Ortho-rhom-bic polymorph of (6,7-dimeth-oxy-1,2,3,4-tetra-hydro-isoquinolin-1-yl)methanol.

The asymmetric unit of the title compound, C(12)H(17)NO(3), contains two mol-ecules with different conformations. It is a polymorph of the monoclinic form [El Antri et al. (2004 ▶). Mol-ecules, 9, 650-657]; the samples were crystallized at different temperatures from the same solvent. In both structures, mol-ecules are linked by O-H⋯N hydrogen bonds, forming chains. The conformations of the chains and their packing differ markedly in the two polymorphs.

Related literature

For background to polymorphism in drugs, see: Brittan (1999 ▶); Bernstein (2002 ▶). For background to alkaloids and their pharmaceutical properties, see: Bently (1998 ▶); Herbert (1985 ▶). Kitamura et al. (1994 ▶); He et al. (2000 ▶); Gray et al. (1989 ▶). For natural-product isolation techniques, see: Dalton (1979 ▶). For the monoclinic polymorph, see: El Antri et al. (2004 ▶).

Experimental

Crystal data

C12H17NO3

M = 223.27

Orthorhombic,

a = 8.9917 (11) Å

b = 13.4769 (12) Å

c = 18.576 (4) Å

V = 2251.0 (6) Å3

Z = 8

Mo Kα radiation

μ = 0.09 mm−1

T = 150 K

0.51 × 0.35 × 0.32 mm

Data collection

Oxford Diffraction Xcalibur 2 diffractometer with a Sapphire 2 CCD detector

30187 measured reflections

2679 independent reflections

1515 reflections with I > 3σ(I)

R int = 0.054

Refinement

R[F 2 > 2σ(F 2)] = 0.041

wR(F 2) = 0.091

S = 1.15

2679 reflections

301 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.24 e Å−3

Δρmin = −0.15 e Å−3

Data collection: CrysAlis CCD (Oxford Diffraction, 2005 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2005 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SIR2002 (Burla et al., 2003 ▶); program(s) used to refine structure: JANA2006 (Petříček et al., 2006 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2005 ▶) and COOT (Emsley et al., 2010 ▶); software used to prepare material for publication: JANA2006.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811019866/hb5884sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811019866/hb5884Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811019866/hb5884Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C12H17NO3	F(000) = 960
Mr = 223.27	Dx = 1.317 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9027 reflections
a = 8.9917 (11) Å	θ = 2.5–26.5°
b = 13.4769 (12) Å	µ = 0.09 mm−1
c = 18.576 (4) Å	T = 150 K
V = 2251.0 (6) Å3	Irregular, colorless
Z = 8	0.51 × 0.35 × 0.32 mm

Oxford Diffraction Xcalibur 2 diffractometer with a Sapphire 2 CCD detector	1515 reflections with I > 3σ(I)
Radiation source: X-ray tube	Rint = 0.054
graphite	θmax = 26.6°, θmin = 2.5°
Detector resolution: 8.3438 pixels mm-1	h = −11→11
Rotation method data acquisition using ω scans	k = −16→16
30187 measured reflections	l = −23→23
2679 independent reflections

Refinement on F2	124 constraints
R[F2 > 2σ(F2)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.091	Weighting scheme based on measured s.u.'s w = 1/[σ2(I) + 0.0016I2]
S = 1.15	(Δ/σ)max = 0.004
2679 reflections	Δρmax = 0.24 e Å−3
301 parameters	Δρmin = −0.15 e Å−3
0 restraints

Refinement. The refinement was carried out against all reflections. The conventional R-factor is always based on F. The goodness of fit as well as the weighted R-factor are based on F and F2 for refinement carried out on F and F2, respectively. The threshold expression is used only for calculating R-factors etc. and it is not relevant to the choice of reflections for refinement.The program used for refinement, Jana2006, uses the weighting scheme based on the experimental expectations, see _refine_ls_weighting_details, that does not force S to be one. Therefore the values of S are usually larger than the ones from the SHELX program.

	x	y	z	Uiso*/Ueq
O1	0.2415 (2)	0.53891 (18)	0.36542 (11)	0.0430 (7)
O2	0.4410 (2)	0.45708 (14)	0.02813 (11)	0.0351 (7)
O3	0.6069 (2)	0.30148 (13)	0.02562 (11)	0.0333 (7)
O4	0.2946 (2)	−0.04072 (18)	0.15204 (13)	0.0501 (8)
O5	0.0403 (2)	0.05130 (14)	0.48188 (10)	0.0355 (7)
O6	−0.0888 (2)	0.22154 (13)	0.47614 (11)	0.0369 (7)
N1	0.4198 (3)	0.37470 (18)	0.34959 (13)	0.0347 (9)
N2	0.0505 (3)	0.09105 (18)	0.15335 (14)	0.0377 (10)
C1	0.3258 (4)	0.4076 (2)	0.28954 (16)	0.0375 (11)
C2	0.4044 (3)	0.3779 (2)	0.21914 (17)	0.0319 (10)
C3	0.3811 (3)	0.4319 (2)	0.15544 (16)	0.0335 (10)
C4	0.4524 (3)	0.4070 (2)	0.09213 (16)	0.0298 (10)
C5	0.5455 (3)	0.3232 (2)	0.09070 (15)	0.0281 (10)
C6	0.5657 (3)	0.2694 (2)	0.15306 (16)	0.0291 (10)
C7	0.4979 (3)	0.2972 (2)	0.21772 (17)	0.0301 (10)
C8	0.5328 (3)	0.2388 (2)	0.28580 (16)	0.0344 (11)
C9	0.4336 (3)	0.2665 (2)	0.34811 (16)	0.0349 (11)
C10	0.3029 (4)	0.5168 (2)	0.29733 (16)	0.0437 (12)
C11	0.3469 (3)	0.5421 (2)	0.02716 (16)	0.0416 (11)
C12	0.7128 (4)	0.2228 (2)	0.02437 (17)	0.0428 (12)
C13	0.1076 (3)	0.0400 (2)	0.21832 (16)	0.0370 (10)
C14	0.0628 (3)	0.09610 (19)	0.28544 (16)	0.0300 (10)
C15	0.0789 (3)	0.0489 (2)	0.35197 (16)	0.0335 (10)
C16	0.0308 (3)	0.0923 (2)	0.41458 (15)	0.0272 (10)
C17	−0.0383 (3)	0.1861 (2)	0.41197 (16)	0.0300 (10)
C18	−0.0500 (3)	0.2338 (2)	0.34686 (16)	0.0310 (11)
C19	0.0006 (3)	0.1904 (2)	0.28279 (16)	0.0288 (10)
C20	−0.0159 (3)	0.2449 (2)	0.21245 (16)	0.0355 (11)
C21	0.0785 (3)	0.1987 (2)	0.15450 (16)	0.0390 (12)
C22	0.2709 (3)	0.0187 (2)	0.21388 (17)	0.0437 (11)
C23	0.1144 (4)	−0.0419 (2)	0.48738 (16)	0.0497 (12)
C24	−0.1827 (4)	0.3079 (2)	0.47324 (17)	0.0472 (12)
H1	0.229284	0.377124	0.289174	0.045*
H3	0.314106	0.487379	0.155936	0.0402*
H6	0.627874	0.211478	0.15206	0.0349*
H8a	0.523519	0.169103	0.276183	0.0413*
H8b	0.634849	0.249268	0.298996	0.0413*
H9a	0.337109	0.237386	0.341366	0.0419*
H9b	0.477612	0.244005	0.392266	0.0419*
H10a	0.396496	0.550278	0.292131	0.0524*
H10b	0.237013	0.539716	0.26024	0.0524*
H11a	0.343252	0.568724	−0.020729	0.0499*
H11b	0.248601	0.523434	0.042067	0.0499*
H11c	0.38554	0.591309	0.059487	0.0499*
H12a	0.752635	0.216224	−0.023333	0.0513*
H12b	0.791882	0.237308	0.057458	0.0513*
H12c	0.665196	0.161952	0.038152	0.0513*
H13	0.061923	−0.024214	0.221065	0.0444*
H15	0.124753	−0.015423	0.353911	0.0402*
H18	−0.093988	0.298619	0.345199	0.0372*
H20a	0.012609	0.31302	0.218823	0.0425*
H20b	−0.118321	0.244051	0.197835	0.0425*
H21a	0.052486	0.226707	0.10869	0.0468*
H21b	0.181588	0.210629	0.164728	0.0468*
H22a	0.324653	0.07989	0.208995	0.0524*
H22b	0.301603	−0.017143	0.256005	0.0524*
H23a	0.120147	−0.061226	0.537046	0.0597*
H23b	0.059956	−0.091076	0.46086	0.0597*
H23c	0.212938	−0.036144	0.467955	0.0597*
H24a	−0.214712	0.324831	0.520983	0.0566*
H24b	−0.127992	0.36243	0.453042	0.0566*
H24c	−0.267876	0.294193	0.443745	0.0566*
H1n	0.374 (3)	0.391 (2)	0.3865 (16)	0.0416*
H2n	0.100 (3)	0.065 (2)	0.1185 (16)	0.0452*
H1o	0.150 (3)	0.547 (3)	0.3609 (18)	0.0516*
H4o	0.378 (4)	−0.059 (3)	0.153 (2)	0.0601*

	U11	U22	U33	U12	U13	U23
O1	0.0483 (13)	0.0424 (12)	0.0382 (13)	0.0103 (13)	0.0071 (12)	−0.0063 (11)
O2	0.0428 (12)	0.0309 (11)	0.0314 (12)	0.0109 (11)	−0.0027 (11)	0.0004 (10)
O3	0.0382 (12)	0.0343 (11)	0.0275 (12)	0.0090 (10)	0.0026 (11)	−0.0006 (10)
O4	0.0534 (16)	0.0548 (14)	0.0420 (13)	0.0117 (14)	0.0041 (13)	−0.0150 (13)
O5	0.0462 (13)	0.0283 (11)	0.0320 (12)	0.0061 (10)	−0.0031 (11)	0.0022 (10)
O6	0.0453 (13)	0.0380 (12)	0.0275 (12)	0.0155 (11)	−0.0011 (12)	−0.0016 (10)
N1	0.0477 (18)	0.0299 (14)	0.0266 (16)	0.0080 (14)	0.0035 (15)	−0.0023 (12)
N2	0.0456 (18)	0.0375 (16)	0.0300 (17)	−0.0004 (14)	0.0011 (14)	−0.0043 (13)
C1	0.046 (2)	0.0340 (18)	0.0328 (18)	0.0017 (16)	0.0025 (18)	0.0002 (15)
C2	0.0337 (18)	0.0305 (16)	0.0316 (18)	0.0013 (15)	−0.0035 (17)	−0.0027 (14)
C3	0.0390 (18)	0.0272 (17)	0.0345 (19)	0.0111 (14)	−0.0050 (16)	−0.0048 (15)
C4	0.0337 (17)	0.0296 (17)	0.0261 (18)	0.0010 (15)	−0.0089 (16)	−0.0028 (14)
C5	0.0261 (17)	0.0301 (17)	0.0281 (19)	0.0014 (15)	−0.0033 (16)	−0.0054 (14)
C6	0.0291 (18)	0.0274 (15)	0.0307 (19)	0.0043 (15)	−0.0019 (17)	−0.0025 (15)
C7	0.0340 (17)	0.0262 (16)	0.0301 (18)	0.0008 (14)	0.0000 (18)	−0.0002 (15)
C8	0.045 (2)	0.0289 (17)	0.0292 (18)	0.0029 (15)	−0.0014 (18)	−0.0017 (14)
C9	0.041 (2)	0.0311 (17)	0.032 (2)	0.0008 (16)	−0.0043 (18)	0.0029 (14)
C10	0.049 (2)	0.044 (2)	0.039 (2)	0.0104 (17)	0.0029 (17)	0.0029 (16)
C11	0.055 (2)	0.0323 (17)	0.0374 (19)	0.0135 (17)	−0.0089 (17)	0.0043 (17)
C12	0.050 (2)	0.049 (2)	0.0290 (17)	0.0168 (18)	0.0033 (18)	−0.0008 (16)
C13	0.0417 (19)	0.0336 (17)	0.0356 (19)	0.0008 (16)	0.0005 (17)	−0.0030 (17)
C14	0.0317 (17)	0.0310 (16)	0.0272 (18)	0.0030 (15)	0.0000 (16)	−0.0032 (14)
C15	0.0362 (18)	0.0256 (16)	0.0387 (19)	−0.0008 (16)	−0.0033 (16)	−0.0024 (15)
C16	0.0289 (17)	0.0273 (16)	0.0253 (18)	−0.0026 (14)	−0.0006 (15)	0.0013 (13)
C17	0.0336 (18)	0.0280 (17)	0.0283 (19)	−0.0001 (15)	−0.0018 (16)	−0.0026 (14)
C18	0.0345 (19)	0.0255 (16)	0.033 (2)	−0.0016 (15)	−0.0054 (17)	−0.0031 (15)
C19	0.0284 (17)	0.0314 (17)	0.0266 (17)	−0.0034 (14)	−0.0029 (17)	0.0013 (15)
C20	0.038 (2)	0.0336 (17)	0.034 (2)	−0.0040 (15)	−0.0028 (18)	0.0034 (15)
C21	0.039 (2)	0.046 (2)	0.032 (2)	−0.0051 (18)	−0.0013 (18)	0.0079 (15)
C22	0.046 (2)	0.047 (2)	0.0387 (18)	0.0051 (17)	0.0048 (18)	−0.0078 (18)
C23	0.076 (3)	0.0306 (17)	0.042 (2)	0.0087 (19)	−0.005 (2)	0.0031 (16)
C24	0.054 (2)	0.050 (2)	0.0378 (19)	0.0244 (19)	−0.001 (2)	−0.0094 (17)

O1—C10	1.412 (4)	C9—H9b	0.96
O1—H1o	0.83 (3)	C10—H10a	0.96
O2—C4	1.371 (4)	C10—H10b	0.96
O2—C11	1.424 (4)	C11—H11a	0.96
O3—C5	1.361 (4)	C11—H11b	0.96
O3—C12	1.425 (4)	C11—H11c	0.96
O4—C22	1.416 (4)	C12—H12a	0.96
O4—H4o	0.79 (3)	C12—H12b	0.96
O5—C16	1.369 (3)	C12—H12c	0.96
O5—C23	1.425 (4)	C13—C14	1.513 (4)
O6—C17	1.362 (4)	C13—C22	1.498 (4)
O6—C24	1.439 (4)	C13—H13	0.96
N1—C1	1.468 (4)	C14—C15	1.398 (4)
N1—C9	1.464 (4)	C14—C19	1.389 (4)
N1—H1n	0.83 (3)	C15—C16	1.372 (4)
N2—C13	1.481 (4)	C15—H15	0.96
N2—C21	1.472 (4)	C16—C17	1.408 (4)
N2—H2n	0.86 (3)	C17—C18	1.374 (4)
C1—C2	1.539 (4)	C18—C19	1.402 (4)
C1—C10	1.493 (4)	C18—H18	0.96
C1—H1	0.96	C19—C20	1.507 (4)
C2—C3	1.405 (4)	C20—C21	1.506 (4)
C2—C7	1.375 (4)	C20—H20a	0.96
C3—C4	1.381 (4)	C20—H20b	0.96
C3—H3	0.96	C21—H21a	0.96
C4—C5	1.406 (4)	C21—H21b	0.96
C5—C6	1.379 (4)	C22—H22a	0.96
C6—C7	1.398 (4)	C22—H22b	0.96
C6—H6	0.96	C23—H23a	0.96
C7—C8	1.522 (4)	C23—H23b	0.96
C8—C9	1.508 (4)	C23—H23c	0.96
C8—H8a	0.96	C24—H24a	0.96
C8—H8b	0.96	C24—H24b	0.96
C9—H9a	0.96	C24—H24c	0.96
C10—O1—H1o	109 (2)	O3—C12—H12a	109.4718
C4—O2—C11	116.8 (2)	O3—C12—H12b	109.4712
C5—O3—C12	116.5 (2)	O3—C12—H12c	109.4707
C22—O4—H4o	108 (3)	H12a—C12—H12b	109.4716
C16—O5—C23	116.8 (2)	H12a—C12—H12c	109.4715
C17—O6—C24	116.5 (2)	H12b—C12—H12c	109.4704
C1—N1—C9	109.6 (2)	N2—C13—C14	110.3 (2)
C1—N1—H1n	105 (2)	N2—C13—C22	112.6 (2)
C9—N1—H1n	108.6 (19)	N2—C13—H13	108.2749
C13—N2—C21	112.7 (2)	C14—C13—C22	113.7 (2)
C13—N2—H2n	104 (2)	C14—C13—H13	107.0055
C21—N2—H2n	109 (2)	C22—C13—H13	104.4393
N1—C1—C2	107.6 (2)	C13—C14—C15	118.3 (2)
N1—C1—C10	107.7 (2)	C13—C14—C19	122.3 (3)
N1—C1—H1	113.3918	C15—C14—C19	119.3 (3)
C2—C1—C10	113.7 (2)	C14—C15—C16	121.5 (3)
C2—C1—H1	107.3416	C14—C15—H15	119.2572
C10—C1—H1	107.3033	C16—C15—H15	119.2563
C1—C2—C3	120.8 (2)	O5—C16—C15	125.6 (2)
C1—C2—C7	120.2 (3)	O5—C16—C17	114.9 (2)
C3—C2—C7	119.0 (3)	C15—C16—C17	119.5 (3)
C2—C3—C4	121.5 (3)	O6—C17—C16	115.6 (2)
C2—C3—H3	119.2635	O6—C17—C18	125.5 (3)
C4—C3—H3	119.2645	C16—C17—C18	118.9 (3)
O2—C4—C3	125.8 (3)	C17—C18—C19	121.8 (3)
O2—C4—C5	115.0 (2)	C17—C18—H18	119.0863
C3—C4—C5	119.2 (3)	C19—C18—H18	119.0868
O3—C5—C4	115.5 (2)	C14—C19—C18	118.8 (3)
O3—C5—C6	125.4 (2)	C14—C19—C20	121.1 (3)
C4—C5—C6	119.0 (3)	C18—C19—C20	120.0 (2)
C5—C6—C7	121.5 (3)	C19—C20—C21	111.2 (2)
C5—C6—H6	119.2431	C19—C20—H20a	109.4705
C7—C6—H6	119.242	C19—C20—H20b	109.4713
C2—C7—C6	119.7 (3)	C21—C20—H20a	109.4716
C2—C7—C8	121.3 (3)	C21—C20—H20b	109.4716
C6—C7—C8	119.0 (2)	H20a—C20—H20b	107.6461
C7—C8—C9	112.8 (2)	N2—C21—C20	108.8 (2)
C7—C8—H8a	109.4715	N2—C21—H21a	109.4714
C7—C8—H8b	109.4718	N2—C21—H21b	109.471
C9—C8—H8a	109.4708	C20—C21—H21a	109.4707
C9—C8—H8b	109.4709	C20—C21—H21b	109.4716
H8a—C8—H8b	105.924	H21a—C21—H21b	110.1482
N1—C9—C8	108.1 (2)	O4—C22—C13	107.5 (2)
N1—C9—H9a	109.4715	O4—C22—H22a	109.4708
N1—C9—H9b	109.4715	O4—C22—H22b	109.4708
C8—C9—H9a	109.4708	C13—C22—H22a	109.4715
C8—C9—H9b	109.4708	C13—C22—H22b	109.4715
H9a—C9—H9b	110.8097	H22a—C22—H22b	111.3954
O1—C10—C1	110.4 (2)	O5—C23—H23a	109.471
O1—C10—H10a	109.4717	O5—C23—H23b	109.4715
O1—C10—H10b	109.4714	O5—C23—H23c	109.4711
C1—C10—H10a	109.4713	H23a—C23—H23b	109.4715
C1—C10—H10b	109.4709	H23a—C23—H23c	109.4704
H10a—C10—H10b	108.4859	H23b—C23—H23c	109.4719
O2—C11—H11a	109.471	O6—C24—H24a	109.4707
O2—C11—H11b	109.4716	O6—C24—H24b	109.4717
O2—C11—H11c	109.4709	O6—C24—H24c	109.4719
H11a—C11—H11b	109.4714	H24a—C24—H24b	109.4711
H11a—C11—H11c	109.4708	H24a—C24—H24c	109.4706
H11b—C11—H11c	109.4716	H24b—C24—H24c	109.4714

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1o···N2i	0.83 (3)	1.92 (3)	2.740 (4)	169 (3)
O4—H4o···N1ii	0.79 (3)	2.03 (3)	2.810 (4)	172 (4)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1o⋯N2i	0.83 (3)	1.92 (3)	2.740 (4)	169 (3)
O4—H4o⋯N1ii	0.79 (3)	2.03 (3)	2.810 (4)	172 (4)

Symmetry codes: (i) ; (ii) .