Structural and spectroscopic characterization of N,N′-bis(2- pyridylmethyl)-ethylenediamine tetrahydrochloride dihydrate

Article abstract of DOI:10.1016/j.molstruc.2011.03.038

The crystal structure of the title compound, [(C₅H ₄NH)-CH₂-NH₂-(CH₂) ₂-NH₂-CH₂(C₅H₄NH)]Cl ₄·2H₂O, a potentially useful agent for chelation therapies, has been determined by single crystal X-ray diffractometry. It crystallizes in the monoclinic space group P2₁/c with Z = 2. The FT-IR and Raman spectra as well as the ¹H and ¹³C NMR spectra of the compound were also recorded and briefly discussed.

Full text of DOI:10.1016/j.molstruc.2011.03.038

Journal of Molecular Structure 994 (2011) 302–305
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Structural and spectroscopic characterization of
N,N0-bis(2-pyridylmethyl)-ethylenediamine tetrahydrochloride dihydrate
J. Zinczuk a, G.A. Echeverría b, O.E. Piro b, B.S. Parajón-Costa c, E.J. Baran c,
⇑
a Instituto de Química de Rosario (IQUIR/CONICET, UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, 2000 Rosario, Argentina
b Departamento de Física and Instituto IFLP (CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Argentina
c Centro de Química Inorgánica (CEQUINOR, CONICET/UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C. Correo 962, 1900 La Plata, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
The crystal structure of the title compound, [(C5H4NH)–CH2–NH2–(CH2)2–NH2–CH2(C5H4NH)]Cl4ꢀ2H2O, a
potentially useful agent for chelation therapies, has been determined by single crystal X-ray diffractom-
etry. It crystallizes in the monoclinic space group P21/c with Z = 2. The FT-IR and Raman spectra as well as
the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed.
Ó 2011 Elsevier B.V. All rights reserved.
Received 21 February 2011
Received in revised form 14 March 2011
Accepted 15 March 2011
Available online 22 March 2011
Keywords:
N,N0-bis(2-pyridylmethyl)-ethylenediamine
tetrahydrochloride dihydrate
Crystal structure
IR spectra
Raman spectra
NMR spectra
1. Introduction
obtained by addition of a solution of 6.0 g (0.1 mol) of ethylenedia-
mine in 15 mL of methanol to a solution of 21.5 g (0.2 mol) of 2-pyr-
There is an increasing interest in the synthesis and characteriza-
tion of polydentate ligands potentially useful as chelating agents in
medicine [1–8]. Recent studies have shown that the tetradentate
idylcarboxaldehyde in 45 mL of methanol. The light brown mixture
was heated to reflux, at 75 °C, in an oil bath for 15 min and then
cooled to room temperature [12]. In the next step an excess of so-
dium borohydride (9.0 g, 0.24 mol) was added in small portions to
the ice-cooled solution of N,N0-bis(2-pyridylmethylen)-ethylenedi-
amine. After the addition, the stirred mixture was gradually heated
to refluxand left overnightat this temperature. After cooling at room
temperature, the reaction mixture was diluted with dichlorometh-
ane (50 mL) and the solution washed with water (30 mL), saturated
solution of NH4Cl (30 mL) and brine (30 mL) and dried over Na2SO4.
Finally, the solvent was evaporated under reduced pressure to give
N,N0-bis(2-pyridylmethyl)-ethylenediamine in the form of an or-
ange oil, and characterized by NMR spectroscopy [12] (21.8 g, yield
90%). In the last step, an ice-cooled and well-stirred solution of
14.52 g (0.06 mol) of the oil in 15 mL of anhydrous ethanol was trea-
ted with 20 mL of 12 N hydrochloric acid. After 1 h the precipitate
was collected by vacuum filtration and dried to give 20.2 g
(yield = 86%) of N,N0-bis(2-pyridylmethyl)-ethylenediamine tetra-
hydrochlorhydrate [13]. The compound was recrystallized from
anhydrous ethanol giving the product as a white powder, m.p.
209–211 °C.
ligand
N,N0-bis(2-pyridylmethyl)-ethylenediamine
(bispicen)
forms relatively stable complexes with Fe(III) [9], Cr(III) [10,11]
as well as with Cu(II) and Zn(II) [4].
To advance in a better characterization of this very interesting
chelating agent, we have now solved the crystal and molecular
structure of its tetrahydrochloride and investigated its spectro-
scopic behavior.
2. Experimental
2.1. Synthesis of the compound
The reagents 2-pyridylcarboxaldehyde and sodium borohy-
dride, purchased from Aldrich; ethylendiamine, hydrochloric acid
and the solvents from Merck, were used as supplied.
The synthesis was performed in three successive steps, as fol-
lows: first, N,N0-bis(2-pyridylmethylen)-ethylenediamine was
Small single crystals, adequate for X-ray diffraction studies
were obtained, in the form of the dihydrate, recrystallizing the
product again from a 1:1 methanol:isopropanol mixture.
⇑
Corresponding author. Tel./fax: +54 221 4259485.
E-mail address: baran@quimica.unlp.edu.ar (E.J. Baran).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.03.038

J. Zinczuk et al. / Journal of Molecular Structure 994 (2011) 302–305
303
Table 1
Table 2
Crystal data, X-ray diffraction data and refinement results for N,N0-bis(2-pyridyl-
methyl)-ethylenediamine tetrahydrochloride dihydrate.
Intramolecular bond distances (Å) and angles (°) for the N,N0-bis(2-pyridylmethyl)-
ethylenediamine cation.
Empirical formula
Formula weight
C14H26Cl4N4O2
424.19
C(1)–N(1)
C(1)–C(6)
C(1)–C(7)
C(3)–N(1)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(7)–N(2)
C(8)–N(2)
C(8)–C(80)
1.339(2)
1.378(2)
1.496(2)
1.341(2)
1.372(3)
1.368(3)
1.376(3)
1.494(2)
1.485(2)
1.505(3)
N(1)–C(1)–C(6)
N(1)–C(1)–C(7)
C(6)–C(1)–C(7)
N(1)–C(3)–C(4)
C(3)–C(4)–C(5)
C(4)–C(5)–C(6)
C(1)–C(6)–C(5)
C(1)–C(7)–N(2)
N(2)–C(8)–C(80)
C(1)–N(1)–C(3)
C(8)–N(2)–C(7)
118.36(16)
117.98(14)
123.66(16)
119.65(19)
119.08(19)
120.04(17)
119.91(18)
109.51(13)
109.40(17)
122.96(16)
112.34(12)
Crystal dimension (mm3)
Crystal system
0.20 ꢂ 0.14 ꢂ 0.10
Monoclinic
Space group
Unit cell dimensions (Å, °)
P21/c (Nr. 14)
a = 8.5298(9), b = 6.8090(6),
c = 17.821(1), b = 93.305(8)
1033.3(2)
Volume (Å3)
Z
2
Calculated density (g cmꢁ3
)
1.363
0.587
Absorption coefficient,
l
(mmꢁ1
)
F(0 0 0)
444
3.20–25.99
C(80) atom is related to C(8) through the inversion symmetry operation: ꢁx + 1,
ꢁy + 1, ꢁz + 1.
h-range for data collection (°)
Index ranges
Number of reflections (total)
Independent reflections
Observed reflections [I P 2
Data/restraints/parameters
Goodness-of-fit on F2
R indices [I P 2
R indices (all data)
Largest peak and hole (e Åꢁ3
ꢁ10 6 h 6 9, ꢁ7 6 k 6 8, ꢁ21 6 l 6 13
4307
2038 [R(int) = 0.0205]
1437
2038/0/161
model refined by full-matrix least-squares procedure on F2 with
SHELXL-97 [16]. The hydrogen atoms were located in a difference
Fourier map and refined isotropically at their found positions.
Crystal data and structure refinement results are summarized in
Table 1.
r(I)]
0.889
r
(I)]
R1 = 0.0297, wR2 = 0.0683
R1 = 0.0465, wR2 = 0.0711
0.177 and ꢁ0.224
)
Tables containing complete information on fractional atomic
coordinates and equivalent isotropic displacement parameters of
the non-H atoms, atomic anisotropic displacement parameters,
and hydrogen atomic positions are available from the authors upon
request and have been deposited at the Cambridge Crystallo-
graphic Data Centre, under deposition number CCDC 805622.
2.2. Crystal structure determination
The measurements were performed on an Oxford Xcalibur, Eos,
Gemini CCD diffractometer with graphite-monochromated Mo K
(k = 0.71073 Å) radiation. X-ray diffraction intensities were col-
lected ( scans with # and -offsets), integrated and scaled with
a
x
j
CrysAlisPro [14] suite of programs. The unit cell parameters were
obtained by least-squares refinement based on the angular settings
for all collected reflections with intensities larger than seven times
the standard deviation of measurement errors, using CrysAlisPro.
Data were corrected empirically for absorption employing the mul-
ti-scan method implemented in CrysAlisPro. The structure was
solved by direct methods with SHELXS-97 [15] and the molecular
2.3. Spectroscopic measurements
The infrared spectra were recorded on a FTIR-Bruker-EQUINOX-
55 spectrophotometer in the spectral range between 4000 and
400 cmꢁ1, using the KBr pellet technique. A total of 80 scans were
accumulated. Raman spectra were obtained with the FRA 106
Fig. 1. Projection of the N,N0-bis(2-pyridylmethyl)-ethylenediamine tetrahydro-chloride dihydrate (bispicen tetrahydrochloride dihydrate) salt down the crystal b-axis
showing the labeling of the non-H atoms and their displacement ellipsoids at the 50% probability level. The H-bonding structure is denoted by dashed lines.

304
J. Zinczuk et al. / Journal of Molecular Structure 994 (2011) 302–305
Table 3
Hydrogen bonds for N,N0-bis(2-pyridylmethyl)-ethylenediamine tetrahydrochloride dihydrate.
D–H
operation
d(D–H)
d(Hꢀ ꢀ ꢀA)
\(D–Hꢀ ꢀ ꢀA)
d(Dꢀ ꢀ ꢀA)
A
Symmetry
N1–H1
N2–H21
N2–H22
O1 W–H11
O1 W–H12
0.939
0.923
0.898
0.799
0.809
2.128
2.151
1.847
2.278
2.266
175.04
174.38
166.35
175.49
171.60
3.065
3.070
2.728
3.076
3.069
Cl2
Cl2
O1 W
Cl1
Cl1
[x + 1, y, z]
[ꢁx + 1, ꢁy + 1, ꢁz + 1]
[ꢁx + 1, ꢁy + 1, ꢁz + 1]
[ꢁx + 1, yꢁ1/2, ꢁz + 1/2]
Fig. 2. FTIR spectrum of N,N0-bis(2-pyridylmethyl)-ethylenediamine tetrahydro-
chloride dihydrate in the spectral range between 3600 and 2100 cmꢁ1
.
accessory of a Bruker IFS 66 FTIR instrument. A total of 60 scans
were accumulated, using the 1064 nm line from a Nd:YAG laser.
NMR spectra were recorded in D2O using a Bruker Avance 300
instrument. Chemical shifts are reported in ppm downfield from
tetramethylsilane. 1H-spectra were recorded at 300 MHz and
13C-spectra at 75 MHz.
3. Results and discussion
3.1. Structural characteristics of the compound
Fig. 3. FT-Raman (above) and FT-IR (below) spectra of N,N0-bis(2-pyridylmethyl)-
ethylenediamine tetrahydrochloride dihydrate in the spectral range between 1700
and 400 cmꢁ1. (⁄this Raman band (1492 cmꢁ1) originates in an instrumental noise).
An ORTEP [17] plot of the N,N0-bis(2-pyridylmethyl)-ethylene-
diamine tetrahydrochloride dihydrate is shown in Fig. 1. Intra-
molecular bond distances and angles within the organic cation
are given in Table 2.
The ionic (+4) organic molecule is sited on a crystallographic
inversion center and their four positive charges are located at the
> NHþ2 and >NH+ groups. The observed covalent bond structure
confirms and quantifies what it is expected for this molecule from
Organic Chemistry’s rules. Particularly, the observed single C—NH2þ
bond distance (average of 1.490 Å) is 0.15 Å longer as compared
with the resonant bond >C–NH+ distances (average of 1.340 Å)
within the pyridyl ring.
of the [(C5H4NH)–CH2–NH2–(CH2)2–NH2–CH2(C5H4NH)]4+ cation,
although structural information exist on a series of metallic com-
plexes of this interesting tetradentate ligand, for example Fe(III),
Cr(III), Mn(II), oxorhenium(V) and V(III) complexes [9–11,13,18].
The sþalt is further stabilized by a complex H-bonding network
of > NH2 ꢀ ꢀ ꢀClꢁ [d(Nꢀ ꢀ ꢀCl) = 3.070 Å, \(N–Hꢀ ꢀ ꢀCl) = 174.4°], > NH2þ
ꢀ ꢀ ꢀOw [d(Nꢀ ꢀ ꢀOw) = 2.728 Å, \ (N–Hꢀ ꢀ ꢀOw) = 166.4°], >N–H+ꢀ ꢀ ꢀClꢁ
[d(Nꢀ ꢀ ꢀCl) = 3.065 Å, \ (N–Hꢀ ꢀ ꢀCl) = 175.0°], and Ow–Hꢀ ꢀ ꢀClꢁ [Ow
ꢀ ꢀ ꢀCl distances of 3.076 and 3.069 Å, and N–Hꢀ ꢀ ꢀCl angles of
175.5° and 171.6°], as shown in the crystal packing diagram of
Fig. 1. Further details of the interesting H-bonding structure are
provided in Table 3.
3.2. Vibrational spectra
The FTIR spectrum of the compound, in the spectral range be-
tween 3600 and 2100 cmꢁ1 is shown in Fig. 2. In this region the
corresponding Raman spectrum shows only a series of relatively
weak and poorly defined bands. The FTIR and Raman spectra be-
tween 1700 and 400 cmꢁ1 are shown in Fig. 3.
The proposed spectral assignment, presented in Table 4 was
performed on the basis of some standard references [19–21]. The
results are briefly commented, as follows:
This study constitutes the first report on the structural
characteristics of the protonated bispicene molecule, in the form

J. Zinczuk et al. / Journal of Molecular Structure 994 (2011) 302–305
305
Table 4
– All the characteristic
m
(CC) stretching modes of the pyridine
Assignment of the vibrational spectra of N,N0-bis(2-pyridylmethyl)-ethylenediamine
tetrahydrochloride dihydrate (band positions in cmꢁ1).
moieties [19] could be identified. They include two quadrant
stretching modes (ca. 1615 and 1510 cmꢁ1), two semicircle
stretching vibrations (ca. 1470 and 1400 cmꢁ1) and the radial
mode (ca. 1010 cmꢁ1). Also typical in-plane and out-of-plane
ring bends (three bands) were identified.
Infrared
Raman
Assignments
3299 vs
3115/3075/3061 vw
2992/2946 w
2745 sh, 2679 vs, 2598 sh 2680 w, 2585 w,br
2425 m
m
m
m
m
(H2O)
3086/3035 vw
2987/2964 vw
(CH)py
(CH2)
(NH+)py +
– As shown in Table 4 some other skeletal and deformational
modes were also assigned.
m
(> NHþ2
)
2440 w
Combination band
2009/1995/1895/1848 w
1728 vw
1633 vs, 1615 vs 1585 sh 1636 s, 1616 m
3.3. NMR spectra
d(H2O) + m )
(CC)py + d(> NHþ2
13
We have recorded the 1H and C NMR spectra of N,N0-bis(2-
1542 m, 1512 vs
1469 vs
1440 w
1402 m, 1375 m
1329 m, 1302 s
1235 s
1179 m
1158 s
1097 w
1046 s
1543 w, 1510 vw
1478 w
1455 vs
1397 w, 1341 m
1315 w, 1259 w
1235 vs
1159 s
1136 w
1099vs/1080 sh
1052 vs
m
m
(CC)py
(CC)py
pyridylmethyl)-ethylenediamine tetrahydrochloride. These spectra
are clearly compatible with the crystal structure of the molecule, as
shown by the data presented in Table 5, analyzed on the basis of
some standard references [23,24].
d(CH2)
m
s
(CC)py
(CH2)
d(NH+)py
m
m
m
(C–N)
(CC)CH2
(CC)CH2/py
(CH)py
Acknowledgements
q
1007 s
1011 vs
968 w, 880 vw
831 vs
738 m
629 vs
m(CC)py
This work was supported by the Universidad Nacional de La
Plata, the Universidad Nacional de Rosario, by CONICET (PIP
1529), and by ANPCyT (PME06 2804 and PICT06 2315) of Argen-
tina. The authors are members of the Research Career from
CONICET.
951 s, 883 s
845 w, 778 vs
736 w
675 s, br, 626 s
610 m
dw(NH+)py
dw(CH)py
d(CC)py
d(CC)py
d(CC)py +
d(CN)
603 w
523 m
q(H2O)
508 s
vs: very strong; s: strong; m: medium; w: weak; vw: very weak; sh: shoulder; br:
broad; py: pyridine.
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