The impact of modular substitution on crystal packing: The tale of two ureas

Article abstract of DOI:10.1039/c6ce01324d

A small library of 13 (3a-m) compounds with modular positioning of iodide and urea/thiourea groups was synthesized in excellent yields in a single step synthetic protocol. The existence of the anticipated (thio)urea derivatives was unambiguously establish

Full text of DOI:10.1039/c6ce01324d

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The impact of modular substitution on crystal packing: The tale of
two ureas
Vijay. S. Koshti,a S. H. Thorat,b R. P. Gote,a S. H. Chikkali,*,a,c and R. G. Gonnade*,b
Received 00th January 20xx,
Accepted 00th January 20xx
A small library of 13 (3a‐3m) compounds with modular positioning of Iodide and urea/thiourea groups was synthesized in
excellent yields in a single step synthetic protocol. The existence of the anticipated (thio)urea derivatives was
unambiguously established using a combination of 1‐2D NMR spectroscopy, ESI‐MS and single crystal X‐ray diffraction
studies. These (thio)urea compounds were classified into four classes as a) mono‐substituted, b) di‐substituted, c) di‐
substituted thiourea and d) electronically tailored di‐substituted thiourea. The changes in molecular conformation and
crystal packing due to the change in the relative positioning of the iodo group at phenyl ring attached to one of the N
atoms and different substituents at other N atoms in urea and thio urea derivatives have been discussed. The urea
derivatives in general, display the chain association through one dimensional three centered N‐H…O hydrogen bonding
interactions due to the trans‐trans orientation of its both NH protons with respect to the carbonyl group. Whereas, the
thiourea compounds exhibit a centrosymmetric dimeric assembly via the complementary N‐H…S interactions because of
the trans‐cis arrangement of NH protons leading to either a helical or a sheet pattern. The presence of nitro group at para
position of thiourea derivative leads to trans‐trans arrangement of both NH protons with respect to the thiocarbonyl
groups thus yielding a chain assembly through one dimensional three centered N‐H…S interactions similar to urea
derivatives. Associations of these chain or sheets in urea/thiourea derivatives through halogen bonding interactions
(hal…hal, hal…, hal…S etc.) generate 2D assembly.
DOI: 10.1039/x0xx00000x
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enables acid catalyzed hydrolysis of ortho‐esters, even in a
basic medium,4 or monoterpene cyclization by exclusion of
water,5 or harnesses aza‐Cope reaction.6 In addition to serving
Introduction
Weak chemical interactions are very creatively and effectively
used by Mother Nature in the complex process of chemical
evolution. For example, many enzymes fold in a particular
shape due to weak hydrogen‐bonding interactions between
the strands and perform a selective reaction that is vital to the
survival of that species. Therefore, it is no wonder that inter‐
and intra‐ molecular interactions are being increasingly used to
design variety of solid state structures such as macrocycles,
cryptands, one dimensional wires, two dimensional grids, to
name a few.1 These non‐covalent interactions which constitute
as a structural unit; the non‐covalent interactions have started
delivering a function. The potential of the non‐covalent
interaction in tailoring the reactivity or selectivity of a
transformation has been lately recognized and last decade has
seen a tremendous growth in supramolecular catalysis.7 For
instance, monodentate ligands with hydrogen‐bonding start
behaving like a bidentate ligand in presence of a metal and
render enhanced selectivity as compared to their non‐
hydrogen‐bonding counter parts.8 This concept has been very
innovatively used to generate a large catalyst library from a
small set of monodentate ligands.9 Apart from serving as
structural units, the supramolecular motifs can be tuned to
serve as directing synthons in supramolecular‐catalysis (see fig.
1). The “directing synthons” can be broadly defined as
supramolecular units that engage in non‐covalent interactions
with the incoming substrate and in turn enhance selectivities.
Notable examples of this type include supramolecular
hydroformylation,10 hydrogenation11 and C‐H activation.12
Amongst such supramolecular synthons, symmetrical or
unsymmetrical N,N’‐di‐substitution of urea is known to form
persistent and robust one dimensional three centered N‐H…O
hydrogen‐bonded chains in solution, fiber, gel or solid state
because of the trans‐trans arrangement of NH protons with
a
supramolecular synthons include hydrogen bonding,
halogen‐bonding,

‐stacking, coordinative interactions etc.2
Drawing the motivation from nature, various supramolecular
architectures were artificially prepared and their selectivity in
various chemical transformations has been tested.3 For
instance, Raymond’s a specially designed cage‐compound
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respect to the C=O group.13 Because of its pronounced
directionality and relatively high strength they are utilized as
building blocks for designing various crystalline frameworks.
excluding 3a‐c. Solvents were dried by standard procedures
unless otherwise mentioned, THF from sodium/benzophenone
and DCM from calcium hydride under argon atmosphere.
Phenylisothicyantes derivatives were purchased from Sigma‐
Aldrich. Iodoanilines were procured from Alfa‐Aesar. All other
reagents/chemicals, solvents were purchased from local
suppliers (Spectrochem Pvt. Ltd.; Avra Synthesis Pvt. Ltd.;
Thomas Baker Pvt. Ltd. etc). Solution NMR spectra were
recorded on a Bruker Avance 200, 400 and 500 MHz
instruments at 298K unless mentioned otherwise. Chemical
shifts are referenced to external reference TMS (1H and 13C).
Coupling constants are given as absolute values. Multiplicities
are given as follows s: singlet, d: doublet, t: triplet, m:
multiplet, quat: quaternary carbon. The single crystal data was
largely collected using Bruker SMART APEX II single crystal X‐
ray CCD diffractometer with graphite‐monochromatised (Mo‐
kα = 0.71073 Ao) radiation. Melting point was determined in an
open capillary on Bio Technics India melting point apparatus.
Synthesis
General procedure
3a‐c: The iodophenyl‐urea compounds were prepared by
modified literature procedure.14 In a 1L flask, iodoaniline (50
mmol) was dissolved in 25 mL of aqueous hydrochloric acid
(2M). 200 mL of water was added to dissolve the solid. In
another beaker KNCO (65 mmol) was dissolved in a minimum
volume of water and was dropwise added to the above
solution. The reaction mixture was stirred for 4 hours at room
temperature; after which the white precipitate was filtered
and washed with water (20 ml × 3 times). The compound was
dried under vacuum, washed with toluene (20 ml × 3 times)
Fig. 1 Representative synthons in supramolecular catalysis; a) synthons as
structural building blocks, b) synthons as functional units, c) Geometrical
representations of Trans‐Trans and Trans‐Cis motifs in urea and thiourea
derivatives.
The good complementarity between the donor (two NH
protons) and acceptor (C=O) groups generates the predictable
self‐assembled one‐dimensional extended hydrogen bonded
chain structure. In contrast, the supramolecular synthons in N,
N’‐di‐substituted thioureas are comparatively less predictable
which could be because of the relatively weak acidic nature of
C=S group thus making it weak proton acceptor.13 CSD survey
revealed two different self‐associative synthons for thioureas
depending on the conformation of the NH protons. The trans‐
trans association leads to hydrogen bonded chain similar to
the ureas, whereas the trans‐cis conformation yields dimeric
N‐H…S hydrogen bond. Therefore, investigating the effect of
substitution patterns on the self‐assembly of urea and
thiourea derivatives is highly desirable.
and dried under vacuum to get the iodophenyl‐urea 3a‐c.
3d‐m: The Phenylisocyanates or isothiocyanates (1 equiv) or
the derivatives of these, were dissolved in dichloromethane (5
mL) at 0°C. Subsequently, iodoanilines (1.4 equiv.), were added
drop wise with constant stirring. The progress of the reaction
was monitored by TLC. After completion of reaction, solvent
was evaporated from the reaction mixture and the product
was purified by column chromatography in excellent yield.15
1
3a: H NMR (500 MHz, DMSO‐d6, 298K) δ = 7.78 (ddd, JH‐H
=
12.3 Hz, 8.3 Hz, 1.4 Hz, 2H, Ar, CH), 7.62 (s, 1H, NH), 7.28 (t, JH‐
H = 7.8 Hz, 1H, Ar, CH), 6.76 (t, JH‐H = 7.5 Hz, 1H, Ar, CH), 6.35 (s,
2H, NH2). 13C NMR (125 MHz, DMSO‐d6, 298K) δ = 155.8 (s,
In this context, we report the synthesis of various derivatives
of urea and thiourea. Further, the effect of modular CO), 140.6 (s, Ar, quat‐CH), 138.7 (s, Ar, CH), 128.4 (s, Ar, CH),
124.4 (s, Ar, CH), 122.8 (s, Ar, CH), 90.8 (s, Ar‐I). IR (cm‐1): 3430
substitution on the molecular conformation, H‐bonding
(NH2), 3298 (NH2), 3200 (NH), 1698 (C=O). ESI‐MS (+ve) (For
C7H7IN2O) m/z = 262.96 [M+H]+, 284.94 [M+Na]+. Mp = 140°C.
3b: H NMR (500 MHz, DMSO‐d6, 298K) δ = 8.66 (s, 1H, NH),
7.98 (s, 1H, Ar, CH), 7.24 (q, JH‐H = 6.7 Hz, 2H, Ar, CH), 6.99 (t,
JH‐H = 8.00 Hz, 1H, Ar, CH), 5.94 (s, 2H, NH2). 13C NMR (125
MHz, THF‐d8, 298K) δ = 157.2 (s, CO), 143.3 (s, Ar, quat‐CH),
131.2 (s, Ar, CH), 131.0 (s, Ar, CH), 127.8 (s, Ar, CH), 118.3 (s,
Ar, CH), 94.8 (s, Ar‐I). IR (cm‐1): 3429 (NH2), 3295 (NH2), 3203
(NH), 1698 (C=O). ESI‐MS (+ve) (For C7H7IN2O) m/z = 262.96
[M+H]+, 284.94 [M+Na]+. Mp = 165°C.
pattern and crystal packing is presented. This investigation
reveals that H‐bonding chain pattern is dominant in urea
derivatives, whereas the dimeric association through N‐H…S
hydrogen bond is preferred mode of interaction in thioureas.
1
Experimental
Methods and materials
All manipulations were carried out under an inert atmosphere
using standard Schlenk technique or m‐Braun glove box,
2 | J. Name., 2012, 00, 1‐3
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1
3c: H NMR (500 MHz, DMSO‐d6, 298K) δ = 8.7 (s, 1H, NH), MS (+ve) (Cal. For C13H11N2SI) m/z = 354.97 [M+H]+, 376.95
7.52 (s, 2H, Ar, CH), 7.26 (s, 2H, Ar, CH), 5.93 (s, 2H, NH2). 13C [M+Na]+. Mp = 160°C.
1
NMR (125 MHz, DMSO‐d6, 298K) δ = 155.8 (s, CO), 140.5 (s, Ar, 3i: H NMR (400 MHz, DMSO‐d6, 298K) δ = 9.95 (s, 1H, NH),
quat‐CH), 137.1 (s, Ar, CH), 120.0 (s, Ar, CH), 83.6 (s, Ar‐I). IR 9.86 (s, 1H, NH), 7.97 (s, 1H, Ar, CH), 7.48 (d, JH‐H = 7.57 Hz, 4H,
(cm‐1): 3423 (NH2), 3303 (NH2), 3259 (NH), 1654 (C=O). ESI‐MS Ar, CH), 7.35 (t, JH‐H = 7.58, 2H, Ar, CH), 7.14 (q, JH‐H = 7.34 Hz,
(+ve) (For C7H7IN2O) m/z = 262.96 [M+H]+, 284.94 [M+Na]+. Mp 2H, Ar, CH ). 13C NMR (100 MHz, DMSO‐d6, 298K) δ = 179.5 (s,
= 220°C.
quat, C=S), 141.0 (s, quat, Ar), 139.1 (s, quat, Ar), 132.7 (s, Ar),
1
3d: H NMR (500 MHz, DMSO‐d6, 298K) δ = 9.44 (s, 1H, NH), 131.7 (s, Ar), 130.3 (s, Ar), 128.5 (s, Ar), 124.6 (s, Ar), 123.3 (s,
7.90 (s, 1H, NH), 7.86 (dd, JH‐H = 7.95 Hz, 1.14Hz, 1H, Ar, CH), Ar), 122.9 (s, Ar), 93.8 (s, quat, Ar). IR (cm‐1): 3323 (NH), 1577
7.83 (dd, JH‐H = 7.92 Hz, 1.12Hz, 1H, Ar, CH), 7.50 (s, 1H, Ar, (C=S). ESI‐MS (+ve) (Cal. For C13H11N2SI) m/z = 354.97 [M+H]+,
CH), 7.48 (s, 1H, Ar, CH),7.34 (s, 1H, Ar, CH), 7.30 (td, 8.6Hz, 376.95 [M+Na]+. Mp =110°C.
1
1.3Hz, 2H, Ar, CH), 6.98 (t, JH‐H = 7.28 Hz, 1H, Ar, CH), 6.83 (td, 3j: H NMR (500 MHz, DMSO‐d6, 298K) δ = 8.78 (s, 1H, NH),
7.65Hz, 1.2Hz, 1H, Ar, CH). 13C NMR (125 MHz, DMSO‐d6, 298K) 8.69 (s, 1H, NH), 7.61 (d, 2H, JH‐H = 8.31 Hz, 2H, Ar, CH), 7.45 (d,
δ = 152.3 (s, quat, C=O), 139.8 (s, quat, Ar), 139.6 (s, quat, Ar), JH‐H = 7.99 Hz, 2H, Ar, CH), 7.27‐7.33 (m, 4H, Ar, CH), 6.98 (t, JH‐
138.9 (s, Ar), 128.8 (s, Ar), 128.5 (s, Ar), 125.0 (s, Ar), 123.0 (s,
= 7.20 Hz, 1H, Ar, CH ). 13C NMR (50 MHz, DMSO‐d6, 298K) δ =
H
Ar), 122.0 (s, Ar), 118.2 (s, Ar), 91.3 (s, quat, Ar, C‐I). IR (cm‐1): 179.4 (s, quat, C=S), 139.4 (s, quat, Ar), 139.3 (s, quat, Ar),
3284 (NH), 1644 (C=O). ESI‐MS (+ve) (Cal. For C13H11N2OI) m/z 137.0 (s, Ar), 128.5 (s, Ar), 125.7 (s, Ar), 124.6 (s, Ar), 123.7 (s,
= 338.99 [M+H]+, 360.98 [M+Na]+. Mp = 190°C.
Ar), 88.5 (s, quat, Ar, C‐I). IR (cm‐1): 3199 (NH), 1587 (C=S). ESI‐
1
3e: H NMR (200 MHz, DMSO‐d6 298K) δ = 8.75 (s, 1H, NH), MS (+ve) (Cal. For C13H11N2SI) m/z = 354.97 [M+H]+, 376.95
8.67 (s, 1H, NH), 7.97 (d, 1.8Hz, 1H, CH), 7.42 (s, 1H, Ar, CH), [M+Na]+. Mp = 140°C.
7.39 (s, 1H, Ar, CH), 7.27‐7.22 (m, 4H, Ar, CH), 7.03 (t, JH‐H
8.32 Hz 1H, Ar, CH), 6.94 (t, JH‐H = 7.33 Hz, 1H, Ar, CH). 13C NMR 10.30 (s, 1H, NH), 8.23 (d, 2H, JH‐H = 9.16 Hz, Ar, CH), 7.95 (s,
(100 MHz, DMSO‐d6, 298K) δ = 152.4 (s, quat, C=O), 141.2 (s, 1H, Ar, CH), 7.83 (d, JH‐H = 9.16 Hz, 2H, Ar, CH), 7.52 (d, JH‐H
=
3k: 1H NMR (500 MHz, , DMSO‐d6, 298K): δ = 10.50 (s, 1H, NH),
=
quat, Ar), 139.4 (s, quat, Ar), 130.8 (s, Ar), 130.3 (s, Ar), 128.8 7.60 Hz, 1H, Ar, CH ), 7.50 (d, JH‐H = 7.85 Hz, 1H, Ar, CH ), 7.17
(s, Ar), 126.3 (s, Ar), 122.1 (s, Ar), 118.4 (s, Ar), 117.5 (s, Ar), (t, JH‐H = 7.93 Hz, 1H, Ar, CH ). 13C NMR (125 MHz, DMSO‐d6,
94.8 (s, quat, Ar). IR (cm‐1): 3295 (NH), 1631 (C=O). ESI‐MS 298K): δ = 179.3 (s, quat, C=S), 145.9 (s, quat, Ar), 142.4 (s,
(+ve) (Cal. For C13H11N2OI) m/z = 338.99 [M+H]+, 360.98 quat, Ar), 140.4 (s, quat, Ar), 133.4 (s, Ar, CH), 131.8 (s, Ar, CH),
[M+Na]+. Mp = 195°C.
130.5 (s, Ar, CH), 124.4 (s, Ar, CH), 123.0 (s, Ar, CH), 121.7 (s,
1
3f: H NMR (400 MHz, DMSO‐d6, 298K) δ = 8.79 (s, 1H, NH), Ar, CH), 93.9 (s, quat, Ar, C‐I). IR (cm‐1): 3216 (NH), 3154 (NH),
8.70 (s, 1H, NH), 7.60 (d, JH‐H = 8.66 Hz, 2H, CH), 7.46 (d, JH‐H
7.66 Hz, 2H, CH), 7.33 (d, JH‐H = 8.66 Hz, 2H, CH), 7.28 (t, JH‐H
=
=
1576 (C=S). ESI‐MS (+ve) (Cal. For C13H10N3O2SI) m/z =
399.96[M+H]+. Mp = 150°C.
1
7.66 Hz, 2H, CH), 6.98 (t, JH‐H = 7.34 Hz, 1H, CH). 13C NMR (100 3l: H NMR (500 MHz, DMSO‐d6, 298K) δ = 9.76 (s, 1H, NH),
MHz, DMSO‐d6, 298K) δ = 152.3 (s, quat, C=O), 139.6 (s, quat, 9.68 (s, 1H, NH), 7.95 (s, 1H, Ar, CH), 7.46 (d, JH‐H = 7.6 Hz, 2H
Ar), 139.5 (s, quat, Ar), 137.3 (s, Ar, CH), 128.3 (s, Ar, CH), Ar, CH), 7.32 (d, JH‐H = 9.0 Hz, 2H, Ar, CH), 7.11 (t, JH‐H = 7.6 Hz,
121.8 (s, Ar, CH), 120.4 (s, Ar, CH), 118.3 (s, Ar, CH), 84.6 (s, 1H, Ar, CH), 6.92 (d, JH‐H = 8.5 Hz, 2H, CH), 3.75 (s, 3H, OCH3).
quat, Ar). IR (cm‐1): 3300 (NH), 1632 (C=O). ESI‐MS (+ve) (Cal. 13C NMR (125 MHz, DMSO‐d6, 298K): δ = 179.7 (s, quat, C=S),
For C13H11N2OI) m/z = 338.99 [M+H]+, 360.98 [M+Na]+. Mp
=
156.7 (s, quat, Ar, C‐OMe), 141.1 (s, quat, Ar), 132.6 (s, Ar, CH),
150°C.
131.6 (s, Ar, CH), 131.7 (s, Ar, CH), 130.2(s, Ar, CH), 126.1 (s, Ar,
1
3g: H NMR (500 MHz, DMSO‐d6, 298K): δ = 8.78 (s, 1H, NH), CH), 122.9 (s, Ar, CH), 113.7 (s, quat, Ar), 93.8 (s, quat, Ar, C‐I),
8.75 (s, 1H, NH), 8.01 (s, 1H, Ar, CH), 7.46 (q, JH‐H = 7.26 Hz, 2H, 55.2 (s, OCH3). IR (cm‐1): 3199 (NH), 1587 (C=S). ESI‐MS (+ve)
Ar, CH), 7.32 (q, JH‐H = 8.98 Hz, 2H, Ar, CH ), 7.12 (t, JH‐H = 7.10 (Cal. For C14H13N2OSI) m/z = 384.98 [M+H]+, 406.96 [M+Na]+.
Hz, 2H, Ar, CH ), 7.06 (t, JH‐H = 7.05 Hz, 1H, Ar, CH ). 13C NMR Mp = 105°C.
1
(125 MHz, DMSO‐d6, 298K): δ = 158.4 (s, quat, C=S), 152.4 (s, 3m: H NMR (400 MHz, DMSO‐d6, 298K) δ = 9.95 (s, 1H, NH),
quat, Ar), 141.2 (s, quat, Ar), 135.7 (s, quat, Ar), 130.7 (s, Ar, 9.04 (s, 1H, NH), 7.95 (s, 1H, Ar, CH), 7.48 (d, 2H, JH‐H = 8.07 Hz,
CH), 130.3 (s, Ar, CH), 126.3 (s, Ar, CH), 120.2 (d, Ar, CH), 117.5 Ar, CH), 7.25 (t, JH‐H = 8.07 Hz, 1H, Ar, CH), 7.16 (s, 1H, Ar, CH),
(s, Ar, CH), 115.2 (s, Ar, CH), 94.7 (s, quat, Ar, C‐I). IR (cm‐1): 7.13 (t, JH‐H = 8.32 Hz, 1H, Ar, CH ), 7.02 (d, JH‐H = 8.00 Hz, 1H,
3300 (NH), 1632 (C=O). ESI‐MS (+ve) (Cal. For C13H11N2OFI) m/z Ar, CH), 6.73 (d, JH‐H = 7.68 Hz, 1H, Ar, CH), 3.75 (s, 3H, OCH3).
= 356.98 [M+H]+, 378.97 [M+Na]+. Mp = 210°C.
13C NMR (100 MHz, DMSO‐d6, 298K) δ = 179.3 (s, quat, C=S),
159.3 (s, quat, Ar, C‐OMe), 140.9 (s, quat, Ar), 140.2 (s, quat,
1
3h: H NMR (400MHz, DMSO‐d6, 298K) δ = 9.93 (s, 1H, NH), Ar), 132.8 (s, Ar), 131.7 (s, Ar), 130.3 (s, Ar), 129.3 (s, Ar), 122.9
9.33 (s, 1H, NH), 7.88 (d, JH‐H = 7.96 Hz, 1H, Ar, CH), 7.56 (d, JH‐H (s, Ar), 115.6 (s, Ar), 110.0 (s, Ar), 109.3 (s, Ar), 93.8 (s, quat,
= 7.71 Hz, 2H, Ar, CH), 7.33‐7.44 (m, 4H, Ar, CH), 7.15 (t, JH‐H
=
Ar, C‐I), 55.1 (s, Ar, OCH3). IR (cm‐1): 3190 (NH), 1580 (C=S). ESI‐
7.20 Hz, 1H, Ar, CH), 7.02 (t, JH‐H = 6.57 Hz, 1H, Ar, CH). 13C MS (+ve) (Cal. For C14H13N2OSI) m/z = 384.98 [M+H]+, 406.96
NMR (100 MHz, DMSO‐d6, 298K) δ = 180.2 (s, quat, C=S), 141.1 [M+Na]+. Mp = 115°C.
(s, quat, Ar), 139.7 (s, quat, Ar), 138.9 (s, Ar), 128.9 (s, Ar),
Crystallization
:
128.5 (s, Ar), 128.5 (s, Ar), 128.2 (s, Ar), 124.6 (s, Ar), 123.8 (s,
Ar), 99.6 (s, quat, Ar, C‐I). IR (cm‐1): 3289 (NH), 1588 (C=S). ESI‐
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Crystallization of compounds 3a‐3c was attempted from the solved by direct methods and refined by full matrix least
mixture of ethanol‐ethyl acetate (1:1, v:v) solvents while that squares, based on F2, using SHELX‐97.16 Molecular diagrams
of 3i from THF‐ethyl acetate (1:1, v:v) whereas other were generated using Mercury programs.17 Geometrical
compounds 3d
acetate solvent mixture (1:1, v:v) at ambient temperature.
‐3h and 3j‐
3m crystallized from DMF‐ethyl calculations were performed using SHELX‐9716 and PLATON.18
A
Table 1 Crystallographic data and structure refinement parameters for 3a‐m.
clear solution was obtained by vigorous shaking and/or
warming of the compound in the solvent and the solution was
allowed to evaporate at room temperature over 1‐2 days to
yield good quality crystals. Crystallization from other solvents
like methanol, ethanol, ethyl acetate, THF, acetonitrile, DMF
and DMSO also was also attempted, however, we failed to
obtain X‐ray quality crystals from these solvents.
Crystallization from other solvents like chloroform,
dichloromethane, toluene, diethyl ether, n‐hexane could not
be carried out because of the solubility issue.
3a
3b
3c
3d
C13H11IN2O
Mol.
Formula
Mr
Temp. (K)
Crystal
System
Space
group
a/Å
C7H7IN2O
C7H7IN2O
C7H7IN2O
262.05
296(2)
Monoclinic
262.05
100(2)
Orthorho
mbic
262.05
150(2)
Monoclinic
338.14
150(2)
Monoclinic
P21/c
Pccn
P21
P21/c
11.8183(6)
7.9251(4)
21.4515(4)
8.44460(1
0)
8.99770(1
0)
90
90
90
4.6211(7)
5.2775(8)
21.0485(13)
4.6303(3)
b/Å
Differential Scanning Calorimetry (DSC) Studies: The thermal
behaviour of all the urea and thioureas derivatives was
investigated by measuring the enthalpy change on a Mettler
Toledo differential scanning calorimeter (DSC 822e). Crystals
obtained from crystallization were first air‐dried before they
were used for DSC analysis. Crystals (~ 3‐5 mg) were placed in
c/Å
8.9570(5)
16.932(3)
12.8294(7)
α/°
β/°
90
90.047(3)
90
838.92(8)
4, 2.075
90
90
96.344(2)
90
102.835(4)
90
1219.12(13)
4, 1.842
γ/°
a sealed aluminium pan (40 L) with crimped pan closure and
V/Å3
1629.93(4)
8, 2.136
410.40(11)
2, 2.121
heated at a rate of 5 °C min‐1 and dry nitrogen gas was used for
purging. Crystals were analysed from room temperature (30°C)
to 250 °C using an empty aluminium pan as reference. DSC
profiles of all the compounds revealed single endotherm
attributed to their melting. No other endothermic/exothermic
peak was observed before the melting endotherm thus ruled
out any phase transition before melting (supporting
information, Figure S70).
Z,Dcalc/g cm‐
3
µ/mm‐1
F (000)
θ max/°
Absor.
Correction
Refln.
Collected
Unique
Refln
3.760
496
34.78
multi‐scan
3.871
992
43.946
multi‐scan
3.843
248
31.586
multi-scan
2.611
656
30.753
multi‐scan
13070
3612
2976
57286
5815
4231
6434
2567
2544
11390
3066
2743
X‐ray Crystallography
Good quality single crystals of all the derivatives were selected
using Leica polarizing microscope MZ75 for the single crystal X‐
ray diffraction studies. The diffraction data measurements
were carried out on a Bruker SMART APEX CCD diffractometer
with graphite‐monochromatized (Mo K = 0.71073Å) radiation
(except for compound 3e). The X‐ray generator was operated
at 50 kV and 30 mA. A preliminary set of cell constants and an
orientation matrix were calculated from total 36 frames. The
optimized strategy used for data collection consisted different
Observed
Refln.
Rint
0.0471
112
0.0447
101
0.0194
100
0.0307
198
No. of
parameter
R1_obs, R1
_all
wR2_obs,
wR2_all
GoF
0.0369,
0.0461
0.0872,
0.0922
1.052
0.0465,
0.0710
0.1360,
0.1520
1.024
0.0148,
0.0150
0.0358,
0.0359
1.103
0.0411,
0.0492
0.0692,
0.0713
1.257
sets of
 and  scans with 0.5° steps in /. Data were
collected keeping the sample‐to‐detector distance fixed at
5.00 cm. The diffraction data measurements on compound 3e
was carried out on a Bruker D8 Venture Kappa diffractometer
∆
1.391,
1.579,
‐2.587
0.534 ,
‐0.761
1.110,
‐1.830
max,∆min/eÅ ‐0.986
‐3
CCDC No.
1046367
1046368
1046369
1483979
with a micro‐focus Cu Kα radiation (= 1.5418 Å) equipped
with a PHOTON‐100 CMOS detector at 150(2) K. X‐ray
generator was operated at 50 kV and 1 mA. A preliminary set
of cell constants and an orientation matrix were calculated
from total 60 frames. The optimized strategy used for data
All the H atoms in compound 3d were located in difference
map and refined isotropically whereas only hydrogen atoms
bound to N‐atoms in compounds 3a were located in the
difference Fourier and refined isotropically. The remaining H‐
atoms for all the compounds were placed in geometrically
idealized positions (C‐H = 0.95 and N‐H = 0.88 Å for the phenyl
and N‐H atoms for compounds 3a, 3b, 3c, 3e, 3f, 3g, 3h, 3i, 3j,
3k, 3l and 3m; C‐H = 0.98 for the methyl H‐atoms in
compounds 3l and 3m) and constrained to ride on their parent
collection consisted different sets of
 and  scans with 0.5°
steps in . Data were collected with a time frame of 30 sec
/
keeping the sample‐to‐detector distance fixed at 5.00 cm. In
both instruments the X‐ray data acquisition was monitored by
APEX2 program suit. All the data were corrected for Lorentz‐
polarization and absorption effects using SAINT and SADABS
programs integrated in APEX2 package. The structures were
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ARTICLE
atoms {[Uiso(H) = 1.2 Ueq(C) and Ueq(N) for phenyl and N‐H
atoms and [Uiso(H) = 1.5 Ueq(C) ] form methyl H‐atoms}.
)
90
(15)
90
0)
90
90
90
90
α/°
β/°
94.006(2 116.180
)
90
96.736(2)
93.6720(10
)
90
Table 1 continued
(4)
90
90
90
γ/°
V/Å3
3e
3f
3g
3h
1372.7(3 1303.2(
)
4,1.714
1424.5(3 2941.9(8)
)
4, 1.861
1416.83(18
)
4, 1.801
Mol.
C13H11IN2O
C13H11IN2O
C13H10FIN2O
C13H11IN2S
2)
Formula
Mr
4, 1.805
8,1.735
Z,Dcalc/g
cm‐3
338.14
150(2)
Monoclinic
338.14
200(2)
Monoclinic
356.13
200(2)
Monoclinic
354.20
150(2)
Monoclinic
Temp. (K)
Crystal
System
Space group
a/Å
b/Å
c/Å
α/°
µ/mm‐1
F (000)
θ max/°
Absor.
Correcti
on
2.464
688
2.596
688
2.399
776
2.312
2.401
1504
752
31.568
Multi‐
scan
40.969
multi‐
scan
31.147
multi‐
scan
31.578
Multi‐scan
31.753
multi‐scan
P21/c
P21/c
P21/c
P21/n
12.683(8)
5.065(3)
20.530(12)
90
27.253(5)
4.6408(9)
9.8532(18)
90
26.1800(17)
4.6273(3)
9.9779(7)
90
27.607(6)
4.6224(11)
9.750(2)
90
19962
4367
3650
33486
5966
5352
18112
4003
3411
43395
9334
8270
22086
4463
4335
Refln.
Coll.
β/°
91.991(6)
90
1245.5(4)
91.646(3)
90
93.235(3)
90
1242.3(5)
4,1.904
2.579
688
31.636
Multi-scan
98.948(8)
90
1302.8(14)
4, 1.806
2.597
688
31.684
multi‐scan
γ/°
Unique
Refln
V/Å3
1208.25(14)
4, 1.859
2.635
656
28.728
Z,Dcalc/g cm‐3 4, 1.803
µ/mm‐1
F (000)
θ max/°
Absor.
Correction
Refln.
20.081
656
68.388
multi-scan
Obs.
Refln.
Rint
0.0465
154
0.0357
154
0.0328
181
0.0513
345
0.0203
181
No.
of
multi-scan
para.
11283
2158
1859
8397
2899
2485
18098
3985
3323
18315
4189
3554
0.0484,
0.0568
0.0549,
0.0639
0.0424,
0.0540
0.0567,
0.0643
0.0257,
0.0267
R1_obs,
R1 _all
wR2_obs
, wR2_all
GoF
Collected
Unique
Refln
Observed
Refln.
0.1309,
0.1354
0.1094,
0.1126
0.0835,
0.0870
0.1265,
0.1300
0.0579,
0.0583
1.054
2.441,
‐1.578
1.240
1.088
1.181
3.494,
‐1.133
1.228
0.808,
‐0.830
2.651 ,
‐1.510
1.431 ,
‐0.817
∆
Rint
No. of
0.0555
154
0.0320
154
0.0411
163
0.0741
154
max,∆min
/eÅ‐3
parameter
R1_obs, R1
_all
wR2_obs,
wR2_all
GoF
1483980 148398
6
1483985
1483982
1483984
CCDC
No.
0.0570,
0.0717
0.1608,
0.1728
1.150
0.0310,
0.0448
0.1004,
0.1446
1.057
0.0316,
0.0409
0.0792,
0.0834
1.040
0.0717,
0.0907
0.1404,
0.1474
1.217
∆
0.659,
1.302,
‐1.206
1.378 ,
‐0.593
2.857,
‐2.746
max,∆min/eÅ‐ ‐0.744
3
CCDC No.
1484013
1483987
1483981
1483978
Table 1 continued
3i
3j
3k
3l
3m
C13H11IN2 C13H11IN
C13H10IN3 C14H13IN2OS C14H13IN2O
Mol.
S
2S
O2S
S
Formula
Mr
354.20
200(2)
354.20
150(2)
399.20
150(2)
384.22
150(2)
384.22
150 (2)
Temp.
(K)
Monocli
nic
Monocli
nic
Orthorh
ombic
Monoclinic
Monoclinic
P21/c
Crystal
System
Space
group
a/Å
P21/n
P21/n
Pna21
P21/c
Chart 1 The three possible isomers of mono‐substituted Iodo‐aryl urea (Cat‐I),
di‐substituted Iodo‐aryl urea (Cat‐II), di‐substituted Iodo‐aryl thiourea (Cat‐III)
and electronically tailored di‐substituted Iodo‐aryl thiourea (Cat‐IV).
12.6626( 15.3895
17) (12)
7.0591(1 5.4985(
0) 5)
15.395(2 17.1612
14.2167( 12.481(2)
19)
14.5308( 9.9446(16)
18)
8.1518(6)
18.2688(13
)
9.5334(7)
b/Å
c/Å
6.8955(1 23.867(4)
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ARTICLE
Journal Name
Results and discussion
solid. The proton resonance at 8.66 and 5.94 ppm (for NH and
The three centered N‐H…O hydrogen bonding synthon in urea NH2 groups respectively) and appearance of carbonyl
is one of the most elegant and robust synthons in resonance at 157.2 ppm suggested formation of desired 3‐
supramolecular chemistry. It is mostly utilized for the iodophenylurea 3b. Infrared spectroscopy and electrospray
designing of various crystalline frameworks because of this ionization mass spectroscopy further confirmed the existence
highly directional and predictable geometry. Further the of 3b. Compound 3b was crystalized from a mixture of ethanol
crystal packing of urea can be readily tuned by substituting the and ethyl acetate (1:1) solution by slow evaporation. The
two protons on nitrogen atoms. As indicated in Chart 1, the crystals were analyzed using single crystal X‐ray diffraction.
resulting 13 compounds have been classified according to Having synthesized the ortho‐ and meta‐substituted urea
substitution pattern; mono‐substituted urea (category‐I), di‐ derivatives, we investigated the influence of para‐substitution
substituted urea (category‐II), di‐substituted thiourea on the weak interactions. Reaction of 4‐iodoaniline with
(category‐III) and electronically tailored di‐substituted thiourea pottasiumisocyanate in acidic media followed by aqueous
(category‐IV). As depicted in scheme 1, two synthetic workup produced the desired 1‐(4‐iodophenyl)urea (3c) in 72%
strategies were adopted to prepare compounds 3a‐m. Mono‐ isolated yield. Preliminary spectroscopic and analytical
substituted urea compounds were prepared by treating evidences suggested formation of 3c
iodoanilines with potassium isocyanate in molar
.
a
2
hydrochloric acid solution. In the second strategy; the di‐ Category II: di‐substituted urea (3
d‐g)
substituted urea and thiourea derivatives were prepared at
Substitution of terminal N‐H proton with a phenyl group might
considerably change the course of secondary interactions. To
investigate this hypothesis, a small library of 4 molecules was
prepared and the crystallographic changes are noted in the
following section. Treatment of 2‐iodoaniline with phenyl‐
isocyanate produced 3d as white solid. Purification by column
chromatography using ethyl acetate and petroleum ether
(10:90) as eluent produced 3d in excellent yield (81%). As
compared to 3a, the urea protons were down field shifted and
appeared at 9.44 and 7.90 ppm. Observation of 13C carbonyl
carbon at 152.3 ppm in combination with proton resonances
supported the formation of 3d. The existence of 3d was
confirmed by ESI‐MS (+ve mode), which revealed a molecular
ion peak at m/z = 338.99 [M+H]+. Compound 3d was
crystalized from 1:1 mixture of DMF and ethyl acetate at room
temperature producing shiny crystals.
0°C in dichloromethane. Detailed synthesis and crystal
structure analyses of all the compounds has been done. None
of the compounds exhibit polymorphism on crystallization
from different solvents as well as polymorphic transition
during DSC measurements. All the inherent structural features
present in these compounds are described below.
Reaction of 3‐iodoaniline with phenyl‐isocyanate in DCM
produced 1‐(3‐iodophenyl)‐3‐phenylurea 3e as a solid melting
at 195°C. Close‐by appearance of the NH protons at 8.75 and
8.67 ppm (as both the N‐atoms have very similar substituents),
attested the formation of desired compound 3e, which was
further confirmed by 13C NMR. Additionally, the infrared
spectroscopy and mass spectroscopy validated the formation
of compound 3e. Suitable crystals were obtained from a
saturated solution (1:1 mixture of DMF and ethyl acetate) of
Scheme 1 General scheme for the synthesis of iodo‐phenylurea/thiourea
compounds.
Category I: Mono‐substituted urea (3a‐c)
The 2‐iodophenylurea 3a was prepared by mixing hydrochloric
acid solution of 2‐iodoaniline with aqueous potassium‐
isocyanate at room temperature. A white precipitate was
observed after 4 hours, which was then washed with water
and toluene respectively to obtain pure 3a. The proton
resonances at 7.62 and 6.35 ppm and a carbon signal at 155.8
ppm indicated formation of the urea motif. A CO stretching
band at 1698 cm‐1 further confirmed the existence of a
carbonyl group. A positive mode electrospray ionization mass
spectroscopy (ESI‐MS) revealed a molecular ion peak at m/z =
262.96 [M+H]+, further corroborating the NMR findings.
Compound 3a was crystalized from a 1:1 mixture of ethanol
and ethyl acetate in open flask. The structure of 3a was
compound 3e
.
Along the same line, reaction of 4‐iodoaniline with
isocyanatobenzene led to the formation of terminal N‐H
proton substituted product 3f. The resultant reaction mixture
was purified by column chromatography (ethyl acetate and
petroleum ether 30:70) to produce 3f in 90% isolated yields.
The relative down field shift and appearance of close‐by N‐H
proton resonances (8.79, 8.70 ppm) indicated formation of
compound 3f. The NMR findings were further supplemented
by IR and mass analysis. The unambiguous proof for the
existence of 3f was obtained from a single crystal X‐ray
diffraction data.
unambiguously ascertained form
a single crystal X‐ray
diffraction. In our attempts to investigate the impact of
positional change on the secondary interaction, we
synthesized 3‐iodophenylurea by treating 3‐iodoaniline with
potassium‐isocyanate in acidic media to produce 3b as white
In our endeavor to examine the impact of electron
withdrawing groups on the secondary interactions, we
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ARTICLE
prepared 1‐(4‐fluorophenyl)‐3‐(3‐iodophenyl)urea (3g). The isothiocyanato‐4‐nitrobenzene. Indeed, the effect of installing
desired compound 3g was isolated in 81% yield after column an electron withdrawing group at para‐postion was very
(ethyl‐acetate: petroleum ether; 60:40). Observation of the significant. As compared to parent compound 3i, the urea
two NH protons (8.78 and 8.75 ppm) and the urea carbonyl protons in 3k appeared further down field at 10.50 and 10.30
carbon (158.4 ppm) confirmed the formation of compound 3g
.
ppm (almost 1.00 ppm shift), whereas the thio‐bound carbon
Crystals of suitable quality were obtained from a solution of 3g remained undisturbed at 179.3 ppm. The NMR findings were
in 1:1 DMF and ethyl acetate mixture.
further corroborated by IR and ESI‐MS and the existence of 3k
was confirmed.
Category III: di‐substituted thiourea (3h‐j)
We anticipated that installing an electron donating substitute
at para‐position to the thiourea nitrogen might display the
opposite behaviour to that of 3k. Reaction of 3‐iodoaniline
with 1‐isothiocyanato‐4‐methoxybenzene led to the
production of yellow powder in 94% isolated yield after
column chromatographic separation. The 1‐(3‐iodophenyl)‐3‐
(4‐methoxyphenyl)thiourea (3l) melted at 105°C, which is
significantly lower than the nitro‐analogue 3k (150°C).
Furthermore, the substitution effect was apparent in proton
NMR; the two NH protons were up‐field shifted to 9.76 and
9.68 ppm. However, as anticipated, the thio‐bound carbon
(C=S) remained unaffected at 179.7 ppm. Slow evaporation of
the solution of 3l (in 1:1 mixture of DMF, ethyl acetate)
produced crystals of suitable size and the existence of 3l was
established from X‐ray diffraction analysis. A detailed account
of these interactions in a solid state is presented in the next
section. Even the relative position of a substituent on the N’‐
substituted phenyl ring seems to challenge the secondary
interactions. For example, meta‐substituted, 1‐(3‐iodophenyl)‐
3‐(3‐methoxyphenyl)thiourea (3m) behaves very differently.
Compared to the para‐methoxy 3l, the thiourea protons in 3m
are relatively down‐field shifted to 9.95, 9.04 ppm, whereas
the C=S carbon remains unaltered at 179.3 ppm.
The sulfur‐analogue of 3d was obtained by reacting 2‐
iodoaniline with phenyl‐isothiocyanate. Work‐up followed by
column purification using ethyl acetate and petroleum ether
(10:90) produced 3h in 62% isolated yield. Relatively down
field shifted NH proton resonances (9.93 and 9.33 ppm) and a
carbon resonance at 180.2 ppm supported formation of 3h
.
The NMR findings were further supported by ESI‐MS (+ve
mode) that disclosed a molecular ion peak at m/z = 354.97
(M+H)+ and 376.96 (M+Na)+. The molecular crystals of 3h were
obtained from 1:1 mixture of DMF and ethyl acetate.
The sulfur counterpart of 3e was obtained by treating 3‐
iodoaniline with isothiocyanatobenzene. Chromatographic
purification of the crude produced the desired compound 3i in
94% isolated yield as a white solid. 1‐(3‐iodophenyl)‐3‐
phenylthiourea (3i) was found to melt at 110°C, which is
significantly lower than the corresponding oxygen analogue
3e. Both the NH protons were down field shifted and appeared
at 9.95 and 9.86 ppm and the sulfur substituted carbon
appeared at 179.5 ppm confirming the formation of 3i. The
infrared spectrum revealed a single NH stretching band at
3323 cm‐1 and the CS band at 1577 cm‐1 attesting the
formation of 3i. The mass‐spectroscopic evidences also
indicated formation of 3i. Crystals of suitable quality were
grown from a 1:1 solution of THF and ethyl acetate at 25°C and
were subjected to X‐ray diffraction analysis.
Crystal Structure Analysis
Category I: mono‐substituted urea (3a‐c)
Similarly, the sulfur analogue of 3f was prepared by treating 4‐
iodoaniline with isothiocyanatobenzene in DCM at 0°C to yield
3j. The crude 1‐(4‐iodophenyl)‐3‐phenylthiourea was purified
by passing it through column (ethyl acetate and petroleum
ether 30:70) to obtain 3j as white solid in 90% yield. As
anticipated, the N‐H protons appeared down field (8.78 and
8.69 ppm) compared to the parent urea 3c and confirmed the
formation of 3j. Further, the C=S carbon appeared at 179.4
ppm and the electrospray ionization mass spectrum revealed
molecular ion peak at m/z = 354.97 [M+H]+, 376.95 [M+Na]+.
Above spectroscopic and analytical data attested the
formation of desired compound 3j. The ultimate proof for the
existence of the 1‐(4‐iodophenyl)‐3‐phenylthiourea came from
the single crystal X‐ray diffraction data.
The Crystals of 3a, 3c and 3b belongs to monoclinic space
group P21/c, orthorhombic space group Pccn and monoclinic
chiral space group P21 respectively. Crystals structures of all
these compounds contain one molecule in the asymmetric unit
(Z’=1). Iodo‐phenyl ring in these compounds showed
significant deviation from the planarity of urea moiety. In 3a it
is almost perpendicular to the basal plane of urea (difference,
74.19

) while in both 3b and 3c compounds it Table 2
from the
Geometrical parameters deviate by almost 50

planarity of urea moiety (Figure 2a). The NH protons in all the
three derivatives took trans‐orientation with respect to the
carbonyl group (In the one dimensional three centered N‐H…O
hydrogen bonding chain formation these trans protons act as
donor and the C=O proton as the acceptor with graph set
૚
notations C(4)[R (6)], wherein C(4) denotes a chain motif with 4
૛
૚
Category IV: Electronically tailored di‐substituted thiourea
(3k‐m)
atoms in the repeat unit, and [R (6)] denotes a hydrogen‐bonded
૛
ring motif consisting of 6 atoms, with 2 donors groups and 1
Secondary interactions are known to be influenced by electron acceptor group.
donating and electron withdrawing groups.
To investigate the effect of electron withdrawing groups on
the secondary interaction, we prepared 1‐(3‐iodophenyl)‐3‐(4‐
nitrophenyl)thiourea (3k) by treating 3‐iodoaniline with 1‐
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ARTICLE
Journal Name
H1∙∙∙O1
Table 2 Geometrical parameters of intermolecular interactions
N2‐
H2∙∙∙O1
C5‐I1...I1
0.88
2.11
2.917(4)
151
x,1+y,z
21
22
En
try
Interacti
ons
D‐H
(Å)
H∙∙∙A
(Å)
D∙∙∙A
(Å)
D‐
H∙∙∙A/

Symmetry
codes
2.101(3 3.880
)
164.04( ‐x,‐
10)
8(6)
2.08
2.09
1/2+y,2.5‐z
(°)
3g
3a
N1‐
H1∙∙∙O1
N2‐
H2∙∙∙O1
C4‐I1...I1
0.88
0.88
2.881(2)
2.893(2)
151
152
x,1+y,z
x,1+y,z
23
24
25
1
2
3
4
N1‐
H1∙∙∙O1
N2‐
H2A∙∙∙O1
N2‐
H2B∙∙∙O1
C3‐I1...I1
0.91(4) 2.10(5
2.914(2)
3.050(3)
2.940(3)
150(4)
141(3)
168(4)
x,1/2‐
y,1/2+z
x,1/2‐
y,1/2+z
‐x,‐y,‐z
)
0.86(4) 2.34(4
)
2.0997( 3.916
18) 8(11)
158.39( 1‐
5) x,1/2+y,1/2‐
0.77(3) 2.19(3
)
2.092(2
)
z
3.855
7(4)
157.93( 1‐x,‐y,‐z
6)
C11‐
F1...F1
1.359(3 2.880(
)
153.80( ‐x,‐y,1‐z
13)
26
2)
3b
3h
5
6
7
8
N1‐
H1∙∙∙O1
N2‐
H2A∙∙∙O1
N2‐
H2B∙∙∙O1
C4‐I1∙∙∙
Cg1
0.88
0.88
0.88
2.10
2.41
2.04
2.895(2)
3.136(3)
2.907(3)
5.402(2)
150
140
167
x,1/2‐y,‐
1/2+z
x,1/2‐y,‐
1/2+z
N1‐
H1∙∙∙I1
N2‐
H2∙∙∙S1
C7‐
H7...S1
C3‐I1...I1
0.88
0.88
0.95
2.95
2.47
2.88
3.618(5)
3.319(5)
3.710
135
162
147
x,‐1+y,z
27
28
29
30
‐x, 1‐y, 1‐z
x,‐1+y,z
1‐x,1‐y,1‐z
2.009(3
)
3.548
3(9)
151.8.6 1/2‐
(7)
2.073(3 3.839(
)
164.70( 1.5‐x, ‐
17)
x,y,1/2+y
2)
1/2+y, 1.5‐z
Cg1= C2
– C7
3i
N1‐
H1∙∙∙I1
N2‐
H2∙∙∙S1
C7‐
H7...S1
C4‐
I1...Cg2
Cg2 = C8
‐C13
0.88
0.88
0.95
2.99
2.49
2.90
3.795(3)
3.292(4)
3.631
153
152
135
3/2‐x, ‐
1/2+y, 1/2‐z
2‐x, 2‐y,‐z
31
32
33
34
3c
9
N1‐
H1∙∙∙O1
N2‐
H2A∙∙∙O1
N2‐
H2B∙∙∙O1
C5‐I1...I1
0.88
0.88
0.88
2.09
2.11
2.10
2.900(2)
2.970(3)
2.896(3)
152
167
159
1+x,y,z
10
11
12
1‐x,1/2+y,1‐
x, ‐1+y,z
z
1+x,y,z
2.093(4 3.684( 5.712(4)
)
162.08( 3/2‐
11)
2)
x,1/2+y,1/2‐
z
2.101(3
)
3.879
3(8)
170.61(
7)
‐x,‐1/2+y,‐z
3d
3j
13
14
15
16
N1‐
H1∙∙∙O1
N2‐
H2∙∙∙O1
C3‐
I1...Cg1
C7‐H7...
Cg2
0.79(5)
0.81(4)
2.19(5 2.925(4)
)
2.09(4 2.866(4)
)
156(4)
159(4)
x,‐1+y,z
x,‐1+y,z
N2‐
H2∙∙∙S1
C7‐
H7...S1
C3‐
H3...I1
C5‐
I1...Cg2
Cg2 = C8
‐C13
0.88
0.95
0.95
2.48
2.93
3.08
3.323(3)
3.791
161
2‐X, ‐Y, 1‐Z
35
36
37
38
151
X, 1+Y, Z
2.095(4 3.740
3.890(4)
78.06(1 x,‐1+y,z
0)
161
3.925
150
3/2‐x,‐
1/2+y,3/2‐z
3/2‐x,‐
)
1(16)
3.202
0.96(4)
4.100
x, ½‐y, ‐
1/2+z
2.101(3 4.063
)
6.061
157.26
1/2+y,3/2‐z
Centroid of the phenyl ring,  is the dihedral angle between planes of
phenyl rings. Cg1 = C2 – C7, Cg2 = C8 – C13.
3e
3k
17
18
19
N1‐
H1∙∙∙O1
N2‐
H2∙∙∙O1
C4‐I1...I1
0.88
0.88
2.08
2.12
2.895(6)
2.924(6)
154
152
x,1+y,z
x,1+y,z
N1‐H1∙∙∙S1
N2‐H2∙∙∙S1
0.88
0.88
2.43
2.59
3.292(5)
3.428(5)
168
160
2‐x,‐y,‐1/2+z
2‐x, ‐y,‐
1/2+z
1/2+x,1/2‐
y,z
‐1/2+x,1/2‐
y,z
x, ‐1+y,z
39
40
C9‐H9∙∙∙O2
C6‐H6…S1
0.95
0.95
2.51
2.93
3.12
3.241(6)
3.671
133
136
162
41
42
43
44
2.105(5 3.947
3(11)
158.98( 2‐x,‐
17)
)
1/2+y,3/2‐z
Table 2 Continued
En Interact D‐H
tr
y
C10‐
H10∙∙∙I1
C4‐I1...O1
0.95
4.029
H∙∙∙A D∙∙∙A
(Å)
D‐
Symmetry
2.097
3.135(
4)
168.65( x,1+y,z
17)
ions
(Å)
(Å)
H∙∙∙A/ codes

(°)
Cg1...Cg2
3.728(
4)
3.2(3)
2‐x, ‐y,‐
1/2+z
45
3f
N1‐
0.88
2.05
2.870(4)
155
x,1+y,z
20
8 | J. Name., 2012, 00, 1‐3
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Cg1...Cg2
3.763(
4)
3.2(3)
2‐x, ‐y,1/2+z
46
3l
N1‐
H1∙∙∙O1‘
N1‘‐
H1‘∙∙∙O1
N2‐
H2∙∙∙S1‘
N2‘‐
H2‘∙∙∙S1
C10‘‐
H10‘∙∙∙S1
0.88
0.88
0.88
0.88
0.95
2.29
2.17
2.48
2.52
2.83
3.069(4)
2.894(5)
3.321(3)
3.329(4)
3.687(5)
148.0
140
x, y,z
x, y,z
47
48
49
50
51
161.0
153
‐1+x, y, z
(a)
1+x, y, z
150.3
1‐x, 2‐y, 1‐z
C6‐H6∙∙∙S1‘ 0.95
2.91
3.18
3.526(6)
3.989(5)
123.7
144.4
2‐x, 2‐y, 1‐z
2‐x, 1/2+y,
1/2‐z
52
53
C9‘‐
0.95
H9‘∙∙∙I1‘
C4‐I1...S1‘
(b)
2.107
2.105
0.95
3.453
4(12)
3.705
8(12)
2.82
168.41( ‐1+x, 3/2‐y,
11)
166.58
54
55
56
1/2+z
1+x,3/2‐y,‐
1/2+z
C4‘‐I1‘...S1
C9‐
3.605(4)
140
1‐x,2‐y,1‐z
H9∙∙∙Cg1
Cg1 = C2 –
C7
3m
N1‐H1∙∙∙O1 0.88
2.19
3.00
2.97
2.88
3.002(2)
3.77(17)
3.909(2)
3.753(2)
154
147
172
154
2‐X, 1‐Y, 2‐Z
1‐x,1‐y,1‐z
1‐X, 1‐Y, 2‐Z
X, 1/2‐Y, ‐
1/2+Z
57
58
59
60
N2‐H2∙∙∙I1
C9‐H9∙∙∙S1
C6‐H6∙∙∙S1
0.88
0.95
0.95
(c)
C4‐I1∙∙∙S1
Cg2∙∙∙ Cg2
2.105
3.606
7(5)
3.776
4(11)
2.76
158.42
0
1+X, Y, Z
61
62
63
1‐x,1‐y,1‐z
C5‐H5∙∙∙
Cg2
0.93
3.526(2)
138
2‐x,‐
1/2+y,3/2‐z
(d)
Fig. 2 (a) Overlay of structures of 3a (gray), 3b (orange) and 3c (cyan), (b) (c) and
Cg2 = C8 – C13.
(d) ORTEPs of 3a, 3b and 3c respectively are showing the atom numbering
scheme. The displacements ellipsoids are drawn at the 50% probability level and
H atoms are shown as small spheres with arbitrary radii.
Crystal structure of 3a and 3b are grossly isostructural whereas
that of 3c differs slightly. Neighboring molecules having c‐glide
relationship in 3a and 3b form a bifurcated N‐H…O hydrogen
bonding chain whereas in 3c unit‐translated molecules
generate the linear chain.
7, 11, Table 2). This shows that the carbonyl oxygen is acting as
a trifurcated proton acceptor for all the NH protons to
generate the monolayer in all the structures (Figure 3). All the
structures differ in the weaving of these monolayers to
generate bilayer structure. In 3a, the adjacent monolayers
interact via centrosymmetric I…I halogen bonding interaction
of type I category, in 3b the bilayers are generated by joining
The geometry of bifurcated N‐H…O interactions differs in
crystals of 3a and 3b whereas it is similar in crystals of 3c
(entries 1, 2, 5, 6, 9, 10, Table 2). The H…O distance involving
unsubstituted N‐H group (N2) is longer and the angle N‐H…O
deviate from the linearity in crystals of 3a and 3b while the
H…O distance involving substituted NH group (N1) is shorter
and the angular approach is moderate. The neighboring
antiparallel chains are stitched centrosymmetrically in 3a and
3b through dimeric N‐H…O interactions whereas in 3c the 21‐
screw axis neighboring chains are linked via monomeric N‐
H…O hydrogen bond engaging cis N‐H proton and carbonyl
oxygen (figure 3). The geometry of this N‐H…O interaction is
stronger compared to bifurcated N‐H…O interactions (Entry 3,
of the c‐glide related neighboring monolayers through C‐I…

interactions whereas in 3c the 21‐screw axis related
neighboring monolayers are linked via I…I halogen bonding
interaction19 of type II category20 (entries 4, 8, 12, Table 2). For
Type I and Type II category halogen bonding interactions
please refer figure S64 in supporting information. The packing
of the molecules in third direction is provided in ESI (Figure
S65).
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(a)
(a)
(b)
(c)
(b)
(d)
(e)
Fig. 4 (a) Overlay of structures of 3d (grey), 3e (purple), 3f (green) and 3g
(orange), (b) (c) (d) and (e) ORTEPs of 3d 3e 3f and 3g respectively are showing
the atom numbering scheme. The displacements ellipsoids are drawn at the 50%
probability level and H atoms are shown as small spheres with arbitrary radii
,
,
(c)
.
Fig. 3. View of molecular packing in crystals of (a) 3a, (b) 3b and (c) 3c. Some of
the atoms in the packing are omitted for clarity. All the marked distances are in
Å unit.
central urea moiety was observed in other derivatives. The
iodo phenyl rings of compounds 3d and 3f have similar
orientations however the N2‐substituent phenyl ring displayed
Category II: di‐substituted urea (3d‐g)
marked difference in orientation (79
the iodo phenyl rings of compounds 3d and 3e showed
significant difference in orientations (71.5 ) whereas the
orientation of other phenyl ring is almost the same (Figure 4a).
Crystal structures of 3e 3f and 3g are grossly isostructural
) (Figure 4a). Conversely,
Crystals of 3d, 3e, 3f and 3g belong to monoclinic space group
P21/c containing one molecule in the asymmetric unit.
Structure overlay reveals similar conformation of molecule in
crystals of 3f and 3g suggested isostructurality in their
molecular organization. Whereas significant difference in the
orientations of substituents (phenyl rings) with respect to the

,
whereas that of 3d differs (Figure 4). Molecules in all these
four compounds form unit‐translated one dimensional three
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(a)
(a)
(b)
(b)
(c)
(c)
(d)
Fig. 6 (a) Overlay of structures of 3h (grey), 3i (cyan), and 3j (pink), (b) (c) and (d)
ORTEPs of 3h 3i, and 3j respectively are showing the atom numbering scheme.
The displacements ellipsoids are drawn at the 50% probability level and H atoms
are shown as small spheres with arbitrary radii
,
.
proton donors and the C=O proton acceptor in bifurcated
૚
(d)
hydrogen bonds with graph set notations C(4)[R (6)], where
૛
૚
C(4) denotes a chain with 4 atoms, and [R (6)] denotes a
Fig. 5 View of molecular packing in crystals of (a) 3d, (b) 3e, (c) 3f and (d) 3g.
Some of the atoms in figure 5a are displayed in wireframe for clear view. All the
marked distances are in Å unit.
૛
hydrogen‐bonded ring motif containing of 6 atoms, with 2
donors groups and 1 acceptor group. The geometry of these
bifurcated N‐H…O interactions in all the compounds is
comparable, the distance is short and the angle is moderate
(entries 13, 14, 17, 18, 20, 21, 23, 24, Table 2). Neighboring c‐
glide symmetry related one dimensional chains in compound
centered N‐H…O hydrogen bonding chain along the b‐axis
(similar to compounds 3a, 3b and 3c) employing their two NH
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I…I halogen bonding (entries 19, 22, 25 Table 2) interactions of
type II category to generate the flat helical structure. The
rather long but linear C7‐H7…
 (Cg1) interaction (entry 16,
Table 2) also supplements the helical assembly in crystals of
3d. The crystallographic 21‐screw related adjoining chains
joined loosely through hydrophobic forces to generate a
bilayer structure in crystals of 3d, 3e and 3f. However, the
neighboring helices in 3g are connected centrosymmetrically
along the a‐axis through F…F21 short (entry 26, Table 2) contact
of type I category to create a 2‐dimensional wavy packing on
the ab plane (Figure 5d). The packing of the molecules in
structures of 3d
in ESI (Figure S66).
, 3e, 3f and 3g along the third direction is provided
(a)
Category III: mono‐substituted thiourea (3h‐j)
Crystals of 3h 3i and 3j belongs to monoclinic P21/n space
,
group containing one molecule in the asymmetric unit.
Structure overlay reveals difference in the orientations of iodo‐
phenyl and other phenyl ring with respect to the central
thiourea moiety due to the free rotation along N‐C bond. The
orientation of phenyl rings of compounds 3h and 3j differ by
79
 while that of 3h and 3i differ by 60. The conformation of
phenyl ring in compounds 3j and 3i differ slightly by ~7

.
Similarly, conformation of iodo phenyl ring showed noticeable
difference. The conformation of iodophenyl ring in 3h and 3j
differ by ~30, that of 3h and 3i by ~36 whereas compounds
3j and 3i displayed significant orientational difference (~66)
(Figure 6a).
Unlike, crystals of substituted urea which form one
dimensional three centered N‐H…O hydrogen bonding chain
structure, thiourea compounds preferred dimeric association.
This is because of the trans‐cis arrangement of NH protons
with respect to the thiocarbonyl group.13 The trans‐cis
arrangement of N‐H protons leads to dimeric self‐assembly
through N‐H…S hydrogen bond. There is also equal probability
of both NH protons adopting anti conformation depending on
the substituents. The trans‐trans orientation leads to
generation of one‐dimensional H‐bonding chain structure
similar to that seen urea derivatives. In crystal structures of 3h,
3i and 3j, H‐atoms have acquired trans‐cis orientations
resulting in the formation of dimeric N‐H…S hydrogen bond
between the neighboring molecules involving cis H‐atom and
C=S group (Figure 7). The geometry of N‐H…S hydrogen bond
in all the compounds is comparable (entries 28, 32, 35, Table
2). The adjacent dimers generate extended ribbon structure
through N‐H…I hydrogen bond involving trans H‐atom and
iodo group in 3h (entry 27, Table 2). The ribbon structure is
also supported by moderate C7‐H7…S1 interaction (Figure 7a,
entry 29, Table 2) engaging ortho C‐H of the iodophenyl ring
and thiocarbonyl group. In crystals of 3i and 3j the trans NH
atom do not participate in any interaction within the chain and
the ribbon structure is solely stabilized by centrosymmetric C7‐
H7…S1 hydrogen bond (Figure 7b and 7c, entries 33, 36, Table
2). The geometrical parameters of C‐H…S interaction are
similar. The adjoining parallel ribbons are stitched differently
in three structures. The adjacent ribbons are linked through
(b)
(c)
Fig. 7 View of molecular packing in crystals of (a) 3h, (b) 3i, and (c) 3j. Some
atoms are omitted and some are displayed in wireframe for clarity. All the
marked distances are in Å unit.
3d are networked through off‐centered C‐I…
(entry 15 Table 2) involving iodo‐phenyl rings along the c‐axis
to generate the bilayer structure (Figure 5a) whereas in
compounds 3e, 3f and 3g the adjacent crystallographic 21‐
 interactions
screw axis related one hydrogen bonded chains linked through
12 | J. Name., 2012, 00, 1‐3
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ARTICLE
(a)
(a)
(b)
(b)
(c)
(c)
Fig. 9 View of molecular packing in crystals of (a) 3k, (b) 3l, and (c) 3m. Some
atoms are displayed in wireframe for clear view. All the marked distances are in
Å unit.
In compounds 3k, 3l, and 3m, the N2‐phenyl ring is substituted
with electron withdrawing (NO2) and electron donor (OMe)
groups to investigate the electronic effect on the orientations
of N‐H atoms with respect to the thiocarbonyl group.
Compound 3k (NO2 substituted) crystallized in orthorhombic
space group Pna21, whereas compounds 3l and 3m (OMe
substituted) crystallized in monoclinic space group P21/c.
Compound 3l contains two molecules in the asymmetric unit
whereas 3k and 3m contained one molecule each. Structure
overlay revealed marked difference in the orientations of iodo‐
(d)
Fig. 8 (a) Overlay of structures of 3k (green), 3l (orange), and 3m (blue), (b) (c)
and (d) ORTEPs of 3k, 3l, and 3m respectively are showing the atom numbering
scheme. The displacements ellipsoids are drawn at the 50% probability level and
H atoms are shown as small spheres with arbitrary radii.
type II category, I…I halogen bonding interaction in 3h (entry
30, Table 2), in 3i the ribbons are connected via N‐H…I
interactions engaging trans N‐H proton and off‐centered C‐I…
halogen bonding interactions (entries 31, 34, Table 2) whereas
in 3j the ribbons are joined through only off‐centered C‐I…
halogen bonding interactions (entry 38, Table 2). The packing
of molecules along the third direction in structures of 3h, 3i
and 3j is displayed in figure S67, ESI.

phenyl ring in crystals of 3l and 3m (~88
difference between the conformations of methoxy substituted
phenyl ring (~31 ). Orientations of iodo‐phenyl ring in 3k and
3l also showed considerable difference (~70 ), this also reveals
the difference in the orientation of iodo‐phenyl ring in
compounds 3k and 3m is ~18 . Similar to compounds 3h 3i
) compared to the




,
Category IV: Electronically tailored di‐substituted thiourea (3k‐m)
and 3j, the N‐H moiety adopts trans‐cis orientations in
methoxy substituted compounds 3l and 3m irrespective of the
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position of methoxy group on the phenyl ring. However, the hydrogen bond between trans N‐H and methoxy O atom
substitution of electron withdrawing NO2 group at para‐ (entries 47‐48, Table 2) of symmetry independent molecules to
position of benzene ring in compound 3k alters the N‐H generate the bilayer structure on the ac plane (Figure 9b). The
conformation to trans‐trans geometry similar to urea neighboring bilayers along the b‐axis are linked via C‐H…S, C‐
derivatives (figure 8a).
H…I and C‐H… interaction (entries 51, 52, 53 and 56, Table 2)
The trans‐trans conformation of N‐H atoms in compounds 3k to reveal the layered packing of molecules (Figure S68b).
resulted in the generation of helical H‐bonding chain The change of methoxy position from para (3l) to meta (3m
)
employing its two NH proton as donors and the C=S as proton has altered the molecular packing significantly. Although the
acceptor in bifurcated (three centered) N‐H…S hydrogen conformation of N‐H hydrogens with respect to the
bonding synthon across the crystallographic 21‐screw axis thiocarbonyl group is trans‐cis in compound 3m, molecules do
(Figure 9a). The geometry of both N‐H…S interaction is not associate in dimeric fashion through N‐H…S=C hydrogen
comparable (entries 39‐40, Table 2). The graph set notations of bond as observed in other thio derivatives having similar
this synthon is similar to three centered N‐H…O hydrogen conformation of N‐H protons with respect to the thiocarbonyl
bonding motif observed in urea moiety. However, there is group. Instead, unit‐translated molecules in 3m generate an
significant difference from urea derivatives with respect to the extended chain through C‐I…S halogen bond running parallel
approach of two NH protons towards thiocarbonyl group. to the a‐axis (entry 61, Table 2, Figure 9c). The approach of I
Although the thiourea derivative 3k having trans‐trans atom to thiocarbonyl group is perpendicular similar to the
orientations of NH protons forms hydrogen bonding chain approach of N‐H hydrogens towards thiocarbonyl group in 3k
similar to those formed by urea moiety. However, the two NH (Figure 9a). The adjacent antiparallel chains stitched
protons and the thiocarbonyl group take almost perpendicular centrosymmetrically through dimeric N‐H…O hydrogen
orientation with respect to each other due to the sideway
bonding interaction engaging trans N‐H and oxygen of the
approach of the NH donors to the thiocarbonyl acceptor. The methoxy group to generate the one dimensional ribbon along
orthogonal approach of trans NH protons towards C=S group the a‐axis (Figure 9c, entry 57, Table 2). The dimeric
generate a zig‐zag pattern in contrast to the linear chain association of molecules through N‐H…O hydrogen bond also
formed by urea derivatives. This difference in the H‐bonding places the phenyl rings of the methoxy benzene group in
pattern of urea and thiourea moiety could be because of the stacking mode to generate intermolecular π‐stacking
differences in the charge distribution around (thio)carbonyl interaction with a Cg∙∙∙Cg distance of 3.7769(15) Å (Cg…Cg is
group. The electron density in thioureas is delocalized on the the distance between ring centroids, entry 62, Table 2). The
surface of C=S bond leading to the generation zig‐zag pattern.
adjacent ribbons are stitched centrosymmetrically through N‐
In crystals of 3k the perpendicular approach of the H…I interactions engaging cis N‐H proton and I atom and C‐
thiocarbonyl groups along the helical chain places the phenyl H…S interactions (entries 58‐60, Table 2) roughly along a‐axis
rings at both ends in stacking mode to generate the extended and to create a compact packing on the ac plane (figure S68c,
‐stacking chain along the direction of c‐axis. Along the chain ESI).
neighboring molecules are stacked through off‐centered
…
aromatic stacking interactions engaging phenyl rings of Cambridge Structural Database (CSD) Survey:
methoxy benzene and iodo benzene groups with the centroid‐
Cambridge Structural Database survey on the preference
centroid distances being ~3.7 Å (entries 45‐46, Table 2). These
neighbouring 21‐screw related helical chains along the b‐axis
are stitched through mono‐coordinated I…NO2 halogen
bonding interaction22 supplemented by C‐H…I interactions
between C‐H of the nitrobenzene group and I atom (Figure 8a,
entries 43‐44, Table 2). Along the a‐axis the adjacent helical
chains are related by a‐glide symmetry and are linked through
short and non‐linear C‐H…O and C‐H…S interactions (entries
41‐42, Table 2) to generate the 2D assembly on the ac plane
(Figure S68a, ESI).
The trans‐cis conformation of N‐H atoms with respect to the
thiocarbonyl group in compound 3l led to the formation of
dimeric N‐H…S=C hydrogen bonding synthon between the
symmetrically independent neighboring molecules involving
cis N‐H and C=S group. The geometries of both these
interactions are comparable (entries 49‐50, Table 2). The
adjacent dimeric synthons generate extended ribbon structure
through dimeric C‐I…S halogen bonding interactions along the
c‐axis.19 The strength of both these halogen bonding
interactions is similar (entries 54‐55, Table 2). The neighboring
ribbons along the a‐axis weaved through dimeric N‐H…O
mode of association of molecules in ureas and thioureas has
already been reported earlier.13 The study reveals that
molecules prefer to associate via chain structure in urea due to
trans‐trans conformation of NH protons. However, in
thioureas two modes of association of molecules were
observed i.e. dimeric motif through N‐H…S hydrogen bonding
interaction with trans‐cis conformation of NH protons and the
second mode is the formation of zig‐zag chain through three
centered N‐H…S interactions similar to those found in ureas
because of the trans‐trans conformation of N‐H protons. CSD
survey revealed equal probabilities for both type of association
in thioureas whereas in case of ureas the chain association was
dominant. In order to further investigate the current trend in
the favored mode of association of molecules in ureas and
thioureas and the effect of substituents on their association, a
survey of the recent version of Cambridge Structural Database
(CSD, Version 5.37, November 2015) was carried out (Figure
S69). All the searches were carried out for the organic
molecules with no restriction on R‐factor, 3D coordinates
determined, error‐free coordinates and restricted entries of
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ARTICLE
disordered, ionic, polymeric and X‐ray powder diffraction derivatives was unambiguously established using
a
structures. Out of 1616 (1072) structures containing urea combination of 1‐2D NMR spectroscopy, ESI‐MS and single
(thiourea) moiety, 773 (258) hits were excluded in which urea crystal X‐ray diffraction. These (thio)urea compounds have
(thiourea) moieties were involved in cyclic structure having cis‐ been classified into four classes; a) mono‐substituted, b) di‐
cis orientation of NH protons (only one example of cis‐cis substituted, c) di‐substituted thiourea and d) electronically
acyclic thiourea was found, refcode: ELOPOK). Similar searches tailored di‐substituted thiourea. The crystal structures of all
with thioureas led to 1072 hits, of which 258 hits were the derivatives were influenced by conformation of N‐H
involved in ring formation and therefore excluded. The protons with respect to the thio(carbonyl) group. Both N‐H
remaining hits were segregated based on the conformation of protons in urea compounds
NH protons (trans‐cis or trans‐trans) using O(S)=C‐N‐H dihedral conformation with respect to the carbonyl group which
angle criterion. The dihedral angle is close to 0 for trans‐cis resulted in the formation three centered N‐H…O hydrogen
conformation and around 180 for trans‐trans geometry of NH bonding motif leading to the generation of one‐dimensional
protons related to O(S)=C group. The dihedral angle criterion hydrogen bonding chain. These neighbouring chains are linked
(3a‐3g) adopt trans‐trans


for trans‐cis conformation were 130
to +50 (cis) whereas for trans‐trans geometry they were 130
to 230

to 230

(trans) and ‐50


via either I…I or C‐I…
construct two dimensional networks. However, in thiourea
 halogen bonding interactions to


. Interestingly, the considerable number of hits 171 was derivatives both N‐H protons take most preferred trans‐cis
found for trans‐cis and maximum number of hits (604) was orientations with respect to the thiocarbonyl group leading to
found for trans‐trans conformation in ureas. In contrast dimeric association of molecules through N‐H…S hydrogen
maximum number of hits (700) was observed for trans‐cis bonding synthon. These dimeirc synthons generate the
conformation and relatively fewer hits (114) could be found extended chain structure through C‐H…S interactions and the
for trans‐trans geometry in thioureas. This reveals that trans‐ neighbouring chains are connected through either I…I or C‐I…

trans conformation of NH protons is the most preferred motif halogen bonding interactions to make two dimensional
in ureas whereas the trend is reverse for the thioureas. packing. The effect of substitution of electron withdrawing or
Custelcean et al. reported that either of these motifs can be donating groups at the phenyl ring on the conformation of two
manipulated by the bulkiness13 of the substituents on the NH protons and its influence on the molecular packing has also
thiourea group whereas no such tendency was observed in been investigated. The presence of electron donating group
ureas. The presence of electron withdrawing group (e.g. NO2, (OMe) do not change the orientations of the NH atoms
F, Cl or Br) on aromatic ring attached to thioureas also favored however it changes the molecular packing depending on its
trans‐trans geometry of NH protons leading to hydrogen position on the phenyl ring. In 3l molecules form dimeric
bonding chain formation. The electron withdrawing group synthon through N‐H…S hydrogen bonding interactions (as
(EWG) increases the acidity of NH protons which then act a observed in earlier thio urea derivatives), the successive
good hydrogen bond donor and seems to be favoring the association of which through N‐H…O and I…S interactions
formation of one dimensional bifurcated N‐H…S hydrogen generate the 2D structure. However, the installation of OMe
bonded chain. The presence and positions of other stronger group at meta position (3m) rules out the dimeric association
proton accepting groups such as C=O, N in thioureas of molecules through N‐H…S interactions. Instead, molecule
containing EWG also influence the conformation of NH protons create dimeric structure via centrosymmetric N‐H…O
considerably. Proximity of such hydrogen atom acceptor atoms interactions engaging trans NH proton and methoxy oxygen.
and NH protons in thioureas facilitate the formation of The neighboring dimers are further linked through dimeric N‐
intramolecular N‐H…O/N‐H…N hydrogen bonds and this could H…I interactions employing cis NH proton and I atom to
be the reason for trans‐cis geometry for NH protons. However, generate an extended chain. The centrosymmetric short I…S
if the proton accepting groups are at a remote distance that contact linked these adjoining chains along the direction of a‐
prevents the formation of intramolecular N‐H…O/N‐H…N axis. The preference for the dimeric association of molecules
hydrogen bonds, in such cases intermolecular N‐H…O/N‐H…N through N‐H…S hydrogen bonds over three centered N‐H…S
hydrogen bonds formation is favored resulting in the trans‐ linked zig‐zag chains is also supplemented by CSD survey.
trans conformation of NH protons. In case of ureas, the Above studies and CSD survey clearly indicates that it is also
presence of other strong proton accepting groups C=O, N (e.g. possible to design the desired supramolecular network using
acyl or pyridine groups) also influence the conformation of NH thioureas akin to ureas by manipulating the positions and the
protons considerably. Proximity of such hydrogen atom nature of the substituents on thioureas. The newly prepared
acceptor atoms and NH protons in ureas also facilitate the iodophenyl (thio)urea’s can be installed on a phosphorus atom
formation of intramolecular N‐H…O/N‐H…N hydrogen bonds to fabricate supramolecular phosphines and the resultant
and this could be the reason for trans‐cis geometry for NH supramolecular phosphines can be used as ligands in various
protons.
organometallic transformation such as asymmetric
hydrogenation.14
In conclusion, a small library of 13 (3a‐3m) compounds with
modular positioning of Iodide and urea/thiourea groups was
synthesized in excellent yields in a single step synthetic
protocol. The existence of the anticipated (thio)urea
Acknowledgements
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Journal Name
Dydio, J. N. H. Reek, Angew. Chem. Int. Ed. 2013, 52, 3878‐
3882; (d) J. Meeuwissen, A. Sandee, B. de Bruin, M. A.
Financial support from DST India (SR/S2/RJN‐11/2012 and
SR/S1/IC‐60/2012) is gratefully acknowledged. VSK thanks UGC
for the senior research fellowship. CSIR‐NCL and SPIRIT (DCPC)
is gratefully acknowledged for additional support. SHC is
indebted to the AvH Foundation, Germany for the equipment
grant. SHT thanks CSIR (INDIA) for a project fellowship under
the ORIGIN program of 12FYP. We are also very grateful to Ms.
Debamitra K. Chakravarty, SP Pune University for her great
help in recording the crystal data on compound 3e. The single
crystal X‐ray facility at Department of Chemistry, SP Pune
University is gratefully acknowledged.
Siegler, A. L. Spek, J. N. H. Reek, Organometallics, 2010, 29
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W. Patureau, J. N. H. Reek, Angew. Chem. Int. Ed. 2009, 48
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characterization and yields.
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16 | J. Name., 2012, 00, 1‐3
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For Table of Content Entry Only
Synthesis of a small library of 13 urea compounds was achieved in a single step and their self-
assembly investigations reveal that urea NH groups prefer to orient in a trans-trans fashion to
produce bifurcated chain structures, whereas the thiourea NH moiety crystalizes in a trans-cis mode
to yield dimeric assemblies.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 17