Exploring intermolecular contacts in multi-substituted benzaldehyde derivatives: X-ray, Hirshfeld surface and lattice energy analyses

Article abstract of DOI:10.1039/c9ra10752e

Crystal structures of six benzaldehyde derivatives (1-6) have been determined and their supramolecular networks were established by an X-ray crystallographic study. The study has shown that the compounds are linked by various intermolecular interactions s

Full text of DOI:10.1039/c9ra10752e

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Exploring intermolecular contacts in multi-
substituted benzaldehyde derivatives: X-ray,
Cite this: RSC Adv., 2020, 10, 16861
Hirshfeld surface and lattice energy analyses†
a
Meloddy H. Manyeruke,a Marcel Louzada,a Sergei Rigin,b
*
Siya T. Hulushe,
Eric C. Hosten
and Gareth M. Watkinsa
c
Crystal structures of six benzaldehyde derivatives (1–6) have been determined and their supramolecular
networks were established by an X-ray crystallographic study. The study has shown that the compounds
are linked by various intermolecular interactions such as weak C–H/O hydrogen bonding, and C–H/p,
p–p and halogen bonding interactions which consolidate and strengthen the formation of these
molecular assemblies. The carbonyl group generates diverse synthons in 1–6 via intermolecular C–H/O
hydrogen bonds. An interplay of C–H/O hydrogen bonds, and C–H/p and p–p stacking interactions
facilitates the formation of multi-dimensional supramolecular networks. Crystal packings in 4 and 5 are
further generated by type I halogen/halogen bonding interactions. The differences in crystal packing
are represented by variation of substitution positions in the compounds. Structure 3 is isomorphous with
4 but there are subtle differences in their crystal packing. The nature of intermolecular contacts in the
structures has been studied through the Hirshfeld surfaces and two-dimensional fingerprint plots which
serve as a comparison in constructing different supramolecular networks. The intermolecular interaction
energies are quantified utilizing theorectical calculations for the title compounds and various analogous
structures retrieved from the Cambridge Structural Database (CSD). Also intermolecular interactions for
the molecular pairs are exctrated from respective crystal structures. Essentially, there are some invariant
and variable intermolecular contacts realized between different groups in all six structures. The ab initio
DFT total lattice energy (ETot) calculations showed a direct correlation with thermal strengths of the title
compounds.
Received 20th December 2019
Accepted 1st April 2020
DOI: 10.1039/c9ra10752e
rsc.li/rsc-advances
50 kJ molꢀ1
.
Intermolecular contacts or weak interactions
2
1. Introduction
(#15 kJ molꢀ1) such as C–H/p, hydrogen/halogen bonds and
p–p stacking are well-known to signicantly inuence the
molecular assembly in organic compounds.3 Numerous syn-
thons that incorporate intermolecular contacts such hydrogen/
halogen bonds, C–H/p, lone pair–p and p–p stacking inter-
actions signicantly affect robustness to produce molecular
solids with promising properties.4 Halogen bonding interac-
tions established in many halogen-containing organic crystals
are believed to enhance crystal stability.5 Essentially, these
intermolecular contacts are said to be independently weaker
and geometrically less well-dened, but their combined effect
can be equally important as strong interactions.6 It is useful to
study the diversity of hydrogen-bonding systems in molecules
that contain a rigid benzyloxy core with different positions of
substituents, and to explore their structural features including
interplay of intermolecular contacts in building the possible
supramolecular networks.7 It is of interest to explore the role of
these intermolecular contacts in the molecular assembly of
halogen-substituted (benzyloxy)benzaldehydes. An additional
interest in the (benzyloxy)benzaldehyde moiety lies in its anti-
cancer activity against HL-60 cells8 and also serves as important
Crystal engineering of supramolecular networks linked via
intermolecular contacts continues to be a dynamic topic in the
solid-state studies of self-assembly.1 Hydrogen bonds are
recognized for their contribution in self-assembly when
extended structures are constructed from synthons with
aromatic moieties.2 Electronegative atoms such as O and N are
recognized to form strong hydrogen bonds D–H/A (D ¼ donor,
A ¼ acceptor) with an estimated interaction energy between 16–
aDepartment of Chemistry, Rhodes University, P.O. Box 94, Grahamstown 6139, South
Africa. E-mail: g11h7156@campus.ru.ac.za
bDepartment of Chemistry, New Mexico Highlands University, Las Vegas, New Mexico,
87701, USA
cDepartment of Chemistry, Nelson Mandela University, P.O. Box 77000, Port Elizabeth
6031, South Africa
† Electronic supplementary information (ESI) available: X-ray crystallographic
les in CIF format for structural determination of 1, (CCDC no. 1898081), 2,
(CCDC no. 1895105), 3, (CCDC no. 1898076), 4, (CCDC no. 1898074), 5, (CCDC
no. 1898075) and 6, (CCDC no. 1898078) and 1H and 13C NMR. CCDC 1898081,
1895105, 1898074–1898076 and 1898078. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c9ra10752e
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precursors in the design of new inhibitors of HIV-1 integrase.9 A or a 400 MHz spectrometer. Spectra were recorded in deuterated
search of the Cambridge Structural Database (version 5.40, solvent CDCl3. All chemical shi values are reported in parts per
November CSD 2018 release)10 for benzyloxybenzene derivatives million (ppm) referenced to residual solvent resonances (CDCl3
(search + restricted to the aldehyde class) among the organic dH 7.26, dC 77.2).
compounds returned 71 hits (excluding duplicate structures).
Further restriction to (benzyloxy)benzaldehyde/(benzyloxy)
benzoic acid derivatives (excluding solvates and cocrystals),
2.2 Synthesis and crystallization
only 15 structures11 with refcodes COBNUC, CUNMAZ, DUTRIU, Compound 1: a mixture of 4-hydroxybenzaldehyde (1.22 g,
DUTRIU01, DUTRIU02, EROHUP, KERDUH, IPEXEH, LELQUQ, 10 mmol) and benzyl bromide (1.18 mL, 10 mmol) was reuxed
LELRAX, MEQLIE, POMLUA, VOQFIS, XEVROF and XIMPAL are in 10% aqueous sodium hydroxide (NaOH, 10 mL) solution for
found. Compound 1 crystallizes in a new crystal form in space thirty minutes and then cooled to room temperature. Water was
group P212121 which is different from the orthorhombic Pna21 then added and the solid which formed was ltered, washed
space group reported previously (DUTRIU, DUTRIU01 and with water, dried and nally crystallised from hexane/water
DUTRIU02). Sze et al., 2011 reported a similar structure to 6 mixture affording 4-(benzyloxy) benzaldehyde as an off-white
(refcode: IPEXEH with space group P1) with different unit cell block crystals (0.8 g, 38%) mp 99–100 ꢁC (lit.8 99–100 ꢁC);
ꢀ
dimensions. Self-assembly mediated by weak interactions has nmax/cmꢀ1 1213 (C–O), 1736 (C]O); dH (400 MHz; CDCl3) 5.15
been established as a convenient and prevailing protocol for the (2H, s, PhCH2), 7.08 (2H, d, J ¼ 8.7 Hz, ArH), 7.34–7.47 (5H, m,
construction of geometrically well-dened structures. A suitable ArH overlapping), 7.84 (2H, d, J ¼ 8.8 Hz, ArH) and 9.89 (1H, s,
approach to deal with crystal structure prediction is represented HC]O); dC (100 MHz; CDCl3) 70.4 (PhCH2), 115.2, 127.6, 128.4,
by Hirshfeld surface12 based tool and this method provides 128.8, 130.2, 132.1, 136.0, 163.8 (ArC) and 190.9 (C]O).
a simplistic way of managing valuable statistics on trends in Compound 2: the procedure described for the synthesis of 1 was
crystal packing. The variations in Hirshfeld surface and the followed using 3-ethoxy-2-hydroxybenzaldehyde (1.66 g, 10
analysis of the resultant 2D ngerprint plot12 offer a powerful mmol). Work up afforded 2-(benzyloxy)-3-ethoxybenzaldehyde
means of quantifying the interactions within the crystal struc- as a white solid which was recrystallized from hexane to
tures, drawing attention to signicant similarity and differences afford colourless rod-like crystals (0.86 g, 34%), mp 78–79 ꢁC
between structures by individuating the packing motifs. In this (lit.13 39–40 ꢁC); nmax/cmꢀ1 1242 (C–O), 1735 (C]O); dH (600
paper, we report the synthesis of a series of multi-substituted MHz; CDCl3) 1.51 (3H, t, J ¼ 7.0 Hz, CH3), 4.15 (2H, q, J ¼ 7.0 Hz,
benzaldehyde derivatives. Their structures were conrmed by CH2) 5.20 (2H, s, PhCH2), 7.11 (1H, t, J ¼ 7.9 Hz, ArH), 7.17 (1H,
spectroscopic methods and X-ray crystallography. Essentially, X- dd, J ¼ 8.0, 1.4 Hz, ArH), 7.32–7.43 (6H, m, ArH overlapping)
ray crystallographic analysis of the structures demonstrates the and 10.27 (1H, s, HC]O); dC (150 MHz; CDCl3) 15.0 (CH3), 64.9
presence of multiple weak and non-covalent C–H/O hydrogen (CH2), 76.4 (PhCH2), 119.2, 119.4, 124.3, 128.6, 128.7, 128.8,
bonding, C–H/p, p–p stacking and halogen/halogen 130.5, 136.7, 151.5, 152.5 (ArC) and 190.4 (C]O). Compound 3:
bonding interactions are likely to play an important role in the the procedure described for the synthesis of 1 was followed
supramolecular ensembles of these non-planar layered benzal- using 5-bromo-2-hydroxybenzaldehyde (2.01 g, 10 mmol). Work
dehyde derivatives in the solid state. To investigate the effect of up afforded 2-(benzyloxy)-5-bromobenzaldehyde as an off-white
substituent positions on the resulting compounds as well as the solid which was recrystallized from hexane/methanol mixture to
molecular packing, we have examined six benzaldehydes (1–6) afford colourless block crystals (1.66 g, 57%), mp 69–70 ꢁC (lit.14
with different substituent positions in the aldehyde skeleton. In 70–71 ꢁC); nmax/cmꢀ1 1234 (C–O), 1735 (C]O); dH (400 MHz;
this paper, we have demonstrated that weak intermolecular CDCl3) 5.18 (2H, s, PhCH2), 6.95 (1H, d, J ¼ 8.9 Hz, 3H), 7.34–
contacts are stronger for benzyloxybenzaldehydes than their 7.46 (5H, m, ArH overlapping), 7.60 (1H, dd, J ¼ 8.9, 2.8 Hz, 4H),
analogous structures reported by Chattopadhyay.4 Also, we have 7.94 (1H, d, J ¼ 2.8 Hz, 6H) and 10.46 (1H, s, HC]O); dC (100
shown that there are subtle differences in crystal packing MHz; CDCl3) 71.0 (PhCH2), 114.0, 115.3, 126.6, 127.5, 128.6,
between these structures. In addition, a study of close inter- 128.9, 131.2, 135.7, 138.3, 160.0 (ArC) and 188.4 (C]O).
molecular contacts in the title derivatives by Hirshfeld surface Compound 4: the procedure described for the synthesis of 1 was
and lattice energy analyses is presented.
followed using 5-chloro-2-hydroxybenzaldehyde (1.57 g, 10
mmol). Work up afforded 2-(benzyloxy)-5-chlorobenzaldehyde
as a white solid which was recrystallized from hexane to
afford pale brown block crystals (2.13 g, 86%), mp 77–79 ꢁC (lit.8
68–69 ꢁC); nmax/cmꢀ1 1233 (C–O), 1734 (C]O); dH (400 MHz;
2. Material and methods
2.1 Materials
All commercially available chemicals and reagents were CDCl3) 5.18 (2H, s, PhCH2), 7.00 (1H, d, J ¼ 8.8 Hz, 3H), 7.34–
purchased from Sigma-Aldrich (Pty) Ltd and Merck (Pty) Ltd, 7.44 (5H, m, ArH overlapping), 7.46 (1H, dd, J ¼ 8.9, 2.8 Hz, 4H),
and were used without further purication unless stated 7.80 (1H, d, J ¼ 2.8 Hz, 6H) and 10.48 (1H, s, HC]O); dC (100
otherwise. Fourier-transform infrared (FT-IR) spectra were MHz; CDCl3) 71.0 (PhCH2), 114.9, 126.2, 126.8, 127.4, 128.1,
collected on PerkinElmer Spectrum 100 spectrometer with an 128.6, 128.9, 135.5, 135.7, 159.5 (ArC) and 188.5 (C]O).
ATR attachment. Mid-infrared (4000–650 cmꢀ1) spectra were Compound 5: the procedure described for the synthesis of 1 was
obtained by placing samples on a ZnSe crystal plate. The 1H and followed using 3,5-dibromo-2-hydroxybenzaldehyde (2.80 g, 10
13C NMR spectra were recorded on either a Bruker Fourier 300 mmol). Work up gave 2-(benzyloxy)-3,5-dibromobenzaldehyde
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as a white uffy solid which was recrystallized from hexane/ surfaces were mapped with dnorm using a red-white-blue colour
water mixture to afford colourless rod-like crystals (1.62 g, scheme, where red highlights shorter contacts, white is used for
44%), mp 66–68 ꢁC lit.15 109.5–110.5 ꢁC; nmax/cmꢀ1 1209 (C–O), contacts around the vdW separation, and blue is for longer
1736 (C]O); dH (400 MHz; CDCl3) 5.12 (2H, s, PhCH2), 7.38– contacts.
7.41 (5H, m, ArH overlapping), 7.86 (1H, d, J ¼ 2.4 Hz, 6 H), 7.98
2.3.2 Quantum chemical calculations
Molecular geometry. All calculations done using Gaussian
(1H, d, J ¼ 2.6 Hz, 4H) and 9.96 (1H, s, HC]O); dC (100 MHz;
CDCl3) 78.13 (PhCH2), 118.4, 119.6, 129.0, 129.1, 129.3, 130.5, 09D.17 All geometry was calculated with the B3LYP18 functional,
132.5, 134.8, 141.5, 157.5 (ArC) and 187.6 (C]O). Compound 6: using the 6-311g(d,p)19 basis set and an Ultrane grid. The
a mixture of 2-hydroxy-3-methoxybenzaldehyde (3.80 g, 25 energy for B3LYP was taken from the same calculation. The
mmol), propargyl bromide (1.93 mL, 25.5 mmol) and K2CO3 M06HF energy was calculated at the same basis set from the
(6.9 g, 50 mmol) was heated at 80 ꢁC in acetonitrile (CH3CN) for B3LYP geometry.
four hours. The solvent was then evaporated and the crude
Crystal geometry. The structures were optimised using a con-
product was dissolved in dichloromethane (CH2Cl2) and strained PBC geometry calculation (with the translation vectors
washed with water. The organic layer was dried and the residue obtained from the CIF les). Energy was calculated for both the
recrystallized in hexane/water mixture to obtain 3-methoxy-2- B3LYP and M06HF20 functionals with the 6-311g(d,p) basis set.
(prop-2-yn-1-yloxy)benzaldehyde as pale bꢁrown block crystals The dispersion effects were accounted for using Grimme's type
(4.37 g, 92%), mp 52–53 C (lit.16 51–52.5 C); nmax/cmꢀ1 1736 3 dispersion (DFT–D3)21 and the Basis Set Superposition Error
ꢁ
(C]O), 3262 (^CH); dH (400 MHz; CDCl3) 2.47 (1H, t, J ¼ (BSSE) was calculated using Gaussian 09's counterpoint
2.4 Hz, 30-CH), 3.90 (3H, s, CH3), 4.87 (2H, d, J ¼ 2.4 Hz, 10-CH2), method.
7.16 (2H, q, J ¼ 7.8 Hz, 4 and 5H), 7.44 (1H, dd, J ¼ 7.0, 2.4 Hz,
2.3.3 Lattice energy calculations. Crystal lattice energies (kJ
6H) and 10.48 (1H, CHO); dC (100 MHz; CDCl3) 56.2 (CH3O), molꢀ1) were calculated from single-crystal X-ray diffraction data
61.0 (C-10), 77.0 (C-30), 78.4 (C-20), 117.9, 119.0, 125.0, 131.3, using the atom–atom force eld with subdivision of the inter-
149.6 and 152.9 (ArC) and 190.7 (C]O).
action energies into coulombic, polarization, London disper-
sion, and Pauli repulsion components (AA-CLP method
implemented in the CLP-PIXEL computer program package,
ver. 3.0; available from http://www.angelogavezzotti.it).22
Default settings were used, and hydrogen atom positions were
assigned by the soware.
2.3 Methods
2.3.1 Hirshfeld surface analysis. The Hirshfeld surfaces are
mapped with dnorm, and 2D ngerprint plots presented in this
work were generated using CrystalExplorer 2.1.12 The 2D plots
2.3.4 Single-crystal X-ray diffraction. All datasets were
collected at 200 K using a Bruker APEX-II CCD diffractometer
equipped with graphite monochromated Mo Ka radiation (l ¼
˚
were shaped by binning (di, de) pairs in intervals of 0.01 A and
colouring each bin of the resulting 2D histogram as a function
of the fraction of surface points in that bin, ranging from blue
through green to red. Graphical plots of the molecular Hirshfeld
˚
0.71073 A). Flack parameters for the non-centrosymmetric
Table 1 Structural data and refinement parameters for compounds 1–6
Compound
CCDC no.
Formula
1
2
3
4
5
6
1898081
C
212.24
0.71073
200
1895105
C14H16O3
256.29
0.71073
200
1898076
C14H11BrO2
291.14
0.71073
200
1898075
C14H11ClO2
246.68
0.71073
200
1898074
C14H10Br2O2
370.04
0.71073
200
1898078
C11H10O3
190.19
0.71073
200
14H12O2
MW/g molꢀ1
˚
l/A
T/K
Crystal system
Space group
Orthorhombic
Pna21
11.5088(5)
12.9889(6)
7.2608(4)
90
Monoclinic
P21/c
15.3768(15)
4.5578(5)
19.4729(19)
90
99.697(5)
90
1345.3(2)
1.265
Monoclinic
P21/n
7.316(4)
13.239(10)
12.300(8)
90
100.36(3)
90
1171.9(13)
1.650
Monoclinic
P21/n
4.9219(2)
16.3089(6)
14.7245(5)
90
99.171(2)
90
1166.84(8)
1.404
Orthorhombic
P212121
4.0992(2)
17.1619(7)
18.9382(8)
90
Triclinicic
P1
ꢀ
˚
a/A
7.7110(4)
7.9405(4)
9.1857(5)
65.896(2)
85.990(2)
70.155(2)
481.36(4)
1.312
˚
b/A
˚
c/A
a/ꢁ
b/ꢁ
g/ꢁ
90
90
90
90
ꢀ3
˚
V/A
1085.39(9)
1.299
1332.30(10)
1.845
Dcalc/mg mꢀ3
Z
4
4
4
4
4
2
m (mmꢀ1
F(000)
2q (ꢁ)
)
0.086
448
56.6
0.087
544
56.8
3.493
584
56.8
0.312
512
56.6
6.074
720
56.6
0.096
200
56.8
R (int)
0.015
0.064
0.027
0.023
0.033
0.015
GOOF
1.05
0.0295
0.0822
1.02
0.0625
0.1769
1.05
0.0263
0.0618
1.05
0.0337
0.0880
1.04
0.0218
0.0472
1.04
0.0366
0.1024
a
R1 (I > 2s(I))
wR2b (I > 2s(I))
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structures 1 and 5 are ꢀ0.01(15) and 0.015(11), respectively. position. Compound 6 differs from the rest of the structures
Data reduction was carried out using the Bruker program with the benzyloxy substituent missing. Compound 2 and 6
SAINT.23 A numerical absorption correction SADABS24 was differ in respect to the ethoxy substituent in the B ring (at 3- and
applied. The structures of the title compounds were solved 2-positions, respectively). The molecule of 1 is essentially planar
˚
using a dual-space algorithm and rened by the full-matrix with r.m.s. deviation of 0.0608 A. In the crystal structures of the
least-square technique on F2 with anisotropic thermal param- compounds, the O/O distances range from 2.686(8)–6.380(2)
˚
eters to describe the thermal motions of all non-hydrogen A. The shortest O/O distances is found in 1 while 2 has the
atoms using the programs SHELXT-2018/2 (ref. 25) and longest. The bond-lengths of the A ring in 1–6 lie between
˚
SHELXL-2018/3 (ref. 26) respectively. The hydrogen atoms of the 1.374(4) to 1.405(3) A, the former being at the aromatic carbon
methyl groups were allowed to rotate with a xed angle around anking the ethoxy substituent in 2, and the latter at the point
the C–C bonds to best t the experimental electron density of substitution of the propargyl (2-propynyl) group in 6 and
while all other hydrogen atoms were placed at geometrically IPEXEH. The internal bond-lengths in the B ring of the
˚
idealized positions. The methyl hydrogen atoms were assigned compounds (1–5) range from 1.334(6) to 1.429(5) A (the bond-
isotropic temperature factors equal to 1.5 times the equivalent lengths reside in C23–C24 and C25–C26 of 2, respectively).
temperature factor of the parent atom whereas the displace-
The bond-angles generally agree well with those featuring in
ment parameters for the other hydrogen atoms were taken as analogous structures.4,11 These bond-lengths do not vary
Uiso(H) ¼ 1.2Ueq.(C). Programs: PLATON,27 Mercury28 and X- signicantly despite the differing intermolecular interaction
Seed.29 For structural data and renement parameters for the patterns observed in various structures.11 The geometry about
title compounds, refer to Table 1.
the C]O group is very similar in all the compounds. The bond-
angles of substituted benzaldehydes of 1–6 agree well with the
mean values of relevant bond-angles obtained with MOGUL
(version 1.75, Nov 2018)30 from searches based on related
molecular fragments on the Cambridge Structural Database
(CSD version 5.40, Nov 2018).10 The dihedral angle between the
A ring and linear propargyloxy group in 6 is the largest angle
equal to 68.37ꢁ which is vastly different from 61.77ꢁ of IPEXEH.
The dihedral angle between the A and B rings vary signicantly
with 1 having the smallest angle equal to 5.40ꢁ (while for
DUTRIU, DUTRIU01 and DUTRIU02 the A/B dihedral angle is
5.23ꢁ,5.86ꢁ and 4.97ꢁ respectively). In all the compounds with
the exception of compound 5; the carbonyl, methoxy and ethoxy
groups as well as the halogens lie in the same plane of the A
ring. In 5, the A ring is slightly distorted and consequently the
2.4 Results and discussion
2.4.1 Structural analysis. X-ray crystallography X-ray crys-
tallography analyses reveal that 1 and 4 crystallize in ortho-
rhombic with space groups Pna21 and P212121, respectively
while 2 crystallizes in monoclinic P21/c; 3 and 5 both crystallize
in monoclinic P21/n space group and 6 crystallizes in triclinic
ꢀ
with P1 space group. ORTEP diagrams of compounds 1–6 drawn
with 50% ellipsoid probability are depicted in Fig. 1. The overall
molecular conformation in 1–5 can be described by the relative
orientation of two phenyl rings (A: C11–C16 atoms, B: C21–C26
atoms) of the benzyloxybenzene core. The structures 2–5 match
the position of benzyloxy substituent in the A ring (at the 2-
position), while 1 has the benzyloxy substituent at the 4-
Fig. 1 ORTEP view and atom numbering scheme of compound 1–6 with displacement ellipsoids at 50% probability level.
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Fig. 2 (a) 3D parallel chains in 1 running along the [001] direction; (b) a stair-case like supramolecular framework in 2 propagating along the [010]
direction. The crystalline solids are generated via C–H/O and C–H/p interactions. Hydrogen atoms not involved in hydrogen bonding have
been omitted.
two substituted Br1 and Br2 atoms both lie just outside the 2 ꢀ y, 1 ꢀ z) hydrogen bonding with distance of 2.463 and 2.475
˚
plane of the ring.
A (Table 2), respectively.
The torsion angle C21–C2–O2–C11 of ꢀ176.4(1)ꢁ, +170.5(2)ꢁ,
The formation of dimers via intermolecular contacts of the
ꢀ177.1(2)ꢁ, ꢀ176.0(2)ꢁ, and +177.2(1)ꢁ in 1–5 displays an anti- nature C1–H1B/O2 and C1–H1A/O2 are respectively seen in 3
conguration of molecules about the C2–O2 bond while the
torsion angle C3–C2–O2–C12 in 6 is ꢀ66.77ꢁ. The crystal
packing in 1–6 (Fig. 2–4) is secured by intermolecular contacts.
The supramolecular assembly in these structures can be readily
seen as substructures of lower dimensionality with synthons as
the building blocks. In 1, the phenyl ring carbon atom C2 in the
molecule at (x, y, z) acts as a hydrogen bond donor to the
carbonyl oxygen atom O1 at (1 ꢀ x, ꢀ1/2 + y, 1/2 ꢀ z). The
propagation of dimers via intermolecular C2–H2A/O1, C2–
˚
H2B/O1 hydrogen bonds and C26–H26/p(arene) (2.790 A) in
1 generates C12(7) parallel chains to which their combination
form three-dimensional polymeric chains (comparably to
DUTRIU, DUTRIU01 and DUTRIU02) running along the [001]
direction (Fig. 2a). In 2, the benzyloxy carbon atom C2 in the
molecule acts as a hydrogen bond donor to the carbonyl oxygen
atom O1 in the molecule at (1 ꢀ x, ꢀ1/2 + y, 1/2 ꢀ z). The
structure is generated via hydrogen bonding interactions to give
rise to the formation of a dimeric R22(14) synthon propagating
along the [100] direction, forming 2D parallel columns (Fig. 2b)
propagating along the [010] plane. Additionally the packing
arrangement of the compound is further generated through
˚
intermolecular C14–H14/p(arene) hydrogen bonding (2.768 A)
˚
and p(lone pair)–p(lone pair) stacking interactions (3.214 A).
Despite the similarity between 3 and 5 in terms of their
molecular geometries, there are subtle differences in their
supramolecular self-organization. In the crystal structures, the
compounds 3 and 5 adopt a dimeric form of C15–H15/O2 (O2
at 3/2 ꢀ x, ꢀ1/2 + y, 1/2 ꢀ z) and C1–H1A/O2 (O2 at ꢀ1/2 + x, 3/
Fig. 3 Monomeric 2D sheets in 3 running along the [100] plane. The
crystalline solids are generated via C–H/O and p/p interactions.
Hydrogen atoms not involved in hydrogen bonding have been
omitted.
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Fig. 4 (a) 3D parallel chains in 4 running along the [100] direction; (b) 2D supramolecular framework in 5 propagating along the [100] plane; (c)
parallel networks in 6 propagating along the [100] direction. Hydrogen atoms not involved in hydrogen bonding have been omitted.
Table 2 Hydrogen bonding geometry of compounds 1–6a
˚
A (ꢀx, ꢀ1/2 + y, 3/2 ꢀ z) type I halogen bonding interactions,
respectively. In 6, the carbonyl oxygen O1 atom in the molecule
D–H/A
d(D–H) d(H/A) d(D/A) L(D–H/A) Lsb
at (x, y, z) acts as hydrogen bond acceptor from the alkyne
carbon C4 at (ꢀx, 1 ꢀ y, 2 ꢀ z), thus constructing chair
conformations propagating along the [100] direction (Fig. 4c).
The structure 6 is generated through C4–H4/O1 and C4–H14/
p(alkyne) hydrogen bonding interactions (Table 2) constructing
1
2
C2–H2B/O1(i)
0.99
2.55
2.79
2.53
2.77
2.46
2.67
2.64
2.48
2.84
2.32
2.81
3.343(2) 142
3.657(5) 152
3.414(1) 149
3.657(1) 156
3.408(4) 173
3.620(2) 162
3.351(2) 132
3.447(8) 167
3.773(8) 169
3.198(6) 154
3.653(6) 148
5.40
C26–H26/Cg(1)(ii) 0.95
C2–H2A/O1(iii)
0.99
22.83
C14–H14/Cg(2)(iv) 0.95
3
4
C15–H15/O1(v)
C2–H2A/O1(vi)
C16–H16/O1(vii)
C2–H2A/O1(viii)
0.95
0.99
0.95
0.99
21.66
23.48
2
a chair-like R2 (18) synthon, which is similar to IPEXEH, to give
rise to the formation of supramolecular networks.
2.4.2 Hirshfeld surface and lattice energy analyses. The
Hirshfeld surfaces of 1–6 are shown in Fig. 5, illustrating
surfaces that have been mapped over dnorm. The surfaces are
presented as transparent to permit visualization of the
substituted benzaldehyde moiety around which they were
calculated. The colour codes from red for short dnorm ranges to
blue for long ranges were presented. The dominant interactions
in the title derivatives can be seen as the bright red areas. Fig. 5
effectively summarizes the Hirshfeld surfaces as large/bright
red areas are indicative of C–H/O and, C–H/p hydrogen
bonding interactions.
Apart from hydrogen bonding, the p–p stacking interactions
are seen on the dnorm surfaces as small red areas in 4 and large
red areas in 6. The other trivial ranges of noticeable red spots
and light-white regions are demonstrative of weaker and longer
contacts other than hydrogen bonds. In addition, Fig. 6 depict
the two-dimensional ngerprint plots that decompose to high-
light particular atoms pair close contacts and in Fig. 7 the
relative contributions of individual intermolecular interactions
to the Hirshfeld surfaces area are shown. In 1, the O/H/H/O
intermolecular interactions appear as a pair of symmetrical
5
6
20.69
68.37
C13–H13/Cg(2)(ix) 0.95
C4–H4/O1(x)
C4–H14/p(xi)
0.95
0.95
Cg(1) and Cg(2) are the centroids of A and B rings, respectively. b A/B
a
ring dihedral angles (in degree). Symmetry codes: (i) ꢀ1/2 + x, 3/2 ꢀ y, z;
(ii) 1/2 + x, 1/2 ꢀ y, z; (iii) 1 ꢀ x, ꢀ1/2 ꢀ y, 1/2 ꢀ z; (iv) x, 1/2 ꢀ y, 1/2 + z; (v)
3/2 ꢀ x, ꢀ1/2 + y, ꢀz; (vi) ꢀ1/2 + x, 1/2 ꢀ y, ꢀ1/2 + z; (vii) ꢀ1/2 + x, 1/2 ꢀ y,
1/2 + z; (viii) ꢀ1/2 + x, 3/2 ꢀ y, 1 ꢀ z; (ix) 1/2 ꢀ x, 1 ꢀ y, ꢀ1/2 + z; (x) ꢀx, 1
ꢀ y, 2 ꢀ z; (xi) ꢀx, 1 ꢀ y, 1 ꢀ z.
2
2
and 5. These hydrogen bonds generate C1 (8), R2 (22) and
6
R4 (28) graph-set motifs respectively propagate along the [100],
[011] and [010] directions in 3 to build three-dimensional
supramolecular networks and R22(14) motif running along the
[001] plane in 5 forming honeycomb sheets running along the
[100] direction (Fig. 3 and 4b). The structure 3 is further stabi-
lized through p–p (3.352 A) stacking interactions (the benzyl
ring (A) carbon atom C16 in the molecule at (x, y, z) acts as
a donor to the centroid of another benzyl ring (B)) while 5 is
˚
˚
stabilized through C13–H13/p(arene) (2.837 A) hydrogen bond
and (lone pair)–p(arene) (3.090 A) stacking interactions. In
˚
˚
large sharp spikes in the ngerprint plots with di + de ¼ 2.45 A
compound 4, perpendicular chains (Fig. 4a) running along the
[100] plane are linked via C2–H2A/O1 (O1 at ꢀ1/2 + x, 1/2 ꢀ y,
ꢀ1/2 + z) and C16–H16/O1 (O1 at ꢀ1/2 + x, 1/2 ꢀ y, 1/2 + z)
which comprise 19.1% of the total Hirshfeld surfaces area. The
C/H/H/C interactions comprise 38.3% of the total Hirshfeld
˚
surfaces and represent two small wings in the region of (1.09 A,
2
hydrogen bond (Table 2) offering a C1 (7) parallel chains similar
˚
1.57 A). Furthermore, the H/H interactions are presented in
to compound 1. In the presence C–H/O hydrogen bond, unlike
compound 3, the crystal packings in 4 and 5 are further
generated by Cl1/Cl1 with interatomic distance 3.227 A (Cl1 at
ꢀ1 ꢀ x, ꢀy, 1 ꢀ z) and Br1/Br2 with interatomic distance 3.515
the distribution of scattered points in the ngerprint plots,
˚
which split-up to di ¼ de ¼ 1.10 A and comprise 42.1% of the
˚
total Hirshfeld surfaces. Contrast to 1, the O/H/H/O inter-
˚
molecular interactions are longer in 2 (di + de ¼ 2.52 A), 4 (di + de
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Fig. 5 Hirshfeld surfaces mapped with dnorm for the title compounds (1–6).
˚
˚
¼ 2.65 A) and 5 (di + de ¼ 2.38 A) but shorter in 3 (di + de ¼ 2.31 calculations showed
a
direct relationship with thermal
˚
˚
A) and 6 (di + de ¼ 2.12 A), respectively, with the following strengths of the title compounds (Table S1 and Fig. S1†). The
percentages 16.8%, 14.6%, 14.4%, 14.6% and 24.6% to the total molecular pair interaction energies for the title compounds are
Hirshfeld surfaces, respectively. However, the C/H/H/C shown in Table S3.† Molecular pairs of 1 (1–5) extracted from
interactions are displayed in two sharp spikes in the ngerprint crystal structure along with their respective interaction energies
˚
plots, which spread up to the longer distance of di + de ¼ 2.73 A, are shown in Fig. 8. The maximum stabilization to the crystal
˚
˚
˚
˚
2.78 A, 2.65 A, 2.71 A and 2.73 A for 2, 3, 4, 5 and 6, respectively, structure comes from C–H/O intermolecular interaction
and contribute 21.4%, 21.0%, 26.5%, 15.2% and 20.2% to the involving H23 with O1. The stabilization energy of the pair is
total Hirshfeld surfaces, respectively. The H/H interactions ꢀ7.0 kJ molꢀ1 (motif 1) obtained using crystalexplorer v17.5.
have more signicant contribution to the total Hirshfeld Another molecular pair (motif 2) has interaction energy of
surfaces in 1 (42.1%) and 6 (44.5%) when compared with ꢀ13.4 kJ molꢀ1 also involves C–H/O intermolecular interac-
˚
compounds 2–5, which spread up to di ¼ de ¼ 2.25 A and di ¼ de tion involving H25 with O2. Motif 3 involves H2B and O1 with
¼ 2.2 A, respectively. The most signicant differences amongst stabilization energy being ꢀ26.6 kJ molꢀ1. The next stabilized
˚
1–6 is the presence of p(lone pair)/p(arene) stacking interac- pair (motif 4) show C–H/p intermolecular interaction between
tions in 2, 3 and 5. The p–p stacking interactions are longer in 2 H26 and C15 atoms with stabilization energy of ꢀ37.0 kJ molꢀ1
.
˚
˚
(di + de ¼ 2.85 A) and in 3 (di + de ¼ 2.3 A) but closer in 5 (di + de Last molecular pair 5 involves the interaction of H12 with O1.
˚
¼ 3.6 A), and the proportions of the total Hirshfeld surfaces are This pair also involves the interaction of H2A with O1 having
4.2%, 8.2% and 8.5%, respectively. The relative contribution of interaction energy contributing towards the stability of crystal
different interactions to the Hirshfeld surfaces was calculated packing. The interaction for motif (1–5) in 1 is primarily
for 1–6 as well as a few benzyloxy-benzaldehyde derivatives dispersive in nature (Table S3†). The most stabilized molecular
retrieved from the CSD. It is evident in Fig. 7 that the molecular pairs (1–5) of 2 along with their stabilization energies are shown
interactions in the title compounds and benzyloxybenzaldehyde in Fig. 9. The most stabilized molecular pair (motif 1) in 2 shows
derivatives mentioned earlier are pre-dominantly of H/H, the presence of C–H/p involving H3A with C12, C13 (of the A
C/H and O/H types, which can account for 87% of the ring), O2 and O3 and provides stabilization of ꢀ46.7 kJ molꢀ1
.
Hirshfeld surface area. Table 3 lists the lattice energies obtained The next stabilized pair (motif 2) shows H/H (involving H15
from AA-CLP20 and ab initio DFT calculations. Quantitative interacting with H15 atom) resulting in a stabilization energy of
comparison between the AA-CLP, B3LYP and M06HF methods ꢀ7.3 kJ molꢀ1. The stabilized pair (motif 3) involves C–H/p
was made possible to explore how similar, or different, are the hydrogen bonding (involving H14 with C23) having an interac-
models. However, the comparison is limited to energies for tion energy of ꢀ11.4 kJ molꢀ1. The second most stabilized pair
small numbers of molecular pairs. A simple regression analysis is motif 4 which shows the presence of C–H/O (involving O1
reveals that overall ETot (AA-CLP) ¼ 2.380 ETot (B3LYP) and ETot interacting with H1, H2A and H22) and lone pair/lone pair
(AA-CLP) ¼ 2.232 ETot (M06HF), although differences between (between C1 and O1) forming dimer having an interaction
the two can be as large as +1.1 and +1.2 kJ molꢀ1 for B3LYP and energy of ꢀ23.7 kJ molꢀ1. Molecular pair 5 shows the presence
M06HF (POMLUA) respectively. This means that the lattice of C–H/p (involving H23 with C15) having an interaction
energy calculated by AA-CLP (ꢀ44.8 kJ molꢀ1) coincide with energy of ꢀ8.9 kJ molꢀ1 that contributes towards the stability of
both B3LYP (ꢀ45.7 kJ molꢀ1) and M06HF (ꢀ45.8 kJ molꢀ1
methods only for POMLUA. The DFT total energy (ETot
)
)
crystal packing. The interaction for motif (1–5) in 2 is similar to
1 and it is primarily dispersive in nature. The extracted
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Fig. 6 Fingerprint plots: full, H/H, C/H/H/C and O/H/H/O contacts for 1–6 displaying percentages of contacts contributed to the total
Hirshfeld surface area of the compounds.
molecular pairs (1–5) of 3 are shown in Fig. 10 along with their acceptor with H15) and also the presence of bifurcated acceptor
stabilization energies. The stabilized molecular pair (motif 1) atom involved in C–H/Br halogen bonding (involving Br1
shows the presence of C–H/O hydrogen bonding (involving O1 interacting with both H2B and H26) with interaction energy of
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Fig. 7 Relative contributions of various intermolecular contacts to the Hirshfeld surface area in 1–6 and some related structures retrieved from
the CSD.
Table 3 Crystal lattice energies (kJ molꢀ1) calculated using AA-CLP and ab initio DFT methods for various compounds
a
b
Compound
EEle
EPol
EDisp
EEx-rep
ETot
ETot
ETot
1
2
3
4
5
6
ꢀ28.1
ꢀ20.2
ꢀ16.0
ꢀ23.5
ꢀ20.6
ꢀ23.5
ꢀ33.5
ꢀ36.2
ꢀ26.3
ꢀ24.2
ꢀ27.4
ꢀ35.3
ꢀ23.5
ꢀ22.7
ꢀ29.1
ꢀ19.2
ꢀ18.4
ꢀ4.20
ꢀ21.0
ꢀ34.4
ꢀ25.2
ꢀ19.2
ꢀ25.2
ꢀ16.8
ꢀ18.4
ꢀ14.1
ꢀ20.1
ꢀ22.3
ꢀ26.5
ꢀ20.3
ꢀ19.3
ꢀ20.6
ꢀ33.4
ꢀ24.7
ꢀ21.1
ꢀ27.8
ꢀ29.3
ꢀ18.4
ꢀ9.60
ꢀ18.5
ꢀ37.1
ꢀ19.1
ꢀ126.4
ꢀ136.1
ꢀ148.6
ꢀ137.2
ꢀ156.2
ꢀ101.9
ꢀ118.7
ꢀ128.9
ꢀ123.8
ꢀ111.2
ꢀ128.0
ꢀ157.9
ꢀ133.6
ꢀ102.7
ꢀ123.0
ꢀ131.3
ꢀ122.9
ꢀ35.10
ꢀ113.4
ꢀ132.2
ꢀ117.9
50.6
50.7
59.0
51.1
65.0
51.3
37.4
61.1
41.9
31.5
45.6
61.0
46.7
43.6
43.4
42.7
32.9
11.5
39.9
50.9
36.3
ꢀ126.3
ꢀ130.8
ꢀ122.4
ꢀ127.9
ꢀ125.8
ꢀ94.20
ꢀ137.0
ꢀ130.5
ꢀ131.8
ꢀ126.3
ꢀ133.6
ꢀ165.7
ꢀ135.1
ꢀ102.9
ꢀ136.6
ꢀ137.0
ꢀ126.8
ꢀ44.60
ꢀ113.0
ꢀ153.2
ꢀ125.9
ꢀ48.9
ꢀ39.7
ꢀ32.2
ꢀ36.6
ꢀ25.9
ꢀ45.4
ꢀ67.7
ꢀ28.2
ꢀ54.3
ꢀ48.9
ꢀ56.2
ꢀ68.1
ꢀ52.1
ꢀ56.0
ꢀ49.1
ꢀ53.2
ꢀ59.7
ꢀ45.7
ꢀ35.1
ꢀ57.2
ꢀ52.9
ꢀ56.4
ꢀ48.1
ꢀ40.4
ꢀ44.8
ꢀ35.0
ꢀ56.3
ꢀ75.8
ꢀ25.4
ꢀ61.8
ꢀ56.3
ꢀ48.9
ꢀ17.8
ꢀ57.0
ꢀ63.3
ꢀ67.5
ꢀ62.0
ꢀ22.5
ꢀ45.8
ꢀ37.6
ꢀ50.7
ꢀ59.8
COBNUC
CUNMAZ
DUTRIU
DUTRIU01
DUTRIU02
EROHUP
KERDUH
IPEXEH
LELQUQ
LELRAX
MEQLIE
POMLUA
VOQFIS
XEVROF
XIMPAL
a
DFT (B3LYP) and; b DFT (M06HF).
ꢀ17.9 kJ molꢀ1. The most stabilized pair (motif 2) shows the ꢀ23.0 kJ molꢀ1. Finally, the least stabilized pair shows C–H/Br
presence of p–p (involving C16 with C24 atoms of the A and B interaction (involving H24 with Br1) having an interaction
rings, respectively) to form a dimer having an interaction energy energy of ꢀ4.0 kJ molꢀ1 which provides additional stabilization
of ꢀ23.3 kJ molꢀ1. Molecular pair 3 shows the presence of both to the crystal packing. The major contribution to the stabiliza-
C–H/O/Br hydrogen/halogen bonding (involving H2B with O1 tion in 3 comes from dispersion component. Molecular pairs of
and H24 interacting with Br1) resulting in a stabilization energy 4 (1–7) extracted from crystal structure along with their
of ꢀ17.4 kJ molꢀ1. The second most stabilized pair (motif 4) respective interaction energies are shown in Fig. 11. The inter-
shows the presence of bifurcated acceptor atom involved in action for motif (1–5) in 4 is primarily repulsive in nature. The
C–H/O hydrogen bonding twice (involving O1 interacting with minimum stabilization to the crystal involves molecular stack-
both H23 and H24) and H/H (involving H2 with H25) to ing to generate dimers and a bifurcated acceptor atom involved
generate a molecular pair having an interaction energy of in C–H/Cl halogen bonding (involving Cl1 interacting with
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Fig. 8 Molecular pairs (1–5) along with their interaction energies (values in blue) in 1.
Fig. 9 Molecular pairs (1–5) along with their interaction energies (values in blue) in 2.
H24 and H25) in both motifs 1 & 2. The stabilization energies of crystal packing. Molecular pair 7 involves two H24 interactions
these pairs are ꢀ5.3 and ꢀ9.6 kJ molꢀ1, respectively and the with O1 to give stabilization energy of ꢀ23.1 kJ molꢀ1. The
combined nature of these interactions is mainly dispersive in molecular pairs (1–6) which provide maximum stabilization to
nature. The most stabilized pair (motif 3) shows the presence of the packing in 5 are shown in Fig. 12. For both structures 5 and
lone pair–p interaction (involving C1 with C14 of the A ring) 6 the interaction for motifs (1–6) and motif (1–7) are predomi-
having an interaction energy of ꢀ34.3 kJ molꢀ1 and is dispersive nantly repulsive in nature. The least stabilized molecular pair in
in nature. Motif 4 shows the presence of a bifurcated interaction 5 involves type I Br/Br intermolecular interaction, (involving
(involving O1 with both H15 and H16) to generate a molecular Br1 with Br2) having an interaction energy of ꢀ4.4 kJ molꢀ1 with
pair having an interaction energy of ꢀ14.7 kJ molꢀ1. Another major contribution from repulsion component. The next most
molecular pair (motif 5) in 4 shows the presence of C–H/O stabilized pair involves C–H/O hydrogen bonding (involving
hydrogen bonding (involving H2A with O1) forming a dimer H2B with O2) resulting in
a stabilization energy of
with interaction energy of ꢀ13.1 kJ molꢀ1. Molecular pair 6 ꢀ49.6 kJ molꢀ1. Molecular pair 3 shows the presence of C–H/p
having an interaction energy of ꢀ25.4 kJ molꢀ1 shows lone pair– (involving H13 and C13 of the B ring) having an interaction
p (involved in C1 and C23 of the B ring) and H/H interaction energy of ꢀ10.9 kJ molꢀ1. The next two stabilized pairs shows
(involving H22 with H22) to contribute towards the stability of C–H/Br hydrogen bonding, motif 4 involves H26 interacting
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Fig. 10 Molecular pairs (1–5) along with their interaction energies (values in blue) in 3.
Fig. 11 Molecular pairs (1–7) along with their interaction energies (values in blue) in 4.
with Br2 resulting in interaction energy of ꢀ8.9 kJ molꢀ1 presence of lone pair–p interaction (involving C1 with O1 of the
whereas motif 5 shows the presence of bifurcated interaction carbonyl) and also C–H/O (involving H4 with O1) having
(involving O1 interacting with both C2 and H2A) forming dimer interaction energy of ꢀ22.6 kJ molꢀ1 and is dispersive in nature.
having an interaction energy of ꢀ27.2 kJ molꢀ1. Last stabilized Motif 3 shows the presence of a lone pair–p interaction between
pair involves C–H/Br halogen bonding (involving H23 with Br1 O1 (carbonyl oxygen) and C2 with interaction energy of
and H24 with Br2) interaction forming a dimer having inter- ꢀ13.0 kJ molꢀ1. Motif 4 shows the presence of bifurcated donor
action energy of ꢀ10.8 kJ molꢀ1. Molecular pairs (1–7) providing atom (involving H5C with both O2 and O3) to generate
signicant contribution towards the stabilization along with
a
molecular pair having an interaction energy of
their interaction energies for 6 are shown in Fig. 13. The ꢀ21.0 kJ molꢀ1. Another molecular pair (motif 5) in 6 shows the
molecular pair with maximum energy stabilization (motif 1) presence of C–H/O hydrogen bonding (involving H2A with O2)
shows the presence of two C–H/p hydrogen bonds (H14 forming a dimer with interaction energy of ꢀ13.9 kJ molꢀ1
.
interacting with C4) resulting in interaction energy of Molecular pair 6 having an interaction energy of ꢀ25.4 kJ molꢀ1
ꢀ40.4 kJ molꢀ1. The next stabilized pair (motif 2) shows the shows C–H/O (involved in O1 with H5C) to contribute towards
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Fig. 12 Molecular pairs (1–6) along with their interaction energies (values in blue) in 5.
Fig. 13 Molecular pairs (1–7) along with their interaction energies (values in blue) in 6.
the stability of crystal packing. Molecular pair 7 involves two H1 but in a cooperative fashion to inuence the out of plane
interactions with O1 to give the least stabilization energy of molecular stacking. The differences in crystal packing are rep-
ꢀ7.1 kJ molꢀ1
.
resented by variation of substitution positions in the
compounds. Interestingly, compounds 3 and 4 are isomor-
phous but their crystal packing is vastly different. Considering
self-organization systems of this manner, the study in the eld
of photo-induced dimerization and crystal engineering in
general looks promising. The crystal packing of all the
compounds has been analysed using both Hirshfeld surface
and theoretical methods. The total energy showed a direct
relationship with thermal strengths (“melts”) of the title
compounds. The structures studied in this work assisted us to
appreciate the inuence of intermolecular contacts in con-
structing supramolecular systems in the solid state.
3 Conclusions
In summary, in our effort to explore the role played by these
intermolecular contacts in the self-assembly of crystal struc-
tures we have studied six related benzaldehyde derivatives by
single crystal X-ray diffraction. It is observed that the carbonyl
group generates hydrogen bonded motifs in all compounds
studied here and their analogous structures (DUTRIU,
DUTRIU01, DUTRIU02 and IPEXEH, shown in Fig. S8†). These
crystalline solid materials demonstrate how self-regulating the
various weak interactions such as C–H/O hydrogen bonding,
p–p and lone pair–p stacking, and type I halogen–halogen
interactions which complement each other in crystal packing.
Furthermore, hydrogen bonding and p–p intermolecular
Conflicts of interest
interactions engineered or manoeuvred themselves abruptly There are no conicts to declare.
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F. C. Pigge, V. R. Vangala and D. C. Swenson, Chem.
Commun., 2006, 20, 2123–2135.
Acknowledgements
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The authors thank Professor Perry Kaye (Rhodes University,
South Africa) for his supervisory role in the synthesis of the
benzaldehyde derivatives and are grateful for the corresponding
funding provided by the South African Medical Research
Council (SAMRC) with funds from National Treasury under its
Economic Competitiveness and Support Package. We also
thank Professor Kelvin Lobb (Rhodes University, South Africa)
and Dr Arcadius V. Krivoshein (University of Houston – Clear
Lake, Houston, Texas, USA) for conducting the crystal lattice
energy calculations shown in Table 3. The authors thank the
anonymous reviewers of the RSC Advances, whose insightful
comments aided us to improve the paper. We would like to
acknowledge the National Research Foundation (NRF) and
Rhodes University Research Council for nancial support.
10 F. H. Allen, Acta Crystallogr., Sect. B: Struct. Sci., 2002, 58,
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