Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807019848/hb2386sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807019848/hb2386Isup2.hkl |
CCDC reference: 647720
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.
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.
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).
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.
C12H14O4 | F(000) = 472 |
Mr = 222.23 | Dx = 1.351 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 10752 reflections |
a = 8.9319 (7) Å | θ = 3.7–27.4° |
b = 7.2870 (5) Å | µ = 0.10 mm−1 |
c = 16.8250 (12) Å | T = 173 K |
β = 94.070 (6)° | Block, colourless |
V = 1092.32 (14) Å3 | 0.44 × 0.36 × 0.35 mm |
Z = 4 |
Stoe IPDSII two-circle diffractometer | 2228 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.037 |
Graphite monochromator | θmax = 27.6°, θmin = 3.6° |
ω scans | h = −11→11 |
13559 measured reflections | k = −9→9 |
2503 independent reflections | l = −21→21 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.036 | H-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 reflections | Δρmax = 0.31 e Å−3 |
149 parameters | Δρmin = −0.18 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.032 (3) |
C12H14O4 | V = 1092.32 (14) Å3 |
Mr = 222.23 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 8.9319 (7) Å | µ = 0.10 mm−1 |
b = 7.2870 (5) Å | T = 173 K |
c = 16.8250 (12) Å | 0.44 × 0.36 × 0.35 mm |
β = 94.070 (6)° |
Stoe IPDSII two-circle diffractometer | 2228 reflections with I > 2σ(I) |
13559 measured reflections | Rint = 0.037 |
2503 independent reflections |
R[F2 > 2σ(F2)] = 0.036 | 0 restraints |
wR(F2) = 0.099 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.31 e Å−3 |
2503 reflections | Δρmin = −0.18 e Å−3 |
149 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.74306 (10) | 0.18545 (11) | 0.48369 (5) | 0.0279 (2) | |
O2 | 0.69416 (9) | 0.34326 (11) | 0.62622 (5) | 0.02385 (19) | |
O3 | 0.74311 (9) | 0.70171 (11) | 0.65236 (4) | 0.0242 (2) | |
O4 | 0.86342 (11) | 0.27959 (15) | 0.32016 (5) | 0.0386 (2) | |
C1 | 0.76746 (11) | 0.37103 (14) | 0.49242 (6) | 0.0200 (2) | |
C2 | 0.74150 (11) | 0.45090 (14) | 0.56521 (6) | 0.0190 (2) | |
C3 | 0.77195 (11) | 0.64021 (14) | 0.57867 (6) | 0.0192 (2) | |
C4 | 0.82703 (11) | 0.74926 (14) | 0.51888 (6) | 0.0211 (2) | |
H4 | 0.8468 | 0.8761 | 0.5275 | 0.025* | |
C5 | 0.85206 (11) | 0.66692 (15) | 0.44633 (6) | 0.0210 (2) | |
C6 | 0.82389 (11) | 0.48094 (15) | 0.43221 (6) | 0.0207 (2) | |
C7 | 0.86659 (12) | 0.43158 (18) | 0.35147 (6) | 0.0268 (3) | |
C8 | 0.91705 (15) | 0.6070 (2) | 0.31223 (7) | 0.0346 (3) | |
H8A | 0.8481 | 0.6376 | 0.2654 | 0.042* | |
H8B | 1.0195 | 0.5919 | 0.2943 | 0.042* | |
C9 | 0.91487 (13) | 0.75968 (18) | 0.37514 (7) | 0.0294 (3) | |
H9A | 1.0173 | 0.8070 | 0.3890 | 0.035* | |
H9B | 0.8498 | 0.8626 | 0.3557 | 0.035* | |
C10 | 0.61698 (14) | 0.13820 (18) | 0.42970 (8) | 0.0324 (3) | |
H10A | 0.5251 | 0.1897 | 0.4492 | 0.049* | |
H10B | 0.6079 | 0.0044 | 0.4263 | 0.049* | |
H10C | 0.6320 | 0.1883 | 0.3768 | 0.049* | |
C11 | 0.53673 (13) | 0.36075 (18) | 0.63795 (8) | 0.0310 (3) | |
H11A | 0.5158 | 0.4856 | 0.6558 | 0.046* | |
H11B | 0.5092 | 0.2726 | 0.6784 | 0.046* | |
H11C | 0.4780 | 0.3360 | 0.5877 | 0.046* | |
C12 | 0.77570 (14) | 0.89208 (16) | 0.66966 (7) | 0.0289 (3) | |
H12A | 0.8829 | 0.9151 | 0.6653 | 0.043* | |
H12B | 0.7494 | 0.9206 | 0.7239 | 0.043* | |
H12C | 0.7169 | 0.9699 | 0.6316 | 0.043* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0334 (4) | 0.0174 (4) | 0.0317 (4) | 0.0008 (3) | −0.0061 (3) | −0.0016 (3) |
O2 | 0.0236 (4) | 0.0224 (4) | 0.0262 (4) | 0.0001 (3) | 0.0064 (3) | 0.0081 (3) |
O3 | 0.0298 (4) | 0.0218 (4) | 0.0216 (4) | −0.0020 (3) | 0.0071 (3) | −0.0021 (3) |
O4 | 0.0362 (5) | 0.0486 (6) | 0.0316 (5) | 0.0022 (4) | 0.0063 (4) | −0.0149 (4) |
C1 | 0.0185 (5) | 0.0176 (5) | 0.0235 (5) | 0.0025 (4) | −0.0015 (4) | 0.0009 (4) |
C2 | 0.0169 (5) | 0.0191 (5) | 0.0209 (5) | 0.0007 (4) | 0.0022 (4) | 0.0043 (4) |
C3 | 0.0174 (5) | 0.0207 (5) | 0.0197 (5) | 0.0016 (4) | 0.0020 (4) | 0.0008 (4) |
C4 | 0.0204 (5) | 0.0186 (5) | 0.0246 (5) | −0.0001 (4) | 0.0026 (4) | 0.0032 (4) |
C5 | 0.0163 (4) | 0.0252 (5) | 0.0216 (5) | 0.0022 (4) | 0.0019 (4) | 0.0059 (4) |
C6 | 0.0170 (5) | 0.0259 (5) | 0.0190 (5) | 0.0041 (4) | 0.0001 (4) | 0.0010 (4) |
C7 | 0.0185 (5) | 0.0409 (7) | 0.0208 (5) | 0.0058 (4) | 0.0005 (4) | −0.0020 (5) |
C8 | 0.0313 (6) | 0.0515 (8) | 0.0218 (5) | 0.0026 (6) | 0.0069 (4) | 0.0061 (5) |
C9 | 0.0270 (6) | 0.0349 (6) | 0.0271 (6) | 0.0030 (5) | 0.0076 (4) | 0.0120 (5) |
C10 | 0.0315 (6) | 0.0287 (6) | 0.0363 (6) | −0.0045 (5) | −0.0026 (5) | −0.0055 (5) |
C11 | 0.0244 (6) | 0.0339 (6) | 0.0357 (6) | −0.0051 (5) | 0.0095 (5) | 0.0039 (5) |
C12 | 0.0348 (6) | 0.0235 (6) | 0.0290 (6) | −0.0027 (5) | 0.0051 (4) | −0.0064 (4) |
O1—C1 | 1.3760 (13) | C7—C8 | 1.5217 (18) |
O1—C10 | 1.4377 (14) | C8—C9 | 1.5366 (19) |
O2—C2 | 1.3818 (12) | C8—H8A | 0.9900 |
O2—C11 | 1.4394 (13) | C8—H8B | 0.9900 |
O3—C3 | 1.3600 (12) | C9—H9A | 0.9900 |
O3—C12 | 1.4429 (14) | C9—H9B | 0.9900 |
O4—C7 | 1.2259 (16) | C10—H10A | 0.9800 |
C1—C2 | 1.3901 (14) | C10—H10B | 0.9800 |
C1—C6 | 1.4122 (15) | C10—H10C | 0.9800 |
C2—C3 | 1.4211 (15) | C11—H11A | 0.9800 |
C3—C4 | 1.3984 (14) | C11—H11B | 0.9800 |
C4—C5 | 1.3924 (15) | C11—H11C | 0.9800 |
C4—H4 | 0.9500 | C12—H12A | 0.9800 |
C5—C6 | 1.3957 (16) | C12—H12B | 0.9800 |
C5—C9 | 1.5171 (14) | C12—H12C | 0.9800 |
C6—C7 | 1.4810 (14) | ||
C1—O1—C10 | 114.45 (9) | C7—C8—H8B | 110.3 |
C2—O2—C11 | 113.90 (8) | C9—C8—H8B | 110.3 |
C3—O3—C12 | 116.89 (8) | H8A—C8—H8B | 108.6 |
O1—C1—C2 | 118.07 (9) | C5—C9—C8 | 104.16 (10) |
O1—C1—C6 | 122.86 (10) | C5—C9—H9A | 110.9 |
C2—C1—C6 | 119.01 (10) | C8—C9—H9A | 110.9 |
O2—C2—C1 | 119.72 (9) | C5—C9—H9B | 110.9 |
O2—C2—C3 | 119.85 (9) | C8—C9—H9B | 110.9 |
C1—C2—C3 | 120.32 (9) | H9A—C9—H9B | 108.9 |
O3—C3—C4 | 124.58 (10) | O1—C10—H10A | 109.5 |
O3—C3—C2 | 114.75 (9) | O1—C10—H10B | 109.5 |
C4—C3—C2 | 120.67 (9) | H10A—C10—H10B | 109.5 |
C5—C4—C3 | 118.18 (10) | O1—C10—H10C | 109.5 |
C5—C4—H4 | 120.9 | H10A—C10—H10C | 109.5 |
C3—C4—H4 | 120.9 | H10B—C10—H10C | 109.5 |
C4—C5—C6 | 121.97 (9) | O2—C11—H11A | 109.5 |
C4—C5—C9 | 126.26 (10) | O2—C11—H11B | 109.5 |
C6—C5—C9 | 111.75 (10) | H11A—C11—H11B | 109.5 |
C5—C6—C1 | 119.85 (9) | O2—C11—H11C | 109.5 |
C5—C6—C7 | 109.69 (10) | H11A—C11—H11C | 109.5 |
C1—C6—C7 | 130.43 (10) | H11B—C11—H11C | 109.5 |
O4—C7—C6 | 127.87 (11) | O3—C12—H12A | 109.5 |
O4—C7—C8 | 124.83 (11) | O3—C12—H12B | 109.5 |
C6—C7—C8 | 107.30 (10) | H12A—C12—H12B | 109.5 |
C7—C8—C9 | 106.90 (9) | O3—C12—H12C | 109.5 |
C7—C8—H8A | 110.3 | H12A—C12—H12C | 109.5 |
C9—C8—H8A | 110.3 | H12B—C12—H12C | 109.5 |
C10—O1—C1—C2 | 111.17 (11) | C4—C5—C6—C1 | 0.38 (15) |
C10—O1—C1—C6 | −71.82 (13) | C9—C5—C6—C1 | 178.89 (9) |
C11—O2—C2—C1 | −103.31 (11) | C4—C5—C6—C7 | −177.77 (9) |
C11—O2—C2—C3 | 80.44 (12) | C9—C5—C6—C7 | 0.73 (12) |
O1—C1—C2—O2 | 0.67 (14) | O1—C1—C6—C5 | −177.24 (9) |
C6—C1—C2—O2 | −176.46 (9) | C2—C1—C6—C5 | −0.25 (15) |
O1—C1—C2—C3 | 176.91 (9) | O1—C1—C6—C7 | 0.48 (17) |
C6—C1—C2—C3 | −0.22 (15) | C2—C1—C6—C7 | 177.47 (10) |
C12—O3—C3—C4 | −1.56 (15) | C5—C6—C7—O4 | 176.68 (11) |
C12—O3—C3—C2 | 178.52 (9) | C1—C6—C7—O4 | −1.22 (19) |
O2—C2—C3—O3 | −3.26 (13) | C5—C6—C7—C8 | −3.29 (12) |
C1—C2—C3—O3 | −179.49 (9) | C1—C6—C7—C8 | 178.82 (10) |
O2—C2—C3—C4 | 176.82 (9) | O4—C7—C8—C9 | −175.48 (11) |
C1—C2—C3—C4 | 0.59 (15) | C6—C7—C8—C9 | 4.49 (12) |
O3—C3—C4—C5 | 179.63 (9) | C4—C5—C9—C8 | −179.50 (10) |
C2—C3—C4—C5 | −0.46 (15) | C6—C5—C9—C8 | 2.07 (12) |
C3—C4—C5—C6 | −0.02 (15) | C7—C8—C9—C5 | −3.94 (12) |
C3—C4—C5—C9 | −178.30 (10) |
Experimental details
Crystal data | |
Chemical formula | C12H14O4 |
Mr | 222.23 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 173 |
a, b, c (Å) | 8.9319 (7), 7.2870 (5), 16.8250 (12) |
β (°) | 94.070 (6) |
V (Å3) | 1092.32 (14) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.44 × 0.36 × 0.35 |
Data collection | |
Diffractometer | Stoe IPDSII two-circle |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13559, 2503, 2228 |
Rint | 0.037 |
(sin θ/λ)max (Å−1) | 0.651 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.099, 1.05 |
No. of reflections | 2503 |
No. of parameters | 149 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.31, −0.18 |
Computer programs: X-AREA (Stoe & Cie, 2001), X-AREA, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97.
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).