Ortho­rhom­bic polymorph of (6,7-dimeth­oxy-1,2,3,4-tetra­hydro­isoquinolin-1-yl)methanol

Aouicha Elkhamlichi; Mohammed Lachkar; Brahim El Bali; Michal Dusek; Karla Fejfarova

doi:10.1107/S1600536811019866

. 2011 Jun 18;67(Pt 7):o1734–o1735. doi: 10.1107/S1600536811019866

Orthorhombic polymorph of (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methanol

Aouicha Elkhamlichi ^a, Mohammed Lachkar ^a, Brahim El Bali ^b,^*, Michal Dusek ^c, Karla Fejfarova ^c

PMCID: PMC3151966 PMID: 21837123

Abstract

The asymmetric unit of the title compound, C₁₂H₁₇NO₃, contains two molecules with different conformations. It is a polymorph of the monoclinic form [El Antri et al. (2004 ▶). Molecules, 9, 650–657]; the samples were crystallized at different temperatures from the same solvent. In both structures, molecules 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 _r = 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
Δρ_max = 0.24 e Å⁻³
Δρ_min = −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.

Supplementary Material

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

e-67-o1734-sup1.cif^{(23.3KB, cif)}

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

e-67-o1734-Isup2.hkl^{(129.1KB, hkl)}

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

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

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)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We acknowledge support by the CNRST (grant No URAC19) and the Praemium Academiae project of Academy of Sciences of the Czech Republic.

supplementary crystallographic information

Comment

Temperature-induced polymorphism is important in pharmaceutical industry and especially, in the study of drug action with respect to their chirality (Brittan, 1999 and Bernstein, 2002). Isoquinoline alkaloids form a large group of compounds which could be extracted from many plants (Bently, 1998). Most of these natural alkaloids are optically active and allow interesting clinical uses such as analgesics, antihypertensives, smooth or skeletal muscle relaxants, antispasmodics, antitussives, antimalarials, narcotics and antipyretics (Kitamura et al., 1994). Worthy also to report that 1-substituted tetrahydroisoquinolines display interesting biological and pharmacological properties (He et al., 2000). Especially 1-methyl- and 1-phenyltetrahydroisoquinoline are involved in the treatment of Parkinson and other nervous system diseases (Gray et al., 1989).

In a previous study (El Antri et al., 2004), a single-crystal of 1-hydroxymethyl-7–8-dimethoxy-1,2,3,4-tetrahydroisoquinoline was measured at 173 K. A monoclinic symmetry (S. G.: P2₁) has been found in the structure. Re-measurement, at 150 K, of another crystal from the same plant extract but crystallised at a different temperature, revealed the same composition C₁₂H₁₇NO₃ (Fig. 1) but with an orthorhombic symmetry (S. G.: P2₁2₁2₁). Testing measurements between 120 K and room temperature revealed however no phase transition. Moreover, no simple transformation between the monoclinic and orthorhombic unit cells could be found. Thus, 1-hydroxymethyl-7–8-dimethoxy-1,2,3,4-tetrahydroisoquinoline exists in two crystallographic forms. We report in the present study on the crystal determination of the new orthorhombic 1-hydroxymethyl-7–8-dimethoxy-1,2,3,4-tetrahydroisoquinoline. As in the monoclinic form, the molecules C₁₂H₁₇NO₃ are connected by strong hydrogen bond O—H···N (Fig. 2). In the monoclinic previously published structure the chain runs along a and the molecules have alternating orientation with respect to the projection of hydrogen bonds into the a axis (Fig. 3a). On the other hand, in the orthorhombic structure reported here the chain direction is along b and the molecules are oriented in one side with respect to the projection of hydrogen bonds into the b axis (Fig. 3 b). The packing of the chains is quite different in both structures. H-bonds interactions are shown in Figs 3a&b as dashed lines and, for the new structure, they are summarized in Tab.3.

The asymmetric unit of the title compound contains two independent molecules, which differ in conformation of the tetrahydroisoquinoline ring (Fig. 4). The nitrogen atoms in each of the molecules are oriented on opposite sides of the ring. The conformation of the molecules may be influenced by intermolecular O—H···N hydrogen bonding involving both N1 and N2 atoms.

Distances and angles are of the same magnitude in the two crystals. The heterocyclic ring of tetrahydroisoquinoline adopts a half chair conformation. The conformation of the asymmetric carbon atoms are the same in both asymmetric molecules.

Experimental

Alkaloids under investigations were extracted from the seeds of Calycotome villosa (Poiret) Link Subsp as in (El Antri et al., 2004). The same procedure was used for extractions and crystals synthesis. However, the experiments took place at different room temperatures.