Oxazoline chemistry - Part IV: Synthesis and characterization of oxazoline complexes of the zinc halides

Article abstract of DOI:10.1139/v03-166

The synthesis and characterization of 11 zinc halide derivatives that contain monodentate oxazoline ligands is described. The treatment of ether solutions of [ZnX₂] (X = Cl, Br, I) with 2-aryl- or 2-methyl-2-oxazolines results in the formation of mildly hygroscopic complexes of the general formulae [ZnX₂(ox)₂] (ox = 2-methyl-2-oxazoline (1), 2,4,4-trimethyl-2-oxazoline (2), 2-phenyl-2-oxazoline (3), or 4,4-dimethyl-2-phenyl-2-oxazoline (4)), except in the case of ZnI ₂, which does not form an isolable complex - likely for steric reasons - with oxazoline 4. Treatment of [ZnBr₂(4)₂] with 1 reveals (¹H NMR) that 1 only sluggishly displaces coordinated 4 at temperatures below 50°C. The structural characterization, via single crystal X-ray diffraction, of six of the complexes, viz. [ZnI ₂(I)₂], [ZnI₂(2)₂], [ZnX ₂(3)₂] (X = Cl, Br, or I), and [ZnBr₂(4) ₂], is also reported. All of these structurally characterized complexes are mononuclear zinc compounds with an overall distorted tetrahedral arrangement of the two halide and two oxazoline ligands around the zinc metal centre. The oxazoline series of complexes reported herein show little structural diversity, a facet which is in contrast to their substituted pyridine analogues.

Full text of DOI:10.1139/v03-166

1482
Oxazoline chemistry — Part IV: Synthesis and
characterization of oxazoline complexes of the
zinc halides1
Tosha M. Barclay, Ignacio del Río, Robert A. Gossage, and Sarah M. Jackson
Abstract: The synthesis and characterization of 11 zinc halide derivatives that contain monodentate oxazoline ligands
is described. The treatment of ether solutions of [ZnX2] (X = Cl, Br, I) with 2-aryl- or 2-methyl-2-oxazolines results in
the formation of mildly hygroscopic complexes of the general formulae [ZnX2(ox)2] (ox = 2-methyl-2-oxazoline (1),
2,4,4-trimethyl-2-oxazoline (2), 2-phenyl-2-oxazoline (3), or 4,4-dimethyl-2-phenyl-2-oxazoline (4)), except in the case
of ZnI2, which does not form an isolable complex — likely for steric reasons — with oxazoline 4. Treatment of
[ZnBr2(4)2] with 1 reveals (1H NMR) that 1 only sluggishly displaces coordinated 4 at temperatures below 50 °C. The
structural characterization, via single crystal X-ray diffraction, of six of the complexes, viz. [ZnI2(1)2], [ZnI2(2)2],
[ZnX2(3)2] (X = Cl, Br, or I), and [ZnBr2(4)2], is also reported. All of these structurally characterized complexes are
mononuclear zinc compounds with an overall distorted tetrahedral arrangement of the two halide and two oxazoline lig-
ands around the zinc metal centre. The oxazoline series of complexes reported herein show little structural diversity, a
facet which is in contrast to their substituted pyridine analogues.
Key words: oxazoline, zinc, X-ray crystal structure, coordination complex, NMR spectroscopy, Zn(II).
Résumé : On décrit la synthèse et la caractérisation d’onze dérivés d’halogénures de zinc contenant des ligands oxazo-
lines monodentates. Le traitement de solutions éthérées de [ZnX2] (X = Cl, Br, I) avec des 2-aryl- ou 2-méthyl-2-
oxazolines conduit à la formation de complexes faiblement hygroscopiques de formule générale [ZnX2(ox)2] (ox =
2-méthyl-2-oxazoline [1], 2,4,4-triméthyl-2-oxazoline [2], 2-phényl-2-oxazoline [3] ou 4,4-diméthyl-2-phényl-2-
oxazoline [4]); exceptionnellement, la réaction ZnI2 avec l’oxazoline 4 ne conduit pas à la formation d’un complexe
1
isolable, probablement en raison d’un encombrement stérique. La RMN du H montre que le traitement du [ZnBr2(4)2]
avec 1, à des températures inférieures à 50 °C, montre que le déplacement de 4 ne se fait que très difficilement. On
rapporte aussi la caractérisation par diffraction des rayons X de six de ces complexes, soit [ZnI2(1)2], [ZnI2(2)2],
[ZnX2(3)2] (X = Cl, Br ou I) et [ZnBr2(4)2]. Tous les complexes dont la structure a été caractérisée sont des composés
mononucléaires du zinc comportant un arrangement global tétraédrique déformé de deux halogènes et de deux ligands
oxazoline autour du zinc central. La série de complexes avec des oxazolines qui est rapportée ici ne présente que de
faibles variations structurales; cette caractéristique est en opposition avec ce qui a été observé avec leurs analogues
comportant des pyridines substituées.
Mots clés : oxazoline, zinc, structure cristalline par diffraction des rayons X, complexe de coordination, spectroscopie
RMN, Zn(II).
[Traduit par la Rédaction] Barclay et al. 1491
Introduction
plexes (2, 3). The high Lewis acid character of the d10 Zn2+
ion leads to the formation of many stable compounds with
N-donor ligands, including heterocycles such as pyridines
(py), imidazoles, pyrazines, oxazoles, and others (3–8).
Zinc complexes are also part of a burgeoning network of
bio-active and (or) pharmaceutical inorganic compounds (9),
The chemistry of zinc is one of the cornerstones of inor-
ganic biochemistry (1). The element is characterized by the
high stability of the +2 oxidation state and by the numerous
examples of robust four-, five-, and six-coordinate zinc com-
Received 30 July 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 30 October 2003.
T.M. Barclay.2 Department of Chemistry, North Harris College, 2700 W. W. Thorne Drive, Houston, TX 77073–3499, U.S.A.
I. del Río.3 Departamento de Química Orgánica e Inorgánica, Facultad de Química, Universidad de Oviedo, c/ Julián Claveria 8, E-
33071 Oviedo, Spain.
R.A. Gossage4 and S.M. Jackson. The David Upton Hill Laboratory of Inorganic Chemistry, 6 University Avenue, Elliott Hall,
Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, Canada.
1For Part III, see K.M. Button and R.A. Gossage. J. Heterocyclic Chem. 40, 513 (2003).
2Corresponding author (crystallography, complexes 10–13 and 15) (e-mail: Tosha.M.Barclay@nhmccd.edu).
3Corresponding author (crystallography, complex 7) (e-mail: irc@sauron.quimica.uniovi.es).
4Corresponding author (general) (e-mail: rgossage@acadiau.ca).
Can. J. Chem. 81: 1482–1491 (2003)
doi: 10.1139/V03-166
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1483
and even simple solutions of Zn2+ ions or [Zn(N-donor)x]2+
complexes have a number of noteworthy biological activities
(10). For example, [ZnCl2(H2NiPr)2] has recently been
shown to prolong (i.e., stabilize) the potency of enzymes in
aqueous media (11). The presence of zinc ions can also in-
crease the potency of certain biologically active compounds,
such as the enzyme inhibitory effect of bis(5-amidino-2-
benzimidazolyl)methane (BABIM). This enhancement has
been shown to be due to the binding of a [Zn(BABIM)]
complex into the active site of a protease enzyme (12a). Re-
cently, zinc complexes of neocuprine, a phenanthroline de-
rivative, have been shown to be site-specific RNA cleavage
agents (12b). Related simple Zn coordination complexes
have also shown promise in the treatment of diabetes (12c,
12d).
Fig. 1.
In direct relation to this study is the hypothesis that
oxazoline-containing drug candidates (12e) such as 4-
carbomethoxy-2-phenyl-2-oxazoline (viz., L-573,655: Fig. 1)
inhibit lipid A biosynthesis by coordination with an enzyme-
bound Zn atom (i.e., a Zn–oxazoline complex is formed with
L-573,655; refs. 12f–12i). As part of a larger study concern-
ing the coordination and medicinal chemistry of zinc (13)
and oxazoline (i.e., 4,5-dihydro-2-oxazole) ligands in gen-
eral (14),5 we have undertaken a study of simple mono-
dentate oxazolines (1–4: Fig. 1) as ligands for binding to the
zinc halides. In this report, we detail the synthesis and char-
acterization (NMR and X-ray analyses, etc.) of a series of
Zn halide complexes that incorporate monodentate 2-
oxazoline (15) derivatives. A further reason for this investi-
gation is the knowledge that zinc halides are commonly used
as catalysts to form oxazolines via treatment of organic
cyanides with amino-alcohols (14c). A possible by-product
of this procedure is an oxazoline–Zn complex, and hence,
we wanted to begin a general investigation of such species.
Examination of 5–15 by elemental analysis measurements
are, in all cases, consistent with the formation of complexes
of general formula [ZnnX2n(oxazoline)2n] (i.e., 2:1 ligand:ZnX2
1
species). Characterization of these complexes by H NMR
spectroscopy reveals the presence of a single oxazoline
1
ligand environment. Further to this, the H NMR resonances
for the presumably coordinated oxazolines are shifted rela-
tive to that of the free ligands,6 a situation that is mimicked
by observation of a decrease in the ν(C=N) IR stretching fre-
quencies of the oxazoline for the complexes, as expected.
1
Specifically, all H NMR chemical shifts of complexes in-
corporating 1 are notably deshielded relative to the free
ligand form,6 an observation consistent with donation of
electron density from the ligand to the Lewis acidic Zn cen-
tre. Complexes of 2 show a similar trend; however, the
methyl resonances on C-2 of the oxazoline are notably
shielded relative to free 2. This suggests that this methyl
group is forced to be in close proximity to the metal centre,
likely because of steric effects of the methyl substituents on
C-4 (vide infra). In the case of ligands 3 and 4, shifts are
less pronounced relative to the free ligands, although the
methylene protons of 3 show a small shift (positive in the
case of the Br and I derivatives and negative for the Cl) upon
coordination.
Zinc halides are often employed as catalysts for the syn-
thesis of 2-oxazolines via treatment of an alkyl or aryl cya-
nide with an appropriate amino-alcohol at elevated
temperatures (14c, 15, 16). With this in mind, it seems feasi-
ble that Zn–oxazoline complexes may also be produced as
by-products in these reactions. We have taken a cursory look
at the stability of some of these species by a simple metathe-
sis reaction. Treatment of complex 15 in an NMR tube with
2 equiv of 1 and maintenance at room temperature (RT) for
a period of 1 day does not result in any loss of signal inten-
sity of 15, nor presence of any form of an intermediate, and
Results and discussion
Syntheses and spectroscopic characterization
The treatment of ether solutions (or suspensions) of the
zinc halides (ZnX2; X = Cl, Br, or I) with an excess of a 2-
oxazoline (Fig. 1) leads to rapid formation of isolable white
precipitates. A sole exception to this observation is the reac-
tion of ZnI2 with oxazoline 4; this particular reaction invari-
ably leads to the formation of oily inextractable mixtures,
from which no pure compounds could be obtained. Metathe-
sis reactions, involving exchange of Br or NO3 anions with
I– sources, were likewise unsuccessful. The aforementioned
isolated materials are moderately hygroscopic, a property
that is more pronounced with the 2-methyl oxazoline com-
plexes (i.e., 5–10) when compared with the 2-phenyl deriva-
tives 11–15. All compounds decomposed on melting in air to
form colourless oils. The initial isolated materials in all
cases are white powders; crystalline samples, obtained as de-
scribed in the Experimental section, are clear and colourless
but darken over several weeks in air.
5 R.A. Gossage, K.J. Haller, H. Jenkins, and S.M. Jackson. Unpublished results.
6 1H NMR data (300 MHz, CDCl3) δ: 1: 4.12 (t, 2H, J = 9.5, CH2O), 3.73 (t, 2H, CH2N), 1.86 (s, 3H, CH3); 2: 3.80 (s, 2H, CH2O), 1.83 (s,
3H, N=C-CH3), 1.14 (s, 6H, CH3); 3: 7.95 (m, 2H, ArH), 7.42 (m, 3H, ArH), 4.40 (t, 2H, CH2O), 4.04 (t, 2H, CH2N); 4: 7.86 (m, 2H, ArH),
7.28 (m, 3H, ArH), 3.95 (s, 2H, CH2), 1.25 (s, 6H, CH3). IR data (thin film; KBr; υ[C=N]): 1: 1670 (st); 2: 1670 (st); 3: 1645 (st); 4: 1648
(st).
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Fig. 2. ORTEP representation of complex 7.
no evidence for the formation of complex 5. Heating this
mixture for 12 h at about 50 °C results in only a small
amount (<10%) of 5 being detected. These results indicate a
robust nature of these materials, and it seems that only by
treating with a large excess of water, as is typically done in
the synthesis of ligands 1–4 employing Zn halides (14c, 15,
16), are the free oxazolines released. This is also suggested
by the relatively hygroscopic nature of these complexes, a
property that is a likely cause of our inability to obtain a re-
producible elemental analysis in the case of complex 14.
metallated (i.e., η2-N,C) 2-aryl-2-oxazolines has been the
subject of numerous studies (15). To our knowledge, there is
no structural data of any Zn halide complex with a mono-
dentate oxazoline; hence, we felt a structural investigation of
this class of materials was in order. Thus, we have carried
out single crystal X-ray structure analysis of six of the com-
plexes (7, 10–13, and 15) synthesized herein. In addition,
there are very few structurally characterized [ZnI2(N-do-
nor)n] complexes (18–20), and thus the characterization of
three (7, 10, and 13) such derivatives will help to expand the
structural database on this class of ZnI2 coordination com-
pounds.
Solid-state (crystal) structures
The molecular structures of complexes 7, 10–13, and 15
can be found in Figs. 2–7, respectively, and the general crys-
tal data can be found in Tables 1 and 2.
Zinc halides are well known to react with N-donor com-
pounds to form mononuclear complexes with an overall dis-
torted tetrahedral disposition of ligands around the Zn atom.
For example, ZnCl2 forms simple complexes of the general
formulae [ZnCl2(N)2] with N = py, 4-(vinyl)py, 4-(NC)py, 4-
(acetyl)py, 3,4,5-Cl3py, 3-(F3C)py, and 4-(Me)py (17). How-
ever, a number of interesting polymeric materials are formed
(3, 6, 17a) with other pyridine derivatives. For example, both
3,5-Cl2py and 3,5-Br2py form polymeric complexes with
ZnCl2 (i.e., [Zn(µ-Cl)2(3,5-Xpy)2]∞) in which the Zn atom is
in an octahedral coordination geometry. Linear (and tetrahe-
dral at Zn) bridged species are formed with 4,4′-bipy and
ZnCl2 (i.e., [ZnCl2(4,4′-bipy)]∞), but Magnus-type salts (i.e.,
[Zn([MeO]2py)4]2+ [Zn2Br6]2–) can be formed by treating
ZnBr2 with 2,6-(MeO)2-py (17a).
All six complexes are mononuclear species in the solid
state with an approximate tetrahedral array of the two halide
and two oxazoline ligands around the metal centre. As
expected, the binding of the oxazoline fragment is, in all
cases, via coordination of the imine N-atom of the hetero-
cyclic ring (15). Comparative examples of related structur-
ally characterized Zn oxazolines are few (21–24) but include
complexes such as [η2-N,N′-(1,2-bis{4S-4-isopropyl-2-oxazolin-
2-yl}benzene} zinc(II) chloride] (21). The bond lengths be-
tween Zn and the donor ligands for complexes 7, 11–13, and
15 are in the range typical (3–8, 15–25) for Zn—N and
Zn—X bonds (Table 2). These data can be compared with,
for example, the halide complexes (4c, 17a, 18b) [ZnCl2(4-
Me-py)2] (Zn—Nav = 2.044 Å; Zn—Clav = 2.208 Å),
[ZnBr2(3-CF3-py)2] (Zn—N = 2.084 Å; Zn—Br = 2.375 Å),
There is currently a dearth of structural information on
monodentate oxazoline complexes (15), despite the fact that
the coordination chemistry of bis-oxazolines and cyclo-
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Barclay et al.
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Fig. 3. ORTEP representation of complex 10.
Fig. 4. ORTEP representation depicting both molecules of complex 11 found in the unit cell.
and [ZnI2(2-amino-2-thiazole)2] (17: Zn—Nav = 2.023 Å;
Zn—Iav 2.384 Å). Complex 10 is perhaps the most unusual
of the set, as it displays Zn—I bonds that are at the upper
range of known Zn—I bond lengths (cf. 17). Similar long
Zn—I bonds are found (18a) in the complex [ZnI2(η2-N,N′-
{C5H4N}3N)] (18). The reason for the long bonds found
here may be because of steric effects imposed on the large I
atoms relative to tightly bound oxazoline 2 (26). Note that
this particular fragment contains two sterically bulky methyl
substituents on carbons (labelled) C4 and C10 (Fig. 3) of the
oxazoline ring. This structure sheds some light on the ob-
served solution properties that involve the shielding of the
proton resonances (vide supra) of the methyl group (C1).
The Zn1—C1 and C7 distances are 3.43 and 3.38 Å, respec-
tively. The I-Zn-I angles (Table 2) of 10 and 13 are consid-
erably narrower than that of 18 (117.48(3)°) but similar to
that found in the complexes [ZnI2(BpsMe2)] (113.48(5)°;
BpsMe2 = [bis(3,5-dimethylpyrazolyl)dimethylsilane]),
[ZnI2(C6H12N4)2] (111.5(1)°), and [ZnI2(3,5-[tBuph]2pzH)2]
(112.2(1)°), all of which have sterically demanding N-donor
ligands (19, 20a, 20b). Complexes 11 and 12 both contain
two unique molecules of the complex in the unit cell. The
main differences between these molecules is the torsion an-
gles between the phenyl group formally on C-2 and the
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Can. J. Chem. Vol. 81, 2003
Fig. 5. ORTEP representation depicting both molecules of complex 12 found in the unit cell.
Fig. 7. ORTEP representation of complex 15.
Fig. 6. ORTEP representation of complex 13.
oxazoline unit. These two materials are virtually
isomorphous. Further structural details for all six complexes
reported here can be found in the supporting data.7
7 Supplementary data may be purchased from the Depository of Unpublished Data, Document Delivery, CISTI, National Research Council
Canada, Ottawa, ON K1A 0S2, Canada (http://www.nrc.ca/cisti/irm/unpub_e.shtml for information on ordering electronically). CCDC
213243–213248 contain the supplementary data for for complexes 7, 10–12, and 15 respectively. These data can be obtained, free of charge,
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, U.K.; fax
+44 1223 336033; or deposit@ccdc.cam.ac.uk).
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Can. J. Chem. Vol. 81, 2003
Table 2. Selected bond lengths (Å) and angles (°) for complexes 7, 10–13, and 15.
Complex
Bond
Bond lengths (Å)
Bonds
Bond angles (°)
7
Zn1—I1
Zn1—I2
Zn—N1
Zn1—N2
N1—Ca
2.567(2)
2.590(2)
2.021(9)
2.004(14)
1.27(2)
I1-Zn1-I2
N1-Zn1-N2
111.67(6)
99.7(5)
10
Zn1—I1
Zn1—I2
Zn1—N1
Zn1—N2
N1—Ca
N2—Ca
2.5937(7)
2.5827(8)
2.059(4)
2.074(4)
1.280(7)
1.268(6)
Cl1-Zn1-Cl2
N1-Zn1-N2
112.18(2)
106.48(15)
11b
12b
13
Zn1—Cl1
Zn1—Cl2
Zn1—N1
Zn1—N2
N1—Ca
2.2352(7)
2.2432(7)
2.026(2)
2.050(2)
1.282(3)
Cl1-Zn1-Cl2
N1-Zn1-N2
111.97(3)
103.70(7)
Zn1—Br1
Zn1—Br2
Zn1—N1
Zn1—N2
N1—Ca
2.3712(7)
2.3712(6)
2.053(3)
2.025(3)
1.285(4)
Br1-Zn1- Br2
N1-Zn1-N2
108.61(3)
104.59(12)
Zn1—I1
Zn1—I2
Zn1—N1
Zn1—N2
N1—Ca
2.5706(8)
2.5937(7)
2.052(3)
2.042(3)
1.282(5)
I1-Zn1-I2
N1-Zn1-N2
110.42(2)
107.51(13)
15
Zn1—Br1
Zn1—N1
N1—Ca
2.3905(5)
2.076(3)
1.269(4)
Br1c-Zn1-Br1
N1c-Zn1-N1
112.92(3)
119.07(14)
aRefers to the formal N=C of the oxazoline ligands containing N1.
bTwo distinct molecules in the unit cell; values given for Zn1 complex only (see Supplementary data).
cSymmetry code = –x – 1/2, –y + 1/2, z.
1
4 Å molecular sieves. H NMR spectra (CDCl3 solution)
were recorded at RT using a Bruker AC-250 NMR spec-
trometer located at the Atlantic Regional Magnetic Reso-
nance Centre (ARMRC) (Halifax, N.S., Canada), operating
at 250 MHz, or were recorded using a Bruker Avance 300
NMR spectrometer located at the Acadia Centre for Micro-
structural Analysis (ACMA) (Wolfville, N.S., Canada), oper-
ating at 300 MHz. Chemical shifts are reported in ppm using
TMS (and (or) residual solvent resonance) as internal stan-
dard (δTMS = 0.00 ppm). Coupling constants are reported in
Hertz. IR spectra were recorded as nujol muls (except where
noted) on a PerkinElmer 683 or 283B IR spectrometer; re-
ported values are in units of cm–1. Melting points were re-
corded in air on a Mel-Temp II apparatus and are
uncorrected. Elemental analyses measurements were per-
formed at the Lakehead University Centre for Analytical
Services (LUCAS) located in Thunder Bay, Ont., Canada.
Conclusions
The treatment of ether solutions of ZnX2 with oxazolines
1–4 results in the formation of mildly hygroscopic mono-
nuclear bis-oxazoline complexes, except in the case of X = I
and oxazoline 4. Six derivatives have been characterized by
single crystal X-ray diffraction. These materials represent
the first series of mononuclear oxazoline complexes of Zn2+
to be fully characterized. The medicinal properties of these
materials are currently under investigation and will be re-
ported in a separate disclosure.
Experimental
General
All reactions were carried out in air, using commercially
available, reagent-grade solvents. Zinc halides and ligands
1–4 (Fig. 1) were purchased commercially and used as re-
ceived, with the exception of ZnCl2. This material was dried
by heating thrice to the melt under vacuum (approximately
(approx.) 2000 Pa), and then the solid was cooled to RT un-
der an atmosphere of dry argon gas. THF was stored over
Synthesis of [dichlorobis{η1-N-(2-methyl-2-oxazoline)}zinc]
(5)
Solid zinc chloride (4.2 g, 31 mmol) was dissolved in
150 mL of diethylether by stirring the mixture at RT for
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Barclay et al.
1489
Synthesis of [diiodobis{η1-N-(2,4,4-methyl-2-
15 min. This mixture was then filtered to remove any undis-
solved material. To the rapidly stirring (clear and colourless)
solution was added (via syringe) 8.0 mL (94 mmol) of 1 in a
single portion. A white precipitate began to form almost im-
mediately. Stirring was continued for a further 12 h at RT,
and the resulting solid was isolated by filtration. This mate-
rial was then washed thrice with Et2O (35 mL) and then al-
lowed to dry in air. Yield 8.0 g (84%) of a white, slightly
hygroscopic solid. Crystals of 5, suitable for X-ray diffrac-
tion, grew after a CH2Cl2 solution of 5, layered with Et2O,
was left standing for several days at RT. mp > 105 °C
oxazoline)}zinc] (10)
As for 5, ZnI2 (3.3 g, 10 mmol; ether suspension) was
treated with 2 (2.7 mL, 21 mmol). Yield 4.9 g (90%). Crys-
tals, suitable for X-ray diffraction, grew from a sealed solu-
tion of 10 (CH2Cl2) layered with Et2O, after standing at RT
1
for several days. mp > 159 °C (decomp.). IR: 1630 (st). H
NMR (250 MHz) δ: 4.17 (s, 2H, CH2O), 2.27 (s, 3H, N=C-
CH3), 1.61 (s, 6H, CH3). Calcd. for C16H18N2O2ZnI2 (%): C
26.42, H 4.06, N 5.14, found: C 26.27, H 3.86, N 5.02.
1
Synthesis of [dichlorobis{η1-N-(2-phenyl-2-
oxazoline)}zinc] (11)
(decomposition temperature (decomp.)). IR: 1650 (st). H
NMR (250 MHz) δ: 4.50 (t, 2H, J = 9.8, CH2O), 3.98 (t, 2H,
J
= 9.8, CH2N), 2.27 (s, 3H, CH3). Calcd. for
As for 5, ZnCl2 (2.0 g, 15 mmol) in Et2O (125 mL) was
treated with 3 (3.9 mL, 30 mmol), and the resulting white
solid was washed with Et2O (2 × 15 mL) and then air-dried.
Yield 4.77 g (74%). mp > 179 °C (decomp.). IR: 1618 (st).
1H NMR δ: 7.78 (d, 2H, J = 7.5, ArH), 7.61 (t, 1H, ArH),
7.41 (t, 2H, J = 7.6, ArH), 4.33 (m, 4H, CH2CH2). Calcd.
for C16H18N2O2Cl2Zn: C 50.20, H 4.21, N 6.51; found: C
50.47, H 4.26, N 6.68.
C8H14N2O2Cl2Zn·(H2O) (%): C 29.72, H 4.55, N 8.67;
found: C 29.72, H 4.97, N 8.63.
Synthesis of [dibromobis{η1-N-(2-methyl-2-oxazoline)}zinc]
(6)
In a reaction analogous to that used to produce 5, zinc
bromide (1.0 g, 4.4 mmol) in Et2O was treated with 1 (2.1
equiv). Yield 1.6 g (92%, hygroscopic solid). mp > 72 °C
(decomp.). IR: 1650 (st). 1H NMR (250 MHz) δ: 4.50 (t, 2H,
J = 9.8, CH2O), 4.00 (t, 2H, J = 9.8, CH2N), 2.29 (s, 3H,
CH3). Calcd. for C8H14N2O2ZnBr2·0.5(H2O): C 23.76, H
3.74, N 6.93; found: C 23.53, H 3.63, N 6.85.
Synthesis of [dibromobis{η1-N-(2-phenyl-2-
oxazoline)}zinc] (12)
As for 5, ZnBr2 (2.1 g, 9.3 mmol) in Et2O (100 mL) was
treated with 3 (2.5 mL, 19 mmol), and the solid was washed
with Et2O (2 × 15 mL) and then air-dried. Yield 4.71 g
1
(48%). mp > 170 °C (decomp.). IR: 1620 (st). H NMR δ:
Synthesis of [diiodobis{η1-N-(2-methyl-2-oxazoline)}zinc]
(7)
7.76 (d, 2H, J = 8.0, ArH), 7.58 (t, 1H, ArH), 7.35 (t, 2H,
J = 7.9, ArH), 4.47 (m, 4H, CH2CH2). Calcd. for
C16H18N2O2ZnBr2: C 41.61, H 3.49, N 5.39; found: C 41.66,
H 3.49, N 5.30.
As for 5, zinc iodide (3.0 g, 9.4 mmol), suspended in
Et2O–THF (60 mL : 10 mL), was treated with 2.4 mL
(28 mmol) of 1. Yield 4.0 g (87%, hygroscopic white solid).
Crystals, suitable for X-ray diffraction, were grown from a
solution of 3 (CH2Cl2 layered with Et2O) that had been left
standing at RT for several days. mp > 94 °C (decomp.). IR:
Synthesis of [diiodobis{η1-N-(2-phenyl-2-oxazoline)}zinc]
(13)
As for 5, ZnI2 (1.4 g, 4.4 mmol) was suspended in Et2O
(25 mL), and the mixture was then treated with 3 (1.1 mL,
8.4 mmol), and the light yellow solid was washed with Et2O
(2 × 10 mL) and then air-dried. Yield 2.55 g (99%). mp >
1
1650 (st). H NMR (250 MHz) δ: 4.50 (t, 2H, J = 9.8,
CH2O), 4.02 (t, 2H, J = 9.8, CH2N), 2.29 (s, 3H, CH3).
Calcd. for C8H14N2O2ZnI2·0.25(H2O): C 19.45, H 2.96, N
5.67; found: C 19.21, H 2.76, N 5.57.
1
193 °C (decomp.). IR: 1620 (st). H NMR δ: 7.76 (d, J =
7.9, 2H, ArH), 7.61 (t, 1H, ArH), 7.38 (t, 2H, J = 8.0, ArH),
4.43 (m, 4H, CH2CH2). Calcd. for C16H18N2O2ZnI2 (%): C
35.24, H 2.96, N 4.57; found: C 34.90, H 2.97, N 4.43.
Synthesis of [dichlorobis{η1-N-(2,4,4-trimethyl-2-
oxazoline)}zinc] (8)
As for 5, zinc chloride (1.2 g, 8.8 mmol) in Et2O was
treated with 2 (2.2 mL, 17 mmol), and the solid was washed
with Et2O (2 × 35 mL) and petroleum ether (50 mL); the
product can be further recrystallized from a 1:1 mixture of
CH2Cl2–Et2O. Yield 2.0 g (65%). mp > 124 °C (decomp.).
Synthesis of [dichlorobis{η1-N-(4,4-dimethyl-2-phenyl-2-
oxazoline)}zinc] (14)
A sample of ZnCl2 (2.25 g, 16.5 mmol) was dissolved in
100 mL of Et2O, and the solution was then filtered. Com-
pound 4 (5.6 mL, 33 mmol) was added, and the mixture was
then stirred at RT for 2 h. The resulting white solid was col-
lected by filtration and washed with Et2O (2 × 25 mL). Yield
1
IR: 1635 (st). H NMR (250 MHz) δ: 4.17 (s, 2H, CH2O),
2.27 (s, 3H, N=C-CH3), 1.61 (s, 6H, CH3). Calcd. for
C12H22N2O2Cl2Zn·0.5(CH2Cl2): C 37.06, H 5.72, N 6.92;
found: C 37.29, H 5.86, N 6.92.
1
4.2 g (58%). mp > 174 °C (decomp.). IR: 1620 (st). H
NMR δ: 7.86 (m, 2H, ArH), 7.28 (m, 3H, ArH), 3.95 (s, 2H,
CH2), 1.25 (s, 6H, CH3). Calcd. for C22H26N2O2Cl2Zn: C
54.29, H 5.38, N 5.76; found: a reproducible elemental anal-
ysis ( 0.4%) could not be obtained for this material.
Synthesis of [dibromobis{η1-N-(2,4,4-trimethyl-2-
oxazoline)}zinc] (9)
As for 5, using ZnBr2 (1.4 g, 6.2 mmol; ether suspension)
and 2 (1.7 mL, 13 mmol). Yield 2.7 g (96%). mp > 172 °C
(decomp.). IR: 1625 (st). 1H NMR (250 MHz) δ: 4.18 (s, 2H,
CH2O), 2.29 (s, 3H, N=C-CH3), 1.68 (s, 6H, CH3). Calcd.
for C12H22N2O2Br2Zn: C 31.92, H 4.91, N 6.20; found: C
32.16, H 4.59, N 6.21.
Synthesis of [dibromobis{η1-N-(4,4-dimethyl-2-phenyl-2-
oxazoline)}zinc] (15)
As for 5, ZnBr2 (2.0 g, 8.9 mmol) in Et2O (100 mL) was
treated with 4 (3.0 mL, 18 mmol), then stirred for 2 h, and
© 2003 NRC Canada

1490
Can. J. Chem. Vol. 81, 2003
4. (a) W.L. Steffen and G.J. Palenik. Inorg. Chem. 16, 1119
(1977); (b) W.L. Steffen and G.J. Palenik. Acta Cryst. B32,
298 (1976); (c) H. Lynton and M.C. Sears. Can. J. Chem. 49,
3418 (1971); (d) S. ¤de, A. Ataç, and Ô. Yurdakul. J. Molecu-
lar Struct. 605, 103 (2002).
5. (a) B.K.S. Lundberg. Acta Cryst. 21, 901 (1966); (b) N.
Galván-Tejada, S. Bernès, S.E. Castillo-Blum, H. Nöth, R.
Vicente, and N. Barba-Behrens. J. Inorg. Biochem. 91, 339
(2002).
then evaporated at RT. Yield 2.0 g (65%). mp > 168 °C
1
(decomp.). IR: 1618 (st). H NMR δ: 7.86 (m, 2H, ArH),
7.28 (m, 3H, ArH), 3.95 (s, 2H, CH2), 1.25 (s, 6H, CH3).
Calcd. for C22H26N2O2ZnBr2: C 45.90, H 4.55, N 4.87;
found: C 45.68, H 4.46, N 4.84.
Single crystal X-ray structure determinations
X-ray structure of 7
6. C. Hu and U. Englert. Acta Cryst. C57, 1251 (2001).
7. B. Hajjem, A. Kallel, I. Svoboda, and J. Sakurai. Acta Cryst.
C48, 1002 (1992).
Suitable white crystals were obtained by slow diffusion of
Et2O into a CHCl3 solution of the complex. Diffraction data
were collected on a Nonius Kappa-CCD diffractometer
equipped with a 95 mm CCD camera and a k-goniostat, us-
ing graphite-monochromated Cu Kα radiation. Data were re-
8. Purine: (a) H.L. Laity and M.R. Taylor. Acta Cryst. C51, 1791
(1995); Quinoline: (b) Y. Cui, D. Long, W. Chen, and J.
Huang. Acta Cryst. C54, 1605 (1998); Thiadiazole: (c) K.Sh.
Khusenov, B.B. Umarov, M.M. Ishankhodzhaeva, N.A.
Parpiev, S.A. Talipov, and B.T. Ibragimov. Koord. Khim. 23,
596 (1997); Russ. J. Coord. Chem. 23, 555 (1997);
Antazoline: (d) M. Parvez and M. Rusiewicz. Acta Cryst. C51,
2277 (1995); Guanine: (e) F. Zamora and M. Sabat. Inorg.
Chem. 41, 4976 (2002).
2
duced to Fo values. A numerical absorption correction was
applied using Gaussian integration (27), with max and min
transmission factors of 0.024 and 0.009, respectively. The
structure was solved by Patterson interpretation, using the
program DIRDIF-96 (28). Isotropic and full matrix
anisotropic least-squares refinements were carried out using
SHELXL-97 (29). All non-H atoms were refined anisotro-
pically, except N2, C5, and O2, which were isotropically re-
fined. All the hydrogen atom positions were geometrically
calculated and refined riding on their parent atoms. The mo-
lecular plots were made with the EUCLID program package
(30). The WINGX program system (31) was used through-
out the structure determinations.
9. See, for example: P.J. Blower. Ann. Rep. Prog. Chem. Sect. A.
95, 631 (1999); 96, 645 (2000); 97, 587 (2001); 98, 615
(2002).
10. (a) A. Monstrolorenzo, A. Scozzafava, and C.T. Supuran. Eur.
J. Pharm. Sci. 11, 99 (2000); (b) K.D. Rainsford and M.W.
Whitehouse. J. Pharm. Pharmacol. 44, 476 (1992); (c) A.
Scozzafava, L. Menabuoni, F. Minicione, G. Minicione, and
C.T. Supuran. Bioorg. Med. Chem. Lett. 11, 575 (2001);
(d) Tz.B. Kovachev, P.N. Stamberov, D.S. Ivanov, M.K.
Mitcheva, S.P. Marinova, H.A. Astroug, and J.N. Stoychkov.
Pharmazie, 49, 25 (1994); (e) G. Abou-Mohamed, A.
Papapetropoulos, J.D. Catavas, and R.W. Caldwell. Eur. J.
Pharmacol. 341, 265 (1998).
X-ray structures of 10–13 and 15
Suitable crystals were grown from solutions of the com-
plexes in dichloromethane that had been layered with Et2O
and allowed to stand at RT (or at –10 °C) for several days.
Crystals were mounted on a glass fibre, covered in epoxy,
and data was collected on a Smart 1000 CCD diffractometer
using Mo Kα radiation (graphite monochromated). Isotropic
and full matrix anisotropic least-squares refinements were
carried out using SHELXL-97 (29). It should be noted that
complex 15 has twofold imposed crystallographic symmetry.
11. J. García-Cañadas, J.M. Pérez, A.G. Quiroga, M.A. Fuertas, C.
Alonso, and C. Navarro-Ranninger. J. Chem. Soc. Dalton
Trans. 2283 (2002).
12. (a) B.A. Katz, J.M. Clark, J.S. Finer-Moore, T.E. Jenkins, C.R.
Johnson, M.J. Ross, C. Luong, W.R. Moore, and R.M. Stroud.
Nature (London), 391, 608 (1998); (b) A. Whitney, G. Gavory,
and S. Balasubramanian. Chem. Commun. 36 (2003); (c) Y.
Yoshikawa, E. Ueda, H. Sakurai, and Y. Kojima. Chem.
Pharm. Bull. 51, 230 (2003); (d) H. Sakurai, Y. Kojima, Y.
Yoshima, K. Kawabe, and H. Yasui. Coord. Chem. Rev. 226,
187 (2002); (e) C.H. Stammer, A.N. Wilson, C.F. Spencer,
F.W. Bachelor, F.W. Holly, and K. Folkers. J. Am. Chem. Soc.
79, 3236 (1957); (f) H.R. Onishi, B.A. Pelak, L.S.
Gerckens, L.L. Silver, F.W. Kahan, M.-H. Chen, A.A. Patchett,
S.M. Galloway, S.A. Hyland, M.S. Anderson, and C.R.H.
Raetz. Nature (London), 274, 980 (1996); (g) M.-H. Chen,
M.G. Steiner, S.E. de Laszlo, A.A. Patchett, M.S. Anderson,
S.A. Hyland, H.R. Onishi, L.L. Silver, and C.R.H. Raetz.
Bioorg. Med. Chem. Lett. 9, 313 (1999); (h) T. Kline, N.H.
Anderson, E.A. Harwood, J. Bowman, A. Malada, S. Endsley,
A.L. Erwin, M. Doyle, S. Fong, A.L. Harris, B. Mendelsohn,
K. Mdluli, C.R.H. Raetz, C.K. Stover, P.R. White, A.
Yabannavar, and S. Zhu. J. Med. Chem. 45, 3112 (2002);
(i) M.C. Rirrung, N. Tumey, A.L. McClerren, and C.R.H.
Raetz. J. Am. Chem. Soc. 125, 1575 (2003).
Acknowledgements
The authors are indebted to the support of the Natural Sci-
ence and Engineering Research Council (NSERC) (RAG),
Acadia University (RAG), and MCYT (BQU2002–02623:
IdR). Mr. Ramsey E. Beveridge is thanked for recording
some NMR spectra.
References
1. (a) S. Rahuel-Clermont and M.F. Dunn. The biological chem-
istry of zinc. In Copper and zinc in inflammatory and degener-
ative diseases. Edited by K.D. Rainsford, R. Milanino, J.R.J.
Sorenson, and G.P. Velo. Kluwer Academic Publications,
Boston. 1998. Chap 4, pp. 47–59; (b) J.F. Riordan. Med. Clin.
N. Am. 60, 661 (1976); (c) B.L. Vallee and D.S. Auld. Bio-
chemistry, 29, 5647 (1990); (d) C.L. Keen and M.E. Gershwin.
Ann. Rev. Nutr. 10, 415 (1990); (e) B.L. Vallee and D.S. Auld.
Acc. Chem. Res. 26, 543 (1993).
13. I. del Río, R.A. Gossage, M.S. Hannu, M. Lutz, A.L. Spek,
and G. van Koten. Can. J. Chem. 78, 1620 (2000).
2. F.A. Cotton and G. Wilkinson. Advanced inorganic chemistry.
4th ed. John Wiley & Sons, Toronto. 1980. Chap 19, pp. 589–
616.
14. (a) K.M. Button and R.A. Gossage. J. Heterocyclic Chem. 40,
513 (2003); (b) J.T. Banks, K.M. Button, R.A. Gossage, T.D.
Hamilton, and K.E. Kershaw. Heterocycles, 55, 2251 (2001);
3. C. Hu and U. Englert. CrystEngComm. 23, 1 (2001).
© 2003 NRC Canada

Barclay et al.
(c) K.M. Button, R.A. Gossage, and R.K.R. Phillips. Synth.
Commun. 32, 363 (2002); (d) K.M. Button, R.A. Gossage, and
H. Jenkins. Poster P-207. International Conference on
Organometallic Chemistry. 20th. Corfu, Greece. 2002.
15. M. Gómez, G. Muller, and M. Rocamora. Coord. Chem. Rev.
193–195, 769 (1999), and refs. therein.
1491
García-Vásquez, and A. Sousa. Z. Anorg. Allg. Chem. 628,
1210 (2002).
23. G.K. Patra, I. Goldberg, A. Sarkar, S. Chowdhury, and D.
Datta. Inorg. Chim. Acta, 344, 7 (2003).
24. H. Kooijman, A.L. Spek, C. Zondervan, and B.L. Feringa.
Acta Cryst. E58, m429 (2002).
16. (a) H. Witte and W. Seeliger. Liebigs Ann. Chem. 999 (1974);
(b) A.I. Meyers. J. Heterocyclic Chem. 35, 991 (1998), and
refs. therein.
17. (a) D.J. Darensbourg, S.J. Lewis, J.L. Rodgers, and J.C.
Yarbrough. Inorg. Chem. 42, 581 (2003); (b) E. Ôahin, S. ¤de,
A. Ataç, and Ô. Yurdakul. J. Molecular Struct. 616, 253
(2002); (c) E. Ôahin, S. ¤de, M. Kurt, and Ô. Yurdakul. J. Mo-
lecular Struct. 616, 259 (2002).
18. (a) J. Ni, Y. Xie, X. Liu, and Q. Liu. Appl. Organomet. Chem.
17, 315 (2003); (b) K. Davarski, J. Macicek, and L.
Konovalov. J. Coord. Chem. 38, 123 (1996).
19. L.M. Richberg, J.A. Farouq, C.D. Incarvito, A.L. Rheingold,
and D. Rabinovich. Polyhedron, 19, 1815 (2000).
20. (a) E. Libertini, K. Yoon, and G. Parkin. Polyhedron, 12, 2539
(1993); (b) J. Pickardt and P. Droas. Acta Cryst. C45, 360
(1989).
25. C. Pettinari, A. Cingolani, and B. Bovio. Polyhedron, 15, 115
(1996).
26. M.A. Weinberger and R. Greenhalgh. Can. J. Chem. 41, 1038
(1963).
27. P. Coppens. In Crystallographic computing. Edited by F.R.
Ahmed, S.R. Hall, and C.P. Huber. Munksgaard, Copenhagen.
1970. pp. 255–270.
28. P.T. Beurskens, G. Beurskens, W.P. Bosman, R. de Gelder, S.
García-Granda, R.O. Gould, R. Israël, and J.M.M. Smits. The
DIRDIF-96 program system [computer program]. Crystallog-
raphy Laboratory, University of Nijmegen, The Netherlands.
1996.
29. G.M. Sheldrick. SHELXL97 [computer program]. Version 97-
2. University of Göttingen, Germany. 1997.
30. A.L. Spek. The EUCLID package. In Computational crystal-
lography. Edited by D. Sayre. Clarendon Press, Oxford, U.K.
1982. p. 528.
21. C. Bolm, K. Weickhardt, M. Zehnder, and T. Ranff. Chem.
Ber. 124, 1173 (1991).
31. L.J. Farrugia. J. Appl. Crystallogr. 32, 837 (1999).
22. J. Castro, S. Cabeliero, P. Perez-Lourido, J. Romero, J.A.
© 2003 NRC Canada