Crystal and molecular structure of meso-2,6-dibromoheptanedioic acid (meso-2,6-dibromopimelic acid)

The molecular structure of the title compound, confirms the meso-(2R,6S) configuration. In the crystal, molecules are linked by pairs of O—H⋯O=C hydrogen bonds, forming chains parallel to the c axis. Adjacent chains are linked by C=O⋯Br halogen bonds.


Chemical context
meso-2,6-Dibromopimelic acid is a convenient starting point for preparing derivatives 2,6-disubstituted with non-halogen functional groups (for examples : Schotte, 1956b;Lingens, 1960;Yuan & Lu, 2009). It also has utility in the synthesis of heterocycles (Schotte, 1956b;Miyake et al., 2000;Peters et al., 2006;Hamon et al., 2007). In an ongoing study of disulfides, the title compound was required as precursor to meso-3,7dicarboxy-1,2-dithiepane. Surprisingly, other than the melting point reported by Schotte (1956a), no further analytical data have been published on the dibromo acid. Original stereochemical assignment was based on the lack of optical activity of the acid isolated through crystallization of the acid brucine salt (Schotte, 1956a). The need to confirm the meso configuration motivated the crystal structure determination.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1; the (2R,6S) configuration is apparent, confirming the meso form of the compound. All bond lengths and angles are within normal ranges.

Supramolecular features
In the crystal, the molecules are linked in head-to-tail fashion by pairs of O-HÁ Á ÁO C hydrogen bonds (Table 1) between their terminal carboxyl groups in an R 2 2 (8) motif, forming extended chains that propagate parallel to the c axis (Fig. 2a). ISSN 2056-9890 Adjacent chains are cross-linked by interactions between a carboxyl C O group in one chain with a Br atom in an adjacent chain. These linkages meet the criteria for halogen bonds (Desiraju et al., 2013) (2) and 3.058 (2) Å for O1Á Á ÁBr2 iii and O3Á Á ÁBr6 iv , respectively [symmetry codes: (iii) 1 2 À x, y À 1 2 , z; (iv) 3 2 À x, y À 1 2 , z] are less than the sum of the van der Waals radii of 3.35 Å (Mantina et al., 2009;Alvarez, 2013

Synthesis and crystallization
The title compound was first prepared in pure form and its stereochemistry deduced by Fehnel & Oppenlander (1953). The synthesis for the present work followed the method of Schotte (1956a). Pimelic (heptanedioic) acid was converted into the diacid chloride by heating with thionyl chloride. Removal of excess SOCl 2 under reduced pressure left the liquid diacid chloride. Over 1 h, bromine (2.3 equivalents) was added dropwise to the stirred diacid chloride maintained at 363 K. Thereafter, stirring and heating continued for an additional hour. The dibrominated acid chloride was hydrolyzed by gradual addition to vigorously stirred formic acid maintained at 353-363 K. When gas evolution ceased, the reaction mixture was refluxed for 15 min, and then allowed to cool to room temperature. Upon cooling in the refrigerator, over two days, the reaction mixture yielded two crops of solids, which were combined and extracted by shaking with ice-cold CHCl 3 . The remaining solids were recrystallized three times from formic acid to give meso-2,6-dibroheptanedioic acid (26% yield).
The 1 H NMR spectrum, acquired in Me 2 SO-d 6 , is consistent with the molecular structure, with the following resonances ( referenced to Me 4 Si): 13.22, singlet, 2H; 4.43, triplet, 2H, J = 7 Hz; 2.01, multiplet, 2H; 1.88, multiplet, 2H; 1.54, multiplet, 1H; 1.39, multiplet, 1H. The high-resolution mass spectrum (electrospray) showed the expected manifold arising from the two stable isotopes of bromine, with the base peak at m/z = 316.884; species containing halogens other than bromine were not observed. To produce crystals suitable for diffraction, 10 mg of the title compound was dissolved in a capped glass vial in minimal formic acid with warming. Once a few seeds became visible, slow evaporation of the solvent over 14 days yielded crystals of good quality.

Figure 2
The molecular packing, viewed along the b and a axes [panels (a) and (b)]. Intermolecular hydrogen bonding (cyan) between terminal carboxyl groups results in head-to-tail linkage of the molecules into chains extending along [001]. Adjacent chains are linked by halogen bonding (C OÁ Á ÁBr, green).