Multidentate aminophenol ligands prepared with Mannich condensations

Article abstract of DOI:10.1016/j.tetlet.2006.04.077

Mannich condensations were used to prepare a series of multidentate aminophenol compounds from ethylenediamine, various amounts of paraformaldehyde and 2,4-disubstituted phenols. One of these diaminotetraphenol compounds was reacted with Zn(OAc)₂

Full text of DOI:10.1016/j.tetlet.2006.04.077

Tetrahedron Letters 47 (2006) 4419–4423
Multidentate aminophenol ligands prepared with
Mannich condensations
Christine S. Higham,a Daniel P. Dowling,a Janet L. Shaw,b Anil Cetin,b
Christopher J. Zieglerb and Joshua R. Farrella,*
aDepartment of Chemistry, College of the Holy Cross, Worcester, MA 01610, USA
bDepartment of Chemistry, University of Akron, Akron, OH 44325, USA
Received 21 March 2006; revised 12 April 2006; accepted 14 April 2006
Abstract—Mannich condensations were used to prepare a series of multidentate aminophenol compounds from ethylenediamine,
various amounts of paraformaldehyde and 2,4-disubstituted phenols. One of these diaminotetraphenol compounds was reacted with
Zn(OAc)2Æ2H2O and the resulting solid state structure of the pentacoordinated Zn(II) compound was determined by single crystal
X-ray diffraction analysis.
ꢀ 2006 Elsevier Ltd. All rights reserved.
We are reporting the step-wise use of Mannich conden-
sations with substituted phenols, formaldehyde, and eth-
ylenediamine (en) to prepare a series of compounds with
multiple amine and alcohol/aminal groups of increasing
size and complexity (Scheme 1). Our goal was to build a
library of compounds step-wise, in order to have greater
control over the number and placement of heteroatoms
in these potential ligands. These compounds are of inte-
rest as metallochelators and as ligands for bioinorganic
modeling, catalysis, and medical imaging. The Mannich
reaction is a multi-component condensation between a
non-enolizable aldehyde (commonly formaldehyde), an
amine (1ꢁ or 2ꢁ), and an enolizable carbonyl compound.
Mannich condensations have been used to make biolo-
gically relevant molecules since the early 1900s, and
the mechanism has been proposed for the biosynthetic
production of alkaloids.1 In our case, phenols function
as the enolizable carbonyl compound and are reactive
in the 2-, 4-, or 6-position.2–4 By using 2,4-disubstituted
phenols and varying those substituents, we modulate the
electronic and steric properties of the alcohol moieties
affecting both how many phenol groups can bind to a
transition metal and how strongly those phenols will
bind.5–13
The amine for all of the Mannich condensations in this
letter is ethylenediamine, and it is used toward the goal
of preparing a series of multidentate aminoalcohol
ligands. Diaminodiphenols 2a–c15 were prepared by
combining 2 equiv of a phenol (1a–c) with 2 equiv of
paraformaldehyde and 1 equiv of ethylenediamine for
two days (Scheme 1).14 These reactions require neither
solvent nor inert atmosphere conditions. Each com-
pound was isolated by the addition of methanol to a
cooled reaction mixture and filtration of the resulting
precipitate in yields ranging from 35% to 61%. Of these,
compound 2b has been reported several times and is
more commonly prepared by a two-step process in
which 3,5-di-t-butyl-2-hydroxybenzaldehyde is con-
densed with ethylenediamine followed by reduction of
the resulting imines.15–18 The use of a Mannich conden-
sation offers a simple and convenient method for prepar-
ing this family of compounds in a one-pot reaction.
X-ray diffraction studies of single crystals containing
2b ligated to several transition metals have been pub-
lished,15–18 but to the best of our knowledge, the struc-
ture of the free ligand is previously unreported. Clear
block crystals of 2b were grown from the vapor diffusion
of CH2Cl2 solutions of 2b and toluene.19 A thermal
ellipsoid diagram of 2b is presented in Figure 1 and all
spectroscopic data are consistent with the structure.
Scheme 1 illustrates that the series of compounds 2a–c
resemble salen ligands, and one would expect these tetra-
hydrosalen complexes to be both more flexible and
Keywords: Mannich condensation; Zn(II); Benzoxazine.
*
Corresponding author. Tel.: +1 508 793 2793; fax: +1 508 793
3530; e-mail: jfarrell@holycross.edu
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.077

4420
C. S. Higham et al. / Tetrahedron Letters 47 (2006) 4419–4423
R
OH
N
R
R
6 equiv 1a-c
1/2 equiv. en
1 equiv. H2CO
Δ, 2 days
1 equiv. en
4 equiv. H2CO
Δ, 3 days
NH HN
OH HO
R
R
OH
OH
R
R
N
HO
R
R
R
R
1a: R = Me
1b: R = -Bu
1c: R = Cl
R
R
HO
2a: R = Me, 35%
2b: R = -Bu, 64%
2c: R = Cl, 37%
t
R
t
5a: R = Me, 27%
5b: R = -Bu, 65%
5c: R = Cl, 49%
t
1/2 equiv. en
8 equiv. H2CO
C6H5CH3
Δ, 3 days
O
R
N
O
3b, 2 equiv 1b
C6H6, Δ, 3 days
OH
N
R
N
R
N
79%
O
R
3a: R = Me, 34%
3b: R = -Bu, 72%
3c: R = Cl, 77%
OH
t
4
Scheme 1.
with methanol, which results in the isolation of 4 in 79%
yield, Scheme 1.
The synthesis of 5a–c was realized by running the reac-
tions neat, in a pressure flask, with an excess of phenol,
Scheme 1.25 A minimal amount of methanol (5b and 5c)
or ether (5a) was added to the crude reaction mixtures to
wash away the unreacted phenol and the product was
collected by filtration in 27–65% yield. All of the tetra-
phenols were more soluble in halogenated organic sol-
vents such as CH2Cl2 or CHCl3 than in methanol,
with the solubilities decreasing from 5b to 5a to 5c.
Compound 5a has been previously prepared in ꢀ8%
yield for use as a ligand to prepare 68Ga diagnostic
agents for positron emission topography.26 A series of
similar tetraphenols were also synthesized from 2-nap-
thol with ethylenediamine and 1,7-diaminoheptane for
use in preparing dioxoazaborocines toward the goal of
making wood preservatives.27
Figure 1. Thermal ellipsoid plot of the single crystal X-ray crystallo-
graphic structure of 2b. Ellipsoids are drawn at 50% and hydrogens are
omitted for clarity with the exception of the alcohol hydrogens.
have increased N-basicity compared to the dehydroge-
nated salen versions.18,20–22
The products of Mannich condensations have long been
known to be condition dependent.2–4 By increasing the
amount of paraformaldehyde present in the reaction
mixture, the reaction conditions favor the formation of
dibenzoxazines 3a–c (Scheme 1).23 Use of more than
two but less than 8 equiv of paraformaldehyde results
in mixtures of 2 and 3, but at 8 equiv and beyond the
reactions favor the production of pure 3a–c.24 Again,
the compounds are isolated by filtration from the chilled
solvents in yields ranging from 34% to 77%. These benz-
oxazines function as a stable surrogate for the putative
iminium intermediate of the Mannich condensation.
The iminium intermediate is formed under acidic condi-
tions yielding a reactive center for further Mannich and
reverse Mannich condensations, and in the future 3a–c
could serve as starting materials for polymers or com-
pounds with two different types of phenols attached to
the same amine. This reactivity is demonstrated by com-
bining 1 equiv of the dibenzoxazine 3b with 2 equiv of 1b
in refluxing benzene for three days followed by removal
of the solvent and washing of the crude reaction mixture
We are interested in using these compounds as potential
ligands for bioinorganic modeling chemistry. In order to
test the ability of the tetraphenols to bind biologically
relevant metals, 1 equiv of 5a was combined with
1 equiv of Zn(OAc)2Æ(H2O)2 and 4 equiv of NaOH in
methanol at room temperature for three days. After iso-
lation of the solid by evacuation of the solvent and
recrystallization by vapor diffusion of toluene and meth-
anol, we isolated clear block crystals of 6 (Na[Zn(5a)]Æ-
CH3OH) (Fig. 2). The crystal was subjected to a single
crystal X-ray diffraction study and a thermal ellipsoid
diagram of the structure is presented in Figure 2 and
selected bond angles and distances are given in Table
1. In the solid state structure, three of the phenols of
compound 5a have been deprotonated and are bound
to the zinc along with both of the nitrogen atoms in a
distorted trigonal planar geometry. One sodium ion
and one methanol molecule were found in each asym-
metric unit. One nitrogen atom and one oxygen atom

C. S. Higham et al. / Tetrahedron Letters 47 (2006) 4419–4423
4421
were one pot reactions whose workups involved simple
filtrations of highly pure materials. This work should
serve as a starting point for building increasingly com-
plex compounds. Our laboratory is now concentrating
on preparing hetero-phenol compounds, with the goal
of controlling the identity of phenol at each of the four
positions of compounds similar to 5a–c (four different
phenols, three different phenols, two different phenols).
Furthermore, work has begun on incorporating thiophe-
nols into this reaction scheme in order to open up the
possibility of preparing new sulfur containing ligands
for bioinorganic modeling of proteins and metallo-
enzymes that contain cysteine or methionine in their
active sites.
Acknowledgements
J.R.F. thanks the College of the Holy Cross for research
support and the National Science Foundation for funds
to purchase the NMR facilities (CHE-0079348). C.S.H.
acknowledges the Bekton Dickinson Foundation for
support of summer research. C.J.Z. acknowledges the
University of Akron for a faculty research grant
(FRG-1565). We also wish to acknowledge NSF Grant
CHE-0116041 for funds used to purchase the Bruker-
Nonius diffractometer. We acknowledge the UMass
Amherst Mass Spectrometry Center for assistance with
all of the high resolution MS.
Figure 2. Thermal ellipsoid plot of the single crystal X-ray crystallo-
graphic structure of 6, (Na[Zn(5a)]ÆCH3OH). Ellipsoids are drawn at
50% and the sodium ion, the methanol, and all hydrogens except for
the hydrogen bound to O(4) of the protonated phenol are omitted for
clarity.
˚
Table 1. Selected bond lengths (A) and angles (ꢁ) for 6
Zn(1)–N(1)
Zn(1)–N(2)
Zn(1)–O(1)
Zn(1)–O(2)
Zn(1)–O(3)
O(3)–O(4)
N(1)–Zn(1)–N(2)
N(1)–Zn(1)–O(1)
N(1)–Zn(1)–O(2)
N(1)–Zn(1)–O(3)
N(2)–Zn(1)–O(1)
N(2)–Zn(1)–O(2)
N(2)–Zn(1)–O(3)
O(1)–Zn(1)–O(2)
O(1)–Zn(1)–O(3)
O(2)–Zn(1)–O(3)
2.104(2)
2.180(2)
1.977(2)
2.016(2)
2.030(2)
2.596(1)
83.15(9)
94.81(8)
91.21(8)
166.95(8)
133.13(9)
116.34(8)
83.86(8)
110.51(9)
94.95(8)
93.46(8)
Supplementary data
Selected physical and spectral data for 4 and 6 along
with .cif files for 2b and 6 can be found, in the online
version, at doi:10.1016/j.tetlet.2006.04.077.
References and notes
1. Mannich, C.; Jacobsohn, W. Berichte 1910, 43, 189–197.
2. Burke, W. J.; Glennie, E. L. M.; Weatherbee, C. J. Org.
Chem. 1964, 29, 909–912.
3. Burke, W. J.; Nasutavicus, W. A.; Weatherbee, C. J. Org.
Chem. 1964, 29, 407–410.
4. Burke, W. J.; Bishop, J. L.; Glennie, E. L. M.; Bauer, W.
N. J. Org. Chem. 1965, 30, 3423–3427.
5. Tshuva, E. Y.; Goldberg, I.; Kol, M.; Goldschmidt, Z.
Chem. Commun. (Cambridge, United Kingdom) 2001,
2120–2121.
6. Tshuva, E. Y.; Goldberg, I.; Kol, M.; Goldschmidt, Z.
Inorg. Chem. 2001, 40, 4263–4270.
7. Tshuva, E. Y.; Goldberg, I.; Kol, M.; Goldschmidt, Z.
Organometallics 2001, 20, 3017–3028.
8. Tshuva, E. Y.; Goldberg, I.; Kol, M. J. Am. Chem. Soc.
2001, 123, 3621.
9. Tshuva, E. Y.; Gendeziuk, N.; Kol, M. Tetrahedron Lett.
2001, 42, 6405–6407.
serve as the axial donor atoms, positioned across the
zinc at a compressed bond angle of 166.95(8)ꢁ. Two oxy-
gen atoms and one nitrogen atom form the equatorial
ligands, which are separated by a range of 111–133ꢁ.
Of note is the fact that O(4) on the fourth phenol ring
is still protonated, and is hydrogen bonded to the axial
oxygen. This sort of secondary coordination sphere
interaction is common in biology and is an example of
how proteins and metalloenzymes modulate the reactiv-
ities of their active sites. The N2O3 binding demon-
strated by 6 is similar to the zinc centers in the
trinuclear metalloenzymes alkaline phosphatase, phos-
pholipase, and P1 nuclease.28–30 The structure of 6 was
further verified by mass spectroscopy and FTIR.
10. Tshuva, E. Y.; Groysman, S.; Goldberg, I.; Kol, M.;
Goldschmidt, Z. Organometallics 2002, 21, 662–670.
11. Groysman, S.; Tshuva, E. Y.; Goldberg, I.; Kol, M.;
Goldschmidt, Z.; Shuster, M. Organometallics 2004, 23,
5291–5299.
In conclusion, we were able to prepare a series of di-
aminophenol compounds using Mannich condensations.
By controlling the stoichiometry and reaction condi-
tions, one can build increasingly larger molecules rang-
ing from diaminodiphenols up to diaminotetraphenols.
All of the reactions (except for the preparation of 4)
12. Amudha, P.; Kandaswamy, M.; Govindasamy, L.; Vel-
murugan, D. Inorg. Chem. 1998, 37, 4486–4492.

4422
C. S. Higham et al. / Tetrahedron Letters 47 (2006) 4419–4423
˚
˚
13. Amudha, P.; Thirumavalavan, M.; Kandaswamy, M.
Polyhedron 1999, 18, 1363–1369.
16.7210(14) A, c = 17.9212(15) A, b = 105.563(2), V =
4175.9(6) A , Z = 4, Dcalcd = 1.282 Mg/m3, k = 0.71073
3
˚
A, l = 0.646 mmÀ1, F(000) = 1712, T = 100(2) K, R =
˚
14. Typical procedure to make 2a–c: In a 35 mL pressure
flask, 2 equiv of the phenol (30–40 mmol) was combined
with 2–3 equiv of 95% paraformaldehyde, and 1 equiv of
en. The reaction was heated to ꢀ85 ꢁC and stirred for two
days. The reaction, now a yellow-orange oil, was removed
from heat and cooled in an ice bath. Methanol (ꢀ25 mL)
was added to the reaction and the pressure flask was
sonicated. The product as a white precipitate formed and
was isolated from the yellow filtrate by filtration in 33–
0.0527, Rw = 0.1215. These data have been deposited (2b:
CCDC 600756, 6: CCDC 600757) at the Cambridge
Crystallographic Data Centre, Cambridge, UK. Copies of
the data can be obtained, free of charge, on application to
the CCDC, 12 Union Road, Cambridge CB2 1EZ UK
[Fax: +44 0 1223 336033 or email deposit@ccdc.cam.ac.uk].
20. Sanzenbacher, R.; Boettcher, A.; Elias, H.; Hueber, M.;
Haase, W.; Glerup, J.; Jensen, T. B.; Neuburger, M.;
Zehnder, M.; Springborg, J.; Olsen, C. E. Inorg. Chem.
1996, 35, 7493–7499.
21. Amundsen, A. R.; Whelan, J.; Bosnich, B. J. Am. Chem.
Soc. 1977, 99, 6730–6739.
22. Boettcher, A.; Elias, H.; Jaeger, E. G.; Langfelderova, H.;
Mazur, M.; Mueller, L.; Paulus, H.; Pelikan, P.; Rudolph,
M.; Valko, M. Inorg. Chem. 1993, 32, 4131–4138.
1
64% yield. Characterization for 2a: H NMR (CDCl3) d
6.76 (s, 2H), 6.64 (s, 2H), 3.79 (s, 4H, Ph–CH2–N), 2.62
(s, 4H, N–CH2), 2.13 (6H, s, CH3), 2.06 (6H, s, CH3); 13
C
NMR (DMSO) d 153.7, 129.6, 126.5, 126.2, 123.5, 122.2,
51.4, 47.2, 20.1, 15.6; FTIR data (ATR of dry film): m(N–
H) 3302 cmÀ1; HRMS (FAB+) m/z: [M+H]+ calcd
for C20H29N2O2, 329.2229; found, 329.2214; mp 104.9–
105.8 ꢁC. Characterization for 2b found in Ref. 20.
Characterization for 2c: 1H NMR (DMSO) d 7.33 (s,
2H), 7.12 (s, 2H), 3.90 (s, 4H, Ph–CH2–N), 2.69, (s, 4H,
N–CH2); 13C NMR (DMSO) d 154.7, 128.0, 127.7, 127.0,
121.4, 121.3, 50.7, 46.9; FTIR data (ATR of dry film):
m(N–H) 3156 cmÀ1; HRMS (FAB+) m/z: [M+H]+ calcd
for C16H17N2O2Cl4, 409.0044; found, 409.0043; mp 195.2–
196.8 ꢁC.
23. Typical procedure to make 3a–c: 1 equiv of en, 2 equiv of
1a–c, 5 equiv of 95% paraformaldehyde and 10 ml of
toluene were combined in a round bottomed flask
equipped with a condenser and heated at reflux for three
days. The round bottomed flask was cooled and a white
precipitate and brown oil fell out of the solution.
Methanol (10 ml) was added and the flask was sonicated
for 30 min. The resulting white precipitate was isolated by
filtration in 34–77% yield. Characterization of 3a: 1H
NMR (CDCl3) d 6.83 (s, 2H), 6.62 (s, 2H), 4.92 (s, 4H, O–
CH2–N), 4.00 (s, 4H, Ph–CH2–N), 2.98 (s, 4H, N–CH2),
2.24 (s, 6H, CH3), 2.17 (s, 6H, CH3); 13C NMR (CDCl3) d
150.2, 129.8, 129.1, 125.4, 125.4, 119.2, 82.85, 50.6, 49.7,
20.7, 15.7; HRMS (ESI) m/z: [M+H]+ calcd for
C22H28N2O2, 352.222; found, 352.2159; mp 132.8–
133.9 ꢁC. Characterization of 3b: 1H NMR (C6D6) d
7.38 (d, 2H, J = 2.4 Hz), 6.78 (d, 2H, J = 2.4 Hz), 4.59 (s,
4H, O–CH2–N), 3.76 (s, 4H, Ph–CH2–N), 2.80 (s, 4H, N–
15. Subramanian, P.; Spence, J. T.; Ortega, R.; Enemark, J.
H. Inorg. Chem. 1984, 23, 2564–2572.
16. Neves, A.; Ceccato, A. S.; Vencato, I.; Mascarenhas, Y.
P.; Erasmus-Buhr, C. J. Chem. Soc., Chem. Commun.
1992, 652–654.
17. Tshuva, E. Y.; Goldberg, I.; Kol, M. J. Am. Chem. Soc.
2000, 122, 10706–10707.
18. Balsells, J.; Carroll, P. J.; Walsh, P. J. Inorg. Chem. 2001,
40, 5568–5574.
19. X-ray crystallography: X-ray intensity data for 2b and 6
were measured at 100 K (Bruker KRYO-FLEX) on a Bruker
SMART APEX CCD-based X-ray diffractometer system
CH2), 1.58 (s, 18H, C(CH3)3), 1.32 (s, 18H, C(CH3)3); 13
NMR (C6D6) d 152.0, 142.8, 137.3, 122.9, 122.6, 120.5,
83.0, 52.3, 51.1, 35.8, 35.0, 32.4, 30.6; HRMS (ESI) m/z:
[M+H]+ calcd for C34H53N2O2, 521.4107; found,
C
˚
equipped with a Mo-target X-ray tube (k = 0.71073 A)
operated at 2000 W power. The crystals were mounted on
cryoloops using Paratone N-Exxon oil and placed under a
stream of nitrogen. The detector was placed at a distance
of 5.009 cm from the crystals. Analysis of the data sets
showed negligible decay during data collection. The data
sets were corrected for absorption using the SADABS
program. The structures were refined using the Bruker
SHELXTL Software Package (Version 6.1), and were solved
using direct methods until the final anisotropic full-matrix,
least squares refinement of F2 converged (Sheldrick, G. M.
SHELXTL, Crystallographic Software Package, version
6.10; Bruker-AXS: Madison, WI, 2000.). In compound
2b, all atom positions were located and refined. For
compound 6, all hydrogen atoms, with the exception of
the phenolic hydroxide, were assigned ideal positions and
1
521.4000; mp 153.2–153.8 ꢁC. Characterization of 3c: H
NMR (CDCl3) d 7.23 (d, 2H, J = 2.54 Hz), 6.88 (d, 2H,
J = 2.54 Hz), 5.00 (s, 4H, O–CH2–N), 4.02 (s, 4H, Ph–
CH2–N), 2.96 (s, 4H, N–CH2); 13C NMR (CDCl3) d 148.9,
128.4, 125.9, 125.2, 122.6, 122.1, 84.0, 50.4, 50.0; HRMS
(FAB+) m/z: [M+H]+ calcd for C18H17N2O2Cl4, 433.0044;
found, 433.9930; mp 199.2–200.8 ꢁC.
24. Hemwall, J. B. U.S. Patent 3126290, 1964.
25. Typical procedure to make 5a–c: In a 48 mL pressure
flask, 6 equiv (22.5 mmol) of 5a–c, 4 equiv of 95% para-
formaldehyde, and 1 equiv of en were heated to ꢀ80 ꢁC
and stirred for three days. The reaction was allowed to
cool and approximately 20 mL of ether (5a) or methanol
(5b, c) was added to the oily reaction mixture. The flask
was sonicated for 10 min and a white precipitate fell out.
The precipitate was isolated by vacuum filtration and the
product was isolated as a white solid in 27–65% yield.
refined isotropically.
A disordered solvent methanol
(approximately four per unit cell, one per asymmetric
unit) was modeled as a diffuse contributor to the reflection
array and not assigned specific atom positions. The
density, F(000), and extinction coefficient reflect the full
formula. Crystal data for 2b. Recrystallized from toluene/
CH2Cl2. C32H52N2O2; FW = 496.76 g/mol; crystal size
0.40 · 0.40 · 0.30 mm3; orthorhombic, space group Pbcn;
1
Characterization of 5a: H NMR (CDCl3) d 6.85 (s, 4H),
6.66 (s, 4H), 3.58 (s, 8H, Ph–CH2–N), 2.75 (s, 4H, N–
CH2–CH2–N), 2.21 (s, 12H, CH3), 2.18 (s, 12H, CH3); 13
C
NMR (CDCl3) d 151.7, 130.9, 128.5, 128.4, 124.3, 121.3,
55.9, 50.2, 20.3, 15.7; FTIR data (ATR of dry film): m(N–
H) 3423 cmÀ1; HRMS (ESI) m/z: [M+H]+ calcd for
C38H40N2O4, 596.380; found, 596.3564; mp 186.6–
187.4 ꢁC. Characterization of 5b: 1H NMR (CDCl3) d
7.87 (s, 4H, O–H), 7.27 (d, 4H, J = 2 Hz), 6.90 (d, 4H,
J = 2 Hz), 3.60 (s, 8H, Ph–CH2–N), 2.83 (s, 4H, N–CH2–
CH2–N), 1.39 (s, 18H, C(CH3)3), 1.28 (s, 18H, C(CH3)3);
13C NMR (CDCl3) d 152.1, 141.5, 135.9, 125.0, 123.5,
˚
˚
˚
a = 27.507(2) A, b = 10.7190(9) A, c = 10.2197(8) A,
V =3013.3(4) A , Z = 4, Dcalcd = 1.095 M g/m3, k =
3
˚
0.71073 A, l = 0.067 mmÀ1, F(000) = 1096, T = 100(2) K,
˚
R = 0.0621, Rw = 0.1459. Crystal data for 6. Recrystal-
lized from toluene/methanol. C45H53N2NaO4Zn; FW =
774.25 g/mol; crystal size 0.20 · 0.10 · 0.05 mm3; mono-
˚
clinic, space group P2(1)/n; a = 14.4659(12) A, b =

C. S. Higham et al. / Tetrahedron Letters 47 (2006) 4419–4423
4423
121.3, 57.1, 50.9, 34.7, 34.1, 31.5, 29.6; FTIR data (ATR
of dry film): m(N–H) 3136 cmÀ1; HRMS (FAB+) m/z:
[M+H]+ calcd for C62H97N2O4, 933.7448; found,
933.7771; mp 200.8–201.9 ꢁC. Characterization of 5c: H
NMR (DMSO) d 10.61 (s, 4 H, O–H), 7.35 (d, 4H, J = 2
Hz ), 7.13 (d, 4H, J = 2 Hz), 3.66 (s, 8H, Ph–CH2–N), 2.63
(s, 4H, N–CH2–CH2–N); 13C NMR (DMSO) d 151.2,
128.3, 128.1, 126.6, 122.7, 121.0, 54.3, 49.4; FTIR data
(ATR of dry film): m(N–H) 3378 cmÀ1; HRMS (FAB+) m/
z: [M+H]+ calcd for C30H25N2O4Cl8, 756.9323; found,
756.920; mp 201.7–202.9 ꢁC.
26. Madsen, S. L.; Welch, M. J.; Motekaitis, R. J.; Martell, A.
E. Nucl. Med. Biol. 1992, 19, 431–444.
27. Woodgate, P. D.; Horner, G. M.; Maynard, N. P.;
Rickard, C. E. F. J. Organomet. Chem. 2000, 595, 215–
223.
28. Korupoju, S. R.; Mangayarkarasi, N.; Zacharias, P. S.;
Mizuthani, J.; Nishihara, H. Inorg. Chem. 2002, 41, 4099–
4101.
29. Volbeda, A.; Lahm, A.; Sakiyama, F.; Suck, D. EMBO J.
1991, 10, 1607–1618.
1
30. Weston, J. Chem. Rev. 2005, 105, 2151–2174.