Crystal structure of {[2-hy-droxy-2-(3-meth-oxy-phen-yl)cyclo-hex-yl]meth-yl}di-methyl-ammonium benzoate.

The title compound, C16H26NO2 (+)·C7H5O2 (-), is a benzoate salt of the painkiller Tramadol. The six-membered cyclo-hexane ring of the cation adopts a slightly distorted chair conformation and carries OH and 3-meth-oxy-phenyl substituents at the 2-position and a protonated methyl-aza-niumylmethyl group at the 3-position. In addition, a weak intra-molecular C-H⋯O hydrogen bond is observed in the cation. In the crystal, weak O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds link the components into chains along [010]. A C-H⋯π contact is also observed.

Related literature

For pharmaceutical applications of Tramadol and related analgesics, see: Scott & Perry (2000 ▸). For related structures, see: Tessler & Goldberg (2004 ▸); Arman et al. (2010 ▸); Hemamalini & Fun (2010 ▸); Siddaraju et al. (2011 ▸); Lin & Zhang (2013 ▸); Smith (2014 ▸); Jasinski et al. (2015 ▸); Sun et al. (2012 ▸).

Experimental

Crystal data

C16H26NO2 +·C7H5O2 −

M = 385.49

Triclinic,

a = 9.013 (4) Å

b = 9.767 (4) Å

c = 12.726 (6) Å

α = 75.008 (16)°

β = 89.79 (2)°

γ = 76.493 (16)°

V = 1050.3 (8) Å3

Z = 2

Mo Kα radiation

μ = 0.08 mm−1

T = 293 K

0.55 × 0.51 × 0.3 mm

Data collection

Rigaku Saturn724+ diffractometer

Absorption correction: multi-scan (NUMABS; Rigaku 1999 ▸) T min = 0.955, T max = 0.975

11931 measured reflections

5660 independent reflections

3504 reflections with I > 2σ(I)

R int = 0.029

Refinement

R[F 2 > 2σ(F 2)] = 0.053

wR(F 2) = 0.134

S = 1.03

5660 reflections

257 parameters

H-atom parameters constrained

Δρmax = 0.17 e Å−3

Δρmin = −0.21 e Å−3

Data collection: CrystalClear SM Expert (Rigaku, 2011 ▸); cell refinement: CrystalClear SM Expert; data reduction: CrystalClear SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▸) and Mercury (Macrae et al., 2008 ▸); software used to prepare material for publication: OLEX2.

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989015019362/sj5480sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015019362/sj5480Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989015019362/sj5480Isup3.cml

Click here for additional data file.

. DOI: 10.1107/S2056989015019362/sj5480fig1.tif

A view of the title mol­ecule, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level and an intra­molecular hydrogen bond is drawn as a dashed line.

Click here for additional data file.

a . DOI: 10.1107/S2056989015019362/sj5480fig2.tif

A viewed along the a axis of the crystal packing of the title compound. Hydrogen bonds are drawn as a dashed lines.

CCDC reference: 1425991

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

C16H26NO2+·C7H5O2−	Z = 2
Mr = 385.49	F(000) = 416
Triclinic, P1	Dx = 1.219 Mg m−3
a = 9.013 (4) Å	Mo Kα radiation, λ = 0.71075 Å
b = 9.767 (4) Å	Cell parameters from 5660 reflections
c = 12.726 (6) Å	θ = 3.0–29.5°
α = 75.008 (16)°	µ = 0.08 mm−1
β = 89.79 (2)°	T = 293 K
γ = 76.493 (16)°	Block, colourless
V = 1050.3 (8) Å3	0.55 × 0.51 × 0.3 mm

Rigaku Saturn724+ diffractometer	5660 independent reflections
Radiation source: Sealed tube, Rotating Anode	3504 reflections with I > 2σ(I)
Confocal monochromator	Rint = 0.029
Detector resolution: 28.5714 pixels mm-1	θmax = 29.5°, θmin = 3.0°
profile data from ω–scans	h = −12→11
Absorption correction: multi-scan (NUMABS; Rigaku 1999)	k = −13→13
Tmin = 0.955, Tmax = 0.975	l = −17→14
11931 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.053	H-atom parameters constrained
wR(F2) = 0.134	w = 1/[σ2(Fo2) + (0.0598P)2] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max = 0.001
5660 reflections	Δρmax = 0.17 e Å−3
257 parameters	Δρmin = −0.21 e Å−3
0 restraints

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	0.51600 (17)	0.30154 (17)	0.58415 (12)	0.0418 (4)
C2	0.39216 (17)	0.38352 (18)	0.62190 (13)	0.0502 (4)
H2	0.2941	0.3959	0.5925	0.060*
C3	0.41457 (17)	0.44717 (17)	0.70353 (14)	0.0520 (4)
H3	0.3314	0.5032	0.7290	0.062*
C4	0.56018 (16)	0.42788 (16)	0.74757 (13)	0.0448 (4)
H4	0.5738	0.4708	0.8029	0.054*
C5	0.68653 (15)	0.34553 (14)	0.71072 (11)	0.0332 (3)
C6	0.66294 (15)	0.28320 (15)	0.62715 (11)	0.0366 (3)
H6	0.7459	0.2291	0.6001	0.044*
C8	0.6071 (2)	0.1648 (2)	0.45646 (15)	0.0697 (5)
H8A	0.5688	0.1311	0.4000	0.104*
H8B	0.6659	0.0829	0.5111	0.104*
H8C	0.6707	0.2297	0.4258	0.104*
C9	0.84766 (14)	0.31719 (13)	0.76345 (10)	0.0310 (3)
C11	0.85527 (17)	0.21038 (15)	0.87622 (11)	0.0406 (3)
H11A	0.7688	0.2473	0.9152	0.049*
H11B	0.8451	0.1174	0.8670	0.049*
C12	1.00060 (18)	0.18474 (16)	0.94543 (12)	0.0465 (4)
H12A	1.0865	0.1338	0.9130	0.056*
H12B	0.9923	0.1239	1.0176	0.056*
C13	1.0282 (2)	0.32939 (16)	0.95426 (12)	0.0491 (4)
H13A	0.9471	0.3760	0.9929	0.059*
H13B	1.1243	0.3118	0.9954	0.059*
C14	1.03296 (17)	0.42967 (16)	0.84145 (11)	0.0417 (4)
H14A	1.1171	0.3845	0.8044	0.050*
H14B	1.0512	0.5210	0.8486	0.050*
C15	0.88435 (15)	0.46093 (13)	0.77334 (10)	0.0317 (3)
H15	0.8016	0.5100	0.8107	0.038*
C16	0.88662 (16)	0.56049 (14)	0.65994 (10)	0.0358 (3)
H16A	0.9709	0.5144	0.6235	0.043*
H16B	0.7929	0.5688	0.6190	0.043*
C18	0.77644 (17)	0.79335 (16)	0.70698 (14)	0.0508 (4)
H18A	0.6805	0.8004	0.6709	0.076*
H18B	0.7905	0.8896	0.7005	0.076*
H18C	0.7767	0.7434	0.7826	0.076*
C19	0.9145 (2)	0.79324 (17)	0.54203 (12)	0.0572 (5)
H19A	0.9985	0.7395	0.5112	0.086*
H19B	0.9315	0.8870	0.5410	0.086*
H19C	0.8215	0.8062	0.5001	0.086*
N17	0.90203 (13)	0.71131 (11)	0.65610 (9)	0.0337 (3)
H17	0.9976	0.7013	0.6970	0.040*
O7	0.48324 (13)	0.23977 (15)	0.50425 (10)	0.0642 (3)
O10	0.96103 (10)	0.26098 (10)	0.69699 (8)	0.0372 (2)
H10	0.9774	0.1717	0.7133	0.056*
C20	0.38473 (18)	0.75688 (18)	0.88067 (13)	0.0492 (4)
H20	0.3598	0.6668	0.8964	0.059*
C21	0.29160 (16)	0.87614 (15)	0.80738 (11)	0.0376 (3)
C22	0.33245 (18)	1.00897 (17)	0.78461 (12)	0.0471 (4)
H22	0.2706	1.0903	0.7362	0.056*
C23	0.4632 (2)	1.0218 (2)	0.83276 (14)	0.0564 (4)
H23	0.4902	1.1110	0.8155	0.068*
C24	0.5540 (2)	0.9031 (2)	0.90636 (14)	0.0595 (5)
H24	0.6417	0.9121	0.9396	0.071*
C25	0.51482 (19)	0.7706 (2)	0.93080 (13)	0.0597 (5)
H25	0.5757	0.6903	0.9809	0.072*
C26	0.15086 (16)	0.86086 (15)	0.75316 (12)	0.0385 (3)
O27	0.05139 (13)	0.97122 (11)	0.70637 (10)	0.0600 (3)
O28	0.14406 (12)	0.73144 (11)	0.75774 (9)	0.0529 (3)

	U11	U22	U33	U12	U13	U23
C1	0.0387 (8)	0.0477 (9)	0.0414 (8)	−0.0137 (7)	0.0007 (7)	−0.0132 (7)
C2	0.0321 (8)	0.0561 (10)	0.0601 (10)	−0.0087 (7)	−0.0010 (7)	−0.0132 (8)
C3	0.0344 (8)	0.0496 (9)	0.0740 (12)	−0.0053 (7)	0.0125 (8)	−0.0245 (8)
C4	0.0378 (8)	0.0443 (9)	0.0602 (10)	−0.0115 (7)	0.0102 (7)	−0.0262 (7)
C5	0.0323 (7)	0.0281 (7)	0.0405 (8)	−0.0102 (5)	0.0069 (6)	−0.0088 (6)
C6	0.0330 (7)	0.0382 (7)	0.0400 (8)	−0.0092 (6)	0.0056 (6)	−0.0123 (6)
C8	0.0581 (11)	0.0930 (15)	0.0678 (12)	−0.0084 (10)	−0.0036 (9)	−0.0474 (11)
C9	0.0315 (7)	0.0276 (6)	0.0357 (7)	−0.0079 (5)	0.0060 (6)	−0.0110 (5)
C11	0.0485 (9)	0.0320 (7)	0.0422 (8)	−0.0154 (6)	0.0049 (7)	−0.0066 (6)
C12	0.0566 (10)	0.0363 (8)	0.0421 (8)	−0.0103 (7)	−0.0034 (7)	−0.0031 (6)
C13	0.0608 (10)	0.0446 (9)	0.0418 (8)	−0.0145 (8)	−0.0104 (8)	−0.0094 (7)
C14	0.0459 (8)	0.0378 (8)	0.0459 (8)	−0.0181 (7)	−0.0024 (7)	−0.0117 (6)
C15	0.0373 (7)	0.0265 (6)	0.0340 (7)	−0.0107 (5)	0.0048 (6)	−0.0103 (5)
C16	0.0453 (8)	0.0308 (7)	0.0353 (7)	−0.0145 (6)	0.0059 (6)	−0.0109 (6)
C18	0.0457 (9)	0.0358 (8)	0.0688 (11)	−0.0039 (7)	0.0084 (8)	−0.0157 (8)
C19	0.0827 (13)	0.0446 (9)	0.0448 (9)	−0.0267 (9)	0.0087 (9)	−0.0026 (7)
N17	0.0359 (6)	0.0283 (6)	0.0367 (6)	−0.0095 (5)	0.0029 (5)	−0.0068 (5)
O7	0.0439 (7)	0.0989 (10)	0.0628 (7)	−0.0173 (6)	−0.0012 (6)	−0.0441 (7)
O10	0.0351 (5)	0.0303 (5)	0.0485 (6)	−0.0063 (4)	0.0100 (4)	−0.0159 (4)
C20	0.0484 (9)	0.0480 (9)	0.0520 (9)	−0.0139 (7)	0.0082 (8)	−0.0130 (7)
C21	0.0389 (8)	0.0382 (8)	0.0414 (8)	−0.0117 (6)	0.0102 (7)	−0.0181 (6)
C22	0.0516 (9)	0.0422 (9)	0.0537 (9)	−0.0166 (7)	0.0031 (8)	−0.0189 (7)
C23	0.0552 (10)	0.0590 (11)	0.0692 (11)	−0.0273 (9)	0.0082 (9)	−0.0298 (9)
C24	0.0468 (10)	0.0835 (14)	0.0627 (11)	−0.0240 (10)	0.0060 (9)	−0.0373 (10)
C25	0.0486 (10)	0.0716 (12)	0.0551 (10)	−0.0090 (9)	−0.0020 (8)	−0.0146 (9)
C26	0.0404 (8)	0.0322 (7)	0.0480 (9)	−0.0109 (6)	0.0092 (7)	−0.0180 (6)
O27	0.0577 (7)	0.0345 (6)	0.0870 (8)	−0.0044 (5)	−0.0161 (7)	−0.0205 (6)
O28	0.0441 (6)	0.0321 (5)	0.0852 (8)	−0.0119 (5)	−0.0046 (6)	−0.0178 (5)

C1—C2	1.377 (2)	C14—C15	1.5229 (19)
C1—C6	1.389 (2)	C15—H15	0.9800
C1—O7	1.3739 (19)	C15—C16	1.5204 (18)
C2—H2	0.9300	C16—H16A	0.9700
C2—C3	1.379 (2)	C16—H16B	0.9700
C3—H3	0.9300	C16—N17	1.5000 (17)
C3—C4	1.381 (2)	C18—H18A	0.9600
C4—H4	0.9300	C18—H18B	0.9600
C4—C5	1.3881 (18)	C18—H18C	0.9600
C5—C6	1.3944 (19)	C18—N17	1.4771 (17)
C5—C9	1.5359 (19)	C19—H19A	0.9600
C6—H6	0.9300	C19—H19B	0.9600
C8—H8A	0.9600	C19—H19C	0.9600
C8—H8B	0.9600	C19—N17	1.4833 (18)
C8—H8C	0.9600	N17—H17	0.9800
C8—O7	1.4126 (19)	O10—H10	0.8200
C9—C11	1.5314 (19)	C20—H20	0.9300
C9—C15	1.5507 (18)	C20—C21	1.385 (2)
C9—O10	1.4257 (15)	C20—C25	1.386 (2)
C11—H11A	0.9700	C21—C22	1.389 (2)
C11—H11B	0.9700	C21—C26	1.502 (2)
C11—C12	1.515 (2)	C22—H22	0.9300
C12—H12A	0.9700	C22—C23	1.376 (2)
C12—H12B	0.9700	C23—H23	0.9300
C12—C13	1.522 (2)	C23—C24	1.376 (2)
C13—H13A	0.9700	C24—H24	0.9300
C13—H13B	0.9700	C24—C25	1.379 (2)
C13—C14	1.521 (2)	C25—H25	0.9300
C14—H14A	0.9700	C26—O27	1.2412 (17)
C14—H14B	0.9700	C26—O28	1.2661 (17)
C2—C1—C6	120.59 (14)	C9—C15—H15	107.9
O7—C1—C2	115.75 (14)	C14—C15—C9	110.98 (11)
O7—C1—C6	123.65 (14)	C14—C15—H15	107.9
C1—C2—H2	120.2	C16—C15—C9	109.26 (10)
C1—C2—C3	119.53 (14)	C16—C15—C14	112.67 (11)
C3—C2—H2	120.2	C16—C15—H15	107.9
C2—C3—H3	119.9	C15—C16—H16A	108.4
C2—C3—C4	120.17 (15)	C15—C16—H16B	108.4
C4—C3—H3	119.9	H16A—C16—H16B	107.5
C3—C4—H4	119.4	N17—C16—C15	115.49 (10)
C3—C4—C5	121.20 (14)	N17—C16—H16A	108.4
C5—C4—H4	119.4	N17—C16—H16B	108.4
C4—C5—C6	118.22 (13)	H18A—C18—H18B	109.5
C4—C5—C9	121.36 (12)	H18A—C18—H18C	109.5
C6—C5—C9	120.36 (12)	H18B—C18—H18C	109.5
C1—C6—C5	120.28 (13)	N17—C18—H18A	109.5
C1—C6—H6	119.9	N17—C18—H18B	109.5
C5—C6—H6	119.9	N17—C18—H18C	109.5
H8A—C8—H8B	109.5	H19A—C19—H19B	109.5
H8A—C8—H8C	109.5	H19A—C19—H19C	109.5
H8B—C8—H8C	109.5	H19B—C19—H19C	109.5
O7—C8—H8A	109.5	N17—C19—H19A	109.5
O7—C8—H8B	109.5	N17—C19—H19B	109.5
O7—C8—H8C	109.5	N17—C19—H19C	109.5
C5—C9—C15	111.34 (10)	C16—N17—H17	107.6
C11—C9—C5	107.75 (10)	C18—N17—C16	112.99 (11)
C11—C9—C15	110.47 (11)	C18—N17—C19	110.77 (12)
O10—C9—C5	110.85 (11)	C18—N17—H17	107.6
O10—C9—C11	111.47 (11)	C19—N17—C16	110.13 (10)
O10—C9—C15	105.01 (10)	C19—N17—H17	107.6
C9—C11—H11A	108.6	C1—O7—C8	117.87 (12)
C9—C11—H11B	108.6	C9—O10—H10	109.5
H11A—C11—H11B	107.6	C21—C20—H20	119.7
C12—C11—C9	114.67 (12)	C21—C20—C25	120.58 (16)
C12—C11—H11A	108.6	C25—C20—H20	119.7
C12—C11—H11B	108.6	C20—C21—C22	118.47 (14)
C11—C12—H12A	109.6	C20—C21—C26	120.42 (13)
C11—C12—H12B	109.6	C22—C21—C26	121.10 (13)
C11—C12—C13	110.42 (12)	C21—C22—H22	119.5
H12A—C12—H12B	108.1	C23—C22—C21	120.94 (15)
C13—C12—H12A	109.6	C23—C22—H22	119.5
C13—C12—H12B	109.6	C22—C23—H23	119.9
C12—C13—H13A	109.6	C24—C23—C22	120.10 (16)
C12—C13—H13B	109.6	C24—C23—H23	119.9
H13A—C13—H13B	108.1	C23—C24—H24	120.1
C14—C13—C12	110.39 (12)	C23—C24—C25	119.87 (16)
C14—C13—H13A	109.6	C25—C24—H24	120.1
C14—C13—H13B	109.6	C20—C25—H25	120.0
C13—C14—H14A	109.3	C24—C25—C20	120.03 (16)
C13—C14—H14B	109.3	C24—C25—H25	120.0
C13—C14—C15	111.70 (12)	O27—C26—C21	120.10 (13)
H14A—C14—H14B	107.9	O27—C26—O28	124.15 (14)
C15—C14—H14A	109.3	O28—C26—C21	115.75 (13)
C15—C14—H14B	109.3
C1—C2—C3—C4	−0.4 (2)	C12—C13—C14—C15	59.28 (17)
C2—C1—C6—C5	1.2 (2)	C13—C14—C15—C9	−56.84 (15)
C2—C1—O7—C8	174.83 (15)	C13—C14—C15—C16	−179.74 (12)
C2—C3—C4—C5	0.4 (2)	C14—C15—C16—N17	−63.19 (16)
C3—C4—C5—C6	0.4 (2)	C15—C9—C11—C12	−51.00 (15)
C3—C4—C5—C9	−176.79 (13)	C15—C16—N17—C18	−59.79 (16)
C4—C5—C6—C1	−1.23 (19)	C15—C16—N17—C19	175.76 (12)
C4—C5—C9—C11	71.47 (15)	O7—C1—C2—C3	178.80 (14)
C4—C5—C9—C15	−49.81 (16)	O7—C1—C6—C5	−177.88 (13)
C4—C5—C9—O10	−166.32 (11)	O10—C9—C11—C12	65.34 (15)
C5—C9—C11—C12	−172.82 (11)	O10—C9—C15—C14	−68.97 (13)
C5—C9—C15—C14	171.00 (10)	O10—C9—C15—C16	55.87 (13)
C5—C9—C15—C16	−64.15 (13)	C20—C21—C22—C23	0.7 (2)
C6—C1—C2—C3	−0.3 (2)	C20—C21—C26—O27	164.70 (14)
C6—C1—O7—C8	−6.0 (2)	C20—C21—C26—O28	−16.30 (19)
C6—C5—C9—C11	−105.71 (14)	C21—C20—C25—C24	−1.2 (2)
C6—C5—C9—C15	133.01 (13)	C21—C22—C23—C24	−1.4 (2)
C6—C5—C9—O10	16.51 (16)	C22—C21—C26—O27	−16.0 (2)
C9—C5—C6—C1	176.03 (12)	C22—C21—C26—O28	163.00 (13)
C9—C11—C12—C13	53.62 (16)	C22—C23—C24—C25	0.8 (2)
C9—C15—C16—N17	172.96 (11)	C23—C24—C25—C20	0.5 (2)
C11—C9—C15—C14	51.32 (14)	C25—C20—C21—C22	0.6 (2)
C11—C9—C15—C16	176.17 (11)	C25—C20—C21—C26	179.94 (13)
C11—C12—C13—C14	−56.17 (17)	C26—C21—C22—C23	−178.64 (13)

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O10	0.93	2.42	2.775 (2)	102
C14—H14B···O28i	0.97	2.41	3.251 (2)	144
N17—H17···O28i	0.98	1.65	2.6120 (18)	165
O10—H10···O27ii	0.82	1.94	2.7269 (17)	161
C23—H23···Cg1iii	0.93	2.83	3.684 (3)	153

Table 1

Hydrogen-bond geometry (, )

Cg1 is the centroid of the C1C6 benzene ring.

DHA	DH	HA	D A	DHA
C6H6O10	0.93	2.42	2.775(2)	102
C14H14BO28i	0.97	2.41	3.251(2)	144
N17H17O28i	0.98	1.65	2.6120(18)	165
O10H10O27ii	0.82	1.94	2.7269(17)	161
C23H23Cg1iii	0.93	2.83	3.684(3)	153

Symmetry codes: (i) ; (ii) ; (iii) .