Pyrrolylamidourea based anion receptors

Article abstract of DOI:10.1039/b603223k

The anion binding behaviour of a number of pyrrolylamidourea and thiourea compounds have been studied in DMSO solution. Mono-amidothioureapyrrole compounds were found to be deprotonated by basic anions such as fluoride, acetate, benzoate or dihydrogenphos

Full text of DOI:10.1039/b603223k

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PAPER
www.rsc.org/njc | New Journal of Chemistry
Pyrrolylamidourea based anion receptorswz
Louise S. Evans, Philip A. Gale,* Mark E. Light and Roberto Quesada*
Received (in Durham, UK) 3rd March 2006, Accepted 25th April 2006
First published as an Advance Article on the web 24th May 2006
DOI: 10.1039/b603223k
The anion binding behaviour of a number of pyrrolylamidourea and thiourea compounds have
been studied in DMSO solution. Mono-amidothioureapyrrole compounds were found to be
deprotonated by basic anions such as fluoride, acetate, benzoate or dihydrogenphosphate with
the structure of the deprotonated species elucidated by X-ray crystallography. 2,5-Bis-
amidoureapyrroles were synthesized and found to be effective anion receptors for a range of
putative anionic guests.
to signal the binding event by a change of colour produced by
Introduction
intramolecular charge transfer processes.7 Receptors 1–7 were
synthesized according to the route depicted in Scheme 1. 5-
Methyl-3,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester
88 and 3,4-diphenyl-1H-pyrrole-2,5-dicarboxylic acid diethyl
ester 109 were treated with an excess of hydrazine hydrate in
refluxing ethanol to yield the corresponding carbohydrazide
derivatives 9 and 11 as white, crystalline solids. Reaction of
these compounds with the appropriate isocyanate or isothio-
cyanate gave receptors 1–7 in moderate to good yields.
Crystals of compound 9 were grown by slow evaporation of
a methanolic solution of the receptor. In the solid state,
compound 9 forms hydrogen-bonded chains by dimerization
of the amidopyrrole and hydrazine groups through N–Hꢀ ꢀ ꢀO
interactions and N–Hꢀ ꢀ ꢀN interactions (Fig. 1). Representa-
tive bond distances and angles are: N4ꢀ ꢀ ꢀO1 2.844(4) A,
N1ꢀ ꢀ ꢀO2 2.854(4) A, N–Hꢀ ꢀ ꢀO with bond angles being
158(3) and 159(3)1, respectively, and N2ꢀ ꢀ ꢀN6i 3.007(4) A,
N5ꢀ ꢀ ꢀN3ii 3.072(4) A with N–Hꢀ ꢀ ꢀN with bond angles of
141(3) and 142(3)1, respectively (Fig. 1).
The development of anion sensors and receptors has attracted
a great deal of interest and effort from the supramolecular
chemistry community due to the importance of anions in many
biological and chemical processes.1 Hydrogen-bond donating
amide, pyrrole and urea/thiourea groups have been employed
in a wide range of synthetic anion receptors and sensors and a
variety of neutral hydrogen bond donor groups are employed
in selective biological anion binding agents such as the sulfate
binding protein.2 Over recent years we have extensively stu-
died the anion binding properties of 2,5-dicarboxamidopyrrole
systems. These compounds have been found to be effective
anion receptors showing selectivity for oxoanions in competi-
tive solvent media (DMSO/water).3 In the past few years,
amidothiourea compounds have been used as anion receptors,
and examples of selective colorimetric and fluorimetric anion
sensors containing this motif have been reported.4 Very re-
cently Gunnlaugsson, Kruger and co-workers reported the use
of a naphthalimide–amidothiourea derivative for colorimetric
sensing of anions in highly competitive aqueous media.5
Continuing our efforts in producing new anion receptors
and sensors we set out to synthesize a family of compounds
containing both amidopyrrole and urea groups and to study
their anion binding properties. Aspects of this work have been
communicated recently.6
Crystals of compound 2 were obtained by slow evaporation
of a methanol solution of the receptor. In the solid state the
pyrrole N–H group and the carbonyl group of the amido
moiety adopt a cis arrangement, with a torsion angle of 941
between the planes defined by the pyrroleamido and urea
functionalities (Fig. 2).10 This receptor is further arranged
Results and discussion
Synthesis
We decided to produce a series of increasingly acidic com-
pounds containing a 2-amido(thio)urea substituted pyrrole
unit 1–4, and also the 2,5-amidourea substituted pyrrole
derivatives 5–7. Nitroaromatic substituents were introduced
in some of the hosts as chromophores which have the potential
School of Chemistry, University of Southampton, Southampton, UK
SO17 1BJ. E-mail: philip.gale@soton.ac.uk. E-mail: r.quesada-
pato@soton.ac.uk; Fax: þ44 (0)23 8059 6805; Tel: þ44 (0)23 8059
3332
w The HTML version of this article has been enhanced with colour
images.
z Electronic supplementary information (ESI) available: Additional
Scheme 1 Synthesis of receptors 1–7. (i) NH2NH2/EtOH; (ii) RCNX
(X = O or S)/CHCl3.
experimental data. See DOI: 10.1039/b603223k
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Fig. 1 Hydrogen bonded chains, running along the a axis, formed by
compound 9 in the solid state (symmetry code: (i) ꢂ1 þ x, y, z).
Fig. 4 X-Ray crystal structure of compound 5. Thermal ellipsoids are
drawn at the 50% probability level.
into hydrogen-bonded sheets through urea–urea and amido-
pyrrole–amidopyrrole interactions with Nꢀ ꢀ ꢀO distances of
N1ꢀ ꢀ ꢀO1i 2.857(2) A, N3–H3ꢀ ꢀ ꢀO2ii 2.811(2) and N4ꢀ ꢀ ꢀO2ii
3.003(2) A and N–Hꢀ ꢀ ꢀO bond angles of 161.3, 135.5 and
151.01, respectively (symmetry codes: (i) ꢂx, ꢂy þ 1, ꢂz þ 1;
(ii) ꢂx, y ꢂ 1/2, ꢂz þ 1/2) (Fig. 3).
N2ꢀ ꢀ ꢀO1ii 2.8744(18)
A
and N–Hꢀ ꢀ ꢀO bond angles
N1–H1Aꢀ ꢀ ꢀO1 156.51 and N2–H2Aꢀ ꢀ ꢀO1ii 142.01, preventing
the participation of the 2,5-amidopyrrole moiety in any hydro-
gen bond (Fig. 5) (symmetry codes: (ii) x, ꢂy, z ꢂ 1/2).
Anion binding studies
Crystals of compound 5 were grown by slow evaporation of
an acetonitrile solution of the receptor and was also charac-
terized by means of X-ray diffraction. The molecule lies about
a twofold axis through the pyrrole N–H bond. The pyrrole
N–H and carbonyl groups adopt a similar cis conformation to
receptor 2 in the solid state (Fig. 4). In this case, the urea
groups form hydrogen-bonded chains through DDA contacts,
with Nꢀ ꢀ ꢀO bond distances of N1ꢀ ꢀ ꢀO1ii 2.8975(19) A and
The anion binding abilities of the new receptors were studied
by means of UV-Vis and 1H NMR titration experiments using
DMSO and DMSO-d6 as solvents, respectively. Upon addi-
tion of anions to compound 1, no significant changes were
observed in either UV/Vis or 1H NMR spectra, indicating that
the receptor is not interacting significantly with the putative
anionic guests in this competitive solvent medium. The 1H
NMR spectra of the more acidic 4-nitrophenyl substituted
derivative 2 showed a significant broadening of all the NH
signals upon addition of tetrabutylammonium fluoride, ace-
tate, benzoate and dihydrogenphosphate, indicating an inter-
action between the receptor and the anions through hydrogen
bonds. These changes are accompanied by a gradual but
visible change of colour from an almost colourless solution
to dark yellow. UV-Vis spectra reflected these changes with an
increase of the absorbance in the 450 nm region and appear-
ance of two isosbestic points at ca. 280 and 340 nm (Fig. 6).
The changes in the absorbance as function of the concentra-
tion of anion added can be fitted to a 1 : 1 binding equilibrium
model,11 giving association constants of 3010 Mꢂ1 (Fꢂ), 5580
Fig. 2 X-ray crystal structure of compound 2. Thermal ellipsoids are
drawn at the 50% probability level.
Fig. 3 Hydrogen bonded sheets formed by compound 2 in the solid
state viewed looking down the a axis. Non-acidic hydrogen atoms,
phenyl and nitrobenzene groups are omitted for clarity (symmetry
codes: (i) ꢂx, 1 ꢂ y, 1 ꢂ z; (ii) x, 0.5 ꢂ y, 0.5 þ z).
Fig. 5 Hydrogen bonded chain defined by compound 5 along the
crystallographic c axis (symmetry code: (i) x, ꢂy, ꢂ0.5 þ z).
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Fig. 7 DMSO solutions (2 ꢄ 10ꢂ3 M) of compounds 2 (left group)
and 4 (right group). From left to right within each group: solution of
receptor, and solution of receptor in the presence of one equivalent of
tetrabutylammonium fluoride, acetate, benzoate and dihydrogen
phosphate.
Fig. 6 UV-Vis absorption spectrophotometric titration of compound
2 with tetrabutylammonium acetate in DMSO at 25 1C. Inset: increase
of absorbance at 390 nm vs. equivalents of acetate.
Table 1 Association constants Ka (Mꢂ1) for receptors 2 and 5–7 with
different anions (added as tetrabutylammonium salts) at 298 K in
DMSOa as determined by UV/Vis titration techniques
2
5
6
7
Fꢂ
3010
1440
5880
1060
3890
5000
3610
4010
8590
9630
6830
8220
15 300
16 600
13 800
13 000
C6H5COOꢂ
CH3COOꢂ
H2PO4
ꢂ
a
Fig. 8 UV-Vis absorption spectrophotometric titration of compound
4 with tetrabutylammonium acetate in DMSO at 25 1C. Inset: varia-
tion of absorbance at 450 nm vs. equivalents of acetate.
Errors estimated to be no more than ꢃ10%.
Mꢂ1 (CH3CO2ꢂ), 1440 Mꢂ1 (PhCO2ꢂ) and 1060 Mꢂ1
(H2PO4ꢂ) (Table 1). Smaller changes in the UV/Vis spectra
were observed upon addition of less basic anions (Clꢂ, Brꢂ or
HSO4ꢂ) that were insufficient to provide a reliable value of the
association constant.
The analogous thiourea receptors 3 and 4 were evaluated,
and addition of Fꢂ, CH3COOꢂ, PhCO2 or H2PO4 as tetra-
butylammonium salts to solutions of compound 3 or 4 in
DMSO resulted in dramatic changes in the UV-vis spectra of
the receptors, with new intense absorption bands appearing at
330 and 430 nm, respectively. Following the changes in the
absorbance as function of the concentration of anion resulted in
a steep curve, preventing the calculation of an apparent stability
constant. In the case of compound 4, a distinctive change of
colour from yellow to red is observed (see Fig. 7 and 8).
Proton NMR titration experiments in DMSO-d6 shed light
on the interaction of the anions and receptor 4. Instead of a
broadening of the NH signals, as was observed with com-
pound 2, a new set of three sharp signals at 11.3, 9.6 and 8.7
ppm, corresponding to three NH groupsꢂappeared (Fig. 9)
upon addition of Fꢂ, CH3COOꢂ, PhCO2 or H2PO4ꢂ, sug-
gesting the formation of a new compound.
ꢂ
ꢂ
Fig. 9 Stack plot of the 1H NMR spectra of compound 4 in the
presence of increasing amounts of tetrabutylammonium benzoate
recorded in DMSO-d6.
tion of the thiourea had occurred at N103 (NH hydrogens
were located in the X-ray crystal structure, see Fig. 10). A
proton NMR the tetrabutylammonium salt of (4 ꢂ H1)ꢂ in
DMSO-d6 gave an identical spectrum to those obtained after
the addition of one equivalent of tetrabutylammonium fluor-
ide, acetate, benzoate or dihydrogen phosphate, evidence that
leads us to suggest that these four anions deprotonate com-
pound 4 in DMSO solution. Crystallisation of compound 4
Red crystals were formed upon slow evaporation of a
dichloromethane–diethyl ether solution compound 4 contain-
ing one equivalent of tetrabutylammonium fluoride. The
X-ray crystal structure showed that the crystals were the
tetrabutylammonium salt of (4 ꢂ H1)ꢂ and that deprotona-
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bonding array in this system which fails to adopt a geometry
suitable for the stabilization of a hydrogen-bonded complex,
leading to a neat deprotonation. We12 and other research
groups13 have reported colour changes in different receptors
identified as deprotonation processes, however, in previous
studies, two equivalents of anion (frequently fluoride) have
been necessary to achieve deprotonation (the formation of
HF2ꢂ drives the deprotonation process in these cases). This is
not the case with compound 4, as deprotonation is complete
after addition of only one equivalent of anionic guest. Re-
1
ceptor 3 shows the same behaviour in the H NMR titration
experiments, but complete deprotonation is not achieved until
an excess of the anion is added (presumably due to this
compound being less acidic than 4). When UV-Vis titration
experiments of compound 4 were performed employing a 9 : 1
mixture of DMSO–water a virtually equivalent family of
spectra was obtained, indicating that the same ‘neat’ depro-
tonation process is occurring in this solvent media. Solubility
problems prevented the use of more water-rich mixtures.
Disubstitution of the pyrrole ring in compounds 5–7, should
result in a more favourable cleft-like binding mode and
increased affinity for anions was anticipated. In order to avoid
deprotonation processes in the bis-substituted pyrrole com-
pounds, only urea derivatives were prepared. Unlike mono-
substituted derivative 1, addition of tetrabutylammonium
fluoride, acetate, benzoate and dihydrogenphosphate to com-
pound 5 produced a significant broadening of all the NH
signals in the 1H NMR spectrum (Fig. 12) with similar changes
being observed in the case of receptors 6 and 7. This broad-
ening of signals in the 1H NMR spectra precluded the calcula-
tion of association constants of anions with these receptors
using this technique.
Fig. 10 X-Ray crystal structure of the tetrabutylammonium salt of
deprotonated compound 4. Thermal ellipsoids are drawn at the 35%
probability level. The deprotonated species adopts an essentially
planar conformation. Only part of the asymmetric unit is shown; the
full unit comprises two anions in general positions, one cation in a
general position, one half cation ordered about a twofold axis, and
another half cation disordered about a twofold axis.
Changes in the UV/Vis spectra of the bis-substituted com-
pounds were seen upon addition of tetrabutylammonium
anion salts, consisting in an increase of the absorbance in
the 330 nm region for derivatives 5 and 7 and in the 400 nm
region for the 4-nitrophenyl substituted compound 6 (Fig. 13)
with all the putative anionic guests (see ESIz for more details).
The UV/Vis titrations all fit satisfactorily to a 1 : 1 receptor :
anion binding model and the stability constants are calculated
on this basis. It is however possible that other equilibria are
present in solution and hence these values should be treated
with caution (Table 1). Nonetheless, the results show that
while compounds 5–7 show an enhanced affinity for anions as
compared to the mono-substituted derivative 2, they are not
selective under these experimental conditions.
Fig. 11 Part of the hydrogen-bonded chain defined by the deproto-
nated amidothiourea (4 ꢂ H1)ꢂ in the solid state (symmetry codes: (i)
1 ꢂ x, 1 ꢂ y, ꢂz, (ii) 1 þ x, y, z).
from a solution containing one equivalent of tetrabutylammo-
nium benzoate also led to the formation of identical red
crystals and also colourless needles which proved to be benzoic
acid. The deprotonated species appears to be stabilized by an
intramolecular hydrogen bond from the CH at the ortho-
proton of the 4-nitrophenyl group (N103ꢀ ꢀ ꢀC109 2.823 A)
with the deprotonated species now adopting an essentially
planar arrangement (Fig. 10). In the solid state the receptor
forms hydrogen-bonded chains through interactions of the
amidopyrrole and thiourea groups (Fig. 11) with N102ꢀ ꢀ ꢀS101
2.881(5) A, N101ꢀ ꢀ ꢀS201i 3.311(5) A, N204ꢀ ꢀ ꢀO101i 2.894(6) A
and N201ꢀ ꢀ ꢀO201ii 2.826(6) A; N102ꢂH102ꢀ ꢀ ꢀS101 11.71,
N101–H101ꢀ ꢀ ꢀS201i 157.91, N204–H204ꢀ ꢀ ꢀO101i 163.31 and
N201–H201ꢀ ꢀ ꢀO201ii 159.81 (symmetry codes: (i) ꢂx, y, ꢂz þ
1/2; (ii) ꢂx þ 1, y, ꢂz ꢂ 1/2).
Conclusions
There has been intense interest recently in the use of amido
(thio)ureas as anion sensors and also in the interaction of basic
anions with neutral hydrogen-bond donor systems as in some
cases deprotonation occurs after addition of two equivalents
of basic anion. In this paper we have shown that a pyrrolyla-
midothiourea is deprotonated upon addition of only one
equivalent of anions such as acetate and dihydrogen phos-
phate. This work serves to illustrate that care must be taken
when studying anion receptors containing acidic neutral hy-
drogen bond donor groups as deprotonation processes can
The increased acidity of the thiourea N–H groups resulted
in the deprotonation of the receptor upon addition of anions
with the red colour the result of the formation of the amidour-
ea anion and not the formation of a receptor–anion complex.
This may be due to the non-convergent nature of the hydrogen
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Experimental
General
1H and 13C NMR experiments were recorded on a Bruker
AV-300 NMR spectrometer. Chemical shifts are reported in
ppm and referenced to solvent. Deuterated solvents were
purchased from Apollo Ltd. Reagents were purchased from
the Aldrich Chemical Co. and used without further purifica-
tion. Elemental analyses were conducted by Medac Ltd. Mass
spectrometry was carried out at the University of Southamp-
ton Mass Spectrometry Service. UV-Vis absorption spectra
were recorded on a Shimadzu UV-1601 spectrometer.
Data obtained from UV-Vis titration experiments were
processed using Origin 7.0 software package. For further
details and titration curves see ESI.z
Syntheses
5-Methyl-3,4-diphenyl-1H-pyrrole-2 carbohydrazide 9. 5-
Methyl-3,4-diphenyl-1H-pyrrole-2 carboxylic acid ethyl ester
(1 g, 3.46 mmol) was added to a large excess of hydrazine
hydrate (5 mL, 100 eq.). Enough ethanol to produce dissolu-
tion was added and the reaction was heated at reflux for 48 h,
and then allowed to cool to room temperature. 100 mL of
water was added, inducing precipitation of the product as a
white crystalline solid. This was collected by filtration, washed
with water (3 ꢄ 10 mL) and dried (717 mg, 71%). Micro-
analysis: Calc. for C18H17N3O: C, 74.2; H, 5.9; N, 14.4.
1
Found: C, 74.1; H, 5.9; N, 14.2%. H NMR (CDCl3): d 9.67
(br s, 1H, pyrrole NH), 7.26–6.91 (m, 10H, Ar H), 6.62 (br s,
1H, NH), 3.79 (br s, 2H, NH2), 2.29 (s, 3H, CH3). Solubility
problems precluded the acquisition of a 13C NMR spectrum.
MS (ES1): m/z 605.1 (2M þ Na1). Suitable crystals for X-ray
diffraction were obtained by slow evaporation of a methanol
solution of the compound.
Fig. 12 Stack plot of the 1H NMR spectra of compound 5 in the
presence of increasing amounts of tetrabutylammonium fluoride
recorded in DMSO-d6.
3,4-Diphenyl-1H-pyrrole-2-dicarbohydrazide 11. 3,4-Diphe-
nyl-1H-pyrrole-2,5-dicarboxylic acid diethyl ester (334 mg,
0.92 mmol) was mixed with a large excess of hydrazine hydrate
(8 mL) and enough ethanol was added to achieve dissolution
(approx. 10 mL). The reaction was heated at reflux for 48 h
and then allowed to cool. Water was then added (100 mL) and
a precipitate formed. This was collected, washed with water (3
ꢄ 10 mL) and dried to give a white solid (234 mg, 76%).
Microanalysis: Calc for C18H17N5O2: C, 64.5; H, 5.1; N, 20.9.
1
Found: C, 64.3; H, 5.0; N, 21.0%. H NMR (DMSO-d6): d
11.75 (br s, 1H, pyrrole NH), 8.41 (s, 2H, NH), 7.18 (m, 6H,
Ar H), 7.06 (m, 4H, Ar H), 4.32 (s, 4H, NH2). Solubility
problems precluded the acquisition of a 13C NMR spectrum.
MS (ES1): m/z 336.4 (M þ H1).
Fig. 13 UV-Vis absorption spectrophotometric titration of com-
pound 6 with tetrabutylammonium acetate in DMSO at 25 1C. Inset:
change of absorbance at 390 nm vs. equivalents of acetate.
2-(5-Methyl-3,4-diphenyl-1H-pyrrole-2-carbonyl)-N-phenyl-
hydrazinecarboxamide 1. Phenyl isocyanate (76 mL, 0.70
mmol) was dissolved in chloroform, and the solution degassed
for 10 min. 5-Methyl-3,4-diphenyl-1H-pyrrole-2-carbohydra-
zide (203 mg, 0.70 mmol) was added, and the reaction stirred
at room temperature for 24 h. A precipitate formed, which was
collected by filtration, washed with dichloromethane (3 ꢄ 10
mL) and dried affording a white solid, 137 mg, yield 46%.
Microanalysis: Calc. for C25H22O2N4 ꢀ H2O: C, 70.1; H, 5.65;
occur with a range of different anions. Pyrroles functionalised
with two amidourea groups function as anion receptors in
DMSO but are not selective in their anion complexation
properties.
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N, 13.1. Found: C, 70.1; H, 5.2; N, 13.1%. 1H NMR (DMSO-
d6): d 11.67 (s, 1H, NH), 8.72 (s, 1H, NH), 8.30 (br s, 1H, NH),
8.10 (s, 1H, NH), 7.48 (m, 2H, Ar H), 7.25 (m, 10H, Ar H),
7.04 (m, 2H, Ar H), 2.31 (s, 3H, CH3). 13C NMR (DMSO-d6):
d 180.5, 160.6, 138.9, 134.8, 134.6, 130.7, 129.8, 128.9, 128.2,
127.9, 127.0, 126.6, 125.6, 124.9, 122.4, 118.7, 11.7. MS ES1:
m/z 433.2 (M þ Na1), 843.4 (2M þ Na1), 1253.8 (3M þ Na1).
ESꢂ: m/z 409.3 (M ꢂ H1)ꢂ.
N, 14.85. Found: C, 63.7; H, 4.5; N, 14.9%. 1H NMR
(acetone-d6): d 11.92 (s, 1H, pyrrole NH), 9.60 (s, 1H, NH),
9.02 (s, br, 1H, NH), 8.09 (m, 5H, CH and NH), 7.21 (m, 10H,
CH), 2.37 (s, 3H, CH3). 13C NMR (DMSO-d6): d 161.4, 146.3,
144.6, 135.8, 135.7, 131.7, 131.5, 131.0, 129.7, 128.8, 128.5,
128.0, 126.7, 124.8, 124.5, 123.3, 119.7, 12.0. MS ES1: m/z
471.9 (M1), 535.0 (M þ Na1 þ CH3CN), 965.1 (2M þ Na1).
N,N-Bis((phenylcarbomoyl)hydrazine)-3,4-diphenyl-1H-pyr-
role-2,5-carboxamide 5. 3,4-Diphenyl-1H-pyrrole-2-dicarbo-
hydrazide 11 (75 mg, 0.22 mmol) was dissolved in DMSO
(2.5 mL) and the solution degassed for 10 min. Phenyl
isocyanate (49 mL, 0.45 mmol) was added and the reaction
stirred at room temperature for 24 h. The reaction mixture was
poured onto water and a fine white precipitate was formed.
Gentle heating induced more precipitate to form which was
collected by filtration giving an overall yield of product of
40.62 mg, 32%. X-Ray quality crystals were obtained by slow
evaporation of an acetonitrile solution of the receptor. Micro-
analysis: Calc. for C32H27N7O4 ꢀ H2O: C, 65.0; H, 4.9; N: 16.6.
Found: C, 65.4; H, 4.65; N, 16.55%. 1H NMR (DMSO-d6): d
12.27 (br s, 1H, pyrrole NH), 9.18 (br s, 2H, NH), 8.76 (s, 2H,
NH), 8.19 (s, 2H, NH), 7.45 (m, 4H, Ar H), 7.19 (m, 14H, Ar
H), 6.97 (m, 2H, Ar H). 13C NMR (DMSO-d6): d 160.5, 155.4,
139.4, 133.4, 130.6, 128.6, 127.6, 126.7, 122.8, 122.0, 118.7. MS
ES1: m/z 596.3 (M þ Na1), 1170.7 (2M þ Na1). ESꢂ: m/z
572.4 (M ꢂ H1)ꢂ, 1145.8 (2M ꢂ H1)ꢂ.
2-(5-Methyl-3,4-diphenyl-1H-pyrrole-2-carbonyl)-N-(4-nitro-
phenyl)hydrazinecarboxamide 2. 4-Nitrophenyl isocyanate (115
mg, 0.70 mmol) was dissolved in chloroform (10 mL) and
degassed for 10 min. 5-Methyl-3,4-diphenyl-1H-pyrrole-2-car-
bohydrazide (204 mg, 0.70 mmol) was added and the reaction
stirred at room temperature for 24 h. A precipitate formed,
which was collected by filtration, washed with dichloro-
methane (3 ꢄ 10 mL) and dried. A cream powder was
produced, 280 mg, 87% yield. Microanalysis: Calc. for:
C25H21N5O4: C, 65.9; H, 4.65; N, 15.4. Found: C, 65.5; H,
1
4.6; N, 15.05%. H NMR (DMSO-d6): d 11.62 (s, 1H, NH),
9.43 (br s, 1H, NH), 8.43 (br s, 1H, NH), 8.33 (br s, 1H, NH),
8.17 (d, 2H, Ar H, J = 9.15 Hz), 7.71 (d, 2H, Ar H, J = 9.15
Hz), 7.18 (m, 8H, Ar H), 6.99 (m, 2H, Ar H), 2.27 (s, 3H,
CH3). 13C NMR (DMSO-d6): d 160.9, 146.2, 141.1, 134.8,
134.7, 130.6, 129.8, 129.0, 127.8, 126.8, 126.6, 125.6, 125.0,
122.3, 118.6, 117.7, 11.7. MS ES1: m/z 478.2 (M þ Na1),
933.5 (2M þ Na1). MS ESꢂ: m/z 454.3 (M ꢂ H1)ꢂ, 909.5
(2M ꢂ H1)ꢂ. Crystals suitable for X-ray crystallographic
analysis were obtained by slow evaporation of a methanol
solution of the product.
N,N-Bis((4-nitrophenylcarbomoyl)hydrazine)-3,4-diphenyl-1H-
pyrrole-2,5-carboxamide 6. 3,4-Diphenyl-1H-pyrrole-2-dicar-
bohydrazide 11 (50 mg, 0.15 mmol) was dissolved in DMSO
(2.5 mL) and the solution degassed for 10 min. 4-Nitrophenyl
isocyanate (50 mg, 0.30 mmol) was then added and the
reaction stirred at room temperature for 72 h. The solution
was poured onto water, left to stand and a white precipitate
was formed. This was collected by filtration, washed repeat-
edly with dichloromethane and dried, affording a cream
coloured solid as a DMSO solvate. Yield 75 mg, 74%.
Microanalysis: Calc. for C32H25N9O8 ꢀ 2/3C2H6SO: C, 55.9;
2-(5-Methyl-3,4-diphenyl-1H-pyrrole-2-carbonyl)-N-phenyl-
hydrazinecarbothioamide 3. 5-Methyl-3,4-diphenyl-1H-pyr-
role-2 carbohydrazide (200 mg, 0.686 mmol), was added to a
degassed solution of phenyl isothiocyanate (82 mL, 0.69 mmol)
in chloroform (10 mL). The reaction was stirred at room
temperature for 72 h after which time a white precipitate
had formed. This was collected by filtration, washed with
dichloromethane and dried to produce 214 mg of product as
1
a
white powder, 73% yield. Microanalysis: Calc. for:
H, 4.1; N, 17.6. Found: C, 56.1; H, 4.0; N, 17.4%. H NMR
C25H22N4OS: C, 70.4; H, 5.2; N, 13.1. Found: C, 70.6; H,
5.3; N, 13.05%. 1H NMR (DMSO-d6): d 11.60 (s, 1H, pyrrole
NH), 9.62 (br s, 1H, NH), 9.52 (br s, 1H, NH), 8.86 (br s, 1H,
NH), 7.46 (d, 2H, CH, J = 7.92 Hz), 7.33 (m, 2H, Ar H), 7.19
(m, 9H, Ar H), 6.97 (d, 2H, Ar H, J = 6.78 Hz), 2.26 (s, 3H,
CH3). 13C NMR (DMSO-d6): d 180.5, 160.6, 138.9, 134.8,
134.6, 130.7, 129.8, 128.9, 128.2, 127.9, 127.0, 126.6, 125.6,
124.9, 122.4, 118.7, 11.7. MS ES1: m/z 449.1 (M þ Na1),
875.3 (2M þ Na1).
(DMSO-d6): d 12.32 (br s, 1H, pyrrole NH), 9.57 (s, 2H, NH),
9.35 (br s, 2H, NH), 8.64 (s, 2H, NH), 8.23 (d, 4H, Ar H, J =
9.15 Hz), 7.77 (d, 4H, Ar H, J = 9.15 Hz), 7.22 (m, 10H, Ar
H). 13C NMR (DMSO-d6): d 160.4, 154.8, 146.2, 141.2, 133.3,
130.6, 127.8, 127.6, 126.7, 125.0, 122.8, 117.8. MS ES1:
m/z 686.3 (M þ Na1), 1349.9 (2M þ Na1). ESꢂ: m/z 662.3
(M ꢂ H), 1325.9 (2M ꢂ H1)ꢂ.
N,N-Bis((3,5-dinitrophenylcarbomoyl)hydrazine)-3,4-diphen-
yl-1H-pyrrole-2,5-carboxamide 7. DMSO (2.5 mL) was
degassed for 10 min and 3,4-diphenyl-1H-pyrrole-2-dicarbo-
hydrazide 11 (69 mg, 0.21 mmol) and 3,5-dinitrophenyl iso-
cyanate (86 mg, 0.41 mmol) were added. The solution, which
initially turned an orange colour, was stirred at room tem-
perature for 24 h. The reaction was poured onto water and a
yellow precipitate formed. This was collected by filtration,
affording 105 mg of the product as a yellow powder, 65%
yield. Microanalysis: Calc. for C32H23N11O12 ꢀ 3/2H2O: C,
2-(5-Methyl-3,4-diphenyl-1H-pyrrole-2-carbonyl)-N-(4-nitro-
phenyl)hydrazinecarbothioamide 4. 5-Methyl-3,4-diphenyl-1H-
pyrrole-2-carbohydrazide (400 mg, 1.37 mmol) was added to a
degassed solution of 4-nitrophenylisothiocyanate (248 mg,
1.38 mmol) in chloroform (15 mL). The reaction was stirred
at room temperature for 24 h during which time a yellow
precipitate formed. The solution was filtered and the precipi-
tate washed with dichloromethane (3 ꢄ 10 ml) and dried in
vacuo affording 550 mg of product as a yellow solid, 85%
yield. Microanalysis: Calc. for: C25H21N5O3S: C, 63.7; H, 4.5;
1
49.2; H, 3.4; N, 19.7. Found: C, 49.3; H, 3.1; N, 19.3%. H
NMR (DMSO-d6): d 12.26 (br s, 1H, pyrrole NH), 9.80 (s, 2H,
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1024 | New J. Chem., 2006, 30, 1019–1025

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NH), 9.32 (br s, 2H, NH), 8.84 (s, 4H, ArH), 8.84 (br s, 2H,
NH), 8.42 (s, 2H, ArH), 7.14 (m, 10H, Ar H). 13C NMR
(DMSO-d6): d 160.36, 135.31, 148.21, 142.12, 133.28, 130.60,
127.91, 127.61, 126.75, 122.85, 117.84, 110.88. MS ES1:
m/z 776.2 (M þ Na1). ESꢂ: m/z 375.8 1/2(M ꢂ 2H1), 752.3
(M ꢂ H1)ꢂ.
Acknowledgements
PAG would like to thank the Royal Society for a University
Research Fellowship and RQ would like to thank the Spanish
Ministerio de Educacion y Ciencia for a Postdoctoral Grant.
´
The authors thank the EPSRC and Mike Hursthouse for
access to the crystallographic facilities at the University of
Southampton and W. Clegg at the EPSRC single-crystal
synchrotron service at Daresbury.
Crystallography
Data for 2, 5 and 9 were collected on a BrukerNonius
KappaCCD diffractometer mounted at the window of a Mo
rotating anode. Data for the tetrabutylammonium salt of
(4 ꢂ H1)ꢂ were collected on a Bruker SMART APEX2
CCD diffractometer at Daresbury SRS station 9.8 using a
wavelength of 0.6814.14
References
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Crystal data for 9. C18H17N3O, Mr = 291.35, T = 120(2) K,
monoclinic, space group P21/n, a = 10.990(4), b = 18.366(9),
c = 15.123(4) A, V = 3033(2) A3, Dc = 1.276 g cm ꢂ3, m =
0.081 mmꢂ1, Z = 8 (2 molecules in the asymmetric unit),
reflections collected: 27627, independent reflections: 6610 (Rint
= 0.1582), final R indices [I > 2sI]: R1 = 0.0685, wR2 =
0.1249, R indices (all data): R1 = 0.2330. wR2 = 0.1765.
Crystal data for 2. C25H21N5O4, Mr = 455.47, T = 120(2)
K, monoclinic, space group P21/c, a = 18.0210(4), b =
8.0777(2), c = 16.7769(4) A, b = 115.5230(10)1, V =
2203.86(9) A3, Dc = 1.373 g cm ꢂ3, m = 0.096 mmꢂ1, Z = 4,
reflections collected: 20202, independent reflections: 5054
(Rint = 0.0486), final R indices [I > 2sI]: R1 = 0.0548, wR2
= 0.1218, R indices (all data): R1 = 0.0834. wR2 = 0.1352.
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Crystal data for 5. C32H27N7O4, Mr = 573.61, T = 120(2)
K, monoclinic, space group C2/c, a = 31.1616(11), b =
10.9342(4), c = 8.3276(3) A, b = 104.131(2)1, V =
2751.58(1) A3, Dc = 1.373 g cm ꢂ3, m = 0.096 mmꢂ1, Z = 4,
reflections collected: 18483, independent reflections: 3160
(Rint = 0.0560), final R indices [I > 2sI]: R1 = 0.0481, wR2
= 0.1073, R indices (all data): R1 = 0.0695. wR2 = 0.1168.
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C41H56N6O3S, Mr = 712.98, T = 120(2) K, monoclinic, space
group P2/c, a = 22.9059(19), b = 8.5806(7), c = 40.738(3) A,
b = 93.308(2)1, V = 7993(11) A3, Dc = 1.185 g cm ꢂ3, m =
0.125 mmꢂ1, Z = 8, reflections collected: 43492, independent
reflections: 9695 (Rint = 0.0869), final R indices [I > 2sI]:
R1 = 0.0901, wR2 = 0.2368, R indices (all data): R1 =
0.1344. wR2 = 0.2735.
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For crystallographic data in CIF or other electronic format
see DOI: 10.1039/b603223k
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