Intermolecular hydrogen bonds and the supramolecular structure of N,N′-bis(p-tolylsulfonyl)diethylenetriamine

Article abstract of DOI:10.1007/s10870-008-9337-7

The title compound N,N′-bis(p-tolylsulfonyl)diethylenetriamine (1) was synthesized and its crystal structure determined by X-ray diffraction. Adjacent molecules of 1, symmetrically related through a c-glide, are linked by alternating hydrogen bonds that f

Full text of DOI:10.1007/s10870-008-9337-7

J Chem Crystallogr (2008) 38:577–582
DOI 10.1007/s10870-008-9337-7
ORIGINAL PAPER
Intermolecular Hydrogen Bonds and the Supramolecular
Structure of N,N0-Bis(p-tolylsulfonyl)diethylenetriamine
K. Padayachy Æ M. A. Fernandes Æ H. M. Marques Æ
A. S. de Sousa
Received: 27 September 2007 / Accepted: 18 March 2008 / Published online: 9 April 2008
Ó Springer Science+Business Media, LLC 2008
Abstract The title compound N,N0-bis(p-tolylsulfonyl)
diethylenetriamine (1) was synthesized and its crystal struc-
ture determined by X-ray diffraction. Adjacent molecules of
1, symmetrically related through a c-glide, are linked by
alternating hydrogen bonds that form molecular chains along
[0 0 1]. Two molecular chains occur in each unit cell and pack
to form alternating layers in a three-dimensional supramo-
lecular structure. The compound crystallizes in the Pca21
space group stabilized by the inclusion of solvent dichloro-
methane molecules in structural voids between molecules
of 1. The dichloromethane molecules are related through a
twofold screw rotation axis and are not disordered.
of a condensation reaction between the sodium sulfonamide
salt and the glycol derivatives under Richman–Atkins
conditions [2]. The rich chemistry of macrocyclic-based
metal complexes has seen these being investigated for their
possible use as imaging agents or biosensors for an ever
increasing array of biologically significant molecules or
ions [3–5]. Acyclic chelates have, however, retained their
importance due to their equally robust coordination chem-
istry and metal complexes based upon acyclic chelates have
been approved for commercial use [6]. Designing synthetic
pathways for asymmetrically substituted macrocyclic and
acyclic chelating systems [7] potentially leads to significant
improvements of presently used metal complexes in clinical
applications. The synthetic successes surrounding asym-
metrically substituted azamacrocylic compounds and their
acyclic analogues, is attributed to the steric characteristics
[8] imposed upon sulfonamides in which tosyl groups, in
particular, are protecting groups that mask the nucleophi-
licity of the nitrogen atom.
Keywords Sulfonamide ꢀ Hydrogen-bonding ꢀ
Supramolecular ꢀ Graph set analysis
Introduction
Conversion of amines into N-substituted sulfonamides has
enjoyed several uses in analytical and synthetic organic
chemistry. For example, the Hinsberg test exploits the
reaction of amines in general with substituted benzene
sulfonyl chloride derivatives to isolate the sulfonamides of
amine mixtures, relying upon the different solubilities of the
resultant sulfonamides in aqueous solution for distinguish-
ing primary, secondary, and tertiary amines [1].
Sulfonamides played a crucial role in the synthesis of
macrocyclic polyamines, which are the cyclization products
Isolating convenient sulfonamide-based synthetic build-
ing blocks for designing new chelating systems remains an
important endeavor for bioinorganic and organic chemists
alike. Our interest in synthesizing asymmetric diethylene-
triamine-based chelates led to the synthesis of the title
compound so as to determine the solid state structure and
investigate the influence hydrogen-bonding arrays may
have on the geometry surrounding the sulfonamide moiety.
Experimental Section
K. Padayachy ꢀ M. A. Fernandes ꢀ H. M. Marques ꢀ
A. S. de Sousa (&)
Molecular Sciences Institute, School of Chemistry, University
of the Witwatersrand, Private Bag 3, Wits, 2050
Johannesburg, South Africa
Solvents and Chemicals
All chemical solvents were distilled and dried prior to use in
synthetic procedures. Diethanolamine, 1,2-diaminoethane,
e-mail: Alvaro.DeSousa@wits.ac.za
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J Chem Crystallogr (2008) 38:577–582
and p-toluenesulfonyl chloride were purchased from
Aldrich and used as received.
Table 1 Crystal data and structure refinement for the title compound
CCDC deposit no.
Empirical formula
Chemical formula
Formula weight
Color/shape
CCDC 662299
19H27Cl2N3O4S2
C
Physical Measurements
C18H25N3O4S2CH2Cl2
496.46
The 1H and 13C NMR spectra were obtained with a Bruker
300 MHz spectrometer in deuterated chloroform.
A crystal of dimensions 0.50 9 0.37 9 0.25 mm3 of (1)
was used for collection of intensity data on a Bruker APEX
II CCD area detector diffractometer with graphite mono-
chromated Mo Ka radiation (50 kV, 30 mA) using the
APEX 2 [9] data collection software. The collection
method involved x-scans of width 0.5° and 512 9 512 bit
data frames. Data reduction was carried out using the
program SAINT-NT [10].
Colorless needles
172(2)
Temperature (K)
˚
Wavelength (A)
0.71073
Crystal system
Space group
Orthorhombic
Pca21
˚
a = 25.4644(4) A
Unit cell dimensions
˚
b = 11.2639(2) A
˚
c = 8.10410(10) A
a = 90°
b = 90°
c = 90°
2324.49(6)
4
The crystal structure was solved by direct methods using
SHELXTL [11]. Non-hydrogen atoms were first refined
isotropically followed by anisotropic refinement by full
matrix least-squares calculations based on F2 using
SHELXTL. Hydrogen atoms were first located in the dif-
ference map then positioned geometrically and allowed to
ride on their respective parent atoms. Hydrogen atoms
involved in hydrogen-bonding were located in the differ-
ence map and refined freely. Diagrams and publication
material were generated using SHELXTL, PLATON [12],
and ORTEP-3 [13]. Details of the data collection are given
in Table 1.
3
˚
Volume (A)
Z
Density (calculated) (g cm-3
)
1.419
Absorption coefficient (mm-1
)
0.489
F(000)
1040
Crystal size (mm3)
h range for data collection (°)
Limiting indices
0.50 9 0.37 9 0.25
1.60–28.00
-33 \ h \ 31, -14 \ k \ 14,
-9 \ l \ 10
23,941
Reflections measured
Independent/observed reflections
Rint
5,474
0.0311
Starting Materials
Completeness to h = 28.00°
Absorption correction
Refinement method
100.0%
None
Full-matrix least-squares on F2
N-p-Tolylsulfonylethylenediamine [14] and N-p-tolylsulf-
onylaziridine [15, 16] were prepared according to literature
procedures and used for synthesizing compound 1 via a
modified procedure [16].
Data/restraints/parameters
Goodness of fit F2
5474/4/285
1.046
Final R indices [I [ 2r(I)]
R indices (all data)
R1 = 0.0471, wR2 = 0.1173
R1 = 0.0563, wR2 = 0.1232
0.05(7)
Synthesis of N,N0-Bis(p-tolylsulfonyl)
diethylenetriamine (1) (Scheme 1)
Absolute structure parameter
Largest differential peak and
-3
0.388 and -0.384
˚
hole (e A
)
N-p-Tolylsulfonylethylenediamine (1.0 g, 4.67 mmol) was
dissolved in CH3CN and heated to reflux under argon. A
CH3CN solution (11 mL) of N-p-tolylsulfonylaziridine
(0.92 g, 4.67 mmol) was added dropwise over a period of
3 h and the mixture was allowed to further reflux for 12 h.
This was then cooled to room temperature affording a pale
yellow oil after removal of the solvent under reduced
pressure. The compound was crystallized from dichloro-
methane/diethyl ether (50:50) to give (1) as a crystalline
solid. Yield: 70%. dH(CDCl3): 2.418 (6H; Ts-CH3), 2.606
(4H; CH2NCH2), 2.948 (4H; Ts-NCH2), 7.285 (4H;
CH3CH Ar), 7.734 (4H; CHC-SO2 Ar). dC(CDCl3): 21.921
(Ts-CH3), 42.962 (CH2NCH2), 48.152 (Ts-NCH2),
127.615, 130.075, 137.146, 143.812 (Ts-CH; Ts-C-).
Results and Discussion
The use of p-toluenesulphonyl groups as protecting groups
in the synthesis of macrocyclic compounds is not uncom-
mon and it is therefore surprising that relatively few
structures of diethylenetriamine derivatives bearing tosyl
groups have been reported. Compound 1 has been syn-
thesized as outlined in Scheme 1 with the specific aim of
protecting the terminal nitrogen atoms. Further substitution
at the central nitrogen affords C2 symmetry to related
acyclic chelating systems using 1 as a convenient synthetic
precursor [17].
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579
Scheme 1 Synthetic outline of
compound 1
O
O
1) TsCl
NH2
N S
S
O
1
HO
2) NaOH
NH
O
NH
H
N
O
NH
S
O
TsCl
NH2
S
H2N
O
H2N
O
The asymmetric unit consists of a single molecule of
compound 1 and the inclusion of a dichloromethane solvent
molecule as indicated in the ORTEP diagram shown in
Fig. 1. The inclusion of this volatile solvent in crystal lat-
tices is not uncommon. Inclusion of dichloromethane is
reported [18] to be the most frequent amongst structures of
metalloorganic compounds and second only to methanol in
structures of organic compounds. Host–guest interactions
[19] have previously been reported for calixarenes in which
the dichloromethane inclusion is facilitated by participation
in hydrogen-bonding networks. No disorder is associated
with the dichloromethane solvent molecule, often the result
of intermolecular non-bonding interactions. The distance
between the chlorine atoms of the dichloromethane and the
than the observed HꢀꢀꢀO distances for analogous interactions
in the solvate structure of 1. The significance of these weak
CHꢀꢀꢀO interactions between the dichloromethane molecule
and the p-toluenesulphonyl groups, and their contribution
towards aligning molecules of 1 within the crystal lattice,
previously reported for aromatic compounds [20] is unclear.
The donor–acceptor (DꢀꢀꢀA) proximity in these CHꢀꢀꢀO
interactions is misleading and may be rationalized by their
inherent D–HꢀꢀꢀA angle defined by the location of the
hydrogen atom. The proximity of the donor carbon in the
dichloromethane to the oxygen acceptor of the sulphonyl
moiety in this structure is underlined by a D–HꢀꢀꢀA angle of
163°. It is clear, however, that the dichloromethane mole-
cules occupy cavities between the larger solute molecules
(Fig. 2) of compound 1, a phenomenon reported to be cru-
cial in stabilizing structures and facilitating crystallization
[18]. Adjacent solvent molecules are symmetrically related
through a twofold screw axis at y = ½ and run parallel to the
[0 0 1] direction between molecular chains of 1.
˚
p-toluenesulphonyl groups, in excess of 5 A, excludes the
feasibility of any C–HꢀꢀꢀCl interactions between these enti-
ties. Intermolecular CHꢀꢀꢀO interactions, in which the
dichloromethane molecule acts as a donor via the C–H
bonds to oxygen atoms of sulphonyl moieties, are identified
on 361 occasions in the CCDC database. These interactions
The unit cell contains two molecular chains of com-
pound 1 formed via an intricate hydrogen-bonding array
˚
have an average HꢀꢀꢀO distance of 2.57 A, which is shorter
Fig. 1 ORTEP drawing of title
compound (50% probability
ellipsoids)
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J Chem Crystallogr (2008) 38:577–582
consisting of N–HꢀꢀꢀN and N–HꢀꢀꢀO intermolecular inter-
actions (Table 2). The molecular chains are symmetrically
equivalent through a twofold screw axis at (½, ½, 0) and
are parallel to [0 0 1]. Adjacent molecules in each chain are
related via a c-glide at a = ¼ that oscillates hydrogen-
bonding motifs (Fig. 3) along [0 0 1].
A C(5) chain motif [21] is defined by an intermolecular
N–HꢀꢀꢀN hydrogen bond in which the terminal tosylated
nitrogen N(1) acts as a donor via H(1H) to the central
amino atom N(2) at (1½ - x, y, z + ½). Tosylated nitro-
gen atom N(3) acts as a hydrogen donor via H(3H) to
oxygen O(2) in the sulfonyl group at (1½ - x, y, z - ½)
completing a N–HꢀꢀꢀO intermolecular interaction that
defines a C(10) chain. The described C(5) and C(10)
chains, parallel to [0 0 1], constitute the basic unitary graph
set. A basic binary graph set includes a C22ð15Þ descriptor
when combining N–HꢀꢀꢀN and N–HꢀꢀꢀO interactions via
translation along [0 0 1]. The binary graph set is elaborated
by a c-glide at a = ¼ with a glide component ½/c/ that
further combines these intermolecular interactions to
describe a ring motif R22ð9Þ (Fig. 3).
Fig. 2 Spacefill diagram of included DCM molecules (solid shading)
viewed along [0 1 0]
˚
Table 2 Hydrogen bonds for 1 (A) and (°)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
p(DHA)
The graphs sets describing the hydrogen-bonding array
in compound 1 are comparable to that observed for a
structurally similar triazaheptane derivative [7]. In the
structure of di-p-toluenesulfonyl-2,6-di(methylethyl)-1,4,
7-triazaheptane (2, Chart 1) N–HꢀꢀꢀO intermolecular
N(1)–H(1H)ꢀꢀꢀN(2)i
0.80(2)
0.79(2)
2.19(2)
2.60(3)
2.994(3)
3.307(4)
174(3)
150(3)
N(3)–H(3H)ꢀꢀꢀO(2)ii
Note: Symmetry codes: i = (1½ - x, y, z + ½); ii = (1½ - x, y,
z - ½)
b
c
c
0
0
a
a
C(10)
C(5)
b
a
0
c
R22(9)
Fig. 3 Graph sets for N–HꢀꢀꢀO and N–HꢀꢀꢀN interactions along [0 0 1]. Hydrogen atoms removed for clarity
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J Chem Crystallogr (2008) 38:577–582
581
Chart 1 Compounds
discussed: REFCODE 2
(LAHKIP); 3 (IFECUR)
N
N
H
N
3
O
O
O
O
NH
HN
NH
HN
S
S
S
S
O
2
O
O
O
Table 3 Selected bond angles
(°) for 1
interactions are the only interactions present, where nitro-
gen atoms in amino groups acts as donors to the oxygen
atoms of sulfonyl moieties. The C(10) chain motifs and a
chain of rings C22ð20Þ R22ð8Þ motifs describe the basic
unitary and basic binary graph set along [1 0 0], respec-
tively. Expected distorted tetrahedral geometries occur at
the sulfur atom in the p-toluenesulfonyl groups (Table 3).
The imposed restriction to rotation [8] about bonds to
amine nitrogens protected by bulky p-toluenesulfonyl
groups, predisposing these compounds toward cyclization
products, becomes evident from the structures of 1 and 2.
The diethylenetriamine backbone in both structures does
not assume an orientation typical of primary alkylamines
[22]. The diethylenetriamine backbone in bis((p-toluene-
sulfonylamido)ethyl)-2-(aminomethyl) pyridine) [17] (3,
Chart 1) adopts a conformation that more closely resem-
bles that observed in azamacrocycles.
O(1)–S(1)–O(2)
O(1)–S(1)–N(1)
O(2)–S(1)–N(1)
O(1)–S(1)–C(1)
O(2)–S(1)–C(1)
N(1)–S(1)–C(1)
O(3)–S(2)–O(4)
O(3)–S(2)–N(3)
O(4)–S(2)–N(3)
119.59(14)
108.67(13)
105.58(13)
108.03(13)
107.65(13)
106.64(12)
120.07(16)
105.97(13)
107.12(15)
107.87(16)
107.49(13)
107.80(14)
O(3)–S(2)–C(12)
O(4)–S(2)–C(12)
N(3)–S(2)–C(12)
convincing argument cannot be advanced for p-toluene-
sulfonyl groups masking the nucleophilicity of nitrogen
atoms through steric control in diethylenetriamine deriva-
tives. The discussion alluding to the minimal loss of
internal entropy that favors cyclization products perhaps
affords a more plausible explanation.
Dihedral angles in the structure of 3 for cis configura-
tions between O=S bonds, in p-toluenesulfonyl groups, and
N–H bonds, of the amine moieties they are protecting,
range between 35 and 42°. In compound 3 two crystallo-
graphically independent molecules occupy the asymmetric
unit and N–HꢀꢀꢀO and O–HꢀꢀꢀN intermolecular interactions
occur only with included ethanol solvent molecules. Sev-
eral discrete, D(2), interactions describe the hydrogen-
bonding pattern with the solvent molecule in which the
ethanolic oxygen acts as a donor to the pyridine nitrogen or
as an acceptor for the interaction with the amine nitrogen
atom. On a binary level these interactions result in R22ð10Þ
motifs. A R21ð10Þ motif describes the hydrogen-bonding
pattern for the N–HꢀꢀꢀO intermolecular interactions
between two amine nitrogen atoms in the diethylenetria-
mine backbone and the oxygen of the same ethanol
molecule. Larger variations occur for analogous dihedral
angles in 1 and 2 where N–HꢀꢀꢀO interactions involve the
oxygen atom of the sulfonyl moieties. The dihedral angle
O2S1N1H1H = 44.2(1) in 1 and O3S2N3H37 = 41.3(1) in 2
compare with the dihedral angles observed in the structure
of 3. Anomalies are O2S1N1H35 = 2.4(1) in 2, that places
the sulfonyl oxygen and amino hydrogen atom in a pseudo-
eclipsed position, and O3S2N3H3H = 62.2(1) in 1, where
the sulfonyl moiety does not participate in the hydrogen-
bonding array. Given the above crystallographic data a
Supplementary Material
CCDC 662299 contains the supplementary crystallographic
data for this paper. Copies may be obtained free of charge
from the Director, CDC, 12 Union Road, Cambridge, CB2
1EZ, UK; e-mail: deposit@ccdc.cam.ac.uk or http://www.
ccdc.cam.ac.uk.
Acknowledgments We thank the H. E. Griffin Trust (A.S.S.), the
University of the Witwatersrand (A.S.S., H.M.M.), the National
Research Foundation (K.P., H.M.M.), the South African Research
Chairs Initiative of the Department of Science and Technology, and
the National Research Foundation (H.M.M.) for financial support.
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