One-pot metal templated synthesis for the preparation of 2-quinoxalinol salen metal complexes

Article abstract of DOI:10.1016/j.poly.2008.10.050

Metal complexes of 2-quinoxalinol salen (salqu) ligands can be prepared in a one-pot metal templated synthesis resulting in significantly enhanced yields than if the ligand were prepared and isolated prior to introducing the metal for complexation. Using

Full text of DOI:10.1016/j.poly.2008.10.050

Polyhedron 28 (2009) 360–362
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Polyhedron
journal homepage: www.elsevier.com/locate/poly
One-pot metal templated synthesis for the preparation of 2-quinoxalinol salen
metal complexes
*
Xianghong Wu, Hannah K. Hubbard, Brandon K. Tate, Anne E.V. Gorden
179 Chemistry Building, Department of Chemistry and Biochemistry, College of Science and Mathematics, Auburn University, Auburn, AL 36849-5319, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Metal complexes of 2-quinoxalinol salen (salqu) ligands can be prepared in a one-pot metal templated
synthesis resulting in significantly enhanced yields than if the ligand were prepared and isolated prior
to introducing the metal for complexation. Using this method, 12 salqu metal complexes have been pre-
pared and characterized from +2 metal ions.
Received 23 September 2008
Accepted 29 October 2008
Available online 10 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Salen
Quinoxolinol
Copper
Uranyl
Templating
One-pot multicomponent syntheses have received increasing
attention of late, because they not only address fundamental prin-
ciples of synthetic efficiency and reaction design [1–3], but they
also expand the possibilities for extending one-pot reactions into
combinatorial and solid-phase methods [3,4]. This presents a
new way of thinking about ‘‘greener” chemistry by allowing for
the reduction of synthetic steps, purification solvents, and wastes.
A one-pot metal templated strategy for the preparation of metal
complexes for use in applications offers the distinct advantages
of reduced environmental impacts and easier procedures for
workup.
Salen or salph complexes have been used widely in applications
for everything from catalysts to molecular recognition. For exam-
ple, salen Cu, Mn, or Ru complexes have been used as catalysts in
the catalytic oxidation of secondary amines [5], as the basis for
enantioselective catalysts [6], and as catalysts for ring-opening
metathesis [7]. Uranyl (UO22þ) salophen complexes have been used
in molecular recognition studies [8–10]. In addition, salen Mn com-
plexes can act as catalytic scavengers of hydrogen peroxide and
have been demonstrated to have a degree of cytoprotectivity [11].
Symmetric and unsymmetric 2-quinoxolinol salen ligands
(abbreviated salqu, e.g. 3) have been synthesized for use in catalysis
using solution phase and combinatorial strategies [12,13]. A disad-
vantage of this reaction scheme was an extended reaction time re-
quired to obtain the optimal yields. Metal complexes of this series
of ligands were then prepared by a standard proton transfer proce-
dure [14]. Because applications in solid-phase extraction and cata-
lysts of salqu metal complexes have been developed [15,16], it was
thought that it would to be advantageous to find a more efficient,
economical method to prepare salqu metal complexes. Here, a one-
pot synthetic method based on a metal template synthesis to ac-
cess salqu metal complexes will be introduced. With this method,
12 salqu metal complexes have been synthesized from diamino-2-
quinoxalinol (1, Scheme 1) in significantly higher yields in a short-
er time than when the ligand is isolated and purified prior to
complexation.
Previously, to prepare the salqu metal complexes, two steps
were required. The first being the preparation of salqu ligands fol-
lowed by preparation of the salqu metal complex. In the synthesis
of symmetric salqu ligands, the final optimized conditions required
that the diamino-2-quinoxalinol intermediate 1 be reacted with
10 equiv. of the desired salicylaldhyde derivatives (2) at reflux
temperature in methanol for 48 h [12]. The ligand must then be
isolated prior to the addition of the metal to prepare the metal
complex, resulting in yields around 60.0%. Metal complexes are
then prepared from a reaction of the salqu ligand (3) with
1.2 equiv. of the desired metal acetate at reflux temperature in
either DMF or DCM with MeOH reacted for 2–12 h [14]. The final
yields for this step are around 85.0%, resulting in an overall yield
for both reactions close to 50%.
Using a metal templating strategy for a one-pot synthetic meth-
od, the diamino-2-quinoxalinol intermediate 1 is reacted with
2.1 equiv. of the salicylaldhyde derivative (2) and 1.1 equiv. of me-
tal acetate is added directly to the reaction mixture. This also does
not require a mixed solvent system, only methanol is used. The
mixture was then heated to reflux temperature and allowed to
react for 6 h. After the reaction was determined to be complete,
* Corresponding author. Tel.: +1 334 663 3223; fax: +1 334 844 4043.
E-mail address: gordeae@auburn.edu (A.E.V. Gorden).
0277-5387/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2008.10.050

X. Wu et al. / Polyhedron 28 (2009) 360–362
361
R2
R2
O
N
O
N
N
R1
UO2(OAc)2
O
O
N
N
N
N
R1
H2N
H2N
N
N
R1
CHO
OH
O
U
M(OAc)
or
2
M
or
R2
(1 equiv)
O
N
OH
OH
OH
MeOH
R2
R2
2
1
3
(2.1 equiv)
(1 equiv)
Scheme 1. Method for a one-pot synthesis of salqu metal complexes.
Table 1
Salqu metal complexes synthesized using a one-pot metal templated method.
nation site can also be shown a shift in the C–O band for the metal
complexes between 1199 and 1213 cmꢀ1 as compared to the sharp
peak in the free ligands (1263–1276 cmꢀ1) [18]. (3j is lower
1146 cmꢀ1 although there is not a peak seen as in the range char-
acteristic of the C–O stretch in the starting material.)
[M]2+
Cu2+
R1
R2
Yield
72.8
3a
3,5-di-tert-butyl
The spectra of the free ligands have peaks around 1654–
1658 cmꢀ1 for the carbon–nitrogen imine stretch. This is seen to
shift to 1599–1620 cmꢀ1 (3f–3l) for the uranyl complexes and is
indicative of coordinated imine nitrogens [16,17]. This peak is seen
at 1616–1614 cmꢀ1 in the Ni2+ and Co2+ complexes, and in the Cu2+
complex (3b) but is not as well defined in the Mn2+or in the Cu2+
(3a) in which the metal may not be strongly coordinating to the
imines. Bands around 900 cmꢀ1 (897–903 cmꢀ1) seen in the uranyl
complexes (3f–3l) are due to the asymmetric and symmetric UO2
stretching characteristic of linear uranyl ion in the complex [17].
In the 1H NMR spectra of the uranyl (UO22þ) complexes, a signif-
icant shift in the imine CH@N proton is observed in the uranyl me-
tal complexes (9.5–9.8 ppm for 3f–3l) as compared to the free
ligands (8.9–9.3 ppm). This is indicative of the imine nitrogen lone
pairs coordinating to the metal center. In a similar fashion, there
are three hydroxyl peaks in the 1H NMR spectra of the free ligands
(12.1–13.3 ppm) while in the uranyl (UO22þ) complexes, only one
from the quinoxolinol hydroxyl group remains (12.6–12.7 ppm
for 3f, 3h, and 3j–3l, 12.2–12.3 ppm for 3g and 3i). (The slight dif-
ference seen in the data for 3g is presumably due to the difference
in solvation of the more subsituted and is comparable to 3i.)
The advantages of the one-pot synthetic method for preparing
salqu metal complexes are the shortened reaction time from more
than 2 days to 6 h and improved final yields from less than 50.0%
to over 60–85%. This also allows us to simplify the procedure and
to conserve the amounts of the salicylaldhyde derivatives (2) used
while avoiding the use of the more troublesome solvent DMF. This
method could be a method for synthesis of these complexes using
combinatorial methods because of the simple procedure and high
yields.
3b
3c
3d
3e
3f
Cu2+
H
80.0
76.5
69.4
62.7
84.5
62.0
61.2
65.3
63.4
67.0
69.8
Mn2+
Co2+
3,5-di-tert-butyl
3,5-di-tert-butyl
Ni2+
3,5-di-tert-butyl
UO22þ
UO22þ
UO22þ
UO22þ
UO22þ
UO22þ
UO22þ
3-OH
3g
3h
3i
3,5-di-tert-butyl
H
3,5-di-tert-butyl
3j
H
H
H
3k
3l
In conclusion, a one-pot methodology based on a metal tem-
plating synthesis using +2 metal ions to more easily and rapidly
prepare salqu metal complexes is an efficient method to prepare
these metal complexes. With this method, several salqu metal
complexes have been synthesized and identified. This will be a
more convenient synthetic method in exploring the use of such
metal complexes. In the future, a new salqu metal complex library
will be prepared in this way.
S
a large quantity of red or black solid was found to precipitate from
solution. The precipitates were filtered and washed with ethanol
five times. The solids were dried to obtain salqu metal complexes
with purity greater than 95% (purity was identified by NMR and
TLC.) Yields were found to range from 60% to 85%. The results are
listed in Table 1.
General procedure and data
The IR spectral results are indicative of metal complexation.
Broad peaks in free ligands seen around 3400 cmꢀ1 (3400–
3448 cmꢀ1) are indicative of the presence of the hydroxyl groups
on the free ligand. These broad signals are seen to be absent in
the Cu, Mn, Co, Ni, and UO2 metal complexes indicating the forma-
tion of the metal complex with these oxygens. Coordination
through the phenolic hydroxyl unit in the salicylaldehyde coordi-
All amino acid methyl esters, DFDNB, HCl (37%) and aldehydes
were purchased from Acros. Ammonium hydroxide (5.0 N), palla-
dium on carbon (wet, 5%) were purchased from Aldrich. Starting
materials were used as received. All organic solvents were pur-
chased from Fisher Scientific and were used directly for synthesis.
1H and 13C NMR spectra were recorded on Bruker AC 250 spec-
trometer (operated at 250 and 62.5 MHz, respectively) or Bruker

362
X. Wu et al. / Polyhedron 28 (2009) 360–362
AV 400 spectrometer (operated at 400 and 100 MHz, respectively).
Chemical shifts are reported as d values (ppm). The solvents used
are indicted in the experimental details. Electrospray ionization
mass spectrometry was performed on a Micromass QTOF mass
spectrometer (Waters Corp, Milford MA). Direct probe samples
were on a VG-70S mass spectrometer (Waters Corp, Milford MA).
Reaction progress was monitored by thin-layer chromatography
(TLC) using 0.25 mm Whatman Aluminum silica gel 60-F254 pre-
coated plates with visualization by irradiation with a Mineralight
UVGL-25 lamp. IR spectroscopic data were collected using a SHIM-
SDZU Inc. IR, Prestige-21 Fourier Transform Infrared Spectropho-
tometer and KBr solid samples.
(s, 1H), 12.28 (bs, 1H). 13C NMR: 173.3, 172.6, 153.4, 148.6,
144.6, 144.4, 143.3, 136.8, 135.7, 134.4, 128.9, 123.3, 110.4, 40.4,
38.6, 36.4, 35.1, 25.1. IR: 3444, 2958, 1710, 1666, 1587, 1423,
1371, 1224, 898 cmꢀ1
(919.4514); calc. (919.4524).
.
MS: 919.2 (M+H); HRMS: found
3j: 1H NMR (400 MHz DMSO-d6): d 1.28 (d, 6H), 3.56 (m, 1H),
6.74–8.17 (m, 10H), 9.61 (s, 1H), 9.81 (s, 1H), 12.58 (bs, 1H). 13C
NMR: 170.8, 170.2, 170.0, 167.9, 166.6, 154.6, 148.3, 143.5,
137.2, 136.5, 132.5, 131.9, 124.8, 124.6, 121.4, 121.0, 119.4,
117.4, 106.2, 30.5, 20.6. IR: 3406, 2966, 1654, 1602, 1539, 1463,
1400, 1384, 1145, 898 cmꢀ1. MS: 736.2 (M+H); HRMS: found
(736.2280); calc. (736.2285).
To a 5 ml methanol solution of intermediate 1 (0.05 mmol),
3k: 1H NMR (400 MHz DMSO-d6): d 1.00 (d, 6H), 2.28 (m, 1H),
2.74 (d, 2H), 6.75 (t, 2H), 7.03 (t, 2H), 7.44 (s, 1H), 7.65 (m, 2H),
7.87 (t, 2H), 8.19 (s, 1H), 9.61 (s, 1H), 9.78 (s, 1H), 12.54 (bs, 1H).
13C NMR: 170.8, 170.2, 162.3, 155.2, 148.3, 143.4, 137.2, 136.5,
132.6, 132.0, 124.8, 124.6, 121.4, 121.1, 119.3, 117.4, 106.2, 42.1,
26.8, 23.1. IR: 3395, 2927, 1637, 1606, 1539, 1463, 1435, 1383,
1282, 937 cmꢀ1. MS: 709.2 (M+H); HRMS: found (709.2167); calc.
(709.2176).
2.1 equiv. of the desired salicylaldehyde derivatives (e.g.,
2
0.105 mmol) and 1.1 equiv. of metal acetate (0.055 mmol) are
added. The mixture was heated to reflux temperature with stirring
and allowed to react for 6 h. At this time, a dark red or black solid pre-
cipitates out, indicating the completion of the reaction. The precipi-
tates were filtered from the reaction solution. They were then
washed with ethanol five times. Finally, the solids were dried under
high vacuum.
3l: 1H NMR (400 MHz DMSO-d6): d 2.15 (s, 3H), 2.96 (t, 2H),
3.16 (t, 2H), 6.75 (t, 2H), 7.03 (t, 2H), 7.46 (s, 1H), 7.66 (m, 2H),
7.87 (t, 2H), 8.19 (s, 1H), 9.62 (s, 1H), 9.78 (s, 1H), 12.64 (bs,
1H).). 13C NMR: 170.8, 170.2, 168.0, 167.2, 161.1, 155.0, 148.5,
143.5, 137.3, 136.5, 132.7, 131.2, 124.7, 121.4, 121.0, 119.4,
117.5, 106.3, 33.3, 30.5, 15.2. IR: 3395, 2927, 1637, 1606, 1539,
1463, 1435, 1383, 1282, 937 cmꢀ1. IR: 3408, 1655, 1637, 1601,
3a: IR: 3067, 2955, 1661, 1586, 1528, 1491, 1416, 1377, 1260,
1209, 1173, 1130 cmꢀ1
.
MS: 760.0 (M+H); HRMS: found
(760.3413); calc. (760.3422).
3b: IR: 3510, 3392, 1655, 1605, 1587, 1560, 1526, 1499, 1442,
1382, 1331, 1200, 1178, 1151 cmꢀ1. MS: 536.1 (M+H); HRMS:
found (536.0912); calc. (536.0909).
3c: IR: 3385, 3248, 3208, 2955, 2911, 1670, 1582, 1532, 1462,
1416, 1317, 1248, 1177, 1130 cmꢀ1. MS: 751.3 (M+H); HRMS:
found (751.3420); calc. (751.3429).
1583, 1537, 1464, 1440, 1382, 1300, 1199, 1150, 897, 760 cmꢀ1
MS: 768.2 (M+H); HRMS: found (768.2013); calc. (768.2006).
.
3d: IR: 3066, 2957, 1665, 1614, 1572, 1524, 1501, 1462, 1410,
1256, 1180, 1128 cmꢀ1
.
MS: 755.3 (M+H); HRMS: found
Acknowledgment
(755.3369); calc. (755.3372).
We would like to express our appreciation to Dr. Thomas Car-
rington of Auburn University for his help and helpful discussions.
3e: IR: 3067, 2955, 2870, 1665, 1616, 1584, 1533, 1598, 1464,
1414, 1379, 1260, 1182, 1130 cmꢀ1. MS: 755.3 (M+H); HRMS:
found (755.3461); calc. 755.3471.
3f: 1H NMR (400 MHz DMSO-d6): d 4.22 (s, 2H), 6.54–8.67 (m,
13H), 9.55 (s, 1H), 9.71 (s, 1H), 11.77 (bs, 1H), 11.82 (bs, 1H),
12.69 (bs, 1H). 13C NMR: 160.2, 159.4, 155.0, 137.8, 132.8, 132.0,
129.7, 128.9, 126.9, 126.3, 124.1, 124.0, 123.9, 119.5, 117.1,
106.3, 42.0. IR: 3397, 3337, 2965, 1657, 1620, 1582, 1545, 1491,
1445, 1204, 903 cmꢀ1. MS: 816.2 (M+H+CH3CN); HRMS: found
(816.2178); cal (816.2183).
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3g: 1H NMR (400 MHz DMSO-d6): d 1.19 (s, 18H), 1.64 (s, 18H),
4.11 (s, 2H), 7.09–7.63 (m, 10H), 7.70(s, 1H), 9.19 (s, 1H), 9.32 (s,
1H), 12.18 (bs, 1H). 13C NMR: 173.3, 173.0, 171.2, 165.1, 153.8,
148.8, 144.6, 144.3, 143.5, 142.0, 137.1, 135.9, 134.2, 133.1,
131.3, 128.9, 123.3, 110.6, 42.0, 40.3, 38.6, 36.3, 35.1. IR: 3433,
2957, 1655, 1620, 1383, 1283, 1229, 1153, 937, 760 cmꢀ1. MS:
967.4 (M+H); HRMS: found (967.4514); calc. (967.4524).
3h: 1H NMR (400 MHz DMSO-d6): d 4.20 (s, 2H), 6.73–6.77 (t,
2H), 7.00–7.04 (t, 2H), 7.24–7.88 (m, 10H), 8.12(s, 1H), 9.60 (s,
1H), 9.76 (s, 1H), 12.67 (bs, 1H). 13C NMR: 170.8, 170.2, 168.0,
167.3, 161.3, 155.0, 148.9, 143.6, 137.8, 137.3, 136.5, 132.8,
129.7, 128.9, 126.9, 124.8, 121.4, 121.0, 119.5, 117.4, 106.3, 42.3.
IR: 3397, 3337, 2965, 1657, 1620, 1582, 1545, 1491, 1445, 1204,
1144, 1040 cmꢀ1
. MS: 784.0 (M+H+CH3CN); HRMS: found
(784.2280); calc. (784.2285).
3i: 1H NMR (400 MHz DMSO-d6): d 1.22 (d, 6H), 1.26 (s, 18H),
1.69 (s, 18H), 3.50 (m, 1H), 7.26–7.80 (m, 6H), 9.30 (s, 1H), 9.46
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