed. With
regards to the IR spectra of V-VII, it must be stressed that: (a) the band due to the C=N bond
stretching does not shift significantly relative to those of the parent compounds; (b) no bands due to
NH2 stretching are present; and (c) new absorptions can be found at values characteristic of aromatic
and aliphatic ether groups of crown-ethers: ν(Ar-O-C)= 1268-1266 cm-1 and ν(C-O-C)= 1131-1125
cm-1 [19]. These observations indicate that benzo-15-crown-5 have reacted with the NH2
functionalized Schiff bases. The electronic spectrum of compound V shows one band at 356 nm, with
shoulders at low and high energies, very similar to that of VI, but which has the band at 349 nm. That
of VII exhibits four bands at 371, 387, 404 and 438 nm.
The bands in the electronic spectra of compounds I-III and V-VII are assigned to π*←n and to
π*←π transitions of the aromatic moieties, as crown ethers do not absorb above 330 nm. The
observation that compounds derived from naphthaldehyde exhibit two more bands in the spectral range

Molecules 2003, 8
897
used, is a consequence of the more extensive π delocalisation in the naphthaldehyde moiety that lowers
the energy of the π orbitals.
Conclusions
Our motivation behind the synthesis of this type of ligands, formed by condensation of
salicylaldehyde (or derived) and NH2-functionalized crown ether was is to obtain the respective
transition metal (Ni(II) and Cu(II)) complexes. Applications can be envisaged in cation recognition
processes, using the spectroscopic and redox properties of transition metal complexes bound to the
Schiff base.
Acknowledgments
C.S. thanks "Fundação para a Ciência e Tecnologia" (FCT; Lisboa; Portugal) and FSE for a
fellowship (SFRH/ BPD/ 5678/ 2001).
Experimental
General
All solvents were from Merck and all other reagents from Aldrich; all were used as received.
Solvents for syntheses were reagent grade and those for UV/Vis studies of analytical grade. Elemental
analysis (C, H, N) were performed at the Instituto de Tecnologia Química e Biológica, Universidade
Nova de Lisboa (Portugal), and EI and FAB mass spectra at the Facultad de Química, Universidad de
Santiago de Compostela (Spain), using 3-nitrobenzylalcohol (NBA) as matrix (FAB). 1H-NMR spectra
were recorded on a Bruker AC 200 at 200 MHz (298 K). Chemical shifts are reported in ppm relative
to TMS, used as internal standard. IR spectra in the 400-4000 cm-1 region were recorded on a Biorad
FTS 155, using KBr pellets. UV/Vis spectra were recorded in the 600-330 nm range on a Unicam UV-
2, at room temperature, using quartz cells with a 1 cm optical path.
Syntheses
N-(aminoformimidoyl)phenol (Hsh, I).
An ethanolic solution of salicylaldehyde (0.99 g, 8.2 mmol) was added dropwise, at room
temperature and with stirring, over 1 hour to hydrazine hydrate (98 %) (2.06 g, 40.3 mmol). After the
addition was complete, the mixture was stirred for 10 min, and upon cooling in ice, a whitish solid
appeared, which was collected by filtration, washed with diethyl ether and dried under vacuum. Yield
0.83 g (79.8 %). Anal. Calcd. for C7H8ON2: C, 61.75; H, 6.09; N, 20.58. Found: C, 62.08; H, 6.11; N,

Molecules 2003, 8
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20.62. 1H-NMR (CDCl3): δ 11.07 (s, 1H, -OH), 7.87 (s, 1H, -CHN), 7.22-7.18 (m, 1H, arom H), 7.12-
7.09 (m, 1H, arom H), 6.96-6.93 (m, 1H, arom H), 6.89-6.86 (m, 1H, arom H), 5.43 (s, 2H, -NH2). MS
(EI) m/z (%): 136 (M+, 100). IR (KBr) ν/cm-1: 3383, 3280, 1617, 1572, 1491, 1465, 1405, 1271, 1198,
1097, 940, 898, 784, 749, 705, 642, 558. UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 355 (504).
N-(aminoformimidoyl)-6-methoxyphenol (Hmsh, II).
A hydrazine hydrate solution (80 %) (2.80 g, 44.7 mmol) was added dropwise, at room temperature
and with stirring, over 5 min to an ethanolic solution of 3-methoxysalicylaldehyde (4.82 g, 31.7
mmol). The resulting light yellow coloured solid was washed with diethyl ether and dried under
vacuum. Yield 3.52 g (66.2 %). Anal. Calcd. for C8H10O2N2: C, 57.82; H, 6.07; N, 16.86. Found: C,
1
57.97; H, 5.95; N, 16.93. H-NMR (CDCl3): δ 11.20 (s, 1H, -OH), 7.86 (s, 1H, -CHN), 6.85-6.72 (m,
3H, arom H), 5.48 (s, 2H, -NH2), 3.90 (s, 3H, -OCH3). MS (EI) m/z (%): 166 (M+, 100). IR (KBr)
ν/cm-1: 3416, 3369, 1623, 1573, 1468, 1411, 1320, 1257, 1247, 1089, 1072, 965, 928, 838, 813, 777,
731, 620. UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 358 (856).
N-(aminoformimidoyl)naphthol (Hnh, III).
This compound was prepared following the procedure described for I, but adding a methanolic
solution of 2-hydroxy-1-naphtlaldehyde (0.87 g, 5.1 mmol) to hydrazine hydrate (98 %) (1.29 g, 25.3
mmol). After the addition was complete, the yellow-golden solid was collected by filtration, washed
with diethyl ether and dried under vacuum. Yield 0.62 g (65.9 %). Anal. Calcd for C11H10ON2: C,
70.95; H, 5.41; N, 15.04. Found: C, 70.53; H, 5.65; N, 15.22. 1H-NMR (CDCl3): δ 12.33 (s, 1H, -OH),
8.80 (s, 1H, -CHN), 8.00-7.97 (d, 1H, arom H), 7.78-7.71 (m, 2H, arom H), 7.51-7.46 (m, 1H, arom
H), 736-7.31 (t, 1H, arom H), 7.21-7.18 (d, 1H, arom H), 5.54 (s, 2H, -NH2). MS (EI) m/z (%): 186
(M+, 100). IR (KBr) ν/cm-1: 3390, 3375, 1621, 1603, 1579, 1466, 1417, 1315, 1281, 1241, 1181, 1082,
794, 747. UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 348 (9415), 361 (9353), 410 (2383), 430 (1908).
4’-Formylbenzo-15-crown-5 (IV).
This compound [20] was prepared from the reaction of 1,11-dichloro-3,6,9-trioxaundecane (53.3 g,
180.0 mmol) with 3,4-dihydroxybenzaldehyde (25.0 g, 181.0 mmol) and NaOH (15.1 g, 377.5 mmol)
in water/n-butanol. After recrystallization from hot n-heptane and activated charcoal, a white
crystalline solid was obtained (12.44 g). Yield 23.3 %. 1H-NMR (CDCl3): δ 9.83 (s, 1H, -CHO), 7.46-
7.38 (m, 2H, arom H), 6.96-6.92 (d, 1H, arom H), 4.23-4.17 (m, 4H, -CH2), 3.96-3.90 (m, 4H, -CH2),
3.80-3.75 (m, 8H, -CH2). MS (EI) m/z (%): 416 (M+, 100).

Molecules 2003, 8
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N-(formimidoyl-benzo-15-crown-5)-N´-(formimidoyl)phenol (Hsh-b-15-c-5, V).
To an ethanolic solution of IV (0.88 g, 3.0 mmol) was added a solution of I (0.34 g, 2.5 mmol) in
ethanol. The mixture was refluxed for 3 h. The resulting light yellow compound was washed with
ethanol. The compound was recrystallized from methanol and dried under vacuum. Yield 0.69 g (66.6
%). Anal. Calcd for C22H26O6N2: C, 63.76; H, 6.32; N, 6.76. Found: C, 64.34; H, 6.70; N, 6.58.
1H-NMR (CDCl3): δ 11.85 (s, 1H, -OH), 8.75-8.73 (d, 1H, -CHN), 8.56-8.53 (d, 1H, -CHN), 7.50-7.22
(m, 4H, arom H), 7.04-6.66 (m, 3H, arom H), 4.26-4.18 (m, 4H, -CH2), 3.97-3.92 (m, 4H, -CH2), 3.71-
3.68 (m, 8H, -CH2). MS (EI) m/z (%): 414 (M+, 100). IR (KBr) ν/cm-1: 2932, 2867, 1622, 1598, 1567,
1508, 1449, 1428, 1411, 1344, 1306, 1268, 1226, 1174, 1125, 1055, 1017, 986, 968, 941, 844, 813,
746. UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 344 (26137), 356 (26698).
N-(formimidoyl-benzo-15-crown-5)-N´-(formimidoyl)-6-methoxyphenol (Hmsh-b-15-c-5 VI).
This compound was prepared by the procedure described for V, but using II (0.17 g, 1.0 mmol)
and IV (0.37 g, 1.2 mmol). The resulting light yellow solid was washed with diethyl ether. The
compound was recrystallized from methanol and dried under vacuum. Yield 0.37 g (81.6 %). Anal.
1
Calcd for C23H28O7N2: C, 62.15; H, 6.35; N, 6.30. Found: C, 61.63; H, 6.40; N, 6.42. H-NMR
(CDCl3): δ 11.81 (s, 1H, -OH), 8.75-8.71 (d, 1H, -CHN), 8.56-8.52 (d, 1H, -CHN), 7.49 (s, 1H, arom
H), 7.29-7.26 (m, 1H, arom H), 7.00-6.87 (m, 4H, arom H), 4.26-4.18 (m, 4H, -CH2), 3.94-3.92 (m,
7H, -CH2, -OCH3), 3.78-3.75 (m, 8H, -CH2). MS (FAB) m/z (%): 445 ([M+H]+, 15). IR (KBr) ν/cm-1:
2930, 2874, 1623, 1601, 1577, 1511, 1464, 1436, 1310, 1266, 1131, 1095, 1078, 1052, 966, 736.
UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 340 (39706), 349 (38578).
N-(formimidoyl-benzo-15-crown-5)-N´-(formimidoyl)-naphthol (Hnh-b-15-c-5 VII).
This compound was prepared by a modification of the procedure described for V. To a methanolic
solution of IV (0.20 g; 0. 7 mmol) was added a solution of III (0.10 g; 0.5 mmol) in methanol. The
mixture was refluxed for 4.5 h. The resulting yellow solid was washed with diethyl ether,
recrystallized from ethanol and dried under vacuum. Yield 0.09 g (35.9 %). Anal. Calcd for
1
C23H28O7N2·1/2 C3H5O: C, 66.51; H, 6.41; N, 5.70. Found: C, 66.73; H, 6.15; N, 5.68. H-NMR
((CD3)2SO): δ 13.02 (s; 1H, -OH), 9.87 (d; 1H, -CHN), 8.78 (d; 1H, -CHN), 8.67-8.49 (m; 1H, arom
H), 8.06-7.88 (m; 2H, arom H), 7.62-7.42 (m; 6H, arom H), 4.13-4.11 (m; 4H, -CH2), 3.81-3.80 (m;
4H, -CH2), 3.68-3.67 (m; 8H, -CH2). MS (FAB) m/z (%): 464 ([M+H]+, 84). IR (KBr) ν/cm-1: 3445,
3408, 2931, 2876, 1720, 1623, 1580, 1544, 1512, 1436, 1419, 1405, 1278, 1239, 1183, 1137, 1052,
721, 501. UV/Vis (DMF) λmax/nm (ε/dm3mol-1cm-1): 339 (27858), 371 (30539), 387 (33496), 404
(27812), 438 (4165).

Molecules 2003, 8
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