Dextromethorphan, an antitussive agent

The title compound, 4-meth­oxy-12-meth­yl-12-aza­tetra­cyclo­[9.3^1,10.0^2,7]hepta­deca-2(7),3,5-triene, C₁₈H₂₅NO, has a T-shaped configuration, with the benzene ring (A) and the fused carbocyclic ring (C) forming the upright stock; the other carbocyclic ring (D) and the piperidine ring (E) are in the arm positions. Rings C, D and E have sofa, chair and chair conformations, respectively. In the crystal packing, the mol­ecules are joined through C—H...O hydrogen bonding into chains running along the c axis.

Key indicators

• Single-crystal X-ray study
• T = 273 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.038
• wR factor = 0.102
• Data-to-parameter ratio = 11.3

checkCIF/PLATON results

No syntax errors found



Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.99
           From the CIF: _reflns_number_total               2066
           Count of symmetry unique reflns         2097
           Completeness (_total/calc)             98.52%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   0 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

---

Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995).

4-methoxy-12-methyl-12-azatetracyclo[9.3^1.10.0^2.7] heptadeca-2(7),3,5-triene

Crystal data

C18H25NO	F(000) = 592
Mr = 271.39	Dx = 1.195 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 6946 reflections
a = 14.0356 (12) Å	θ = 2.7–27.8°
b = 15.0658 (13) Å	µ = 0.07 mm^−1
c = 7.1354 (6) Å	T = 273 K
V = 1508.8 (2) Å^3	Needle, colourless
Z = 4	0.22 × 0.18 × 0.16 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer	1963 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.021
Graphite monochromator	θmax = 28.0°, θmin = 2.0°
ω scans	h = −18→18
13046 measured reflections	k = −19→19
2066 independent reflections	l = −9→9

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.102	H-atom parameters constrained
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0624P)^2 + 0.1352P] where P = (Fo^2 + 2Fc^2)/3
2066 reflections	(Δ/σ)max = 0.001
183 parameters	Δρmax = 0.23 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

Special details

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	1.13876 (11)	0.25661 (11)	0.7611 (2)	0.0413 (4)
H1	1.1531	0.3167	0.7508	0.050*
C2	1.19995 (12)	0.19619 (12)	0.6849 (2)	0.0443 (4)
H2	1.2549	0.2149	0.6236	0.053*
C3	1.17914 (11)	0.10603 (12)	0.7000 (2)	0.0406 (4)
C4	1.09516 (11)	0.07922 (10)	0.7868 (2)	0.0377 (3)
H4	1.0804	0.0191	0.7930	0.045*
C5	0.89891 (12)	0.02597 (11)	0.8931 (3)	0.0433 (4)
H5A	0.9470	−0.0198	0.8795	0.052*
H5B	0.8510	0.0043	0.9797	0.052*
C6	0.85252 (14)	0.04260 (13)	0.7034 (3)	0.0547 (5)
H6A	0.9011	0.0590	0.6131	0.066*
H6B	0.8224	−0.0116	0.6600	0.066*
C7	0.77850 (14)	0.11596 (14)	0.7154 (3)	0.0593 (5)
H7A	0.7263	0.0969	0.7949	0.071*
H7B	0.7531	0.1278	0.5914	0.071*
C8	0.82238 (13)	0.20085 (12)	0.7951 (3)	0.0483 (4)
H8A	0.8693	0.2237	0.7077	0.058*
H8B	0.7730	0.2454	0.8097	0.058*
C9	0.91478 (11)	0.26648 (11)	1.0712 (2)	0.0384 (3)
H9	0.8650	0.3120	1.0783	0.046*
C10	0.99298 (12)	0.30212 (10)	0.9411 (2)	0.0410 (3)
H10A	0.9632	0.3360	0.8415	0.049*
H10B	1.0331	0.3424	1.0118	0.049*
C11	1.05504 (10)	0.23151 (10)	0.8543 (2)	0.0356 (3)
C12	1.03261 (10)	0.14125 (10)	0.8649 (2)	0.0342 (3)
C13	0.94546 (10)	0.10962 (10)	0.9759 (2)	0.0347 (3)
C14	0.86987 (10)	0.18396 (10)	0.9845 (2)	0.0374 (3)
H14	0.8199	0.1639	1.0706	0.045*
C15	0.97785 (12)	0.09145 (11)	1.1794 (2)	0.0419 (4)
H15A	0.9247	0.0675	1.2499	0.050*
H15B	1.0280	0.0471	1.1782	0.050*
C16	1.01421 (12)	0.17438 (12)	1.2771 (2)	0.0447 (4)
H16A	1.0268	0.1612	1.4078	0.054*
H16B	1.0735	0.1931	1.2197	0.054*
C17	0.97607 (15)	0.32453 (13)	1.3656 (3)	0.0557 (5)
H17A	1.0355	0.3447	1.3142	0.083*
H17B	0.9846	0.3099	1.4955	0.083*
H17C	0.9293	0.3707	1.3542	0.083*
C18	1.22770 (17)	−0.04348 (14)	0.6454 (4)	0.0662 (6)
H18A	1.1722	−0.0581	0.5731	0.099*
H18B	1.2169	−0.0586	0.7744	0.099*
H18C	1.2814	−0.0762	0.5989	0.099*
O1	1.24627 (9)	0.04877 (10)	0.6304 (2)	0.0565 (4)
N1	0.94412 (10)	0.24632 (9)	1.2641 (2)	0.0423 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0389 (7)	0.0397 (8)	0.0452 (8)	−0.0099 (6)	−0.0021 (7)	0.0055 (7)
C2	0.0330 (7)	0.0566 (9)	0.0432 (8)	−0.0091 (7)	0.0036 (7)	0.0043 (8)
C3	0.0339 (7)	0.0496 (8)	0.0384 (8)	−0.0030 (6)	0.0025 (6)	−0.0032 (7)
C4	0.0354 (7)	0.0381 (7)	0.0394 (8)	−0.0041 (6)	0.0006 (6)	−0.0011 (6)
C5	0.0385 (7)	0.0369 (8)	0.0545 (10)	−0.0073 (6)	0.0045 (7)	0.0033 (7)
C6	0.0552 (10)	0.0491 (9)	0.0599 (11)	−0.0131 (8)	−0.0099 (9)	−0.0073 (9)
C7	0.0521 (9)	0.0603 (11)	0.0655 (12)	−0.0104 (9)	−0.0200 (10)	0.0016 (10)
C8	0.0433 (8)	0.0466 (9)	0.0551 (10)	0.0007 (7)	−0.0133 (8)	0.0046 (8)
C9	0.0379 (7)	0.0376 (7)	0.0397 (7)	0.0049 (6)	0.0004 (7)	0.0018 (6)
C10	0.0459 (8)	0.0345 (7)	0.0425 (8)	−0.0017 (6)	0.0033 (7)	0.0029 (6)
C11	0.0349 (7)	0.0374 (7)	0.0345 (7)	−0.0031 (6)	−0.0021 (6)	0.0036 (6)
C12	0.0316 (6)	0.0384 (7)	0.0325 (7)	−0.0037 (6)	−0.0013 (6)	0.0027 (6)
C13	0.0319 (6)	0.0356 (7)	0.0367 (7)	−0.0021 (6)	0.0027 (6)	0.0049 (6)
C14	0.0316 (6)	0.0402 (8)	0.0404 (7)	−0.0004 (6)	0.0019 (6)	0.0043 (7)
C15	0.0426 (8)	0.0431 (8)	0.0402 (8)	0.0037 (7)	0.0030 (7)	0.0105 (7)
C16	0.0450 (8)	0.0523 (9)	0.0370 (8)	0.0039 (7)	−0.0045 (7)	0.0054 (7)
C17	0.0617 (11)	0.0564 (11)	0.0489 (9)	−0.0015 (9)	−0.0027 (9)	−0.0098 (9)
C18	0.0637 (11)	0.0522 (11)	0.0827 (15)	0.0017 (9)	0.0251 (12)	−0.0183 (11)
O1	0.0439 (6)	0.0561 (8)	0.0696 (9)	−0.0027 (6)	0.0182 (7)	−0.0100 (7)
N1	0.0450 (7)	0.0445 (7)	0.0372 (7)	0.0026 (6)	0.0009 (6)	−0.0014 (6)

Geometric parameters (Å, º)

C1—C2	1.365 (2)	C9—C10	1.535 (2)
C1—C11	1.402 (2)	C9—H9	0.9800
C1—H1	0.9300	C10—C11	1.508 (2)
C2—C3	1.394 (3)	C10—H10A	0.9700
C2—H2	0.9300	C10—H10B	0.9700
C3—O1	1.371 (2)	C11—C12	1.398 (2)
C3—C4	1.392 (2)	C12—C13	1.533 (2)
C4—C12	1.398 (2)	C13—C14	1.544 (2)
C4—H4	0.9300	C13—C15	1.546 (2)
C5—C6	1.522 (3)	C14—H14	0.9800
C5—C13	1.538 (2)	C15—C16	1.519 (2)
C5—H5A	0.9700	C15—H15A	0.9700
C5—H5B	0.9700	C15—H15B	0.9700
C6—C7	1.519 (3)	C16—N1	1.467 (2)
C6—H6A	0.9700	C16—H16A	0.9700
C6—H6B	0.9700	C16—H16B	0.9700
C7—C8	1.529 (3)	C17—N1	1.454 (2)
C7—H7A	0.9700	C17—H17A	0.9600
C7—H7B	0.9700	C17—H17B	0.9600
C8—C14	1.529 (2)	C17—H17C	0.9600
C8—H8A	0.9700	C18—O1	1.418 (2)
C8—H8B	0.9700	C18—H18A	0.9600
C9—N1	1.468 (2)	C18—H18B	0.9600
C9—C14	1.525 (2)	C18—H18C	0.9600
C2—C1—C11	122.45 (15)	H10A—C10—H10B	107.6
C2—C1—H1	118.8	C12—C11—C1	118.46 (15)
C11—C1—H1	118.8	C12—C11—C10	122.29 (14)
C1—C2—C3	119.18 (15)	C1—C11—C10	119.25 (14)
C1—C2—H2	120.4	C11—C12—C4	119.17 (14)
C3—C2—H2	120.4	C11—C12—C13	120.66 (14)
O1—C3—C4	124.12 (15)	C4—C12—C13	119.94 (14)
O1—C3—C2	116.19 (14)	C12—C13—C5	113.29 (13)
C4—C3—C2	119.66 (15)	C12—C13—C14	110.08 (12)
C3—C4—C12	121.02 (14)	C5—C13—C14	108.54 (12)
C3—C4—H4	119.5	C12—C13—C15	107.79 (12)
C12—C4—H4	119.5	C5—C13—C15	109.93 (13)
C6—C5—C13	112.86 (14)	C14—C13—C15	107.03 (13)
C6—C5—H5A	109.0	C9—C14—C8	113.78 (13)
C13—C5—H5A	109.0	C9—C14—C13	108.88 (12)
C6—C5—H5B	109.0	C8—C14—C13	112.64 (13)
C13—C5—H5B	109.0	C9—C14—H14	107.1
H5A—C5—H5B	107.8	C8—C14—H14	107.1
C7—C6—C5	111.24 (17)	C13—C14—H14	107.1
C7—C6—H6A	109.4	C16—C15—C13	112.60 (13)
C5—C6—H6A	109.4	C16—C15—H15A	109.1
C7—C6—H6B	109.4	C13—C15—H15A	109.1
C5—C6—H6B	109.4	C16—C15—H15B	109.1
H6A—C6—H6B	108.0	C13—C15—H15B	109.1
C6—C7—C8	110.72 (14)	H15A—C15—H15B	107.8
C6—C7—H7A	109.5	N1—C16—C15	110.70 (13)
C8—C7—H7A	109.5	N1—C16—H16A	109.5
C6—C7—H7B	109.5	C15—C16—H16A	109.5
C8—C7—H7B	109.5	N1—C16—H16B	109.5
H7A—C7—H7B	108.1	C15—C16—H16B	109.5
C14—C8—C7	111.43 (15)	H16A—C16—H16B	108.1
C14—C8—H8A	109.3	N1—C17—H17A	109.5
C7—C8—H8A	109.3	N1—C17—H17B	109.5
C14—C8—H8B	109.3	H17A—C17—H17B	109.5
C7—C8—H8B	109.3	N1—C17—H17C	109.5
H8A—C8—H8B	108.0	H17A—C17—H17C	109.5
N1—C9—C14	109.12 (13)	H17B—C17—H17C	109.5
N1—C9—C10	116.03 (13)	O1—C18—H18A	109.5
C14—C9—C10	109.60 (13)	O1—C18—H18B	109.5
N1—C9—H9	107.2	H18A—C18—H18B	109.5
C14—C9—H9	107.2	O1—C18—H18C	109.5
C10—C9—H9	107.2	H18A—C18—H18C	109.5
C11—C10—C9	114.50 (13)	H18B—C18—H18C	109.5
C11—C10—H10A	108.6	C3—O1—C18	117.59 (14)
C9—C10—H10A	108.6	C17—N1—C16	111.13 (14)
C11—C10—H10B	108.6	C17—N1—C9	112.70 (14)
C9—C10—H10B	108.6	C16—N1—C9	113.60 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C18—H18B···O1^i	0.96	2.60	3.480 (3)	153

Symmetry code: (i) −x+5/2, −y, z+1/2.