A new monoclinic polymorph of methyl p-aminobenzoate

Article abstract of DOI:10.1107/S0108270103027422

The crystal structure of methyl-p-aminobenzoate (MAB) was analyzed. A P2₁/c polymorph of MAB was found and the intra and intermolecular geometries were compared with those of the previously known C2/c structure. It was found that in the C2/c polymorph, two hydrogen bonds formed infinite chains along the [110] and [110] directions. The molecule was also found to be almost flat, and the largest deviations from the least square plane through the aromatic rings were 0.300 (3) and 0.180 (2) A for the atoms C8 and O2 respectively.

Full text of DOI:10.1107/S0108270103027422

organic compounds
Ê
through the aromatic ring are 0.300 (3) and 0.180 (2) A for
Acta Crystallographica Section C
Crystal Structure
Communications
atoms C8 and O2, respectively. The main geometric para-
meters are given in Table 1. As expected, the observed
geometry of the molecule agrees well with the geometries of
similar derivatives (e.g. Elbasyouny et al., 1983; Peters et al.,
1998; Lynch & McClenaghan, 2002).
ISSN 0108-2701
A new monoclinic polymorph of
methyl p-aminobenzoate
Antonio C. Doriguetto,a* Carlos H. T. de Paula Silva,a
Daniela G. Rando,b Elizabeth I. Ferreirab and Javier
Ellenaa
a
Â
Instituto de Fõsica de Sao Carlos, Universidade de Sao Paulo, Caixa Postal 369, CEP
Ä
Ä
b
Â
13560-970, Sao Carlos, SP, Brazil, and Departamento de Farmacia, Faculdade de
Ä
Ã
Ã
Ciencias Farmaceuticas, Universidade de Sao Paulo, Av. Prof. Lineu Prestes 580,
Ä
Bloco 13, CEP 05508-900, Sao Paulo, SP, Brazil
Ä
Correspondence e-mail: dorigue@if.sc.usp.br
Received 2 October 2003
Accepted 28 November 2003
Online 13 December 2003
Single crystals of methyl-p-aminobenzoate (MAB), C8H9NO2,
were obtained during the synthesis of 4-amino-N0-(5-nitro-2-
thienylmethylene)benzohydrazide. A P21/c polymorph [a =
Ê
Ê
Ê
8.5969 (4) A, b = 5.6053 (2) A, c = 15.5397 (7) A and ꢀ =
96.172 (2)ꢀ] of MAB was found and the intra- and inter-
molecular geometries were compared with those of the
Ê
Longarte et al. (1999) calculated the MAB ground-state
structure and vibrational frequencies using the GAUSSIAN98
package (Frisch et al., 1998) and concluded that a sensible
molecular±electronic description requires diffuse functions
and polarizabilities in the theoretical calculations. In this
way, they found that the NH2 H atoms form a 22.38ꢀ angle
with the molecular plane, as expected (Kydd & Krueger,
1977; Hollas et al., 1983). In order to check the conclusion of
Longarte et al., the positional parameters of the two H atoms
connected to the N atoms were not constrained during the
re®nements performed here. Our experimental data show that
the dihedral angles between the NH2 groups and the aromatic
ring plane are 25 (1) and 14 (1)ꢀ for the H11ÐN1ÐC1ÐC6
and H12ÐN1ÐC1ÐC2 angles, respectively, thus con®rming
the results of Kydd & Krueger (1977) and Hollas et al. (1983).
Comparison of the Longarte et al. (1999) 6-31+G* model with
previously known C2/c structure [a = 16.242 (2) A, b =
8.113 (2) A, c = 12.724 (2) A and ꢀ = 69.17 (1)ꢀ; Xianti
(1983). Jiegou Huaxue, 2, 219±221].
Ê
Ê
Comment
Tuberculosis (TB) has re-emerged as one of the leading causes
of death, accounting for nearly three million deaths annually
(Bloom & Murray, 1992). Although there are treatment
regimens based on long-term and combined chemotherapy,
the emergence of AIDS and the decline of socio-economic
standards contribute to the disease's resurgence in indus-
trialized countries and to the emergence of multidrug-resistant
strains of Mycobacterium tuberculosis (Barnes et al., 1991).
Therefore, the search for new therapeutics against tubercu-
losis is of utmost importance.
This work reports the structure of methyl-p-aminobenzoate
(MAB), (I), an intermediate used to obtain 4-amino-N0-(5-
nitro-2-thienylmethylene)benzohydrazide, (II) (see scheme),
which has been shown to be active against tuberculosis
(Rando et al., 2002). Since MAB is part of the synthesized
benzohydrazide, a knowledge of the crystal-packing forces in
(I), in addition to its molecular geometry, could be important
in explaining some aspects of the activity of (II).
The crystal structure of (I) was determined in space group
P21/c. The molecule is almost ¯at; considering the non-H
atoms, the largest deviations from the least-squares plane
Figure 1
A view of (I), with displacement ellipsoids shown at the 50% probability
level.
Acta Cryst. (2004). C60, o69±o71
DOI: 10.1107/S0108270103027422
# 2004 International Union of Crystallography o69

organic compounds
Crystal data
3
C8H9NO2
Mr = 151.16
Dx = 1.349 Mg m
Mo Kꢁ radiation
Monoclinic, P21=c
Cell parameters from 13 722
re¯ections
Ê
a = 8.5969 (4) A
ꢂ = 3.4±27.5ꢀ
Ê
b = 5.6053 (2) A
1
Ê
c = 15.5397 (7) A
ꢃ = 0.10 mm
T = 120 (2) K
ꢀ = 96.172 (2)ꢀ
V = 744.49 (6) A
Z = 4
3
Ê
Needle, yellow
0.17 Â 0.06 Â 0.02 mm
Data collection
Nonius KappaCCD diffractometer
' scans, and ! scans with ꢄ offsets
15 706 measured re¯ections
1313 independent re¯ections
1040 re¯ections with I > 2ꢅ(I)
Rint = 0.070
ꢂmax = 25ꢀ
h = 10 ! 10
k = 6 ! 6
l = 18 ! 18
Re®nement
Re®nement on F2
R(F) = 0.040
w = 1/[ꢅ2(F2o) + (0.0631P)2
+ 0.0853P]
wR(F2) = 0.104
S = 1.05
where P = (F2o + 2Fc2)/3
(Á/ꢅ)max < 0.001
3
Ê
Figure 2
The crystal packing of the P21/c polymorph of (I). Hydrogen bonds are
1313 re¯ections
108 parameters
Áꢆmax = 0.17 e A
3
Ê
0.26 e A
Áꢆmin
=
1
2
H atoms treated by a mixture of
independent and constrained
re®nement
indicated by dashed lines. [Symmetry codes: (i) 1 + x, y, z; (ii) 2 x, y
,
1
2
z; (iii) 2 x, y + 12, 21 z.]
our experimental MAB P21/c polymorphs by the Kabsch
(1976) method showed the polymorphs to be similar, with an
Ê
r.m.s. deviation between analogous atoms of 0.064 A.
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
The MAB structure was previously determined by X-ray
diffraction (Xianti, 1983) as belonging to space group C2/c
C1ÐN1
C4ÐC7
C7ÐO1
1.385 (2)
1.472 (2)
1.216 (2)
C7ÐO2
C8ÐO2
1.341 (2)
1.441 (2)
Ê
Ê
Ê
[a = 16.242 (2) A, b = 8.113 (2) A, c = 12.724 (2) A and
ꢀ = 69.17 (1)ꢀ], while it is determined here as a new P21/c
monoclinic polymorph. Comparison of these polymorphs
using the Kabsch method (Kabsch, 1976) showed them to be
very similar, with an r.m.s. deviation between analogous atoms
N1ÐC1ÐC2
N1ÐC1ÐC6
C3ÐC4ÐC7
C5ÐC4ÐC7
120.9 (1)
120.5 (1)
119.0 (1)
122.3 (1)
O1ÐC7ÐO2
O1ÐC7ÐC4
O2ÐC7ÐC4
C7ÐO2ÐC8
122.2 (1)
125.1 (1)
112.7 (1)
115.3 (1)
Ê
of 0.043 A. Therefore, the two polymorphs have the same
molecular shape. The P21/c polymorph exhibits two indepen-
dent intermolecular hydrogen bonds (Fig. 2 and Table 2). The
packing is very similar to that observed in the monoclinic form
of ethyl 4-aminobenzoate (benzocaine) determined by Lynch
& McClenaghan (2002), with the molecules arranged head-to-
tail in linear ribbon arrays via NÐHÁ Á ÁO C associations
along the [100] direction. These ribbons form a herring-bone
structure, connected via NÐHÁ Á ÁN associations along the
[010] direction. Therefore, the ribbons are themselves
hydrogen bonded, forming an in®nite two-dimensional
network parallel to the (001) plane. In the C2/c polymorph,
two independent hydrogen bonds form in®nite chains along
the [110] and [110] directions; however, both take place via
NÐHÁ Á ÁO C associations, with NÁ Á ÁO separations of about
Table 2
Hydrogen-bonding geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH11Á Á ÁO1i
0.88 (2)
0.91 (2)
2.08 (2)
2.37 (2)
2.959 (2)
3.256 (2)
175.1 (16)
164.4 (16)
N1ÐH12Á Á ÁN1ii
1
2
1
2
Symmetry codes: (i) 1 ‡ x; y; z; (ii) 2 x; y
;
z.
H atoms of the phenyl and methyl groups were positioned
stereochemically and were re®ned with ®xed individual displacement
parameters [Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethoxy)] using a riding
Ê
model, with aromatic CÐH distances of 0.95 A and methyl CÐH
Ê
distances of 0.98 A. The two amine H atoms were located by differ-
ence Fourier synthesis and were set as isotropic.
Ê
3 A.
Data collection: COLLECT (Nonius, 1998); cell re®nement: HKL
SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL
Experimental
DENZO (Otwinowski
& Minor, 1997) and SCALEPACK;
MAB was obtained from benzoic acid (30 mmol) under re¯ux with
methanol (60 mmol) and concentrated sulfuric acid (0.06 ml) for 4 h.
The reaction pH was then adjusted to ꢂ7 with a solution of 10%
NaOH. The resulting yellow crystals were ®ltered off, washed with
small amounts of cold water, and dried under reduced pressure and
phosphorus pentoxide.
program(s) used to solve structure: SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); soft-
ware used to prepare material for publication: WinGX (Farrugia,
1999).
ꢁ
o70 Antonio C. Doriguetto et al.
C8H9NO2
Acta Cryst. (2004). C60, o69±o71

organic compounds
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A.,
Cheeseman, J. R., Zakrzewski, V. G., Montgomery, J. A. Jr, Stratmann,
R. E., Burant, J. C., Dapprich, S., Millam, J. M., Daniels, A. D., Kudin, K. N.,
Strain, M. C. et al. (1998). GAUSSIAN98. Revision A.3. Gaussian Inc.,
Pittsburgh, PA, USA.
Hollas, J. M., Howson, M. R., Ridley, T. & Halonen, L. (1983). Chem. Phys.
Lett. 98, 611±614.
Kabsch, W. (1976). Acta Cryst. A32, 922±923.
This work was supported by Brazilian agencies FAPESP,
CNPq and CAPES. ACD and CHTPS thank FAPESP for
postdoctoral fellowships. DGR tranks CAPES for a PhD
fellowship.
Kydd, R. A. & Krueger, P. J. (1977). Chem. Phys. Lett. 49, 539±543.
Â
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: TY1003). Services for accessing these data are
described at the back of the journal.
Longarte, A., Fernandez, J. A., Unamuno, I. & CastanÄo, F. (1999). Chem. Phys.
Lett. 308, 516±522.
Lynch, D. E. & McClenaghan, I. (2002). Acta Cryst. E58, o708±o709.
Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,
Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M.
Sweet, pp. 307±326. New York: Academic Press.
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Acta Cryst. (2004). C60, o69±o71
Antonio C. Doriguetto et al. C8H9NO2 o71