1-(2-Fluoro­phen­yl)-6,7-dimethoxy­isochroman

Aamer Saeed; Jim Simpson; Roderick G Stanley

doi:10.1107/S160053680900926X

. 2009 Mar 25;65(Pt 4):o867–o868. doi: 10.1107/S160053680900926X

1-(2-Fluorophenyl)-6,7-dimethoxyisochroman

Aamer Saeed ^a,^*, Jim Simpson ^b, Roderick G Stanley ^b

PMCID: PMC2969092 PMID: 21582580

Abstract

In the title compound, C₁₇H₁₇FO₃, the benzene ring of the isochroman unit is inclined at 84.96 (7)° to the fluorobenzene ring plane, and the pyran ring adopts a half-boat conformation. In the crystal structure, C—H⋯O hydrogen bonds link molecules into rows along the c axis, while C—H⋯O interactions and C—H⋯F hydrogen bonds to the fluorine acceptor stack the molecules down the b axis. In addition, the crystal structure exhibits a weak C—H⋯π interaction between a methyl H atom of the methoxy group and the dimethoxybenzene ring of an adjacent molecule.

Related literature

For details of naturally occurring isochromans, see: Imamura et al. (2000 ▶); Ogawa et al. (2004 ▶); Peng et al. (1999 ▶); Kunesch et al. (1987 ▶). For the biological activity of isochromans, see: Zhang et al. (2008 ▶); Lorenz et al. (2005 ▶); Togna et al. (2003 ▶); Bianchi et al. (2004 ▶); Cutler et al. (1997 ▶); Liu et al. (2005 ▶); TenBrink et al. (1996 ▶); Frater et al. (1999 ▶); Dobson & Humber (1975 ▶); Yamato et al. (1985 ▶); McCall et al. (1982 ▶). For the synthesis of isochromans, see: Guiso et al. (2001 ▶). For related structures, see: Saeed & Flörke (2006a ▶,b ▶). For ring puckering analysis, see: Cremer & Pople (1975 ▶); and for reference structural data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₇H₁₇FO₃
M _r = 288.31
Monoclinic,
a = 15.730 (2) Å
b = 5.2328 (8) Å
c = 16.477 (2) Å
β = 93.108 (8)°
V = 1354.3 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 89 K
0.29 × 0.22 × 0.13 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.789, T _max = 0.986
13466 measured reflections
2371 independent reflections
1864 reflections with I > 2σ(I)
R _int = 0.072

Refinement

R[F ² > 2σ(F ²)] = 0.074
wR(F ²) = 0.261
S = 1.28
2371 reflections
193 parameters
H-atom parameters constrained
Δρ_max = 0.45 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2 and SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) and TITAN2000 (Hunter & Simpson, 1999 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97, enCIFer (Allen et al., 2004 ▶), PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680900926X/lx2092sup1.cif

e-65-0o867-sup1.cif^{(18.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680900926X/lx2092Isup2.hkl

e-65-0o867-Isup2.hkl^{(116.5KB, hkl)}

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
C1—H1B⋯O2ⁱ	0.99	2.59	3.360 (5)	134
C7—H7⋯F1ⁱⁱ	0.95	2.45	3.360 (4)	160
C17—H17B⋯O1ⁱⁱⁱ	0.98	2.49	3.430 (4)	160
C17—H17A⋯Cgⁱⁱ	0.98	2.70	3.557 (3)	146

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg2 is the centroid of the C3–C8 benzene ring.

Acknowledgments

The authors thank the University of Otago for the purchase of the diffractometer.

supplementary crystallographic information

Comment

Isochroman is a common structural motif found in many natural products. For example 1,6,8-trihydroxy-3-heptyl-7-carboxyisochroman, is an antibiotic and topoisomerase II inhibitor from Penicillum sp. (Imamura et al., 2000), pseudodeflectusin is a selective human cancer cytotoxin from Aspergillus pseudodeflectus, (Ogawa et al., 2004), in softwood lignin (Peng et al., 1999) and in the male wing gland pheromone of Aphomia sociella (Kunesch et al., 1987). A novel isochroman derivative inhibited apoptosis in vascular endothelial cells by depressing the levels of integrin 4, p53 and ROS (Zhang et al., 2008). 1-Phenyl- and 1-(3-methoxy-4-hydroxy)phenyl-6,7-dihydroxyisochromans identified in extra-virgin olive oil exhibit beneficial antioxidant effects (Lorenz et al., 2005) and antiplatelet activity (Togna et al., 2003). Isochroman derivatives also show plant-growth regulatory and herbicidal activities (Bianchi et al., 2004; Cutler et al., 1997), these are oestrogen receptors (Liu et al., 2005), dopamine receptor ligands (TenBrink et al., 1996), and fragrances, such as galaxolide (Frater et al., 1999). 1-Aryl-6,7-dimethoxyisochromans are known to demonstrate analgesic, muscle relaxant, antidepressant, antiinflammatory, antihistaminic and anticoagulant activity and are adrenergic antagonists (Dobson & Humber 1975; Yamato et al., 1985; McCall et al., 1982). The title dimethoxyisochroman derivative (I), Fig. 1, was prepared by the oxa-Pictet–Spengler reaction for the preparation of isochromans (Guiso et al., 2001) using 2-(3,4-dimethoxyphenyl)ethanol and 2-fluorobenzaldehyde.

The pyran ring of (I) adopts a half-boat conformation (Cremer & Pople, 1975) with the O1 atom 0.639 (3) Å from the least-squares plane through atoms C1–C3, C8, C9. The r.m.s. deviation from this plane was 0.083 Å. The benzene ring of the isochroman unit is inclined at 84.96 (7) ° to the fluorobenzene ring plane. Both the C and O atoms of the two methoxy substituents lie close to the aromatic ring plane (maximum deviation 0.310 (5) Å for C16).

In the molecular packing (Fig. 2), C17—H17B···O1 hydrogen bonds link the molecules into rows along the c axis (Fig. 2 and Table 1; symmetry codes as in Fig. 2). The F1 atom acts as an acceptor in a C7—H7···F1 hydrogen bond that, together with C1—H1B···O2 interactions, stacks molecules from individual rows down the the b axis (Fig. 2, Fig 3 and Table 1; symmetry codes as in Fig. 2). Additionally, a weak C—H···π interaction in the structure was observed between a methyl H atom of the methoxy group and the dimethoxybenzene ring of an adjacent molecule, with a C17—H17A···Cgⁱ separation of 2.70 Å (Table 1 and Fig. 2; Cg is the centroid of the C3–C8 benzene ring, symmetry codes as in Fig. 2).)

Experimental

A homogenized mixture of 2-(3,4-dimethoxyphenyl)ethanol (0.18g, 1 mmol) and 4-fluorobenzaldehyde (0.12g 1 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate was irradiated for 1.3 min. The product was purified by thin layer chromatography using petroleum ether and ethyl acetate (7:2 v:v) to afford the title compound (0.91 mmol, 91%) which was recrystallized from ethyl acetate. Analysis calculated for C₁₇H₁₇O₃F: C, 70.82%, H, 5.94% found, 70.69%, H, 5.97%.