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The crystal structure of the title compound, C12H16O3, an analogue of the naturally occurring 1,3-di­methyl­isochromans or the related naphtho­[2,3-c]­pyrans, confirms that the C-3 methyl substituent adopts an equatorial position in the solid state.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803013151/cf6261sup1.cif
Contains datablocks global, 2

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536803013151/cf62612sup2.hkl
Contains datablock 2

CCDC reference: 217469

Key indicators

  • Single-crystal X-ray study
  • T = 293 K
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.056
  • wR factor = 0.179
  • Data-to-parameter ratio = 15.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry








Comment top

The synthesis of substituted 1,3-dimethylisochromans or the related naphtho[2,3-c]pyrans is important as a result of the biological activities of both these classes of compounds (Thomson, 1987). For example, the recently isolated bioxanthracenes, such as compound (1), show promising antimalarial activity (Isaka et al., 2001). A large number of these types of compounds have been synthesized by several research groups but only a few X-ray crystallographic studies have been carried out (Cook et al., 2002; Zhang et al., 1997; Giles et al., 1988; Zhengxiong et al., 1986; Egert et al., 1983; Cooke et al., 1980; Cameron et al., 1977). From these X-ray crystallographic studies, it is clear that the C-1 methyl group of the fused pyran ring adopts a pseudo-axial position, while the C-3 methyl substituent adopts an equatorial position.

As part of our ongoing research programme on the syntheses of substituted isochromans, we needed to synthesize compounds lacking the C-1 methyl substituent. The synthesis of 3-methylisochromane, (2), was therefore pursued. This was achieved by reacting the benzylic alcohol (3) with potassium t-butoxide in DMF, as previously described (Green et al., 1995), or by the reduction of the corresponding isochromene (4), as detailed in the Experimental and shown in the Scheme. A single-crystal X-ray structure determination on the product, (2), confirmed that the heterocyclic ring adopts a half-chair conformation, with the C-3 methyl substituent in an equatorial position (Figs. 1 and 2).

Experimental top

10% Pd/C (24 mg) and 1 drop of concentrated hydrochloric acid were added to ethyl acetate (6.3 ml) in a two-necked 50 ml flask. The system was purged for 15 min by exposing the suspension to hydrogen gas before isochromene (4) (99.8 mg) was introduced. The reaction mixture was then stirred under a hydrogen gas pressure of 2.5 atm for 24 h. The reaction mixture was filtered through a silica gel plug, followed by removal of solvent in vacuo. The crude material was purified by silica-gel column chromatography (20% ethyl acetate/hexane) to afford (±)-5,8-dimethoxy-3-methylisochromane, (2) (90.7 mg), in 90% yield. The compound was recrystallized from CH2Cl2 by slow evaporation, to afford colourless block-like crystals [m.p. 346–347 K, literature 347–348 K (Green et al., 1995)].

Refinement top

H atoms were positioned geometrically and allowed to ride on their respective parent atoms, with Uiso(H) = 1.2Ueq(C) [1.5Ueq(C) for methyl groups].

Computing details top

Data collection: SMART-NT (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Bruker, 1999); program(s) used to refine structure: SHELXTL; molecular graphics: PLATON (Spek, 1990); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. A view of (2) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. A side view of (2), showing the equatorial C-3 methyl group.
5,8-Dimethoxy-3-methyl-1H-isochroman top
Crystal data top
C12H16O3F(000) = 448
Mr = 208.25Dx = 1.220 Mg m3
Monoclinic, P21/cMelting point = 346–347 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 13.2543 (15) ÅCell parameters from 701 reflections
b = 5.9923 (7) Åθ = 3.1–23.2°
c = 14.5744 (17) ŵ = 0.09 mm1
β = 101.633 (2)°T = 293 K
V = 1133.8 (2) Å3Block, colourless
Z = 40.30 × 0.26 × 0.17 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
2219 independent reflections
Radiation source: fine-focus sealed tube1431 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.049
ϕ and ω scansθmax = 26.0°, θmin = 1.6°
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
h = 1616
Tmin = 0.975, Tmax = 0.985k = 77
6472 measured reflectionsl = 1715
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.1085P)2]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.056(Δ/σ)max = 0.001
wR(F2) = 0.179Δρmax = 0.17 e Å3
S = 1.03Δρmin = 0.21 e Å3
2219 reflectionsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
140 parametersExtinction coefficient: 0.028 (7)
0 restraints
Crystal data top
C12H16O3V = 1133.8 (2) Å3
Mr = 208.25Z = 4
Monoclinic, P21/cMo Kα radiation
a = 13.2543 (15) ŵ = 0.09 mm1
b = 5.9923 (7) ÅT = 293 K
c = 14.5744 (17) Å0.30 × 0.26 × 0.17 mm
β = 101.633 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer
2219 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
1431 reflections with I > 2σ(I)
Tmin = 0.975, Tmax = 0.985Rint = 0.049
6472 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0560 restraints
wR(F2) = 0.179H-atom parameters constrained
S = 1.03Δρmax = 0.17 e Å3
2219 reflectionsΔρmin = 0.21 e Å3
140 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
O90.50285 (10)0.2117 (2)0.89740 (10)0.0679 (5)
O20.73492 (9)0.6133 (2)1.03766 (9)0.0624 (4)
C4A0.76055 (13)0.3825 (3)0.87837 (13)0.0536 (5)
C8A0.66753 (13)0.3635 (3)0.90751 (12)0.0509 (5)
C80.59316 (13)0.2098 (3)0.86396 (13)0.0539 (5)
O110.87556 (11)0.2677 (3)0.78487 (11)0.0810 (5)
C50.78005 (15)0.2404 (3)0.80701 (14)0.0593 (5)
C70.61220 (14)0.0759 (3)0.79265 (14)0.0589 (5)
H70.56250.02500.76370.071*
C10.64551 (13)0.5085 (4)0.98574 (13)0.0591 (5)
H1A0.59600.62230.95950.071*
H1B0.61460.41771.02780.071*
C40.83867 (14)0.5537 (4)0.92275 (14)0.0635 (6)
H4A0.86640.62850.87420.076*
H4B0.89510.47910.96410.076*
C60.70626 (14)0.0916 (3)0.76381 (14)0.0611 (6)
H60.71910.00160.71540.073*
C30.79179 (15)0.7250 (3)0.97790 (15)0.0615 (6)
H30.74430.81860.93390.074*
C100.42779 (15)0.0477 (4)0.86299 (17)0.0736 (7)
H10A0.40480.06640.79660.110*
H10B0.37030.06370.89340.110*
H10C0.45730.09810.87560.110*
C130.87016 (18)0.8737 (4)1.03799 (19)0.0865 (7)
H13A0.83610.97071.07450.130*
H13B0.90480.96150.99870.130*
H13C0.91960.78351.07910.130*
C120.90347 (19)0.1157 (5)0.7204 (2)0.0936 (8)
H12A0.89960.03380.74310.140*
H12B0.97260.14620.71330.140*
H12C0.85720.13130.66090.140*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O90.0473 (7)0.0815 (10)0.0778 (10)0.0147 (6)0.0191 (7)0.0171 (7)
O20.0530 (8)0.0737 (9)0.0608 (8)0.0128 (6)0.0124 (7)0.0086 (6)
C4A0.0422 (9)0.0647 (11)0.0537 (10)0.0021 (8)0.0089 (8)0.0040 (9)
C8A0.0429 (9)0.0589 (10)0.0498 (9)0.0010 (8)0.0067 (8)0.0052 (9)
C80.0412 (9)0.0627 (11)0.0573 (10)0.0008 (8)0.0090 (8)0.0028 (9)
O110.0545 (9)0.1081 (13)0.0876 (10)0.0065 (8)0.0316 (8)0.0250 (9)
C50.0446 (10)0.0742 (13)0.0604 (11)0.0048 (9)0.0133 (9)0.0002 (10)
C70.0492 (10)0.0625 (12)0.0622 (11)0.0005 (9)0.0047 (9)0.0037 (10)
C10.0461 (10)0.0710 (12)0.0621 (11)0.0078 (9)0.0153 (9)0.0068 (10)
C40.0460 (10)0.0787 (14)0.0676 (12)0.0084 (9)0.0154 (10)0.0014 (11)
C60.0559 (11)0.0693 (13)0.0577 (11)0.0080 (9)0.0102 (9)0.0064 (9)
C30.0489 (10)0.0644 (12)0.0712 (12)0.0069 (9)0.0117 (10)0.0035 (10)
C100.0515 (11)0.0740 (14)0.0980 (16)0.0162 (10)0.0215 (11)0.0105 (12)
C130.0726 (14)0.0857 (16)0.1034 (18)0.0254 (12)0.0231 (14)0.0207 (14)
C120.0727 (15)0.111 (2)0.1086 (18)0.0032 (14)0.0459 (14)0.0255 (16)
Geometric parameters (Å, º) top
O9—C81.380 (2)C1—H1B0.970
O9—C101.416 (2)C4—C31.513 (3)
O2—C11.418 (2)C4—H4A0.970
O2—C31.428 (2)C4—H4B0.970
C4A—C8A1.387 (2)C6—H60.930
C4A—C51.408 (3)C3—C131.508 (3)
C4A—C41.507 (3)C3—H30.980
C8A—C81.404 (3)C10—H10A0.960
C8A—C11.508 (3)C10—H10B0.960
C8—C71.376 (3)C10—H10C0.960
O11—C51.378 (2)C13—H13A0.960
O11—C121.411 (3)C13—H13B0.960
C5—C61.379 (3)C13—H13C0.960
C7—C61.397 (3)C12—H12A0.960
C7—H70.930C12—H12B0.960
C1—H1A0.970C12—H12C0.960
C8—O9—C10117.80 (15)H4A—C4—H4B107.9
C1—O2—C3111.68 (14)C5—C6—C7120.01 (18)
C8A—C4A—C5118.89 (17)C5—C6—H6120.0
C8A—C4A—C4120.05 (16)C7—C6—H6120.0
C5—C4A—C4121.06 (16)O2—C3—C13108.02 (18)
C4A—C8A—C8120.14 (17)O2—C3—C4109.25 (15)
C4A—C8A—C1120.22 (16)C13—C3—C4113.64 (17)
C8—C8A—C1119.64 (15)O2—C3—H3108.6
O9—C8—C7125.14 (16)C13—C3—H3108.6
O9—C8—C8A114.51 (16)C4—C3—H3108.6
C7—C8—C8A120.33 (17)O9—C10—H10A109.5
C5—O11—C12117.13 (17)O9—C10—H10B109.5
O11—C5—C6124.80 (18)H10A—C10—H10B109.5
O11—C5—C4A114.55 (17)O9—C10—H10C109.5
C6—C5—C4A120.65 (17)H10A—C10—H10C109.5
C8—C7—C6119.93 (18)H10B—C10—H10C109.5
C8—C7—H7120.0C3—C13—H13A109.5
C6—C7—H7120.0C3—C13—H13B109.5
O2—C1—C8A112.98 (14)H13A—C13—H13B109.5
O2—C1—H1A109.0C3—C13—H13C109.5
C8A—C1—H1A109.0H13A—C13—H13C109.5
O2—C1—H1B109.0H13B—C13—H13C109.5
C8A—C1—H1B109.0O11—C12—H12A109.5
H1A—C1—H1B107.8O11—C12—H12B109.5
C4A—C4—C3111.69 (15)H12A—C12—H12B109.5
C4A—C4—H4A109.3O11—C12—H12C109.5
C3—C4—H4A109.3H12A—C12—H12C109.5
C4A—C4—H4B109.3H12B—C12—H12C109.5
C3—C4—H4B109.3
C5—C4A—C8A—C82.1 (3)C4—C4A—C5—C6176.95 (17)
C4—C4A—C8A—C8177.68 (16)O9—C8—C7—C6178.96 (17)
C5—C4A—C8A—C1178.19 (17)C8A—C8—C7—C60.5 (3)
C4—C4A—C8A—C12.0 (3)C3—O2—C1—C8A50.7 (2)
C10—O9—C8—C77.0 (3)C4A—C8A—C1—O215.0 (3)
C10—O9—C8—C8A174.38 (16)C8—C8A—C1—O2165.36 (16)
C4A—C8A—C8—O9178.14 (16)C8A—C4A—C4—C314.8 (2)
C1—C8A—C8—O91.5 (2)C5—C4A—C4—C3164.98 (17)
C4A—C8A—C8—C70.5 (3)O11—C5—C6—C7179.27 (19)
C1—C8A—C8—C7179.82 (18)C4A—C5—C6—C71.9 (3)
C12—O11—C5—C67.1 (3)C8—C7—C6—C50.3 (3)
C12—O11—C5—C4A174.0 (2)C1—O2—C3—C13167.14 (17)
C8A—C4A—C5—O11178.22 (16)C1—O2—C3—C468.79 (19)
C4—C4A—C5—O112.0 (3)C4A—C4—C3—O248.6 (2)
C8A—C4A—C5—C62.9 (3)C4A—C4—C3—C13169.26 (19)

Experimental details

Crystal data
Chemical formulaC12H16O3
Mr208.25
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)13.2543 (15), 5.9923 (7), 14.5744 (17)
β (°) 101.633 (2)
V3)1133.8 (2)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.30 × 0.26 × 0.17
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 1999)
Tmin, Tmax0.975, 0.985
No. of measured, independent and
observed [I > 2σ(I)] reflections
6472, 2219, 1431
Rint0.049
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.179, 1.03
No. of reflections2219
No. of parameters140
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.17, 0.21

Computer programs: SMART-NT (Bruker, 1998), SAINT (Bruker, 1999), SAINT, SHELXTL (Bruker, 1999), SHELXTL, PLATON (Spek, 1990).

 

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