2,3,4-Tri­hydroxy­benzo­phenone monohydrate

In the crystal structure of the title compound, phenyl(2,3,4-tri­hydroxy­phenyl)­methano­ne monohydrate, C₁₃H₁₀O₄·H₂O, two benzene rings are inclined at 44.6 (5)° to each other, and the carbonyl O atom of the benzoyl group lies nearly in the 2,3,4-tri­hydroxy­benzene ring plane. The H atoms of the three hydroxyl groups are oriented in the same direction around the ring and form intra- and intermolecular hydrogen bonds. The crystal structure is stabilized by all of the available hydrogen bonds and by stacking interactions between adjacent mol­ecules.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.043
• wR factor = 0.184
• Data-to-parameter ratio = 16.1

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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S1. Comment

The title compound, (I), is a model compound of exifone (Adlone^R), a drug which was launched in France for the treatment of cognitive disorders in the elderly. Exifone has three hydroxyl groups at positions 2,3,4- and three at positions 3',4',5'- on the two benzene rings of the molecule. It has demonstrated remarkable scavenger properties against free radicals; this may be an etiological factor, but it was withdrawn from the market because of its hepatotoxic effects (Largeron et al., 1995, 1998). The oxidation chemistry of exifone was studied to obtain information about the mechanism of the pharmacological action of exifone, and (I) was used as the starting material. In that study, the hydrogen bonding between the OH group at the 2-position of the 2,3,4-trihydroxyphenyl ring and the O atom of the carbonyl of the benzoyl group are supposed to be important for formation of a 1,4-benzoxazine derivative of compound (I). The authors noticed the strong intramolecular hydrogen bond reported in the crystal structures of 2-hydroxy-4-methoxybenzophenone (Liebich & Parthé, 1974) and 2,4-dihydroxybenzophenone (Liebich, 1979). We have been interested in the structural features of polyphenols, because some polyphenols, such as gallic acid (3,4,5-trihydroxybenzoic acid) and protocathecuic acid (3,4-dihydroxybenzoic acid), have anti-oxidative and antitumor activity (Isuzugawa et al., 2001; Sakaguchi et al., 1999; Satoh & Sakagami, 1997; Kawase et al., 1998). We aimed to determine the structure of (I), which is a polyphenol.

The molecular structure of compound (I) is shown in Fig. 1. The two benzene rings are inclined to each other, as indicated by the torsion angle of 44.6 (5)° for C1—C7—C8—C9, and the carbonyl O atom of the benzoyl group lies nearly in the trihydroxybenzene ring plane, as indicated by the torsion angle of 8.9 (5)° for O5—C7—C1—C2. All three hydroxyl groups form intra- and intermolecular hydrogen bonds involving the hydrate water molecule, as shown in Table 2. Considering the distances between the donor and the acceptor O atoms, the hydrogen bonding between the hydroxyl group at the 2-position and the O atom of the carbonyl of the benzoyl group seems to be the strongest. The distance of 2.555 Å agrees well with those of the corresponding hydrogen bond, of 2.55 Å in 2-hydroxy-4-methoxybenzophenones (Liebich & Parthé, 1974) and of 2.550 (4) Å in 2,4-dihydroxybenzophenone (Liebich, 1979). The presence of this strong intramolecular hydrogen bond in compound (I) may provide direct evidence for the hypothesis in the oxidation reaction of 2,3,4-trihydroxybenzophenone reported by Largeron et al. (1995, 1998). The hydroxyl groups at positions 3 and 4 are linked to the water O atom by bifurcated hydrogen bonds. The orientation of the three hydroxyl groups and the formation of intramolecular hydrogen bonds are similar to those observed in gallic acid (3,4,5-trihydroxybenzoic acid) (Okabe et al., 2001), propyl gallate (Okabe & Kyoyama, 2002) and octyl gallate (Jeffrey & Yeon, 1990). The hydrogen-bonding patterns observeded in this study may have a role in the biological activity or oxidation reactions of many antioxidative polyphenols. The crystal structure is stabilized by all of the available hydrogen bonds involving the water molecule and by stacking interactions between symmetry-related rings of adjacent molecules.

S2. Experimental

A pale-yellow needle crystal was obtained by slow evaporation from a 50% methanol–water solution.

S3. Refinement

All H atoms were located from difference Fourier maps; their positions were idealized and refined with a riding model. Restraints were applied to the H atoms of the water molecule.

Computing details

Data collection: MSC/AFC (Molecular Structure Corporation, Rigaku Corporation, 1999); cell refinement: MSC/AFC; data reduction: TEXSAN (Molecular Structure Corporation & Rigaku Corporation, 1999); program(s) used to solve structure: SIR97 (Altomare et al., 1999) and 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.

Figures

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

(I)

Crystal data

C13H10O4·H2O	F(000) = 1040.0
Mr = 248.23	Dx = 1.412 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: -C 2yc	Cell parameters from 25 reflections
a = 33.365 (4) Å	θ = 11.3–13.2°
b = 3.991 (2) Å	µ = 0.11 mm^−1
c = 20.837 (3) Å	T = 296 K
β = 122.679 (9)°	Needle, pale yellow
V = 2335.5 (12) Å^3	0.50 × 0.15 × 0.05 mm
Z = 8

Data collection

Rigaku AFC-5R diffractometer	θmax = 27.5°
ω–2θ scans	h = 0→42
3112 measured reflections	k = 0→5
2675 independent reflections	l = −27→22
1050 reflections with I > 2σ(I)	3 standard reflections every 150 reflections
Rint = 0.057	intensity decay: 0.2%

Refinement

Refinement on F^2	H-atom parameters not refined
R[F^2 > 2σ(F^2)] = 0.044	w = 1/[σ^2(Fo^2) + (0.1P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.184	(Δ/σ)max < 0.001
S = 0.86	Δρmax = 0.21 e Å^−3
2675 reflections	Δρmin = −0.21 e Å^−3
166 parameters

Special details

Refinement. Refinement using reflections with F² > -10.0 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
O2	0.77764 (7)	−0.0444 (7)	0.0854 (1)	0.0573 (7)
O3	0.77694 (7)	0.0804 (7)	0.2131 (1)	0.0516 (7)
O4	0.85390 (8)	0.3741 (8)	0.3361 (1)	0.0630 (8)
O5	0.82160 (8)	0.0127 (8)	0.0167 (1)	0.0649 (8)
O6	0.78910 (7)	−0.1207 (6)	−0.1346 (1)	0.0506 (7)
C1	0.8571 (1)	0.1898 (8)	0.1432 (2)	0.0374 (7)
C2	0.8166 (1)	0.1023 (8)	0.1447 (2)	0.0377 (7)
C3	0.8156 (1)	0.1609 (9)	0.2096 (2)	0.0385 (7)
C4	0.8537 (1)	0.3130 (8)	0.2722 (2)	0.0403 (8)
C5	0.8930 (1)	0.4161 (8)	0.2705 (2)	0.0448 (8)
C6	0.8946 (1)	0.3544 (8)	0.2077 (2)	0.0407 (8)
C7	0.8582 (1)	0.1151 (9)	0.0762 (2)	0.0442 (8)
C8	0.9027 (1)	0.1483 (8)	0.0752 (2)	0.0388 (7)
C9	0.9462 (1)	0.0318 (9)	0.1340 (2)	0.0459 (8)
C10	0.9856 (1)	0.0469 (10)	0.1289 (2)	0.0544 (10)
C11	0.9818 (1)	0.180 (1)	0.0649 (2)	0.060 (1)
C12	0.9386 (1)	0.294 (1)	0.0059 (2)	0.060 (1)
C13	0.8988 (1)	0.2783 (10)	0.0100 (2)	0.0510 (9)
H2	0.7804	−0.0536	0.0487	0.0859*
H3	0.7604	−0.0561	0.1796	0.0774*
H4	0.8323	0.2686	0.3347	0.0945*
H5	0.9180	0.5268	0.3122	0.0560*
H6	0.9211	0.4227	0.2072	0.0509*
H9	0.9489	−0.0575	0.1774	0.0574*
H10	1.0148	−0.0329	0.1687	0.0680*
H11	1.0085	0.1930	0.0616	0.0755*
H12	0.9361	0.3825	−0.0374	0.0748*
H13	0.8696	0.3542	−0.0304	0.0637*
H14	0.7766	0.0626	−0.1581	0.0949*
H15	0.7997	−0.0766	−0.0880	0.0949*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O2	0.043 (1)	0.096 (2)	0.035 (1)	−0.020 (1)	0.023 (1)	−0.019 (1)
O3	0.044 (1)	0.076 (2)	0.044 (1)	−0.015 (1)	0.030 (1)	−0.016 (1)
O4	0.063 (2)	0.095 (2)	0.043 (1)	−0.026 (2)	0.036 (1)	−0.025 (1)
O5	0.047 (1)	0.113 (2)	0.036 (1)	−0.018 (2)	0.024 (1)	−0.015 (1)
O6	0.054 (1)	0.068 (2)	0.036 (1)	−0.005 (1)	0.028 (1)	−0.005 (1)
C1	0.039 (2)	0.045 (2)	0.030 (1)	0.001 (2)	0.020 (1)	0.003 (1)
C2	0.034 (2)	0.047 (2)	0.031 (1)	−0.001 (2)	0.017 (1)	−0.001 (2)
C3	0.035 (2)	0.046 (2)	0.037 (2)	0.002 (2)	0.021 (1)	0.000 (2)
C4	0.043 (2)	0.047 (2)	0.035 (1)	−0.003 (2)	0.025 (1)	−0.006 (2)
C5	0.043 (2)	0.051 (2)	0.037 (1)	−0.010 (2)	0.020 (1)	−0.011 (2)
C6	0.037 (2)	0.047 (2)	0.041 (2)	−0.007 (2)	0.023 (1)	−0.003 (2)
C7	0.045 (2)	0.055 (2)	0.033 (2)	−0.001 (2)	0.022 (1)	0.000 (2)
C8	0.042 (2)	0.045 (2)	0.033 (1)	−0.005 (2)	0.023 (1)	−0.006 (1)
C9	0.052 (2)	0.049 (2)	0.042 (2)	−0.002 (2)	0.028 (2)	−0.001 (2)
C10	0.046 (2)	0.063 (3)	0.052 (2)	−0.002 (2)	0.024 (2)	−0.009 (2)
C11	0.055 (2)	0.080 (3)	0.062 (2)	−0.016 (2)	0.043 (2)	−0.019 (2)
C12	0.069 (2)	0.075 (3)	0.051 (2)	−0.016 (2)	0.042 (2)	−0.003 (2)
C13	0.056 (2)	0.063 (2)	0.038 (2)	−0.004 (2)	0.028 (2)	0.003 (2)

Geometric parameters (Å, º)

O2—C2	1.351 (3)	C5—C6	1.363 (6)
O2—H2	0.820	C5—H5	0.930
O3—C3	1.370 (5)	C6—H6	0.930
O3—H3	0.820	C7—C8	1.500 (6)
O4—C4	1.350 (5)	C8—C9	1.380 (4)
O4—H4	0.820	C8—C13	1.393 (6)
O5—C7	1.250 (3)	C9—C10	1.377 (7)
O6—H14	0.853	C9—H9	0.930
O6—H15	0.854	C10—C11	1.377 (6)
C1—C2	1.411 (5)	C10—H10	0.930
C1—C6	1.409 (4)	C11—C12	1.371 (4)
C1—C7	1.449 (5)	C11—H11	0.930
C2—C3	1.392 (5)	C12—C13	1.377 (7)
C3—C4	1.375 (4)	C12—H12	0.930
C4—C5	1.393 (6)	C13—H13	0.930
O2···O6^i	3.204 (4)	O3···O3^iv	3.545 (5)
O2···O5^i	3.373 (3)	O3···O3^v	3.545 (5)
O2···O2^i	3.416 (4)	O4···O6^iii	2.737 (4)
O2···O5^ii	3.519 (3)	O4···C13^vi	3.382 (4)
O3···O6^i	2.646 (3)	O4···C12^vi	3.385 (4)
O3···O6^ii	2.879 (3)	O6···C3^ii	3.482 (4)
O3···O6^iii	2.978 (4)	C1···C6^vii	3.559 (4)
C2—O2—H2	109.5	O5—C7—C1	120.2 (4)
C3—O3—H3	109.5	O5—C7—C8	117.4 (3)
C4—O4—H4	109.5	C1—C7—C8	122.4 (2)
H14—O6—H15	104.4	C7—C8—C9	122.1 (3)
C2—C1—C6	117.6 (3)	C7—C8—C13	118.3 (3)
C2—C1—C7	119.5 (2)	C9—C8—C13	119.4 (4)
C6—C1—C7	122.9 (3)	C8—C9—C10	120.5 (4)
O2—C2—C1	123.3 (3)	C8—C9—H9	119.8
O2—C2—C3	116.4 (3)	C10—C9—H9	119.8
C1—C2—C3	120.3 (2)	C9—C10—C11	120.0 (3)
O3—C3—C2	122.0 (2)	C9—C10—H10	120.0
O3—C3—C4	117.8 (3)	C11—C10—H10	120.0
C2—C3—C4	120.1 (3)	C10—C11—C12	119.9 (4)
O4—C4—C3	121.8 (4)	C10—C11—H11	120.1
O4—C4—C5	117.9 (3)	C12—C11—H11	120.1
C3—C4—C5	120.4 (4)	C11—C12—C13	120.8 (4)
C4—C5—C6	119.8 (3)	C11—C12—H12	119.6
C4—C5—H5	120.1	C13—C12—H12	119.6
C6—C5—H5	120.1	C8—C13—C12	119.5 (3)
C1—C6—C5	121.6 (3)	C8—C13—H13	120.3
C1—C6—H6	119.2	C12—C13—H13	120.2
C5—C6—H6	119.2
O2—C2—C1—C6	177.4 (3)	C2—C1—C6—C5	2.5 (5)
O2—C2—C1—C7	−1.4 (5)	C2—C1—C7—C8	−169.7 (3)
O2—C2—C3—O3	−1.2 (5)	C2—C3—C4—C5	1.4 (5)
O2—C2—C3—C4	−179.2 (3)	C3—C2—C1—C6	−3.6 (5)
O3—C3—C2—C1	179.8 (3)	C3—C2—C1—C7	177.6 (3)
O3—C3—C4—O4	1.8 (5)	C3—C4—C5—C6	−2.5 (5)
O3—C3—C4—C5	−176.7 (3)	C5—C6—C1—C7	−178.8 (3)
O4—C4—C3—C2	179.9 (3)	C6—C1—C7—C8	11.7 (5)
O4—C4—C5—C6	178.9 (3)	C7—C8—C9—C10	175.7 (3)
O5—C7—C1—C2	8.9 (5)	C7—C8—C13—C12	−176.3 (3)
O5—C7—C1—C6	−169.8 (3)	C8—C9—C10—C11	0.3 (6)
O5—C7—C8—C9	−134.0 (4)	C8—C13—C12—C11	0.6 (6)
O5—C7—C8—C13	41.1 (5)	C9—C8—C13—C12	−1.1 (5)
C1—C2—C3—C4	1.7 (5)	C9—C10—C11—C12	−0.8 (6)
C1—C6—C5—C4	0.5 (5)	C10—C9—C8—C13	0.7 (5)
C1—C7—C8—C9	44.6 (5)	C10—C11—C12—C13	0.4 (6)
C1—C7—C8—C13	−140.3 (3)	C10—C11—C12—C13	0.4 (6)

Symmetry codes: (i) −x+3/2, −y−1/2, −z; (ii) −x+3/2, −y+1/2, −z; (iii) x, −y, z+1/2; (iv) −x+3/2, y+1/2, −z+1/2; (v) −x+3/2, y−1/2, −z+1/2; (vi) x, −y+1, z+1/2; (vii) x, y−1, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O5	0.82	1.84	2.553 (3)	145
O3—H3···O6^i	0.82	1.90	2.646 (3)	152
O3—H3···O2	0.82	2.33	2.720 (3)	110
O4—H4···O6^iii	0.82	1.96	2.737 (3)	158
O4—H4···O3	0.82	2.31	2.726 (3)	112
O6—H14···O3^ii	0.85	2.08	2.879 (4)	156
O6—H15···O5	0.85	1.92	2.776 (3)	178

Symmetry codes: (i) −x+3/2, −y−1/2, −z; (ii) −x+3/2, −y+1/2, −z; (iii) x, −y, z+1/2.