3,4-Di­hydroxy­phenyl­acetic acid

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.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](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

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S1. Comment

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.

S2. Experimental

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.

S3. Refinement

All H atoms were located from difference Fourier maps but were not refined.

Computing details

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).

Figures

Fig. 1. ORTEPII (Johnson, 1976) drawing of the title compound with the atomic numbering scheme. Ellipsoids for non-H atoms are shown at the 50% probability level.

(I)

Crystal data

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) Å^3	Thin plate, colorless
Z = 8	0.35 × 0.20 × 0.02 mm
F(000) = 704.00

Data collection

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

Refinement on F^2	H-atom parameters not refined
R[F^2 > 2σ(F^2)] = 0.051	w = 1/[σ^2(Fo^2) + (0.1P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 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

Special details

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 (Ų)

	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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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···O2^i	2.670 (6)	O2···O3^ii	3.470 (5)
O1···O3^ii	3.258 (5)	O2···C4^vi	3.526 (7)
O1···C5^iii	3.305 (7)	O2···O4^ii	3.540 (6)
O1···O4^iv	3.351 (6)	O3···O4^vii	2.844 (5)
O1···C8^i	3.459 (7)	O3···C8^viii	3.471 (6)
O1···O1^i	3.500 (8)	O3···C8^iv	3.577 (7)
O1···O3^v	3.580 (6)	O4···O4^vii	3.284 (7)
O2···O4^vi	2.845 (6)	O4···C8^viii	3.357 (7)
O2···O3^v	3.339 (6)	O4···C7^viii	3.361 (6)
O2···C5^vi	3.429 (6)	C1···C6^ix	3.543 (8)
O2···O2^i	3.430 (8)	C1···C5^ix	3.568 (8)
O2···C8^i	3.454 (7)	C6···C7^x	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)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H9···O2^i	1.046	1.667	2.674 (6)	160.1
O3—H3···O4	0.891	2.248	2.745 (5)	114.8
O4—H4···O2^xi	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.