Inhibition of metal ion complexation by an N2O2-donor macrocycle by incorporation of an intramolecularly hydrogen-bonding pendant phenolic group

Article abstract of DOI:10.1007/s10847-011-9988-4

The synthesis and X-ray structure of a new pendant-arm derivative of a parent 14-membered N₂O₂-donor macrocycle bearing an N-substituted 6-methylene-2,4-dimethylphenol group is presented. A single crystal X-ray study shows a strong intramolecular hydrogen-bond between the pendant phenol proton and the tertiary nitrogen of the macrocyclic ring, which may inhibit its ability to bind with selected transition and post-transition metal ions.

Full text of DOI:10.1007/s10847-011-9988-4

J Incl Phenom Macrocycl Chem (2011) 71:589–592
DOI 10.1007/s10847-011-9988-4
ORIGINAL ARTICLE
Inhibition of metal ion complexation by an N2O2-donor
macrocycle by incorporation of an intramolecularly
hydrogen-bonding pendant phenolic group
•
Xue-Kui Ji Leonard F. Lindoy
•
•
Brian W. Skelton Allan H. White
Received: 21 March 2011 / Accepted: 10 May 2011 / Published online: 28 May 2011
Ó Springer Science+Business Media B.V. 2011
Abstract The synthesis and X-ray structure of a new
pendant-arm derivative of a parent 14-membered N2O2-
donor macrocycle bearing an N-substituted 6-methylene-
2,4-dimethylphenol group is presented. A single crystal
X-ray study shows a strong intramolecular hydrogen-bond
between the pendant phenol proton and the tertiary nitro-
gen of the macrocyclic ring, which may inhibit its ability to
bind with selected transition and post-transition metal ions.
characteristically resemble both simple macrocyclic and
open-chain ligand categories in their metal binding prop-
erties. For example, the resulting metal complexes often
exhibit the enhanced stability typical of macrocyclic sys-
tems while showing some degree of the coordination
flexibility characteristic of many non-macrocyclic systems
[9]. Overall, it has also been well demonstrated that the
introduction of appropriate pendant functional donor
groups generally enhances the cation-binding capacity of
simple macrocycle ligands.
Keywords Crystal structure ꢀ Hydrogen bond ꢀ
Macrocycle ꢀ N-substitution ꢀ Pendant arm ꢀ Phenol
substituent
In a previous study we have synthesised the pendant-arm
ligand 1, derived from its parent macrocyclic ring 2 (see
Scheme 1) and demonstrated that it is an excellent coordi-
nating agent towards copper(II), zinc(II), cadmium(II), sil-
ver(I) and lead(II) [7].
Introduction
The metal-ion chemistry of macrocycles that incorporate
additional donor functional groups incorporated in side
chains appended to their macrocyclic ring has been
investigated for many years [1–3]. For example, we have
undertaken studies in which various pendant arms have
been attached to both nitrogen [4–7] and carbon [8] atoms
of a macrocycle ring. Such pendant-arm derivatives
A tribute to the outstanding contribution of Len Lindoy to Inorganic,
Macrocyclic and Supramolecular Chemistry.
X.-K. Ji ꢀ L. F. Lindoy
Each of these ions forms a 1:1 complex with 1, with
individual log K values in 95% methanol (0.1 Et4ClO4,
25 °C) ranging from 6.7 (Pb) to[14 (Cu and Ag). In part,
these results motivated us to probe the metal ion binding
properties of the related 6-methylene-2,4-dimethylphenol
pendant-arm macrocycle 3 (also derived from 2, see
Scheme 1). It was anticipated that the singularly charged,
School of Chemistry, The University of Sydney, Sydney,
NSW 2006, Australia
B. W. Skelton ꢀ A. H. White (&)
Chemistry M313, School of Biomedical, Biomolecular
and Chemical Sciences, The University of Western Australia,
Crawley, WA 6009, Australia
e-mail: ahw@cyllene.uwa.edu.au
123

590
J Incl Phenom Macrocycl Chem (2011) 71:589–592
Scheme 1 Synthesis of the
6-methylene-2,4-
dimethylphenol pendant-arm
macrocycle 3
deprotonated form of 3 might lead to interesting new
metal ion chemistry when reacted with ions such as those
mentioned above. Accordingly, the synthesis of 3 was
undertaken and a preliminary investigation of its inter-
action with individual transition and post-transition metals
was made.
113.8, 121.4, 121.9, 124.8, 126.8, 127.1, 128.8, 130.0,
136.6, 144.1, 153.8, 154.5, 155.4, 156.6.
Structure determination
A full sphere of CCD/area detector diffractometer data was
measured (Bruker AXS instrument; monochromatic Mo Ka
˚
radiation, k = 0.71073 A, x-scans, 2hmax 588; T ca. 153 K)
yielding 34,166 reflections, these merging to 8,721 inde-
pendent, after ‘empirical’/multiscan ‘absorption correction’
(lMo = 0.071 mm-1; specimen: 0.55 9 0.40 9 0.02 mm;
‘T’min/max = 0.79; Rint = 0.084) which were used in the
full matrix least squares refinements on F2 (reflection
weights: (r2(Fo2) ? (0.085P)2)-1 (P = (Fo2 þ 2Fc2Þ=3)),
refining anisotropic displacement parameter forms for the
non-hydrogen atoms, hydrogen atom treatment following a
riding model, the phenolic hydrogen excepted, which was
refined in (x,y,x,Uiso). Residuals at convergence were
R1 = 0.065 (3582 reflections, I [ 2r(I)), wR2 = 0.17;
Experimental
Materials and instrumentation
1H and 13C NMR spectra were recorded in CDCl3 using a
Bruker AC200 spectrometer. Where available, all reagents
were of analytical grade and were used without further
purification. The synthesis of the precursor macrocycle 2
has been reported previously by us [7].
Synthesis of 3
S = 0.86; |Dqmax| was 0.36 eA-3. Pertinent results are
˚
given below and in Fig. 1 which shows non-hydrogen
Precursor macrocycle 2 (1.3 g, 3 mmol), 2,4-dimethyl-
phenol (0.5 g, 4 mmol) and 37% formaldehyde solution
(1 mL) were added to toluene (5 mL) and water (10 mL).
The resultant mixture was refluxed with stirring for 24 h
and then cooled to room temperature. The crude product
(3) was extracted with dichloromethane (150 mL 9 2).
The combined extracts were dried over anhydrous sodium
sulfate and evaporated on a rotary evaporator to give a
crude powder which was slurried in cold methanol and
collected as a white solid (1.15 g, 68%). This was then
recrystallised from a mixture of ethanol and dichloro-
methane (5:1) over 3 days to yield colourless crystals; mp
213–215 °C; a crystal from this batch was used for the
X-ray diffraction study. Calc. for C38H46 N2O3: C, 78.86;
atoms with 50% probability amplitude displacement
˚
envelopes, hydrogen atoms having arbitrary radii of 0.1 A.
Neutral atom complex scattering factors were employed
within the SHELXL 97 program [10].
Crystal data
C38H46N2O3, M = 578.8. Monoclinic, space group P21/c
ðC25h; No: 14Þ, a = 19.028(7), b = 16.675(6), c = 11.049
3
˚
˚
(4) A, b = 104.148(7)°, V = 3399(2) A . Dc (Z = 4) =
1.131 g cm-3
.
1
H, 8.01; N, 4.58. Found: C, 78.81 H, 7.94; N, 4.58%. H
Results and discussion
NMR (CDCl3) d 1.25 (s, (CH3)3, 18 H), 2.19 (s, CH3–4Ph,
3H), 2.21 (s, CH3–2Ph, 3H), 3.66 (s, PyCH2N, 2 H), 3.87
(s, (CH2N, 4 H), 5.19 (s, CH2O, 4 H), 6.64 (s, H–3Ph, 1H),
6.84 (d, J = 9 Hz, H-60, 2 H), 7.14 (dd, J = 2, 4 Hz, H-50),
7.18 (H–5Ph), 7.26 (d, J = 2 Hz, H-3(5), 2 H), 7.34 (d,
J = 2 Hz, H-30, 2 H), 7.61 (t, J = 8 Hz, H-4, 1 H); 13C
NMR (CDCl3) d 15.8, 20.4, 31.4, 34.1, 53.6, 57.2, 72.0,
The pendant-arm product 3 was obtained by reaction of the
macrocyclic precursor 2 with 2,4-dimethylphenol and
formaldehyde in a ‘one pot’ condensation procedure
1
(Scheme 1). The H and 13C NMR spectra (in CDCl3) as
well as the microanalytical data were in accord with the
expected structure.
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J Incl Phenom Macrocycl Chem (2011) 71:589–592
591
with the usual norms. A powerful determinant of confor-
mational stereochemistry, bearing on (at the least) local
potential coordination characteristics in the vicinity of the
phenolic oxygen appears to arise in the form of the strong
intramolecular interaction found between the phenolic
hydrogen and the nearby pyramidal macrocyclic nitrogen
atom, the lone pair of the latter being appropriately directed
C43
C42
C44
C45
C46
C1
N41
C3
C4
O4
C31
O1
C21
C244
˚
(N_H,O 1.82(3), 2.713(3) A, angle sum at N 339.6°), a
C22
stabilising six-membered ring being thereby formed. An
analogous six-membered ring involving an intramolecular
phenol-amine hydrogen bond has been reported previously
in the solid state structure of a related twenty-membered
N2O4-donor macrocyclic ligand bearing a substituted
methylenephenol pendant group [17].
C32
C243
C241
N2
C2
C33
C342
C344
C242
C341
C5
O52
C343
C51
C56
C52
C53
Conclusion
C531
C55
C54
If the strong hydrogen-bonded arrangement in the neutral
ligand is maintained in solution it will clearly inhibit metal
binding by the tertiary nitrogen donor in the macrocyclic
ring. Such an arrangement will also likely restrict the
remainder of the fourteen-membered ring to an unfavour-
able conformation for metal binding. It appears that
strongly basic conditions may be necessary to break this
hydrogen bond but, under the conditions employed by us,
any complexation behaviour has been accompanied by
hydrolysis such that only (insoluble) intractable species
could be isolated.
C551
Fig. 1 Molecular projection of 3, through the macrocycle with
crystallographic numbering scheme. O(1)–C(1,21) are 1.429(3),
˚
1.383(3); O(4)–C(4,31) 1.431(3), 1.395(2) A; C(52)–O(52) is
˚
1.371(3) A. Intraring angles at C(24,34,53,55) are 116.8(2),
116.6(2), 117.2(2), 117.5(3); angles at O(1,4) are 118.5(2), 116.4(2)°
Despite reports that some other macrocyclic systems
bearing appended phenol groups do yield stable complexes
with individual transition and post transition metal ions in
their phenol-deprotonated forms [11–16], preliminary
attempts at obtaining pure complexes of 3 with ions of the
type previously employed in the formation of these com-
plexes were unsuccessful. Where solids were obtained they
presented as intractable mixtures of metal hydrolysis
products, reflecting the basic conditions employed. In the
absence of base no products were isolated; we find no other
records of structure determinations of ligands or complexes
with the skeleton of 3 (i.e., devoid of methyl or t-butyl
groups) recorded in the Cambridge Structural Database
although structures of copper(II), silver(I) and lead(II) have
been reported for the same macrocycle with pendant
2-CH2–C5H4N (methyl pyridyl) [5], namely 1 mentioned
earlier [7]. The reluctance of 3 to yield isolable pure
complexes under neutral or basic conditions was initially
surprising and led to a single crystal X-ray study. The
structure was consistent with the stoichiometry and con-
nectivity proposed for 3 on the basis of the physical mea-
surements; a single molecule devoid of crystallographic
symmetry, and well removed from any potential mirror
symmetry as suggested in the representation in Scheme 1,
comprises the asymmetric unit for the structure (Fig. 1).
Intramolecular geometries are unremarkable and consistent
Supplementary material
Crystallographic data for 3 have been deposited with
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, CCDC
733225. Copies of this information can be obtained free of
charge on request by e-mail at deposit@ccdc.cam.ac.uk or
at http://www.ccdc.cam.ac.uk.
Acknowledgment We thank the Australian Research Council for
support.
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