1-Phenyl-1H-pyrrole-2,5-dicarboxylic acid derivatives as versatile hydrogen-bonding motifs for the formation of one-, two- and three-dimensional networks in the solid state

Article abstract of DOI:10.1039/a803966f

A series of 1-phenyl-1H-pyrrole-2,5-dicarboxylic acid derivatives were prepared and their solid state structures were investigated. Small structural changes in the monomeric subunit can lead to the formation of one-dimensional linear ribbons, two-dimensional sheets and three-dimensional networks. In each case a consistent feature of the solid state structures is the formation of bidentate hydrogen bonded contacts between the 2,5-carboxylic acid groups on adjacent pyrrole subunits. The exact nature of the crystal packing is strongly influenced by the substitution on the phenyl ring.

Full text of DOI:10.1039/a803966f

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1-Phenyl-1H-pyrrole-2,5-dicarboxylic acid derivatives as versatile
hydrogen-bonding motifs for the formation of one-, two- and three-
dimensional networks in the solid state†
Qing Lin,‡ Steven J. Geib and Andrew D. Hamilton*,‡
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
A series of 1-phenyl-1H-pyrrole-2,5-dicarboxylic acid derivatives were prepared and their solid state
structures were investigated. Small structural changes in the monomeric subunit can lead to the formation
of one-dimensional linear ribbons, two-dimensional sheets and three-dimensional networks. In each case
a consistent feature of the solid state structures is the formation of bidentate hydrogen bonded contacts
between the 2,5-carboxylic acid groups on adjacent pyrrole subunits. The exact nature of the crystal
packing is strongly influenced by the substitution on the phenyl ring.
Introduction
The design of molecular subunits that self-assemble into well-
defined structures in the solid state remains an area of intense
interest.1 Particular emphasis has been placed on the search for
components that result in the ordered formation of one-,2 two-3
or three-dimensional4 arrangements (Fig. 1). Hydrogen bonds,
because of their strength, directionality and selectivity, have
attracted most attention among efforts aimed at controlling
solid state structures. Many hydrogen-bonding motifs that can
direct the formation of predictable and ordered solid state
structures have recently been reported. These have included the
linear aggregation of diaryl ureas,2a the association of mela-
mine and barbituric acid derivatives into hydrogen bonded
tapes or rosettes,2b,c the formation of porous three-dimensional
networks by pyridone and 2,4-diaminotriazine derivatives,4b,c
and the design of functional networks of anthracene-
bisresorcinal derivatives.3d
Our approach to this problem has centered on the hydrogen
Fig. 1 One-, two- and three-dimensional arrangements of subunits
bonding properties of carboxylic acids, both with comple-
mentary acylaminopyridine derivatives5 and with themselves.6
In particular, we have been inspired by the solid state properties
of trimesic acid. This remarkable molecule takes up a structure
in the crystal in which all carboxylic acid groups are satisfied by
bidentate hydrogen bonding to three neighboring molecules.7
The result is a two-dimensional sheet structure in which six
trimesic acid molecules define a cavity 14 Å in diameter. With
simple trimesic acid these pores are filled by three perpendicular
hydrogen bonded sheets in a triply concatenated arrangement.8
Addition of certain alkane cosolvents9 or substitution on the
trimesic acid10 can prevent concatenation and lead to the
formation of planar sheet aggregates.
In an effort to isolate the essential ribbon and ring motifs
seen in the structure of trimesic acid, we have investigated the
solid state behavior of isophthalic acid derivatives and found
that the nature of the aggregate depends critically on the sub-
stituent in the 5-position. In the case of 5-unsubstituted11 and
5-methoxyisophthalic acid12 a linear ribbon arrangement is
formed (Fig. 2A). When certain long chain substituents (e.g.
decyloxy- or octyloxy-) are present in the 5-position, then cyclic
hexameric aggregates result as in Fig. 2B.6a In both cases the
120Њ angle between the hydrogen bonding groups dictates the
overall shape of the aggregate, whether the ribbon angle in
Fig. 2A or the hexameric stoichiometry in Fig. 2B.
We were interested in determining the scope of these aro-
matic bis- and tris-carboxylic acids for controlling the form-
ation of cyclic, one-, two- and three-dimensional structures
in the solid state. One simple modification would be to vary
the relative angle between the two hydrogen bonding groups.
For example, with readily available N-phenylpyrrole-2,5-
dicarboxylic acid derivatives the angle between the two carb-
oxylic acid groups is approximately 135Њ. This should lead to
more extended ribbon aggregates with the phenyl substituents
projecting perpendicularly and potentially able to interact with
adjacent strands. With the correct positioning of the strands
this may lead to the formation and stabilization of pores within
the solid (Fig. 2C). In the case of cyclic aggregation, N-
phenylpyrrole-2,5-dicarboxylic acid would be expected (due to
the 135Њ angle) to form a hydrogen bonded octamer in which
the eight phenyl groups project into the central cavity (Fig. 2D).
In this paper we describe the synthesis and solid state structures
of several N-phenylpyrrole-2,5-dicarboxylic acid derivatives
and show that they represent a robust and simple motif for
crystal engineering (Table 1).
† Full crystallographic details, excluding structure factor tables, have
been deposited at the Cambridge Crystallographic Data Centre
(CCDC). For details of the deposition scheme, see ‘Instructions for
Authors’, J. Chem. Soc., Perkin Trans. 2, available via the RSC Web
page (http://www.rsc.org/authors). Any request to the CCDC for this
material should quote the full literature citation and the reference
number 188/141.
Synthesis
A wide variety of substituted N-phenylpyrrole-2,5-dicarboxylic
acid derivatives were available by a three step sequence
‡ Present address: Department of Chemistry, Yale University, New
Haven, CT 06511, USA.
J. Chem. Soc., Perkin Trans. 2, 1998
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Fig. 2 Hydrogen bonding arrangement of (A) isophthalic acid and (B) 5-decyloxyisophthalic acid in the solid state; and possible hydrogen bonded
packing arrangements for N-phenylpyrrole-2,5-dicarboxylic acid in (C) linear and (D) cyclic forms
from ethyl bromopyruvate and the corresponding aniline. Zinc
promoted radical coupling of the bromoester gave 2,5-
dihydroxyhexa-2,4-dienedioic acid diethyl ester (1).13 Paal–
Knorr reaction14 with various aniline derivatives gave the
corresponding diethyl pyrrole-2,5-dicarboxylates which were
then hydrolyzed in basic ethanol to afford the final pyrrole-
dicarboxylic acids (Scheme 1). In this way the parent N-
phenyl- (2), 3,5-dimethylphenyl- (3), 4-carboxyphenyl- (4),
4-biphenyl- (8) and 4-hydroxyphenyl- (9) pyrroledicarboxylic
acid derivatives were prepared. The use of a 4,4Ј-biphenyl-
diamine in the Paal–Knorr reaction allowed the formation of
a bis(pyrrole-2,5-dicarboxylic acid) derivative 6.
Unsubstituted 1-phenyl-1H-pyrrole-2,5-dicarboxylic acid might
be expected to form either cyclic aggregates or extended one-
dimensional ribbons of the type shown in Fig. 2. Diffraction
quality crystals of 2 were grown by diffusing hexane into a THF
¯
solution of the diacid and were triclinic in the P1 space group.
X-Ray analysis showed that the diacid forms ribbon aggregates
in the solid state through carboxylic acid dimer hydrogen bond-
ing interactions (CO ؒ ؒ ؒ OC 2.60–2.61 Å) (Fig. 3A). However,
the ribbon is limited in size to four subunits stabilized by six
hydrogen bonds. These four molecules comprise pairs of
crystallographically independent hydrogen bonded molecules
which are further linked to their centrosymmetrically related
counterparts. Further extension of the strands was interrupted
due to hydrogen bonding of the terminal carboxylic acid
groups to disordered THF molecules. Interestingly, the complex
does not take up an alternating projection of phenyl groups
(as in Fig. 2C) but instead forms two adjacent pairs with the
phenyl groups on the same side. Each pair corresponds to
one quadrant of the octameric aggregate in Fig. 2D. The
origin of this effect can be seen in the side view (Fig. 3B) of
the hydrogen bonded ribbons, where each pair can be seen to
project one phenyl group up and the other down to form
an offset π–π stacking interaction with phenyl groups from
One-dimensional aggregates
1-Phenyl-1H-pyrrole-2,5-dicarboxylic acid (2)
2110
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Table 1 X-Ray structure determination summary
Crystal data
2
3
4
8
9
Empirical formula
Formula weight
2ؒ1/2 THF
263.22
C15H9NO4
267.23
4ؒ2/3 THF
383.37
8ؒTHF
252.93
9ؒTHF
308.24
Temperature/K
Wavelength/Å
Crystal system
Space group
293(2)
293(2)
293(2)
293(2)
293(2)
0.71073
Triclinic
¯
P1
1.54178
Orthorhombic
Pbcn
0.71073
Triclinic
¯
P1
0.71073
Monoclinic
P21/n
0.71073
Monoclinic
P21/n
Unit cell dimensions
a/Å
b/Å
c/Å
α/Њ
β/Њ
6.967(3)
9.831(3)
20.245(6)
87.78(3)
87.74(3)
78.52(3)
1357.1(9)
4
14.529(3)
8.372(2)
19.611(4)
90
90
90
2385.4(8)
8
1.488
0.920
1104
5.695(5)
10.315(7)
16.789(6)
92.28(4)
96.30(6)
91.85(6)
978.8(11)
2
18.616(4)
5.5570(11)
20.558(4)
90
109.11(3)
90
2009.5(7)
4
1.254
14.219(3)
6.0854(12)
18.510(4)
90
90.98(3)
90
1601.4(5)
4
1.279
γ/Њ
Volume/Å3
Z
Density (calcd.)/g cmϪ3
Absorption coefficient/mmϪ1
F(000)
1.288
0.098
544
1.301
0.101
404
0.089
800
0.098
632
Crystal size/mm
0.20 × 0.20 ×
0.30
0.31 × 0.31 ×
0.36
0.24 × 0.24 ×
0.08
0.08 × 0.29 ×
0.36
0.22 × 0.24 ×
0.34
θ range for data
collection/Њ
Limiting indices
2.01 to 24.00
4.51 to 60.06
1.98 to 24.00
1.80 to 22.50
1.79 to 23.99
0 ≤ h ≤ 7,
Ϫ11 ≤ k ≤ 11,
Ϫ23 ≤ l ≤ 23
4646
0 ≤ h ≤ 16,
Ϫ1 ≤ k ≤ 9,
Ϫ22 ≤ l ≤ 0
1779
0 ≤ h ≤ 6,
Ϫ11 ≤ k ≤ 11,
Ϫ19 ≤ l ≤ 19
3431
0 ≤ h ≤ 20,
0 ≤ k ≤ 5,
Ϫ22 ≤ l ≤ 20
2696
0 ≤ h ≤ 16,
0 ≤ k ≤ 6,
Ϫ21 ≤ l ≤ 21
2609
Reflections collected
Independent reflections
4248 (Rint
0.0342)
None
Full-matrix least-
squares on F2
4244, 0, 378
=
1776 (Rint
0.0276)
None
Full-matrix least-
squares on F2
1774, 0, 228
=
3082 (Rint
0.0292)
None
Full-matrix least-
squares on F2
3082, 0, 236
=
2613 (Rint
0.0093)
None
Full-matrix least-
squares on F2
2613, 0, 295
=
2509 (Rint
0.0315)
None
Full-matrix least-
squares on F2
2509, 0, 241
=
Absorption correction
Refinement method
Observed reflections,
restraints, parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
1.057
1.000
1.072
1.020
1.055
R1 = 0.0602,
wR2 = 0.1391
R1 = 0.1187,
wR2 = 0.1829
0.008(2)
R1 = 0.0467,
wR2 = 0.1576
R1 = 0.0676,
wR2 = 0.1772
0.0011(3)
R1 = 0.1376,
wR2 = 0.3665
R1 = 0.2608,
wR2 = 0.4985
0.000(13)
R1 = 0.0602,
wR2 = 0.1315
R1 = 0.1142,
wR2 = 0.1643
0.0007(8)
R1 = 0.0694,
wR2 = 0.1815
R1 = 0.1202,
wR2 = 0.2228
0.004(3)
R indices (all data)
Extinction coefficient
Largest diff. peak and
hole/e ÅϪ3
0.278 and Ϫ0.175
0.232 and Ϫ0.257
0.678 and Ϫ0.240
0.272 and Ϫ0.252
0.516 and Ϫ0.230
Fig. 3 X-ray structure of 2, (A) top view (B) side view. Carboxylic acid
hydrogens were not resolved.
Scheme 1
the adjacent layers (closest phenyl-H ؒ ؒ ؒ phenyl centroid,
3.6 Å).
rhombic crystals in the Pbcn space group. Once again, the biden-
tate carboxylic acid dimer motif was the dominating influence
on the crystal packing (CO ؒ ؒ ؒ OC was 2.62–2.64 Å with θ of
162Њ). However, in this case a continuous one-dimensional rib-
bon was formed with alternating and perpendicular projection
of the phenyl groups (Fig. 4A). Adjacent ribbons are aligned in
such a way as to position the 3,5-dimethylphenyl groups on
each strand close to each other (4H ؒ ؒ ؒ 4H, 2.72 Å). This results
1-(3,5-Dimethylphenyl)-1H-pyrrole-2,5-dicarboxylic acid (3)
The incorporation of substituents onto the phenyl ring might
be expected to disrupt the interlayer packing seen in Fig. 3B
and induce the formation of more extended aggregates. To
test this the 3,5-dimethylphenyl derivative 3 was prepared and
crystallized by the vapor diffusion method to give large ortho-
J. Chem. Soc., Perkin Trans. 2, 1998
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Fig. 5 Top and side views of the pores formed in the crystal structure
of 4, showing a rhombic shape with the size 15.61 × 15.13 Å
¯
the P1 space group. The basic packing motif contains rhombic
shaped cavities (Fig. 5) formed by cross linking the hydrogen
bonded ribbons through benzoic acid dimer motifs with center
inversion symmetry (CO ؒ ؒ ؒ OC, 2.66–2.67 Å, θ = 156Њ). The
primary deviations from the idealized representation in Fig. 2C
occur in the hydrogen bonded ribbons. Normal bidentate carb-
oxylic acid interactions (CO ؒ ؒ ؒ OC, 2.65 Å) alternate with a
slipped positioning of the neighboring pair. This places the
pyrrole-3H 2.44 Å from the corresponding carboxylate car-
bonyl, forming a stabilizing CH ؒ ؒ ؒ O hydrogen bonding
interaction.15
Fig. 4 Packing arrangement of 3, (A) infinite linear strands and (B) a
perpendicular strand penetrating through the interstrand cavity. H–π
interactions are shown
The cavities formed in this structure are 15.61 × 15.13 Å
(pyrrole-N to pyrrole-N) in size and formed from the involve-
ment of six subunit molecules (Fig. 6). Each is filled by dis-
ordered solvent molecules. The hydrogen bonded layers were
packed in a slightly offset arrangement with an interlayer dis-
tance of ca. 4.0 Å. The controlling feature of the layer–layer
interactions appears to be the slipped face-to-face stacking of
the phenyl rings (centroid ؒ ؒ ؒ centroid, 5.6 Å; closest phenyl-
H ؒ ؒ ؒ centroid, 3.8 Å). The result is a series of solvent-filled
channels passing through the structure.
in the formation of an almost rectangular cavity, 17.3 Å in
length and 6.2 Å in width defined by the pyrrole rings of two
and the phenyl rings of four subunits. These large pores were
occupied by similar, perpendicularly oriented ribbons in an
interpenetrating pseudo-catenated manner (Fig. 4B). Edge-to-
face π–π interactions were observed between the phenyl-H
(Hx in Fig. 4B) and phenyl rings of the concatenated strand
with the distance Hx ؒ ؒ ؒ centroid, 3.07 Å.
Three-dimensional networks
Extension of this strategy from two dimensions to three can be
envisaged by building a subunit composed of two pyrrole-2,5-
dicarboxylic acid units arranged in a perpendicular orientation
(as in 5). This should lead to an orthogonal projection of
hydrogen bonded strands to form a three-dimensional network.
For example, two pyrrole-2,5-dicarboxylic acid units linked
through a 2,2Ј-disubstituted biphenyl will show a non-planar
disposition of the carboxylic acid groups. In order to test this
we have prepared the unsubstituted analog, biphenyl-4,4Ј-
bis(pyrrole-2,5-dicarboxylic acid) (6 where X = H), via the
reaction of 4,4Ј-diaminobiphenyl with 2,5-dihydroxyhexa-2,4-
dienedioic acid diethyl ester (1) followed by hydrolysis. While
at this point we have been unable to obtain diffraction
quality crystals of this compound, we have observed an analo-
gous perpendicular disposition of two pyrrole rings in the
crystal structure of 1-(biphenyl-4-yl)-1H-pyrrole-2,5-dicarb-
oxylic acid (8) which replaces the covalent bond (in 6) and
Two-dimensional aggregates
The close positioning of the 3,5-dimethylphenyl units in 3 clear-
ly pointed to a further stabilization of the structure by
incorporating complementary substituents into the phenyl 4-
positions (as in Fig. 2C). For example, the 4-carboxyphenyl
derivative should form, in addition to the parallel ribbons, a
cross linking hydrogen bonding interaction between the two
carboxylic acid 4-substituents. This would lead to a two-
dimensional sheet structure in which large rectangular cavities
would be stabilized by hydrogen bonding along the sides
(through the pyrrole carboxylic acids) and edges (through the
benzoic acids).
1-(4-Carboxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (4)
To test this idea tricarboxylic acid 4 was synthesized and
recrystallized from THF–hexane. The crystals were triclinic in
2112
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Fig. 6 Top view (A) and side view (B) of one layer structure of 4; hydrogen bonds are linked and disordered solvent molecules are seen in the cavities
acid hydrogen bonds (CO ؒ ؒ ؒ OC 2.60 Å, θ = 174Њ), possessing
21 screw symmetry. The two biphenyl groups in the dimer are
projected parallel to each other. Each biphenyl forms a double
edge-to-face stacking interaction (H ؒ ؒ ؒ centroid 2.84–3.21 Å)
with the biphenyl of an adjacent, perpendicularly orientated
hydrogen bonded dimer. Due to the size of the biphenyl groups
the distance between hydrogen bonded dimers in the same
plane increases to 18.6 Å. The additional space is filled by two
ordered THF molecules which form hydrogen bonds (CO ؒ ؒ ؒ O
2.58 Å) to the free carboxylic acid groups from dimers in the
perpendicular plane (not shown in Fig. 7). A second hydrogen
bond to the free carbonyl oxygen is formed from the biphenyl-
4H (H ؒ ؒ ؒ OC 2.41 Å, θ = 136Њ), which also contributes to the
overall stabilization of the three-dimensional structure.
1-(4-Hydroxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (9)
positions the two pyrrole groups at right angles to each other
(as in 7).
1-(Biphenyl-4-yl)-1H-pyrrole-2,5-dicarboxylic acid (8)
Crystals of 8 were grown by vapor diffusion from THF–hexane
and were monoclinic with a P21/n space group. The packing
arrangement (Fig. 7) shows the formation of a dimeric aggre-
gate in the solid state stabilized by two bidentate carboxylic
A closely related structure is formed by hydroxyphenyl deriv-
ative 9. Monoclinic crystals of 9 were grown by the vapor diffu-
J. Chem. Soc., Perkin Trans. 2, 1998
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Fig. 7 Top view (A) and side view (B) of one layer crystal packing16 of 8. The hydrogen bonds are linked and the H–π interactions are shown.
sion method from THF–hexane mixtures in the P21/n space
group. Once again hydrogen bonded dimers were formed with
an O ؒ ؒ ؒ O distance of 2.62 Å (Fig. 8). Furthermore, edge-to-
face interactions between the phenyl rings on perpendicular
dimers (H ؒ ؒ ؒ centroid, 3.09 Å) are seen, leading to a similar
three-dimensional network to that of 8. In this case, however,
the phenyl-OH has taken the place of the biphenyl-4H in Fig. 7
to form a stabilizing hydrogen bond (PhO ؒ ؒ ؒ OC 2.76 Å,
θ = 174Њ) to the pyrrole carboxylic acid not involved in dimer
formation. Interestingly, only one THF molecule is found in
each cavity of the H-bonded network, presumably due to the
decreased pore size compared to 8.
every case ribbons of bidentate carboxylic acid dimers are
formed. However, this work also underlines the problems
associated with trying to predict solid state structures based on
these motifs. Despite the presence of a common 1-arylpyrrole-
2,5-dicarboxylic core, we find that relatively minor variations in
the substitution of the phenyl ring lead to large differences in
the packing arrangements in the crystal. We are presently
investigating further the solid state properties of di- and triacids
of this type by modifying the relative angle between the hydro-
gen bonding groups and the range of hydrophobic substituents.
Experimental
General
Conclusions
1H NMR and 13C NMR spectra were recorded on a Bruker
AM-300 (300 and 75 MHz). NMR chemical shifts are reported
in ppm downfield from internal TMS. J values are given in Hz.
Mass spectra were determined at the Department of Chemistry,
University of Pittsburgh. EI and FAB mass spectra (MS) were
obtained using a Varian MAT CH-5 or VG 7070 mass spectro-
meter under the direction of Dr Kasi V. Somayajula. Melting
points were determined using an Electrothermal capillary melt-
ing point apparatus and are uncorrected.
We have shown that simple 1-phenylpyrrole-2,5-dicarboxylic
acid derivatives form versatile components for the assembly of
solid state structures. In the case of unsubstituted or alkyl-
substituted phenyl derivatives one-dimensional hydrogen
bonded ribbons are formed. Incorporation of
a self-
complementary carboxylic acid group into the 4-position of the
phenyl induces a hydrogen bonded alignment of the pyrrole
diacid ribbons and the formation of two-dimensional sheet
structures with large solvent-filled channels. Three-dimensional
aggregates are formed when the interaction between the phenyl
groups is of an edge-to-face type. This leads to the perpendicu-
lar disposition of the two pyrrole diacids and the formation of a
three-dimensional hydrogen bonded lattice. These results point
to the power of hydrogen bonding interactions in controlling
the solid state structure of carboxylic acid derivatives, since in
2,5-Dihydroxyhexa-2,4-dienedioic acid diethyl ester (1)
Zinc (activated, 3.0 g, 0.046 mol) was suspended in 100 mL
acetone and the suspension was refluxed for several minutes. To
the above solution was added ethyl bromopyruvate (21.07 g,
0.097 mol) and the mixture was refluxed under argon for 45
min. Large amounts of a yellow solid appeared during reflux
2114
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Fig. 8 Top view (A) and side view (B) of one layer crystal packing of 9. The hydrogen bonding and H–π interactions are shown.
and were filtered off. The solid was washed twice with 1  H2SO4
and was recrystallized from methyl ethyl ketone–toluene to give
the first crop of product. The filtrate was poured into 50 mL 1 
H2SO4 and the resulting white precipitate was collected and
recrystallized to give a second crop of product. Two crops were
combined to give the white crystalline compound (1.230 g,
11%): mp 185–190 ЊC; δH(300 MHz, CDCl3) 6.63 (s, 2H), 6.20
(s, 2H), 4.33 (q, J 7.1, 4H), 1.36 (t, J 7.1, 6H); HRMS m/e calcd.
for C10H14O6 230.0790, found 230.0787.
off and dried in vacuo to give light yellow crystals (0.035 g,
76%): mp 140–144 ЊC; δH(300 MHz, DMSO-d6) 12.55 (s, 2H),
7.38 (m, 3H), 7.22 (m, 2H), 6.94 (s, 2H); δC(75 MHz, DMSO-d6)
160.6, 139.3, 129.5, 127.9, 127.9, 127.8, 116.3; HRMS m/e
calcd. for C12H9NO4 231.0532, found 231.0533.
1-(3,5-Dimethylphenyl)-1H-pyrrole-2,5-dicarboxylic acid (3)
Mp 184 ЊC (dec.); δH(300 MHz, DMSO-d6) 11.93 (s, 1H), 7.01
(s, 1H), 6.91 (s, 2H), 6.82 (s, 2H), 2.27 (s, 6H); δC(75 MHz,
DMSO-d6) 160.5, 139.1, 136.8, 129.5, 125.3, 116.2, 21.2;
HRMS m/e calcd. for C14H13NO4 259.0845, found 259.0844.
Typical procedure for the synthesis of 1-phenylpyrrole-2,5-
dicarboxylic acid derivatives.
1-Phenyl-1H-pyrrole-2,5-dicarboxylic acid (2)
1-(4-Carboxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (4)
Mp 238 ЊC (dec.); δH(300 MHz, DMSO-d6) 11.60 (s, 3H), 7.93 (d,
J 8.4, 2H), 7.36 (d, J 8.4, 2H), 7.00; δC(75 MHz, DMSO-d6)
167.0, 160.5, 143.4, 130.2, 129.5, 129.1, 128.2, 116.7; HRMS
m/e calcd. for C13H9NO6 275.0430, found 275.0426.
To a solution of 1 (0.438 g, 1.9 mmol) in 60 mL glacial acetic
acid was added aniline (0.354 g, 3.8 mmol) and the mixture was
refluxed for 20 min under argon. The solvent was evaporated
and the residue was chromatographed on silica gel using
CH2Cl2 as the eluent. The correct fraction was collected and
evaporated in vacuo to give diethyl 1-phenylpyrrole-2,5-
dicarboxylate (0.350 g, 64%): mp 122–123 ЊC; δH(300 MHz,
CDCl3) 7.44 (m, 3H), 7.24 (m, 2H), 7.04 (s, 2H), 4.11 (q, J 7.1,
4H), 1.14 (t, J 7.1, 6H); HRMS m/e calcd. for C16H17NO4
287.1158, found 287.1151.
Diethyl 1-phenylpyrrole-2,5-dicarboxylate (0.057 g, 0.2
mmol) was dissolved in 30 mL absolute ethanol and KOH
(0.195 g, 3.5 mmol) was added. The mixture was refluxed for 5
h. After removal of the solvent, the residue was dried in vacuo.
The solid was then dissolved in 10 mL H2O and the solution
was titrated to pH = 3 with 1  HCl. The precipitate was filtered
1-(Biphenyl-4-yl)-1H-pyrrole-2,5-dicarboxylic acid (8)
Mp 239–243 ЊC; δH(300 MHz, DMSO-d6) 11.81 (s, 2H), 7.72
(m, 4H), 7.70 (m, 2H), 7.40 (m, 1H), 7.31 (m, 2H), 6.97 (s, 2H);
δC(75 MHz, DMSO-d6) 160.6, 146.9, 146.7, 146.4, 146.1, 145.9,
145.5, 139.4, 138.8, 129.6; HRMS m/e calcd. for C18H13NO4
307.0845, found 307.0857.
1-(4-Hydroxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (9)
Mp 243–245 ЊC; δH(300 MHz, DMSO-d6) 11.94 (s, 2H), 9.56
(s, 1H), 6.97 (d, J 8.6, 2H), 6.89 (s, 2H), 6.70 (d, J 8.6, 2H);
δC(75 MHz, DMSO-d6) 159.2, 157.2, 129.1, 128.6, 116.3, 114.5,
J. Chem. Soc., Perkin Trans. 2, 1998
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For recent examples, see a special issue on Molecular Networks, in
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74.4; HRMS m/e calcd. for C12H9NO5 247.0481, found
247.0475.
Biphenyl-4,4Ј-bis(1H-pyrrole-2,5-dicarboxylic acid) (6)
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8 D. J. Duchamp and R. E. Marsh, Acta Crystallogr., Sect. B, 1969,
25, 5.
9 mL conc. HCl (37%) was dissolved in 100 mL absolute etha-
nol in an ice–water bath. N,NЈ-Diphenylhydrazine (1.84 g, 0.01
mol) was added to the above solution under argon and the
mixture was stirred for 2.5 h. The precipitate was filtered off,
washed with water and dried in vacuo to give a light yellow solid
(0.216 g). The organic solvent was evaporated and the solution
was titrated to pH = 12 with 1 NaOH. The white solid was
filtered off and dried in vacuo (0.719 g). Two crops were
combined to give biphenyl-4,4Ј-diamine (0.935 g, 51%): mp
116–118 ЊC; δH(300 MHz, DMSO-d6) 7.19 (d, J 8.4, 4H), 6.57
(d, J 8.4, 4H), 4.99 (s, 4H); HRMS m/e calcd. for C12H12N2
184.1000, found 184,1003.
To a solution of 1 (0.230 g, 1.0 mmol) in 50 mL glacial acetic
acid was added biphenyl-4,4Ј-diamine (0.100 g, 0.5 mmol) and
the mixture was refluxed for 1 h under argon. The solvent was
evaporated and the residue was purified by silica gel chrom-
atography using acetone–CH2Cl2(3:100) as the eluent to give
biphenyl-4,4Ј-bis[2,5-bis(ethoxycarbonyl)-1H-pyrrole] (0.145 g,
51%): mp 214–215 ЊC; δH(300 MHz, CDCl3) 7.71 (d, J 8.5, 4H),
7.32 (d, J 8.3, 4H), 7.07 (s, 4H), 4.13 (q, J 7.1, 8H), 1.15 (t, J 7.1,
12H); HRMS m/e calcd. for C32H32N2O8 572.2159, found
572.2149.
To a solution of biphenyl-4,4Ј-bis[2,5-bis(ethoxycarbonyl)-
1H-pyrrole] (0.125 g, 0.22 mmol) in 40 mL absolute ethanol was
added KOH (0.28 g, 5.0 mmol) and the mixture was refluxed for
5 h. The solvent was evaporated and the residue was dried in
vacuo overnight. The solid was dissolved in 50 mL H2O and the
solution was titrated to pH = 4 with 1  HCl. The precipitate
was filtered off and washed with water several times and dried
in vacuo to give the title compound (0.123 g, 84%): mp 290 ЊC
(dec.); δH(300 MHz, DMSO-d6) 11.81 (s, 4H), 7.77 (d, J 8.4,
4H), 7.34 (d, J 8.4, 4H), 6.98 (s, 4H); ES-MS m/e calcd. for
C24H16N2O8 460.39, found 461.11.
9 F. H. Herbstein, M. Kapon and G. M. Reisner, J. Inclusion Phenom.,
1987, 5, 211.
10 S. V. Kolotuchin, E. E. Fenlon, S. R. Wilson, C. J. Loweth and S. C.
Zimmerman, Angew. Chem., Int. Ed. Engl., 1995, 34, 2654.
11 R. Alcala and S. Martinez-Carrera, Acta Crystallogr., Sect. B,
1972, 28, 1671.
12 J. Yang, S. J. Geib and A. D. Hamilton, unpublished results.
13 R. Kuhn, Ann. Chem., 1949, 564, 32.
14 For Paal–Knorr reaction, see: Pyrroles, Part I, ed. R. A. Joans,
Wiley, New York, 1990, pp. 206–216.
X-Ray structure determination
A Siemens P3 diffractometer controlled via Siemens P3/PC
software was used for the collection of data. A Siemens
SHELXTL package was used for the solutions and refinements
of the X-ray structures.
15 For a recent discussion on CH ؒ ؒ ؒ O hydrogen bonding, see: G. R.
Desiraju, Acc. Chem. Res., 1996, 29, 441.
16 Only one orientation of the outer phenyl rings (disordered in
two 50:50 orientations, the other one is slightly different) is shown.
This type of disorder is very common and is discussed in Crystal
Structure Analysis for Chemists and Biologists, J. P. Glusker, VCH,
New York, 1994, ch. 13.
Acknowledgements
We thank the National Science Foundation (CHE 9213937) for
their financial support of this work.
References
Paper 8/03966F
Received 27th May 1998
Accepted 5th August 1998
1 (a) G. R. Desiraju, Crystal Engineering: The Design of Organic
Solids, Elsevier, Amsterdam, 1989; (b) J. D. Wright, Molecular
2116
J. Chem. Soc., Perkin Trans. 2, 1998