1,4 Bis(4 meth­oxy­phenyl)­piperazine 2,5 dione

organic papers

o1494

Structure Reports Online

ISSN 1600-5368

1,4-Bis(4-methoxyphenyl)piperazine-2,5-dione

Yong-Hong Wen, Shu-Sheng Zhang,* Bao-Hui Yu and Xue-Mei Li

College of Chemistry and Molecular

Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, People's Republic of China

Correspondence e-mail: zhangshush@public.qd.sd.cn

Key indicators Single-crystal X-ray study

T= 293 K

Mean(C±C) = 0.002 AÊ

Rfactor = 0.042

wRfactor = 0.119

Data-to-parameter ratio = 10.7

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2004 International Union of Crystallography Printed in Great Britain ± all rights reserved

In the title compound, C18H18N2O4, the molecule has a

crystallographically imposed center of symmetry. The dihedral angles between the piperazinedione ring and the two outer aromatic rings are 57.25 (7)_{. Molecules of (I) interact via} weak intermolecular CÐH O interactions, forming ribbons along thebaxis.

Comment

Piperazinedione and its derivatives are the smallest structural cyclodipeptides and are regarded as a by-product in the synthesis, especially in the solid-phase synthesis, of peptides (Gisin & Merri®eld, 1972; Khosla et al., 1972; Giralt et al., 1981). Two hydrogen-bond donors and two acceptors are present in the molecule of piperazinedione, so its derivatives have been widely used in pharmaceutical chemistry, e.g. for the inhibition of cell growth cycles of mammals (Cui et al., 1996; Edmondsonet al., 1999), the inhibition of glutathione-S -transferase (Sanatamariaet al., 1999) and the inhibition of the activated factor of thrombocytes (Chu et al., 1993). In the present paper, we describe the synthesis of the title compound, (I) (Fig. 1). An X-ray crystal analysis of (I) was undertaken to establish its molecular structure.

The title molecule has a crystallographically imposed center of symmetry. All bond lengths and angles in (I) have normal values (Allenet al., 1987). The three rings are each coplanar with their attached groups, excluding methyl H atoms and the H atoms attached to the piperazinedione ring, while the whole molecule is not planar, with dihedral angles of 57.25 (7) between the piperazinedione and the two aromatic rings. The

Received 19 July 2004 Accepted 2 August 2004 Online 7 August 2004

Figure 1

sum of the bond angles around atom N1 [359.85_{] indicates a} planar con®guration, different from the normal pyramidal con®guration of an N atom. This difference is mainly due to theconjugation effects arising from the presence of the two C O double bonds.

Molecules of (I) interact via weak intermolecular CÐ H O interactions (Table 2) to form ribbons along thebaxis (Fig. 2). The packing is further stabilized by van der Waals forces.

Experimental

N-p-Methoxyphenyl chloroacetamide was prepared by the reaction of p-methoxyaniline and chloroacetyl chloride in the presence of triethylamine according to the method of Li (2001). To a solution of N-p-methoxyphenyl chloroacetamide (3.9 g, 20 mmol) in acetone (30 ml) were added K2CO3(3.04 g, 22 mmol) and NaI (0.5 g), and the

mixture was stirred at 329 K for 5 h. The mixture was washed three times with water and then ®ltered. The ®lter cake was washed with a small amount of acetone and water. The title compound was obtained after the resulting white powder had been dried at room temperature for 48 h. Colorless single crystals suitable for X-ray diffraction analysis were obtained, after 7 d, by slow evaporation of a CHCl3±

CH3CH2OH (1:1,v/v) solution.

Crystal data

C18H18N2O4

Mr= 326.24

Monoclinic,P21=c

a= 16.9231 (17) AÊ b= 5.8166 (6) AÊ c= 8.0580 (8) AÊ = 92.687 (2)

V= 792.32 (14) AÊ3

Z= 2

Dx= 1.368 Mg mÿ3

MoKradiation Cell parameters from 1695

re¯ections = 2.4±26.1

= 0.10 mmÿ1

T= 293 (2) K Column, colorless 0.420.210.19 mm

Data collection

Simens SMART 1000 CCD area-detector diffractometer !scans

Absorption correction: empirical (SADABS; Sheldrick, 1996) Tmin= 0.960,Tmax= 0.982

4225 measured re¯ections

1557 independent re¯ections 1318 re¯ections withI> 2(I) Rint= 0.018

max= 26.1

h=ÿ18!20 k=ÿ7!6 l=ÿ8!9

Re®nement

Re®nement onF2

R[F2_{> 2(F}2_{)] = 0.042}

wR(F2_{) = 0.119}

S= 1.04 1557 re¯ections 146 parameters

All H-atom parameters re®ned

w= 1/[2_(F

o2) + (0.0631P)2

+ 0.1534P]

whereP= (Fo2+ 2Fc2)/3

(/)max< 0.001

max= 0.15 e AÊÿ3

min=ÿ0.15 e AÊÿ3

Extinction correction:SHELXL97 Extinction coef®cient: 0.028 (5)

Table 1

Selected geometric parameters (AÊ,_).

O1ÐC2 1.3736 (18)

O1ÐC1 1.419 (2)

O2ÐC9 1.2278 (16)

N1ÐC9 1.3436 (17)

N1ÐC5 1.4399 (17)

N1ÐC8 1.4569 (16)

C2ÐO1ÐC1 117.45 (14)

C9ÐN1ÐC5 120.56 (11) C9ÐN1ÐC8C5ÐN1ÐC8 122.62 (11)116.67 (10)

Table 2

Intermolecular CÐH O contacts (A,_).

DÐH A DÐH H A D A DÐH A

C8ÐH8A O2i _{0.98 (1) 2.42 (1) 3.389 (1) 174 (1)}

Symmetry code: (i)x;1‡y;z.

All H atoms were located in difference Fourier maps and were re®ned isotropically [CÐH = 0.946 (18)±1.04 (2) AÊ].

Data collection:SMART(Siemens, 1996); cell re®nement:SAINT (Siemens, 1996); data reduction:SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to re®ne structure:SHELXTL; molecular graphics:SHELXTL; software used to prepare material for publication:SHELXTL,PARST(Nardelli, 1995) andPLATON(Spek, 2003).

This project was supported by the National Natural Science Foundation of China (grant No. 20275020), the State Key Laboratory Foundation of Electroanalytical Chemistry of Changchun Institute of Applied Chemistry (grant No. SKLEAC 2004-8) and the Outstanding Adult±Young Scien-ti®c Research Encouraging Foundation of Shandong Province (grant No. 03BS081).

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987).J. Chem. Soc. Perkin Trans.2, pp. S1±19.

Chu, M., Mierzwa, R., Fruumees, I., Gentile, F., Patel, M., Gullo, V., Chan, T.-M. & Puar, M. S. (1993).Tetrahedron Lett.34, 7537±7540.

Cui, C. B., Kakeya, H. & Osada, H. (1996).Tetrahedron,52, 12651±12666. Edmondson, S., Danishefsky, S. J., Sepp-Lorenzino, L. & Rosen, N. (1999).J.

Am. Chem. Soc.121, 2147±2155.

Giralt, E., Eritja, R. & Pedroso, E. (1981).Tetrahedron Lett.22, 3779±3782. Gisin, B. F. & Merri®eld, R. B. (1972).J. Am. Chem. Soc.94, 3102±3106. Khosla, M. C., Smeby, R. R. & Bumpus, F. (1972).J. Am. Chem. Soc.94, 4721±

4724.

Li, Z. G. (2001).Preparation of Organic Intermediates, pp. 103±107. Beijing: Chemical Industry Press.

Nardelli, M. (1995).J. Appl. Cryst.28, 659.

Sanatamaria, A., Cabezas, N. & Avendano, C. (1999).Tetrahedron,55, 1173± 1186.

organic papers

Acta Cryst.(2004). E60, o1494±o1496 Wen, Zhang, Yu and Li C₁₈H₁₈N₂O₄

o1495

Figure 2

A packing diagram of (I), showing the formation of ribbons along theb

Sheldrick, G. M. (1996).SADABS.University of GoÈttingen, Germany. Sheldrick, G. M. (1997).SHELXTL.Version 5.1. Bruker AXS Inc., Madison,

Wisconsin, USA.

Siemens (1996).SMARTandSAINT.Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

Spek, A. L. (2003).J. Appl. Cryst.36, 7±13.

organic papers

supporting information

sup-1 Acta Cryst. (2004). E60, o1494–o1496

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Acta Cryst. (2004). E60, o1494–o1496 [https://doi.org/10.1107/S1600536804018914]

1,4-Bis(4-methoxyphenyl)piperazine-2,5-dione

Yong-Hong Wen, Shu-Sheng Zhang, Bao-Hui Yu and Xue-Mei Li

1,4-Bis(4-methoxyphenyl)piperazine-2,5-dione

Crystal data

C18H18N2O4

Mr = 326.24 Monoclinic, P21/c

a = 16.9231 (17) Å b = 5.8166 (6) Å c = 8.0580 (8) Å β = 92.687 (2)° V = 792.32 (14) Å3

Z = 2

F(000) = 344 Dx = 1.368 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 4504 reflections θ = 2.4–26.1°

µ = 0.10 mm−1

T = 293 K Column, colorless 0.42 × 0.21 × 0.19 mm

Data collection

Simens SMART 1000 CCD area-detector diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

Detector resolution: 8.33 pixels mm-1

ω scans

Absorption correction: empirical (using intensity measurements)

(SADABS; Sheldrick, 1996)

Tmin = 0.960, Tmax = 0.982 4225 measured reflections 1557 independent reflections 1318 reflections with I > 2σ(I) Rint = 0.018

θmax = 26.1°, θmin = 2.4°

h = −18→20 k = −7→6 l = −8→9

Refinement

Refinement on F2 Least-squares matrix: full R[F2 _{> 2σ(F}2_{)] = 0.042}

wR(F2_{) = 0.119}

S = 1.04 1557 reflections 146 parameters 0 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

All H-atom parameters refined w = 1/[σ2_(F

o2) + (0.0631P)2 + 0.1534P] where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001 Δρmax = 0.15 e Å−3 Δρmin = −0.15 e Å−3

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sup-2 Acta Cryst. (2004). E60, o1494–o1496

Special details

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 F}2_, conventional R-factors R are based on F, with F set to zero for negative F2_{. The threshold expression of F}2 _{> σ(F}2_{) 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2₎

x y z Uiso*/Ueq

O1 0.91274 (6) 0.0420 (2) 0.59156 (18) 0.0707 (4)

O2 0.57510 (6) −0.32730 (17) 0.67867 (14) 0.0527 (3)

N1 0.58278 (6) 0.00831 (18) 0.53827 (14) 0.0372 (3)

C1 0.95255 (12) 0.2387 (4) 0.6576 (4) 0.0768 (6)

H1C 1.0084 (14) 0.206 (4) 0.650 (3) 0.093 (7)*

H1B 0.9340 (12) 0.385 (4) 0.591 (3) 0.091 (7)*

H1A 0.9410 (14) 0.268 (4) 0.772 (4) 0.115 (9)*

C2 0.83149 (8) 0.0451 (3) 0.5847 (2) 0.0491 (4)

C3 0.79465 (9) −0.1439 (3) 0.5095 (2) 0.0543 (4)

H3 0.8273 (10) −0.268 (3) 0.466 (2) 0.067 (5)*

C4 0.71347 (9) −0.1567 (3) 0.4950 (2) 0.0481 (4)

H4 0.6873 (9) −0.286 (3) 0.439 (2) 0.054 (4)*

C5 0.66774 (8) 0.0189 (2) 0.55692 (16) 0.0387 (4)

C6 0.70421 (9) 0.2080 (3) 0.62934 (19) 0.0460 (4)

H6 0.6719 (10) 0.332 (3) 0.668 (2) 0.062 (5)*

C7 0.78627 (9) 0.2220 (3) 0.6440 (2) 0.0509 (4)

H7 0.8099 (10) 0.355 (3) 0.693 (2) 0.068 (5)*

C8 0.54371 (8) 0.1941 (2) 0.44506 (19) 0.0397 (4)

H8B 0.5690 (10) 0.213 (3) 0.340 (2) 0.057 (5)*

C9 0.54327 (8) −0.1734 (2) 0.59541 (16) 0.0372 (3)

H8A 0.5512 (9) 0.338 (3) 0.506 (2) 0.058 (5)*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

O1 0.0371 (6) 0.0754 (9) 0.0992 (10) 0.0025 (6) −0.0018 (6) −0.0069 (7)

O2 0.0495 (6) 0.0455 (6) 0.0619 (7) 0.0015 (4) −0.0088 (5) 0.0178 (5)

N1 0.0361 (6) 0.0341 (6) 0.0411 (6) 0.0019 (4) −0.0005 (5) 0.0023 (4)

C1 0.0435 (10) 0.0915 (16) 0.0948 (17) −0.0083 (10) −0.0042 (10) −0.0103 (13)

C2 0.0377 (8) 0.0561 (9) 0.0534 (9) 0.0031 (6) 0.0005 (6) 0.0048 (7)

C3 0.0455 (8) 0.0479 (9) 0.0696 (11) 0.0098 (7) 0.0033 (7) −0.0036 (8)

C4 0.0455 (8) 0.0406 (8) 0.0579 (9) 0.0039 (6) −0.0016 (7) −0.0054 (7)

C5 0.0378 (7) 0.0398 (7) 0.0382 (7) 0.0015 (5) 0.0001 (5) 0.0036 (5)

C6 0.0422 (8) 0.0451 (8) 0.0511 (9) 0.0009 (6) 0.0053 (6) −0.0071 (6)

C7 0.0456 (9) 0.0528 (9) 0.0543 (9) −0.0062 (7) 0.0013 (7) −0.0085 (7)

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sup-3 Acta Cryst. (2004). E60, o1494–o1496

C9 0.0430 (7) 0.0332 (7) 0.0352 (7) 0.0022 (5) −0.0002 (5) 0.0001 (5)

Geometric parameters (Å, º)

O1—C2 1.3736 (18) C3—H3 0.984 (18)

O1—C1 1.419 (2) C4—C5 1.3883 (19)

O2—C9 1.2278 (16) C4—H4 0.972 (16)

N1—C9 1.3436 (17) C5—C6 1.3776 (19)

N1—C5 1.4399 (17) C6—C7 1.391 (2)

N1—C8 1.4569 (16) C6—H6 0.966 (18)

C1—H1C 0.97 (2) C7—H7 0.946 (18)

C1—H1B 1.04 (2) C8—C9i _{1.4974 (19)}

C1—H1A 0.96 (3) C8—H8B 0.974 (19)

C2—C7 1.381 (2) C8—H8A 0.976 (18)

C2—C3 1.389 (2) C9—C8i _{1.4974 (19)}

C3—C4 1.375 (2)

C2—O1—C1 117.45 (14) C6—C5—C4 119.57 (13)

C9—N1—C5 120.56 (11) C6—C5—N1 120.25 (12)

C9—N1—C8 122.62 (11) C4—C5—N1 120.11 (12)

C5—N1—C8 116.67 (10) C5—C6—C7 120.56 (14)

O1—C1—H1C 105.4 (13) C5—C6—H6 118.9 (10)

O1—C1—H1B 109.7 (12) C7—C6—H6 120.5 (10)

H1C—C1—H1B 113.3 (18) C2—C7—C6 119.64 (14)

O1—C1—H1A 112.7 (15) C2—C7—H7 121.4 (11)

H1C—C1—H1A 110 (2) C6—C7—H7 119.0 (11)

H1B—C1—H1A 106.0 (19) N1—C8—C9i _{118.06 (11)}

O1—C2—C7 124.48 (14) N1—C8—H8B 108.9 (10)

O1—C2—C3 115.77 (13) C9i_{—C8—H8B 106.7 (10)}

C7—C2—C3 119.74 (14) N1—C8—H8A 109.5 (10)

C4—C3—C2 120.40 (14) C9i_{—C8—H8A 106.3 (9)}

C4—C3—H3 120.4 (10) H8B—C8—H8A 106.8 (13)

C2—C3—H3 119.2 (10) O2—C9—N1 123.24 (12)

C3—C4—C5 120.07 (14) O2—C9—C8i _{117.51 (12)}

C3—C4—H4 120.9 (9) N1—C9—C8i _{119.24 (11)}

C5—C4—H4 119.0 (9)

C1—O1—C2—C7 −2.9 (3) C4—C5—C6—C7 −1.4 (2)

C1—O1—C2—C3 175.98 (18) N1—C5—C6—C7 −178.39 (13)

O1—C2—C3—C4 −179.43 (15) O1—C2—C7—C6 179.45 (14)

C7—C2—C3—C4 −0.5 (2) C3—C2—C7—C6 0.6 (2)

C2—C3—C4—C5 −0.5 (2) C5—C6—C7—C2 0.3 (2)

C3—C4—C5—C6 1.5 (2) C9—N1—C8—C9i _{−3.3 (2)}

C3—C4—C5—N1 178.51 (13) C5—N1—C8—C9i _{172.34 (11)}

C9—N1—C5—C6 −126.95 (14) C5—N1—C9—O2 7.0 (2)

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sup-4 Acta Cryst. (2004). E60, o1494–o1496

C9—N1—C5—C4 56.05 (18) C5—N1—C9—C8i _{−172.13 (11)}

C8—N1—C5—C4 −119.65 (14) C8—N1—C9—C8i _{3.3 (2)}

Symmetry code: (i) −x+1, −y, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

C6—H6···O2ii _{0.97 (1) 2.58 (1) 3.510 (2) 163 (1)}

C8—H8A···O2ii _{0.98 (1) 2.42 (1) 3.389 (1) 174 (1)}

C8—H8B···O2iii _{0.97 (1) 2.60 (1) 3.090 (1) 111 (1)}