Hydrogen-bonding and C-H...π interactions in ethyl 4-acetyl-5-methyl-3-phenyl-1H-pyrrole-2-carboxylate monohydrate

Article abstract of DOI:10.1107/S0108270102018255

The hydrogen-bonding and C-H···π interactions in ethyl 4-acetyl-5-methyl-3-phenyl-1H-pyrrole-2-carboxylate monohydrate were studied. In the above compound three strong hydrogen bonds link substituted pyrrole and water molecules to form infinite chains in

Full text of DOI:10.1107/S0108270102018255

organic compounds
Acta Crystallographica Section C
Crystal Structure
was undertaken to clarify the conformation of the molecule.
The results are presented here.
Communications
ISSN 0108-2701
Hydrogen-bonding and CÐHÁ Á Áp
interactions in ethyl 4-acetyl-
5-methyl-3-phenyl-1H-pyrrole-
2-carboxylate monohydrate
The weighted average of the absolute torsion angles of the
pyrrole ring of (I) is 0.42 (6)ꢀ, indicating that the heterocyclic
ring is almost perfectly planar. The internal ring angles range
from 106.38 (10) to 110.47 (10)ꢀ, showing a small distortion
from C2v symmetry. The acetyl group at C4 and the ethoxy-
carbonyl group at C2 in¯uence the ꢀ-electron distribution
within the pyrrole ring, which results in a shortening of the
C4ÐC15 and C2ÐC6 bond distances with respect to the usual
a
a
Â
Â
Manuela Ramos Silva, * Ana Matos Beja, Jose Antonio
a
b
b
Â
PaixÄao, Abõlio J. F. N. Sobral, Susana H. Lopes and
A. M. d'A. Rocha Gonsalvesb
a
Â
Ã
CEMDRX, Departamento de Fõsica, Faculdade de Ciencias e Tecnologia,
Universidade de Coimbra, P-3004-516 Coimbra, Portugal, and bDepartamento
value found for Csp2ÐCaryl bonds [1.483 (15) A; Allen et al.,
Ê
Ã
Â
de Quõmica, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra,
1987]. The same effect accounts for the asymmetric nature of
the two NÐC bonds within the heterocyclic ring [usual
Ê
average value 1.372 (16) A; Allen et al., 1987].
P-3004-535 Coimbra, Portugal
Correspondence e-mail: manuela@pollux.fis.uc.pt
Atoms C15, C17 and C6 are approximately coplanar with
the pyrrole ring and deviate by only 0.003 (2), 0.044 (2)
Ê
and 0.046 (2) A, respectively, from the least-squares plane of
Received 27 September 2002
Accepted 4 October 2002
Online 31 October 2002
the pyrrole ring. On the other hand, atoms O1, O2 and O3 are
tilted out of the ring plane by 0.219 (2), 0.137 (3) and
In the title compound, C16H17NO3ÁH2O, the pyrrole ring is
distorted slightly from ideal C2v symmetry. Three strong
hydrogen bonds link the substituted pyrrole and water
molecules to form in®nite chains, in which the hydrogen
bonds form rings and chain patterns. Two intermolecular CÐ
HÁ Á Áꢀ interactions maintain the internal cohesion between
these chains. The molecular structure differs slightly from that
of the isolated molecule calculated by ab initio quantum-
mechanical calculations. In the latter model, the non-H
substituent atoms share the plane of the pyrrole ring, except
for the phenyl group, which lies almost perpendicular to this
plane.
Ê
0.265 (3) A, respectively. The angle between the least-squares
planes of the phenyl and pyrrole rings is 76.93 (5)ꢀ. The
ethoxycarbonyl group adopts an anti conformation with
respect to the heterocyclic N atom. In this group, the C6Ð
O2ÐC7ÐC8 torsion angle is 161.41 (15)ꢀ, which shows that
atom C8 does not share the plane de®ned by atoms O1, C6, O2
and C7. The acetyl group is oriented so as to minimize the
steric interaction between the C16 and C17 methyl groups.
Three strong hydrogen bonds link the molecules of (I)
together into in®nite one-dimensional chains and exhaust all
donor sites of the substituted pyrrole and water molecules
Comment
Pyrroles are important compounds in many ®elds of research,
from materials to pharmaceutical sciences. They are precur-
sors of porphyrins and related macrocycles (Baltazzi &
Krimen, 1963; Chadwick, 1990), and are also suitable for the
assembly of Langmuir±Blodgett ®lms when substituted with
amphiphilic chains (Ramos Silva et al., 2002a). In the phar-
maceutical sciences, 2-(alkoxycarbonyl)pyrrole derivatives
have attracted much interest, as they display a broad spectrum
of biological activities, including analgesic, spasmolytic and
even anti-HIV-1 activity (Artico et al., 1996; Gribble, 1996).
Some pyrrole alkaloid derivatives show anticancer properties
È
because of their DNA-cleaving capabilities (Furstner et al.,
2002). Following our work on the synthesis and structure
determination of several substituted pyrroles (PaixaÄo et al.,
2002; Ramos Silva et al., 2000, 2002a,b), which are intended for
incorporation at the ꢁ-pyrrole ring of porphyrins, the title
compound, (I), was synthesized and an X-ray diffraction study
Figure 1
A view of the molecule of (I). Displacement ellipsoids are drawn at the
50% probability level.
Acta Cryst. (2002). C58, o685±o687
DOI: 10.1107/S0108270102018255
# 2002 International Union of Crystallography o685

organic compounds
(Table 2). Looking at the conventional hydrogen-bonding
pattern, one can recognize the formation of chains and rings
which can be characterized using Etter's graph-set analysis
(Bernstein et al., 1995). At the basic binary level are centro-
symmetric rings which can be described by the R44(14) motif
and which involve the pyrrole NÐH atom and one water H
atom as donors, and the water and ethoxycarbonyl O atoms as
acceptors. A larger ring is formed at the binary level when
both of the water H atoms act as donors, thereby involving
four molecules in the sequence water±substituted pyrrole±
water±substituted pyrrole. This pattern has a graph-set motif
of R44(20). Finally, chains with the motif C22(8) are formed by
the N1ÐH1Á Á ÁO4i and O4ÐH42Á Á ÁO3ii hydrogen bonds
[symmetry codes: (i) 1 x, y, 1 z; (ii) x, y, 1 z].
Two CÐHÁ Á Áꢀ intermolecular interactions can also be
observed in (I), thereby exhausting the capacity of the pyrrole
ꢀ electrons to act as acceptors. In one of the interactions,
phenyl atom C10 acts as the donor, while in the other, one of
the methyl H atoms bonded to atom C17 is the donor. The
HÁ Á ÁCg (Cg is the centroid of the pyrrole ring) distances are
program GAMESS (Schmidt et al., 1993). The atomic wave
functions were expanded on a standard 3-21G basis set. The
optimization was conducted starting from the experimental
crystal structure geometry without imposing any symmetry
constraints on the molecule. Each self-consistent ®eld calcu-
3
lation was iterated until a Áꢂ of less than 10 5 bohr was
achieved. The ®nal equilibrium geometry at the minimum
energy had a maximum gradient in the internal coordinates of
1
10 5 Hartree bohr or Hartree rad 1. These results repro-
duce well the observed asymmetry in the pyrrole ring of (I).
However, the minimum energy of the isolated molecule occurs
ꢀ
Ê
2.84 and 2.90 A, and the CÐHÁ Á Áꢀ angles are 147.3 and 150.6 ,
for the two types of bonds, respectively. The angles of
approach of the HÁ Á ÁCg vector to the plane of the aromatic
ring are 76.0 and 80.4ꢀ, respectively, and the perpendicular
projections of the H atoms onto the pyrrole ring plane are 0.69
Figure 3
A view of the unit-cell packing in (I), with the CÐHÁ Á Áꢀ bonding scheme
shown as dashed lines. H atoms not participating in the CÐHÁ Á Áꢀ
interactions have been omitted for clarity.
Ê
and 0.49 A, respectively, from the centroid of the ring. In the
former interaction, the H atom lies above the centre of the
ring, with the CÐH bond pointing towards a pyrrole ring C
atom. This corresponds to a type III interaction, according to
the classi®cation of Malone et al. (1997). The latter interaction
corresponds to a type I interaction, with the classical T-shaped
geometry. It has been recognized that these weak CÐHÁ Á Áꢀ
interactions play an appreciable role in determining the
conformations of organic compounds (Umezawa et al., 1999).
To investigate the effect of these intermolecular interac-
tions on the conformation of the molecule of (I), we have
carried out an optimization of the geometry of the isolated
molecule by ab initio quantum-mechanical molecular orbital
Hartree±Fock (MO-HF) calculations using the computer
for a geometry where the non-H substituent atoms are prac-
tically in the ring plane, except for the phenyl group, which lies
perpendicular to the heterocyclic ring (C2ÐC3ÐC9ÐC14 =
88.9ꢀ; cf. Table 1). The twists observed in the solid state are
therefore probably due to the hydrogen bonding with the
water molecule and to the CÐHÁ Á Áꢀ intermolecular interac-
tions.
Experimental
Ethyl oximinobenzoylacetate was prepared by the dropwise addition
of an acetic acid solution (8 ml) of ethyl benzoylacetate (5 ml,
0.0025 mol) to aqueous sodium nitrite (3.00 g, 0.0044 mol; in 20 ml
water) and then stirring for 72 h at 293 K. A mixture of acetylacetone
(2.50 g, 0.0025 mol), Zn dust (5.00 g, 0.00724 mol) and glacial acetic
acid (35 ml) was placed in a 500 ml round-bottomed ¯ask ®tted with a
re¯ux condenser and a silica guard tube. After the dissolution of all
reactants, the oxime (ethyl oximinobenzoylacetate) was added slowly.
The mixture was stirred and heated under re¯ux for 4 h. The hot
reaction mixture was decanted from the zinc sludge before zinc
acetate or a new compound could crystallize. To promote precipita-
tion of the pyrrole, several volumes of water were added slowly to the
reaction. After a few hours, the product was ®ltered off, washed
thoroughly with water and recrystallized from hot n-hexane.
Compound (I) was obtained in 14% yield (m.p. 326±328 K). Spec-
troscopic analysis, IR (ꢃ, cm 1): 1523 (aromatic CÐC), 1662 (C O),
1
2965 (aromatic CÐH), 3508 (NÐH); H NMR (CDCl3, ꢄ, p.p.m.):
Figure 2
1.00 (t, 3H, CH3±CH2O, J = 7.00 Hz), 1.82 (s, 3H, position 4 COCH3),
2.58 (s, 3H, position 5 CH3), 4.09 (q, 2H, OCH2±CH3, J = 7.25 Hz),
7.37 (m, 5H, position 3 aromatic H), 10.0 (sl, 1H, NH).
A view of the unit-cell packing in (I), with the hydrogen-bonding scheme
shown as dashed lines. H atoms not participating in the hydrogen bonding
have been omitted for clarity.
ꢁ
o686 Manuela Ramos Silva et al.
C16H17NO3ÁH2O
Acta Cryst. (2002). C58, o685±o687

organic compounds
Ê
Ê
Crystal data
the range 0.93±0.97 A and NÐH distances of 0.86 A, and constrained
to ride on their parent atoms with Uiso(H) = 1.2Ueq(parent atom),
with the exception of the H atoms of the water molecule, the posi-
tions and atomic displacement parameters of which were re®ned
freely. Examination of the crystal structure with PLATON (Spek,
2002) showed that there are no solvent-accessible voids in the crystal
lattice.
3
C16H17NO3ÁH2O
Dx = 1.244 Mg m
Cu Kꢅ radiation
Mr = 289.32
Monoclinic, P21=c
Cell parameters from 25
re¯ections
Ê
a = 8.9102 (4) A
ꢆ = 18.9±35.4ꢀ
ꢇ = 0.74 mm
T = 293 (2) K
Ê
b = 17.1911 (10) A
1
Ê
c = 10.4861 (10) A
ꢁ = 105.859 (8)ꢀ
V = 1545.08 (19) A
Z = 4
3
Ê
Prism, yellow
0.46 Â 0.27 Â 0.18 mm
Data collection: CAD-4 Software (Enraf±Nonius, 1989); cell
re®nement: CAD-4 Software; data reduction: HELENA (Spek, 1997);
program(s) used to solve structure: SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: ORTEPII (Johnson, 1976); software used to
prepare material for publication: SHELXL97.
Data collection
Enraf±Nonius CAD-4
diffractometer
!/2ꢆ scans
Absorption correction: scan
(North et al., 1968)
Tmin = 0.853, Tmax = 0.876
6215 measured re¯ections
3048 independent re¯ections
2726 re¯ections with I > 2ꢈ(I)
Rint = 0.035
max = 72.5ꢀ
ꢆ
h = 11 ! 11
k = 0 ! 21
l = 12 ! 12
Ã
Financial assistance from the FundacËaÄo para a Ciencia e a
Tecnologia (Sapiens POCTI/QUI/42536) and Chymiotechnon,
Portugal, is acknowledged.
3 standard re¯ections
frequency: 180 min
intensity decay: 2%
Re®nement
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: LN1152). Services for accessing these data are
described at the back of the journal.
Re®nement on F2
R[F2 > 2ꢈ(F2)] = 0.040
wR(F2) = 0.110
S = 1.05
3048 re¯ections
202 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
w = 1/[ꢈ2(Fo2) + (0.0573P)2
+ 0.2709P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢈ)max < 0.001
3
Ê
Áꢂmax = 0.19 e A
3
Ê
0.20 e A
Áꢂmin
=
References
Extinction correction: SHELXL97
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ꢀ
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1.3255 (15)
1.3371 (16)
N1ÐC2
C2ÐC6
C4ÐC15
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È
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C5ÐN1ÐC2
N1ÐC2ÐC3
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110.47 (10)
108.09 (10)
118.96 (11)
C2ÐC3ÐC4
C5ÐC4ÐC3
106.38 (10)
107.02 (11)
C3ÐC4ÐC5ÐN1
C5ÐC4ÐC15ÐO3
C3ÐC4ÐC15ÐO3
C5ÐC4ÐC15ÐC16
C3ÐC4ÐC15ÐC16
0.22 (13)
15.1 (2)
165.61 (14)
162.52 (14)
16.8 (2)
C2ÐC3ÐC9ÐC10
C4ÐC3ÐC9ÐC10
C2ÐC3ÐC9ÐC14
C6ÐO2ÐC7ÐC8
78.88 (16)
104.56 (15)
101.68 (14)
161.41 (15)
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Table 2
Hydrogen-bonding geometry (A, ).
ꢀ
Ê
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& Rocha Gonsalves, A. M. d'A. (2002a). Acta Cryst. C58, o572±o574.
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DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1Á Á ÁO4i
O4ÐH42Á Á ÁO3ii
O4ÐH41Á Á ÁO1iii
0.86
0.92 (2)
0.87 (2)
2.10
1.92 (2)
2.06 (2)
2.8966 (14)
2.8386 (16)
2.9077 (16)
155
173 (2)
167 (2)
Symmetry codes: (i) 1 x; y; 1 z; (ii) x; y; 1 z; (iii) x 1; y; z.
È
Gottingen, Germany.
The methyl H atoms were constrained to an ideal geometry, with
Ê
CÐH distances of 0.96 A and Uiso(H) = 1.5Ueq(C), but were allowed
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Tetrahedron, 55, 10047±10056.
to rotate freely about the CÐC bonds. All remaining H atoms were
placed in geometrically idealized positions, with CÐH distances in
ꢁ
Acta Cryst. (2002). C58, o685±o687
Manuela Ramos Silva et al. C16H17NO3ÁH2O o687