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The bicyclic ring system of the title compound, C12H14O4, is essentially planar. One of the meth­oxy groups is almost coplanar with the ring system, but the other two are considerably twisted out of its plane.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807019848/hb2386sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536807019848/hb2386Isup2.hkl
Contains datablock I

CCDC reference: 647720

Key indicators

  • Single-crystal X-ray study
  • T = 173 K
  • Mean [sigma](C-C) = 0.002 Å
  • R factor = 0.036
  • wR factor = 0.099
  • Data-to-parameter ratio = 16.8

checkCIF/PLATON results

No syntax errors found



Alert level C PLAT180_ALERT_3_C Check Cell Rounding: # of Values Ending with 0 = 3
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 1 ALERT level C = Check and explain 0 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 1 ALERT type 3 Indicator that the structure quality may be low 0 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check

Comment top

Indanones are useful precursors in the synthesis of a variety of biologically active compounds including indacrinone (Hanna & Lau-cam, 1989), indanoyl isoleucine conjugates (Mithofer et al., 2005), indanocines (Andreani et al., 2000) and other medicinally important products (Pinkerton et al., 2005, Yamamoto et al., 1994, Briggs et al., 1976). Donepezil, a 5,6-dimethoxyindanone and its derivatives, are acetyl cholinesterase inhibitors used in treatment of Alzheimer disease (Omran et al., 2005). A number of donepezil analogues have been prepared with prospective in the treatment of Alzheimer disease (Andreani et al., 2000). 1-Indanones are also important precursors in the regiospecific synthesis of 2-fluoro-1-naphthols (Cai et al., 2005). 5-Chloro-1-indanone has been used to synthesize important biomedical compounds as anticonvulsants (Kwiecien et al., 1991), anticholinergics (De Paulis et al., 1981) and diarylsulfonylureas, which show great activity against solid tumours (Howbert et al.,1990).

The title compound, (I), was prepared as an intermediates for an isocoumarin synthesis and for the systematic study of its bioactivity. The synthesis was carried out by cyclodehydration of 3-(3,4,5-trimethoxyphenyl)propanoic acid using polyphosphoric acid.

A perspective view of (I) is shown in Fig. 1. Bond lengths and angles can be regarded as normal (Cambridge Crystallographic Database, Version 5.28, November 2006; Mogul Version 1.1; Allen, 2002, Bruno et al., 2004). The atoms comprising the two rings are essentially planar (r.m.s. deviation for the nine C atoms 0.016 Å). Whereas one of the methoxy groups is almost coplanar with the aromatic ring, the other two are considerably twisted out of the plane of the aromatic ring (Table 1).

Related literature top

For background literature on indanones and their biological applications, see: Andreani et al. (2000); Cai et al. (2005); De Paulis et al. (1981); Hanna & Lau-cam (1989); Howbert & Crowell (1990); Kwiecien et al. (1991); Mithofer et al. (2005); Omran et al. (2005); Pinkerton et al. (2005); Yamamoto et al. (1994).

For related literature, see: Allen (2002); Biggs et al. (1976); Bruno et al. (2004); Rambaldi et al. (2001).

Experimental top

3-(3,4,5-Trimethoxyphenyl)propanoic acid (1 g, 4.5 mmol) was dissolved in polyphosphoric acid (12.5 g) and the resulting yellow solution was heated along with stirring at 363 K for 2 h. The cooled solution was added to 200 ml ice water and extracted with ethyl acetate (4 × 100 ml). The combined extracts were washed with 5% sodium bicarbonate solution and then with water until the washings were neutral. The organic layer was dried (MgSO4), filtered and rotary evaporated to dryness. Recrystallization from ethyl acetate afforded (I) as colorless crystals (0.758 g, 76%) m.p. 386 K; Rf 0.461 (Hexane-ethyl acetate 3:2 v/v); IR(cm-1) 1685, 1590; 1H NMR (400 MHz, C6D6O): δ 2.54 (m, 2H, H-3), 3.02 (m, 2H, H-2), 3.93 (s, 3H, OMe) 3.94 (s, 6H, OMe ×2), 6.89 (s, 1H, H-4); 13C NMR (100 MHz, C6D6O): δ 25.26 (C-3), 36.7 (C-2),

55.73 (OMe) 66.4 (OMe), 61.16 (OMe), 104.29 (C-4), 122.68, 140.75, 151.38, 153.25, 159.66, 205 (CO); MS (70 eV): m/z (%) = 222 [M+] (26), 194 (53), 180 (70), 179 (82). Anal. Calcd. For C12H14O4: C 64.85, H 6.35; Found C 64.78, H 6.25.

Refinement top

The H atoms were found in a difference map, relocated to idealized locations (C—H = 0.95–1.00 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl). The methyl groups were allowed to rotate but not to tip to best fit the electron density.

Structure description top

Indanones are useful precursors in the synthesis of a variety of biologically active compounds including indacrinone (Hanna & Lau-cam, 1989), indanoyl isoleucine conjugates (Mithofer et al., 2005), indanocines (Andreani et al., 2000) and other medicinally important products (Pinkerton et al., 2005, Yamamoto et al., 1994, Briggs et al., 1976). Donepezil, a 5,6-dimethoxyindanone and its derivatives, are acetyl cholinesterase inhibitors used in treatment of Alzheimer disease (Omran et al., 2005). A number of donepezil analogues have been prepared with prospective in the treatment of Alzheimer disease (Andreani et al., 2000). 1-Indanones are also important precursors in the regiospecific synthesis of 2-fluoro-1-naphthols (Cai et al., 2005). 5-Chloro-1-indanone has been used to synthesize important biomedical compounds as anticonvulsants (Kwiecien et al., 1991), anticholinergics (De Paulis et al., 1981) and diarylsulfonylureas, which show great activity against solid tumours (Howbert et al.,1990).

The title compound, (I), was prepared as an intermediates for an isocoumarin synthesis and for the systematic study of its bioactivity. The synthesis was carried out by cyclodehydration of 3-(3,4,5-trimethoxyphenyl)propanoic acid using polyphosphoric acid.

A perspective view of (I) is shown in Fig. 1. Bond lengths and angles can be regarded as normal (Cambridge Crystallographic Database, Version 5.28, November 2006; Mogul Version 1.1; Allen, 2002, Bruno et al., 2004). The atoms comprising the two rings are essentially planar (r.m.s. deviation for the nine C atoms 0.016 Å). Whereas one of the methoxy groups is almost coplanar with the aromatic ring, the other two are considerably twisted out of the plane of the aromatic ring (Table 1).

For background literature on indanones and their biological applications, see: Andreani et al. (2000); Cai et al. (2005); De Paulis et al. (1981); Hanna & Lau-cam (1989); Howbert & Crowell (1990); Kwiecien et al. (1991); Mithofer et al. (2005); Omran et al. (2005); Pinkerton et al. (2005); Yamamoto et al. (1994).

For related literature, see: Allen (2002); Biggs et al. (1976); Bruno et al. (2004); Rambaldi et al. (2001).

Computing details top

Data collection: X-AREA (Stoe & Cie, 2001); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. Reaction scheme.
5,6,7-Trimethoxy-2,3-dihydroinden-1-one top
Crystal data top
C12H14O4F(000) = 472
Mr = 222.23Dx = 1.351 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 10752 reflections
a = 8.9319 (7) Åθ = 3.7–27.4°
b = 7.2870 (5) ŵ = 0.10 mm1
c = 16.8250 (12) ÅT = 173 K
β = 94.070 (6)°Block, colourless
V = 1092.32 (14) Å30.44 × 0.36 × 0.35 mm
Z = 4
Data collection top
Stoe IPDSII two-circle
diffractometer
2228 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.037
Graphite monochromatorθmax = 27.6°, θmin = 3.6°
ω scansh = 1111
13559 measured reflectionsk = 99
2503 independent reflectionsl = 2121
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.099 w = 1/[σ2(Fo2) + (0.0517P)2 + 0.3007P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2503 reflectionsΔρmax = 0.31 e Å3
149 parametersΔρmin = 0.18 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.032 (3)
Crystal data top
C12H14O4V = 1092.32 (14) Å3
Mr = 222.23Z = 4
Monoclinic, P21/nMo Kα radiation
a = 8.9319 (7) ŵ = 0.10 mm1
b = 7.2870 (5) ÅT = 173 K
c = 16.8250 (12) Å0.44 × 0.36 × 0.35 mm
β = 94.070 (6)°
Data collection top
Stoe IPDSII two-circle
diffractometer
2228 reflections with I > 2σ(I)
13559 measured reflectionsRint = 0.037
2503 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0360 restraints
wR(F2) = 0.099H-atom parameters constrained
S = 1.05Δρmax = 0.31 e Å3
2503 reflectionsΔρmin = 0.18 e Å3
149 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
O10.74306 (10)0.18545 (11)0.48369 (5)0.0279 (2)
O20.69416 (9)0.34326 (11)0.62622 (5)0.02385 (19)
O30.74311 (9)0.70171 (11)0.65236 (4)0.0242 (2)
O40.86342 (11)0.27959 (15)0.32016 (5)0.0386 (2)
C10.76746 (11)0.37103 (14)0.49242 (6)0.0200 (2)
C20.74150 (11)0.45090 (14)0.56521 (6)0.0190 (2)
C30.77195 (11)0.64021 (14)0.57867 (6)0.0192 (2)
C40.82703 (11)0.74926 (14)0.51888 (6)0.0211 (2)
H40.84680.87610.52750.025*
C50.85206 (11)0.66692 (15)0.44633 (6)0.0210 (2)
C60.82389 (11)0.48094 (15)0.43221 (6)0.0207 (2)
C70.86659 (12)0.43158 (18)0.35147 (6)0.0268 (3)
C80.91705 (15)0.6070 (2)0.31223 (7)0.0346 (3)
H8A0.84810.63760.26540.042*
H8B1.01950.59190.29430.042*
C90.91487 (13)0.75968 (18)0.37514 (7)0.0294 (3)
H9A1.01730.80700.38900.035*
H9B0.84980.86260.35570.035*
C100.61698 (14)0.13820 (18)0.42970 (8)0.0324 (3)
H10A0.52510.18970.44920.049*
H10B0.60790.00440.42630.049*
H10C0.63200.18830.37680.049*
C110.53673 (13)0.36075 (18)0.63795 (8)0.0310 (3)
H11A0.51580.48560.65580.046*
H11B0.50920.27260.67840.046*
H11C0.47800.33600.58770.046*
C120.77570 (14)0.89208 (16)0.66966 (7)0.0289 (3)
H12A0.88290.91510.66530.043*
H12B0.74940.92060.72390.043*
H12C0.71690.96990.63160.043*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0334 (4)0.0174 (4)0.0317 (4)0.0008 (3)0.0061 (3)0.0016 (3)
O20.0236 (4)0.0224 (4)0.0262 (4)0.0001 (3)0.0064 (3)0.0081 (3)
O30.0298 (4)0.0218 (4)0.0216 (4)0.0020 (3)0.0071 (3)0.0021 (3)
O40.0362 (5)0.0486 (6)0.0316 (5)0.0022 (4)0.0063 (4)0.0149 (4)
C10.0185 (5)0.0176 (5)0.0235 (5)0.0025 (4)0.0015 (4)0.0009 (4)
C20.0169 (5)0.0191 (5)0.0209 (5)0.0007 (4)0.0022 (4)0.0043 (4)
C30.0174 (5)0.0207 (5)0.0197 (5)0.0016 (4)0.0020 (4)0.0008 (4)
C40.0204 (5)0.0186 (5)0.0246 (5)0.0001 (4)0.0026 (4)0.0032 (4)
C50.0163 (4)0.0252 (5)0.0216 (5)0.0022 (4)0.0019 (4)0.0059 (4)
C60.0170 (5)0.0259 (5)0.0190 (5)0.0041 (4)0.0001 (4)0.0010 (4)
C70.0185 (5)0.0409 (7)0.0208 (5)0.0058 (4)0.0005 (4)0.0020 (5)
C80.0313 (6)0.0515 (8)0.0218 (5)0.0026 (6)0.0069 (4)0.0061 (5)
C90.0270 (6)0.0349 (6)0.0271 (6)0.0030 (5)0.0076 (4)0.0120 (5)
C100.0315 (6)0.0287 (6)0.0363 (6)0.0045 (5)0.0026 (5)0.0055 (5)
C110.0244 (6)0.0339 (6)0.0357 (6)0.0051 (5)0.0095 (5)0.0039 (5)
C120.0348 (6)0.0235 (6)0.0290 (6)0.0027 (5)0.0051 (4)0.0064 (4)
Geometric parameters (Å, º) top
O1—C11.3760 (13)C7—C81.5217 (18)
O1—C101.4377 (14)C8—C91.5366 (19)
O2—C21.3818 (12)C8—H8A0.9900
O2—C111.4394 (13)C8—H8B0.9900
O3—C31.3600 (12)C9—H9A0.9900
O3—C121.4429 (14)C9—H9B0.9900
O4—C71.2259 (16)C10—H10A0.9800
C1—C21.3901 (14)C10—H10B0.9800
C1—C61.4122 (15)C10—H10C0.9800
C2—C31.4211 (15)C11—H11A0.9800
C3—C41.3984 (14)C11—H11B0.9800
C4—C51.3924 (15)C11—H11C0.9800
C4—H40.9500C12—H12A0.9800
C5—C61.3957 (16)C12—H12B0.9800
C5—C91.5171 (14)C12—H12C0.9800
C6—C71.4810 (14)
C1—O1—C10114.45 (9)C7—C8—H8B110.3
C2—O2—C11113.90 (8)C9—C8—H8B110.3
C3—O3—C12116.89 (8)H8A—C8—H8B108.6
O1—C1—C2118.07 (9)C5—C9—C8104.16 (10)
O1—C1—C6122.86 (10)C5—C9—H9A110.9
C2—C1—C6119.01 (10)C8—C9—H9A110.9
O2—C2—C1119.72 (9)C5—C9—H9B110.9
O2—C2—C3119.85 (9)C8—C9—H9B110.9
C1—C2—C3120.32 (9)H9A—C9—H9B108.9
O3—C3—C4124.58 (10)O1—C10—H10A109.5
O3—C3—C2114.75 (9)O1—C10—H10B109.5
C4—C3—C2120.67 (9)H10A—C10—H10B109.5
C5—C4—C3118.18 (10)O1—C10—H10C109.5
C5—C4—H4120.9H10A—C10—H10C109.5
C3—C4—H4120.9H10B—C10—H10C109.5
C4—C5—C6121.97 (9)O2—C11—H11A109.5
C4—C5—C9126.26 (10)O2—C11—H11B109.5
C6—C5—C9111.75 (10)H11A—C11—H11B109.5
C5—C6—C1119.85 (9)O2—C11—H11C109.5
C5—C6—C7109.69 (10)H11A—C11—H11C109.5
C1—C6—C7130.43 (10)H11B—C11—H11C109.5
O4—C7—C6127.87 (11)O3—C12—H12A109.5
O4—C7—C8124.83 (11)O3—C12—H12B109.5
C6—C7—C8107.30 (10)H12A—C12—H12B109.5
C7—C8—C9106.90 (9)O3—C12—H12C109.5
C7—C8—H8A110.3H12A—C12—H12C109.5
C9—C8—H8A110.3H12B—C12—H12C109.5
C10—O1—C1—C2111.17 (11)C4—C5—C6—C10.38 (15)
C10—O1—C1—C671.82 (13)C9—C5—C6—C1178.89 (9)
C11—O2—C2—C1103.31 (11)C4—C5—C6—C7177.77 (9)
C11—O2—C2—C380.44 (12)C9—C5—C6—C70.73 (12)
O1—C1—C2—O20.67 (14)O1—C1—C6—C5177.24 (9)
C6—C1—C2—O2176.46 (9)C2—C1—C6—C50.25 (15)
O1—C1—C2—C3176.91 (9)O1—C1—C6—C70.48 (17)
C6—C1—C2—C30.22 (15)C2—C1—C6—C7177.47 (10)
C12—O3—C3—C41.56 (15)C5—C6—C7—O4176.68 (11)
C12—O3—C3—C2178.52 (9)C1—C6—C7—O41.22 (19)
O2—C2—C3—O33.26 (13)C5—C6—C7—C83.29 (12)
C1—C2—C3—O3179.49 (9)C1—C6—C7—C8178.82 (10)
O2—C2—C3—C4176.82 (9)O4—C7—C8—C9175.48 (11)
C1—C2—C3—C40.59 (15)C6—C7—C8—C94.49 (12)
O3—C3—C4—C5179.63 (9)C4—C5—C9—C8179.50 (10)
C2—C3—C4—C50.46 (15)C6—C5—C9—C82.07 (12)
C3—C4—C5—C60.02 (15)C7—C8—C9—C53.94 (12)
C3—C4—C5—C9178.30 (10)

Experimental details

Crystal data
Chemical formulaC12H14O4
Mr222.23
Crystal system, space groupMonoclinic, P21/n
Temperature (K)173
a, b, c (Å)8.9319 (7), 7.2870 (5), 16.8250 (12)
β (°) 94.070 (6)
V3)1092.32 (14)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.44 × 0.36 × 0.35
Data collection
DiffractometerStoe IPDSII two-circle
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
13559, 2503, 2228
Rint0.037
(sin θ/λ)max1)0.651
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.099, 1.05
No. of reflections2503
No. of parameters149
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.31, 0.18

Computer programs: X-AREA (Stoe & Cie, 2001), X-AREA, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97.

Selected torsion angles (º) top
C10—O1—C1—C671.82 (13)C12—O3—C3—C41.56 (15)
C11—O2—C2—C380.44 (12)
 

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