2-(3-Bromo-4-methoxyphenyl)acetic acid

The title compound C9H9BrO3, was synthesized by the regioselective bromination of 4-methoxyphenylacetic acid using bromine in acetic acid in a 84% yield. In the molecular structure, the methoxy group is almost coplanar with the phenyl ring within 0.06 Å; the acetic acid substituent is tilted by 78.15 (7)° relative to the ring. The C—C—C angles at the OMe, acetyl and Br substituents are 118.2 (2), 118.4 (2) and 121.5 (2)°, respectively, indicating that the Br atom is electron-withdrawing, whereas the other substituents possess electron-donating properties. In the crystal, the molecules form centrosymmetric strongly O—H⋯O hydrogen-bonded dimers of the type R 2 2(8).

The title compound C 9 H 9 BrO 3 , was synthesized by the regioselective bromination of 4-methoxyphenylacetic acid using bromine in acetic acid in a 84% yield. In the molecular structure, the methoxy group is almost coplanar with the phenyl ring within 0.06 Å ; the acetic acid substituent is tilted by 78.15 (7) relative to the ring. The C-C-C angles at the OMe, acetyl and Br substituents are 118.2 (2), 118.4 (2) and 121.5 (2) , respectively, indicating that the Br atom is electronwithdrawing, whereas the other substituents possess electrondonating properties. In the crystal, the molecules form centrosymmetric strongly O-HÁ Á ÁO hydrogen-bonded dimers of the type R 2 2 (8).

Comment
Recently, we have been pursuing simple organic and organometallic compounds as candidates for the introduction of (a) natural product synthesis into the undergraduate teaching laboratory and (b) crystal growing techniques and single crystal X-ray diffraction data analysis into the undergraduate curriculum (Findlater et al., 2010;Guzei at al., 2010a). The 3-bromo-4-methoxyphenylacetic acid I has been employed in the synthesis of natural products such as Combretastatin A-4, (Zou et al., 2008), Verongamine (Wasserman & Wang, 1998) and model Vancomycin-type systems (Ghosh et al., 2009). The iodoanalogue features in the synthesis of the perylenequinones (+)-Phleichrome and (+)-Calphostin D, (Morgan et al., 2010).
Our interest in I stems from its role in the synthesis of the antimitotic compound Combretastatin A-4 via a simple Perkin condensation/decarboxylation sequence (Zou et al., 2008). This concise route, employing commercially available starting materials, followed by the facile purification of I to furnish high quality crystals makes it ideal in both regards. Compound I is readily synthesized by the regioselective bromination of 4-methoxyphenylacetic acid using bromine in acetic acid (Coutts et al., 1970;Morgan et al., 2007;Zou et al., 2008;Ghosh et al., 2009). Compound I was isolated and characterized by NMR, mp, and single-crystal X-ray analysis. There are three main structural aspects students should identify. First, the positions of the alkyl substituents on the phenyl ring. The methoxy-group is almost coplanar with the ring, torsion angle C7-O1-C1-C6 is 1.2 (3)°, whereas the acetic acid terminus is nearly perpendicular to the ring with the dihedral angle between the planes defined by atoms C1-C6 and atoms C4,C8,C9,O2,O3 spanning 78.15 (7)°. Secondly, the distortions of the C-C-C angles from 120° at the substituents of the phenyl ring reflect their electronic properties. The stronger the electron-withdrawing power of a substituent, the larger the C-C-C angle. The angles at OMe, Ac and Br are 118.2 (2), 118.4 (2), and 121.5 (2)°, respectively, indicating that the Br atom is electron-withdrawing, whereas the other substituents possess electron-donating properties. Of course, the magnitude of the values is affected by the neighbouring substituents.
Thirdly, the molecules of I form centrosymmetric strongly hydrogen-bonded dimers in the lattice. The hydrogen bonding motif is R 2 2 (8). A topical discussion of hydrogen bonding motif assignment was published by Guzei et al., 2010b.

Experimental
To a stirred solution of 4-methoxyphenylacetic acid (10 g, 60.2 mmol) in acetic acid (60 ml) was added a solution of bromine (9.62 g, 3.1 ml, 60.2 mmol) in acetic acid (30 ml) slowly dropwise over 30 min. The mixture was stirred at room temperature (60 min) and then poured into 500 ml ice-water. The resultant pale yellow, turbid mixture was stirred (10 min), filtered, rinsed with ice-water (3×10 ml), air-dried (20 min) and recrystallized from hot xylene to give a white crystalline powder. All H-atoms were placed in idealized locations. The C-H distances were 0.98Å for the methyl group, 0.99Å the methylene group, 0.95Å for the sp 2 -hybridized atoms; the O-H distance was fixed at 0.84Å. All H atoms were refined as riding with thermal displacement coefficients U iso (H) set to 1.5U eq (C, O) for the methyl-and hydroxyl-groups and to to 1.2U eq (C) for the CH-and CH 2 -groups.
The outlier reflections were omitted based on the statistics test described by Prince & Nicholson, (1983) and Rollett, (1988), and implemented in program FCF_filter (Guzei, 2007). The number of omitted outliers is 4. Figures   Fig. 1. Molecular structure of I with the atom numbering scheme. The displacement ellipsoids are shown at 50% probability level.

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 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 > σ(F 2 ) is used only for calculating Rfactors(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.