In the title compound, C8H8O4, the acetic acid side chain adopts a roughly perpendicular orientation with respect to the phenyl ring. Hydrogen bonding between carboxyl groups results in the formation of a centrosymmetric dimer. An intramolecular hydrogen bond is formed in the catechol part of the molecule. Molecules are linked together through hydrogen bonds between hydroxyl and carboxylic acid O atoms.
Supporting information
CCDC reference: 170901
Key indicators
- Single-crystal X-ray study
- T = 296 K
- Mean (C-C) = 0.008 Å
- R factor = 0.051
- wR factor = 0.220
- Data-to-parameter ratio = 15.7
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
The colorless thin plate crystal used for analysis was obtained by slow
evaporation from a solution in a mixture of diethyl ether and n-hexane (6:1
volume ratio) at room temperature.
All H atoms were located from difference Fourier maps but were not refined.
Data collection: MSC/AFC(Molecular Structure Corporation,
Rigaku Corporation, 1999); cell refinement: MSC/AFC(Molecular Structure Corporation,
Rigaku Corporation, 1999); data reduction: TEXSAN Version 1.10 (Molecular Structure Corporation,
Rigaku Corporation, 1999); program(s) used to solve structure: SIR88 (Burla et al., 1989) & DIRDIF94
(Beurskens et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: TEXSAN Version 1.10 (Molecular Structure Corporation,
Rigaku Corporation, 1999).
Crystal data top
C8H8O4 | Dx = 1.496 Mg m−3 |
Mr = 168.14 | Mo Kα radiation, λ = 0.7107 Å |
Orthorhombic, Pbca | Cell parameters from 18 reflections |
a = 16.181 (2) Å | θ = 10.1–13.1° |
b = 11.625 (2) Å | µ = 0.12 mm−1 |
c = 7.938 (3) Å | T = 296 K |
V = 1493.2 (6) Å3 | Thin plate, colorless |
Z = 8 | 0.35 × 0.20 × 0.02 mm |
F(000) = 704.00 | |
Data collection top
Rigaku AFC-5R diffractometer | θmax = 27.5°, θmin = 4° |
ω–2θ scans | h = 0→21 |
1714 measured reflections | k = 0→15 |
1714 independent reflections | l = −10→0 |
493 reflections with I > 2σ(I) | 3 standard reflections every 150 reflections |
Rint = 0.000 | intensity decay: 0.2% |
Refinement top
Refinement on F2 | H-atom parameters not refined |
R[F2 > 2σ(F2)] = 0.051 | w = 1/[σ2(Fo2) + (0.1P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.220 | (Δ/σ)max < 0.001 |
S = 0.84 | Δρmax = 0.25 e Å−3 |
1714 reflections | Δρmin = −0.30 e Å−3 |
109 parameters | |
Crystal data top
C8H8O4 | V = 1493.2 (6) Å3 |
Mr = 168.14 | Z = 8 |
Orthorhombic, Pbca | Mo Kα radiation |
a = 16.181 (2) Å | µ = 0.12 mm−1 |
b = 11.625 (2) Å | T = 296 K |
c = 7.938 (3) Å | 0.35 × 0.20 × 0.02 mm |
Data collection top
Rigaku AFC-5R diffractometer | Rint = 0.000 |
1714 measured reflections | 3 standard reflections every 150 reflections |
1714 independent reflections | intensity decay: 0.2% |
493 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | 109 parameters |
wR(F2) = 0.220 | H-atom parameters not refined |
S = 0.84 | Δρmax = 0.25 e Å−3 |
1714 reflections | Δρmin = −0.30 e Å−3 |
Special details top
Refinement. Refinement using reflections with F2 > 0.0 σ(F2). The
weighted R-factor (wR) and goodness of fit (S) are based
on F2. R-factor (gt) are based on F. The threshold
expression of F2 > 2.0 σ(F2) is used only for calculating
R-factor (gt). |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.9152 (2) | −0.0207 (3) | 0.3666 (6) | 0.055 (1) | |
O2 | 0.9798 (2) | 0.1389 (4) | 0.4402 (5) | 0.046 (1) | |
O3 | 0.5970 (2) | −0.0461 (3) | 0.3061 (5) | 0.047 (1) | |
O4 | 0.5340 (2) | 0.1330 (3) | 0.4918 (5) | 0.042 (1) | |
C1 | 0.7766 (3) | 0.1434 (5) | 0.3191 (7) | 0.029 (1) | |
C2 | 0.7254 (3) | 0.0496 (5) | 0.2849 (7) | 0.034 (1) | |
C3 | 0.6453 (3) | 0.0468 (4) | 0.3444 (7) | 0.033 (1) | |
C4 | 0.6155 (3) | 0.1381 (5) | 0.4406 (6) | 0.032 (1) | |
C5 | 0.6653 (3) | 0.2295 (5) | 0.4787 (8) | 0.038 (1) | |
C6 | 0.7463 (3) | 0.2324 (5) | 0.4162 (7) | 0.037 (1) | |
C7 | 0.8644 (3) | 0.1493 (5) | 0.2511 (7) | 0.038 (1) | |
C8 | 0.9250 (3) | 0.0904 (5) | 0.3625 (8) | 0.034 (1) | |
H2 | 0.7460 | −0.0133 | 0.2208 | 0.0406* | |
H3 | 0.5458 | −0.0298 | 0.3404 | 0.0464* | |
H4 | 0.4987 | 0.1916 | 0.5362 | 0.0464* | |
H5 | 0.6452 | 0.2904 | 0.5471 | 0.0453* | |
H6 | 0.7808 | 0.2963 | 0.4406 | 0.0445* | |
H7 | 0.8798 | 0.2278 | 0.2406 | 0.0450* | |
H8 | 0.8658 | 0.1137 | 0.1434 | 0.0450* | |
H9 | 0.9579 | −0.0777 | 0.4190 | 0.0464* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.046 (2) | 0.035 (2) | 0.083 (3) | 0.001 (2) | −0.023 (2) | 0.005 (2) |
O2 | 0.031 (2) | 0.041 (2) | 0.066 (3) | −0.005 (2) | −0.012 (2) | 0.004 (2) |
O3 | 0.034 (2) | 0.034 (2) | 0.075 (3) | −0.005 (2) | 0.010 (2) | −0.008 (2) |
O4 | 0.026 (2) | 0.039 (2) | 0.060 (3) | 0.002 (2) | 0.005 (2) | −0.007 (2) |
C1 | 0.022 (2) | 0.037 (3) | 0.030 (3) | 0.002 (2) | −0.002 (2) | 0.008 (3) |
C2 | 0.029 (3) | 0.028 (3) | 0.046 (4) | 0.003 (2) | 0.006 (3) | 0.001 (3) |
C3 | 0.032 (3) | 0.028 (3) | 0.039 (3) | −0.004 (2) | −0.008 (3) | 0.004 (3) |
C4 | 0.026 (2) | 0.034 (3) | 0.036 (3) | 0.006 (3) | 0.005 (2) | 0.003 (3) |
C5 | 0.039 (3) | 0.034 (3) | 0.042 (4) | 0.003 (3) | −0.003 (3) | −0.011 (3) |
C6 | 0.027 (2) | 0.034 (3) | 0.052 (4) | −0.008 (3) | −0.006 (3) | −0.005 (3) |
C7 | 0.031 (3) | 0.044 (3) | 0.041 (3) | −0.003 (3) | −0.001 (2) | 0.005 (3) |
C8 | 0.025 (3) | 0.034 (3) | 0.043 (4) | 0.004 (3) | 0.003 (3) | 0.001 (3) |
Geometric parameters (Å, º) top
O1—C8 | 1.301 (7) | C2—C3 | 1.379 (7) |
O1—H9 | 1.044 | C2—H2 | 0.951 |
O2—C8 | 1.219 (7) | C3—C4 | 1.394 (8) |
O3—C3 | 1.368 (6) | C4—C5 | 1.367 (8) |
O3—H3 | 0.891 | C5—C6 | 1.402 (7) |
O4—C4 | 1.381 (6) | C5—H5 | 0.950 |
O4—H4 | 0.957 | C6—H6 | 0.948 |
C1—C2 | 1.397 (7) | C7—C8 | 1.489 (8) |
C1—C6 | 1.381 (8) | C7—H7 | 0.950 |
C1—C7 | 1.520 (7) | C7—H8 | 0.950 |
| | | |
O1···O2i | 2.670 (6) | O2···O3ii | 3.470 (5) |
O1···O3ii | 3.258 (5) | O2···C4vi | 3.526 (7) |
O1···C5iii | 3.305 (7) | O2···O4ii | 3.540 (6) |
O1···O4iv | 3.351 (6) | O3···O4vii | 2.844 (5) |
O1···C8i | 3.459 (7) | O3···C8viii | 3.471 (6) |
O1···O1i | 3.500 (8) | O3···C8iv | 3.577 (7) |
O1···O3v | 3.580 (6) | O4···O4vii | 3.284 (7) |
O2···O4vi | 2.845 (6) | O4···C8viii | 3.357 (7) |
O2···O3v | 3.339 (6) | O4···C7viii | 3.361 (6) |
O2···C5vi | 3.429 (6) | C1···C6ix | 3.543 (8) |
O2···O2i | 3.430 (8) | C1···C5ix | 3.568 (8) |
O2···C8i | 3.454 (7) | C6···C7x | 3.550 (8) |
| | | |
C8—O1—H9 | 124.0 | C4—C5—C6 | 119.4 (5) |
C3—O3—H3 | 107.2 | C4—C5—H5 | 120.3 |
C4—O4—H4 | 130.4 | C6—C5—H5 | 120.3 |
C2—C1—C6 | 118.9 (4) | C1—C6—C5 | 120.8 (5) |
C2—C1—C7 | 121.4 (5) | C1—C6—H6 | 119.5 |
C6—C1—C7 | 119.7 (5) | C5—C6—H6 | 119.8 |
C1—C2—C3 | 120.6 (5) | C1—C7—C8 | 112.6 (5) |
C1—C2—H2 | 119.7 | C1—C7—H7 | 108.7 |
C3—C2—H2 | 119.7 | C1—C7—H8 | 108.8 |
O3—C3—C2 | 118.7 (5) | C8—C7—H7 | 108.7 |
O3—C3—C4 | 121.6 (4) | C8—C7—H8 | 108.6 |
C2—C3—C4 | 119.7 (5) | H7—C7—H8 | 109.5 |
O4—C4—C3 | 117.3 (5) | O1—C8—O2 | 122.4 (5) |
O4—C4—C5 | 122.1 (5) | O1—C8—C7 | 113.0 (5) |
C3—C4—C5 | 120.6 (5) | O2—C8—C7 | 124.6 (5) |
| | | |
O1—C8—C7—C1 | 68.1 (6) | C2—C1—C6—C5 | −0.4 (8) |
O2—C8—C7—C1 | −113.5 (6) | C2—C1—C7—C8 | −86.2 (6) |
O3—C3—C2—C1 | 179.2 (5) | C2—C3—C4—C5 | −1.1 (8) |
O3—C3—C4—O4 | −1.9 (7) | C3—C2—C1—C6 | 1.1 (8) |
O3—C3—C4—C5 | 179.3 (5) | C3—C2—C1—C7 | −178.5 (5) |
O4—C4—C3—C2 | 177.7 (5) | C3—C4—C5—C6 | 1.8 (8) |
O4—C4—C5—C6 | −176.9 (5) | C5—C6—C1—C7 | 179.3 (5) |
C1—C2—C3—C4 | −0.4 (8) | C6—C1—C7—C8 | 94.1 (6) |
C1—C6—C5—C4 | −1.0 (8) | | |
Symmetry codes: (i) −x+2, −y, −z+1; (ii) x+1/2, y, −z+1/2; (iii) −x+3/2, y−1/2, z; (iv) −x+3/2, −y, z−1/2; (v) −x+3/2, −y, z+1/2; (vi) x+1/2, −y+1/2, −z+1; (vii) −x+1, −y, −z+1; (viii) x−1/2, y, −z+1/2; (ix) x, −y+1/2, z−1/2; (x) x, −y+1/2, z+1/2. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H9···O2i | 1.046 | 1.667 | 2.674 (6) | 160.1 |
O3—H3···O4 | 0.891 | 2.248 | 2.745 (5) | 114.8 |
O4—H4···O2xi | 0.957 | 2.000 | 2.843 (6) | 145.8 |
Symmetry codes: (i) −x+2, −y, −z+1; (xi) x−1/2, −y+1/2, −z+1. |
Experimental details
Crystal data |
Chemical formula | C8H8O4 |
Mr | 168.14 |
Crystal system, space group | Orthorhombic, Pbca |
Temperature (K) | 296 |
a, b, c (Å) | 16.181 (2), 11.625 (2), 7.938 (3) |
V (Å3) | 1493.2 (6) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.35 × 0.20 × 0.02 |
|
Data collection |
Diffractometer | Rigaku AFC-5R diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1714, 1714, 493 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.650 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.220, 0.84 |
No. of reflections | 1714 |
No. of parameters | 109 |
No. of restraints | ? |
H-atom treatment | H-atom parameters not refined |
Δρmax, Δρmin (e Å−3) | 0.25, −0.30 |
Selected geometric parameters (Å, º) topO1—C8 | 1.301 (7) | C1—C7 | 1.520 (7) |
O2—C8 | 1.219 (7) | C2—C3 | 1.379 (7) |
O3—C3 | 1.368 (6) | C3—C4 | 1.394 (8) |
O4—C4 | 1.381 (6) | C4—C5 | 1.367 (8) |
C1—C2 | 1.397 (7) | C5—C6 | 1.402 (7) |
C1—C6 | 1.381 (8) | C7—C8 | 1.489 (8) |
| | | |
C2—C1—C6 | 118.9 (4) | O4—C4—C5 | 122.1 (5) |
C2—C1—C7 | 121.4 (5) | C3—C4—C5 | 120.6 (5) |
C6—C1—C7 | 119.7 (5) | C4—C5—C6 | 119.4 (5) |
C1—C2—C3 | 120.6 (5) | C1—C6—C5 | 120.8 (5) |
O3—C3—C2 | 118.7 (5) | C1—C7—C8 | 112.6 (5) |
O3—C3—C4 | 121.6 (4) | O1—C8—O2 | 122.4 (5) |
C2—C3—C4 | 119.7 (5) | O1—C8—C7 | 113.0 (5) |
O4—C4—C3 | 117.3 (5) | O2—C8—C7 | 124.6 (5) |
| | | |
O1—C8—C7—C1 | 68.1 (6) | C2—C1—C6—C5 | −0.4 (8) |
O2—C8—C7—C1 | −113.5 (6) | C2—C1—C7—C8 | −86.2 (6) |
O3—C3—C2—C1 | 179.2 (5) | C2—C3—C4—C5 | −1.1 (8) |
O3—C3—C4—O4 | −1.9 (7) | C3—C2—C1—C6 | 1.1 (8) |
O3—C3—C4—C5 | 179.3 (5) | C3—C2—C1—C7 | −178.5 (5) |
O4—C4—C3—C2 | 177.7 (5) | C3—C4—C5—C6 | 1.8 (8) |
O4—C4—C5—C6 | −176.9 (5) | C5—C6—C1—C7 | 179.3 (5) |
C1—C2—C3—C4 | −0.4 (8) | C6—C1—C7—C8 | 94.1 (6) |
C1—C6—C5—C4 | −1.0 (8) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H9···O2i | 1.046 | 1.667 | 2.674 (6) | 160.1 |
O3—H3···O4 | 0.891 | 2.248 | 2.745 (5) | 114.8 |
O4—H4···O2ii | 0.957 | 2.000 | 2.843 (6) | 145.8 |
Symmetry codes: (i) −x+2, −y, −z+1; (ii) x−1/2, −y+1/2, −z+1. |
It is important to clarify the detailed structure of the catecholamine metabolites in order to study catecholamine action as well as the metabolic pathway. In this context, the structures of the dopamine metabolites 3-methoxytyramine (Okabe, Mori & Sasaki, 1991; Okabe & Mori, 1992) and homovanillic acid (Okabe, Hatanaka & Sasaki, 1991), the noradrenaline metabolite normetanephrine (Pattanayek et al., 1984) and the adrenaline metabolite 4-hydroxy-3-methoxymandelic acid (Okabe et al., 1995) have been reported. We report here the crystal structure of the title compound, (I).
This compound is the principal metabolite of dopamine, but its structure could not be determined for a long time because of the difficulty of crystallization. The acetic acid side chain is oriented roughly perpendicularly to the catechol ring of the molecule [torsion angle C2—C1—C7—C8 - 87.2 (6)°]. This conformational feature of the molecule resembles that observed for dopamine, adrenaline and the corresponding amines (Barlow et al., 1989), as well as the catecholamine metabolites homovanillic acid (Okabe, Hatanaka & Sasaki, 1991), 3-methoxytyramine (Okabe & Mori, 1992) and 4-hydroxy-3-methoxymandelic acid (Okabe, Suga & Kohyama, 1995). This seems to be one of the important structural requirements for enzymatic recognition through the metabolic pathway. There is an intramolecular hydrogen bond between the two hydroxyl groups of the catechol ring (Table 2). This had not been observed in the crystal structures of the main catechol amine metabolites, dopamine hydrochloride (Giesecke, 1980), (-)-adrenaline (Andersen, 1975a), (-)-noradrenaline (Andersen, 1975b) or noradrenaline hydrochloride (Carlstro¨m & Bergin, 1967). Two molecules of (I) form a centrosymmetric dimer by hydrogen bonding between the carboxyl groups.