The structural properties of a noncentrosymmetric polymorph of 4-amino­benzoic acid

The crystal structure of a polymorph of 4-amino­benzoic acid (PABA), C₇H₇NO₂, at 100 K is noncentrosymmetric, as opposed to centrosymmetric in the structures of the other known polymorphs. The two crystallographically independent PABA mol­ecules form pseudocentrosymmetric O—H...O hydrogen-bonded dimers that are further linked by N—H...O hydrogen bonds into a three-dimensional network. The benzene rings stack in the b direction. The CO₂ moieties are bent out slightly from the benzene ring plane.

S1. Introduction

Polymorphism and associated phenomena have been actively studied over the last few decades for both scientific aspects and industrial problems (Bernstein et al., 1999; Brittain, 1999; Bernstein, 2002; Kitamura, 2002; Blagden & Davey, 2003). It is well established that different polymorphs have different structural and physical properties due to different crystal packing arrangements and/or different molecular conformations. The control of such properties presents a main challenge in crystal engineering and also in the quality control of the molecular material, especially in the industrial elaboration process, such as pharmaceuticals (Herbstein, 2004). Although several studies highlight the effects of the competition between the nucleation–growth process and the transformation mechanism in the crystallization of polymorphous compounds, the conditions for the appearance and disappearance of polymorphs are still not completely understood. Among the most investigated systems are amino acids and their derivatives. These compounds have attracted major inter­est owing to their use in drug design processing based on hydrogen bonding and inter­molecular inter­actions. Many of them are known to crystallize in polymorphic forms, for example, glutamic acid, asparagine, aspartic acid (Ono et al., 2004; Ni et al., 2004; Doki et al., 2004; Bendeif & Jelsch, 2007) and 4-amino­benzoic acid (PABA). PABA is known for its biological properties and is well suited for use in medicine and is also used in the synthesis of target esters, salts, folic acid, azo dyes and many other organic compounds. Because of its pharmaceutical and physical properties, the crystal structure of PABA has been studied since the early 1960s (Killean et al., 1965; Alleaume et al., 1966; Lai & Marsh, 1967). It has two known polymorphs, viz. the α and the β forms. In the α-form, the PABA molecules are connected through alternating O—H···O and N—H···O inter­actions to form chains, while in the β-form, the PABA molecules are related via O—H···N and N—H···O hydrogen bonds to form a three-dimensional network. The crystal structures of the PABA polymorphs have been reinvestigated recently by various groups (Gracin & Rasmuson, 2004; Gracin & Fischer, 2005; Athimoolam & Natarajan, 2007). So far, four polymorphs of PABA are known in the literature, all of which are centrosymmetric. In the present study, the low-temperature structural properties of a new noncentrosymmetric PABA polymorph are discussed and compared with those reported previously.

S2. Experimental

S2.1. Synthesis and crystallization

While attempting to synthesize a single-crystal of `4-amino­benzoic selenous acid', the title compound crystallized out. The single crystals grow rapidly in the form of long colourless needles from an aqueous solution containing a mixture of 4-amino­benzoic acid and selenous acid (H₂SeO₃).

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. The electron density of the H atoms was clearly identified in the Fourier difference maps and their atomic coordinates and isotropic displacements parameters were refined with restrained O—H distances [O—H = 0.96 (2) Å]. The Flack (1983) parameter refined with 1654 Bijvoet pairs to the meaningless value of -0.1 (13).

S3. Results and discussion

The asymmetric unit of this new polymorph of PABA comprises two structurally independent molecules, as shown in Fig. 1. The geometric parameters (Table 2) are in agreement with previously reported results (Lai & Marsh, 1967; Athimoolam & Natarajan, 2007). The aromatic C—-C bond lengths range from 1.377 (5) to 1.402 (5) Å, with average values of 1.392 (4) and 1.396 (4) Å for molecule A and B, respectively. It is worth noting that the C1i—C2i and C5i—N1i (i = A or B) bond lengths are significantly shorter (by about 0.07 Å) than classical single C—C and C—N bonds. This was also observed in the earliest work of Lai & Marsh (1967) and reveals the inter­esting quinoid structure of the studied polymorph. The molecular structure is also characterized by a slightly distorted planar geometry. The distortion from a perfect planar configuration is essentially due the different inter­molecular inter­actions that involve the amino and the carboxyl­lic acid groups. These groups are bent out, in the same direction, from the mean plan of the aromatic ring of each of the structurally distinct molecules by 0.089 (3) and 0.100 (3) Å, respectively, for molecule A, and by 0.097 (3) and 0.127 (3)Å for molecule B. The bending out of the carb­oxy­lic acid group is commonly found in PABA compounds (Athimoolam & Natarajan, 2007) and the angles of this bending are 2.57 (18)° for molecule A and 3.03 (17)° for molecule B.

The crystal packing consists of pairs of PABA molecules linked together head-to-head to form [PABA]₂ dimers via strong and pseudocentrosymmetric O—H···O hydrogen bonds [2.610 (2) and 2.631 (2) Å] (Fig. 2 and Table 3). The dimers are themselves connected via a moderate N—H···O hydrogen bond [2.958 (3) Å] extending along the c axis. Moreover, the amino group of molecule B acts as a hydrogen-bond donor to two neighbouring carb­oxy­lic acid groups of A molecules lying one on top of the other through two weak N1B—H3···O2A inter­actions [3.305 (3) and 3.312 (3) Å] and ensure therefore the connection along the b axis.

Besides these hydrogen bonds, the crystal packing is also characterized by π–π stacking inter­actions and by additional C—H···N short contacts (Fig. 2), allowing the formation of a highly linked three-dimensional network of inter­molecular inter­actions (Fig. 3). Furthermore, a detailed examination of the molecular packing reveals that the average spacing between the A molecules [3.317 (2) Å] is slightly larger compared to that between the B molecules [3.306 (3) Å]. This may be explained by the twisting out of the carb­oxy­lic acid group from the mean plane of the aromatic ring.

Related literature

For related literature, see: Alleaume et al. (1966); Athimoolam & Natarajan (2007); Bendeif & Jelsch (2007); Bernstein (2002); Bernstein et al. (1999); Blagden & Davey (2003); Brittain (1999); Doki et al. (2004); Gracin & Fischer (2005); Gracin & Rasmuson (2004); Herbstein (2004); Killean et al. (1965); Kitamura (2002); Lai & Marsh (1967); Ni et al. (2004); Ono et al. (2004).

Computing details

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008) and WinGX (Farrugia, 2012); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: enCIFer (Allen et al., 2004).

Figures

	Fig. 1. The asymmetric unit of PABA, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small grey spheres of arbitrary radii.
	Fig. 2. The molecular packing of PABA, showing the O—H···O and N—H···O hydrogen-bonded molecules (dotted lines).
	Fig. 3. A projection of the three-dimensional network of intermolecular interactions of PABA(dotted lines).

4-Aminobenzoic acid

Crystal data

C7H7NO2	F(000) = 576
Mr = 137.14	Dx = 1.427 Mg m^−3
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 2789 reflections
a = 26.9945 (8) Å	θ = 3.0–31.8°
b = 3.7322 (3) Å	µ = 0.11 mm^−1
c = 12.6731 (8) Å	T = 100 K
V = 1276.80 (14) Å^3	Needle, colorless
Z = 8	0.12 × 0.05 × 0.04 mm

Data collection

Agilent SuperNova (Dual, Cu at zero, Eos) diffractometer	3604 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	2986 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.043
Detector resolution: 8.1207 pixels mm^-1	θmax = 30.0°, θmin = 3.0°
ω scans	h = −38→38
Absorption correction: analytical [CrysAlis PRO (Agilent, 2012), based on expressions derived by Clark & Reid (1995)]	k = −5→5
Tmin = 0.959, Tmax = 0.997	l = −17→17
9638 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.051	Hydrogen site location: difference Fourier map
wR(F^2) = 0.130	All H-atom parameters refined
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0624P)^2 + 0.4328P] where P = (Fo^2 + 2Fc^2)/3
3604 reflections	(Δ/σ)max = 0.003
237 parameters	Δρmax = 0.49 e Å^−3
2 restraints	Δρmin = −0.21 e Å^−3

Special details

Experimental. Absorption correction: CrysAlisPro (2012), Agilent Technologies UK Ltd, Oxford, UK, Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET) (compiled Dec 3 2012,18:21:49) Analytical numeric absorption correction using a multifaceted crystal model based on expressions derived byby Clark & Reid, 1995.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1A	0.32623 (9)	0.2235 (7)	0.1596 (2)	0.0207 (6)
O2A	0.34318 (8)	0.4714 (7)	0.0030 (2)	0.0205 (5)
N1A	0.11867 (10)	−0.0303 (8)	−0.0574 (2)	0.0205 (6)
C1A	0.31417 (11)	0.3118 (9)	0.0621 (3)	0.0156 (6)
C2A	0.26421 (12)	0.2071 (9)	0.0305 (3)	0.0155 (7)
C3A	0.24705 (12)	0.2927 (9)	−0.0704 (3)	0.0164 (7)
C4A	0.19931 (13)	0.2119 (9)	−0.1005 (3)	0.0161 (6)
C5A	0.16700 (11)	0.0401 (9)	−0.0299 (2)	0.0158 (6)
C6A	0.18435 (11)	−0.0478 (9)	0.0708 (2)	0.0159 (6)
C7A	0.23219 (11)	0.0357 (9)	0.1009 (2)	0.0158 (6)
O1B	0.42862 (9)	0.7458 (6)	0.0618 (2)	0.0189 (6)
O2B	0.41094 (8)	0.4964 (6)	0.21799 (19)	0.0187 (5)
N1B	0.63292 (10)	1.0268 (9)	0.2935 (3)	0.0232 (6)
C1B	0.43984 (11)	0.6638 (9)	0.1609 (3)	0.0150 (6)
C2B	0.48920 (12)	0.7752 (8)	0.1957 (3)	0.0133 (6)
C3B	0.50488 (12)	0.6946 (9)	0.2982 (3)	0.0162 (6)
C4B	0.55198 (13)	0.7817 (9)	0.3318 (3)	0.0168 (7)
C5B	0.58484 (10)	0.9554 (9)	0.2627 (2)	0.0161 (6)
C6B	0.56921 (11)	1.0398 (8)	0.1602 (3)	0.0155 (6)
C7B	0.52193 (11)	0.9513 (8)	0.1272 (2)	0.0154 (6)
H1	0.1118 (17)	−0.006 (12)	−0.131 (4)	0.039 (13)*
H2	0.1035 (17)	−0.193 (12)	−0.015 (4)	0.029 (12)*
H3	0.6389 (16)	1.003 (11)	0.358 (4)	0.029 (12)*
H4	0.6483 (19)	1.201 (14)	0.258 (4)	0.039 (14)*
H4A	0.1889 (17)	0.266 (11)	−0.183 (4)	0.032 (14)*
H4B	0.5636 (16)	0.729 (11)	0.397 (4)	0.021 (12)*
H1A	0.3571 (17)	0.34 (2)	0.182 (6)	0.10 (3)*
H1B	0.3975 (13)	0.685 (10)	0.046 (3)	0.008 (8)*
H3A	0.2683 (14)	0.412 (11)	−0.118 (3)	0.018 (10)*
H3B	0.4825 (15)	0.564 (12)	0.349 (3)	0.027 (11)*
H6A	0.1624 (14)	−0.176 (12)	0.123 (3)	0.019 (10)*
H6B	0.5897 (15)	1.155 (12)	0.115 (3)	0.024 (10)*
H7A	0.2443 (14)	−0.027 (10)	0.175 (3)	0.018 (10)*
H7B	0.5112 (14)	1.017 (11)	0.051 (3)	0.018 (10)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0178 (11)	0.0297 (15)	0.0147 (12)	−0.0060 (9)	−0.0030 (10)	0.0029 (10)
O2A	0.0177 (10)	0.0273 (14)	0.0164 (10)	−0.0036 (9)	0.0003 (8)	0.0021 (10)
N1A	0.0177 (12)	0.0272 (17)	0.0167 (12)	−0.0042 (11)	−0.0022 (10)	0.0021 (12)
C1A	0.0170 (13)	0.0149 (15)	0.0149 (13)	0.0020 (11)	0.0008 (11)	−0.0007 (13)
C2A	0.0155 (13)	0.0141 (16)	0.0168 (16)	0.0020 (11)	−0.0005 (11)	−0.0009 (12)
C3A	0.0181 (14)	0.0163 (16)	0.0146 (16)	−0.0008 (11)	0.0025 (12)	−0.0013 (12)
C4A	0.0198 (15)	0.0163 (16)	0.0124 (14)	0.0031 (11)	−0.0025 (11)	0.0012 (12)
C5A	0.0176 (13)	0.0144 (16)	0.0153 (13)	0.0030 (11)	−0.0003 (10)	−0.0009 (11)
C6A	0.0173 (13)	0.0152 (16)	0.0154 (13)	0.0004 (11)	0.0012 (11)	0.0005 (12)
C7A	0.0174 (13)	0.0134 (15)	0.0168 (13)	0.0025 (11)	−0.0004 (10)	0.0015 (12)
O1B	0.0184 (11)	0.0228 (14)	0.0155 (12)	−0.0035 (8)	−0.0024 (9)	0.0035 (9)
O2B	0.0174 (10)	0.0234 (12)	0.0154 (10)	−0.0046 (9)	−0.0001 (8)	0.0016 (9)
N1B	0.0183 (12)	0.0317 (18)	0.0194 (14)	−0.0025 (12)	−0.0026 (10)	0.0006 (13)
C1B	0.0175 (13)	0.0136 (14)	0.0139 (13)	0.0010 (12)	0.0010 (11)	−0.0023 (13)
C2B	0.0162 (13)	0.0111 (15)	0.0127 (14)	0.0005 (10)	−0.0001 (11)	−0.0008 (11)
C3B	0.0176 (14)	0.0147 (16)	0.0162 (15)	0.0008 (11)	0.0006 (12)	0.0011 (13)
C4B	0.0186 (14)	0.0160 (17)	0.0157 (16)	0.0014 (11)	−0.0009 (12)	−0.0014 (12)
C5B	0.0150 (13)	0.0157 (15)	0.0175 (13)	0.0015 (11)	−0.0017 (10)	−0.0058 (12)
C6B	0.0171 (13)	0.0131 (15)	0.0162 (12)	0.0002 (10)	0.0017 (11)	−0.0001 (13)
C7B	0.0173 (13)	0.0143 (15)	0.0145 (13)	0.0014 (11)	0.0007 (10)	−0.0014 (11)

Geometric parameters (Å, º)

O1A—C1A	1.320 (4)	O1B—C1B	1.327 (4)
O1A—H1A	0.97 (3)	O1B—H1B	0.89 (3)
O2A—C1A	1.237 (4)	O2B—C1B	1.234 (4)
N1A—C5A	1.376 (4)	N1B—C5B	1.381 (4)
N1A—H1	0.96 (5)	N1B—H3	0.83 (5)
N1A—H2	0.91 (5)	N1B—H4	0.89 (5)
C1A—C2A	1.460 (4)	C1B—C2B	1.464 (4)
C2A—C3A	1.397 (5)	C2B—C3B	1.399 (5)
C2A—C7A	1.397 (5)	C2B—C7B	1.402 (5)
C3A—C4A	1.377 (5)	C3B—C4B	1.380 (5)
C3A—H3A	0.95 (4)	C3B—H3B	1.01 (4)
C4A—C5A	1.404 (5)	C4B—C5B	1.405 (5)
C4A—H4A	1.10 (5)	C4B—H4B	0.91 (5)
C5A—C6A	1.399 (4)	C5B—C6B	1.402 (4)
C6A—C7A	1.382 (4)	C6B—C7B	1.383 (4)
C6A—H6A	1.01 (4)	C6B—H6B	0.91 (4)
C7A—H7A	1.02 (4)	C7B—H7B	1.04 (4)
C1A—O1A—H1A	112 (5)	C1B—O1B—H1B	111 (2)
C5A—N1A—H1	114 (3)	C5B—N1B—H3	116 (3)
C5A—N1A—H2	114 (3)	C5B—N1B—H4	116 (3)
H1—N1A—H2	124 (4)	H3—N1B—H4	119 (5)
O2A—C1A—O1A	122.1 (3)	O2B—C1B—O1B	121.8 (3)
O2A—C1A—C2A	123.2 (3)	O2B—C1B—C2B	122.9 (3)
O1A—C1A—C2A	114.7 (3)	O1B—C1B—C2B	115.3 (3)
C3A—C2A—C7A	118.9 (3)	C3B—C2B—C7B	119.0 (3)
C3A—C2A—C1A	119.8 (3)	C3B—C2B—C1B	119.6 (3)
C7A—C2A—C1A	121.3 (3)	C7B—C2B—C1B	121.4 (3)
C4A—C3A—C2A	120.9 (3)	C4B—C3B—C2B	121.0 (3)
C4A—C3A—H3A	120 (2)	C4B—C3B—H3B	118 (2)
C2A—C3A—H3A	119 (2)	C2B—C3B—H3B	121 (2)
C3A—C4A—C5A	120.3 (3)	C3B—C4B—C5B	119.9 (3)
C3A—C4A—H4A	118 (2)	C3B—C4B—H4B	123 (3)
C5A—C4A—H4A	122 (2)	C5B—C4B—H4B	117 (3)
N1A—C5A—C6A	120.3 (3)	N1B—C5B—C6B	120.1 (3)
N1A—C5A—C4A	121.0 (3)	N1B—C5B—C4B	120.4 (3)
C6A—C5A—C4A	118.7 (3)	C6B—C5B—C4B	119.4 (3)
C7A—C6A—C5A	120.8 (3)	C7B—C6B—C5B	120.3 (3)
C7A—C6A—H6A	118 (2)	C7B—C6B—H6B	119 (3)
C5A—C6A—H6A	121 (2)	C5B—C6B—H6B	121 (3)
C6A—C7A—C2A	120.4 (3)	C6B—C7B—C2B	120.4 (3)
C6A—C7A—H7A	120 (2)	C6B—C7B—H7B	119 (2)
C2A—C7A—H7A	119 (2)	C2B—C7B—H7B	121 (2)
O2A—C1A—C2A—C3A	−1.0 (5)	O2B—C1B—C2B—C3B	−0.7 (5)
O1A—C1A—C2A—C3A	178.8 (3)	O1B—C1B—C2B—C3B	−178.7 (3)
O2A—C1A—C2A—C7A	−178.2 (3)	O2B—C1B—C2B—C7B	177.2 (3)
O1A—C1A—C2A—C7A	1.6 (5)	O1B—C1B—C2B—C7B	−0.8 (5)
C7A—C2A—C3A—C4A	0.3 (5)	C7B—C2B—C3B—C4B	−0.8 (5)
C1A—C2A—C3A—C4A	−177.0 (3)	C1B—C2B—C3B—C4B	177.1 (3)
C2A—C3A—C4A—C5A	−0.2 (5)	C2B—C3B—C4B—C5B	0.3 (5)
C3A—C4A—C5A—N1A	177.5 (3)	C3B—C4B—C5B—N1B	−176.5 (3)
C3A—C4A—C5A—C6A	−0.2 (5)	C3B—C4B—C5B—C6B	0.3 (5)
N1A—C5A—C6A—C7A	−177.2 (3)	N1B—C5B—C6B—C7B	176.5 (3)
C4A—C5A—C6A—C7A	0.6 (5)	C4B—C5B—C6B—C7B	−0.3 (5)
C5A—C6A—C7A—C2A	−0.5 (5)	C5B—C6B—C7B—C2B	−0.3 (5)
C3A—C2A—C7A—C6A	0.1 (5)	C3B—C2B—C7B—C6B	0.8 (5)
C1A—C2A—C7A—C6A	177.3 (3)	C1B—C2B—C7B—C6B	−177.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1A—H1A···O2B	0.97 (3)	1.64 (4)	2.610 (2)	176 (5)
O1B—H1B···O2A	0.89 (3)	1.76 (4)	2.631 (2)	166 (4)
N1A—H1···O2B^i	0.96 (5)	2.00 (5)	2.958 (3)	171 (4)
N1B—H3···O2A^ii	0.83 (5)	2.59 (3)	3.305 (3)	143 (3)
N1B—H3···O2A^iii	0.83 (5)	2.73 (3)	3.312 (3)	128 (3)

Symmetry codes: (i) −x+1/2, y−1/2, z−1/2; (ii) −x+1, −y+1, z+1/2; (iii) −x+1, −y+2, z+1/2.