Comparison of the crystal structures of methyl 4-bromo-2-(methoxymethoxy)benzoate and 4-bromo-3-(methoxymethoxy)benzoic acid

The crystal structures of two bromo–hydroxy–benzoic acid derivatives, namely, methyl 4-bromo-2-(methoxymethoxy)benzoate, (I), and 4-bromo-3-(methoxymethoxy)benzoic acid, (II), are compared. Compound (II) crystallizes with two independent molecules in the asymmetric unit. In the crystal structures of both compounds, two-dimensional architectures are formed principally by C—H⋯O hydrogen bonds, and by Br⋯O interactions in (I) and by π–π interactions in (II).


Chemical context
Ester derivatives of many compounds exhibit a variety of pharmacological properties, such as anticancer, antitumor and antimicrobial activities (Anadu et al., 2006;Bartzatt et al., 2004;Bi et al., 2012). Salicylic acid and derivatives of salicylic acid are of great biological importance. For example, they are known for their analgesic and anti-inflammatory activities in the treatment of rheumatoid arthritis (Anderson et al., 2014;Hardie, 2013). They are also known for their use as antibacterial and antimycobacterial agents (Silva et al., 2008). In view of the above, compounds (I) and (II) were synthesized and we report herein on their crystal structures.

Structural commentary
The molecular structure of compound (I), is illustrated in Fig. 1. The -O-CH 2 -O-CH 3 side chain is not in its fully extended conformation, with torsion angle O3-C9-O4-C10 being 67.3 (3) . The dihedral angle between the benzene ring and the ester segment (O1/C7/O2/C8) is 14.5 (2) , while the plane through atoms C10/O4/C9 of the methoxymethoxy side chain is inclined to the benzene ring by 82.5 (3) .
The molecular structure of compound (II), is illustrated in Fig. 2. It crystallizes with two independent molecules (A and B) in the asymmetric unit. The conformations of the two molecules differ in the torsion angles of the -O-CH 2 -O-CH 3 side chains and the orientation of the -COO-group with respect to the benzene ring, as shown in the AutoMolFit diagram ( Fig. 3; Spek, 2009). The -O-CH 2 -O-CH 3 side chains in molecules A and B are not in their fully extended conformation; torsion angle O3A-C8A-O4A-C9A in molecule A is À65.8 (3) , and torsion angle O3B-C8B-O4B--C9B in molecule B is À74.1 (3) . The dihedral angle between the benzene ring and the plane through atoms C8A/O4A/C9A of the methoxymethoxy side chain in molecule A is 79.2 (3) , while the corresponding dihedral angle in molecule B, between the benzene ring and plane C9B/O4B/O8B is 67.1 (3) . This is less than in compound (I) and further, the dihedral angle between the benzene ring and the -COOgroup is 6.6 (4) in A and 9.1 (4) in B; also less than observed in compound (I), viz. 14.5 (2) . A view of the molecular structure of compound (I), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
A view of the molecular structure of compound (II), showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. O-HÁ Á ÁO hydrogen bonds are shown as dashed lines (see Table 2).

Figure 3
A view of the molecular fit of molecules A (black) and B (red) of compound (II).

Figure 4
A view along the a axis of the crystal packing of compound (I). C-HÁ Á ÁO and BrÁ Á ÁO interactions are shown as dashed lines (see Table 1). H atoms not involved in these interactions have been omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ) for (I).
Cg1 is the centroid of the C1-C6 benzene ring.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 3 A partial view along the a axis of the crystal packing of compound (II). O-HÁ Á ÁO and C--HÁ Á ÁO hydrogen bonds are shown as dashed lines (see Table 2). H atoms not involved in these interactions have been omitted for clarity.

Figure 7
A view of thestacking observed in the crystal of (II); molecule A green, molecule B blue. (II) were located in a difference Fourier map and refined with a distance restraint: O-H = 0.84 (5) Å . The C-bound H atoms in (I) and (II) were positioned with idealized geometry and refined using a riding model: C-H = 0.95-0.99 Å , with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms.
In the final cycles of refinement reflection (0 0 2) in (I) and reflections (4 1 0), (6 À 4 6), (5 À 5 7), (4 2 0) and (0 À 1 6) in (II) were omitted due to large differences in F 2 obs and F 2 calc , considerably improving the values of R1, wR2, and GOF. For both compounds, data collection: APEX2 (Bruker, 2009); cell refinement: APEX2 and SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus and XPREP (Bruker, 2009). Program(s) used to solve structure: SHELXS97 (Sheldrick, 2008) for (I); SHELXS97 (Sheldrick, 20008) for (II). For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 2008). Molecular graphics: Mercury (Macrae et al., 2008) and PLATON (Spek, 2009) for (I); Mercury (Macrae et al., 2008) for (II). Software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009) for (I); SHELXL97 (Sheldrick, 2008) for (II). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 1.87 e Å −3 Δρ min = −0.97 e Å −3 Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Refinement
Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = 0.039 wR(F 2 ) = 0.120 S = 1.09 3031 reflections 261 parameters 2 restraints Primary atom site location: structure-invariant direct methods Secondary atom site location: difference Fourier map Hydrogen site location: inferred from neighbouring sites H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o 2 ) + (0.0844P) 2 + 0.9411P] where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.67 e Å −3 Δρ min = −1.08 e Å −3 Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2 )
x y z U iso */U eq