Crystal and mol-ecular structure of meso-2,6-di-bromo-hepta-nedioic acid (meso-2,6-di-bromo-pimelic acid).

The mol-ecular structure of the title compound, C7H10Br2O4, confirms the meso (2R,6S) configuration. In the crystal, mol-ecules are linked by pairs of O-H⋯O=C hydrogen bonds between their terminal carboxyl groups in an R 2 (2)(8) motif, forming extended chains that propagate 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-3,7-dicarb­oxy-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.

Figure 1

The mol­ecular structure of the title compound, with non-H atoms labeled. Displacement ellipsoids are shown at the 60% probability level.

Supra­molecular features

In the crystal, the mol­ecules are linked in head-to-tail fashion by pairs of O—H⋯O=C hydrogen bonds (Table 1 ▸) between their terminal carboxyl groups in an (8) motif, forming extended chains that propagate parallel to the c axis (Fig. 2 ▸ a). 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 ▸): (i) the =O⋯Br—C bonds are nearly linear [the =O1⋯Br2—C2 and =O3⋯Br6—C6 angles being 168.06 (8) and 170.26 (8)°, respectively], and (ii) the O⋯Br distances [3.224 (2) and 3.058 (2) Å for O1⋯Br2iii and O3⋯Br6iv, respectively [symmetry codes: (iii)  − x, y − , z; (iv)  − x, y − , z] are less than the sum of the van der Waals radii of 3.35 Å (Mantina et al., 2009 ▸; Alvarez, 2013 ▸). H and Br bonding are shown in Fig. 2 ▸.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3i	0.84	1.80	2.635 (3)	177
O4—H4⋯O1ii	0.84	1.83	2.669 (3)	176

Symmetry codes: (i) ; (ii) .

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=O⋯Br, green).

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 SOCl2 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 CHCl3. The remaining solids were recrystallized three times from formic acid to give meso-2,6-dibrohepta­nedioic acid (26% yield).

The 1H NMR spectrum, acquired in Me2SO-d 6, is consistent with the mol­ecular structure, with the following resonances (δ referenced to Me4Si): 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.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. H-atom U iso parameters were refined to confirm proper positioning of the H atoms; this was particularly important for the carboxyl H atoms. Uniquely for H3, its U iso [0.013 (7)] is smaller than the U eq of C3 [0.022 (4)], to which it is attached, but by less than two s.u.’s. All other H-atom U iso values are consistent with expectation: 0.02–0.3 for CH and CH2, and 0.05 for CO2H. These values are in line with H-atom U iso values in C2–C12 aliphatic acids without heavy-atom substitution, whose structures had been determined at the same temperature (150 K) or lower (Thalladi et al., 2000 ▸; Mitchell et al.,2001 ▸; Peppel et al., 2015a ▸,b ▸; Sonneck et al., 2015a ▸,b ▸). In these structures, U iso values average 0.033±0.006 for CH and CH2, and 0.068±0.033 for reciprocally hydrogen-bonded CO2H.

Table 2

Experimental details

Crystal data
Chemical formula	C7H10Br2O4
M r	317.97
Crystal system, space group	Orthorhombic, P b c a
Temperature (K)	150
a, b, c (Å)	10.4277 (7), 10.7014 (7), 18.7154 (13)
V (Å3)	2088.5 (2)
Z	8
Radiation type	Mo Kα
μ (mm−1)	7.74
Crystal size (mm)	0.35 × 0.27 × 0.09
Data collection
Diffractometer	Bruker SMART APEXII CCD
Absorption correction	Multi-scan (SADABS; Sheldrick, 2008 ▸)
T min, T max	0.231, 0.498
No. of measured, independent and observed [I > 2σ(I)] reflections	35789, 4598, 3488
R int	0.037
(sin θ/λ)max (Å−1)	0.807
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.036, 0.084, 1.08
No. of reflections	4598
No. of parameters	130
H-atom treatment	Only H-atom displacement parameters refined
Δρmax, Δρmin (e Å−3)	2.07, −1.15

Computer programs: APEX2, SAINT and XSHELL (Bruker, 2010 ▸), SHELXS97 (Sheldrick, 2008 ▸), SHELXL2014 (Sheldrick, 2015 ▸), Mercury (Macrae et al., 2008 ▸), PLATON (Spek, 2009 ▸) and publCIF (Westrip, 2010 ▸).

Residual electron density is somewhat high (Δρmax and Δρmin being 2.07 and −1.14 e Å3, respectively) and localizes near the heavier Br atoms, which suggests Fourier truncation as a possible cause. Other reasons could be translational pseudosymmetry (for example, see Kiessling & Zeller, 2011 ▸), or the high geometric anisotropy of the crystal (ratio of largest-to-smallest dimensions being 4), which can yield less accurate absorption correction performed through SADABS software. The irregular shape of the crystal precluded more accurate absorption correction through face indexing.

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989016001754/pk2573sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016001754/pk2573Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016001754/pk2573Isup3.cml

CCDC reference: 1450356

Additional supporting information: crystallographic information; 3D view; checkCIF report

C7H10Br2O4	Dx = 2.023 Mg m−3
Mr = 317.97	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 9811 reflections
a = 10.4277 (7) Å	θ = 2.2–34.7°
b = 10.7014 (7) Å	µ = 7.74 mm−1
c = 18.7154 (13) Å	T = 150 K
V = 2088.5 (2) Å3	Plate, colourless
Z = 8	0.35 × 0.27 × 0.09 mm
F(000) = 1232

Bruker SMART APEXII CCD diffractometer	4598 independent reflections
Radiation source: sealed tube	3488 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.037
Detector resolution: 8.333 pixels mm-1	θmax = 35.0°, θmin = 2.2°
φ and ω scans	h = −16→16
Absorption correction: multi-scan (SADABS; Sheldrick, 2008)	k = −17→17
Tmin = 0.231, Tmax = 0.498	l = −30→30
35789 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.084	Only H-atom displacement parameters refined
S = 1.08	w = 1/[σ2(Fo2) + (0.020P)2 + 6.P] where P = (Fo2 + 2Fc2)/3
4598 reflections	(Δ/σ)max = 0.001
130 parameters	Δρmax = 2.07 e Å−3
0 restraints	Δρmin = −1.14 e Å−3

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.

	x	y	z	Uiso*/Ueq
O1	0.4428 (2)	0.35337 (18)	0.81180 (10)	0.0271 (4)
O2	0.5097 (2)	0.53602 (18)	0.85748 (10)	0.0289 (4)
H2	0.5328	0.4903	0.8916	0.044 (11)*
C1	0.4560 (2)	0.4669 (2)	0.80775 (12)	0.0200 (4)
C2	0.4148 (2)	0.5420 (2)	0.74305 (12)	0.0190 (4)
H2A	0.4858	0.6007	0.7303	0.024 (8)*
Br2	0.26550 (3)	0.64147 (3)	0.77267 (2)	0.02812 (7)
C3	0.3835 (2)	0.4638 (2)	0.67757 (12)	0.0221 (4)
H3A	0.3411	0.5169	0.6413	0.022 (8)*
H3B	0.3233	0.3963	0.6910	0.013 (7)*
C4	0.5050 (3)	0.4068 (3)	0.64587 (13)	0.0241 (5)
H4A	0.5692	0.4736	0.6380	0.030 (9)*
H4B	0.5417	0.3462	0.6802	0.033 (9)*
C5	0.4780 (2)	0.3408 (2)	0.57527 (13)	0.0212 (4)
H5A	0.4112	0.2765	0.5831	0.034 (9)*
H5B	0.4435	0.4024	0.5408	0.037 (10)*
C6	0.5957 (2)	0.2790 (2)	0.54304 (13)	0.0204 (4)
H6A	0.6299	0.2163	0.5778	0.029 (9)*
Br6	0.73130 (2)	0.40137 (2)	0.52174 (2)	0.02402 (6)
C7	0.5646 (2)	0.2132 (2)	0.47354 (12)	0.0204 (4)
O3	0.5852 (2)	0.10197 (18)	0.46621 (11)	0.0296 (4)
O4	0.5102 (2)	0.28358 (18)	0.42491 (10)	0.0300 (4)
H4	0.4863	0.2389	0.3905	0.053 (12)*

	U11	U22	U33	U12	U13	U23
O1	0.0382 (10)	0.0244 (9)	0.0188 (8)	−0.0048 (8)	−0.0049 (7)	0.0012 (7)
O2	0.0425 (11)	0.0238 (9)	0.0205 (8)	−0.0040 (8)	−0.0098 (8)	0.0008 (7)
C1	0.0205 (10)	0.0243 (11)	0.0152 (9)	0.0001 (8)	0.0009 (7)	0.0002 (8)
C2	0.0185 (9)	0.0204 (10)	0.0181 (10)	0.0006 (8)	0.0003 (7)	0.0012 (8)
Br2	0.02097 (11)	0.03372 (14)	0.02965 (13)	0.00479 (10)	0.00001 (10)	−0.00452 (10)
C3	0.0233 (11)	0.0270 (11)	0.0159 (9)	−0.0003 (9)	−0.0012 (8)	0.0008 (8)
C4	0.0264 (11)	0.0294 (12)	0.0166 (9)	0.0032 (9)	−0.0013 (8)	−0.0036 (9)
C5	0.0226 (11)	0.0239 (11)	0.0171 (9)	0.0003 (8)	−0.0008 (8)	−0.0005 (8)
C6	0.0255 (11)	0.0190 (10)	0.0169 (9)	0.0006 (8)	−0.0024 (8)	0.0009 (8)
Br6	0.02087 (10)	0.02733 (12)	0.02386 (11)	−0.00204 (9)	−0.00007 (9)	−0.00097 (9)
C7	0.0218 (10)	0.0228 (10)	0.0165 (9)	−0.0007 (8)	−0.0008 (8)	0.0014 (8)
O3	0.0387 (11)	0.0247 (9)	0.0253 (9)	0.0061 (8)	−0.0103 (8)	−0.0034 (7)
O4	0.0493 (12)	0.0215 (8)	0.0193 (8)	0.0027 (8)	−0.0100 (8)	−0.0001 (7)

O1—C1	1.225 (3)	C4—H4A	0.9900
O2—C1	1.314 (3)	C4—H4B	0.9900
O2—H2	0.8400	C5—C6	1.520 (3)
C1—C2	1.516 (3)	C5—H5A	0.9900
C2—C3	1.519 (3)	C5—H5B	0.9900
C2—Br2	1.966 (2)	C6—C7	1.515 (3)
C2—H2A	1.0000	C6—Br6	1.968 (2)
C3—C4	1.526 (4)	C6—H6A	1.0000
C3—H3A	0.9900	C7—O3	1.217 (3)
C3—H3B	0.9900	C7—O4	1.310 (3)
C4—C5	1.524 (3)	O4—H4	0.8400
C1—O2—H2	109.5	C5—C4—H4B	109.3
O1—C1—O2	124.2 (2)	C3—C4—H4B	109.3
O1—C1—C2	122.9 (2)	H4A—C4—H4B	108.0
O2—C1—C2	112.8 (2)	C6—C5—C4	113.3 (2)
C1—C2—C3	114.4 (2)	C6—C5—H5A	108.9
C1—C2—Br2	106.66 (16)	C4—C5—H5A	108.9
C3—C2—Br2	110.85 (16)	C6—C5—H5B	108.9
C1—C2—H2A	108.2	C4—C5—H5B	108.9
C3—C2—H2A	108.2	H5A—C5—H5B	107.7
Br2—C2—H2A	108.2	C7—C6—C5	111.7 (2)
C2—C3—C4	110.8 (2)	C7—C6—Br6	106.84 (16)
C2—C3—H3A	109.5	C5—C6—Br6	111.78 (16)
C4—C3—H3A	109.5	C7—C6—H6A	108.8
C2—C3—H3B	109.5	C5—C6—H6A	108.8
C4—C3—H3B	109.5	Br6—C6—H6A	108.8
H3A—C3—H3B	108.1	O3—C7—O4	124.1 (2)
C5—C4—C3	111.6 (2)	O3—C7—C6	120.9 (2)
C5—C4—H4A	109.3	O4—C7—C6	114.9 (2)
C3—C4—H4A	109.3	C7—O4—H4	109.5
O1—C1—C2—C3	−13.0 (3)	C3—C4—C5—C6	−178.1 (2)
O2—C1—C2—C3	165.5 (2)	C4—C5—C6—C7	179.3 (2)
O1—C1—C2—Br2	109.9 (2)	C4—C5—C6—Br6	−61.1 (2)
O2—C1—C2—Br2	−71.6 (2)	C5—C6—C7—O3	−122.1 (3)
C1—C2—C3—C4	−70.5 (3)	Br6—C6—C7—O3	115.4 (2)
Br2—C2—C3—C4	168.86 (17)	C5—C6—C7—O4	55.2 (3)
C2—C3—C4—C5	−173.3 (2)	Br6—C6—C7—O4	−67.3 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3i	0.84	1.80	2.635 (3)	177
O4—H4···O1ii	0.84	1.83	2.669 (3)	176