Crystal structure of (2',3,6'-tri-chloro-biphenyl-2-yl)boronic acid tetra-hydro-furan monosolvate.

The title compound, C12H8BCl3O2·C4H8O, crystallizes as a tetra-hydro-furan monosolvate. The boronic acid group adopts a syn-anti conformation and is significantly twisted along the carbon-boron bond by 69.2 (1)°, due to considerable steric hindrance from the 2',6'-di-chloro-phenyl group that is located ortho to the boronic acid substituent. The phenyl rings of the biphenyl are almost perpendicular to one another, with a dihedral angle of 87.9 (1)° between them. In the crystal, adjacent mol-ecules are linked via O-H⋯O inter-actions to form centrosymmetric dimers with R 2 (2)(8) motifs, which have recently been shown to be energetically very favourable. The hy-droxy groups are in an anti conformation and are also engaged in hydrogen-bonding inter-actions with the O atom of the tetra-hydro-furan solvent mol-ecule. Cl⋯Cl halogen-bonding inter-actions [Cl⋯Cl = 3.464 (1) Å] link neigbouring dimers into chains running along [010]. Further aggregation occurs due to an additional Cl⋯Cl halogen bond [Cl⋯Cl = 3.387 (1) Å].

Chemical context

Boronic acids and their derivatives have been studied intensively in recent years due to their numerous applications in organic, analytical and materials chemistry (Hall, 2011 ▸; Furukawa & Yaghi, 2009 ▸). They are widely used in medicine, for example, as anti­fungal and anti­bacterical agents (Adamczyk-Woźniak et al., 2015 ▸; Kane et al., 2003 ▸; Vogt et al., 2013 ▸). Besides these applications, phenyl­boronic acids have also been studied in terms of crystal engineering (Nishiyabu et al., 2011 ▸; Severin, 2009 ▸). In contrast, biphenyl-based boronic acids have been largely neglected. Exceptions to this include reports of the crystal structures of (2-bi­phenyl­yl)boronic acid (Filthaus et al., 2008 ▸) and (2-meth­oxy-3-biphen­yl)boronic acid (Davies et al., 2008 ▸). In this manuscript we focus our attention on a sterically hindered boronic acid derivative based on a biphenyl core with a boronic group located at the 2-position of one benzene ring with a Cl substituent at the 3-position. The second benzene ring of the biphenyl ring system carries chlorine substituents at the 2- and 6-positions. This mol­ecule crystallized as a 1:1 solvate with THF, Fig. 1 ▸.

Figure 1

The structure of 1, showing the atom numbering, with displacement ellipsoids drawn at the 50% probability level.

Structural commentary

The B—C [1.5907 (16) Å] and B—O [1.3514 (14), 1.3641 (14) Å] bonds in the title compound (I) are within the expected range typically observed for boronic acids (Madura et al., 2014 ▸; Luliński et al., 2007 ▸; Maly et al., 2006 ▸; Shimpi et al., 2007 ▸; Durka et al., 2012 ▸). The mol­ecular structure shows that the B(OH)2 group adopts the usual syn–anti conformation (Fig. 1 ▸). The boronic acid substituent is significantly rotated about the C—B bond in order to minimize the steric hindrance between the boronic group and the adjacent 2′,6′-di­chloro­phenyl ring [τ C2—C1—B1—O1 = 69.2 (2)°]. In the structure of the related (2-bi­phenyl­yl)boronic acid (Filthaus et al., 2008 ▸) this torsion angle is some 20° smaller, which clearly shows the influence of the three chlorine substituents on this structure. It is also notable that in (I) the phenyl rings of the biphenyl system are almost perpendicular to one another [τ C1—C6—C7—C11 = 87.9 (1)°], whereas in (2-bi­phenyl­yl)boronic acid they are rotated by only 48.4 or 45.4° for the two unique mol­ecules in the asymmetric unit.

Supra­molecular features

In the crystal, centrosymmetric O—H⋯O hydrogen-bonded dimers are formed. The anti-oriented OH group is engaged in an inter­molecular O—H⋯O hydrogen bond (Table 1 ▸) with the oxygen atom from the tetra­hydro­furan solvate mol­ecule. Because all of the hydrogen-bond acceptor centres are saturated, the syn OH group is not involved in any side hydrogen-bond inter­actions. Neighbouring dimers are connected through Cl⋯Cl halogen bonds [d Cl⋯Cl = 3.464 (1) Å; the sum of the van der Waals radii for Cl is 3.50 Å]. In terms of geometry of this contact, it can be classified as a type I halogen bond (Fig. 2 ▸ a), (Metrangolo et al., 2005 ▸; Nayak et al., 2011 ▸). These contacts result in the formation of mol­ecular chains propagating along [010] (Fig. 3 ▸). A three-dimensional network forms through additional Cl⋯Cl halogen bonds (Fig. 4 ▸) of type II [d Cl⋯Cl = 3.387 (1) Å] (Fig. 2 ▸ b).

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1A⋯O3	0.82 (1)	1.84 (1)	2.6475 (12)	169 (2)
O2—H2A⋯O1i	0.84 (1)	1.96 (1)	2.7997 (12)	175 (2)

Symmetry code: (i) .

Figure 2

Type I (a) and II (b) Cl⋯Cl halogen bonds in (I).

Figure 3

Mol­ecular chains formed along b by type 1 Cl⋯Cl halogen bonds. Also shown are inversion dimers and inclusion of the solvent through O—H⋯O hydrogen bonds. Aromatic H atoms have been omitted for clarity.

Figure 4

Crystal packing showing inter­molecular O—H⋯O and type II Cl⋯Cl inter­actions.

Synthesis and crystallization

Synthesis of (I) A solution of 2-iodo-2′,3,6′-tri­chloro­biphenyl (3.8 g, 10 mmol) in THF (50 mL) was added to a stirred solution of n-BuLi (10 mmol) in THF (30 mL) at 195 K. The resulting colorless solution was stirred for 1 h to give a colorless precipitate. The electrophile, B(OMe)3 (2.1 g, 20 mmol) was then added to the stirred mixture to give a colorless solution which was stirred for 1 h and then hydrolyzed with H2O (100 mL). Dilute aq. H2SO4 was added until the pH was slightly acidic. Et2O (50 mL) was next added and the mixture stirred for 10 min. The organic phase was separ­ated and the aqueous phase was extracted with Et2O (20 mL). The combined organic solutions were dried over MgSO4 and evaporated to give a colorless precipitate, yield 2.0 g (66%). 1H NMR (400 MHz, acetone-d 6): δ = 8.00 (2H, s, OH), 7.51 (2H, m), 7.39 (3H, m), 7.05 (1H, m); 13C{1H} NMR (100.6 MHz, acetone-d 6): δ = 141.49, 139.62, 139 (br), 136.17, 134.84, 130.49, 129.99, 128.24, 128.14, 127.53.

Crystals suitable for X-ray diffraction analysis were grown by slow evaporation of a THF solution.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All CH hydrogen atoms were placed in calculated positions with C—H distances of 0.95 or 0.99 Å. They were included in the refinement in the riding-motion approximation with U iso(phenyl H) = 1.2U eq(C). The positions of the OH hydrogen atoms were first found in a difference map. Then their bond lengths were restrained in the last least-squares cycles, with an O—H distance of 0.85 Å and their coordinates refined with U iso(hydroxyl H) = 1.5U eq(O).

Table 2

Experimental details

Crystal data
Chemical formula	C12H8BCl3O2·C4H8O
M r	373.45
Crystal system, space group	Triclinic, P
Temperature (K)	130
a, b, c (Å)	8.3306 (3), 8.7122 (2), 12.4307 (4)
α, β, γ (°)	98.683 (3), 97.737 (3), 99.398 (3)
V (Å3)	868.07 (5)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.54
Crystal size (mm)	0.15 × 0.12 × 0.10
Data collection
Diffractometer	Agilent SuperNova Dual Source diffractometer with an Atlas detector
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2014 ▸)
T min, T max	0.795, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	28647, 6107, 5162
R int	0.032
(sin θ/λ)max (Å−1)	0.758
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.034, 0.085, 1.05
No. of reflections	6107
No. of parameters	214
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.45, −0.36

Computer programs: CrysAlis PRO (Agilent, 2014 ▸), SHELXS97 (Sheldrick, 2015 ▸), SHELXL2013 (Sheldrick, 2015 ▸), DIAMOND (Brandenburg, 2005 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S205698901502054X/sj5482sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901502054X/sj5482Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901502054X/sj5482Isup3.cdx

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901502054X/sj5482Isup4.cdx

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901502054X/sj5482Isup5.cml

CCDC reference: 1434205

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

C12H8BCl3O2·C4H8O	F(000) = 384
Mr = 373.45	Dx = 1.429 Mg m−3
Triclinic, P1	Melting point: 411 K
a = 8.3306 (3) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.7122 (2) Å	Cell parameters from 14113 reflections
c = 12.4307 (4) Å	θ = 2.4–32.4°
α = 98.683 (3)°	µ = 0.54 mm−1
β = 97.737 (3)°	T = 130 K
γ = 99.398 (3)°	Fragment, colourless
V = 868.07 (5) Å3	0.15 × 0.12 × 0.10 mm
Z = 2

Agilent SuperNova Dual Source diffractometer with an Atlas detector	6107 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	5162 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.032
Detector resolution: 5.2195 pixels mm-1	θmax = 32.6°, θmin = 2.4°
ω scans	h = −12→12
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −13→13
Tmin = 0.795, Tmax = 1.000	l = −18→18
28647 measured reflections

Refinement on F2	2 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.085	w = 1/[σ2(Fo2) + (0.0328P)2 + 0.3549P] where P = (Fo2 + 2Fc2)/3
S = 1.05	(Δ/σ)max = 0.001
6107 reflections	Δρmax = 0.45 e Å−3
214 parameters	Δρmin = −0.36 e Å−3

Experimental. Absorption correction: CrysAlisPro (Agilent Technologies, 2014), Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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
C1	0.77416 (13)	0.33187 (12)	0.22248 (8)	0.01544 (18)
C2	0.85513 (13)	0.33777 (12)	0.13113 (9)	0.01761 (19)
C3	0.77605 (15)	0.28436 (14)	0.02290 (9)	0.0221 (2)
H3	0.8355	0.2914	−0.0368	0.027*
C5	0.52304 (15)	0.21255 (15)	0.09167 (10)	0.0233 (2)
H5	0.4085	0.1690	0.0782	0.028*
C6	0.60414 (13)	0.26808 (13)	0.19972 (9)	0.01703 (19)
C7	0.50529 (13)	0.26201 (13)	0.29144 (9)	0.01742 (19)
C8	0.47656 (14)	0.12861 (13)	0.34104 (9)	0.0188 (2)
C9	0.38144 (14)	0.12012 (15)	0.42447 (10)	0.0230 (2)
H9	0.3646	0.0276	0.4565	0.028*
C10	0.31167 (15)	0.24852 (16)	0.46023 (11)	0.0263 (2)
H10	0.2466	0.2441	0.5172	0.032*
C11	0.43238 (14)	0.38827 (13)	0.33025 (10)	0.0211 (2)
C12	0.33610 (15)	0.38351 (16)	0.41341 (11)	0.0262 (2)
H12	0.2879	0.4714	0.4377	0.031*
C13	0.60897 (16)	0.22065 (15)	0.00366 (10)	0.0257 (2)
H13	0.5531	0.1825	−0.0697	0.031*
C14	0.82695 (16)	0.75012 (14)	0.14313 (10)	0.0241 (2)
H14A	0.7067	0.7154	0.1184	0.029*
H14B	0.8843	0.6702	0.1077	0.029*
C15	0.88574 (17)	0.91105 (15)	0.11452 (11)	0.0283 (3)
H15A	0.8014	0.9785	0.1202	0.034*
H15B	0.9142	0.9012	0.0393	0.034*
C16	1.03885 (18)	0.97668 (16)	0.20241 (12)	0.0325 (3)
H16A	1.1369	0.9378	0.1804	0.039*
H16B	1.0621	1.0937	0.2165	0.039*
C17	0.9899 (2)	0.91251 (17)	0.30259 (12)	0.0358 (3)
H17A	1.0868	0.8873	0.3471	0.043*
H17B	0.9443	0.9914	0.3495	0.043*
B1	0.86796 (14)	0.39672 (14)	0.34516 (10)	0.0160 (2)
O1	0.92407 (11)	0.55444 (9)	0.38238 (7)	0.02050 (16)
O2	0.89019 (11)	0.29285 (10)	0.41379 (7)	0.02293 (17)
O3	0.86646 (12)	0.77103 (10)	0.26144 (7)	0.02631 (19)
Cl1	0.56394 (4)	−0.03377 (3)	0.29838 (2)	0.02648 (7)
Cl2	0.46307 (4)	0.55927 (3)	0.27352 (3)	0.02936 (8)
Cl3	1.06696 (3)	0.41387 (4)	0.15296 (2)	0.02402 (7)
H1A	0.902 (2)	0.6121 (19)	0.3383 (13)	0.036*
H2A	0.941 (2)	0.336 (2)	0.4767 (12)	0.036*

	U11	U22	U33	U12	U13	U23
C1	0.0179 (5)	0.0142 (4)	0.0137 (4)	0.0028 (3)	0.0005 (3)	0.0028 (3)
C2	0.0196 (5)	0.0163 (4)	0.0168 (5)	0.0029 (4)	0.0027 (4)	0.0034 (4)
C3	0.0289 (6)	0.0237 (5)	0.0148 (5)	0.0061 (4)	0.0047 (4)	0.0040 (4)
C5	0.0212 (5)	0.0264 (6)	0.0181 (5)	0.0002 (4)	−0.0030 (4)	0.0013 (4)
C6	0.0186 (5)	0.0169 (4)	0.0146 (4)	0.0025 (4)	0.0002 (4)	0.0028 (4)
C7	0.0156 (4)	0.0194 (5)	0.0152 (4)	0.0009 (4)	0.0001 (3)	0.0015 (4)
C8	0.0197 (5)	0.0202 (5)	0.0150 (5)	0.0025 (4)	0.0003 (4)	0.0014 (4)
C9	0.0208 (5)	0.0284 (6)	0.0192 (5)	0.0013 (4)	0.0022 (4)	0.0065 (4)
C10	0.0186 (5)	0.0363 (7)	0.0236 (6)	0.0033 (5)	0.0060 (4)	0.0044 (5)
C11	0.0176 (5)	0.0196 (5)	0.0243 (5)	0.0016 (4)	0.0010 (4)	0.0027 (4)
C12	0.0193 (5)	0.0296 (6)	0.0293 (6)	0.0065 (4)	0.0056 (4)	0.0005 (5)
C13	0.0305 (6)	0.0290 (6)	0.0138 (5)	0.0024 (5)	−0.0024 (4)	0.0013 (4)
C14	0.0267 (6)	0.0221 (5)	0.0226 (5)	0.0031 (4)	0.0000 (4)	0.0059 (4)
C15	0.0332 (7)	0.0258 (6)	0.0278 (6)	0.0044 (5)	0.0057 (5)	0.0114 (5)
C16	0.0333 (7)	0.0243 (6)	0.0375 (7)	−0.0023 (5)	0.0049 (6)	0.0068 (5)
C17	0.0411 (8)	0.0261 (6)	0.0328 (7)	−0.0066 (5)	−0.0064 (6)	0.0072 (5)
B1	0.0152 (5)	0.0170 (5)	0.0146 (5)	0.0022 (4)	0.0009 (4)	0.0015 (4)
O1	0.0278 (4)	0.0162 (4)	0.0149 (4)	0.0019 (3)	−0.0030 (3)	0.0027 (3)
O2	0.0302 (4)	0.0179 (4)	0.0170 (4)	0.0010 (3)	−0.0053 (3)	0.0036 (3)
O3	0.0328 (5)	0.0202 (4)	0.0233 (4)	−0.0005 (3)	−0.0017 (3)	0.0072 (3)
Cl1	0.04097 (17)	0.02093 (13)	0.02001 (13)	0.00986 (11)	0.00736 (11)	0.00481 (10)
Cl2	0.02627 (15)	0.02037 (13)	0.04284 (18)	0.00462 (10)	0.00663 (12)	0.00884 (12)
Cl3	0.01988 (13)	0.02816 (14)	0.02462 (14)	0.00239 (10)	0.00640 (10)	0.00636 (11)

C1—C2	1.3999 (15)	C11—Cl2	1.7388 (12)
C1—C6	1.4081 (15)	C12—H12	0.9500
C1—B1	1.5907 (16)	C13—H13	0.9500
C2—C3	1.3902 (16)	C14—O3	1.4400 (15)
C2—Cl3	1.7498 (11)	C14—C15	1.5183 (17)
C3—C13	1.3859 (18)	C14—H14A	0.9900
C3—H3	0.9500	C14—H14B	0.9900
C5—C13	1.3900 (17)	C15—C16	1.532 (2)
C5—C6	1.3954 (15)	C15—H15A	0.9900
C5—H5	0.9500	C15—H15B	0.9900
C6—C7	1.4959 (15)	C16—C17	1.517 (2)
C7—C11	1.3959 (16)	C16—H16A	0.9900
C7—C8	1.3976 (15)	C16—H16B	0.9900
C8—C9	1.3908 (16)	C17—O3	1.4465 (16)
C8—Cl1	1.7395 (12)	C17—H17A	0.9900
C9—C10	1.3851 (18)	C17—H17B	0.9900
C9—H9	0.9500	B1—O2	1.3514 (14)
C10—C12	1.3869 (19)	B1—O1	1.3641 (14)
C10—H10	0.9500	O1—H1A	0.821 (14)
C11—C12	1.3924 (17)	O2—H2A	0.838 (14)
C2—C1—C6	116.31 (9)	C3—C13—C5	120.03 (11)
C2—C1—B1	121.95 (9)	C3—C13—H13	120.0
C6—C1—B1	121.73 (9)	C5—C13—H13	120.0
C3—C2—C1	123.29 (10)	O3—C14—C15	105.36 (10)
C3—C2—Cl3	117.77 (9)	O3—C14—H14A	110.7
C1—C2—Cl3	118.93 (8)	C15—C14—H14A	110.7
C13—C3—C2	118.82 (11)	O3—C14—H14B	110.7
C13—C3—H3	120.6	C15—C14—H14B	110.7
C2—C3—H3	120.6	H14A—C14—H14B	108.8
C13—C5—C6	120.36 (11)	C14—C15—C16	102.13 (10)
C13—C5—H5	119.8	C14—C15—H15A	111.3
C6—C5—H5	119.8	C16—C15—H15A	111.3
C5—C6—C1	121.18 (10)	C14—C15—H15B	111.3
C5—C6—C7	118.41 (10)	C16—C15—H15B	111.3
C1—C6—C7	120.40 (9)	H15A—C15—H15B	109.2
C11—C7—C8	116.15 (10)	C17—C16—C15	102.58 (11)
C11—C7—C6	121.66 (10)	C17—C16—H16A	111.3
C8—C7—C6	122.17 (10)	C15—C16—H16A	111.3
C9—C8—C7	122.68 (11)	C17—C16—H16B	111.3
C9—C8—Cl1	118.09 (9)	C15—C16—H16B	111.3
C7—C8—Cl1	119.23 (9)	H16A—C16—H16B	109.2
C10—C9—C8	119.03 (11)	O3—C17—C16	106.63 (11)
C10—C9—H9	120.5	O3—C17—H17A	110.4
C8—C9—H9	120.5	C16—C17—H17A	110.4
C9—C10—C12	120.49 (11)	O3—C17—H17B	110.4
C9—C10—H10	119.8	C16—C17—H17B	110.4
C12—C10—H10	119.8	H17A—C17—H17B	108.6
C12—C11—C7	122.63 (11)	O2—B1—O1	119.71 (10)
C12—C11—Cl2	118.30 (9)	O2—B1—C1	118.96 (9)
C7—C11—Cl2	119.07 (9)	O1—B1—C1	121.33 (9)
C10—C12—C11	119.01 (12)	B1—O1—H1A	115.3 (13)
C10—C12—H12	120.5	B1—O2—H2A	113.1 (12)
C11—C12—H12	120.5	C14—O3—C17	109.77 (10)
C6—C1—C2—C3	−0.15 (16)	Cl1—C8—C9—C10	179.55 (9)
B1—C1—C2—C3	−178.97 (10)	C8—C9—C10—C12	0.09 (18)
C6—C1—C2—Cl3	−179.42 (8)	C8—C7—C11—C12	−0.07 (17)
B1—C1—C2—Cl3	1.76 (14)	C6—C7—C11—C12	178.17 (11)
C1—C2—C3—C13	−0.56 (17)	C8—C7—C11—Cl2	179.60 (8)
Cl3—C2—C3—C13	178.72 (9)	C6—C7—C11—Cl2	−2.15 (15)
C13—C5—C6—C1	−0.63 (18)	C9—C10—C12—C11	−0.26 (19)
C13—C5—C6—C7	177.91 (11)	C7—C11—C12—C10	0.25 (18)
C2—C1—C6—C5	0.74 (16)	Cl2—C11—C12—C10	−179.42 (10)
B1—C1—C6—C5	179.56 (10)	C2—C3—C13—C5	0.69 (18)
C2—C1—C6—C7	−177.77 (9)	C6—C5—C13—C3	−0.11 (19)
B1—C1—C6—C7	1.05 (15)	O3—C14—C15—C16	33.84 (13)
C5—C6—C7—C11	−90.69 (13)	C14—C15—C16—C17	−35.53 (14)
C1—C6—C7—C11	87.86 (13)	C15—C16—C17—O3	25.23 (15)
C5—C6—C7—C8	87.44 (14)	C2—C1—B1—O2	−111.66 (12)
C1—C6—C7—C8	−94.00 (13)	C6—C1—B1—O2	69.59 (14)
C11—C7—C8—C9	−0.11 (16)	C2—C1—B1—O1	69.17 (14)
C6—C7—C8—C9	−178.35 (10)	C6—C1—B1—O1	−109.58 (12)
C11—C7—C8—Cl1	−179.56 (8)	C15—C14—O3—C17	−18.86 (14)
C6—C7—C8—Cl1	2.21 (14)	C16—C17—O3—C14	−4.30 (16)
C7—C8—C9—C10	0.10 (17)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1A···O3	0.82 (1)	1.84 (1)	2.6475 (12)	169 (2)
O2—H2A···O1i	0.84 (1)	1.96 (1)	2.7997 (12)	175 (2)