3,6-Bis­(4-hydroxy­benzyl)­piperazine-2,5-dione

In the title compound, C₁₈H₁₆N₂O₄, the piperidine ring adopts a chair conformation, lying on an inversion centre. The 4-hydroxy­benzyl groups are in quasi-axial positions. A two-dimensional network is formed through N-H...O and O-H...O intermolecular hydrogen bonds and C-H...O interactions.

S1. Comment

The optical properties of the title compound were investigated as a function of molecular conformation (Snow et al., 1977). The synthesis and antimicrobial activity of the title compound were studied by Gadaginamath et al. (1996). Michael & John (1985) studied the organic chemisty of L-tyrosine and concluded several general synthetic methods of chiral piperazines from amino acids. Liebscher & Jin (1999) reviewed the synthetic methods of the piperazine-2,5-diones from 3-ylidenepiperazine-2,5-diones.

In the title compound, (I), the bond lengths and angles of the diketopiperazine ring are comparable with related reported values (Szkaradzinska et al., 1994; Sterns et al., 1989). The piperidine ring adopts a chair conformation inclining towards planarity. The total puckering amplitude Q_T = 0.087 (3) Å (Cremer & Pople, 1975). The O1 atom deviates by 0.125 (2) Å from the mean plane through the piperazine ring. The 4-hydroxybenzyl groups at C8 and C8A are in quasi-axial positions [C7—C8—N1—C9 − 113.4 (2)°]. This conformation is also found in the derivative of lichen diketopiperazine metabolite methylanhydropicroroccellin reported by Sterns et al. (1989). The phenyl rings are planar, making a dihedral angle of 54.6 (1)° with the mean plane of the piperidine ring.

In the crystal, N1—H1B···O2(x, 1 − y, −1/2 + z) and O2—H2B···O1(1/2 − x, −1/2 + y, 3/2 − z) intermolecular hydrogen bonds link the molecules along the c axis. Adjacent chains are interlinked by C4—H4A···O1(−1/2 + x, −1/2 + y, z) interactions. These N—H.·O and O—H.·O intermolecular hydrogen bonds and C—H.·O interactions form a two-dimensional network.

S2. Experimental

The title compound was synthesized under solvothermal conditions. A heavy walled Pyrex tube containing a mixture of NaMe (0.0108 g, 0.2 mmol), L-tyrosine (0.0181 g, 0.1 mmol) and LaCl₃ (0.0246 g, 0.1 mmol) in methanol (1 ml) was frozen and sealed under vacuum and placed inside an oven at 393 K. The colourless prismatic crystals obtained were harvested after two weeks of heating. The IR spectrum confirmed the pure phase.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 1990).

3,6-Bis[(4-hydroxyphenyl)methyl]piperazine-2,5-dione

Crystal data

C18H18N2O4	F(000) = 688
Mr = 326.34	Dx = 1.320 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 16.2590 (6) Å	Cell parameters from 2073 reflections
b = 8.0575 (2) Å	θ = 2.9–28.3°
c = 14.7794 (6) Å	µ = 0.09 mm^−1
β = 121.967 (2)°	T = 293 K
V = 1642.6 (1) Å^3	Plate, colourless
Z = 4	0.22 × 0.16 × 0.06 mm

Data collection

Siemens SMART CCD area-detector diffractometer	1028 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.082
Graphite monochromator	θmax = 27.5°, θmin = 2.9°
Detector resolution: 8.33 pixels mm^-1	h = −11→21
ω scans	k = −10→10
5346 measured reflections	l = −19→18
1876 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.055	H-atom parameters constrained
wR(F^2) = 0.146	w = 1/[σ^2(Fo^2) + (0.065P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.90	(Δ/σ)max < 0.001
1876 reflections	Δρmax = 0.22 e Å^−3
110 parameters	Δρmin = −0.28 e Å^−3
0 restraints	Extinction correction: SHELXTL, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0078 (16)

Special details

Experimental. The data collection covered over a hemisphere of reciprocal space by a combination of three sets of exposures; each set had a different ϕ angle (0, 88 and 180°) for the crystal and each exposure of 10 s covered 0.3° in ω. The crystal-to-detector distance was 4 cm and the detector swing angle was −35°. Crystal decay was monitored by repeating fifty initial frames at the end of data collection and analysing the intensity of duplicate reflections, and was found to be negligible.

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.

After checking their presence in the difference map, all H atoms were geometrically fixed and allowed to ride on their attached atoms.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.38842 (11)	0.4776 (2)	0.60768 (13)	0.0479 (5)
O2	0.17469 (13)	0.2719 (2)	0.86188 (14)	0.0504 (5)
H2B	0.1548	0.1824	0.8691	0.076*
N1	0.23795 (13)	0.4142 (2)	0.47295 (13)	0.0327 (5)
H1B	0.2313	0.5151	0.4512	0.039*
C1	0.16070 (17)	0.4491 (3)	0.6270 (2)	0.0417 (6)
H1A	0.1866	0.5390	0.6108	0.050*
C2	0.18791 (18)	0.4229 (3)	0.7322 (2)	0.0434 (6)
H2A	0.2331	0.4923	0.7859	0.052*
C3	0.14698 (17)	0.2920 (3)	0.75663 (19)	0.0372 (6)
C4	0.08106 (17)	0.1891 (3)	0.6764 (2)	0.0420 (6)
H4A	0.0534	0.1016	0.6923	0.050*
C5	0.05592 (17)	0.2157 (3)	0.5722 (2)	0.0421 (6)
H5A	0.0111	0.1455	0.5188	0.051*
C6	0.09590 (16)	0.3446 (3)	0.54526 (19)	0.0350 (6)
C7	0.07076 (16)	0.3670 (3)	0.43149 (19)	0.0411 (6)
H7A	0.0577	0.4835	0.4125	0.049*
H7B	0.0120	0.3054	0.3840	0.049*
C8	0.15251 (16)	0.3078 (3)	0.41453 (17)	0.0323 (5)
H8A	0.1210	0.3218	0.3254	0.039*
C9	0.32480 (16)	0.3731 (3)	0.55595 (17)	0.0313 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0405 (10)	0.0382 (9)	0.0603 (11)	−0.0115 (8)	0.0235 (9)	−0.0191 (8)
O2	0.0729 (12)	0.0357 (9)	0.0512 (11)	−0.0126 (9)	0.0386 (10)	−0.0064 (8)
N1	0.0396 (11)	0.0238 (9)	0.0371 (11)	−0.0001 (8)	0.0220 (9)	0.0031 (8)
C1	0.0499 (15)	0.0353 (12)	0.0571 (17)	−0.0115 (11)	0.0401 (13)	−0.0097 (12)
C2	0.0539 (16)	0.0386 (13)	0.0507 (16)	−0.0168 (12)	0.0366 (13)	−0.0154 (12)
C3	0.0444 (14)	0.0327 (12)	0.0424 (14)	−0.0014 (11)	0.0284 (12)	−0.0037 (11)
C4	0.0446 (15)	0.0326 (12)	0.0551 (16)	−0.0068 (11)	0.0307 (13)	−0.0014 (12)
C5	0.0362 (14)	0.0365 (13)	0.0514 (16)	−0.0090 (11)	0.0216 (12)	−0.0115 (12)
C6	0.0299 (12)	0.0343 (12)	0.0447 (14)	0.0030 (10)	0.0224 (11)	−0.0038 (11)
C7	0.0341 (13)	0.0404 (13)	0.0443 (14)	0.0072 (11)	0.0176 (11)	−0.0006 (11)
C8	0.0314 (12)	0.0305 (11)	0.0288 (12)	−0.0008 (10)	0.0118 (10)	0.0001 (10)
C9	0.0356 (13)	0.0320 (11)	0.0316 (12)	−0.0009 (11)	0.0214 (11)	−0.0071 (10)

Geometric parameters (Å, º)

O1—C9	1.236 (2)	C4—C5	1.385 (3)
O2—C3	1.381 (3)	C4—H4A	0.9300
O2—H2B	0.8200	C5—C6	1.391 (3)
N1—C9	1.332 (3)	C5—H5A	0.9300
N1—C8	1.463 (3)	C6—C7	1.516 (3)
N1—H1B	0.8600	C7—C8	1.552 (3)
C1—C2	1.389 (3)	C7—H7A	0.9700
C1—C6	1.389 (3)	C7—H7B	0.9700
C1—H1A	0.9300	C8—C9^i	1.510 (3)
C2—C3	1.393 (3)	C8—H8A	1.1383
C2—H2A	0.9300	C9—C8^i	1.510 (3)
C3—C4	1.377 (3)
C3—O2—H2B	109.5	C1—C6—C5	117.2 (2)
C9—N1—C8	127.60 (18)	C1—C6—C7	121.8 (2)
C9—N1—H1B	116.2	C5—C6—C7	120.9 (2)
C8—N1—H1B	116.2	C6—C7—C8	113.03 (18)
C2—C1—C6	121.8 (2)	C6—C7—H7A	109.0
C2—C1—H1A	119.1	C8—C7—H7A	109.0
C6—C1—H1A	119.1	C6—C7—H7B	109.0
C1—C2—C3	119.5 (2)	C8—C7—H7B	109.0
C1—C2—H2A	120.3	H7A—C7—H7B	107.8
C3—C2—H2A	120.3	N1—C8—C9^i	112.63 (17)
C4—C3—O2	122.7 (2)	N1—C8—C7	110.56 (17)
C4—C3—C2	119.6 (2)	C9^i—C8—C7	110.43 (19)
O2—C3—C2	117.7 (2)	N1—C8—H8A	109.3
C3—C4—C5	120.0 (2)	C9^i—C8—H8A	108.7
C3—C4—H4A	120.0	C7—C8—H8A	104.9
C5—C4—H4A	120.0	O1—C9—N1	122.2 (2)
C4—C5—C6	121.8 (2)	O1—C9—C8^i	118.9 (2)
C4—C5—H5A	119.1	N1—C9—C8^i	118.94 (19)
C6—C5—H5A	119.1
C6—C1—C2—C3	−2.2 (4)	C4—C5—C6—C7	177.3 (2)
C1—C2—C3—C4	0.8 (4)	C1—C6—C7—C8	75.2 (3)
C1—C2—C3—O2	−178.9 (2)	C5—C6—C7—C8	−103.6 (2)
O2—C3—C4—C5	179.8 (2)	C9—N1—C8—C9^i	−10.7 (3)
C2—C3—C4—C5	0.1 (4)	C9—N1—C8—C7	113.4 (2)
C3—C4—C5—C6	0.3 (4)	C6—C7—C8—N1	−67.0 (2)
C2—C1—C6—C5	2.6 (3)	C6—C7—C8—C9^i	58.3 (3)
C2—C1—C6—C7	−176.3 (2)	C8—N1—C9—O1	−170.9 (2)
C4—C5—C6—C1	−1.6 (3)	C8—N1—C9—C8^i	11.3 (4)

Symmetry code: (i) −x+1/2, −y+1/2, −z+1.