Synthesis and resolution of 1,11-diamino-dibenzo[d,f][1,3]dioxepine: A route to new asymmetric ligands and their complexes

Article abstract of DOI:10.1016/j.inoche.2009.10.039

Reaction of 2-iodo-3-nitrophenol with methylene iodide and Ullmann intramolecular coupling of the produced 1,1′-[methylenebis(oxy)]bis[2-iodo-3-nitro]benzene afforded 1,11-dinitro-dibenzo[d,f] [1,3]dioxepine, characterized by single crystal X-ray analysis. The title diamine was obtained by reduction of the nitroderivate with hydrazine hydrate. Resolution of the enantiomers of the novel C₂-symmetric ligand can be easily obtained by use of tartaric acid. A test on the coordinating ability of the diamine has produced a complex examined by X-ray diffraction analysis.

Full text of DOI:10.1016/j.inoche.2009.10.039

Inorganic Chemistry Communications 13 (2010) 153–156
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Synthesis and resolution of 1,11-diamino-dibenzo[d,f][1,3]dioxepine: A route
to new asymmetric ligands and their complexes
b
a
Barbara Panunzi a, , Angela Tuzi , Marco Tingoli
*
a Dipartimento di Scienza degli Alimenti, Università degli Studi di Napoli ‘‘Federico II”, via Università 100, 80155 Portici, Napoli, Italy
b Dipartimento di Chimica ‘‘Paolo Corradini”, Università degli Studi di Napoli ‘‘Federico II”, Complesso Universitario di Monte S. Angelo, via Cintia, 80126 Napoli, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of 2-iodo-3-nitrophenol with methylene iodide and Ullmann intramolecular coupling of the
produced 1,10-[methylenebis(oxy)]bis[2-iodo-3-nitro]benzene afforded 1,11-dinitro-dibenzo[d,f] [1,3]-
dioxepine, characterized by single crystal X-ray analysis. The title diamine was obtained by reduction
of the nitroderivate with hydrazine hydrate. Resolution of the enantiomers of the novel C2-symmetric
ligand can be easily obtained by use of tartaric acid. A test on the coordinating ability of the diamine
has produced a complex examined by X-ray diffraction analysis.
Received 6 October 2009
Accepted 28 October 2009
Available online 31 October 2009
Keywords:
Atropoisomerism
Dioxepine
Ó 2009 Elsevier B.V. All rights reserved.
Platinum
Resolution
The attainment of new asymmetric ligands is the subject of con-
tinuous research effort, because of the high specificity displayed by
these molecules in inducing chiral discrimination in asymmetric
syntheses. In this field atropoisomeric ligands attract quite a rele-
vant interest [1].
procedure [7]. Reaction with methylene iodide in presence of
potassium carbonate afforded 1,10-[methylenebis(oxy)]bis[2-
iodo-3-nitro]benzene [8] that underwent intramolecular coupling
prompted by activated copper bronze in dimethylformamide to
give doxp-2NO2 [9].
This investigation deals with dibenzo[d,f][1,3]dioxepine deriva-
tives (doxp-2D, Fig. 1) disubstituted in positions 1,11 with groups
bearing D donor groups.
In addition to the analytical and spectroscopic characterization
performed on all new compounds, in the case of doxp-2NO2, taking
also in count the paucity of structural characterization data for dia-
zepines, the molecular structure was determined by single crystal
X-ray diffraction. Single crystals, suitable for X-ray analysis, were
obtained from a methyl cyanide solution by slow evaporation at
room temperature [10]. The compound crystallizes in the mono-
clinic C2/c group with one half molecule in the independent unit.
The molecule is C2 symmetric, being located in the 4e Wyckoff po-
sition on the binary axis at (0, y, 1/4). The molecular structure is
shown in Fig. 3. Bond distances and angles are in agreement with
those displayed by the only X-ray previously characterized 1,11-
disubstituted diazepine [11]. The O–CH2–O etheral bridge allows
a moderate degree of flexibility to the molecule. The diphenyl
group is not planar (C6–C7–C7i–C6i = 47.7(7)°, i = ꢀx, y, ꢀz + 1/2)
and the deviation from coplanarity is in the range found in similar
compounds [12]. The nitro group is in plane with the attached phe-
nyl ring (distance N1ꢁ ꢁ ꢁN1i = 3.040(6) Å, i = ꢀx, y, ꢀz + 1/2) and is
involved in weak intermolecular C–Hꢁ ꢁ ꢁO interactions in the crys-
tal packing.
As for the choice of this subject we note: (i) it could be observed
that the coordinative environment offered by the doxp ligands is
substantially the same of that of the corresponding C2-symmetric
unbridged bi-arene derivatives. However, the differences in the
residual part of analogous molecules are expected to be responsi-
ble of significant variations of stereoselective ability [2]. For in-
stance, the more rigid doxp core appears more suited to prompt
chelation than a simple diaryl central moiety in case the two do-
nors are different [3]. (ii) Although the preparation of some doxp
type ligands such as doxp-2PPh2 [4], and their use in catalysis
are known by far, the important [5] diaminic (D = NH2) environ-
ment largely useful for the attainment of catalytic complexes has
not yet been described for doxp type compounds. (iii) doxp-
2NH2 is a most suitable starting material for the synthesis of the
di-iodide (D = I), a choice key intermediate for a variety of conceiv-
able doxp ligands.
The synthesis of the diamine is shown in Fig. 2 [6].
The starting 2-iodo-3-nitrophenol was previously obtained
from commercial 2-amino-3-nitrophenol according to a known
According to a few non-optimized preliminary tests the reduc-
tion of doxp-2NO2 to doxp-2NH2 can be effected [13] with
N2H4ꢁH2O in presence of FeCl3 on carbon. The diamine can be easily
recovered from the reaction mixture by removing solids on a filter
and evaporating the solvent from the mother liquor. The residue is
* Corresponding author. Tel.: +39 081 674170; fax: +39 081 674090.
E-mail address: barbara.panunzi@unina.it (B. Panunzi).
1387-7003/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2009.10.039

154
B. Panunzi et al. / Inorganic Chemistry Communications 13 (2010) 153–156
the mean plane of the ligand and are at 2.99 Å distance from each
other, which is consistent with literature data for amido-bridged Pt
complexes [16].
A rough resolution of the diamine was accomplished very sim-
ply by use of tartaric acid [17]. In fact, addition in methanol solu-
tion of ½ equimolar amount of (+)-tartaric acid, slow removal of
solvent and extraction of the microcrystalline residue with Et2O
Fig. 1. General formulae of doxp-2D.
afforded (ꢀ)-doxp-2NH2 ([ D = ꢀ19.6, in diethyl ether at 27 °C).
a
]
After 2 h at 27 °C the specific rotation had lowered to 20% of the
initial value. No attempt was made to recrystallize the tartrate (a
1:1 acid/base associate, according to NMR) or to assess the optical
purity of the diamine.
extracted with diethyl ether and addition of gaseous HCl affords
precipitation of fairly pure diamine hydrochloride.
The synthesis of a platinum complex was attempted by reaction
of the diamine with (Me2S)2PtMeCl [14]. The X-ray analysis on a
single crystal obtained from methanol solution by slow solvent
evaporation displayed the molecular structure shown in Fig. 4.
According to the present X-ray analysis [15], the complex is
formed by centrosymmetric dimers with two dimethylsulfide moi-
eties as the Pt-bridging groups. Each diamine acts as bidentate li-
gand towards two Pt atoms. The two Pt atoms, whose square
planar coordination environment is completed by a methyl and a
dimethylsulfide group, are located up and down with respect to
Further work is in progress, mainly on regard of applications of
metal complexes of doxp-2NH2 and of N-substituted derivatives of
it.
Supplementary material
CCDC 749894 (doxp-2NO2) and CCDC 752587 (complex) con-
tain the supplementary crystallographic data for this paper. These
Fig. 2. Synthetic pathway for the attainment of doxp-2NH2.
Fig. 3. ORTEP view of doxp-2NO2 with ellipsoids drawn at 30% probability level (i = ꢀx, y, ꢀz + 1/2).

B. Panunzi et al. / Inorganic Chemistry Communications 13 (2010) 153–156
155
Fig. 4. Ortep diagram of the platinum complex. Thermal ellipsoids are drawn at 30 % probability level. H atoms are omitted for clarity.
with water (50 mL) and cold acetone (3 ꢂ 15 mL) and dried. Yield 79% (9.8 g).
Further purification of this fairly pure product can be accomplished by
recrystallization from acetone. 1H NMR (CDCl3) d = 8.15 (dd, 2H), 7.60 (m, 4H),
5.51 (m, 2H). 13C NMR (d6-DMSO) d = 157.62, 152.16, 136.48, 133.20, 128.94,
127.36, 108.08. Elemental analysis, calcd. (%) for C13H8N2O6: C 54.18, H 2.80, N
9.72. Found: C 54.11, H 2.91, N 9.60.
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgment
[10] Crystal data for doxp-2NO2: C13H8N2O6, Mr = 288.21, monoclinic, C2/c, Z = 4,
plate shaped orange crystal (0.30 ꢂ 0.25 ꢂ 0.01 mm), a = 13.257(6) Å, b =
We gratefully acknowledge financial support of the Centro
Interdipartimentale di Metodologie Chimico Fisiche (University
‘‘Federico II”) for NMR and X-ray facilities.
9.366(3) Å, c = 10.198(4) Å, b = 91.54(3)°, V = 1265.8(9) Å3, T = 173 K, qcalcd.
=
1.512 g/cm3,
Bruker–Nonius KappaCCD diffractometer (Mo K
rotation images, thick slices, scans + scans to fill asymmeryc unit).
l
= 0.123 mmꢀ1. Data were collected in flowing N2 at 173 K on a
a
radiation, k = 0.71073 Å, CCD
u
x
Semiempirical absorbtion correction (multi-scan SADABS) was applied. The
structure was solved by direct methods (SIR 97 program [A. Altomare, M.C.
Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo, A. Guagliardi, A.G.G. Moliterni,
G. Polidori, R. Spagna, J. Appl. Cryst. 32 (1999) 115]) and refined by the full
matrix least-squares method (SHELX-97 package [G.M. Sheldrick, Acta Cryst. A
64 (2008) 112]) on F2 against all independent measured reflections.
Anisotropic thermal parameters were used for all non-hydrogen atoms. H
atoms placed in calculated positions and refined by the riding method.
References
[1] M. McCarthy, P.J. Guiry, Tetrahedron 57 (2001) 3809.
[2] (a) E. Daura-Oller, A.M. Segarra, J.M. Poblet, C. Claver, E. Fernandez, C. Bo, J.
Org. Chem. 69 (2004) 2669;
(b) Z. Zhang, H. Qian, J. Longmire, X. Zhang, J. Org. Chem. 65 (2000) 6223.
[3] J.W. Faller, N. Sarantopoulos, Organometallics 23 (2004) 2008.
[4] X. Zhang, PCT Int. Appl. (2001) 52.
Refinement converged to R1 = 0.0710, wR2 = 0.1300 [I > 2r(I)]. 5722 reflections
[5] A. Togni, L. Venanzi, Angew. Chem. Int. Ed. Engl. 33 (1994) 497.
[6] Unless otherwise specified, all experiments were performed under nitrogen
using standard Schlenk techniques. All solvents were reagent grade, and, if
necessary, were dried by standard methods. The synthesis of 2-iodo-3-
nitrophenol from commercial 3-nitrophenol was made according to previous
work [7]. The 1H and 13C NMR spectra were recorded on Varian XL 200 MHz
and Gemini 300 MHz instruments. 1H [13C] chemical shifts are referenced
using the residual solvent peak at d 7.26 [77.0] for CDCl3, 2.49 [39.4] for DMSO-
d6 and 2.05 [20.8] for acetone-d6. Routine coupling constants are not listed.
For describing multiciplities the following abbreviations were used: s, singlet;
d, doublet, dd, double doublet; t, triplet; app, apparent; m, multiplet; br, broad.
collected, 1452 unique [Rint = 0.1071], 96 parameters. Largest difference peak
and hole: 0.253 and ꢀ0.238 eÅ3.
[11] A. Panunzi, V. De Felice, N. Fraldi, G. Roviello, F. Ruffo, Inorg. Chem. Commun. 8
(2005) 049.
[12] From search of Cambridge Structural Database, CSD version 5.30 November
2008 F.H. Allen, Acta Cryst. B 58 (2002) 380.
[13] 1,10-Dibenzo[d,f][1,3]dioxepin-1,11-diyl-diamine.
A
mixture of FeCl3ꢁ6H2O
(0.100 g, 0.37 mmol), active charcoal (1 g) and doxp-2NO2 (2.88 g, 10 mmol)
in methanol (50 mL) was refluxed for 10 min in argon atmosphere. To the
refluxing mixture hydrazine hydrate (6.1 mL, 126 mmol) was added dropwise.
Solids were separated by filtration on a small bed of Celite and washed with
methanol. Washing was added to the mother liquor and the solvent was
Mass spectrometry was performed using
equipped with silicone column instrument.
a Shimadzu GC-MS QP-5000
evaporated in vacuo to give
a whitish residue. This crude diamine was
[7] S. Wawzonek, S.C. Wang, J. Org. Chem. 16 (1951) 1271.
extracted with diethyl ether (2 ꢂ 25 mL) and gaseous HCl was bubbled
through the solution to precipitate faitly pure diamine hydrochloride. dopx-
2NH2 was obtained in 23% yield by dissolving the hydrochloride in methanol
containing a slight excess of KOH, removing of solvent in vacuo and recovering
the product with diethyl ether. Analytically pure product could be obtained by
recrystallization from methanol. 1H NMR: (CDCl3.): d = 7.18 (t, 2H), 6.63 (app.
d, 4H), 5.47 (s, 2H). 13C NMR: d = 154.12, 144.19, 129.36, 113.44, 110.89,
102.40. M+ = 228. Elemental analysis, calcd. (%) for C13H12N2O2: C 68.41, H
5.30, N 12.27. Found: C 68.19, H 5.35, N 12.20.
[8] 1,10-[Methylenebis(oxy)]bis[2-iodo-3-nitro]benzene. 2-Iodo-3-nitrophenol (60 g,
p.m. 265.01, 0.226 mol), potassium carbonate (125 g, p.m.138.21, 0.904 mol),
methylene iodide (30.49 g, pm 269.85, 0.113 mol) were added to magnetically
stirred cold dry DMF (300 mL). Stirring of the red mixture was continued at r.t.
during 48 h. The most of DMF was removed in vacuo (bath temperature ca.
50 °C). Ice (200 g) and water (50 mL) were added with stirring. A yellow solid
precipitated and was collected after 1 h on a Gooch filter, washed with water
and dried in air. The crude product was recrystallized from methylene
chloride/methanol: a crop of 37.5 g was recovered. (p.m. 542.03, 61.2% yield).
1H NMR (CDCl3) d = 7.44–7.51 (m, 6H), 5.94 (s, 2H). 13C NMR (CDCl3) d = 157.1,
155.9, 130.6, 119.4, 117.9, 92.1, 81.5. Elemental analysis, calcd. (%) for
C13H8I2N2O6: C 28.81, H 1.49, N 5.17. Found: C 28.96 , H 1.59, N 5.08.
[9] 1,11-dinitro-dibenzo[d,f][1,3]dioxepine. In argon atmosphere to a solution of
1,10-[methylenebis(oxy)]bis[2-iodo-3-nitro]benzene (21.68 g , 40 mmol) in dry
DMF (120 mL), stirred at 155 °C, activated copper bronze (Vogel, Practical
Organic Chemistry, p. 323) (28 g) was added. A second aliquot of copper
bronze (28 g) was added after 3 h and heating and stirring were continued for
16 h. The cooled mixture was filtered and the solvent was removed in vacuo to
give a yellow brown residue. This was added to the copper containing solid
and the combined solids were washed with water (100 mL), dryed in vacuo,
and extracted with methylene chloride in a Soxlet apparatus. The solvent was
removed in vacuo from the extract to afford a yellowish solid, that was washed
[14] A solution of doxp-2NH2 (0.0228 g, 0.1 mmol) in diethyl ether (3 mL) was
added with stirring to solid (Me2S)2PtMeCl (0.0369 g, 0.1 mmol). Stirring was
continued for 20 h and the precipitate was collected by filtration, washed with
1 mL ether and dried. Recrystallization was attained by slow partial
evaporation of solvent from a methanol solution and the precipitate resulted
to be a mixture of different crystals. Manual separation of morphologically
similar single crystals gave a small amount of homogeneous material, used for
X-ray and 1H NMR investigations. 1H NMR (CDCl3 cont. 10% CD3OD.) d = 6.4–
6.7 (m, 12H), 5.48 (br s, 2H), 5.38 (br s, 2H), 2.05 (s, 6H, 3JPt–H = 20 Hz), 1.98 (s,
3
3
6H, JPt–H = 20 Hz), 0.18 (s, 12H, JPt–H = 83 Hz).
[15] Many attempts to obtain single crystals of the complex resulted only in very
small irregular shaped crystals. One of these, thought poor quality and weakly
diffracting, allowed to solve the structure. Crystal data: C34H44N4O4S2Pt4,
Mr = 1417.19, monoclinic, P21/c, T = 173 K, a = 18.826(4) Å, b = 9.512(3) Å,

156
B. Panunzi et al. / Inorganic Chemistry Communications 13 (2010) 153–156
c = 22.969(8) Å, b = 111.24(5)°, V = 3834(2) Å3, Z = 4,
q
calcd. = 2.455 g/cm3,
Pt1). The assignment of phases in the structure is largely dominated by the
heavy atoms, so that light atoms were located with some difficulties in the
difference Fourier maps. Constrains were introduced in the last stage of
refinement to regularize the diphenyl group. ISOR instruction of SHELXL was
also introduced for light atoms (C, O, N) to prevent negative B values in the
anisotropic refinement.
l
= 14.699 mmꢀ1. Data were collected in flowing N2 at 173 K on a Bruker–
Nonius KappaCCD diffractometer (Mo
rotation images, thick slices, scans +
K
x
a
radiation, k = 0.71073 Å, CCD
scans to fill asymmetryc unit).
u
Semiempirical absorbtion correction (multi-scan SADABS) was applied. The
structure was solved by direct methods (SIR 97 program [A. Altomare, M.C.
Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo, A. Guagliardi, A.G.G. Moliterni,
G. Polidori, R. Spagna, J. Appl. Cryst. 32 (1999) 115]) and refined by the full
matrix least-squares method (SHELX-97 package [G.M. Sheldrick, Acta Cryst. A
64 (2008) 112]) on F2 against all independent measured reflections.
Anisotropic thermal parameters were used for all non-hydrogen atoms. H
atoms placed in calculated positions and refined by the riding method.
[16] M.K. Cooper, P.V. Stevens, M. Mc Partlin, J. Chem. Soc. Dalton Trans. (1983)
553.
[17] To the diamine (0.070 g, 0.3 mmol) dissolved in a minimum of ethanol (ca.
5 mL) a saturated solution of (+)-tartaric acid (0.023 g, 0.15 mmol) in the same
solvent was added. The solvent was removed in vacuo (15 Torr) at r.t. The solid
residue was extracted with diethyl ether (6 mL) with a weight loss of 0.026 g.
Refinement converged to R1 = 0.0785, wR2 = 0.1265 [I > 2
r
(I)]. 20,734
The specific rotation (at 27 °C: [
measured ca. 4 min after the extraction. After 2 h at 27 °C the rotation had
dropped to [
D ꢃ ꢀ4.
a]D = ꢀ19.6) of the diethyl ether solution was
reflections collected, 6327 unique [Rint = 0.1863], 223 parameters. Largest
difference peak and hole: 2.452 and ꢀ1.829 eÅ3 (at 1.09 Å and 1.82 Å from
a
]